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Takahara M, Doi A, Inoshita A, Ohori J, Kono M, Hirano A, Kakuki T, Yamada K, Akagi H, Takano K, Nakata S, Harabuchi Y. Guidance of clinical management for patients with tonsillar focal disease. Auris Nasus Larynx 2024; 51:761-773. [PMID: 38875993 DOI: 10.1016/j.anl.2024.05.010] [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: 03/30/2024] [Revised: 05/13/2024] [Accepted: 05/20/2024] [Indexed: 06/16/2024]
Abstract
Tonsillar focal diseases (TFDs) are defined as "diseases caused by organic and/or functional damage in organs distant from tonsil, and the disease outcome is improved by tonsillectomy." Although several reports and reviews have shown the efficacy of tonsillectomy for TFDs, no guidelines for the clinical management of the diagnosis and treatment of TFDs have been reported. Therefore, the Society of Stomato-pharyngology established a committee to guide the clinical management of patients with TFDs, and the original guide was published in May 2023. This article summarizes the English version of the manuscript. We hope that the concept of TFDs will spread worldwide, and that one as many patients with TFDs will benefit from tonsillectomy.
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Affiliation(s)
- Miki Takahara
- Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Midorigaoka higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan.
| | - Akira Doi
- Division of Otolaryngology, Kochi Health Sciences Center
| | - Ayako Inoshita
- Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, 3-1-3 Hongo, Bunkyo-ku, Tokyo, 113-8431, Japan
| | - Junichiro Ohori
- Department of Otolaryngology-Head and Neck Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima, 890-8544, Japan
| | - Masamitsu Kono
- Department of Otorhinolaryngology-Head and Neck Surgery, Wakayama Medical University, 911-1 Kimiidera, Wakayama-shi, 641-8509, Japan
| | - Ai Hirano
- Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi Aoba-ku, Sendai, Miyagi, 980-8575, Japan
| | - Takuya Kakuki
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, S1 W17, Chuo-ku, Sapporo, Hokkaido, 060-8556, Japan
| | - Kentaro Yamada
- Department of Otorhinolaryngology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Kahoku, Ishikawa, 920-0293, Japan
| | | | - Kenichi Takano
- Department of Otolaryngology-Head and Neck Surgery, Sapporo Medical University School of Medicine, S1 W17, Chuo-ku, Sapporo, Hokkaido, 060-8556, Japan
| | - Seiichi Nakata
- Department of Otorhinolaryngology, Fujita Health University Bantane Hospital, 3-6-10 Otohashi, Nakagawa-ku, Nagoya, Aichi, 454-8509, Japan
| | - Yasuaki Harabuchi
- Department of Otolaryngology-Head and Neck Surgery, Asahikawa Medical University, Midorigaoka higashi 2-1-1-1, Asahikawa, Hokkaido, 078-8510, Japan
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Tunnicliffe DJ, Reid S, Craig JC, Samuels JA, Molony DA, Strippoli GF. Non-immunosuppressive treatment for IgA nephropathy. Cochrane Database Syst Rev 2024; 2:CD003962. [PMID: 38299639 PMCID: PMC10832348 DOI: 10.1002/14651858.cd003962.pub3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/02/2024]
Abstract
BACKGROUND IgA nephropathy (IgAN) is the most common primary glomerular disease, with approximately 20% to 40% of patients progressing to kidney failure within 25 years. Non-immunosuppressive treatment has become a mainstay in the management of IgAN by improving blood pressure (BP) management, decreasing proteinuria, and avoiding the risks of long-term immunosuppressive management. Due to the slowly progressive nature of the disease, clinical trials are often underpowered, and conflicting information about management with non-immunosuppressive treatment is common. This is an update of a Cochrane review, first published in 2011. OBJECTIVES To assess the benefits and harms of non-immunosuppressive treatment for treating IgAN in adults and children. We aimed to examine all non-immunosuppressive therapies (e.g. anticoagulants, antihypertensives, dietary restriction and supplementation, tonsillectomy, and herbal medicines) in the management of IgAN. SEARCH METHODS We searched the Cochrane Kidney and Transplant Register of Studies up to December 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and ClinicalTrials.gov. SELECTION CRITERIA Randomised controlled trials (RCTs) and quasi-RCTs of non-immunosuppressive agents in adults and children with biopsy-proven IgAN were included. DATA COLLECTION AND ANALYSIS Two authors independently reviewed search results, extracted data and assessed study quality. Results were expressed as mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI) using random-effects meta-analysis. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS This review includes 80 studies (4856 participants), of which 24 new studies (2018 participants) were included in this review update. The risk of bias within the included studies was mostly high or unclear for many of the assessed methodological domains, with poor reporting of important key clinical trial methods in most studies. Antihypertensive therapies were the most examined non-immunosuppressive therapy (37 studies, 1799 participants). Compared to placebo or no treatment, renin-angiotensin system (RAS) inhibition probably decreases proteinuria (3 studies, 199 participants: MD - 0.71 g/24 h, 95% CI -1.04 to -0.39; moderate certainty evidence) but may result in little or no difference to kidney failure or doubling of serum creatinine (SCr), or complete remission of proteinuria (low certainty evidence). Death, remission of haematuria, relapse of proteinuria or > 50% increase in SCr were not reported. Compared to symptomatic treatment, RAS inhibition (3 studies, 168 participants) probably decreases proteinuria (MD -1.16 g/24 h, 95% CI -1.52 to -0.81) and SCr (MD -9.37 µmol/L, 95% CI -71.95 to -6.80) and probably increases creatinine clearance (2 studies, 127 participants: MD 23.26 mL/min, 95% CI 10.40 to 36.12) (all moderate certainty evidence); however, the risk of kidney failure is uncertain (1 study, 34 participants: RR 0.20, 95% CI 0.01 to 3.88; very low certainty evidence). Death, remission of proteinuria or haematuria, or relapse of proteinuria were not reported. The risk of adverse events may be no different with RAS inhibition compared to either placebo or symptomatic treatment (low certainty evidence). In low certainty evidence, tonsillectomy in people with IgAN in addition to standard care may increase remission of proteinuria compared to standard care alone (2 studies, 143 participants: RR 1.90, 95% CI 1.45 to 2.47) and remission of microscopic haematuria (2 studies, 143 participants: RR 1.93, 95% CI 1.47 to 2.53) and may decrease relapse of proteinuria (1 study, 73 participants: RR 0.70, 95% CI 0.57 to 0.85) and relapse of haematuria (1 study, 72 participants: RR 0.70, 95% CI 0.51 to 0.98). Death, kidney failure and a > 50% increase in SCr were not reported. These trials have only been conducted in Japanese people with IgAN, and the findings' generalisability is unclear. Anticoagulant therapy, fish oil, and traditional Chinese medicines exhibited small benefits to kidney function in patients with IgAN when compared to placebo or no treatment. However, compared to standard care, the kidney function benefits are no longer evident. Antimalarial therapy compared to placebo in one study reported an increase in a > 50% reduction of proteinuria (53 participants: RR 3.13 g/24 h, 95% CI 1.17 to 8.36; low certainty evidence). Although, there was uncertainty regarding adverse events from this study due to very few events. AUTHORS' CONCLUSIONS Available RCTs focused on a diverse range of interventions. They were few, small, and of insufficient duration to determine potential long-term benefits on important kidney and cardiovascular outcomes and harms of treatment. Antihypertensive agents appear to be the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined were predominantly angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The benefits of RAS inhibition appear to outweigh the harms in patients with IgAN. The certainty of the evidence of RCTs demonstrating a benefit of tonsillectomy to patients with Japanese patients with IgAN was low. In addition, these findings are inconsistent across observational studies in people with IgAN of other ethnicities; hence, tonsillectomy is not widely recommended, given the potential harm of therapy. The RCT evidence is insufficiently robust to demonstrate efficacy for the other non-immunosuppressive treatments evaluated here.
