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Bogdan RG, Boicean A, Anderco P, Ichim C, Iliescu-Glaja M, Todor SB, Leonte E, Bloanca VA, Crainiceanu ZP, Popa ML. From Liver to Kidney: The Overlooked Burden of Nonalcoholic Fatty Liver Disease in Chronic Kidney Disease. J Clin Med 2025; 14:2486. [PMID: 40217935 PMCID: PMC11989420 DOI: 10.3390/jcm14072486] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2025] [Revised: 03/30/2025] [Accepted: 04/03/2025] [Indexed: 04/14/2025] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasingly recognized as a contributor to chronic kidney disease (CKD), yet its impact remains underappreciated in clinical practice. Recent studies reveal a strong association between NAFLD and CKD progression, with evidence linking hepatic dysfunction to renal impairment through metabolic and inflammatory pathways. NAFLD not only increases the risk of CKD but also accelerates its progression, leading to worse cardiovascular outcomes and higher mortality, particularly in patients with advanced fibrosis. Despite this growing evidence, NAFLD often goes undiagnosed in CKD patients and routine hepatic evaluation is rarely integrated into nephrology care. Emerging diagnostic tools, including noninvasive biomarkers and imaging techniques, offer potential for earlier detection, yet their clinical implementation remains inconsistent. Although lifestyle modifications remain the foundation of treatment, pharmacotherapeutic strategies, including SGLT2 inhibitors and GLP-1 receptor agonists, have demonstrated potential in mitigating both hepatic and renal impairment. Recognizing the interplay between NAFLD and CKD is essential for improving patient outcomes. A multidisciplinary approach, integrating hepatology and nephrology expertise, is crucial to refining screening strategies, optimizing treatment, and reducing the long-term burden of these coexisting conditions.
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Affiliation(s)
- Razvan George Bogdan
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Adrian Boicean
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
| | - Paula Anderco
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
| | - Cristian Ichim
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
| | - Mihai Iliescu-Glaja
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Samuel Bogdan Todor
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
| | - Elisa Leonte
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Vlad Adam Bloanca
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Zorin Petrisor Crainiceanu
- Plastic Surgery Department, “Victor Babes” University of Medicine and Pharmacy, 300041 Timisoara, Romania; (R.G.B.); (M.I.-G.); (E.L.); (V.A.B.); (Z.P.C.)
| | - Mirela Livia Popa
- Faculty of Medicine, “Lucian Blaga” University of Sibiu, 550024 Sibiu, Romania; (C.I.); (S.B.T.); (M.L.P.)
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Zhang B, Chen L, Li T. Unveiling the effect of urinary xenoestrogens on chronic kidney disease in adults: A machine learning model. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 292:117945. [PMID: 39987685 DOI: 10.1016/j.ecoenv.2025.117945] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 02/07/2025] [Accepted: 02/20/2025] [Indexed: 02/25/2025]
Abstract
Exposure to three primary xenoestrogens (XEs), including phthalates, parabens, and phenols, has been strongly associated with chronic kidney disease (CKD). An interpretable machine learning (ML) model was developed to predict CKD using data from the National Health and Nutrition Examination Survey (NHANES) database spanning from 2007 to 2016. Four ML algorithms-random forest classifier (RF), XGBoost (XGB), k-nearest neighbors (KNN), and support vector machine (SVM)-were used alongside traditional logistic regression to predict CKD. The study included 6910 U.S. adults, with XGB showing the highest predictive accuracy, achieving an area under the curve (AUC) of 0.817 (95 % CI: 0.789, 0.844). The selected model was interpreted using Shapley additive explanations (SHAP) and partial dependence plot (PDP). The SHAP method identified key predictive features for CKD in urinary metabolites of XEs-methyl paraben (MeP), mono-(carboxynonyl) phthalate (MCNP), and triclosan (TCS)-and suggested personalized CKD care should focus on XE control. PDP results confirmed that, within certain ranges, MeP levels positively impacted the model, MCNP levels negatively impacted it, and TCS had a mixed effect. The synergistic effects suggested that managing urinary MeP levels could be essential for the effective control of CKD. In summary, our research highlights the significant predictive potential of XEs for CKD, especially MeP, MCNP, and TCS.
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Affiliation(s)
- Bowen Zhang
- Department of Anesthesiology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China; Laboratory of Mitochondrial Metabolism and Perioperative Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China; Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Liang Chen
- Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Tao Li
- Department of Anesthesiology, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu 610041, China; Laboratory of Mitochondrial Metabolism and Perioperative Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu 610041, China; Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, China.
