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Wang Z, Jiang L, Lu F, Qian L, Pan Y, Zhang C, Huang Z, Zeng M, Sun B, Zhang B, Mao H, Zhang Y, Duan S, Xing C, Yuan Y. Delta corticomedullary apparent diffusion coefficient on MRI as a biomarker for prognosis in IgA nephropathy. Ren Fail 2025; 47:2441394. [PMID: 39689921 DOI: 10.1080/0886022x.2024.2441394] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Revised: 12/05/2024] [Accepted: 12/06/2024] [Indexed: 12/19/2024] Open
Abstract
OBJECTIVES To explore the association of the cortico-medullary difference in apparent diffusion coefficient (ΔADC) with clinicopathological parameters of disease activity at the time of biopsy, and with the prognositic risk stratification in IgA nephropathy (IgAN) patients. METHODS We included 112 patients with biopsy-proven IgAN who measured ΔADC. Patients underwent a kidney biopsy and diffusion-weighted magnetic resonance imaging within one week of the biopsy. Clinicopathological characteristics were compared according to different ΔADC levels. The effect of ΔADC on eGFR and kidney fibrosis was explored using multivariate regression and ROC analysis. An individual's 5-year risk probability of progressing to ESKD or decreasing of eGFR > 50% was calculated by the guidelines-recommended international risk-prediction tool in IgAN. The effect of ΔADC on prognostic risk stratification was assessed. Net reclassification improvement (NRI) was used to evaluate the model performance. RESULTS The average ΔADC was 168.89 ± 85.1 x10-6 mm2/s. ΔADC levels decreased significantly with increasing chronic kidney disease (CKD) stages (p = 0.0038). Spearman correlation analysis revealed that ΔADC was positively correlated with eGFR, hemoglobin, serum albumin, while negatively correlated with levels of serum creatine (Scr), blood urea nitrogen (BUN), T score of Oxford classification and Lee grades (p < 0.05). Moreover, we showed that ΔADC was independently associated with eGFR (β = 0.04, 95% CI = [0.003, 0.077], p = 0.033) demonstrated by a backward stepwise multivariate linear regression analysis. Besides, ΔADC, a combination of ΔADC and eGFR showed an AUC of 0.776 (60% sensitivity and 85.3% specificity) and an AUC of 0.875 (100% sensitivity and 69.6% specificity) respectively for evaluating kidney interstitial fibrosis (IF) severity. Furthermore, ΔADC showed an AUC of 0.792 (95% CI 0.677-0.906) for differentiating higher progression risk categories from lower categories (specificity = 91.6%, sensitivity = 58.8%). The low-ΔADC group (≤ median value 167.1 × 10-6 mm2/s) was associated with 7.509-fold higher likelihood of higher progression risk compared to the high-ΔADC group (>167.1 × 10-6 mm2/s) in a fully-adjusted model. And reclassification analyses confirmed that the final adjusted model improved NRI. CONCLUSIONS ΔADC was significantly associated with kidney function and enabled a reliable evaluation of kidney IF severity in IgAN patients. Low ΔADC can predict a high 5-year kidney progression risk in IgAN, independent of important clinical factors. Moreover, the predictive ability to identify patients at high risk of severe kidney fibrosis and adverse progression estimates with satisfactory accuracy, facilitating ΔADC a promising and noninvasive tool in complementarily evaluating disease activity and the prognostic risk stratification in patients with IgAN.
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Affiliation(s)
- Zitao Wang
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Ling Jiang
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Fang Lu
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Li Qian
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Ying Pan
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Chengning Zhang
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Zhimin Huang
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Ming Zeng
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Bin Sun
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Bo Zhang
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Huijuan Mao
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Yudong Zhang
- Department of Radiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu Province, China
| | - Suyan Duan
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Changying Xing
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
| | - Yanggang Yuan
- Department of Nephrology, the First Affiliated Hospital of Nanjing Medical University, Nanjing Medical University, Nanjing, China
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Zang Z, Fang K, Ma N, Zhang Y, Shu Y, Li Z. Association between different proportions of crescents and adverse renal outcomes in immunoglobulin a nephropathy: a systematic review and meta-analysis. Ren Fail 2025; 47:2495104. [PMID: 40398883 PMCID: PMC12168408 DOI: 10.1080/0886022x.2025.2495104] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2025] [Revised: 03/21/2025] [Accepted: 04/09/2025] [Indexed: 05/23/2025] Open
Abstract
OBJECTIVES Immunoglobulin A nephropathy (IgAN) had several pathological predictive factors, but the predictive value of crescents (C) for renal prognosis was controversial. We conducted a systematic review and meta-analysis to identify the association between crescents and renal outcomes of IgAN patients. METHODS We searched PubMed, the Cochrane library and Ovid from database inception through to August 30, 2024. The analysis utilized risk ratio (RR) or mean difference (MD) along with the corresponding 95% confidence interval (CI). Data analysis was performed using Stata18 MP (Stata Corp) and RevMan 5.4. The proportion of crescents was classified as C0 (no crescents), C1 (crescents <25%), and C2 (crescents ≥25%). RESULTS Eighteen studies were eligible, including 7,567 patients in the C0 group and 4,219 patients in the C group. Our meta-analyses revealed that compared to the C group, the C0 group had significantly lower incidence of composite kidney endpoint [RR = 0.56, 95% CI (0.45, 0.70)] and end-stage renal disease (ESRD) [RR = 0.64, 95% CI (0.51, 0.80)]. The C0 group had significantly higher estimated glomerular filtration rate (eGFR), lower proteinuria, and milder E1, S1, and T1/2 (all P values < 0.05). Compared to the C0 or C1 group, the C2 group was more likely to have composite kidney endpoint and ESRD. We did not find the benefit of immunosuppressant therapy (IST) in the C1, C2, or C group. CONCLUSIONS We found that IgAN patients with crescents had higher risk of composite kidney endpoints and ESRD, especially patients with C2 lesions. IST may not improve renal outcomes in IgAN patients with C1 or C2 lesions.
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Affiliation(s)
- Zhiyun Zang
- Department of Nephrology, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, China
| | - Kewei Fang
- Department of Radiology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China
| | - Niya Ma
- Department of Nephrology, Institute of Nephrology, West China Hospital of Sichuan University, Chengdu, China
| | - Yunyun Zhang
- Department of Nephrology, Institute of Nephrology, West China Hospital of Sichuan University, Chengdu, China
| | - Ying Shu
- Department of Nephrology, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, China
| | - Zi Li
- Department of Nephrology, Institute of Nephrology, West China Hospital of Sichuan University, Chengdu, China
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Alza-Arcila L, Echeverri-Fernández E, Restrepo-Escobar M, Calderón LL, Ustáriz JM, Arias-Restrepo LF, Rodelo-Ceballos JR. Prognostic Utility of the MEST-C Score Combined With Clinical Parameters in Hispanic Patients With IgA Nephropathy. Int J Nephrol 2025; 2025:6974280. [PMID: 40224579 PMCID: PMC11991785 DOI: 10.1155/ijne/6974280] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Accepted: 02/21/2025] [Indexed: 04/15/2025] Open
Abstract
Introduction: The Oxford/MEST-C classification is a histopathological scoring system for patients with IgA nephropathy (IgAN) that has demonstrated prognostic utility. The aim of this study was to evaluate the prognostic utility of the combination of clinical characteristics and MEST-C in Hispanic ethnicity patients. Methods: Retrospective cohort study. Clinical, laboratory, and kidney biopsy information with MEST-C classification was obtained. The primary outcome was the development of end-stage kidney disease (ESKD). Cox regression analysis was performed for factors associated with ESKD, and Kaplan-Meier survival analysis for kidney survival. Results: A total of 397 patients were included, 51% were male, median age was 38 years with an interquartile range (IQR) of 28-53. The main comorbidity was hypertension present in 60.5%. At the time of biopsy, estimated glomerular filtration rate (eGFR) was 54 mL/min (IQR 33-94) and 24 h proteinuria was 1680 mg (IQR 594-3500). 30.7% of patients developed ESKD over a median follow-up of 1702 days (IQR 808-2858). Multivariate analysis of M, E, S, T, and C lesions showed that only S and T lesions correlated with the development of ESKD. The combination of S and T items of the MEST-C score with variables such as age, eGFR, proteinuria, and hypertension were significantly associated with the outcome. Explored prognostic models showed a high Harrel's C concordance index of 0.89. Conclusion: Performing the MEST score, especially the presence of sclerosing (S) and tubular fibrosis/atrophy (T) lesions combined with clinical variables are prognostic variables in the Hispanic population.
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Affiliation(s)
- Lyzinhawer Alza-Arcila
- Department of Internal Medicine, Nephrology Section, Universidad de Antioquia, Medellín, Colombia
| | | | | | - Ligia Lorena Calderón
- Nephrology Service, San Vicente Fundación Hospital, Department of Internal Medicine, Nephrology Section, Universidad de Antioquia, Medellín, Colombia
| | - José Manuel Ustáriz
- Nephrology Service, San Vicente Fundación Hospital, Department of Internal Medicine, Nephrology Section, Universidad de Antioquia, Medellín, Colombia
| | | | - Joaquín Roberto Rodelo-Ceballos
- Nephrology Service, San Vicente Fundación Hospital, Department of Internal Medicine, Nephrology Section, Universidad de Antioquia, Medellín, Colombia
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Satirapoj B, Chueaboonchai T, Nata N, Supasyndh O. Kidney Outcomes with Corticosteroid Treatment in IgA Nephropathy According to the Oxford-MEST-C Classification. GLOMERULAR DISEASES 2025; 5:191-199. [PMID: 40308704 PMCID: PMC12043279 DOI: 10.1159/000545382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Accepted: 03/14/2025] [Indexed: 05/02/2025]
Abstract
Introduction Despite optimization of renin-angiotensin-aldosterone system (RAAS) inhibition, patients with IgA nephropathy remain at risk for kidney failure. The effect of steroids on kidney outcomes in IgA nephropathy with different renal pathologic lesions has been uncertain. Objective This study aimed to evaluate the efficacy of steroid treatment in IgA nephropathy patients classified according to the Oxford-MEST-C classification. Methods We retrospectively studied 67 patients with biopsy-proven IgA nephropathy who were receiving optimized RAAS inhibitor therapy and had persistent proteinuria >1 g/day between January 2016 and December 2020. Clinical parameters, including estimated glomerular filtration rate (GFR) decline, were compared between the corticosteroid and supportive treatment groups. Results Overall, 68.7% of patients received treatment with corticosteroids. The median estimated GFR decline was significantly lower in the steroid group compared to the controls {-0.65 (interquartile range [IQR] -3.45 to 7) vs. -5.75 (IQR -10.65 to -0.7) mL/min/1.73 m2/year, p = 0.025}. The slope of estimated GFR was also significantly different between the steroid and control groups in patients with a baseline GFR >50 mL/min/1.73 m2 (3.90 ± 11.42 vs. -9.31 ± 5.08 mL/min/1.73 m2/year, p = 0.011), mesangial hypercellularity M0 score (4.69 ± 11.37 vs. -2.63 ± 6.42 mL/min/1.73 m2/year, p = 0.049), and C0 score (2.48 ± 12.63 vs. -5.58 ± 8.4 mL/min/1.73 m2/year, p = 0.026). Additionally, rapid GFR decline (>5 mL/min/1.73 m2/year) occurred in 9 patients (19.6%) in the steroid group compared with 11 participants (52.4%) in the control group (p = 0.006). Conclusion Corticosteroid therapy, in addition to optimized RAAS inhibition, lowers the risk of kidney disease progression in patients with IgA nephropathy, particularly those with a baseline GFR >50 mL/min/1.73 m2 and those classified with Oxford scores M0 and C0.
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Affiliation(s)
- Bancha Satirapoj
- Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
| | - Thapana Chueaboonchai
- Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
| | - Naowanit Nata
- Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
| | - Ouppatham Supasyndh
- Division of Nephrology, Department of Medicine, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand
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Friedrich J, Bellmann M, Klank D, Porubsky S, Bergner R. Clinical and histological comparison of IgA nephritis and renal IgA vasculitis. Nephrol Dial Transplant 2024; 40:182-192. [PMID: 38908911 DOI: 10.1093/ndt/gfae143] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Indexed: 06/24/2024] Open
Abstract
BACKGROUND Immunoglobulin A (IgA) nephritis (IgAN) and renal IgA vasculitis (IgAV) show renal IgA deposits, but whether these two diseases are distinct entities or a spectrum of the same condition is under debate. In this study, we add perspective by contrasting the clinical course and histological presentation using the Oxford classification and the National Institutes of Health lupus nephritis activity index (LN-AI) and chronicity index (LN-CI) in IgAN and IgAV. METHODS In this single-centre, retrospective study, kidney biopsies of 163 adult patients with IgAN and 60 adult patients with IgAV were compared according to the Oxford MEST-C score, LN-AI and LN-CI. At the time of biopsy, clinical presentation was compared in terms of age, arterial hypertension, diabetes mellitus, extrarenal manifestations, estimated glomerular filtration rate, proteinuria and urine sediment. IgAV patients and all IgAN patients with crescents received immunosuppressive treatment. After biopsy, kidney function was followed until patients reached end-stage renal disease (ESRD) or they died. RESULTS The clinical course and kidney histology differ in IgAN and IgAV. IgAV patients showed more microhaematuria and nephritic sediment, while IgAN patients had a greater history of arterial hypertension, more proteinuria and a higher risk for ESRD. These clinical differences were associated with histological differences, as kidney biopsies of IgAN patients were characterized by glomerulosclerosis and tubular atrophy while kidney biopsies of IgAV patients were characterized by endocapillary hypercellularity and crescents. Overall, tubular atrophy and an LN-CI ≥4 were associated with a higher risk for ESRD in IgAN and IgAV. CONCLUSION Our study supports the notion that IgAN and IgAV follow distinct courses, suggesting that they require different treatment strategies. Moreover, we make a point that the Oxford classification and LN-CI can be useful in categorizing and predicting long-term prognosis not only in IgAN, but also in IgAV.
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Affiliation(s)
- Julian Friedrich
- Medical Department A, Community Hospital Ludwigshafen, Ludwigshafen am Rhein, Germany
| | - Maren Bellmann
- Medical Department A, Community Hospital Ludwigshafen, Ludwigshafen am Rhein, Germany
| | - David Klank
- Medical Department A, Community Hospital Ludwigshafen, Ludwigshafen am Rhein, Germany
| | - Stefan Porubsky
- Department of Pathology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
| | - Raoul Bergner
- Medical Department A, Community Hospital Ludwigshafen, Ludwigshafen am Rhein, Germany
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Abdullah, Pushkar D, Kaul A, Behera MR, Khurana M, Prasad N, Bhadauria DS, Patel MR, Yachha M, Kushwaha RS. The Outcomes of IgA Nephropathy With Nephrotic Syndrome: A Clinicopathological Study From Northern India. Cureus 2024; 16:e76307. [PMID: 39867081 PMCID: PMC11761544 DOI: 10.7759/cureus.76307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/21/2024] [Indexed: 01/28/2025] Open
Abstract
Introduction Nephrotic syndrome, an unusual clinical presentation of IgA nephropathy (IgAN), occurs only in a few cases. The data regarding its clinical characteristics and treatment outcomes are lacking. Material and methods In this retrospective analysis, we reviewed kidney biopsies conducted between January 2007 and December 2018. All patients with biopsy-proven IgAN and clinical presentation of nephrotic syndrome were included. Results Sixty-seven (11.9%) out of 560 patients with primary IgAN had nephrotic syndrome as the first clinical presentation. On MEST-C scoring, the baseline estimated glomerular filtration rate (eGFR) was significantly lower in the presence of segmental sclerosis (S1) (p=0.04) and >25% tubular atrophy/interstitial fibrosis (T1/2) (p=0.004). With immunosuppression, complete remission (CR), partial remission (PR), and no response (NR) occurred in 28 (41.8%), 32 (47.8%), and 7 (10.4%) patients, respectively. During the median follow-up of 190 weeks, the median absolute change in eGFR was significant between CR and NR groups (p=0.002), and PR and NR groups (p=0.02); however, it was not significant between CR and PR groups (p=0.14). In the CR, PR, and NR groups, 9, 15, and 7 patients had eGFR losses of ≥15 ml/min (p=0.004). No patient in the CR group, one in the PR group, and three in the NR group progressed to end-stage kidney disease (ESKD) (p=0.003). Further, none of the MEST-C scores correlated with the clinical outcome parameters. Conclusion Immunosuppression in treating IgAN accompanied by nephrotic syndrome helps in proteinuria remission. Achieving remission, whether complete or partial, delays disease progression and improves renal survival. Moreover, the baseline eGFR was significantly lower when S1 and T1/2 lesions were present in kidney biopsies.