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Affiliation(s)
| | - Sharon Reid
- Central Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, Australia
| | - Jonathan C Craig
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- College of Medicine and Public Health, Flinders University, Adelaide, Australia
| | - Joshua A Samuels
- Division of Pediatric Nephrology and Hypertension, UT-Houston Health Science Center, Houston, TX, USA
| | - Donald A Molony
- Internal Medicine, UT-Houston Health Science Center, Houston, TX, USA
| | - Giovanni Fm Strippoli
- Cochrane Kidney and Transplant, Centre for Kidney Research, The Children's Hospital at Westmead, Westmead, Australia
- Department of Emergency and Organ Transplantation, University of Bari, Bari, Italy
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Lee M, Suzuki H, Nihei Y, Matsuzaki K, Suzuki Y. Ethnicity and IgA nephropathy: worldwide differences in epidemiology, timing of diagnosis, clinical manifestations, management and prognosis. Clin Kidney J 2023; 16:ii1-ii8. [PMID: 38053973 PMCID: PMC10695519 DOI: 10.1093/ckj/sfad199] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/03/2023] [Indexed: 12/07/2023] Open
Abstract
Immunoglobulin A nephropathy (IgAN), the most common primary glomerulonephritis, is one of the major causes of end-stage renal disease. Significant variances in epidemiology, clinical manifestation, timing of diagnosis, management and renal prognosis of IgAN have been reported worldwide. The incidence of IgAN is the most frequent in Asia, followed by Europe, and lower in Africa. Moreover, Asian patients show more frequent acute lesions in renal histology and present poorer renal outcomes compared with Caucasians. The comorbidities also show the difference between Asians and Caucasians. Although the frequency of gross hematuria with upper respiratory tract infection is not different, comorbidities with gastrointestinal diseases are reported to be higher in Europe. Recently, genetic studies for variant ethnic patients revealed widely ranging genetic risks in each ethnicity. A genetic risk score is most elevated in Asians, intermediate in Europeans and lowest in Africans, consistent with the disease prevalence of IgAN globally. Ethnic variance might be highly affected by the difference in genetic background. However, it is also essential to mention that the different timing of diagnosis due to variant urinary screening systems and the indication for renal biopsy in different countries may also contribute to these variances. The management of IgAN also varies internationally. Currently, several novel therapies based on the pathogenesis of IgAN are being assessed and are expected to become available soon. Further understanding the ethnic variance of IgAN might help establish individualized care for this disease. Here, we review the issues of ethnic heterogeneities of IgAN.
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Affiliation(s)
- Mingfeng Lee
- Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Hitoshi Suzuki
- Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
- Department of Nephrology, Juntendo University Urayasu Hospital, Chiba, Japan
| | - Yoshihito Nihei
- Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
| | - Keiichi Matsuzaki
- Department of Public Health, Kitasato University School of Medicine, Kanagawa, Japan
| | - Yusuke Suzuki
- Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
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Li Y, Wan Q, Lan Z, Xia M, Liu H, Chen G, He L, Wang C, Liu H. Efficacy and indications of tonsillectomy in patients with IgA nephropathy: a retrospective study. PeerJ 2022; 10:e14481. [PMID: 36523468 PMCID: PMC9745907 DOI: 10.7717/peerj.14481] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2021] [Accepted: 11/08/2022] [Indexed: 12/12/2022] Open
Abstract
Background The efficacy and indications of tonsillectomy in IgA nephropathy (IgAN) remain uncertain. Methods We performed a retrospective cohort study of 452 patients with primary IgAN, including 226 patients who received tonsillectomy and 226 controls selected by propensity score matching who had never undergone tonsillectomy. Study outcomes were clinical remission defined as negative hematuria and proteinuria on three consecutive visits over a 6-month period, the endpoint defined as end-stage renal disease or an irreversible 100% increase in serum creatinine from the baseline value. In addition, we further analyzed the critical level of proteinuria in the efficacy of tonsillectomy and the correlation between MEST-C score and tonsillectomy. Results Up to December 2019, the follow-up period lasted 46 ± 23 months (12-106 months). Kaplan-Meier and multivariate Cox regression analysis revealed that tonsillectomy was beneficial for clinical remission and renal survival. Whether proteinuria was ≤ 1 g/24h or >1 g/24h, the clinical remission and renal survival rates were greater in patients treated with tonsillectomy than without. When the pathological damage was mild or relatively severe, tonsillectomy may be beneficial to clinical remission or renal survival. Conclusions Tonsillectomy had a favorable effect on clinical remission and delayed renal deterioration in IgAN. In addition to patients with early stage IgAN, it may also be beneficial to IgAN patients with higher levels of proteinuria and relatively severe pathological damage.
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Affiliation(s)
- Yan Li
- Department of Nephrology, Hunan Provincial People’s Hospital, Hunan Normal University, Changsha, Hunan, China
| | - Qi Wan
- Department of Orthopedic Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Zhixin Lan
- Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan, China
| | - Ming Xia
- Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan, China
| | - Haiyang Liu
- Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan, China
| | - Guochun Chen
- Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan, China
| | - Liyu He
- Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan, China
| | - Chang Wang
- Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan, China
| | - Hong Liu
- Department of Nephrology, The Second Xiangya Hospital, Central South University, Hunan Key Laboratory of Kidney Disease and Blood Purification, Changsha, Hunan, China
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Mucosal Immune System Dysregulation in the Pathogenesis of IgA Nephropathy. Biomedicines 2022; 10:biomedicines10123027. [PMID: 36551783 PMCID: PMC9775168 DOI: 10.3390/biomedicines10123027] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2022] [Revised: 11/20/2022] [Accepted: 11/22/2022] [Indexed: 11/25/2022] Open
Abstract
The mucosal immune system, via a dynamic immune network, serves as the first line of defense against exogenous antigens. Mucosal immune system dysregulation is closely associated with the pathogenesis of immunoglobulin A nephropathy (IgAN), as illustrated by IgAN having the clinical feature of gross hematuria, often concurrent with mucosal infections. Notably, previous studies have demonstrated the efficacy of tonsillectomy and found that a targeted-release formulation of budesonide reduced proteinuria in patients with IgAN. However, it remains unclear how exogenous antigens interact with the mucosal immune system to induce or exacerbate IgAN. Thus, in this review, we focus on the dysregulation of mucosal immune response in the pathogenesis of IgAN.
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The influences of α-hemolytic Streptococcus on class switching and complement activation of human tonsillar cells in IgA nephropathy. Immunol Res 2021; 70:86-96. [PMID: 34642907 DOI: 10.1007/s12026-021-09223-2] [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: 01/21/2021] [Accepted: 07/25/2021] [Indexed: 10/20/2022]
Abstract
While β-hemolytic streptococcus (β-HS) infections are known to predispose patients to acute poststreptococcal glomerulonephritis, there is evidence that implicates α-hemolytic streptococcus (α-HS) in IgA nephropathy (IgAN). The alternative pathway of the complement system has also been implicated in IgAN. We aimed to explore the association between α-HS and complement activation in human tonsillar mononuclear cells (TMCs) in IgAN. In our study, α-HS induced higher IgA levels than IgG levels, while β-HS increased higher IgG levels than IgA levels with more activation-induced cytidine deaminase, in TMCs in the IgAN group. Aberrant IgA1 O-glycosylation levels were higher in IgAN patients with α-HS. C3 and C3b expression was decreased in IgAN patients, but in chronic tonsillitis control patients, the expression decreased only after stimulation with β-HS. Complement factor B and H (CFH) mRNA increased, but the CFH concentration in culture supernatants decreased with α-HS. The percentage of CD19 + CD35 + cells/complement receptor 1 (CR1) decreased with α-HS more than with β-HS, while CD19 + CD21 + cells/complement receptor 2 (CR2) increased more with β-HS than with α-HS. The component nephritis-associated plasmin receptor (NAPlr) of α-HS was not detected on tonsillar or kidney tissues in IgAN patients and was positive on cultured TMCs and mesangial cells. We concluded that α-HS induced the secretion of aberrantly O-glycosylated IgA while decreasing the levels of the inhibitory factor CFH in culture supernatants and CR1 + B cells. These findings provide testable mechanisms that relate α-HS infection to abnormal mucosal responses involving the alternative complement pathway in IgAN.
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Impact of the number of steroid pulses in tonsillectomy combined with steroid pulse therapy: a nationwide retrospective study in Japan. Clin Exp Nephrol 2020; 25:19-27. [PMID: 32880761 DOI: 10.1007/s10157-020-01960-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2020] [Accepted: 08/21/2020] [Indexed: 12/20/2022]
Abstract
BACKGROUND Steroid pulse therapy with tonsillectomy is known as a major treatment for IgA nephropathy (IgAN). However, its protocol was different among institutions and the effects of varying the number of steroid pulses remain unclear. METHODS From a total of 1,174 IgAN patients in a multicenter retrospective cohort analysis in Japan, 195 patients were treated by tonsillectomy combined with corticosteroid. They were divided into four groups based on the number of administered steroid pulses from 0 to three (TSP0-3), and remission of urinary abnormalities and renal survival until 1.5-fold increase in serum creatinine level from baseline were analyzed among the four groups and between TSP1 and TSP3. RESULTS Among the four groups, renal function was relatively good when the estimated glomerular filtration rate was approximately 80-90 mL/min/1.73m2 and proteinuria was relatively mild (< 1.0 g/gCre). The ratio of patients who developed renal dysfunction was < 5% in all groups, and the cumulative renal survival rate by Kaplan-Meier analysis was similar among groups (log-rank test, p = 0.37), despite varying clinical backgrounds and treatments. After adjustment of the background variables between TSP1 and TSP3, the remission rates of urinary abnormalities were similar and the renal survival rate also remained similar (66.8 vs. 85.4%, p = 0.45). CONCLUSIONS In patients with mild proteinuria and good renal function, the number of steroid pulses did not affect the renal outcome in steroid pulse therapy with tonsillectomy. The adaptation and protocols, such as the number of steroid pulses, should be determined for each IgAN patient's background.