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Qin Y, Xuan L, Wu Z, Deng Y, Liu B, Wang S. Use of consensus clustering to identify distinct subtypes of chronic kidney disease and associated mortality risk. Sci Rep 2024; 14:29893. [PMID: 39623025 PMCID: PMC11611901 DOI: 10.1038/s41598-024-81208-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Accepted: 11/25/2024] [Indexed: 12/06/2024] Open
Abstract
BACKGROUND Chronic kidney disease (CKD) is a complex condition with diverse etiology and outcomes. Utilizing a data-driven clustering approach holds promise in identifying distinct CKD subgroups associated with specific risk profiles for death. METHODS Unsupervised consensus clustering was utilized to classify chronic kidney disease (CKD) into subtypes based on 45 baseline characteristics in a cohort of 6,526 participants from the US National Health and Nutrition Examination Survey (NHANES) spanning the years 1999-2000 to 2017-2018.We examined the associations between CKD subgroups and clinical endpoints related to mortality, including all-cause mortality, cardiovascular disease mortality, cancer mortality, and mortality due to other causes. RESULTS A total of 6,526 individuals with CKD were classified into four clusters at baseline. Cluster 1 (n = 508) comprised patients with relatively favorable levels of cardiac and kidney function markers, lower prevalence of cancer and higher prevalence of obesity, lower medication usage, and younger age. Cluster 4 (n = 2,029) comprised patients with the worst cardiac and kidney function markers. The characteristics of cluster 2 (n = 1,439) and 3 (n = 2,550) fell in between these two clusters. From cluster 1 to cluster 4, we observed a gradual increase in the hazard ratios of all-cause mortality, cardiovascular disease mortality, and mortality due to other causes. Additionally, further sensitivity analysis revealed patient heterogeneity among predefined subgroups with similar baseline kidney function and mortality risks. CONCLUSIONS Consensus clustering integrated baseline clinical and laboratory measures, revealing distinct CKD subgroups with markedly different risks of death, suggesting that further examination of patient subgroups could advance precision medicine.
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Affiliation(s)
- Yi Qin
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Liping Xuan
- Department of Endocrinology, Guangdong Provincial Geriatrics Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China
| | - Zhe Wu
- Department of Thoracic Surgery, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Yujie Deng
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Bin Liu
- Department of Rheumatology, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Shujie Wang
- Department of Geriatric Medicine, The Affiliated Hospital of Qingdao University, Jiangsu Road No.19, Qingdao, China.
- Department of Endocrinology and Metabolism, The Affiliated Hospital of Qingdao University, Qingdao, China.
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Liu Y, Chai S, Zhang X. Effect of MAFLD on albuminuria and the interaction between MAFLD and diabetes on albuminuria. J Diabetes 2024; 16:e13501. [PMID: 37974383 PMCID: PMC10859309 DOI: 10.1111/1753-0407.13501] [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] [Received: 07/25/2023] [Revised: 09/29/2023] [Accepted: 10/30/2023] [Indexed: 11/19/2023] Open
Abstract
OBJECTIVE To investigate the effects of metabolic associated fatty liver disease (MAFLD) on chronic kidney disease (CKD) and abnormal albuminuria and the interaction between MAFLD and diabetes on abnormal albuminuria. METHODS Data of participants in the American 2017-2018 National Health and Nutrition Examination Survey were analyzed. Hepatic steatosis was defined as median controlled attenuation parameter ≥248 dB/m, which was measured by ultrasound transient elastography. MAFLD was defined by evidence of hepatic steatosis on ultrasound in addition to any metabolic dysregulation. Hepatic fibrosis was detected by FibroScan and quantified by parameter of stiffness (E). Hepatic fibrosis was defined as E ≥ 9.7 kPa. As component of CKD, reduced estimated glomerular filtration rate (eGFR) was defined as<60 mL/min/1.73 m2 and abnormal albuminuria was defined as urinary albumin-to-creatinine ratio ≥ 30 mg/g. RESULTS Data pertaining to 5119 participants were included in the analysis, with 40.6% hepatic normal, 52.1% MAFLD, and 7.2% hepatic fibrosis. Multivariable regression analyses showed that for abnormal albuminuria, the odds ratio (OR) was 0.82 (0.65-1.04) for MAFLD group and 1.73 (1.14.-,2.63) for hepatic fibrosis group, both taking the hepatic healthy group as reference. As for reduced eGFR, the OR was 0.68 (0.51-0.92) for MAFLD group and 0.93 (0.56-1.53) for hepatic fibrosis group. Diabetes was significantly related to greater risk of abnormal albuminuria (3.04 [2.70-3.42]) and reduced eGFR (1.53 [1.33-1.77]). With regard to the prevalence of abnormal albuminuria, the OR was 1.64 (1.03-2.60) for those with hepatic fibrosis only, 3.30 (2.80-3.89) for those with diabetes only, and 5.05 (3.30-7.72) for those with both two conditions. But there were neither additive interaction (relative excess risk due to interaction 0.56 [-1.41-.53], p = .577) nor multiplicative interaction (OR 0.81 [0.45-1.47], p = .492) between hepatic fibrosis and diabetes on the prevalence of abnormal albuminuria. CONCLUSION MAFLD with hepatic fibrosis is an independent risk factor for abnormal albuminuria, but it does not have interaction with diabetes on abnormal albuminuria.