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Affiliation(s)
- Abdullah
- Nephrology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, IND
| | | | - Anupma Kaul
- Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Manas R Behera
- Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Mudit Khurana
- Nephrology, Sarojini Naidu Medical College, Agra, IND
| | - Narayan Prasad
- Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | | | - Manas R Patel
- Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Monika Yachha
- Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
| | - Ravi S Kushwaha
- Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, IND
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Yu L, Zhang H, Wu Y. Association between different proportions of crescents and the progression of IgA nephropathy (IgAN): a systematic review and meta-analysis. BMC Nephrol 2024; 25:396. [PMID: 39501179 PMCID: PMC11536721 DOI: 10.1186/s12882-024-03839-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2024] [Accepted: 10/27/2024] [Indexed: 11/09/2024] Open
Abstract
BACKGROUND Immunoglobulin A nephropathy (IgAN) is a complex renal disease with a highly variable clinical course. Identifying reliable prognostic markers is crucial for risk stratification and treatment decisions. This study aimed to understand the influence of different proportions of crescents (Cs) on the progression of IgAN. METHODS Four databases (PubMed, Web of Science, Embase, and Cochrane Library) were searched until September 25, 2023. The study encompassed IgAN patients, focusing on kidney outcomes and end-stage kidney disease (ESKD). Statistical analysis included calculating hazard ratios (HR) for binary outcomes and examining publication bias. RESULTS The meta-analysis involved thirteen studies comprising 11,849 patients. For kidney outcomes, crescent formation may be linked to an elevated risk (HR = 2.01, 95%CI 1.40-2.87, P < 0.001). Furthermore, significantly increased risks of kidney outcomes were observed with a crescent proportion > 10 (HR = 1.8, 95%CI 1.32-2.45, P < 0.001) and > 25%(HR = 2.11, 95% CI 1.47-3.02, P < 0.001). Regarding ESKD, a proportion > 25% also displayed an elevated risk (HR = 1.70, 95% CI 1.18-2.44, P = 0.004). However, a proportion > 10% (including > 25%) did not show a significant association with ESKD (HR = 1.12, 95% CI 0.36-3.47, P = 0.842) versus less. CONCLUSIONS This systematic review and meta-analysis established a strong association between crescent proportions and the progression of IgAN. Higher proportions, notably exceeding 25%, were reliable prognostic markers, indicating a greater risk of adverse kidney outcomes and ESKD. These findings have significant clinical implications, offering the potential for more precise risk stratification in IgAN patients.
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Affiliation(s)
- Li Yu
- Traditional Chinese Medicine Department, Boao-Yiling Life Care Center, Qionghai, Hainan, China
| | - Hao Zhang
- Traditional Chinese Medicine Department, Boao-Yiling Life Care Center, Qionghai, Hainan, China
| | - Yunfeng Wu
- Traditional Chinese Medicine Department, Boao-Yiling Life Care Center, Qionghai, Hainan, China.
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Shukla M, Malhotra KP, Chandra A, Rao NS, Ahmad MK. Correlation of Serum Galactose-Deficient IgA1 and Oxford Class in Cases of IgA Nephropathy. Arch Pathol Lab Med 2024; 148:1244-1250. [PMID: 38289288 DOI: 10.5858/arpa.2023-0190-oa] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/20/2023] [Indexed: 10/29/2024]
Abstract
CONTEXT.— Galactose-deficient immunoglobulin A1 (Gd-IgA1) deposition in the renal mesangium plays a role in the pathogenesis of IgA nephropathy. OBJECTIVE.— To assess the serum Gd-IgA1 level in biopsy-proven IgA nephropathy cases at diagnosis and 3 months post treatment and its relation with histologic Oxford classification. DESIGN.— In this hospital-based prospective cohort study, 40 cases and 20 controls were enrolled. Serum samples of biopsy-proven IgA nephropathy cases collected on the day of biopsy and 3 months post treatment were evaluated. Solid-phase ELISA (enzyme-linked immunosorbent assay) was performed for assessment of Gd-IgA1 level. All renal biopsies were scored by using the Oxford classification (C-MEST score). The association of serum Gd-IgA1 levels with other established prognostic parameters was assessed. To estimate the prognostic value of markers, logistic regression analysis and Kruskal-Wallis ANOVA (analysis of variance) were used. RESULTS.— A significant difference was observed in the serum Gd-IgA1 level values in the IgA nephropathy cases and healthy controls (P = .001) at baseline. However, no significant correlation between serum Gd-IgA1 levels at baseline and 3 months of follow-up (P = .31) or between baseline levels and age, proteinuria, hematuria, or estimated glomerular filtration rate was noted. There was no significant correlation between C-MEST score and serum Gd-IgA1 levels at baseline (P > .05); however, the distribution of Gd-IgA1 at 3 months was found to differ significantly between different grades of S score (P = .008). CONCLUSIONS.— Serum Gd-IgA1 levels may be of utility in predicting disease progression in IgA nephropathy cases. Measurement of serum Gd-IgA1 levels for the diagnosis and prognosis of IgA nephropathy may preclude the need for invasive renal biopsies.
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Affiliation(s)
- Monika Shukla
- From the Departments of Pathology (Shukla, Malhotra) and Nephrology (Chandra, Rao), Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India
| | - Kiran Preet Malhotra
- From the Departments of Pathology (Shukla, Malhotra) and Nephrology (Chandra, Rao), Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India
| | - Abhilash Chandra
- From the Departments of Pathology (Shukla, Malhotra) and Nephrology (Chandra, Rao), Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India
| | - Namrata Sarvepalli Rao
- From the Departments of Pathology (Shukla, Malhotra) and Nephrology (Chandra, Rao), Dr. Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India
| | - Mohammad Kaleem Ahmad
- the Department of Biochemistry, King George's Medical University, Lucknow, India (Ahmad)
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Yang HT, Park TI, Kim YJ, Kim MS, Park SH, Lim JH, Kang YN, Kim D, Han MH. Significance of intrarenal vascular lesions in Ig A nephropathy prognosis. BMC Nephrol 2024; 25:355. [PMID: 39415107 PMCID: PMC11484363 DOI: 10.1186/s12882-024-03803-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Accepted: 10/07/2024] [Indexed: 10/18/2024] Open
Abstract
BACKGROUND Immunoglobulin A nephropathy (IgAN) is the predominant primary glomerulonephritis globally and remains a subject of active research with a focus on understanding its course and prognosis. Although vascular lesions are associated with IgAN, the current histopathological grading systems do not consider intrarenal vascular lesions when predicting patient prognosis. Therefore, this retrospective study conducted at Kyungpook National University Hospital between October 2016 and December 2021, aimed to elucidate the significance of intrarenal vascular lesions in IgAN by comparing the clinical data of patients with and without such lesions. METHODS Data of patients with biopsy-confirmed primary IgAN between October 2016 and June 2021 at Kyungpook National University Hospital (Daegu, South Korea) were collected, and their medical records were reviewed. All slides from these 138 cases were independently pathologically reviewed by two nephropathologists (Y. J. K. and M. S. K.) using light microscope. The vascular lesions included in this study were fibrous intimal thickening, arteriolar wall thickening, and arteriolar hyalinosis. All cases were reviewed according to the Oxford Classification of IgA Nephropathy (2016) and Haas classification. RESULTS Of the 138 patients, 88 exhibited at least one intrarenal vascular lesion. Patients with arteriolar wall thickening demonstrated a reduced estimated glomerular filtration rate (eGFR), elevated serum creatinine level and urine protein-to-creatinine ratio, an increased proportion of global glomerulosclerosis, and a higher histologic grade of interstitial fibrosis and tubular atrophy at the time of biopsy. CONCLUSION Arteriolar wall thickening in IgAN are associated with reduced eGFR and global glomerulosclerosis. Moreover, reduced eGFR and global glomerulosclerosis are correlated with the progression to end-stage renal disease. Although the direct correlation between vascular lesions and end-stage renal disease is not entirely clear, a marginally significant association (log-rank test, p = 0.06) was observed with arterial wall thickening. This study suggests the potential importance of vascular lesions in the prognosis of IgAN, encouraging further investigation using larger cohort studies to establish a clearer association.
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Affiliation(s)
- Hyeon Tae Yang
- Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - Tae In Park
- Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - Yong-Jin Kim
- Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - Mee-Seon Kim
- Department of Pathology, School of Dentistry, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - Sun-Hee Park
- Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - Jeong-Hoon Lim
- Division of Nephrology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - Yoo Na Kang
- Department of Forensic Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - DongJa Kim
- Department of Forensic Medicine, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea
| | - Man-Hoon Han
- Department of Pathology, School of Medicine, Kyungpook National University, Kyungpook National University Hospital, Daegu, 41944, Republic of Korea.
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10
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Choi YH, Kim JE, Lee RW, Kim B, Shin HC, Choe M, Kim Y, Park WY, Jin K, Han S, Paek JH, Kim K. Histopathological correlations of CT-based radiomics imaging biomarkers in native kidney biopsy. BMC Med Imaging 2024; 24:256. [PMID: 39333936 PMCID: PMC11428854 DOI: 10.1186/s12880-024-01434-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2024] [Accepted: 09/18/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND Kidney biopsy is the standard of care for the diagnosis of various kidney diseases. In particular, chronic histopathologic lesions, such as interstitial fibrosis and tubular atrophy, can provide prognostic information regarding chronic kidney disease progression. In this study, we aimed to evaluate historadiological correlations between CT-based radiomic features and chronic histologic changes in native kidney biopsies and to construct and validate a radiomics-based prediction model for chronicity grade. METHODS We included patients aged ≥ 18 years who underwent kidney biopsy and abdominal CT scan within a week before kidney biopsy. Left kidneys were three-dimensionally segmented using a deep learning model based on the 3D Swin UNEt Transformers architecture. We additionally defined isovolumic cortical regions of interest near the lower pole of the left kidneys. Shape, first-order, and high-order texture features were extracted after resampling and kernel normalization. Correlations and diagnostic metrics between extracted features and chronic histologic lesions were examined. A machine learning-based radiomic prediction model for moderate chronicity was developed and compared according to the segmented regions of interest (ROI). RESULTS Overall, moderate correlations with statistical significance (P < 0.05) were found between chronic histopathologic grade and top-ranked radiomic features. Total parenchymal features were more strongly correlated than cortical ROI features, and texture features were more highly ranked. However, conventional imaging markers, including kidney length, were poorly correlated. Top-ranked individual radiomic features had areas under receiver operating characteristic curves (AUCs) of 0.65 to 0.74. Developed radiomics models for moderate-to-severe chronicity achieved AUCs of 0.89 (95% confidence interval [CI] 0.75-0.99) and 0.74 (95% CI 0.52-0.93) for total parenchymal and cortical ROI features, respectively. CONCLUSION Significant historadiological correlations were identified between CT-based radiomic features and chronic histologic changes in native kidney biopsies. Our findings underscore the potential of CT-based radiomic features and their prediction model for the non-invasive assessment of kidney fibrosis.
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Affiliation(s)
- Yoon Ho Choi
- Department of Artificial Intelligence and Informatics, Mayo Clinic, Jacksonville, FL, USA
| | - Ji-Eun Kim
- Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University Hospital, Inha University College of Medicine, Incheon, Republic of Korea
| | - Ro Woon Lee
- Department of Radiology, Inha University College of Medicine, Incheon, Republic of Korea
| | - Byoungje Kim
- Department of Radiology, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Hyeong Chan Shin
- Department of Pathology, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Misun Choe
- Department of Pathology, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Yaerim Kim
- Division of Nephrology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Woo Yeong Park
- Division of Nephrology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Kyubok Jin
- Division of Nephrology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Seungyeup Han
- Division of Nephrology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Jin Hyuk Paek
- Division of Nephrology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Republic of Korea.
| | - Kipyo Kim
- Division of Nephrology and Hypertension, Department of Internal Medicine, Inha University Hospital, Inha University College of Medicine, Incheon, Republic of Korea.
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11
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Ghaddar M, Canney M, Barbour SJ. IgA Nephropathy: Epidemiology and Disease Risk Across the World. Semin Nephrol 2024; 44:151564. [PMID: 40082162 DOI: 10.1016/j.semnephrol.2025.151564] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/16/2025]
Abstract
Despite decades of research, our knowledge of the global epidemiology of IgA nephropathy remains limited. Much of what we know about IgA nephropathy incidence comes from biopsy registry studies that are subject to bias related to differences in screening programs, referral patterns, and access to healthcare. Fewer epidemiologic studies used an appropriate data infrastructure that includes a well-defined source population. Nonetheless, all these studies show considerable geographic variation in disease incidence with an increase from west to east and south to north across Eurasia. This pattern is partly explained by the distribution of genetic risk alleles in individuals of European and East Asian ancestry. Although historically thought to be an indolent disease, recent long-term follow-up studies have demonstrated an exceptionally high lifetime risk of kidney failure. The International IgA Nephropathy Prediction Tool, derived and validated in multiple ethnically diverse cohorts, has improved our ability to identify patients at high risk of progression who may benefit from therapies being tested in clinical trials. The earlier identification of high-risk patients, evaluation of novel risk factors, and accurate assessment of global disease burden require high-quality regional data infrastructures and broad collaborative efforts to ensure the impact of new treatments is maximized.
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Affiliation(s)
- Malak Ghaddar
- Division of Nephrology, University of British Columbia, Canada; British Columbia Renal Agency, Vancouver, British Columbia, Canada
| | - Mark Canney
- Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ontario, Canada
| | - Sean J Barbour
- Division of Nephrology, University of British Columbia, Canada; British Columbia Renal Agency, Vancouver, British Columbia, Canada.
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12
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Roberts ISD. Pathology of IgA nephropathy: A global perspective. Nephrology (Carlton) 2024; 29 Suppl 2:71-74. [PMID: 39327761 DOI: 10.1111/nep.14343] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 03/24/2024] [Accepted: 06/25/2024] [Indexed: 09/28/2024]
Abstract
Worldwide adoption of the Oxford Classification of IgA nephropathy (IgAN) has enabled comparison of pathology data from clinicopathological studies in different regions of the world. It is apparent that the frequency of Oxford Classification MEST-C scores shows geographic variations. These in part reflect differences in the stage of disease at diagnosis, criteria for performing biopsies and inclusion in clinical studies, and pathologist reporting practice. However, there appears to be a true geographic difference in the frequency of glomerular inflammation and crescents with a 2-3 fold greater proportion of patients showing these changes in East Asia when compared to Europe and North America. This indicates that the pathology of IgAN is influenced by genetic background. Geographic differences in the pathology of IgAN might underly the reported differences in clinical presentation and outcome in different regions of the world, and has important implications for clinical trials and patient management.
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Affiliation(s)
- Ian S D Roberts
- Department of Cellular Pathology, Oxford University Hospitals NHS FT, Oxford, UK
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13
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Cetinkaya H, Gursu M, Yazici H, Cebeci E, Eren N, Altiparmak MR, Akcay OF, Sahin G, Dheir H, Basturk T, Atilgan KG, Aydemir N, Turgutalp K, Yilmaz M, Sirali SK, Tatar E, Boz EG, Mirioglu S, Kazan S, Aydin E, Aydin Z, Turkmen K, Kutlay S, Karagoz F, Ogutmen MB, Ozturk S, Ozkan O, Yildiz N, Dincer T, Yasar E, Gok M, Turkmen A, Dede F, Derici U. Could mesangial C3 deposition be an independent prognostic marker in immunoglobulin A nephropathy? J Nephrol 2024; 37:923-932. [PMID: 37947938 DOI: 10.1007/s40620-023-01770-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2023] [Accepted: 08/18/2023] [Indexed: 11/12/2023]
Abstract
BACKGROUND Immunoglobulin A nephropathy (IgAN) is a common primary glomerulonephropathy. There is evidence that mesangial C3 deposition plays a role in the development of the disease. The aim of this study was to examine the effect of C3 deposition on the prognosis of IgAN patients. METHOD The study included 1135 patients with biopsy-confirmed IgAN from the database of the Turkish Nephrology Association Glomerular Diseases Working Group (TSN-GOLD). Patients were excluded from the study if they were aged < 18 or > 75 years or if C3 staining had not been performed in the immunofluorescent analysis. C3 deposition was defined as an immunofluorescence intensity of C3 ≥ 2 + within the mesangium. The primary endpoints were the development of end-stage renal disease, a 30% decrease in glomerular filtration rate compared to the basal value or an elevation in proteinuria to a nephrotic level (3.5 gr/day). RESULTS Mesangial C3 deposition was observed in 603 (53.1%) patients. No statistically significant difference was found at baseline between the groups with and without mesangial C3 deposition, as for age, sex, BMI, proteinuria level, or the presence of hypertension. In the follow-up period with a mean duration of 78 months, no significant difference was found between the two groups regarding the primary endpoints (p = 0.43). A significant correlation between C3 deposition and segmental glomerulosclerosis (S1) according to the Oxford MEST-C classification was found (p = 0.001). CONCLUSION Although a correlation was observed between mesangial C3 deposition and the S1 MEST-C classification, mesangial C3 deposition was not a prognostic factor in IgAN.