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Hirano K, Matsuzaki K, Yasuda T, Nishikawa M, Yasuda Y, Koike K, Maruyama S, Yokoo T, Matsuo S, Kawamura T, Suzuki Y. Association Between Tonsillectomy and Outcomes in Patients With Immunoglobulin A Nephropathy. JAMA Netw Open 2019; 2:e194772. [PMID: 31150076 PMCID: PMC6547111 DOI: 10.1001/jamanetworkopen.2019.4772] [Citation(s) in RCA: 68] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
IMPORTANCE Immunoglobulin A nephropathy is a major cause of end-stage renal disease worldwide; previous methods of medical management, including use of renin-angiotensin system inhibitors and corticosteroids, remain unproven in clinical trials. OBJECTIVE To investigate the possible association between tonsillectomy and outcomes in patients with IgA nephropathy. DESIGN, SETTING, AND PARTICIPANTS This cohort study included 1065 patients with IgA nephropathy enrolled between 2002 and 2004 and divided into 2 groups, those who underwent tonsillectomy and those who did not. Initial treatments (renin-angiotensin system inhibitors or corticosteroids) within 1 year after renal biopsy were also evaluated. A 1:1 propensity score matching was performed to account for between-group differences and 153 matched pairs were obtained. Follow-up concluded January 31, 2014. Analysis was conducted between September 11, 2017, and July 31, 2018. EXPOSURE Tonsillectomy. MAIN OUTCOMES AND MEASURES The primary outcome was the first occurrence of a 1.5-fold increase in serum creatinine level from baseline or dialysis initiation. Secondary outcomes included additional therapy with renin-angiotensin system inhibitors or corticosteroids initiated 1 year after renal biopsy and adverse events. RESULTS In 1065 patients (49.8% women; median [interquartile range] age, 35 [25-52] years), the mean (SD) estimated glomerular filtration rate was 76.6 (28.9) mL/min/1.73 m2 and the median (interquartile range) proteinuria was 0.68 (0.29-1.30) g per day. In all, 252 patients (23.7%) underwent tonsillectomy within 1 year after renal biopsy and 813 patients (76.3%) did not undergo tonsillectomy. The primary outcome was reached by 129 patients (12.1%) during a median (interquartile range) follow-up of 5.8 (1.9-8.5) years. In matching analysis, tonsillectomy was associated with primary outcome reduction (hazard ratio, 0.34; 95% CI, 0.13-0.77; P = .009). In subgroup analyses, benefit associated with tonsillectomy was not modified by baseline characteristic differences. Those undergoing tonsillectomy required fewer additional therapies 1 year following renal biopsy (adjusted hazard ratio, 0.37; 95% CI, 0.20-0.63; P < .001) without increased risks for adverse events, except transient tonsillectomy-related complications. CONCLUSIONS AND RELEVANCE This study found that tonsillectomy was associated with a lower risk of renal outcomes in patients with IgA nephropathy. The potential role of tonsillectomy should be considered for preventing end-stage renal disease in patients with IgA nephropathy.
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Affiliation(s)
- Keita Hirano
- Division of Nephrology, Department of Internal Medicine, Ashikaga Red Cross Hospital, Ashikaga, Japan
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
| | - Keiichi Matsuzaki
- Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
- Kyoto University Health Service, Kyoto, Japan
| | - Takashi Yasuda
- Department of Internal Medicine, Kichijoji Asahi Hospital, Kyoto, Japan
| | - Masako Nishikawa
- Clinical Research Support Center, Jikei University School of Medicine, Tokyo, Japan
| | | | - Kentaro Koike
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
| | | | - Takashi Yokoo
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
| | - Seiichi Matsuo
- Department of Nephrology, Nagoya University, Nagoya, Japan
| | - Tetsuya Kawamura
- Division of Nephrology and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan
| | - Yusuke Suzuki
- Department of Nephrology, Juntendo University Faculty of Medicine, Tokyo, Japan
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Matsumoto K, Ikeda Y, Yamaguchi S, Sanematsu M, Fukuda M, Takashima T, Kishi T, Miyazono M, Uchiumi S, Yoshizaki M, Nonaka Y, Matsumoto R, Kanaya A, Fukunari K, Ikeda Y. Long-term outcomes of tonsillectomy for IgA nephropathy patients: A retrospective cohort study, two-centre analysis with the inverse probability therapy weighting method. Nephrology (Carlton) 2017; 23:846-854. [PMID: 28703898 DOI: 10.1111/nep.13108] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/03/2017] [Indexed: 11/25/2022]
Abstract
AIM The effect of tonsillectomy on IgA nephropathy remains controversial. The aim of this study was to compare the effect of tonsillectomy on the outcome, end stage kidney disease (ESKD) and all-cause death in IgA nephropathy patients who did and did not undergo tonsillectomy. METHODS All basic data were retrospectively gathered from patients who had undergone renal biopsies at two Japanese clinical centres. Two hundred and twenty-seven patients were eligible for the study, with a median age of 34 (Interquartile range (IQR): 25-43) years and median follow-up of 92 (IQR: 40-178) months. The primary endpoint was the composite outcome of the onset of ESKD and all-cause death before ESKD. We performed a Cox proportional hazard regression analysis after adjusting for patient characteristics using the inverse probability therapy weighting (IPTW) method and a Cox analysis using the Matching method. Similarly, we analyzed these outcomes in a mild cohort. RESULTS We were unable to find any significant advantages of tonsillectomy in either analysis (IPTW and matching, HR: 0.40 (0.12-1.36) P = 0.072 and 0.78 (0.13-4.64) P = 0.786). However, in the mild cohort analysis, our data showed that the Tonsillectomy group tended to be less likely to reach the composite outcomes than the Not Tonsillectomy group with statistical significance (hazard ratio (HR), <0.001 [CI <0.001 to <0.001, P = 0.039]). CONCLUSION In this study, our findings led us to conclude that performing tonsillectomy in an early and timely manner may have predisposition of less poor prognosis.
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Affiliation(s)
- Keiichiro Matsumoto
- Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan
| | - Yuki Ikeda
- Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan
| | - Sae Yamaguchi
- Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan
| | - Mai Sanematsu
- Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan
| | - Makoto Fukuda
- Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan
| | - Tsuyoshi Takashima
- Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan
| | - Tomoya Kishi
- Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan
| | - Motoaki Miyazono
- Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan
| | - Saori Uchiumi
- Department of Nephrology, Sasebo Kyosai Hospital, Nagasaki, Japan
| | - Mai Yoshizaki
- Department of Nephrology, Sasebo Kyosai Hospital, Nagasaki, Japan
| | - Yasunori Nonaka
- Department of Nephrology, Sasebo Kyosai Hospital, Nagasaki, Japan
| | - Ryoko Matsumoto
- Department of Nephrology, Sasebo Kyosai Hospital, Nagasaki, Japan
| | - Akiko Kanaya
- Department of Nephrology, Sasebo Kyosai Hospital, Nagasaki, Japan
| | - Kenichi Fukunari
- Department of Nephrology, Sasebo Kyosai Hospital, Nagasaki, Japan
| | - Yuji Ikeda
- Department of Internal Medicine, Saga University Faculty of Medicine, Saga, Japan
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Sato M, Adachi M, Kosukegawa H, Nomura Y, Watanabe K, Sato T, Taguma Y. The size of palatine tonsils cannot be used to decide the indication of tonsillectomy for IgA nephropathy. Clin Kidney J 2017; 10:221-228. [PMID: 28396738 PMCID: PMC5381239 DOI: 10.1093/ckj/sfw125] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2016] [Accepted: 10/19/2016] [Indexed: 11/21/2022] Open
Abstract
Background. Tonsillectomy is one of the treatment strategies for immunoglobulin A nephropathy (IgAN). The relationship between the indication of tonsillectomy and the size of palatine tonsils (PTs) in patients with IgAN remains controversial. Methods. This retrospective cohort study investigated 57 patients with IgAN who underwent tonsillectomy combined with steroid pulse therapy (SPT). They were classified into two groups, the hypertrophy group and the nonhypertrophy group, according to the weight of their excised PTs. The effects of tonsillectomy combined with SPT on clinical remission (CR) and the histopathological findings of PTs were compared between the two groups. Results. During the mean follow-up period of 45.5 (range 6–133) months, 78.9% of the patients achieved CR (79.3 versus 78.6%, P = 0.945) and the baseline serum creatinine doubled only in one patient in the nonhypertrophy group (0 versus 3.6%, P = 0.491). No significant difference was observed in the incidence of CR between the two groups by the Kaplan–Meier method (P = 0.839). The predictor for CR, identified in Cox proportional hazards models, was baseline proteinuria [hazard ratio 0.14 (95% CI 0.032–0.621) P = 0.010]. Although macroscopic pus plugs were observed on the surface of PTs in almost 60% of patients in each group, microscopic pus plugs in the crypt and the enlarged interfollicular area were observed in all patients. Conclusions. The treatment effect of tonsillectomy combined with SPT and the pathological features of PTs in IgAN were equal, regardless of the size of the PTs. Therefore, the size of PTs should not be included as a factor when deciding the indication of tonsillectomy for IgAN.