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Affiliation(s)
- Yufang Liu
- Department of EndocrinologyPeking University International HospitalBeijingChina
| | - Sanbao Chai
- Department of EndocrinologyPeking University International HospitalBeijingChina
| | - Xiaomei Zhang
- Department of EndocrinologyPeking University International HospitalBeijingChina
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Moritz L, Schumann A, Pohl M, Köttgen A, Hannibal L, Spiekerkoetter U. A systematic review of metabolomic findings in adult and pediatric renal disease. Clin Biochem 2024; 123:110703. [PMID: 38097032 DOI: 10.1016/j.clinbiochem.2023.110703] [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: 06/16/2023] [Revised: 12/03/2023] [Accepted: 12/07/2023] [Indexed: 12/29/2023]
Abstract
Chronic kidney disease (CKD) affects over 0.5 billion people worldwide across their lifetimes. Despite a growingly ageing world population, an increase in all-age prevalence of kidney disease persists. Adult-onset forms of kidney disease often result from lifestyle-modifiable metabolic illnesses such as type 2 diabetes. Pediatric and adolescent forms of renal disease are primarily caused by morphological abnormalities of the kidney, as well as immunological, infectious and inherited metabolic disorders. Alterations in energy metabolism are observed in CKD of varying causes, albeit the molecular mechanisms underlying pathology are unclear. A systematic indexing of metabolites identified in plasma and urine of patients with kidney disease alongside disease enrichment analysis uncovered inborn errors of metabolism as a framework that links features of adult and pediatric kidney disease. The relationship of genetics and metabolism in kidney disease could be classified into three distinct landscapes: (i) Normal genotypes that develop renal damage because of lifestyle and / or comorbidities; (ii) Heterozygous genetic variants and polymorphisms that result in unique metabotypes that may predispose to the development of kidney disease via synergistic heterozygosity, and (iii) Homozygous genetic variants that cause renal impairment by perturbing metabolism, as found in children with monogenic inborn errors of metabolism. Interest in the identification of early biomarkers of onset and progression of CKD has grown steadily in the last years, though it has not translated into clinical routine yet. This systematic review indexes findings of differential concentration of metabolites and energy pathway dysregulation in kidney disease and appraises their potential use as biomarkers.
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Affiliation(s)
- Lennart Moritz
- Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany; Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany
| | - Anke Schumann
- Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany; Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany
| | - Martin Pohl
- Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany
| | - Anna Köttgen
- Institute of Genetic Epidemiology, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany
| | - Luciana Hannibal
- Laboratory of Clinical Biochemistry and Metabolism, Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany.
| | - Ute Spiekerkoetter
- Department of General Pediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center, University of Freiburg, 79106 Freiburg, Germany.
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He I, Poirier B, Jensen E, Kaur S, Hedges J, Jesudason S, Jamieson L, Sethi S. Demystifying the connection between periodontal disease and chronic kidney disease - An umbrella review. J Periodontal Res 2023; 58:874-892. [PMID: 37477165 DOI: 10.1111/jre.13161] [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: 02/21/2023] [Revised: 06/07/2023] [Accepted: 06/30/2023] [Indexed: 07/22/2023]
Abstract
Chronic kidney disease (CKD) and poor oral health are inter-related and their significant impact on each other is well established in the literature. Many systematic reviews and meta-analyses have demonstrated a strong relationship between CKD and periodontitis, where periodontal treatment has shown potential in improving CKD outcomes. However, the quality of the studies and heterogeneity of the results show variation. The aim of this umbrella review was to review the quality of the current systematic reviews on the relationship between CKD and oral health with an emphasis on periodontal disease and to generate clinically relevant guidelines to maintain periodontal health in patients with CKD. This umbrella review was conducted and reported in alignment with the Joanna Briggs Institute and the PRISMA 2020 guidelines. The review protocol was established prior to commencing the review and registered on JBI and PROSPERO (CRD42022335209). Search strings were established for PubMed, Embase, Web of Science, Cochrane Database of Systematic Reviews, and Dentistry & Oral Science Source up to April 2022. All systematic reviews and meta-analyses that considered the relationship between CKD and periodontitis or periodontal treatment were included. Of 371 studies identified through the systematic search, 18 systematic reviews met the inclusion criteria. Ten studies assessed the relationship between oral health status and CKD with a focus on periodontitis and CKD, five reviewed the impact of periodontal treatment on CKD outcomes, two included both relationship and effectiveness of periodontal treatment and one qualitatively reviewed oral health-related quality of life in patients with kidney failure. Findings indicate there is a bidirectional relationship between CKD and periodontal disease. In view of the heterogeneity of the existing literature on CKD and periodontal disease, specific recommendations for the management of periodontitis among patients with CKD are proposed for medical professionals, dental professionals, and aged care workers based on the evidence collated in this review.