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Affiliation(s)
- Hakki Cetinkaya
- Department of Nephrology, Sultan Abdulhamid Han Training and Research Hospital, University of Health Sciences, Istanbul, Turkey.
| | - Meltem Gursu
- Medical Faculty, Nephrology, Bezmialem Vakif University, Istanbul, Turkey
| | - Halil Yazici
- Istanbul Medical Faculty, Nephrology, Istanbul University, Istanbul, Turkey
| | - Egemen Cebeci
- Department of Nephrology, Haseki Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Necmi Eren
- Medical Faculty, Nephrology, Kocaeli University, Izmit, Kocaeli, Turkey
| | | | | | - Gulizar Sahin
- Department of Nephrology, Sultan Abdulhamid Han Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Hamad Dheir
- Medical Faculty, Nephrology, Sakarya University, Adapazari, Sakarya, Turkey
| | - Taner Basturk
- Department of Nephrology, Sisli Hamidiye Etfal Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Kadir Gokhan Atilgan
- Department of Nephrology, Diskapi Training and Research Hospital, University of Health Sciences, Ankara, Turkey
| | - Nihal Aydemir
- Department of Nephrology, Ankara Bilkent City Hospital, University of Health Sciences, Ankara, Turkey
| | - Kenan Turgutalp
- Division of Nephrology, Department of Internal Medicine, Mersin University School of Medicine, Mersin, Turkey
| | - Murvet Yilmaz
- Department of Nephrology, Bakirkoy Dr. Sadi Konuk Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Semahat Karahisar Sirali
- Department of Nephrology, Ankara Training and Research Hospital, University of Health Sciences, Ankara, Turkey
| | - Erhan Tatar
- Department of Nephrology, Bozyaka Training and Research Hospital, University of Health Sciences, Izmir, Turkey
| | - Elif Gullulu Boz
- Division of Nephrology, Department of Internal Medicine, Uludag University School of Medicine, Bursa, Turkey
| | - Safak Mirioglu
- Medical Faculty, Nephrology, Bezmialem Vakif University, Istanbul, Turkey
| | - Sinan Kazan
- Department of Nephrology, Afyonkarahisar School of Medicine, University of Health Sciences, Afyonkarahisar, Turkey
| | - Emre Aydin
- Medical Faculty, Nephrology, Dicle University, Diyarbakir, Turkey
| | - Zeki Aydin
- Department of Nephrology, Darica Farabi Training and Research Hospital, University of Health Sciences, Darica, Kocaeli, Turkey
| | - Kultigin Turkmen
- Meram Medical Faculty, Nephrology, Necmettin Erbakan University, Konya, Turkey
| | - Sim Kutlay
- Medical Faculty, Nephrology, Ankara University, Ankara, Turkey
| | - Ferdi Karagoz
- Medical Faculty, Nephrology, Trakya University, Edirne, Turkey
| | - Melike Betul Ogutmen
- Department of Nephrology, Haydarpasa Numune Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Savas Ozturk
- Istanbul Medical Faculty, Nephrology, Istanbul University, Istanbul, Turkey
| | - Oktay Ozkan
- Department of Nephrology, Haseki Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Nuriye Yildiz
- Medical Faculty, Nephrology, Kocaeli University, Izmit, Kocaeli, Turkey
| | - Tamer Dincer
- Cerrahpasa Medical Faculty, Nephrology, Istanbul University, Istanbul, Turkey
| | - Emre Yasar
- Medical Faculty, Nephrology, Gazi University, Ankara, Turkey
| | - Mahmut Gok
- Department of Nephrology, Sultan Abdulhamid Han Training and Research Hospital, University of Health Sciences, Istanbul, Turkey
| | - Aydın Turkmen
- Istanbul Medical Faculty, Nephrology, Istanbul University, Istanbul, Turkey
| | - Fatih Dede
- Department of Nephrology, Ankara Bilkent City Hospital, University of Health Sciences, Ankara, Turkey
| | - Ulver Derici
- Medical Faculty, Nephrology, Gazi University, Ankara, Turkey
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14
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Nachiappa Ganesh R, Garcia G, Truong L. Monocytes and Macrophages in Kidney Disease and Homeostasis. Int J Mol Sci 2024; 25:3763. [PMID: 38612574 PMCID: PMC11012230 DOI: 10.3390/ijms25073763] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Revised: 03/19/2024] [Accepted: 03/25/2024] [Indexed: 04/14/2024] Open
Abstract
The monocyte-macrophage lineage of inflammatory cells is characterized by significant morphologic and functional plasticity. Macrophages have broad M1 and M2 phenotype subgroups with distinctive functions and dual reno-toxic and reno-protective effects. Macrophages are a major contributor to injury in immune-complex-mediated, as well as pauci-immune, glomerulonephritis. Macrophages are also implicated in tubulointerstitial and vascular disease, though there have not been many human studies. Patrolling monocytes in the intravascular compartment have been reported in auto-immune injury in the renal parenchyma, manifesting as acute kidney injury. Insights into the pathogenetic roles of macrophages in renal disease suggest potentially novel therapeutic and prognostic biomarkers and targeted therapy. This review provides a concise overview of the macrophage-induced pathogenetic mechanism as a background for the latest findings about macrophages' roles in different renal compartments and common renal diseases.
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Affiliation(s)
- Rajesh Nachiappa Ganesh
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USA;
- Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry 605006, India
| | - Gabriela Garcia
- Department of Medicine, Renal Division, University of Colorado, Anschutz Medical Campus, Aurora, CO 605006, USA;
| | - Luan Truong
- Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX 77030, USA;
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15
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Chen CH, Wu MJ, Tsai SF. Validating the association of Oxford classification and renal function deterioration among Taiwanese individuals with Immunoglobulin A nephropathy. Sci Rep 2023; 13:21904. [PMID: 38082065 PMCID: PMC10713632 DOI: 10.1038/s41598-023-49331-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2023] [Accepted: 12/07/2023] [Indexed: 12/18/2023] Open
Abstract
Validation of the Oxford classification (MEST and MEST-C) for Immunoglobulin A nephropathy (IgAN) in the Taiwanese population is lacking. Our study aimed to validate this classification and assess individual lesion impact. We conducted a retrospective cohort study at Taichung Veterans General Hospital, Taiwan (Jan 2011-Jul 2023). Composite renal outcomes were evaluated using clinical conditions and estimated glomerular filtration rate (eGFR). We used Kaplan-Meier, univariable/multivariable logistic regression and ROC curves. Subgroup analysis considered eGFR < or ≥ 30.0 ml/min/1.73 m2. In 366 renal biopsies, serum creatinine was 1.34 mg/dl, eGFR 53.8 ml/min/1.73 m2, urine protein-creatinine ratio 1159 mg/g. T1/T2 lesions had lowest baseline eGFR (39.6/11.5 ml/min/1.73 m2), correlating with poorest renal survival (median survival 54.7/34.4 months). Univariable analysis linked all individual variables to worse renal outcomes. Multivariable analysis (MEST/MEST-C) showed only T1/T2 linked to worse outcomes. T score had highest predictive power (AUC 0.728, sensitivity 60.2%, specificity 83.6%), with MEST having high AUC (0.758). No extra predictive power was seen transitioning MEST to MEST-C. Subgroup analysis (eGFR < 30.0 ml/min/1.73 m2) associated C1 with improved renal outcomes (odds ratio 0.14, 95% CI 0.03-0.65). T lesion correlated with worse outcomes across subgroups. The T lesion consistently correlated with worse renal outcomes across all groups and baseline statuses. Integrating the C lesion into the transition from MEST to MEST-C did not enhance predictive power. Importantly, the C1 lesion was linked to improved renal outcomes in the eGFR < 30.0 ml/min/1.73 m2 subgroup, likely due to treatment effects.
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Affiliation(s)
- Cheng-Hsu Chen
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, 160, Sec. 3, Taiwan Boulevard, Taichung, 407, Taiwan
- Department of Life Science, Tunghai University, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
- Ph. D. Program in Tissue Engineering and Regenerative Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Ming-Ju Wu
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, 160, Sec. 3, Taiwan Boulevard, Taichung, 407, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Shang-Feng Tsai
- Division of Nephrology, Department of Internal Medicine, Taichung Veterans General Hospital, 160, Sec. 3, Taiwan Boulevard, Taichung, 407, Taiwan.
- Department of Life Science, Tunghai University, Taichung, Taiwan.
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan.
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16
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Liang P, Yuan G, Li S, Peng Y, Xu C, Benkert T, Hu D, Han M, Li Z. Noninvasive Assessment of the Renal Function, Oxford Classification and Prognostic Risk Stratification of IgAN by Using Intravoxel Incoherent Motion Diffusion-Weighted Imaging and Blood Oxygenation Level-Dependent MRI. J Magn Reson Imaging 2023; 58:879-891. [PMID: 36527202 DOI: 10.1002/jmri.28565] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/29/2022] [Accepted: 12/01/2022] [Indexed: 12/23/2022] Open
Abstract
BACKGROUND Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Oxford classification including mesangial hypercellularity (M), endothelial hypercellularity (E), segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T), and crescent (C) were recommended to predict the prognosis of IgAN. PURPOSE To explore whether multiparametric magnetic resonance imaging (MRI) can be applied to assess the renal function, Oxford classification, and risk of progression to end-stage kidney disease within 5 years of IgAN. STUDY TYPE Prospective. POPULATION A total of 46 patients with pathologically confirmed IgAN and 20 healthy volunteers. FIELD STRENGTH/SEQUENCE A 3-T, blood oxygenation level-dependent (BOLD)-MRI, intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI). ASSESSMENT Two radiologists measured the cortex and medulla T2*, apparent diffusion coefficient (ADC), true diffusion (Dt), pseudo-diffusion (Dp), perfusion fraction (fp). All participants were divided into three groups: group 1, healthy volunteers; group 2, patients with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 ; group 3, patients with eGFR <60 mL/min/1.73 m2 . Or two groups: group A, 5-year risk scores ≤10% and group B, 5-year risk scores >10%. STATISTICAL TESTS Intraclass correlation coefficient, one-way analysis of variance, least-significant difference, Student's t-test, Pearson product-moment correlation, Spearman's rank correlation, and receiver operating characteristics (ROC) with the area under the curve (AUC). A P value <0.05 was considered statistically significant. RESULTS Except for cortical Dp, all other MRI parameters showed significant differences between group 1 and group 2. None of the MRI parameters showed a significant correlation with M, E, or C scores. Cortical T2*, Dt, fp, and medullary Dt and fp showed low-to-moderate significant correlations with S scores. Except for cortical and medullary Dp, all other MRI parameters were significantly correlated with T scores. Cortical Dt showed the largest AUC for differentiating group A from group B (AUC = 0.927) and T0 from T1/T2 (AUC = 0.963). DATA CONCLUSION Imaging by IVIM-DWI and BOLD-MRI could facilitate noninvasive assessment of the renal function, Oxford classification, and prognostic risk of IgAN patients. EVIDENCE LEVEL 2. TECHNICAL EFFICACY Stage 3.
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Affiliation(s)
- Ping Liang
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Guanjie Yuan
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Shichao Li
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Yang Peng
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Chuou Xu
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Thomas Benkert
- MR Application Predevelopment, Siemens Healthcare Gmbh, Erlangen, Germany
| | - Daoyu Hu
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Min Han
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
| | - Zhen Li
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China
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Lv Y, Fu R, Peng XJ, Wang Y, Yin TT, Deng YQ. Comparative study on clinicopathological features and prognosis of IgA vasculitis nephritis and IgA nephropathy in children. BMC Pediatr 2023; 23:423. [PMID: 37620917 PMCID: PMC10464207 DOI: 10.1186/s12887-023-04243-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Accepted: 08/11/2023] [Indexed: 08/26/2023] Open
Abstract
BACKGROUND IgA vasculitis nephritis (IgAVN) and IgA nephropathy (IgAN) share several clinical and pathological characteristics, though distinctions also exist. Their interrelation, however, remains undefined. This study investigates the clinicopathological divergences and prognostic disparities in pediatric patients with IgAVN and IgAN. METHODS Our study encompasses 809 pediatric patients with IgAVN and 236 with IgAN, all of whom underwent kidney biopsy. We utilized the Semiquantitative Classification (SQC) scoring system to juxtapose the pathologies of the two conditions, and performed a COX regression analysis to examine factors influencing their prognoses. RESULTS Both patient groups demonstrated a predominance of males. A seasonality was observed, with a higher incidence of IgAN in the summer, and IgAVN in the fall (P < 0.0001). Patients with IgAN exhibited more severe tubulointerstitial injury, higher chronicity index, and total biopsy scores compared to those with IgAVN (P < 0.0001). Mesangial deposition intensity of complement C3, and the rate of pure IgA deposition, were found to be greater in patients with IgAVN compared to those with IgAN (P < 0.0001). The intensity of IgA deposition was also significantly higher in IgAVN patients (P = 0.003). IgAVN demonstrated a superior prognosis, with a higher rate of kidney remission (P < 0.0001). COX regression analysis indicated that interstitial fibrosis, as identified in the SQC pathology system, was associated with the prognosis of both conditions. Furthermore, the findings suggest that IgA deposition levels (IgA + + and IgA + + +) could potentially influence the prognosis of IgAVN. CONCLUSIONS Compared to IgAVN, IgAN manifests more severely with regard to renal impairment, interstitial damage, and prognosis. The disparities in immune complex deposition levels and locations within the kidneys support the hypothesis of IgAVN and IgAN as distinct diseases. Interstitial fibrosis may serve as a key pathological indicator within the SQC system associated with kidney prognosis in children with IgAVN and IgAN. The degree of IgA deposition could also be linked with the prognosis of IgAVN.
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Affiliation(s)
- Yan Lv
- Department of Nephrology, Jiangxi Provincial Children's Hospital, Nanchang, China
- Nanchang University, Nanchang, Jiangxi Province, China
| | - Rui Fu
- Department of Nephrology, Jiangxi Provincial Children's Hospital, Nanchang, China
| | - Xiao-Jie Peng
- Department of Nephrology, Jiangxi Provincial Children's Hospital, Nanchang, China.
| | - Ying Wang
- Nanchang University, Nanchang, Jiangxi Province, China
| | - Ting-Ting Yin
- Nanchang University, Nanchang, Jiangxi Province, China
| | - Yan-Qing Deng
- Nanchang University, Nanchang, Jiangxi Province, China
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18
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Liang PI, Lin WC, Wen MC, Huang SC, Fang PW, Chuang HW, Lin YJ, Chien HP, Chen HD, Chen TD. Learning more from the inter-rater reliability of interstitial fibrosis assessment beyond just a statistic. Sci Rep 2023; 13:13260. [PMID: 37582967 PMCID: PMC10427633 DOI: 10.1038/s41598-023-40221-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Accepted: 08/07/2023] [Indexed: 08/17/2023] Open
Abstract
Interstitial fibrosis assessment by renal pathologists lacks good agreement, and we aimed to investigate its hidden properties and infer possible clinical impact. Fifty kidney biopsies were assessed by 9 renal pathologists and evaluated by intraclass correlation coefficients (ICCs) and kappa statistics. Probabilities of pathologists' assessments that would deviate far from true values were derived from quadratic regression and multilayer perceptron nonlinear regression. Likely causes of variation in interstitial fibrosis assessment were investigated. Possible misclassification rates were inferred on reported large cohorts. We found inter-rater reliabilities ranged from poor to good (ICCs 0.48 to 0.90), and pathologists' assessments had the worst agreements when the extent of interstitial fibrosis was moderate. 33.5% of pathologists' assessments were expected to deviate far from the true values. Variation in interstitial fibrosis assessment was found to be correlated with variation in interstitial inflammation assessment (r2 = 32.1%). Taking IgA nephropathy as an example, the Oxford T scores for interstitial fibrosis were expected to be misclassified in 21.9% of patients. This study demonstrated the complexity of the inter-rater reliability of interstitial fibrosis assessment, and our proposed approaches discovered previously unknown properties in pathologists' practice and inferred a possible clinical impact on patients.
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Affiliation(s)
- Peir-In Liang
- Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wei-Chou Lin
- Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan
| | - Mei-Chin Wen
- Department of Pathology, China Medical University Hsinchu Hospital, Hsinchu, Taiwan
| | - Shun-Chen Huang
- Department of Anatomic Pathology, Chang Gung Memorial Hospital Kaohsiung Branch, Kaohsiung, Taiwan
| | - Pei-Wei Fang
- Department of Pathology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, New Taipei City, Taiwan
| | - Hao-Wen Chuang
- Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Yi-Jia Lin
- Department of Pathology, Tri-service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Hui-Ping Chien
- Department of Pathology and Laboratory Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
| | - Huan-Da Chen
- Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Tai-Di Chen
- Department of Anatomic Pathology, Chang Gung Memorial Hospital Linkou Main Branch, Taoyuan, Taiwan.