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Affiliation(s)
- Mitsuhiro Sato
- Department of Nephrology, Japan Community Healthcare Organization Sendai Hospital, Sendai, Miyagi, Japan
| | - Mika Adachi
- Department of Otorhinolaryngology, Head and Neck Surgery, Tohoku University School of Medicine, Sendai, Miyagi, Japan
| | - Hideyuki Kosukegawa
- Department of Nephrology, Japan Community Healthcare Organization Sendai Hospital, Sendai, Miyagi, Japan
| | - Yuri Nomura
- Department of Otorhinolaryngology, Head and Neck Surgery, Tohoku University School of Medicine, Sendai, Miyagi, Japan
| | - Kenichi Watanabe
- Department of Otorhinolaryngology, Head and Neck Surgery, Tohoku University School of Medicine, Sendai, Miyagi, Japan
| | - Toshinobu Sato
- Department of Nephrology, Japan Community Healthcare Organization Sendai Hospital, Sendai, Miyagi, Japan
| | - Yoshio Taguma
- Department of Nephrology, Japan Community Healthcare Organization Sendai Hospital, Sendai, Miyagi, Japan
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Windfuhr JP. Indications for tonsillectomy stratified by the level of evidence. GMS CURRENT TOPICS IN OTORHINOLARYNGOLOGY, HEAD AND NECK SURGERY 2016; 15:Doc09. [PMID: 28025609 PMCID: PMC5169082 DOI: 10.3205/cto000136] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Background: One of the most significant clinical trials, demonstrating the efficacy of tonsillectomy (TE) for recurrent throat infection in severely affected children, was published in 1984. This systematic review was undertaken to compile various indications for TE as suggested in the literature after 1984 and to stratify the papers according to the current concept of evidence-based medicine. Material and methods: A systematic Medline research was performed using the key word of "tonsillectomy" in combination with different filters such as "systematic reviews", "meta-analysis", "English", "German", and "from 1984/01/01 to 2015/05/31". Further research was performed in the Cochrane Database of Systematic Reviews, National Guideline Clearinghouse, Guidelines International Network and BMJ Clinical Evidence using the same key word. Finally, data from the "Trip Database" were researched for "tonsillectomy" and "indication" and "from: 1984 to: 2015" in combination with either "systematic review" or "meta-analysis" or "metaanalysis". Results: A total of 237 papers were retrieved but only 57 matched our inclusion criteria covering the following topics: peritonsillar abscess (3), guidelines (5), otitis media with effusion (5), psoriasis (3), PFAPA syndrome (6), evidence-based indications (5), renal diseases (7), sleep-related breathing disorders (11), and tonsillitis/pharyngitis (12), respectively. Conclusions: 1) The literature suggests, that TE is not indicated to treat otitis media with effusion. 2) It has been shown, that the PFAPA syndrome is self-limiting and responds well to steroid administration, at least in a considerable amount of children. The indication for TE therefore appears to be imbalanced but further research is required to clarify the value of surgery. 3) Abscesstonsillectomy as a routine is not justified and indicated only for cases not responding to other measures of treatment, evident complications, or with a significant history of tonsillitis. In particular, interval-tonsillectomy is not justified as a routine. 4) TE, with or without adenoidectomy, is efficacious to resolve sleep-related breathing disorders resulting from (adeno)tonsillar hypertrophy in children. However, the benefit is reduced by co-morbidities, such as obesity, and further research is required to identify prognostic factors for this subgroup of patients. Further research is indicated to clarify selection criteria not only for this subpopulation that may benefit from less invasive procedures such as tonsillotomy in the long-term. 5) Further trials are also indicated to evaluate the efficacy of TE on the clinical course in children with psoriasis guttata as well as on psoriasis vulgaris in adults, not responding to first-line therapy. 6) Conflicting results were reported concerning the role of TE in the concert to treat Ig-A nephropathy, mandating further clinical research. 7) Most importantly, randomized-controlled clinical trials with an adequate long-term follow-up are desirable to clarify the benefit of TE in patients with recurrent episodes of tonsillitis, with or without pharyngitis. Factors like age, spontaneous healing rate and postoperative quality of life have to be included when comparing TE with antibiotic therapy.
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Affiliation(s)
- Jochen P. Windfuhr
- Department of Otolaryngology, Head & Neck Surgery, Allergology, Kliniken Maria Hilf, Mönchengladbach, Germany
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Duan J, Liu D, Duan G, Liu Z. Long-term efficacy of tonsillectomy as a treatment in patients with IgA nephropathy: a meta-analysis. Int Urol Nephrol 2016; 49:103-112. [PMID: 27722990 DOI: 10.1007/s11255-016-1432-7] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2016] [Accepted: 09/27/2016] [Indexed: 12/12/2022]
Abstract
PURPOSE IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide and will lead some unfavorable outcomes such as end-stage renal disease. The efficacy of tonsillectomy remains controversial in both Asian and Caucasian ethnicity. Our meta-analysis was aiming at exploring its long-term efficacy and providing further evidences for clinical treatment. METHODS Prospective and retrospective studies that compared the rate of clinical remission and/or end-stage renal disease in IgAN patients who applied tonsillectomy were involved in our meta-analysis. The online databases we searched were PubMed, Embase, Cochrane Library, and Web of Science RESULTS: Nineteen studies with a total of 3483 participants are involved in our meta-analysis. It is found that treatment of tonsillectomy is significantly associated with a higher rate of clinical remission (15 studies, 3059 participants; pooled OR 3.30, 95 % CI 2.47-4.40). Meanwhile, tonsillectomy shows positive effect on refraining from developing end-stage renal disease (9 studies, 1804 participants; pooled OR 0.33, 95 % CI 0.16-0.69). In following two subgroup analyses, we integrate studies with more than 5 years of follow-up from clinical remission group and end-stage renal disease group. Both of them show that tonsillectomy has favorable long-term efficacy, pooled OR 3.37 (95 % CI 2.68-4.24) and 0.20 (95 % CI 0.12-0.33), respectively. CONCLUSIONS Long-term efficacy of tonsillectomy indicates that this treatment is helpful in inducing clinical remission and inhibiting development of end-stage renal disease in patients with IgAN and should be considered for addition into standard clinical treatment.
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Affiliation(s)
- Jiayu Duan
- Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Research Institute of Nephrology, Zhengzhou University, Zhengzhou, Henan, China
| | - Dongwei Liu
- Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Research Institute of Nephrology, Zhengzhou University, Zhengzhou, Henan, China
| | - Guangcai Duan
- Henan Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine, Xinxiang Medical University Xinxiang, Xinxiang, Henan, China.
| | - Zhangzuo Liu
- Department of Nephrology, First Affiliated Hospital of Zhengzhou University, Research Institute of Nephrology, Zhengzhou University, Zhengzhou, Henan, China.
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Vibration Induces BAFF Overexpression and Aberrant O-Glycosylation of IgA1 in Cultured Human Tonsillar Mononuclear Cells in IgA Nephropathy. BIOMED RESEARCH INTERNATIONAL 2016; 2016:9125960. [PMID: 27672662 PMCID: PMC5031824 DOI: 10.1155/2016/9125960] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 07/09/2016] [Accepted: 07/19/2016] [Indexed: 11/23/2022]
Abstract
Objective. To investigate the influence of in vitro vibratory stimulation of human tonsillar mononuclear cells (TMCs). Methods. Fourteen IgA nephropathy (IgAN) patients with chronic tonsillitis (CT) and 12 CT patients with no renal pathology were enrolled. Group A TMCs were collected after 24 hours of culture and used to determine baseline levels. TMCs in groups B, C, D, E, and F were exposed to vibratory stimulation (60 Hz) for 0 (as the control group), 1, 3, 5, and 10 minutes, respectively. Results. Baseline concentrations of B-cell-activation factor (BAFF) and IgA1, BAFF mRNA expression, and aberrant O-glycosylation IgA1 level were higher in the IgAN group as compared to that in the CT group, and all increased after vibratory stimulation. Baseline mRNA expressions of core β1,3-galactosyltransferase (C1GALT1) and core β1,3GalT-specific molecular chaperone (Cosmc) were lower in the IgAN group; the levels decreased further after vibratory stimulation. Conclusion. In patients with IgAN, vibratory stimulation of TMCs appears to induce IgA1 secretion through activation of BAFF release and to aberrant O-glycosylation IgA1 by suppressing C1GALT1 and Cosmc expression. In vitro vibratory stimulation of human TMCs mimics the vibratory simulation of palatine tonsils produced by vocal cords during phonation.