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Affiliation(s)
- Isaac He
- Adelaide Dental School, University of Adelaide, Adelaide, South Australia, Australia
| | - Brianna Poirier
- Australian Research Centre for Population Oral Health, Adelaide Dental School, University of Adelaide, Adelaide, South Australia, Australia
| | - Emilija Jensen
- Adelaide Dental School, University of Adelaide, Adelaide, South Australia, Australia
| | - Sushil Kaur
- Adelaide Dental School, University of Adelaide, Adelaide, South Australia, Australia
| | - Joanne Hedges
- Australian Research Centre for Population Oral Health, Adelaide Dental School, University of Adelaide, Adelaide, South Australia, Australia
| | - Shilpanjali Jesudason
- Central and Northern Adelaide Renal and Transplantation Services (CNARTS), Royal Adelaide Hospital, Adelaide, South Australia, Australia
- Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia
| | - Lisa Jamieson
- Australian Research Centre for Population Oral Health, Adelaide Dental School, University of Adelaide, Adelaide, South Australia, Australia
| | - Sneha Sethi
- Australian Research Centre for Population Oral Health, Adelaide Dental School, University of Adelaide, Adelaide, South Australia, Australia
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Nysather J, Kaya E, Manka P, Gudsoorkar P, Syn WK. Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease Cross Talk. ADVANCES IN KIDNEY DISEASE AND HEALTH 2023; 30:315-335. [PMID: 37657879 DOI: 10.1053/j.akdh.2023.04.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 12/14/2022] [Accepted: 04/04/2023] [Indexed: 09/03/2023]
Abstract
Nonalcoholic fatty liver disease is a multisystem condition with effects beyond the liver. The identification of chronic kidney disease as an independent mediator of nonalcoholic fatty liver disease or associated entity with shared cardiometabolic risk factors remains controversial and continues to draw scientific interest. With increasing prevalence of nonalcoholic fatty liver disease and lack of Food and Drug Administration approved therapies, these shared cardiometabolic risk factors have drawn significant attention. In this article, we review shared pathophysiological mechanisms between nonalcoholic fatty liver disease and chronic kidney disease along with current treatment strategies that might be useful for both disease processes.
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Affiliation(s)
- Jacob Nysather
- Division of Nephrology and Kidney C.A.R.E. Program, University of Cincinnati, OH
| | - Eda Kaya
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Paul Manka
- Department of Internal Medicine, University Hospital Knappschaftskrankenhaus Bochum, Ruhr-University Bochum, Bochum, Germany
| | - Prakash Gudsoorkar
- Division of Nephrology and Kidney C.A.R.E. Program, University of Cincinnati, OH
| | - Wing-Kin Syn
- Division of Gastroenterology and Hepatology, Saint Louis University School of Medicine, St. Louis, MO; Division of Gastroenterology and Hepatology, Medical University of South Carolina, Charleston, SC; Department of Physiology, Faculty of Medicine and Nursing, University of the Basque Country, Euskal Herriko Unibertsitatea/Universidad del País Vasco, Leioa, Spain.
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Onwuzo SS, Hitawala AA, Boustany A, Kumar P, Almomani A, Onwuzo C, Monteiro JM, Asaad I. Prevalence of non-alcoholic fatty liver disease in patients with nephrotic syndrome: A population-based study. World J Hepatol 2023; 15:265-273. [PMID: 36926242 PMCID: PMC10011912 DOI: 10.4254/wjh.v15.i2.265] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2022] [Revised: 01/21/2023] [Accepted: 02/08/2023] [Indexed: 02/24/2023] Open
Abstract
BACKGROUND Non-alcoholic fatty liver disease (NAFLD) is a global health concern with a prevalence of about 25% amongst United States adults. Its increased prevalence is attributed to increase in patients with obesity and metabolic syndrome, partly due to similar mechanisms of injury. Nephrotic syndrome (NS) is a clinical entity resulting from extensive proteinuria leading to hypoalbuminemia, hyperlipidemia, edema, and other complications. Given its association with hyperlipidemia, there is concern that patients with NS may be at increased risk of NAFLD.
AIM To perform a cross-sectional population-based study to investigate the prevalence and risk factors of NAFLD in patients with NS.
METHODS A large multicenter database (Explorys Inc., Cleveland, OH, United States) was utilized for this retrospective cohort study. A cohort of 49700 patients with a diagnosis of “Non-Alcoholic fatty liver disease” using the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT) between 1999-2022 was identified. Inclusion criteria were age ≥ 18 years, presence of NAFLD, presence of NS. There were no specific exclusion criteria. Univariate and multivariate analysis were performed to adjust for multiple risk factors including age, gender, Caucasian race, NS, type II diabetes mellitus, hypothyroidism, dyslipidemia, obesity, metabolic syndrome and chronic kidney disease. Statistical analysis was conducted using R, and for all analyses, a 2-sided P value of < 0.05 was considered statistically significant.