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19
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Howie AJ, Lalayiannis AD. Systematic Review of the Oxford Classification of IgA Nephropathy: Reproducibility and Prognostic Value. KIDNEY360 2023; 4:1103-1111. [PMID: 37357346 PMCID: PMC10476683 DOI: 10.34067/kid.0000000000000195] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Accepted: 06/06/2023] [Indexed: 06/27/2023]
Abstract
Key Points The Oxford classification of IgA nephropathy defined five features scored subjectively in renal biopsies, identified by the initials MESTC. Two large studies with independent observers showed reproducibility was moderate for T, moderate or poor for M and S, and poor for E and C. In multivariate analyses including clinical features, T was related to 58% of outcomes, with no correlation of MESTC with 24% of outcomes. Background The Oxford classification of IgA nephropathy defined five prognostic features scored subjectively in renal biopsies: mesangial cellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T), and (fibro)cellular crescents (C). Pathological scoring systems should be reproducible and have prognostic value independently of clinical features. Reproducibility of the classification was not previously investigated in a systematic review, and the most recent systematic reviews of prognostic value were in 2017. Methods This systematic review followed PRISMA 2020 guidelines. MEDLINE, PUBMED, and EMBASE databases were searched using the terms “IgA nephropathy” and “Oxford.” Eligible papers applied the classification and mentioned statistical analysis of interobserver reproducibility and/or included multivariate analysis of outcomes related to individual Oxford scores and clinical features, including treatment with corticosteroids or other immunosuppressive drugs. Results There were 99 suitable papers before September 23, 2022. Of 12 papers that mentioned reproducibility, only six reported statistics for MEST/MESTC scoring. Four of these were small studies and/or had observers at the same institution. These were considered less representative of application of the classification than two large studies with independent observers, in which agreement was moderate for T, either moderate or poor for M and S, and poor for E and C. In 92 papers with 125 multivariate analyses of various outcomes, the commonest Oxford element associated with outcomes was T (73 of 125, 58%), with no correlation of any element with outcomes in 30 analyses (24%). Treatment with immunosuppression was often related to scores, particularly C and E, without consistent relations between Oxford scores and outcomes in immunosuppressed patients. Conclusions This systematic review showed limitations of the Oxford classification in practice, particularly the moderate or poor reproducibility of scores. T was the Oxford score most often related to clinical outcomes, but even this was not consistently reliable as a prognostic indicator.
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Affiliation(s)
- Alexander J. Howie
- Department of Pathology, University College London, London, United Kingdom
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20
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Liu Y, Gong Y, Xu G. The role of mononuclear phagocyte system in IgA nephropathy: pathogenesis and prognosis. Front Immunol 2023; 14:1192941. [PMID: 37529043 PMCID: PMC10390225 DOI: 10.3389/fimmu.2023.1192941] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2023] [Accepted: 06/12/2023] [Indexed: 08/03/2023] Open
Abstract
Although the "multiple hits" theory is a widely accepted pathogenesis in IgA nephropathy (IgAN), increasing evidence suggests that the mononuclear/macrophage system plays important roles in the progression of IgAN; however, the exact mechanism is unclear. In the present study, we explored 1,067 patients in 15 studies and found that the number of macrophages per glomerulus was positively related with the degree of hematuria, and the macrophages in the glomeruli were mainly related to mesangial proliferation (M) in renal biopsy. In the tubulointerstitium, macrophages were significantly paralleled to tubulointerstitial α-SMA and NF-kB expression, tubulointerstitial lesion, tubule atrophy/interstitial fibrosis (T), and segmental glomerulosclerosis (S). In the glomeruli and tubulointerstitium, M1 accounted for 85.41% in the M classification according to the Oxford MEST-C, while in the blood, M1 accounted for 100%, and the patients with low CD89+ monocyte mean fluorescence intensity displayed more severe pathological characteristics (S1 and T1-2) and clinical symptoms. M1 (CD80+) macrophages were associated with proinflammation in the acute phase; however, M2 (CD163+) macrophages participated in tissue repair and remodeling, which correlated with chronic inflammation. In the glomeruli, M2 macrophages activated glomerular matrix expansion by secreting cytokines such as IL-10 and tumor necrosis factor-β (TGF-β), and M0 (CD68+) macrophages stimulated glomerular hypercellularity. In the tubulointerstitium, M2 macrophages played pivotal roles in renal fibrosis and sclerosis. It is assumed that macrophages acted as antigen-presenting cells to activate T cells and released diverse cytokines to stimulate an inflammatory response. Macrophages infiltrating glomeruli destroy the integrity of podocytes through the mesangio-podocytic-tubular crosstalk as well as the injury of the tubule.
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Affiliation(s)
- Yiwen Liu
- Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Second Clinical Medical College of Nanchang University, Nanchang, Jiangxi, China
| | - Yan Gong
- Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Gaosi Xu
- Department of Nephrology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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21
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Zhang X, Luo F, Chen R, Shen J, Liu X, Shi Y, Yang Q, Huang T, Li H, Hu Y, Wan Q, Chen C, Jia N, Cao Y, Li Y, Zhao H, Su L, Gao P, Xu X, Nie S, Hou FF. Use of Histologic Parameters to Predict Glomerular Disease Progression: Findings From the China Kidney Biopsy Cohort Study. Am J Kidney Dis 2023; 81:416-424.e1. [PMID: 36252881 DOI: 10.1053/j.ajkd.2022.08.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 08/29/2022] [Indexed: 11/24/2022]
Abstract
RATIONALE & OBJECTIVE Challenges in achieving valid risk prediction and stratification impede treatment decisions and clinical research design for patients with glomerular diseases. This study evaluated whether chronic histologic changes, when complementing other clinical data, improved the prediction of disease outcomes across a diverse group of glomerular diseases. STUDY DESIGN Multicenter retrospective cohort study. SETTING & PARTICIPANTS 4,982 patients with biopsy-proven glomerular disease who underwent native biopsy at 8 tertiary care hospitals across China in 2004-2020. NEW PREDICTORS & ESTABLISHED PREDICTORS Chronicity scores depicted as 4 categories of histological chronic change, as well as baseline clinical and demographic variables. OUTCOME Progression of glomerular disease defined as a composite of kidney failure or a ≥40% decrease in estimated glomerular filtration rate from the measurement at the time of biopsy. ANALYTICAL APPROACH Multivariable Cox proportional hazard models. The performance of predictive models was evaluated by C statistic, time-dependent area under the receiver operating characteristic curve (AUROC), net reclassification index, integrated discrimination index, and calibration plots. RESULTS The derivation and validation cohorts included 3,488 and 1,494 patients, respectively. During a median of 31 months of follow-up, a total of 444 (8.9%) patients had disease progression in the 2 cohorts. For prediction of the 2-year risk of disease progression, the AUROC of the model combining chronicity score and the Kidney Failure Risk Equation (KFRE) in the validation cohort was 0.76 (95% CI, 0.65-0.87); in comparison with the KFRE model (AUROC, 0.68 [95% CI, 0.56-0.79]), the combined model was significantly better (P = 0.04). The combined model also had a better fit, with a lower Akaike information criterion and a significant improvement in reclassification as assessed by the integrated discrimination improvements and net reclassification improvements. Similar improvements in predictive performance were observed in subgroup and sensitivity analyses. LIMITATIONS Selection bias, relatively short follow-up, lack of external validation. CONCLUSIONS Adding histologic chronicity scores to the KFRE model improved the prediction of kidney disease progression at the time of kidney biopsy in patients with glomerular diseases. PLAIN-LANGUAGE SUMMARY Risk prediction and stratification remain big challenges for treatment decisions and clinical research design for patients with glomerular diseases. The extent of chronic changes is an important component of kidney biopsy evaluations in glomerular disease. In this large multicenter cohort including 4,982 Chinese adults undergoing native kidney biopsy, we evaluated whether histologic chronicity scores, when added to clinical data, could improve the prediction of disease prognosis for a diverse set of glomerular diseases. We observed that adding histologic chronicity scores to the kidney failure risk equation improved the prediction of kidney disease progression at the time of kidney biopsy in patients with glomerular diseases.
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Affiliation(s)
- Xiaodong Zhang
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University
| | - Fan Luo
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University
| | - Ruixuan Chen
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University
| | - Jie Shen
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University
| | | | - Yongjun Shi
- Department of Nephrology, Huizhou Municipal Central Hospital, Sun Yat-Sen University, Huizhou
| | - Qiongqiong Yang
- Department of Nephrology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou
| | - Ting Huang
- Department of Nephrology, The First Affiliated Hospital of University of Science and Technology of China, Anhui
| | - Hua Li
- Department of Nephrology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
| | - Ying Hu
- Department of Nephrology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou
| | - Qijun Wan
- Department of Nephrology, The Second People's Hospital of Shenzhen, Shenzhen University, Shenzhen
| | - Chunbo Chen
- Department of Critical Care Medicine, Maoming People's Hospital, Southern Medical University, Maoming, China
| | - Nan Jia
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University
| | - Yue Cao
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University
| | - Yanqin Li
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University
| | - Hao Zhao
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University
| | - Licong Su
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University
| | - Peiyan Gao
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University
| | - Xin Xu
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University
| | - Sheng Nie
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University.
| | - Fan Fan Hou
- National Clinical Research Center for Kidney Disease, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University.
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22
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Structural modeling for Oxford histological classifications of immunoglobulin A nephropathy. PLoS One 2022; 17:e0268731. [PMID: 36084046 PMCID: PMC9462802 DOI: 10.1371/journal.pone.0268731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 08/16/2022] [Indexed: 12/03/2022] Open
Abstract
In immunoglobulin A nephropathy (IgAN), Cox regression analysis can select independent prognostic variables for renal functional decline (RFD). However, the correlation of the selected histological variables with clinical and/or treatment variables is unknown, thereby making histology-based treatment decisions unreliable. We prospectively followed 946 Japanese patients with IgAN for a median of 66 mo. and applied structural equation modeling (SEM) to identify direct and indirect effects of histological variables on RFD as a regression line of estimated glomerular filtration rate (eGFR) via clinical variables including amount of proteinuria, eGFR, mean arterial pressure (MAP) at biopsy, and treatment variables such as steroid therapy with/without tonsillectomy (ST) and renin–angiotensin system blocker (RASB). Multi-layered correlations between the variables and RFD were identified by multivariate linear regression analysis and the model’s goodness of fit was confirmed. Only tubular atrophy/interstitial fibrosis (T) had an accelerative direct effect on RFD, while endocapillary hypercellularity and active crescent (C) had an attenuating indirect effect via ST. Segmental sclerosis (S) had an attenuating indirect effect via eGFR and mesangial hypercellularity (M) had accelerative indirect effect for RFD via proteinuria. Moreover, M and C had accelerative indirect effect via proteinuria, which can be controlled by ST. However, both T and S had additional indirect accelerative effects via eGFR or MAP at biopsy, which cannot be controlled by ST. SEM identified a systemic path links between histological variables and RFD via dependent clinical and/or treatment variables. These findings lead to clinically applicable novel methodologies that can contribute to predict treatment outcomes using the Oxford classifications.
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23
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Trimarchi H, Haas M, Coppo R. Crescents and IgA Nephropathy: A Delicate Marriage. J Clin Med 2022; 11:jcm11133569. [PMID: 35806856 PMCID: PMC9267724 DOI: 10.3390/jcm11133569] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 06/06/2022] [Accepted: 06/18/2022] [Indexed: 12/20/2022] Open
Abstract
IgA nephropathy (IgAN) is a progressive disease with great variability in the clinical course. Among the clinical and pathologic features contributing to variable outcomes, the presence of crescents has attracted particular interest as a distinct pathological feature associated with severity. Several uncontrolled observations have led to the general thought that the presence and extent of crescents was a prognostic indicator associated with poor outcomes. However, KDIGO 2021 guidelines concluded that either the presence or the relative number of crescents should not be used to determine the progression of IgAN nor should they suggest the choice of immunosuppression. Our aim is to report and discuss recent data on the debated issue of the value of active (cellular and fibrocellular) crescents in the pathogenesis and clinical progression of IgAN, their predictive value, and the impact of immunosuppression on renal function. We conclude that the value of crescents should not be disregarded, although this feature does not have an independent predictive value for progression in IgAN, particularly when considering immunosuppressed patients. An integrated overall evaluation of crescents with other active MEST scores, clinical data, and novel biomarkers must be considered in achieving a personalized therapeutic approach to IgAN patients.
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Affiliation(s)
- Hernán Trimarchi
- Nephrology Service, Hospital Britanico de Buenos Aires, Buenos Aires C1280 AEB, Argentina;
| | - Mark Haas
- Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
- Correspondence: ; Tel.: +1-310-248-6695; Fax: +1-310-423-5881
| | - Rosanna Coppo
- Fondazione Ricerca Molinette, Regina Margherita Hospital, 10126 Turin, Italy;
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Joo YS, Kim HW, Baek CH, Park JT, Lee H, Lim BJ, Yoo TH, Moon KC, Chin HJ, Kang SW, Han SH. External validation of the International Prediction Tool in Korean patients with immunoglobulin A nephropathy. Kidney Res Clin Pract 2022; 41:556-566. [PMID: 35545218 PMCID: PMC9576458 DOI: 10.23876/j.krcp.22.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2022] [Accepted: 03/02/2022] [Indexed: 11/11/2022] Open
Abstract
Background The International IgA Nephropathy Prediction Tool (International IgA Nephropathy Prediction Tool) has been recently developed to estimate the progression risk of immunoglobulin A nephropathy (IgAN). This study aimed to evaluate the clinical performance of this prediction tool in a large IgAN cohort in Korea. Methods The study cohort was comprised of 2,064 patients with biopsy-proven IgAN from four medical centers between March 2012 and September 2021. We calculated the predicted risk for each patient. The primary outcome was occurrence of a 50% decline in estimated glomerular filtration rate (eGFR) from the time of biopsy or end-stage kidney disease. The model performance was evaluated for discrimination, calibration, and reclassification. We also constructed and tested an additional model with a new coefficient for the Korean race. Results During a median follow-up period of 3.8 years (interquartile range, 1.8–6.6 years), 363 patients developed the primary outcome. The two prediction models exhibited good discrimination power, with a C-statistic of 0.81. The two models generally underestimated the risk of the primary outcome, with lesser underestimation for the model with race. The model with race showed better performance in reclassification compared to the model without race (net reclassification index, 0.13). The updated model with the Korean coefficient showed good agreement between predicted risk and observed outcome. Conclusion In Korean IgAN patients, International IgA Nephropathy Prediction Tool had good discrimination power but underestimated the risk of progression. The updated model with the Korean coefficient showed acceptable calibration and warrants external validation.
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Affiliation(s)
- Young Su Joo
- Department of Internal Medicine and Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea
- Division of Nephrology, Department of Internal Medicine, Yongin Severance Hospital, Yonsei University College of Medicine, Yongin, Republic of Korea
| | - Hyung Woo Kim
- Department of Internal Medicine and Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chung Hee Baek
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Jung Tak Park
- Department of Internal Medicine and Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hajeong Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Beom Jin Lim
- Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Tae-Hyun Yoo
- Department of Internal Medicine and Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kyung Chul Moon
- Department of Pathology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Ho Jun Chin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
| | - Shin-Wook Kang
- Department of Internal Medicine and Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Seung Hyeok Han
- Department of Internal Medicine and Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, Republic of Korea
- Correspondence: Seung Hyeok Han Department of Internal Medicine and Institute of Kidney Disease Research, Yonsei University College of Medicine, Seoul, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Republic of Korea. E-mail:
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25
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Schena FP, Tripepi G, Rossini M, Abbrescia DI, Manno C. Randomized clinical study to evaluate the effect of personalized therapy on patients with immunoglobulin A nephropathy. Clin Kidney J 2022; 15:895-902. [PMID: 35498888 PMCID: PMC9050523 DOI: 10.1093/ckj/sfab263] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Indexed: 11/17/2022] Open
Abstract
Background Randomized controlled trials (RCTs) have been conducted, stratifying idiopathic immunoglobulin A nephropathy (IgAN) patients based on the laboratory findings [serum creatinine, estimated glomerular filtration rate (eGFR) and daily proteinuria]. In contrast, data from kidney biopsy have been used only for clinical diagnosis. Therefore, IgAN patients with active or chronic renal lesions have been receiving the same therapy in experimental and control arms of randomized clinical trials (RCTs). Methods Our clinical study of IgAN (CLIgAN) is a multicentre, prospective, controlled and open-label RCT based on patients' stratification at the time of their kidney biopsy. We will consider, first, the type of renal lesions, followed by serum creatinine values, eGFR and proteinuria. Primary and secondary endpoints will be monitored. Then, we will determine whether personalized therapy can slow the decline of renal function and delay end-stage kidney disease. Results We will enrol 132 IgAN patients with active renal lesions (66 patients per arm) in the first RCT (ACIgAN). They will receive corticosteroids combined with renin-angiotensin system blockers (RASBs) or only RASBs. A total of 294 IgAN patients with chronic or moderate renal lesions at high or very high risk of chronic kidney disease (147 patients per arm) will be enrolled in the second RCT (CHRONIgAN), in which they will receive dapagliflozin, a sodium-glucose cotransporter 2 inhibitor, combined with RASBs, or RASBs alone. Conclusion Using this approach, we hypothesize that patients could receive personalized therapy based on renal lesions to ensure that the right drug gets to the right patient at the right time.