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Hoshino Y, Moriyama T, Uchida K, Tsuchiya K, Nitta K. Comparison of oral steroids with tonsillectomy plus steroid pulse therapy in patients with IgA nephropathy. Clin Exp Nephrol 2016; 21:617-623. [PMID: 27549901 DOI: 10.1007/s10157-016-1324-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Accepted: 08/14/2016] [Indexed: 11/27/2022]
Abstract
BACKGROUND Treatment of IgA nephropathy (IgAN) in Japan has recently changed, from oral prednisolone (oPSL) to tonsillectomy plus steroid pulse (TSP) therapy. However, a few studies have compared their efficacy and safety. METHODS IgAN patients diagnosed in our institution between 1991 and 2013, treated with TSP or oPSL, aged ≥16 years, with ≥1 g/day proteinuria, and estimated glomerular filtration rate (eGFR) ≥30 ml/min/1.73 m2, and no other renal disease were selected. Baseline clinical and histological findings, clinical outcomes, and adverse events were compared. Clinical remission (CR) was defined as <0.3 g/day proteinuria and <5 urinary red blood cells per high-powered field. RESULTS Sixty-six patients were identified; after propensity score adjustment, 26 patients were selected in each group. CR rates were significantly higher at 12 (30.8 % vs. 3.9 %), 36 (47.3 % vs. 7.9 %), and 72 (57.8 % vs. 20.1 %) months (p < 0.01), and the renal survival rate, defined as the development of a 25 % reduction from baseline eGFR, was significantly higher at 12 (96.2 % vs. 69.2 %), 36 (96.2 % vs. 61.5 %), and 72 (96.2 % vs. 41.0 %) months in the TSP than the oPSL group (p < 0.001). Multivariate analysis showed that TSP was the only independent factor associated with CR (hazard ratio, 3.58; 95 % confidence interval, 1.32-10.91, p = 0.01). The number of patients with adverse events was significant lower in TSP group than in oPSL group (11.5 % vs. 34.6 %, p = 0.04). CONCLUSIONS CR rates are higher; protection of renal function and prevention from adverse events were superior with TSP than with oPSL in patients with IgAN and moderate-to-severe proteinuria.
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Affiliation(s)
- Yoshie Hoshino
- Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Takahito Moriyama
- Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
| | - Keiko Uchida
- Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Ken Tsuchiya
- Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
| | - Kosaku Nitta
- Department of Medicine, Kidney Center, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan
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Salvadori M, Rosso G. Update on immunoglobulin a nephropathy. Part II: Clinical, diagnostic and therapeutical aspects. World J Nephrol 2016; 5:6-19. [PMID: 26788460 PMCID: PMC4707169 DOI: 10.5527/wjn.v5.i1.6] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Revised: 11/13/2015] [Accepted: 12/03/2015] [Indexed: 02/06/2023] Open
Abstract
Immunoglobulin A nephropathy (IgAN) is characterized by different clinical manifestations and by long-term different outcomes. Major problem for the physicians is to understanding which patients are at risk of a disease evolution and to prescribe the right therapy to the right patients. Indeed, in addition to patients with a stable disease with no trend to evolution or even with a spontaneous recovery, patients with an active disease and patients with a rapidly evolving glomerulonephritis are described. Several histopathological, biological and clinical markers have been described and are currently used to a better understanding of patients at risk, to suggest the right therapy and to monitor the therapy effect and the IgAN evolution over time. The clinical markers are the most reliable and allow to divide the IgAN patients into three categories: The low risk patients, the intermediate risk patients and the high risk patients. Accordingly, the therapeutic measures range from no therapy with the only need of repeated controls, to supportive therapy eventually associated with low dose immunosuppression, to immunosuppressive treatment in the attempt to avoid the evolution to end stage renal disease. However the current evidence about the different therapies is still matter of discussion. New drugs are in the pipeline and are described. They are object of randomized controlled trials, but studies with a number of patients adequately powered and with a long follow up are needed to evaluate efficacy and safety of these new drugs.
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Feehally J, Coppo R, Troyanov S, Bellur SS, Cattran D, Cook T, Roberts ISD, Verhave JC, Camilla R, Vergano L, Egido J, Wiecek A, Karkoszka H, Tesar V, Maixnerova D, Ots-Rosenberg M, Quaglia M, Rollino C, Magistroni R, Cusinato S, Cravero R, Peruzzi L, Lundberg S, Gesualdo L, Cancarini G, Feriozzi S, Ferrario F. Tonsillectomy in a European Cohort of 1,147 Patients with IgA Nephropathy. Nephron Clin Pract 2015; 132:15-24. [PMID: 26586175 DOI: 10.1159/000441852] [Citation(s) in RCA: 55] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2015] [Accepted: 10/20/2015] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND Tonsillectomy has been considered a treatment for IgA nephropathy (IgAN). It is aimed at removing a source of pathogens, reducing mucosa-associated lymphoid tissue and decreasing polymeric IgA synthesis. However, its beneficial effect is still controversial. In Asia, favorable outcomes have been claimed mostly in association with corticosteroids. In Europe, small, single-center uncontrolled studies have failed to show benefits. METHODS The European validation study of the Oxford classification of IgAN (VALIGA) collected data from 1,147 patients with IgAN over a follow-up of 4.7 years. We investigated the outcome of progression to end-stage renal disease (ESRD) and/or 50% loss of estimated glomerular filtration rate (eGFR) and the annual loss of eGFR in 61 patients who had had tonsillectomy. RESULTS Using the propensity score, which is a logistic regression model, we paired 41 patients with tonsillectomy and 41 without tonsillectomy with similar risk of progression (gender, age, race, mean blood pressure, proteinuria, eGFR at renal biopsy, previous treatments and Oxford MEST scores). No significant difference was found in the outcome. Moreover, we performed an additional propensity score pairing 17 patients who underwent tonsillectomy after the diagnosis of IgAN and 51 without tonsillectomy with similar risk of progression at renal biopsy and subsequent treatments. No significant difference was found in changes in proteinuria, or in the renal end point of 50% reduction in GFR and/or ESRD, or in the annual loss of eGFR. CONCLUSION In the large VALIGA cohort of European subjects with IgAN, no significant correlation was found between tonsillectomy and renal function decline.
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Abstract
The IgA nephropathy (IgAN) is a very common glomerulonephritis and can result in end-stage renal disease. From a clinical point of view, IgAN is characterised by repeated events of macrohaematuria associated with infections of the upper airways. In IgAN, the IgA released by the tonsillar lymphatic tissue into blood circulation are defective in glycosylation. These aberrant IgA can reach the glomeruli and deposit into mesangium causing an inflammation with cellular proliferation. The treatment is not yet well defined: steroids and immunosuppressive drugs are suggested in cases with a progressive disease. Tonsillectomy was proposed to reduce the infective events of upper airways and the lymphatic tissue producing undergalactosylated IgA. The experiences in literature coming from Asia report positive effects of tonsillectomy on IgAN. In patients with tonsillectomy, the renal signs improved (less haematuria and proteinuria) and the renal outcome was better (slower progression of renal damage). These were uncontrolled studies and tonsillectomy was associated with steroid and immunosuppressive treatment, so it is not possible to tell the real effect of tonsillectomy. In contrast, the European studies reported that the tonsillectomy was not associated with a better outcome of IgAN. A critical review of the subject reveals that most of the papers with positive results were uncontrolled retrospective experiences, while in a randomised controlled trial paper the advantages of tonsillectomy disappeared. In conclusion, this review, in agreement with the international guidelines, concludes that tonsillectomy does not play any role in the progression of IgAN.
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Hoshino J, Fujii T, Usui J, Fujii T, Ohashi K, Takaichi K, Suzuki S, Ubara Y, Yamagata K. Renal outcome after tonsillectomy plus corticosteroid pulse therapy in patients with immunoglobulin A nephropathy: results of a multicenter cohort study. Clin Exp Nephrol 2015; 20:618-627. [DOI: 10.1007/s10157-015-1194-z] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2015] [Accepted: 10/28/2015] [Indexed: 12/26/2022]
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Lai KN, Leung JCK, Tang SCW. The Treatment of IgA Nephropathy. KIDNEY DISEASES 2015; 1:19-26. [PMID: 27536661 DOI: 10.1159/000381508] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2015] [Revised: 03/03/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND IgA nephropathy (IgAN) is a very common glomerulonephritis worldwide. Nevertheless, treatment options for primary IgAN are still largely based on opinion or weak evidence. There is a lack of large randomized controlled trials (RCT) that provide a definitive immunosuppressive protocol for IgAN. The recent KDIGO Clinical Practice Guidelines for Glomerulonephritis have assigned low levels of evidence for almost all recommendations and suggestions related to this nephropathy. SUMMARY In this article, we review different treatment options and emphasize that the key to therapeutic decision-making is the assessment of an individual's prognosis. The risk of disease progression is closely related to clinical parameters such as proteinuria, hypertension, and impaired glomerular filtration rate. For patients with minor urinary abnormalities, the mainstay of treatment is long-term regular follow-up to detect renal progression and hypertension. Optimized supportive care aiming to maintain proteinuria <1 g/day is preferred in the typical patient presenting with microhematuria, significant but nonnephrotic proteinuria, hypertension, and variable degrees of renal failure. The atypical patient with overt nephritic syndrome or rapidly progressive kidney injury that represents a vasculitic form of IgAN should be treated with immunosuppression. Finally, the variant of overlapping syndrome of IgAN and lipoid nephrosis that runs a good prognosis should be treated as lipoid nephrosis. KEY MESSAGE The treatment of IgAN should be structured according to the clinical scenario.