RESULTS Among the 78734750 individuals screened in this database, there were a total of 49700 subjects with NAFLD. In univariate analysis, the odds of having NAFLD in patients with NS, type 2 diabetes mellitus, hypothyroidism, dyslipidemia, obesity, metabolic syndrome and chronic kidney disease were 14.84 [95% confidence interval (95%CI) 13.67-16.10], 17.05 (95%CI 16.78-17.32), 6.99 (95%CI 6.87-7.11), 13.61 (95%CI 13.38-13.84), 19.19 (95%CI 18.89-19.50), 29.09 (95%CI 28.26--29.95), and 9.05 (95%CI 8.88-9.22), respectively. In multivariate analysis, the odds of having NAFLD amongst patients with NS were increased to 1.85 (95%Cl 1.70-2.02), while the odds were also remained high in patients that have type 2 diabetes mellitus [odds ratio (OR) 3.84], hypothyroidism (OR 1.57), obesity (OR 5.10), hyperlipidemia (OR 3.09), metabolic syndrome (OR 3.42) and chronic kidney disease (OR 1.33).
CONCLUSION Patients with NS are frequently found to have NAFLD, even when adjusting for common risk factors. Hence, clinicians should maintain a high index of suspicion regarding presence of NAFLD in patients with NS.
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Affiliation(s)
| | - Asif Ali Hitawala
- Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
| | - Antoine Boustany
- Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
| | - Prabhat Kumar
- Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
| | - Ashraf Almomani
- Digestive Disease and Hepatology, Cleveland Clinic Foundation Florida, Weston, FI 33331, United States
| | - Chidera Onwuzo
- Department of Medicine & Surgery, General Hospital Lagos Island, Lagos Island 101223, Lagos, Nigeria
| | | | - Imad Asaad
- Digestive Disease and Hepatology, Cleveland Clinic Foundation, Cleveland, OH 44111, United States
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A Novel and Noninvasive Risk Assessment Score and Its Child-to-Adult Trajectories to Screen Subclinical Renal Damage in Middle Age. Bioengineering (Basel) 2023; 10:bioengineering10020257. [PMID: 36829751 PMCID: PMC9952229 DOI: 10.3390/bioengineering10020257] [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: 01/13/2023] [Revised: 02/10/2023] [Accepted: 02/13/2023] [Indexed: 02/18/2023] Open
Abstract
This study aimed to develop a noninvasive, economical and effective subclinical renal damage (SRD) risk assessment tool to identify high-risk asymptomatic people from a large-scale population and improve current clinical SRD screening strategies. Based on the Hanzhong Adolescent Hypertension Cohort, SRD-associated variables were identified and the SRD risk assessment score model was established and further validated with machine learning algorithms. Longitudinal follow-up data were used to identify child-to-adult SRD risk score trajectories and to investigate the relationship between different trajectory groups and the incidence of SRD in middle age. Systolic blood pressure, diastolic blood pressure and body mass index were identified as SRD-associated variables. Based on these three variables, an SRD risk assessment score was developed, with excellent classification ability (AUC value of ROC curve: 0.778 for SRD estimation, 0.729 for 4-year SRD risk prediction), calibration (Hosmer-Lemeshow goodness-of-fit test p = 0.62 for SRD estimation, p = 0.34 for 4-year SRD risk prediction) and more potential clinical benefits. In addition, three child-to-adult SRD risk assessment score trajectories were identified: increasing, increasing-stable and stable. Further difference analysis and logistic regression analysis showed that these SRD risk assessment score trajectories were highly associated with the incidence of SRD in middle age. In brief, we constructed a novel and noninvasive SRD risk assessment tool with excellent performance to help identify high-risk asymptomatic people from a large-scale population and assist in SRD screening.