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Affiliation(s)
- Francesco P Schena
- Department of Emergency and Organ Transplantation, University of
Bari, Bari, Italy
- Fondazione Schena, Policlinic, Bari,
Italy
| | - Giovanni Tripepi
- CNR-IFC, Institute of Clinical Physiology, Reggio Calabria,
Italy
| | | | | | - Carlo Manno
- Department of Emergency and Organ Transplantation, University of
Bari, Bari, Italy
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Li J, Guo L, Shi S, Zhou X, Zhu L, Liu L, Lv J, Zhang H. The Role of Complement in Microangiopathic Lesions of IgA Nephropathy. Kidney Int Rep 2022; 7:1219-1228. [PMID: 35685318 PMCID: PMC9171706 DOI: 10.1016/j.ekir.2022.03.028] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2021] [Revised: 03/08/2022] [Accepted: 03/28/2022] [Indexed: 11/26/2022] Open
Abstract
Introduction Methods Results Conclusion
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Bhat MA, Sofi IS, Sheikh RY, Wani I. Incidence, demographic, biochemical, and clinicopathological profile of primary IgAN in a tertiary care center from Northern India. THE EGYPTIAN JOURNAL OF INTERNAL MEDICINE 2022. [DOI: 10.1186/s43162-022-00109-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Abstract
Background
Primary IgA nephropathy (IgAN) has variable distribution and clinicopathological spectrum throughout the world. We report the incidence, demographic, and clinicopathological profile of primary IgAN from a tertiary care center in Northern India.
Methods
This is a single-center, prospective, observational study conducted at Sheri- Kashmir Institute of Medical Sciences, J&K, India, from January 2015 to December 2018. The study was approved by the hospital ethical committee.
Results
A total of 106 patients were included in this study, accounting for 19% (106/558) of all native kidney biopsies done during the period from January 2015 till December 2018. Males and females accounted for 60.4% (64/106) and 39.6% (42/106), respectively, with a ratio of 1.5:1. The mean age was 31.37±11.60 years. Edema and hypertension were the most common presenting symptoms and signs, seen in 69 (65.1%) and 72 (67.9%) patients, respectively. The baseline 24-h urine protein excretion was 2.32 ±1.34 g, Nephrotic range proteinuria (≥3.5g/day) was seen in 23/106 (21.7%). Average serum creatinine was 1.6±0.80 mg/dl and estimated glomerular filtration rate using CKD-EPI was <60 ml/min/1.73 m2 in 48.1% of patients (51/106). In patients with < 1 g proteinuria, 36.8% had E1, 78.9% had S1, 36.8% had T1, and 42.1% had T2 lesions.
Conclusions
IgAN is common in North India and has a more severe histopathological presentation, characterized by extensive sclerosis and tubulointerstitial fibrosis. Renal dysfunction and nephrotic range proteinuria are common. Hypertension, low eGFR, and proteinuria correlate with the presence of segmental scarring, endocapillary hypercellularity, and IFTA. Screening of asymptomatic individuals might help in early diagnosis and long-term preservation of renal function.
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Haaskjold YL, Bjørneklett R, Bostad L, Bostad LS, Lura NG, Knoop T. Utilizing the MEST score for prognostic staging in IgA nephropathy. BMC Nephrol 2022; 23:26. [PMID: 35016634 PMCID: PMC8753851 DOI: 10.1186/s12882-021-02653-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 12/23/2021] [Indexed: 12/23/2022] Open
Abstract
Background The Oxford classification/MEST score is an established histopathologic scoring system for patients with IgA nephropathy (IgAN). The objective of this study was to derive a prognostic model for IgAN based on the MEST score and histopathologic features. Methods A total of 306 patients with biopsy-proven primary IgAN were included. Histopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry and reclassified according to the Oxford classification. The study endpoint was end-stage renal disease (ESRD). Patients were subclassified into three risk models based on histologic features (Model A), a composite score calculated from the adjusted hazard ratio values (Model B), and on quartiles (Model C). Results The mean follow-up time was 16.5 years (range 0.2–28.1). In total, 61 (20%) patients reached ESRD during the study period. Univariate analysis of M, E, S, T and C lesions demonstrated that all types were associated with an increased risk of ESRD; however, a multivariate analysis revealed that only S, T and C lesions were associated with poor outcomes. Statistical analysis of 15-year data demonstrated that Models A and B were as predictive as the MEST score, with an area-under-the-curve at 0.85. The Harrel c index values were 0.81 and 0.80 for the MEST score and Models A and B, respectively. In the present cohort, adding C lesions to the MEST score did not improve the models prognostic value. Conclusions Patients can be divided into risk classes based on their MEST scores. Histopathologic data provide valuable prognostic information at the time of diagnosis. Model B was the most suitable for clinical practice because it was the most user-friendly. Supplementary Information The online version contains supplementary material available at 10.1186/s12882-021-02653-y.
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Xu RC, Guo JY, Cao T, Xu Y, Liao Y, Chen YN, Song HY, Chen XJ, Guan MJ, Tang F, Xiang Q, Chen XL, Wan QJ. A mixed-method evaluation of the relationship between Oxford classification scores and longitudinal changes in proteinuria in patients with immunoglobulin A nephropathy. Front Endocrinol (Lausanne) 2022; 13:890900. [PMID: 36704031 PMCID: PMC9871483 DOI: 10.3389/fendo.2022.890900] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 10/25/2022] [Indexed: 01/11/2023] Open
Abstract
INTRODUCTION This study aimed to investigate the relationship between Oxford Classification scores and longitudinal changes in proteinuria in patients with immunoglobulin A nephropathy (IgAN). METHODS The study was a single-center retrospective cohort study involving 358 patients with primary IgAN who were treated at the Shenzhen Second People's Hospital, China, between January 2011 and May 2021. Multivariate linear regression and generalized additive mixed models (GAMMs), adjusted for traditional risk confounders, were used to evaluate the correlation between scores for mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), tubular atrophy/interstitial fibrosis (T), and crescents (C) (known as the Oxford Classification MEST-C score system), with proteinuria/creatinine ratio (PCR) at the time of renal biopsy and longitudinal changes in PCR, respectively. RESULTS The median PCR was 1061 mg/g, and it increased on average by 68.82 mg/g per year in these patients. Among patients with renal insufficiency, compared with patients without relative lesions, those with E present (E1) (1153.44; 95% confidence interval [CI], 188.99-2117.89 mg/g) and C > 0 (C1/2) (1063.58; 95% CI, 185.25-1941.90 mg/g) were associated with increased PCR levels at the time of renal biopsy. What's more, S present (S1) (194.96; 95% CI, 54.50-335.43 mg/g per year) was associated with the fastest PCR increase; C > 0 (C1/2) (147.59; 95% CI, 8.32-286.86 mg/g per year) and T >25% (T1/2) (77.04; 95% CI, 7.18-146.89 mg/g per year), were also correlated with a faster PCR increase. In patients with normal kidney function, associations between S1 (55.46; 95% CI, 8.93-101.99 mg/g per year) and E1 (94.02; 95% CI, 21.47-166.58 mg/g per year) and PCR change could be observed. Additionally, in patients with overweight/obesity, S1 (156.09; 95% CI, 52.41-259.77 mg/g per year), E1 (143.34; 95% CI, 35.30-251.38 mg/g per year), T1/2 (116.04; 95% CI, 22.58-209.51 mg/g per year), as well as C1/2 (134.03; 95% CI, 41.73-226.32 mg/g per year) were associated with noticeably quicker PCR increase. CONCLUSIONS Overall, E1 and C1/2 were independently associated with raised proteinuria levels at the time of renal biopsy, and S1, E1, T1/2, C1/2 were independently associated with a longitudinal increase in proteinuria in the patients with IgAN, especially in those with renal insufficiency or overweight/obesity, suggesting that currently available treatments might not be satisfactory, and weight control might be beneficial. Individual therapy development might benefit from the use of the Oxford Classification system.
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Affiliation(s)
- Ri-Cong Xu
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Department of Nephrology, The Second People's Hospital of Shenzhen, Shenzhen, China
| | - Jian-Ying Guo
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Department of Nephrology, The Second People's Hospital of Shenzhen, Shenzhen, China
| | - Tao Cao
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Department of Nephrology, The Second People's Hospital of Shenzhen, Shenzhen, China
| | - Yi Xu
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Department of Nephrology, The Second People's Hospital of Shenzhen, Shenzhen, China
| | - Ying Liao
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Department of Nephrology, The Second People's Hospital of Shenzhen, Shenzhen, China
| | - Yu-Na Chen
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Department of Nephrology, The Second People's Hospital of Shenzhen, Shenzhen, China
| | - Hai-Ying Song
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Department of Nephrology, The Second People's Hospital of Shenzhen, Shenzhen, China
| | - Xiao-Jie Chen
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Department of Nephrology, The Second People's Hospital of Shenzhen, Shenzhen, China
| | - Mi-Jie Guan
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Department of Nephrology, The Second People's Hospital of Shenzhen, Shenzhen, China
| | - Fei Tang
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Department of Nephrology, The Second People's Hospital of Shenzhen, Shenzhen, China
| | - Qiong Xiang
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Department of Nephrology, The Second People's Hospital of Shenzhen, Shenzhen, China
| | - Xing-Lin Chen
- Department of Epidemiology and Biostatistics, Empower U, X&Y solutions Inc., Boston, MA, United States
| | - Qi-Jun Wan
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China
- Department of Nephrology, The Second People's Hospital of Shenzhen, Shenzhen, China
- *Correspondence: Qi-Jun Wan,
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Dong L, Tan J, Li F, Wang S, Jiang Z, Qin A, Zhong Z, Zhou X, Tang Y, Qin W. Arterial-Arteriolar Sclerosis Is Independently Associated With Poor Renal Outcome in IgA Nephropathy Patients. Front Med (Lausanne) 2021; 8:761897. [PMID: 34869465 PMCID: PMC8637863 DOI: 10.3389/fmed.2021.761897] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 10/07/2021] [Indexed: 02/05/2023] Open
Abstract
Aim: This study aimed to investigate the clinicopathological features and prognosis of immunoglobulin A nephropathy (IgAN) with arterial-arteriolar sclerosis (AS). Methods: Patients with biopsy-proven IgAN from the West China Hospital of Sichuan University were retrospectively enrolled. Clinicopathological features were collected. Patients were categorized based on the presence and the severity of the AS. All the patients were regularly followed-up until a composite end point. The correlation between AS and prognosis of IgAN was assessed. Results: A total of 1,424 patients were recruited and followed for 60.0 ± 28.7 months. Patients with AS tended to have older age, higher blood pressure, heavier proteinuria, higher serum creatinine, uric acid, and total triglyceride (TG). Meanwhile, they were more likely to have a lower estimated glomerular filtration rate (eGFR), hemoglobin, and albumin. At the end of follow-up, 126 patients in the AS group and 47 patients in the non-AS group had reached the composite end point (p < 0.001). AS was associated with the renal outcome (log-rank p < 0.001) and was an independent risk factor for the progression of IgAN (p = 0.049). The severity of AS was associated with renal outcomes (log-rank p < 0.001) and there was a trend that it might serve as an independent risk marker for progression of IgAN. In the subgroup analysis, patients presenting with AS and lower eGFR, albumin, and hemoglobin or higher proteinuria, uric acid, and TG had a significant trend for a shorter time to reach the end point (log-rank p < 0.001). Conclusion: AS was commonly seen in patients with IgAN and was independently associated with the poor prognosis.
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Affiliation(s)
- Lingqiu Dong
- West China School of Medicine, Sichuan University, Chengdu, China.,Division of Nephrology, Department of Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Jiaxing Tan
- West China School of Medicine, Sichuan University, Chengdu, China.,Division of Nephrology, Department of Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Fangming Li
- West China School of Medicine, Sichuan University, Chengdu, China.,Division of Nephrology, Department of Medicine, Chengdu Seventh People's Hospital, Chengdu, China
| | - Siqing Wang
- West China School of Medicine, Sichuan University, Chengdu, China.,Division of Nephrology, Department of Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Zheng Jiang
- West China School of Medicine, Sichuan University, Chengdu, China.,Division of Nephrology, Department of Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Aiya Qin
- West China School of Medicine, Sichuan University, Chengdu, China.,Division of Nephrology, Department of Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Zhengxia Zhong
- Division of Nephrology, Department of Medicine, Affiliated Hospital of Zunyi Medical College, Zunyi, China
| | - Xiaoyuan Zhou
- West China School of Public Health, West China Forth Hospital of Sichuan University, Chengdu, China
| | - Yi Tang
- Division of Nephrology, Department of Medicine, West China Hospital of Sichuan University, Chengdu, China
| | - Wei Qin
- Division of Nephrology, Department of Medicine, West China Hospital of Sichuan University, Chengdu, China
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Huerta A, Mérida E, Medina L, Fernandez M, Gutierrez E, Hernandez E, Lopez P, Sevillano A, Portolés J, Trimarchi H, Praga M. Corticosteroids and mycophenolic acid analogs in IgA nephropathy with progressive decline in kidney function. Clin Kidney J 2021; 15:771-777. [PMID: 35371455 PMCID: PMC8967683 DOI: 10.1093/ckj/sfab244] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Indexed: 11/13/2022] Open
Abstract
Abstract
Background
A randomized controlled trial (RCT) demonstrated a beneficial effect of corticosteroids (CS) plus cyclophosphamide followed by azathioprine in progressive IgA nephropathy (IgAN). Although treatment with CS and mycophenolic acid analogs (MPAA) remains controversial in IgAN, there is no information about their effect in progressive IgAN.
Methods
Patients with progressive IgAN, defined by a decrease in estimated glomerular filtration rate (eGFR) of at least 10 ml/min/1.73 m2 in the 12 months prior to the start of treatment, proteinuria ≥ 0.75 g/24h despite maximum tolerated doses of renin-angiotensin system blockers (RASB) and persistent hematuria, who had received treatment with CS+MPAA were included in this retrospective study. The main outcome was the difference between the eGFR slope from the start of treatment with CS+MPAA to the last visit with this treatment with respect to the eGFR slope during the 12 months prior to start of treatment.
Results
Twenty-five patients were included in the study. Mean duration of CS+MPAA treatment was 24.7±15.2 months. In the 12 months prior to treatment the median rate of kidney function decline was -23 [-32 to -16] ml/min/1.73 m2 per year. After the onset of treatment, the median eGFR slope was +5 [+3 to +9] ml/min/1.73 m2 per year (P = 0.001 with respect to the 12 months prior to treatment). Proteinuria decreased from 1.8 (1.0-2.5) g/day at baseline to 0.6 (0.3-1.2) g/day at the end of treatment (P = 0.01) and hematuria disappeared in 40% of the patients. There were no serious adverse effects requiring treatment discontinuation.
Conclusions
CS + MPAA is an effective treatment in IgAN patients with a sustained decline in kidney function accompanied by persistent proteinuria and hematuria despite optimized conservative treatment. Prospective studies are needed to confirm these results.
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Affiliation(s)
- Ana Huerta
- Department of Nephrology, Hospital Universitario Puerta del Hierro Majadahonda, Madrid, Spain
- REDInREN ISCIII 016/009, Spain
| | - Eva Mérida
- REDInREN ISCIII 016/009, Spain
- Department of Nephrology, Hospital Hospital Universitario Doce de Octubre, Madrid, Spain
| | - Laura Medina
- Department of Nephrology, Hospital Universitario Infanta Leonor, Madrid, Spain
| | - Maria Fernandez
- Department of Nephrology, Hospital Hospital Universitario Doce de Octubre, Madrid, Spain
| | - Eduardo Gutierrez
- REDInREN ISCIII 016/009, Spain
- Department of Nephrology, Hospital Hospital Universitario Doce de Octubre, Madrid, Spain
| | - Eduardo Hernandez
- REDInREN ISCIII 016/009, Spain
- Department of Nephrology, Hospital Hospital Universitario Doce de Octubre, Madrid, Spain
| | - Paula Lopez
- Department of Nephrology, Hospital Universitario Puerta del Hierro Majadahonda, Madrid, Spain
| | - Angel Sevillano
- REDInREN ISCIII 016/009, Spain
- Department of Nephrology, Hospital Hospital Universitario Doce de Octubre, Madrid, Spain
| | - Jose Portolés
- Department of Nephrology, Hospital Universitario Puerta del Hierro Majadahonda, Madrid, Spain
- REDInREN ISCIII 016/009, Spain
| | - Hernan Trimarchi
- Department of Nephrology, Hospital Británico de Buenos Aires, Argentina
| | - Manuel Praga
- REDInREN ISCIII 016/009, Spain
- Research Institute Hospital Universitario 12 de Octubre (imas12), Madrid, Spain
- Department of Medicine, Complutense University, Madrid, Spain
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Caliskan Y, Demir E, Karatay E, Ozluk Y, Mirioglu S, Dirim AB, Artan AS, Usta Akgul S, Oto OA, Savran Oguz F, Turkmen A, Lentine KL, Yazici H. Oxidative stress and macrophage infiltration in IgA nephropathy. J Nephrol 2021; 35:1101-1111. [PMID: 34787798 DOI: 10.1007/s40620-021-01196-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Accepted: 09/27/2021] [Indexed: 12/21/2022]
Abstract
BACKGROUND The aim of this study was to evaluate the interactions among serum levels of galactose-deficient IgA1 (Gd-IgA1), oxidative stress and macrophage infiltration and their clinical correlates in patients with IgA Nephropathy (IgAN). METHODS A total of 47 patients with biopsy-proven primary IgAN, aged between 16 and 79 years, with a follow-up period ≥ 1 year or who showed progression to end stage kidney disease (ESKD) regardless the duration of follow-up were included. Study endpoint was the progression to ESKD. Serum Gd-IgA1 and advanced oxidation protein product (AOPP) levels were measured using ELISA assays. Kidney biopsies were evaluated according to the Oxford MEST-C scoring, with C4d and CD68 staining. RESULTS Seventeen patients (36%) experienced ESKD during a median follow-up time of 6 years (IQR 3.7-7.5). Serum AOPP levels were correlated with the intensity of glomerular C3 deposition (r = 0.325, p = 0.026), glomerular (r = 0.423, p = 0.003) and interstitial CD68 + cell count (r = 0.298, p = 0.042) and Gd-IgA1 levels (r = 0.289, p = 0.049). Serum Gd-IgA1 levels were correlated with the intensity of C3 deposition (r = 0.447, p = 0.002). eGFR at biopsy (adjusted HR (aHR) 0.979 p = 0.011), and E score (aHR, 8.305, p = 0.001) were associated with progression to ESKD in multivariate analysis. 5-year ESKD-free survival rate was significantly lower in patients with higher E score compared to patients with E score 0 [p = 0.021]. CONCLUSIONS An increased number of macrophages in the glomerular and tubulointerstitial area may play a role in oxidative stress and complement system activation. Endocapillary hypercellularity is a predictive factor for poor prognosis in IgAN.