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Affiliation(s)
- Kar Neng Lai
- Nephrology Center, Hong Kong Sanatorium and Hospital, University of Hong Kong, Hong Kong, SAR, China; Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, SAR, China
| | - Joseph C K Leung
- Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, SAR, China
| | - Sydney C W Tang
- Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong, SAR, China
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Suzuki Y, Suzuki H, Yasutake J, Tomino Y. Paradigm shift in activity assessment of IgA nephropathy – optimizing the next generation of diagnostic and therapeutic maneuvers via glycan targeting. Expert Opin Biol Ther 2015; 15:583-93. [DOI: 10.1517/14712598.2015.1006624] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
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Liu LL, Wang LN, Jiang Y, Yao L, Dong LP, Li ZL, Li XL. Tonsillectomy for IgA nephropathy: a meta-analysis. Am J Kidney Dis 2014; 65:80-7. [PMID: 25446024 DOI: 10.1053/j.ajkd.2014.06.036] [Citation(s) in RCA: 52] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2014] [Accepted: 06/19/2014] [Indexed: 12/16/2022]
Abstract
BACKGROUND The efficacy of tonsillectomy in immunoglobulin A nephropathy (IgAN) remains controversial. Our meta-analysis was intended to investigate its efficacy as an adjunct or independent treatment. STUDY DESIGN Meta-analysis of prospective and retrospective studies using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. SETTING & POPULATION Patients with IgAN treated with or without tonsillectomy. SELECTION CRITERIA FOR STUDIES Studies that compared clinical remission or end-stage renal disease (ESRD) in patients with IgAN with or without tonsillectomy. INTERVENTION Tonsillectomy. OUTCOMES Clinical remission and ESRD. RESULTS 14 studies (1,794 patients) were included and a random-effects model was applied. There were significantly greater odds of clinical remission with tonsillectomy (10 studies, 1,431 patients; pooled OR, 3.40; 95% CI, 2.58-4.48; P<0.001). Sensitivity analysis to exclude the effects of renin-angiotensin system inhibitors yielded consistent results (6 studies, 671 patients; pooled OR for remission, 2.80; 95% CI, 1.91-4.09; P<0.001). In subgroup analysis of the remission outcome, tonsillectomy plus steroid pulse therapy was superior to steroid pulse therapy alone (7 studies, 783 patients; pooled OR, 3.15; 95% CI, 1.99-5.01; P<0.001), and tonsillectomy plus conventional steroid therapy was superior to conventional steroid therapy alone (2 studies, 159 patients; pooled OR, 4.13; 95% CI, 1.23-13.94; P=0.02). Tonsillectomy was superior to general treatment (3 studies, 187 patients; pooled OR for remission, 2.21; 95% CI, 1.20-4.05; P=0.01). In addition, tonsillectomy was associated with decreased odds of ESRD (9 studies, 873 patients; pooled OR, 0.25; 95% CI, 0.12-0.52; P<0.001). 2 sensitivity analyses, one excluding studies with less than 5 years' follow-up and another excluding the confounding effect of renin-angiotensin system inhibitors, yielded nearly the same reduction in ESRD risk (6 studies, 691 patients; pooled OR, 0.20; 95% CI, 0.11-0.36; P<0.001; and 6 studies, 547 patients; pooled OR, 0.24; 95% CI, 0.14-0.44; P<0.001). LIMITATIONS Most included studies were retrospective cohort studies; we were unable to adjust uniformly for potential confounding variables. CONCLUSIONS As adjunct or independent therapy, tonsillectomy may induce clinical remission and reduce the rates of ESRD in patients with IgAN.
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Affiliation(s)
- Lin-lin Liu
- Department of Nephrology, The First Affiliated Hospital of China Medical University, Shen Yang, People's Republic of China
| | - Li-ning Wang
- Department of Nephrology, The First Affiliated Hospital of China Medical University, Shen Yang, People's Republic of China.
| | - Yi Jiang
- Central Laboratory, The First Affiliated Hospital of China Medical University, Shen Yang, People's Republic of China
| | - Li Yao
- Department of Nephrology, The First Affiliated Hospital of China Medical University, Shen Yang, People's Republic of China
| | - Li-ping Dong
- The Library of China Medical University, Shen Yang, People's Republic of China
| | - Zi-long Li
- Department of Nephrology, The First Affiliated Hospital of China Medical University, Shen Yang, People's Republic of China
| | - Xiao-li Li
- Department of Nephrology, The First Affiliated Hospital of China Medical University, Shen Yang, People's Republic of China
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Kovács T, Vas T, Kövesdy CP, Degrell P, Nagy G, Rékási Z, Wittmann I, Nagy J. Effect of tonsillectomy and its timing on renal outcomes in Caucasian IgA nephropathy patients. Int Urol Nephrol 2014; 46:2175-82. [PMID: 25181956 DOI: 10.1007/s11255-014-0818-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2014] [Accepted: 08/10/2014] [Indexed: 11/26/2022]
Abstract
PURPOSE The role of tonsillectomy in the treatment of IgA nephropathy in Caucasian patients is controversial. METHODS A retrospective cohort study was conducted in 264 patients with biopsy-proven primary IgA nephropathy to examine the association between tonsillectomy and long-term renal survival, defined as the incidence of estimated glomerular filtration rates (eGFRs) of ≤30 ml/min/1.73 m(2) or end-stage renal disease (the composite of initiation of dialysis treatment or renal transplantation). The association of tonsillectomy with renal end-points was examined using the Kaplan-Meier method and Cox models. RESULTS One-hundred and sixty-six patients did not undergo tonsillectomy (Group I, follow-up 130 ± 101 months) and 98 patients underwent tonsillectomy (Group II, follow-up 170 ± 124 months). The mean renal survival time was significantly longer for both end-points between those patients who underwent tonsillectomy (Group II) versus patients without tonsillectomy (Group I) (p < 0.001 and p = 0.005). The mean renal survival time was significantly longer for both end-points between those patients who had macrohaematuric episodes versus patients who had no macrohaematuric episodes (p = 0.035 and p = 0.019). Tonsillectomy, baseline eGFR and 24-h proteinuria were independent risk factors for both renal end-points. CONCLUSION Tonsillectomy may delay the progression of IgA nephropathy mainly in IgA nephropathy patients with macrohaematuria. Prospective investigation of the protective role of tonsillectomy in Caucasian patients is needed.
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Affiliation(s)
- Tibor Kovács
- 2nd Department of Internal Medicine and Nephrological Center, Clinical Center, University of Pécs, Pacsirta Str. 1, Pecs, 7624, Hungary
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Vergano L, Loiacono E, Albera R, Coppo R, Camilla R, Peruzzi L, Amore A, Donadio ME, Chiale F, Boido A, Mariano F, Mazzucco G, Ravera S, Cancarini G, Magistroni R, Beltrame G, Rollino C, Stratta P, Quaglia M, Bergia R, Cravero R, Cusinato S, Benozzi L, Savoldi S, Licata C. Can tonsillectomy modify the innate and adaptive immunity pathways involved in IgA nephropathy? J Nephrol 2014; 28:51-8. [PMID: 24756968 DOI: 10.1007/s40620-014-0086-8] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2014] [Accepted: 03/27/2014] [Indexed: 12/23/2022]
Abstract
The benefits of tonsillectomy in IgA nephropathy (IgAN) are still debated. Tonsillectomy may remove pathogen sources and reduce the mucosal associated lymphoid tissue (MALT), limiting degalactosylated IgA1 (deGal-IgA1) production, which is considered to be the initiating pathogenetic event leading to IgA glomerular deposition. In the European network VALIGA, 62/1147 IgAN patients underwent tonsillectomy (TxIgAN). In a cross-sectional study 15 of these patients were tested and compared to 45 non-tonsillectomized IgAN (no-TxIgAN) and healthy controls (HC) regarding levels of deGal-IgA1, and markers of innate immunity and oxidative stress, including toll-like receptors (TLR)2, 3, 4 and 9 mRNAs, proteasome (PS) and immunoproteasome (iPS) mRNAs in peripheral blood mononuclear cells (PBMC), and advanced oxidation protein products (AOPP). Levels of deGal-IgA1 were lower in TxIgAN than in no-TxIgAN (p = 0.015), but higher than in HC (p = 0.003). TLR mRNAs were more expressed in TxIgAN than in HC (TLR4, p = 0.021; TLR9, p = 0.027), and higher in TxIgAN than in no-TxIgAN (p ≤ 0.001 for TLR2, 4, 9). A switch from PS to iPS was detected in PBMC of TxIgAN in comparison to HC and it was higher than in no-TxIgAN [large multifunctional peptidase (LMP)2/β1, p = 0.039; LPM7/β5, p < 0.0001]. The levels of AOPP were significantly higher in TxIgAN than HC (p < 0.001) and no-TxIgAN (p = 0.033). In conclusion, the activation of innate immunity via TLRs and ubiquitin-proteasome pathways and the pro-oxidative milieu were not affected by tonsillectomy, even though the levels of aberrantly galactosylated IgA1 were lower in patients with IgAN who had tonsillectomy. The residual hyperactivation of innate immunity in tonsillectomized patients may result from extra-tonsillar MALT.