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Cojocariu C, Popa C, Muzica C, Stanciu C, Cuciureanu T, Trifan A. Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease. ESSENTIALS OF NON-ALCOHOLIC FATTY LIVER DISEASE 2023:171-181. [DOI: 10.1007/978-3-031-33548-8_15] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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11
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Hu Q, Chen Y, Bao T, Huang Y. Association of metabolic dysfunction-associated fatty liver disease with chronic kidney disease: a Chinese population-based study. Ren Fail 2022; 44:1996-2005. [DOI: 10.1080/0886022x.2022.2144373] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Affiliation(s)
- Qian Hu
- Health Management Center, West China Hospital of Sichuan University, Chengdu, China
| | - Yao Chen
- Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu, China
| | - Ting Bao
- Health Management Center, West China Hospital of Sichuan University, Chengdu, China
| | - Yan Huang
- Health Management Center, West China Hospital of Sichuan University, Chengdu, China
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12
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Afonso R, Marques RC, Borges H, Cabrita A, Silva AP. The Usefulness of Calcium/Magnesium Ratio in the Risk Stratification of Early Onset of Renal Replacement Therapy. Diagnostics (Basel) 2022; 12:diagnostics12102470. [PMID: 36292159 PMCID: PMC9600033 DOI: 10.3390/diagnostics12102470] [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: 08/30/2022] [Revised: 10/02/2022] [Accepted: 10/10/2022] [Indexed: 11/16/2022] Open
Abstract
Background: A growing number of studies have reported a close relationship between high serum calcium (Ca)/low serum magnesium (Mg) and vascular calcification. Endothelial dysfunction and vascular inflammation seem plausible risk factors for the enhanced progression of kidney disease. The aim of this study was to evaluate the role of the Ca/Mg ratio as a predictor of the early onset of renal replacement therapy (RRT). Methods: This was a prospective study conducted in an outpatient low-clearance nephrology clinic, enrolling 693 patients with stages 4−5 of CKD. Patients were divided into two groups according to the start of renal replacement therapy (RRT). Results: The kidney’s survival at 120 months was 60% for a Ca−Mg ratio < 6 and 40% for a Ca−Mg ratio ≥ 6 (p = 0.000). Patients who started RRT had lower levels of Hb, Ca, Mg, albumin, and cholesterol and higher values of phosphorus, the Ca/Mg ratio, and PTH. High values of phosphorus and the Ca/Mg ratio and low levels of Mg and GFR were independent predictors of entry into RRT. A high Ca/Mg ratio, high phosphorus levels, and low levels of GFR were associated with a cumulative risk for initiation of RRT. Conclusions: In our population, the Ca/Mg ratio is an independent predictive factor for the initiation of a depurative technique.
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Affiliation(s)
- Rita Afonso
- Nephrology Department, Centro Hospitalar Universitário do Algarve, 8000-836 Faro, Portugal
- Correspondence: ; Tel.: +351-289-891-100
| | - Roberto Calças Marques
- Nephrology Department, Centro Hospitalar Universitário do Algarve, 8000-836 Faro, Portugal
| | - Henrique Borges
- Nephrology Department, Centro Hospitalar Universitário do Algarve, 8000-836 Faro, Portugal
| | - Ana Cabrita
- Nephrology Department, Centro Hospitalar Universitário do Algarve, 8000-836 Faro, Portugal
| | - Ana Paula Silva
- Nephrology Department, Centro Hospitalar Universitário do Algarve, 8000-836 Faro, Portugal
- Department of Biomedical Sciences and Medicine, Universidade do Algarve, 8005-139 Faro, Portugal
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13
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Ong SW, Wong JV, Auguste BL, Logan AG, Nolan RP, Chan CT. Design and Development of a Digital Counseling Program for Chronic Kidney Disease. Can J Kidney Health Dis 2022; 9:20543581221103683. [PMID: 35747169 PMCID: PMC9210079 DOI: 10.1177/20543581221103683] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2021] [Accepted: 04/12/2022] [Indexed: 11/15/2022] Open
Abstract
Background: Self-management has shown to improve the quality of life in patients with chronic kidney disease (CKD). Readily accessible self-management tools are essential in promoting adherence to self-care behaviors. In recognizing that digital health facilitates efficient access to self-management programs, we developed a digital counseling program, ODYSSEE Kidney Health, to promote self-care behaviors while supporting health-related quality of life. Objective: To present the design and development of ODYSSEE Kidney Health for digital counseling for patients with CKD. Design: The study involved an iterative design process based on user-centered design principles to develop the digital counseling program, ODYSSEE Kidney Health. Setting: A sample of 10 to 15 participants were purposively sampled from nephrology clinics at the University Health Network, Toronto, Canada. Methods: Participants underwent 2 phases in the development process. In each phase, participants were presented with a component of the program, asked to perform goal-oriented tasks, and participate in the “think-aloud” process. Semi-structured interviews followed the first phase to identify feedback about the overall program. Thematic analysis of the interviews identified themes from the usability testing. Descriptive statistics were used to summarize patient demographic data. Results: We enrolled 11 participants (n = 7 males, n = 4 females, ages 30-82). The main themes generated anchored on (1) impact on nephrology care, (2) technical features, and (3) CKD content. Overall, participants reported positive satisfaction toward the navigation, layout, and content of the program. They cited the value of the program in their daily CKD care. Limitations: Study limitations included using a single center to recruit participants, most of the participants having prior technology use, and using one module as a representative of the entire digital platform. Conclusion: The acceptability of a digital counseling program for patients with CKD relies on taking the patients’ perspective using a user-centered design process. It is vital in ensuring adoption and adherence to self-management interventions aimed at sustaining behavioral change.