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Affiliation(s)
- Yasar Caliskan
- Division of Nephrology, Saint Louis University School of Medicine, 3660 Vista Ave, Saint Louis, MO, USA. .,Division of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.
| | - Erol Demir
- Division of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ecem Karatay
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Yasemin Ozluk
- Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Safak Mirioglu
- Division of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey.,Division of Nephrology, Bezmialem Vakif University School of Medicine, Istanbul, Turkey
| | - Ahmet Burak Dirim
- Division of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ayse Serra Artan
- Division of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Sebahat Usta Akgul
- Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Ozgur Akin Oto
- Division of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Fatma Savran Oguz
- Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Aydin Turkmen
- Division of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
| | - Krista L Lentine
- Division of Nephrology, Saint Louis University School of Medicine, 3660 Vista Ave, Saint Louis, MO, USA
| | - Halil Yazici
- Division of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey
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Liu Y, Wei W, Yu C, Xing L, Wang M, Liu R, Ma J, Liu X, Xie R, Sui M. Epidemiology and risk factors for progression in Chinese patients with IgA nephropathy. Med Clin (Barc) 2021; 157:267-273. [PMID: 32826075 DOI: 10.1016/j.medcli.2020.05.064] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Revised: 05/26/2020] [Accepted: 05/28/2020] [Indexed: 01/05/2023]
Abstract
BACKGROUND IgA nephropathy (IgAN) is one of the main causes of primary glomerulonephritis worldwide, and it is also the main primary disease leading to chronic kidney disease. The purpose of this study is to evaluate the epidemiology and risk factors for progression in Chinese patients with IgAN. METHODS In this retrospective study, 246 patients with renal biopsy-proven IgAN were enrolled from January 2012 to June 2018. The patients' data were divided into two groups according to eGFR at the end of follow-up: a high-eGFR group (eGFR≥60ml/min) and a low-eGFR group (eGFR<60ml/min). RESULTS At the end of the study, we identified 49 (19.92%) patients with low-eGFR from 246 IgAN patients. Renal function, represented by serum creatinine, urea nitrogen and cystatin-C, was significantly decreased in the low-eGFR group (P<0.001 for all) at the time of renal biopsy. Compared with the high-eGFR group, the age, mean arterial blood pressure (MAP), proteinuria, cholesterol, triglycerides and serum uric acid were significantly higher (P<0.05 for all). According to the Oxford evaluation, the proportion of S1-2 (59.2%) and T1-2 (65.3%) was significantly increased (P<0.001 for both) and the proportion that had a MEST-C score ≥3 was statistically increased in the low-eGFR group (83.7%, P=0.001). CONCLUSIONS Male, MAP, haematuria, Scr, cholesterol, hemoglobin, Lee classification more than 3 and C1-2 are independent risk factors for low-eGFR in Chinese IgAN patients.
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Affiliation(s)
- Yang Liu
- Department of Nephrology, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Wei Wei
- Department of Nephrology, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Chengyuan Yu
- Department of Gerontology, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Li Xing
- Department of Nephrology, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Mingao Wang
- Department of Nephrology, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Ruichan Liu
- Department of Nephrology, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Jing Ma
- Department of Nephrology, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiaogang Liu
- Department of Nephrology, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Rujuan Xie
- Department of Nephrology, First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Manshu Sui
- Department of Nephrology, First Affiliated Hospital of Harbin Medical University, Harbin, China.
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Zhang H, Barratt J. Is IgA nephropathy the same disease in different parts of the world? Semin Immunopathol 2021; 43:707-715. [PMID: 34417628 DOI: 10.1007/s00281-021-00884-7] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Accepted: 07/29/2021] [Indexed: 12/30/2022]
Abstract
Since it was first described in 1968, immunoglobulin A nephropathy (IgAN) is understood to be the most common form of glomerulonephritis worldwide. The diagnosis of IgAN depends on the presence of dominant mesangial IgA1 deposition by renal biopsy. To date, a wide spectrum of clinical and pathologic features of IgAN have been observed, implying that IgAN might not be the same disease across the world. Here, we review the characteristics of IgAN from perspectives of epidemiology, clinical-pathological patterns, disease pathogenesis, and treatment response across different ethnic populations. Overall, IgAN is most prevalent in Asians, followed by Caucasians, and relatively rare in Africans. More severe clinical presentation and higher risk of disease progression have been reported in Asians than Europeans. Moreover, active lesions, such as endocapillary hypercellularity and crescents, are more commonly reported in Asians than Europeans. Response to corticosteroid/immunosuppression therapy is variably reported, with greater apparent efficacy reported in Asian than European studies. Although a multi-hit hypothesis has been suggested for IgAN, the relative importance of each "hit" may vary in different ethnic populations and this variation underlies the differences in presentation of IgAN. In the future, a better understanding of pathogenic pathways operating in different ethnic populations may help provide better biomarkers of disease and more precise targeting of treatment strategies for IgAN.
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Affiliation(s)
- Hong Zhang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.
- Institute of Nephrology, Peking University, Beijing, China.
- Key Laboratory of Renal Disease, Ministry of Health of China, Beijing, China.
- Key Laboratory of Chronic Kidney Disease Prevention and Treatment (Peking University), Ministry of Education, Beijing, China.
| | - Jonathan Barratt
- Department of Cardiovascular Sciences, University of Leicester and Leicester General Hospital, Leicester, UK.
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Pillebout E, Sunderkötter C. IgA vasculitis. Semin Immunopathol 2021; 43:729-738. [PMID: 34170395 DOI: 10.1007/s00281-021-00874-9] [Citation(s) in RCA: 77] [Impact Index Per Article: 19.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Accepted: 05/26/2021] [Indexed: 10/21/2022]
Abstract
IgA vasculitis (IgAV) is an inflammation of small vessels caused by perivascular deposition of IgA and activation of neutrophils. It may present as systemic vasculitis (IgAV - Henoch-Schönlein purpura) or as a variant restricted to the skin (skin-limited IgAV), while IgA nephropathy presents a variant restricted to the kidneys. Systemic IgAV affects children more frequently than adults (150 to 200 for 1; incidence 1 in 1 million/year). In the latter, disease more often leads to chronic renal disease. The dominant clinical features include round or oval and retiform palpable purpura predominantly on the lower legs, arthralgia or arthritis, gastrointestinal bleeding or pain and glomerulonephritis with mesangial IgA deposits (IgAVN). Pulmonary, cardiac, genital and neurological involvement occurs, but is rare. Immune complexes containing galactose-deficient IgA1 play a pivotal role in the pathophysiology of IgAV; via the Fc alpha receptor (CD89), they induce neutrophilic inflammation around cutaneous vessels and mesangial proliferation and inflammation in the glomerulus. In case of self-limited disease, only symptomatic treatment is recommended. Treatment of severe IgAV, nephritis or gastrointestinal manifestations, is not established, but some studies reported a benefit of corticosteroids, combined with immunosuppressive drugs. Short-term outcome depends on the severity of gastrointestinal manifestations, while long-term prognosis depends on the severity of nephritis.
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Affiliation(s)
- Evangéline Pillebout
- Nephrology Unit, Saint Louis Hospital, INSERM 1149, CRI, 1 Av C. Vellefaux, 75010, Paris, France.
| | - Cord Sunderkötter
- Department of Dermatology and Venereology, University Hospital Halle, Martin-Luther-University Halle-Wittenberg, Ernst-Grube-Str. 40, 06120, Halle/Saale, Germany
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Trimarchi H, Coppo R. Glomerular endothelial activation, C4d deposits and microangiopathy in immunoglobulin A nephropathy. Nephrol Dial Transplant 2021; 36:581-586. [PMID: 31755918 DOI: 10.1093/ndt/gfz241] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2019] [Indexed: 11/14/2022] Open
Abstract
Immunoglobulin A nephropathy (IgAN) is considered as mesangiopathy since it initiates in the mesangium; however, other glomerular components are involved and the glomerular capillary wall offers the first contact to circulating macromolecular IgA1. Acute and active forms of IgAN are associated with endocapillary hypercellularity and vascular damage of various degrees, in severe cases with microangiopathy (MA) without or with thrombosis [thrombotic microangiopathy (TMA)]. Vascular damage activates complement and coagulation cascades. A defective complement regulation has recently been detected in active and progressive cases of IgAN. C4d deposits in renal biopsies have been found to be an early risk factor. These observations have raised interest in manifestation of MA and TMA in progressive cases of IgAN. MA-TMA lesions have been found in various percentages (2-53%) of patients with IgAN according to patients' selection and pathology definition of TMA. The association with hypertension (HTN) was so strong that it led to the hypothesis that MA/TMA in IgAN was a mere consequence of severe HTN. Old and new clinical and experimental data indicate that in IgAN the interaction of the glomerular capillary wall with immune reactants and complement uncontrolled activation leading to C4b deposits favours the development of MA-TMA, which plays a role in progression and renal function decline. The central role of complement activation is relevant also for the new therapeutic interventions offered by the pharma.
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Affiliation(s)
- Hernán Trimarchi
- Nephrology Service, Hospital Británico de Buenos Aires, Buenos Aires, Argentina
| | - Rosanna Coppo
- Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy
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37
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Xu R, Li Z, Cao T, Xu Y, Liao Y, Song H, Chen X, Tang F, Xiang Q, Wan Q. The Association of the Oxford Classification Score with Longitudinal Estimated Glomerular Filtration Rate Decline in Patients with Immunoglobulin A Nephropathy: A Mixed-Method Study. Int J Gen Med 2021; 14:2655-2663. [PMID: 34177274 PMCID: PMC8219302 DOI: 10.2147/ijgm.s313333] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 05/28/2021] [Indexed: 11/23/2022] Open
Abstract
Introduction The Oxford Classification score, which predicts renal outcomes for immunoglobulin A nephropathy (IgAN), is widely used in clinical practice. Nevertheless, the relationship between these markers and longitudinal changes in renal function are poorly understood. Methods This was a population-based retrospective cohort study of 280 adults with biopsy-proven primary IgAN from 2011 to 2018. We used generalized additive mixed models to control for traditional kidney disease risk factors to analyze the associations between Oxford Classification MEST-C scores (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T; crescents, C) and longitudinal changes in the estimated glomerular filtration rate (eGFR) after renal biopsy. Results The median eGFR was 78.2 mL/min/1.73 m2 at baseline, and then it decreased on average by 1.3 mL/min/1.73 m2 per year in the entire cohort. In adjusted models, compared with patients without relative lesions, the presence of T > 50% (T2) (−5.7; 95% confidence interval [CI], −9.5 to −2.0 mL/min/1.73m2 per year) was associated with the fastest eGFR decline. S present (S1) (−2.9; 95% CI, −4.6 to −1.1 mL/min/1.73m2 per year) and C > 25% glomeruli (C2) (−3.4; 95% CI, −6.4 to −0.5 mL/min/1.73m2 per year) also demonstrated steeper eGFR declines. However, we found no association between M > 0.5 (M1), E present (E1), T 26%–50% (T1), and C present ≥ 1 glomerulus (C1), and progressive eGFR decline (p > 0.05). Conclusion The Oxford Classification scores, S1, T2, and C2, were independently associated with the longitudinal decreases in renal function in patients with IgAN. These findings suggested therapies targeted at improving early damage to these lesions might be essential to delay renal progression.
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Affiliation(s)
- Ricong Xu
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, People's Republic of China.,The Second People's Hospital of Shenzhen, Shenzhen, People's Republic of China
| | - Zhijian Li
- Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People's Republic of China.,Key Laboratory of Nephrology, National Health Commission and Guangdong Province, Guangzhou, Guangdong, People's Republic of China
| | - Tao Cao
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, People's Republic of China.,The Second People's Hospital of Shenzhen, Shenzhen, People's Republic of China
| | - Yi Xu
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, People's Republic of China.,The Second People's Hospital of Shenzhen, Shenzhen, People's Republic of China
| | - Ying Liao
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, People's Republic of China.,The Second People's Hospital of Shenzhen, Shenzhen, People's Republic of China
| | - Haiying Song
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, People's Republic of China.,The Second People's Hospital of Shenzhen, Shenzhen, People's Republic of China
| | - Xiaojie Chen
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, People's Republic of China.,The Second People's Hospital of Shenzhen, Shenzhen, People's Republic of China
| | - Fei Tang
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, People's Republic of China.,The Second People's Hospital of Shenzhen, Shenzhen, People's Republic of China
| | - Qiong Xiang
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, People's Republic of China.,The Second People's Hospital of Shenzhen, Shenzhen, People's Republic of China
| | - Qijun Wan
- Department of Nephrology, The First Affiliated Hospital of Shenzhen University, Shenzhen, People's Republic of China.,The Second People's Hospital of Shenzhen, Shenzhen, People's Republic of China
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Hu Y, Shang M, Shi Y, Tao M, Yuan W, Tang L, Ma X, Cui B, Chen H, Zhou X, Zhuang S, Liu N. Correlation analysis between expression of histone deacetylase 6 and clinical parameters in IgA nephropathy patients. Ren Fail 2021; 43:684-697. [PMID: 33896334 PMCID: PMC8079031 DOI: 10.1080/0886022x.2021.1914657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/03/2022] Open
Abstract
Background It has been demonstrated that histone deacetylase 6 (HDAC6) is involved in various kidney diseases in experimental study. However, correlation between HDAC6 and clinical parameters in IgA nephropathy (IgAN) patients is still unknown. Methods A total of 46 human kidney biopsy specimens with IgAN were selected as observation group, specimens of normal renal cortex tissue that was not affected by the tumor from patients with renal carcinoma (n = 7) served as control. We investigated the relationship between HDAC6 and clinical parameters in IgAN. Results HDAC6 was highly expressed in human kidney biopsy specimens with IgAN compared with control group, while the number of acetyl histone H3 positive cells were significantly decreased. There was a statistical difference in the indexes of albumin, estimated glomerular filtration rate (eGFR), serum urea, serum creatinine, serum uric acid, β2-microglobulin, cystatin C, cholesterol, high-density lipoprotein, low-density lipoprotein, and HDAC6 positive area among the different Oxford Classification (p < 0.05). The expression of HDAC6 was different in various eGFR levels, the expression of HDAC6 increased with the decreasing of eGFR level, the expression of acetyl histone H3 decreased with the decreasing of eGFR level. In addition, the expression of HDAC6 positively correlated with Masson trichrome positive area, serum urea, serum creatinine, β2 macroglobulin, and cystatin C, while negatively correlated with eGFR and acetyl histone H3. Multivariate linear regression analysis demonstrated that eGFR and cystatin C were independently associated with HDAC6, respectively (p < 0.05). Conclusions These results suggested that high level of HDAC6 expression in IgAN is correlated with renal dysfunction.