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Affiliation(s)
- Luca Vergano
- Division of Otorhinolaryngology, University Hospital Città della Salute e della Scienza di Torino, Turin, Italy
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Zand L, Fervenza FC. Does tonsillectomy have a role in the treatment of patients with immunoglobulin A nephropathy? Nephrol Dial Transplant 2014; 29:1456-9. [PMID: 24723547 DOI: 10.1093/ndt/gfu068] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023] Open
Affiliation(s)
- Ladan Zand
- Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN, USA
| | - Fernando C Fervenza
- Division of Nephrology and Hypertension, Mayo Clinic College of Medicine, Rochester, MN, USA
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Evaluation of tonsillectomy before kidney transplantation in patients with IgA nephropathy. Transpl Immunol 2013; 30:12-7. [PMID: 24246415 DOI: 10.1016/j.trim.2013.11.001] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2013] [Revised: 11/01/2013] [Accepted: 11/07/2013] [Indexed: 01/12/2023]
Abstract
The effectiveness of a tonsillectomy before kidney transplantation (KTx) in suppressing the recurrence of IgA nephropathy (IgAN) has never been studied. The aim of this study was to analyze the effectiveness of a preoperative tonsillectomy for preventing IgAN recurrence and to identify predictive risk factors for IgAN recurrence. Of the 462 recipients who underwent a KTx between 2006 and 2011, a total of 78 patients had biopsy-proven IgAN as their primary disease. Among these 78 patients, 28 patients (group 1) underwent a tonsillectomy and 50 patients (group 2) did not undergo a tonsillectomy before KTx. The time to recurrence was 15.5±8.7months, in group 1 and 20.2±18.6months in group 2. No significant difference was observed between the two groups (P=0.63). Using a multivariate Cox regression analysis, ABO incompatible KTx and acute rejection were associated with a lower incidence of recurrence (P=0.02 and 0.002 respectively). These results suggested that a preoperative tonsillectomy might not affect the recurrence of IgAN during a short-term follow-up period, whereas preoperative desensitization and the use of a higher steroid dose were effective for suppressing the recurrence of IgAN.
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Nishi S. [IgA nephropathy and tonsillectomy]. ACTA ACUST UNITED AC 2013; 115:1009-15. [PMID: 24024263 DOI: 10.3950/jibiinkoka.115.1009] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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NISHI HITOMI, SUGIMOTO KEISUKE, FUJITA SHINSUKE, MIYAZAKI KOHEI, MIYAZAWA TOMOKI, SAKATA NAOKI, OKADA MITSURU, TAKEMURA TSUKASA. Effect and therapeutic mechanisms of tonsillectomy for childhood IgA nephropathy. Nephrology (Carlton) 2012; 17:658-64. [DOI: 10.1111/j.1440-1797.2012.01620.x] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
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Wang T, Ye F, Meng H, Zhang L, Jin X. Comparison of clinicopathological features between children and adults with IgA nephropathy. Pediatr Nephrol 2012; 27:1293-300. [PMID: 22562475 DOI: 10.1007/s00467-012-2139-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2011] [Revised: 01/29/2012] [Accepted: 02/01/2012] [Indexed: 11/27/2022]
Abstract
BACKGROUND IgA nephropathy (IgAN) is prevalent among both children and adults. Illumination of the differences between them is important for clinical doctors. METHODS We retrospectively compared clinicopathological features in 110 children and 908 adults with IgAN. RESULTS The male to female ratio was 1.62:1 in children and 0.85:1 in adults. Most patients lacked triggers, but IgAN was preceded by upper respiratory infection (URI) in 45.5% of children and 20.2% of adults. Gross hematuria was the most common initial symptom in children (53.6%), especially in those associated with URI (82.0%), while other symptoms and abnormal laboratory parameters were more common in adults. Estimated glomerular filtration rate (eGFR) was higher in children than in adults. Co-deposition of IgA and C3 were found in 50.9% of children, while IgA deposit was often accompanied by two or more immune complexes in adults. The frequency of subclass I was significantly higher in children than in adults. Mild histological lesions were more common in pediatric IgAN patients associated with URI than other patients. CONCLUSIONS Pediatric patients showed relatively mild clinical manifestations and histological lesions compared with adult patients. URI was the most important trigger for IgAN, particularly in children. IgAN associated with URI was relatively mild.
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Affiliation(s)
- Tianzhen Wang
- Department of Pathology, Basic Medical Science College, Harbin Medical University, 157 Baojian Road, Harbin, Nangang District 150081, China
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Komatsu H, Fujimoto S, Kikuchi M, Sato Y, Kitamura K. Tonsillectomy Delays Progression of Advanced IgA Nephropathy to End-Stage Kidney Disease. Ren Fail 2012; 34:448-53. [DOI: 10.3109/0886022x.2011.653775] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
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Floege J. The Pathogenesis of IgA Nephropathy: What Is New and How Does It Change Therapeutic Approaches? Am J Kidney Dis 2011; 58:992-1004. [DOI: 10.1053/j.ajkd.2011.05.033] [Citation(s) in RCA: 68] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2011] [Accepted: 05/26/2011] [Indexed: 02/07/2023]
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Imai H, Miura N. A treatment dilemma in adult immunoglobulin A nephropathy: what is the appropriate target, preservation of kidney function or induction of clinical remission? Clin Exp Nephrol 2011; 16:195-201. [PMID: 22086123 PMCID: PMC3328677 DOI: 10.1007/s10157-011-0552-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/19/2011] [Accepted: 10/12/2011] [Indexed: 11/25/2022]
Abstract
Immunoglobulin (Ig) A nephropathy is the most common type of glomerulonephritis worldwide. Data on its natural history suggest that approximately 40% of patients progress to end-stage renal failure after 20 years. Various therapies such as antiplatelet medication, fish oil, oral prednisolone, intravenous prednisolone, tonsillectomy, and tonsillectomy plus steroid pulse (TSP) have been proposed. Japanese nephrologists face challenging issues regarding this disease, such as the usefulness of the annual urinary screening system (kenshin) and kidney biopsies, the desire of patients and their families for treatment despite insufficient clinical evidence, and the risk of overtreatment with TSP versus the loss of a ‘golden period’ with late intervention. We review the current literature on tonsillectomy, steroid therapy, and TSP, which was first proposed in Japan, and present some perspectives on the treatment of IgA nephropathy.
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Affiliation(s)
- Hirokazu Imai
- Division of Nephrology and Rheumatology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute-cho, Aichi, 480-1195, Japan.
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Pathological role of tonsillar B cells in IgA nephropathy. Clin Dev Immunol 2011; 2011:639074. [PMID: 21785618 PMCID: PMC3139900 DOI: 10.1155/2011/639074] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2011] [Accepted: 05/17/2011] [Indexed: 01/09/2023]
Abstract
Although impaired immune regulation along the mucosa-bone marrow axis has been postulated to play an important role, the pathogenesis of IgA nephropathy (IgAN) is unknown; thus, no disease-specific therapy for this disease exists. The therapeutic efficacy of tonsillectomy or tonsillectomy in combination with steroid pulse therapy for IgAN has been discussed. Although randomized control trials for these therapies are ongoing in Japan, the scientific rationale for these therapies remains obscure. It is now widely accepted that abnormally glycosylated IgA1 and its related immune complex (IC) are probably key molecules for the pathogenesis, and are thus considered possible noninvasive biomarkers for this disease. Emerging evidence indicates that B cells in mucosal infections, particularly in tonsillitis, may produce the nephritogenic IgA. In this paper, we briefly summarize characteristics of the nephritogenic IgA/IgA IC, responsible B cells, and underlying mechanisms. This clinical and experimental information may provide important clues for a therapeutic rationale.