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Affiliation(s)
- Stephanie W Ong
- Connected Care, University Health Network, Toronto, ON, Canada.,Division of Nephrology, University Health Network, Toronto, ON, Canada.,Leslie Dan Faculty of Pharmacy, University of Toronto, ON, Canada.,Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada
| | - Julia V Wong
- Cardiac eHealth and Behavioural Cardiology Research Unit, Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada
| | - Bourne L Auguste
- Division of Nephrology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.,Faculty of Medicine, University of Toronto, ON, Canada
| | - Alexander G Logan
- Division of Nephrology, University Health Network, Toronto, ON, Canada.,Faculty of Medicine, University of Toronto, ON, Canada.,Department of Medicine, University Health Network, Toronto, ON, Canada.,Institute of Health Policy, Management and Evaluation, University of Toronto, ON, Canada.,Lunenfeld-Tanenbaum Research Institute, Sinai Health, Toronto, ON, Canada
| | - Robert P Nolan
- Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.,Cardiac eHealth and Behavioural Cardiology Research Unit, Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada.,Ted Rogers Centre of Excellence in Heart Function, Peter Munk Cardiac Centre, University Health Network, Toronto, ON, Canada.,Psychiatry Department and Institute of Medical Science, Faculty of Graduate Studies, University of Toronto, ON, Canada
| | - Christopher T Chan
- Division of Nephrology, University Health Network, Toronto, ON, Canada.,Toronto General Hospital Research Institute, University Health Network, Toronto, ON, Canada.,Faculty of Medicine, University of Toronto, ON, Canada.,Department of Medicine, University Health Network, Toronto, ON, Canada
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14
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Xiong Y, Zhang Y, Zhang F, Wu C, Luo P, Qin F, Yuan J. Genetic Evidence Supporting the Causal Role of Homocysteine in Chronic Kidney Disease: A Mendelian Randomization Study. Front Nutr 2022; 9:843534. [PMID: 35495913 PMCID: PMC9048023 DOI: 10.3389/fnut.2022.843534] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Accepted: 03/15/2022] [Indexed: 01/09/2023] Open
Abstract
Background The causal relationship between homocysteine (Hcy) levels and chronic kidney disease (CKD) remains unclear. This study was performed to estimate the potential causal effects of Hcy on the estimated glomerular filtration rate (eGFR) and CKD. Materials and Methods The single nucleotide polymorphisms (SNPs) associated with one standard deviation (SD) Hcy increase were identified using the genome-wide association study (GWAS). The summary statistics of the eGFR and CKD were from the CKDGen project in the European ancestry and the Population Architecture using Genomics and Epidemiology (PAGE) project in the non-European ancestry. Two-sample Mendelian randomization (MR) analyses were used in this study to verify the causal effects among Hcy, eGFR, and CKD. Results The results showed that 1-SD Hcy increase was causally associated with eGFR decline in the CKDGen project (β = −0.027 log ml.min–1/1.73 m2, p < 0.01 for the overall cohort; β = −0.028 log ml.min–1/1.73 m2, p < 0.01 after excluding the patients with diabetes). In addition, 1-SD Hcy increase was associated with a 1.32-fold risk of CKD in the PAGE project (95% CI = 1.06–1.64, p < 0.05). The association was directionally similar in the CKDGen project [odds ratio (OR) = 1.08, 95% CI = 0.97–1.44, p = 0.098]. The pooled OR of CKD was 1.24 (95% CI = 1.07–1.44, p < 0.05) per 1-SD Hcy increase. Conclusion Using genetic data, Hcy increase is causally associated with renal function injury and further CKD.
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Affiliation(s)
- Yang Xiong
- Andrology Laboratory, West China Hospital, Sichuan University, Chengdu, China
- Department of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Yangchang Zhang
- Department of Epidemiology and Health Statistics, School of Public Health and Management, Chongqing Medical University, Chongqing, China
| | - Fuxun Zhang
- Andrology Laboratory, West China Hospital, Sichuan University, Chengdu, China
- Department of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Changjing Wu
- Andrology Laboratory, West China Hospital, Sichuan University, Chengdu, China
| | - Peiyi Luo
- Department of Nephrology, Kidney Research Institute, West China Hospital, Sichuan University, Chengdu, China
| | - Feng Qin
- Andrology Laboratory, West China Hospital, Sichuan University, Chengdu, China
| | - Jiuhong Yuan
- Andrology Laboratory, West China Hospital, Sichuan University, Chengdu, China
- Department of Urology, West China Hospital, Sichuan University, Chengdu, China
- *Correspondence: Jiuhong Yuan,
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15
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Tao Z, Li Y, Cheng B, Zhou T, Gao Y. Influence of Nonalcoholic Fatty Liver Disease on the Occurrence and Severity of Chronic Kidney Disease. J Clin Transl Hepatol 2022; 10:164-173. [PMID: 35233386 PMCID: PMC8845149 DOI: 10.14218/jcth.2021.00171] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 07/10/2021] [Accepted: 08/25/2021] [Indexed: 12/04/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is reported to affect 20-30% of adults and is accompanied by various metabolic comorbidities, where the economic and clinical burden of NAFLD is attributed to the progression of liver disease as well as the presence of extrahepatic diseases. Chronic kidney disease (CKD), which has a high incidence rate, high morbidity and mortality rates, and high medical costs, has been linked to NAFLD. CKD is associated with some metabolism-related risk factors that overlap with metabolic comorbidities of NAFLD. Therefore, to investigate the potential factors that influence CKD occurrence, the association between NAFLD and CKD should be clarified. Some studies have confirmed that NAFLD influences the occurrence and severity of CKD, whereas some studies have indicated that there is no correlation. In this review, the results of a few studies have been discussed, the potential risk factors for CKD in NAFLD are explored, and the respective biological mechanisms are elaborated to help clinicians identify CKD in patients much earlier than it is diagnosed now and thus help in reducing the incidence of liver and kidney transplants.