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Affiliation(s)
- Yan Hu
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Minghua Shang
- Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yingfeng Shi
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Min Tao
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Weijie Yuan
- Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Lunxian Tang
- Emergency Department of Critical Care Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xiaoyan Ma
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Binbin Cui
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Hui Chen
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Xun Zhou
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Shougang Zhuang
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.,Department of Medicine, Rhode Island Hospital and Alpert Medical School, Brown University, Providence, RI, USA
| | - Na Liu
- Department of Nephrology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
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Jhee JH, Nam BY, Park JT, Kim HW, Chang TI, Kang EW, Lim BJ, Yoo TH, Kang SW, Jeong HJ, Han SH. CD71 mesangial IgA1 receptor and the progression of IgA nephropathy. Transl Res 2021; 230:34-43. [PMID: 33122053 DOI: 10.1016/j.trsl.2020.10.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 10/12/2020] [Accepted: 10/21/2020] [Indexed: 10/23/2022]
Abstract
The transferrin receptor (CD71) is known as a receptor for IgA1 on mesangial cells, but the role of CD71 in IgA nephropathy (IgAN) is unknown. We studied clinical implication of mesangial CD71 in 282 patients with biopsy-proven IgAN (2005-2018). The transcript and protein expression of glomerular CD71 was determined by real-time polymerase chain reaction and immunohistochemistry. Ten subjects with microscopic hematuria only and no evidence of histologic abnormalities on kidney biopsy were considered as controls. Human mesangial cells (HMCs) were treated with sera from IgAN patients and expression levels of CD71 and inflammatory cytokine markers were compared according to disease status. Disease progression was defined as a ≥30% decline in estimated glomerular filtration rate from the baseline value. During a mean follow up of 53.5 (18.3-75.9) months, 80 (28.4%) patients developed disease progression. The mRNA expression of CD71 was significantly higher in progressors than in nonprogressors (P = 0.001). Among the Oxford classification scores, patients with M1 had significantly higher CD71 expression levels than those with M0. In a multivariable Cox model, elevated transcript levels of CD71 were significantly associated with 4.32-fold higher risk of disease progression (P = 0.009). Furthermore, CD71 expression levels independently predicted the increase in proteinuria of ≥50% from the baseline (P = 0.03). Finally, HMCs treated with sera from IgAN patients with the higher Oxford score (M1E1S1T0) more increased the mRNA expression of CD71 and inflammatory markers than those with sera from negative score (M0E0S0T0). However, silencing CD71 significantly reduced expression levels of the inflammatory cytokine genes. Our results show that mesangial CD71 is significantly associated with disease progression and may play a biologic role in IgAN.
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Affiliation(s)
- Jong Hyun Jhee
- Division of Nephrology, Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
| | - Bo Young Nam
- Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, Brain Korea 21 PLUS, Yonsei University, Seoul, South Korea
| | - Jung Tak Park
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, South Korea
| | - Hyung Woo Kim
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, South Korea
| | - Tae Ik Chang
- Division of Nephrology, Department of Internal Medicine, National Health Insurance Service Medical Center, Ilsan Hospital, Goyang, Gyeonggi-do, South Korea
| | - Ea Wha Kang
- Division of Nephrology, Department of Internal Medicine, National Health Insurance Service Medical Center, Ilsan Hospital, Goyang, Gyeonggi-do, South Korea
| | - Beom Jin Lim
- Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea
| | - Tae-Hyun Yoo
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, South Korea
| | - Shin-Wook Kang
- Department of Internal Medicine, College of Medicine, Severance Biomedical Science Institute, Brain Korea 21 PLUS, Yonsei University, Seoul, South Korea; Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, South Korea
| | - Hyeon Joo Jeong
- Department of Pathology, Yonsei University College of Medicine, Seoul, South Korea
| | - Seung Hyeok Han
- Department of Internal Medicine, College of Medicine, Institute of Kidney Disease Research, Yonsei University, Seoul, South Korea.
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Hwang D, Choi K, Cho NJ, Park S, Yu BC, Gil HW, Lee EY, Choi SJ, Park MY, Kim JK, Hwang SD, Kwon SH, Jeon JS, Noh H, Han DC, Kim H. Validation of an international prediction model including the Oxford classification in Korean patients with IgA nephropathy. Nephrology (Carlton) 2021; 26:594-602. [PMID: 33624915 PMCID: PMC8248408 DOI: 10.1111/nep.13865] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2020] [Revised: 01/19/2021] [Accepted: 02/17/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Recently, a new international risk prediction model including the Oxford classification was published which was validated in a large multi-ethnic cohort. Therefore, we aimed to validate this risk prediction model in Korean patients with IgA nephropathy. METHODS This retrospective cohort study was conducted with 545 patients who diagnosed IgA nephropathy with renal biopsy in three medical centers. The primary outcome was defined as a reduction in estimated glomerular filtration rate (eGFR) of >50% or incident end-stage renal disease (ESRD). Continuous net reclassification improvement (cNRI) and integrated discrimination improvement (IDI) were used to validate models. RESULTS During the median 3.6 years of follow-up period, 53 (9.7%) renal events occurred. In multivariable Cox regression model, M1 (hazard ratio [HR], 2.22; 95% confidence interval [CI], 1.02-4.82; p = .043), T1 (HR, 2.98; 95% CI, 1.39-6.39; p = .005) and T2 (HR, 4.80; 95% CI, 2.06-11.18; p < .001) lesions were associated with increased risk of renal outcome. When applied the international prediction model, the area under curve (AUC) for 5-year risk of renal outcome was 0.69, which was lower than previous validation and internally derived models. Moreover, cNRI and IDI analyses showed that discrimination and reclassification performance of the international model was inferior to the internally derived models. CONCLUSION The international risk prediction model for IgA nephropathy showed not as good performance in Korean patients as previous validation in other ethnic group. Further validation of risk prediction model is needed for Korean patients with IgA nephropathy.
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Affiliation(s)
- Dohui Hwang
- Division of Nephrology, Soonchunhyang University Seoul Hospital, Seoul, South Korea
| | - Kyoungjin Choi
- Division of Nephrology, Soonchunhyang University Seoul Hospital, Seoul, South Korea
| | - Nam-Jun Cho
- Division of Nephrology, Soonchunhyang University Cheonan Hospital, Chungcheongnam-do, South Korea
| | - Samel Park
- Division of Nephrology, Soonchunhyang University Cheonan Hospital, Chungcheongnam-do, South Korea
| | - Byung Chul Yu
- Division of Nephrology, Soonchunhyang University Bucheon Hospital, Gyeonggi-do, South Korea
| | - Hyo-Wook Gil
- Division of Nephrology, Soonchunhyang University Cheonan Hospital, Chungcheongnam-do, South Korea
| | - Eun Young Lee
- Division of Nephrology, Soonchunhyang University Cheonan Hospital, Chungcheongnam-do, South Korea
| | - Soo Jeong Choi
- Division of Nephrology, Soonchunhyang University Bucheon Hospital, Gyeonggi-do, South Korea
| | - Moo Yong Park
- Division of Nephrology, Soonchunhyang University Bucheon Hospital, Gyeonggi-do, South Korea
| | - Jin Kuk Kim
- Division of Nephrology, Soonchunhyang University Bucheon Hospital, Gyeonggi-do, South Korea
| | - Seung Duk Hwang
- Division of Nephrology, Soonchunhyang University Bucheon Hospital, Gyeonggi-do, South Korea
| | - Soon Hyo Kwon
- Division of Nephrology, Soonchunhyang University Seoul Hospital, Seoul, South Korea.,Hyonam Kidney Laboratory, Soonchunhyang University Hospital, Seoul, South Korea
| | - Jin Seok Jeon
- Division of Nephrology, Soonchunhyang University Seoul Hospital, Seoul, South Korea.,Hyonam Kidney Laboratory, Soonchunhyang University Hospital, Seoul, South Korea
| | - Hyunjin Noh
- Division of Nephrology, Soonchunhyang University Seoul Hospital, Seoul, South Korea.,Hyonam Kidney Laboratory, Soonchunhyang University Hospital, Seoul, South Korea
| | - Dong Cheol Han
- Division of Nephrology, Soonchunhyang University Seoul Hospital, Seoul, South Korea.,Hyonam Kidney Laboratory, Soonchunhyang University Hospital, Seoul, South Korea
| | - Hyoungnae Kim
- Division of Nephrology, Soonchunhyang University Seoul Hospital, Seoul, South Korea.,Hyonam Kidney Laboratory, Soonchunhyang University Hospital, Seoul, South Korea
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Grading system utilising the total score of Oxford classification for predicting renal prognosis in IgA nephropathy. Sci Rep 2021; 11:3584. [PMID: 33574388 PMCID: PMC7878747 DOI: 10.1038/s41598-021-82967-x] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 01/11/2021] [Indexed: 01/07/2023] Open
Abstract
The Oxford classification of IgA nephropathy (IgAN) can evaluate each MEST-C score individually. We analysed a new grading system that utilised the total MEST-C score in predicting renal prognosis. Altogether, 871 IgAN patients were classified into three groups using the new Oxford classification system (O-grade) that utilised the total MEST-C score (O-grade I: 0–1, II: 2–4, and III: 5–7 points), and the 10-year renal prognosis was analysed. The clinical findings became significantly severer with increasing O-grades, and the renal survival rate by the Kaplan–Meier method was 94.1%, 86.9%, and 74.1% for O-grades I, II, and III, respectively. The hazard ratios (HRs) for O-grades II and III with reference to O-grade I were 2.8 (95% confidence interval [CI] 1.3–6.0) and 6.3 (95% CI 2.7–14.5), respectively. In the multivariate analysis, mean arterial pressure and eGFR, proteinuria at the time of biopsy, treatment of corticosteroids/immunosuppressors, and O-grade (HR 1.63; 95% CI 1.11–2.38) were the independent factors predicting renal prognosis. Among the nine groups classified using the O-grade and Japanese clinical-grade, the renal prognosis had an HR of 15.2 (95% CI 3.5–67) in the severest group. The O-grade classified by the total score of the Oxford classification was associated with renal prognosis.
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Kawakita C, Mise K, Onishi Y, Sugiyama H, Yoshida M, Yamada M, Wada J. Novel urinary glycan profiling by lectin array serves as the biomarkers for predicting renal prognosis in patients with IgA nephropathy. Sci Rep 2021; 11:3394. [PMID: 33564009 PMCID: PMC7873239 DOI: 10.1038/s41598-020-77736-1] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2020] [Accepted: 11/17/2020] [Indexed: 01/18/2023] Open
Abstract
In IgA nephropathy (IgAN), IgA1 molecules are characterized by galactose deficiency in O-glycans. Here, we investigated the association between urinary glycosylation profile measured by 45 lectins at baseline and renal prognosis in 142 patients with IgAN. The primary outcome was estimated glomerular filtration rate (eGFR) decline (> 4 mL/min/1.73 m2/year), or eGFR ≥ 30% decline from baseline, or initiation of renal replacement therapies within 3 years. During follow-up (3.4 years, median), 26 patients reached the renal outcome (Group P), while 116 patients were with good renal outcome (Group G). Multivariate logistic regression analyses revealed that lectin binding signals of Erythrina cristagalli lectin (ECA) (odds ratio [OR] 2.84, 95% confidence interval [CI] 1.11–7.28) and Narcissus pseudonarcissus lectin (NPA) (OR 2.32, 95% CI 1.11–4.85) adjusted by age, sex, eGFR, and urinary protein were significantly associated with the outcome, and they recognize Gal(β1-4)GlcNAc and high-mannose including Man(α1-6)Man, respectively. The addition of two lectin-binding glycan signals to the interstitial fibrosis/tubular atrophy score further improved the model fitness (Akaike’s information criterion) and incremental predictive abilities (c-index, net reclassification improvement, and integrated discrimination improvement). Urinary N-glycan profiling by lectin array is useful in the prediction of IgAN prognosis, since ECA and NPA recognize the intermediate glycans during N-glycosylation of various glycoproteins.
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Affiliation(s)
- Chieko Kawakita
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Koki Mise
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
| | - Yasuhiro Onishi
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan
| | - Hitoshi Sugiyama
- Department of Human Resource Development of Dialysis Therapy for Kidney Disease, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Michihiro Yoshida
- Center for Innovative Clinical Medicine, Okayama University Hospital, Okayama, Japan
| | | | - Jun Wada
- Department of Nephrology, Rheumatology, Endocrinology and Metabolism, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-cho, Kita-ku, Okayama, 700-8558, Japan.
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Alexander S, Varughese S, Franklin R, Roy S, Rebekah G, David VG, Mohapatra A, Valson AT, Jacob S, Koshy PM, Rajan G, Daha MR, Feehally J, Barratt J, John GT. Epidemiology, baseline characteristics and risk of progression in the first South-Asian prospective longitudinal observational IgA nephropathy cohort. Kidney Int Rep 2021; 6:414-428. [PMID: 33615067 PMCID: PMC7879115 DOI: 10.1016/j.ekir.2020.11.026] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 11/17/2020] [Accepted: 11/19/2020] [Indexed: 01/18/2023] Open
Abstract
INTRODUCTION Glomerular Research And Clinical Experiments-IgA Nephropathy in Indians (GRACE-IgANI) is the first prospective South Asian IgAN cohort with protocolized follow-up and extensive biosample collection. Here we report the baseline clinical, biochemical, and histopathologic characteristics of GRACE IgANI and calculate baseline risk of progression for the cohort. METHODS 201 incident adults with kidney biopsy-proven primary IgAN were recruited into GRACE-IgANI between March 2015 and September 2017. As of April 30, 2020, the cohort had completed a median follow-up of 30 months (interquartile range [IQR] 16-39). RESULTS The commonest clinical presentation in GRACE IgANI was hypertension, with or without proteinuria, and nephrotic-range proteinuria was present in 34%, despite <10 months of lead time to kidney biopsy. The GRACE-IgANI kidney biopsy data demonstrated a disproportionate absence of active glomerular lesions and overrepresentation of segmental sclerosing lesions and tubulointerstitial fibrosis at presentation, often coexistent with relatively well-preserved estimated glomerular filtration rate (eGFR) and low levels of proteinuria, especially in males. Baseline risk of progression was calculated for each evaluable patient using 2 different risk prediction tools. The median 5-year absolute risk of end-stage kidney disease (ESKD) was 19.8% (IQR 2.7-57.4) and median 5-year risk of progression to the combined endpoint of 50% decline in eGFR or ESKD was 35.5% using the 2 tools. CONCLUSIONS The predicted risk of progression in this cohort was considerable. Over the next 5 years, we will dissect the pathogenic pathways that underlie this severe South Asian IgAN phenotype.
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Affiliation(s)
| | | | | | - Sanjeet Roy
- Department of General Pathology, Christian Medical College, Vellore, India
| | - Grace Rebekah
- Department of Biostatistics, Christian Medical College, Vellore, India
| | | | - Anjali Mohapatra
- Department of Nephrology, Christian Medical College, Vellore, India
| | - Anna T. Valson
- Department of Nephrology, Christian Medical College, Vellore, India
| | - Shibu Jacob
- Department of Nephrology, Christian Medical College, Vellore, India
| | | | - Gautham Rajan
- Department of Nephrology, Christian Medical College, Vellore, India
| | | | - John Feehally
- University of Leicester College of Medicine Biological Sciences and Psychology, UK
| | - Jonathan Barratt
- University of Leicester College of Medicine Biological Sciences and Psychology, UK
| | - George T. John
- Department of Nephrology, Christian Medical College, Vellore, India
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Canney M, Barbour SJ, Zheng Y, Coppo R, Zhang H, Liu ZH, Matsuzaki K, Suzuki Y, Katafuchi R, Reich HN, Cattran D, for the International IgA Nephropathy Network*. Quantifying Duration of Proteinuria Remission and Association with Clinical Outcome in IgA Nephropathy. J Am Soc Nephrol 2021; 32:436-447. [PMID: 33514642 PMCID: PMC8054888 DOI: 10.1681/asn.2020030349] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Accepted: 10/22/2020] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND On the basis of findings of observational studies and a meta-analysis, proteinuria reduction has been proposed as a surrogate outcome in IgA nephropathy. How long a reduction in proteinuria needs to be maintained to mitigate the long-term risk of disease progression is unknown. METHODS In this retrospective multiethnic cohort of adult patients with IgA nephropathy, we defined proteinuria remission as a ≥25% reduction in proteinuria from the peak value after biopsy, and an absolute reduction in proteinuria to <1 g/d. The exposure of interest was the total duration of first remission, treated as a time-varying covariate using longitudinal proteinuria measurements. We used time-dependent Cox proportional hazards regression models to quantify the association between the duration of remission and the primary outcome (ESKD or a 50% reduction in eGFR). RESULTS During a median follow-up of 3.9 years, 274 of 1864 patients (14.7%) experienced the primary outcome. The relationship between duration of proteinuria remission and outcome was nonlinear. Each 3 months in sustained remission up to approximately 4 years was associated with an additional 9% reduction in the risk of disease progression (hazard ratio [HR], 0.91; 95% confidence interval [95% CI], 0.89 to 0.93). Thereafter, each additional 3 months in remission was associated with a smaller, nonsignificant risk reduction (HR, 0.99; 95% CI, 0.96 to 1.03). These findings were robust to multivariable adjustment and consistent across clinical and histologic subgroups. CONCLUSIONS Our findings support the use of proteinuria as a surrogate outcome in IgA nephropathy, but additionally demonstrate the value of quantifying the duration of proteinuria remission when estimating the risk of hard clinical endpoints.