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Moriyama T, Nitta K. Tonsillectomy and Steroid Pulse Therapy for IgA Nephropathy. TOHOKU J EXP MED 2011; 224:243-50. [DOI: 10.1620/tjem.224.243] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/18/2022]
Affiliation(s)
- Takahito Moriyama
- Department of Medicine, Kidney Center, Tokyo Women's Medical University
| | - Kosaku Nitta
- Department of Medicine, Kidney Center, Tokyo Women's Medical University
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Wang Y, Chen J, Wang Y, Chen Y, Wang L, Lv Y. A meta-analysis of the clinical remission rate and long-term efficacy of tonsillectomy in patients with IgA nephropathy. Nephrol Dial Transplant 2010; 26:1923-31. [PMID: 21081691 DOI: 10.1093/ndt/gfq674] [Citation(s) in RCA: 58] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND We wished to evaluate the clinical remission rate and long-term efficacy of tonsillectomy for patients with IgA nephropathy. METHODS We searched a number of databases, including PubMed, CNKI, Wanfang and others, for clinical case-control studies of tonsillectomy in patients with IgA nephropathy. We then performed a meta-analysis of these studies. After evaluating total clinical remission rates, we compared the remission rates for specific treatments: tonsillectomy plus steroid pulse, tonsillectomy plus normal-dose steroid, and general treatment using neither tonsillectomy nor steroids. We also compared the rates of end-stage renal failure (ESRF) at last follow-up to estimate the long-term renal survival rate associated with each treatment. RESULTS Seven retrospective studies met the inclusion criteria and were included. These included a total of 858 patients, in which 534 underwent tonsillectomy and 324 did not. The total clinical remission rate was higher in the operative group, while the ESRF rate was higher in the non-operative group. The clinical remission rate in patients who underwent tonsillectomy remained higher than in the non-operative group at both 5- and 10-year follow-up. The clinical remission rate in patients who underwent tonsillectomy plus steroid pulse was higher than in those treated with steroid pulse alone, normal-dose steroids or general treatment alone (P < 0.05). However, the clinical remission rate of simple tonsillectomy was not higher than that of general treatment (P > 0.05). CONCLUSIONS Whereas neither tonsillectomy nor steroid treatment alone increased remission rates in patients with IgA nephropathy, tonsillectomy combined with either normal steroid or steroid pulse treatment resulted in higher remission rates with favourable long-term efficacy.
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Affiliation(s)
- You Wang
- Department of Nephrology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Street, Wuhan 430030, People’s Republic of China.
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Coppo R. Can a dysregulated mucosal immune system in IgA nephropathy be controlled by tonsillectomy? Nephrol Dial Transplant 2010; 25:2395-7. [PMID: 20488821 DOI: 10.1093/ndt/gfq266] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
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Piccoli A, Codognotto M, Tabbi MG, Favaro E, Rossi B. Influence of tonsillectomy on the progression of mesangioproliferative glomerulonephritis. Nephrol Dial Transplant 2010; 25:2583-9. [PMID: 20200005 DOI: 10.1093/ndt/gfq107] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
BACKGROUND Little information is available about the efficacy of tonsillectomy on long-term renal survival of patients with primary IgA nephropathy (IgAN). METHODS In this retrospective cohort study, we considered 61 patients with IgAN who had tonsillectomy (n = 15) or not (n = 46) and compared them with 121 control patients with mesangioproliferative glomerulonephritis (MesGN) free of IgA deposits, who had tonsillectomy (n = 49) or not (n = 72). We evaluated the progression from a normal function [estimated glomerular filtration rate 60-220 mL/min/1.73 m(2), chronic kidney disease (CKD) stage 1 and 2] to a moderate renal dysfunction in CKD stage 3, which was considered the outcome. RESULTS The mean duration of follow-up was 250 months (12-300 months) in the whole group of 182 patients. The survival to progression to stage 3 was 88% after 10 years, 71% after 20 years and 53% after 25 years. It was 72% after 20 years in both groups. Tonsillectomy was not significantly associated with CKD progression. Significant prognostic factors were age (P = 0.01), initial CKD stage (P = 0.03), proteinuria (P = 0.03), persistent proteinuria (P < 0.001) and diastolic blood pressure (P = 0.01). In the multivariate analysis (Cox model), there was no significant effect of tonsillectomy adjusted for the type of glomerulonephritis, initial CKD stage, persistent proteinuria, diastolic blood pressure and age. Only persistent proteinuria adjusted for the other factors was significantly associated with CKD progression (hazard ratio of 6.2, 95% confidence interval 3.1-12.7, P < 0.001). CONCLUSIONS Tonsillectomy was not associated with a different progression rate of IgAN nor of MesGN after 20 years of follow-up.
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Affiliation(s)
- Antonio Piccoli
- Department of Medical and Surgical Sciences, Nephrology Clinic, University of Padova, Padova, Italy.
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Harabuchi Y, Takahara M. [Otorhinolaryngology and translational research--study of the etiological mechanism in IgA nephropathy having its foci at the tonsils]. NIHON JIBIINKOKA GAKKAI KAIHO 2009; 112:689-96. [PMID: 19960626 DOI: 10.3950/jibiinkoka.112.689] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Ushigome H, Suzuki T, Fujiki M, Nobori S, Sakamoto S, Okamoto M, Urasaki K, Yoshimura N. Efficacy of tonsillectomy for patients with recurrence of IgA nephropathy after kidney transplantation. Clin Transplant 2009; 23 Suppl 20:17-22. [PMID: 19594590 DOI: 10.1111/j.1399-0012.2009.01003.x] [Citation(s) in RCA: 23] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
From January 2007, we started to perform the tonsillectomy for every patient with recurrent IgA nephropathy (IgAN) after kidney transplantation. Up to September 2008, four recipients with primary IgAN had biopsy-proven recurrent IgAN. They had also progressive hematuria or proteinuria from on the average 14.3 months after transplantation. Then their specimens diagnosed as recurrent IgAN were collected and they underwent tonsillectomies on the average 52.3 months after transplantation. Abnormal urinary findings of all patients favorably improved after tonsillectomy. All cases but one had mild renal injury, where the severity of glomerular lesions, glomerular hypercellularity, segmental lesions, and sclerosis was mild, and no deteriorated serum creatinine (SCr) before their tonsillectomies. Even the case with exacerbated SCr and severe renal injury, where the severity of glomerular lesions was severe, had her urinary findings ameliorated promptly after tonsillectomy likely as others. At present, they have almost no symptoms after tonsillectomy and no remarkable change of SCr level compared with before and after tonsillectomy and maintain ameliorated urinary findings continuously. Tonsillectomy had possibility to be a favorable treatment of hematuria or proteinuria in recurrent IgAN recipients.
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Affiliation(s)
- Hidetaka Ushigome
- Department of Transplantation and Regenerative Surgery, Kyoto Prefectural University Graduate School of Medical Science, Kyoto, Japan.
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Komatsu H, Fujimoto S, Hara S, Sato Y, Yamada K, Kitamura K. Effect of tonsillectomy plus steroid pulse therapy on clinical remission of IgA nephropathy: a controlled study. Clin J Am Soc Nephrol 2008; 3:1301-7. [PMID: 18508946 DOI: 10.2215/cjn.00310108] [Citation(s) in RCA: 96] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
Abstract
BACKGROUND AND OBJECTIVES Few well-designed investigations have examined how tonsillectomy plus steroid pulse therapy affects IgA nephropathy. A prospective, controlled study therefore was performed to compare the effects of combined therapy with those of steroid pulse alone in patients with IgA nephropathy. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Fifty-five patients were followed up for 54.0 +/- 21.2 mo. Thirty-five of them underwent tonsillectomy and steroid pulse therapy (group C), and 20 received steroid pulse monotherapy (group M). Both groups received methylprednisolone intravenously, followed by oral prednisolone (initial dosage 0.5 mg/kg per d) for 12 to 18 mo. Primary evaluation items were a 100% increase in serum creatinine from baseline levels or the disappearance of urinary protein (UP) and/or occult blood (UOB) indicating clinical remission. RESULTS At 24 mo after the initial treatment, the ratios of the UP and UOB disappearance were higher in group C than in group M, and the therapeutic effect persisted until the final observation. None of group C achieved a 100% increase in serum creatinine from the baseline level, whereas one patient in group M developed ESRD during the observation period. The histologic findings of repeated biopsy specimens from 18 patients revealed that mesangial proliferation and IgA deposition were significantly more reduced in group C than in group M. The Cox regression model showed that the combined therapy was approximately six-fold more effective in causing the disappearance of UP than steroid pulse monotherapy. CONCLUSION Tonsillectomy combined with steroid pulse treatment can induce clinical remission in patients with IgA nephropathy.
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Affiliation(s)
- Hiroyuki Komatsu
- Circulatory and Body Fluid Regulation, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, Kiyotake, Miyazaki, 889-1692, Japan.
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