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Affiliation(s)
- Mark Canney
- Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada
- BC Renal, Provincial Health Services Authority, British Columbia, Canada
- Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
| | - Sean J. Barbour
- Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada
- BC Renal, Provincial Health Services Authority, British Columbia, Canada
| | - Yuyan Zheng
- BC Renal, Provincial Health Services Authority, British Columbia, Canada
| | - Rosanna Coppo
- Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy
| | - Hong Zhang
- Institute of Nephrology, Peking University, Beijing, China
| | - Zhi-Hong Liu
- School of Medicine, Nanjing University, Nanjing, China
| | | | - Yusuke Suzuki
- Faculty of Medicine, Juntendo University, Tokyo, Japan
| | - Ritsuko Katafuchi
- National Hospital Organization Fukuoka Higashi Medical Center, Fukuoka, Japan
| | - Heather N. Reich
- Division of Nephrology, University of Toronto, Toronto, Ontario, Canada
| | - Daniel Cattran
- Division of Nephrology, University of Toronto, Toronto, Ontario, Canada
| | - for the International IgA Nephropathy Network*
- Division of Nephrology, University of British Columbia, Vancouver, British Columbia, Canada
- BC Renal, Provincial Health Services Authority, British Columbia, Canada
- Department of Medicine, University of Ottawa and the Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
- Fondazione Ricerca Molinette, Regina Margherita Hospital, Turin, Italy
- Institute of Nephrology, Peking University, Beijing, China
- School of Medicine, Nanjing University, Nanjing, China
- Faculty of Medicine, Juntendo University, Tokyo, Japan
- National Hospital Organization Fukuoka Higashi Medical Center, Fukuoka, Japan
- Division of Nephrology, University of Toronto, Toronto, Ontario, Canada
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Lu P, Li X, Zhu N, Deng Y, Cai Y, Zhang T, Liu L, Lin X, Guo Y, Han M. Serum uric acid level is correlated with the clinical, pathological progression and prognosis of IgA nephropathy: an observational retrospective pilot-study. PeerJ 2020; 8:e10130. [PMID: 33194389 PMCID: PMC7646298 DOI: 10.7717/peerj.10130] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 09/17/2020] [Indexed: 12/14/2022] Open
Abstract
Objectives This study was aimed to assess the relationship between serum uric acid (SUA) level and the clinical, pathological phenotype of IgA nephropathy (IgAN), and to determine the role of SUA level in the progression and prognosis of IgAN. Methods A total of 208 patients with IgAN were included in this study, and were classified into the normo-uricemia group and hyperuricemia group according to the SUA level. The clinical data at baseline, IgAN Oxford classification scores (MEST-C scoring system), and other pathological features were collected and further analyzed. All patients were followed up and the prognosis was assessed using Kaplan-Meier survival curves. GraphPad Prism 7.0 and SPSS 23.0 were used for statistical analyses. Results In clinical indicators, patients with hyperuricemia had the significantly higher proportion of males to females, mean arterial pressure, the levels of total cholesterol, triglyceride, Scr, BUN, 24 hour-urine protein, C3, and C4, the lower levels of high-density lipoprotein cholesterol and eGFR than those without (p < 0.05). In terms of pathological characteristics, the tubular atrophy/interstitial fibrosis scores, vascular injury scores, and glomerular sclerosis percentage were significantly higher in patients with hyperuricemia compared with those without (p < 0.01). There was no significant difference in the scores of mesangial hypercellularity, endocapillary hypercellularity, focal segmental glomerulosclerosis, as well as crescents between the two groups (p > 0.05). As for the depositions of immune complexes deposition in IgAN, the hyperuricemia group had less deposition of immunoglobulin G and FRA than the normo-uricemia group (p < 0.05), while the deposition of immunoglobulin A, immunoglobulin M, and complement C3 in the two groups showed no statistical difference. The survival curve suggested that patients in the hyperuricemia group have significantly poorer renal outcome than those in the normo-uricemia group (p = 0.0147). Results also revealed that the SUA level is a valuable predictor of renal outcome in patients with IgAN. The optimal cutoff value was 361.1 µmol/L (AUC = 0.76 ± 0.08167) and 614 µmol/L (AUC = 0.5728 ± 0.2029) for female and male, respectively. Conclusions The level of SUA is associated with renal function level and pathological severity of IgAN, and maybe a prognostic indicator of IgAN.
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Affiliation(s)
- Pingfan Lu
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaoqing Li
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Na Zhu
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yuanjun Deng
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yang Cai
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Tianjing Zhang
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lele Liu
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xueping Lin
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yiyan Guo
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Min Han
- Division of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Lee JH, Jang SH, Cho NJ, Heo NH, Gil HW, Lee EY, Moon JS, Park S. Severity of foot process effacement is associated with proteinuria in patients with IgA nephropathy. Kidney Res Clin Pract 2020; 39:295-304. [PMID: 32773390 PMCID: PMC7530366 DOI: 10.23876/j.krcp.20.017] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2020] [Revised: 06/01/2020] [Accepted: 06/04/2020] [Indexed: 11/04/2022] Open
Abstract
Background Proteinuria is a significant risk factor for progression of IgA nephropathy (IgAN) and has a positive correlation with severity of foot process effacement (FPE). We evaluated the relationship of FPE with proteinuria and histologic characteristics, including the Oxford classification. Methods Patients who underwent renal biopsy and were diagnosed with IgAN at a single center were retrospectively reviewed. Patients aged less than 18 years and those with the possibility of secondary causes were excluded from the study. Subsequently, we evaluated the association between degree of proteinuria, severity of FPE, and histologic characteristics, including the Oxford classification and other immunofluorescence stains. Results A total of 805 cases of renal biopsy was performed at our institution, and 327 patients were diagnosed with IgAN. Among them, 82 patients were excluded. Severity of FPE had an impact on the degree of proteinuria. Notably, the group with diffuse FPE had more than about 1.3 g/day of urine protein compared to those with rare FPE. Among the histologic characteristics, M1 score and immune deposition of IgG affected severity of FPE (hazard ratios [95% confidence interval], 1.90 [1.10 to 3.26], and 3.77 [1.66 to 8.54], respectively). Conclusion Severity of FPE had an impact on the degree of proteinuria and may be associated with the pathogenesis of IgAN.
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Affiliation(s)
- Ji-Hye Lee
- Department of Pathology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea
| | - Si-Hyong Jang
- Department of Pathology, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea
| | - Nam-Jun Cho
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
| | - Nam Hun Heo
- Department of Biostatistics, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
| | - Hyo-Wook Gil
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea
| | - Eun Young Lee
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea.,Institute of Tissue Regeneration, College of Medicine, Soonchunhyang University, Cheonan, Republic of Korea
| | - Jong-Seok Moon
- Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan, Republic of Korea
| | - Samel Park
- Department of Internal Medicine, Soonchunhyang University Cheonan Hospital, Cheonan, Republic of Korea.,Soonchunhyang Institute of Medi-bio Science, Soonchunhyang University, Cheonan, Republic of Korea
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47
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An JN, Li L, Lee J, Yu SS, Kim JH, Lee J, Kim YC, Kim DK, Oh YK, Lim CS, Kim YS, Kim S, Yang SH, Lee JP. Urinary cMet as a prognostic marker in immunoglobulin A nephropathy. J Cell Mol Med 2020; 24:11158-11169. [PMID: 32822114 PMCID: PMC7576300 DOI: 10.1111/jcmm.15636] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2020] [Revised: 06/09/2020] [Accepted: 06/25/2020] [Indexed: 12/18/2022] Open
Abstract
The prediction of prognosis in patients with immunoglobulin A nephropathy (IgAN) is challenging. We investigated the correlation between urinary cMet (ucMet) levels and clinical parameters and examined the effects of cMet agonistic antibody (cMet Ab) in an in vitro IgAN model. Patients diagnosed with IgAN (n = 194) were divided into three groups representing undetectable (Group 1), below‐median (Group 2) and above‐median (Group 3) levels of ucMet/creatinine (ucMet/Cr). Stained kidney biopsy samples were graded according to cMet intensity. Primary‐cultured human mesangial cells were stimulated with recombinant tumour necrosis factor (TNF)‐α and treated with cMet Ab. Our results showed that ucMet/Cr levels positively correlated with proteinuria (P < .001). During the follow‐up, patients in Group 3 showed a significantly lower probability of complete remission (CR; uPCr < 300 mg/g) than those in groups 1 and 2, after adjusting for blood pressure, estimated glomerular filtration rate, and proteinuria, which influence clinical prognosis (HR 0.60, P = .038); moreover, ucMet/Cr levels were also associated with glomerular cMet expression. After TNF‐α treatment, the proliferation of mesangial cells and increased interleukin‐8 and intercellular adhesion molecule‐1 expression were markedly reduced by cMet Ab in vitro. In conclusion, ucMet/Cr levels significantly correlated with proteinuria, glomerular cMet expression, and the probability of CR. Further, cMet Ab treatment alleviated the inflammation and proliferation of mesangial cells. Hence, ucMet could serve as a clinically significant marker for treating IgAN.
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Affiliation(s)
- Jung Nam An
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Anyang, Korea
| | - Lilin Li
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.,Department of Intensive Care Unit, Yanbian University Hospital, Jilin, China
| | - Junghun Lee
- R&D Center for Innovative Medicines, Helixmith Co., Ltd., Seoul, Korea
| | - Seung-Shin Yu
- R&D Center for Innovative Medicines, Helixmith Co., Ltd., Seoul, Korea
| | - Jin Hyuk Kim
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Jeonghwan Lee
- Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Yong Chul Kim
- Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Dong Ki Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.,Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Yun Kyu Oh
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.,Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Chun Soo Lim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.,Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
| | - Yon Su Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.,Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea
| | - Sunyoung Kim
- R&D Center for Innovative Medicines, Helixmith Co., Ltd., Seoul, Korea
| | - Seung Hee Yang
- Seoul National University Kidney Research Institute, Seoul, Korea.,Biomedical Research Institute, Seoul National University Hospital, Seoul, Korea
| | - Jung Pyo Lee
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.,Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea
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Yu B, Shi S, Hou W, Liu L, Lv J, Wang S, Zhang H. Evaluation of the Oxford classification in immunoglobulin A vasculitis with nephritis: a cohort study and meta-analysis. Clin Kidney J 2020; 14:516-525. [PMID: 33623674 PMCID: PMC7886544 DOI: 10.1093/ckj/sfaa129] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2020] [Indexed: 12/21/2022] Open
Abstract
Background Similarities in clinicopathological presentations in immunoglobulin A (IgA) nephropathy and IgA vasculitis with nephritis (IgAVN) raise the question of the utility of the Oxford classification in the latter. The aim of this study was to evaluate the Oxford classification in IgAVN. Methods We conducted a retrospective cohort study and meta-analysis following systematic searching of the MEDLINE and Excerpta Medica Database (EMBASE) databases between January 2009 and September 2019. We modeled the association of 30 and 50% decline in estimated glomerular filtration rate or end-stage renal disease with pathologic lesions of the Oxford classification including mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental glomerulosclerosis (S), interstitial fibrosis/tubular atrophy (T) and crescents (C). Results were pooled using random-effects meta-analysis. Results The cohort study included 132 patients, and only T lesion was an independently risk factor in IgAVN. The meta-analysis yielded six retrospective studies with 721 patients and 139 endpoints. In multivariate model, T lesion was significantly associated with renal outcome (hazard ratio = 2.45, P = 0.007). M and C lesions could not predict renal outcome without evidence of heterogeneity. E and S lesions could not predict renal outcome with evidence of heterogeneity (I 2 = 66.6%; P = 0.01, and I 2 = 65.8%; P = 0.03, respectively). Subgroup analysis showed that the possible reasons to the heterogeneity were from usage of immunosuppressant, sample size and follow-up time. Conclusions The study suggests that the Oxford classification could not be fully validated in IgAVN. Higher portion of immunosuppressant especially before renal biopsy might be the main confounder for the predictive value of Oxford classification in IgAVN.
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Affiliation(s)
- Bingxin Yu
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
| | - Sufang Shi
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
| | - Wanyin Hou
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
| | - Lijun Liu
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
| | - Jicheng Lv
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
| | - Suxia Wang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China.,Electron Microscopy Laboratory, Peking University First Hospital, Beijing, China
| | - Hong Zhang
- Renal Division, Department of Medicine, Peking University First Hospital, Beijing, China
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Zeng C, Nan Y, Xu F, Lei Q, Li F, Chen T, Liang S, Hou X, Lv B, Liang D, Luo W, Lv C, Li X, Xie G, Liu Z. Identification of glomerular lesions and intrinsic glomerular cell types in kidney diseases via deep learning. J Pathol 2020; 252:53-64. [PMID: 32542677 PMCID: PMC7496925 DOI: 10.1002/path.5491] [Citation(s) in RCA: 49] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2020] [Revised: 05/26/2020] [Accepted: 06/05/2020] [Indexed: 12/14/2022]
Abstract
Identification of glomerular lesions and structures is a key point for pathological diagnosis, treatment instructions, and prognosis evaluation in kidney diseases. These time‐consuming tasks require a more accurate and reproducible quantitative analysis method. We established derivation and validation cohorts composed of 400 Chinese patients with immunoglobulin A nephropathy (IgAN) retrospectively. Deep convolutional neural networks and biomedical image processing algorithms were implemented to locate glomeruli, identify glomerular lesions (global and segmental glomerular sclerosis, crescent, and none of the above), identify and quantify different intrinsic glomerular cells, and assess a network‐based mesangial hypercellularity score in periodic acid–Schiff (PAS)‐stained slides. Our framework achieved 93.1% average precision and 94.9% average recall for location of glomeruli, and a total Cohen's kappa of 0.912 [95% confidence interval (CI), 0.892–0.932] for glomerular lesion classification. The evaluation of global, segmental glomerular sclerosis, and crescents achieved Cohen's kappa values of 1.0, 0.776, 0.861, and 95% CI of (1.0, 1.0), (0.727, 0.825), (0.824, 0.898), respectively. The well‐designed neural network can identify three kinds of intrinsic glomerular cells with 92.2% accuracy, surpassing the about 5–11% average accuracy of junior pathologists. Statistical interpretation shows that there was a significant difference (P value < 0.0001) between this analytic renal pathology system (ARPS) and four junior pathologists for identifying mesangial and endothelial cells, while that for podocytes was similar, with P value = 0.0602. In addition, this study indicated that the ratio of mesangial cells, endothelial cells, and podocytes within glomeruli from IgAN was 0.41:0.36:0.23, and the performance of mesangial score assessment reached a Cohen's kappa of 0.42 and 95% CI (0.18, 0.69). The proposed computer‐aided diagnosis system has feasibility for quantitative analysis and auxiliary recognition of glomerular pathological features. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.
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Affiliation(s)
- Caihong Zeng
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China
| | - Yang Nan
- Ping An Healthcare Technology, Shang Hai, PR China
| | - Feng Xu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China
| | - Qunjuan Lei
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China
| | - Fengyi Li
- Ping An Healthcare Technology, Shang Hai, PR China
| | - Tingyu Chen
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China
| | - Shaoshan Liang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China
| | | | - Bin Lv
- Ping An Healthcare Technology, Shang Hai, PR China
| | - Dandan Liang
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China
| | - WeiLi Luo
- Ping An Healthcare Technology, Shang Hai, PR China
| | - Chuanfeng Lv
- Ping An Healthcare Technology, Shang Hai, PR China
| | - Xiang Li
- Ping An Healthcare Technology, Shang Hai, PR China
| | - Guotong Xie
- Ping An Healthcare Technology, Shang Hai, PR China
| | - Zhihong Liu
- National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing University School of Medicine, Nanjing, PR China
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50
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Validation of the revised Oxford classification for IgA nephropathy considering treatment with corticosteroids/immunosuppressors. Sci Rep 2020; 10:11151. [PMID: 32636449 PMCID: PMC7341848 DOI: 10.1038/s41598-020-68087-y] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2020] [Accepted: 06/18/2020] [Indexed: 11/18/2022] Open
Abstract
The Oxford classification for IgA nephropathy (IgAN) was updated in 2017. We have validated the revised Oxford classification considering treatment with corticosteroids/immunosuppressors. In this retrospective analysis, 871 IgAN patients were enrolled. Patients were divided into two groups, those treated with or without corticosteroids/immunosuppressors. The 20-year renal prognosis up to end-stage renal disease was assessed using the Oxford classification. In all patients, the renal survival rate was 87.5% at 10 years and 72.6% at 20 years. The T score alone was significantly related to renal prognosis in the Kaplan–Meier analysis and multivariate Cox regression analysis. In the non-treatment group (n = 445), E, S, T, and C scores were significantly related to renal survival rates, however, in the treatment group (n = 426), T score alone was significantly related to renal prognosis on Kaplan–Meier analysis, indicating that corticosteroids/immunosuppressors improved renal prognosis in E1, S1, and C1. In patients with E1, S1, or C1, the treatment group showed significantly better renal prognosis than the non-treatment group in univariate and multivariate analysis. The Oxford classification and T score were used to determine renal prognosis in IgAN patients. Corticosteroids/immunosuppressors improved renal prognosis, especially E1, S1, and C1 scores.
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