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Affiliation(s)
| | | | | | | | - Yanjing Gao
- Correspondence to: Yanjing Gao, Department of Gastroenterology, Qilu Hospital of Shandong University, 107 Wenhua Xi Road, Jinan, Shandong 250012, China. ORCID: https://orcid.org/0000-0001-8153-3754. Tel: +86-18560086087, E-mail:
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16
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Yu TH, Hsuan CF, Wu CC, Hung WC, Lee TL, Tsai IT, Wei CT, Houng JY, Chung FM, Lee YJ, Lu YC. Association of plasma fatty acid-binding protein 3 with estimated glomerular filtration rate in patients with type 2 diabetes mellitus. Int J Med Sci 2022; 19:82-88. [PMID: 34975301 PMCID: PMC8692122 DOI: 10.7150/ijms.66876] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 11/10/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Fatty acid-binding protein 3 (FABP3) located in renal mesangial and distal tubular cells, and had been shown to be a sensitive marker of renal injury, potentially be a mediator in pathogenesis of chronic kidney disease (CKD). Our previous study revealed that plasma FABP1 and FABP2 were independently associated with CKD, however, little is known about the relationship between plasma FABP3 level and CKD. The aim of this study was therefore to evaluate the plasma levels of FABP3 at different stages of estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes mellitus (T2DM). Methods: A total of 334 subjects with T2DM who enrolled in a disease management program were included in this study and stratified according to eGFR. Plasma FABP3 concentrations were measured by an enzyme-linked immunosorbent assay. Results: FABP3 levels increased in parallel with the eGFR level. Increasing concentrations of FABP3 were independently and significantly associated with eGFR stage G2-G4. Age- and sex-adjusted FABP3 levels were positively associated with uric acid, urinary albumin-to-creatinine ratio, FABP1, FABP2, and fatty liver index, but negatively associated with eGFR and hemoglobin. Conclusion: Our results indicate that circulating FABP3 in patients with T2DM is associated with eGFR, which suggests that increased plasma FABP3 may be involved in the pathogenesis of CKD.
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Affiliation(s)
- Teng-Hung Yu
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445 Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 82445 Taiwan
| | - Chin-Feng Hsuan
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445 Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 82445 Taiwan.,Division of Cardiology, Department of Internal Medicine, E-Da Dachang Hospital, Kaohsiung, 80794 Taiwan
| | - Cheng-Ching Wu
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445 Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 82445 Taiwan
| | - Wei-Chin Hung
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445 Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 82445 Taiwan
| | - Thung-Lip Lee
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445 Taiwan.,School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, 82445 Taiwan
| | - I-Ting Tsai
- Department of Emergency, E-Da Hospital, Kaohsiung 82445 Taiwan.,School of Medicine, College of Medicine, I-Shou University, Kaohsiung, 82445 Taiwan
| | - Ching-Ting Wei
- Division of General Surgery, Department of Surgery, E-Da Hospital, Kaohsiung 82445 Taiwan.,School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, 82445 Taiwan.,Department of Biomedical Engineering, I-Shou University, Kaohsiung, 82445 Taiwan.,Department of Electrical Engineering, I-Shou University, Kaohsiung, 82445 Taiwan
| | - Jer-Yiing Houng
- Department of Nutrition, College of Medicine, I-Shou University, Kaohsiung, 82445 Taiwan.,Department of Chemical Engineering, I-Shou University, Kaohsiung, 82445 Taiwan
| | - Fu-Mei Chung
- Division of Cardiology, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445 Taiwan
| | | | - Yung-Chuan Lu
- Division of Endocrinology and Metabolism, Department of Internal Medicine, E-Da Hospital, Kaohsiung 82445 Taiwan.,School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, 82445 Taiwan
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17
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Lee SB, Park BJ, Lee YJ, Jung DH. Early Chronic Kidney Disease (G1-G3a) in Combination with Steatosis as a Predictor of Incident Ischemic Heart Disease: A Longitudinal Study in Non-Diabetic Koreans. Biomedicines 2021; 9:biomedicines9101358. [PMID: 34680475 PMCID: PMC8533481 DOI: 10.3390/biomedicines9101358] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/25/2021] [Accepted: 09/28/2021] [Indexed: 12/26/2022] Open
Abstract
Hepatic steatosis and chronic kidney disease (CKD) in the advanced stages are closely related to cardiovascular diseases. Despite the potential connection between early CKD (G1-G3a) and hepatic steatosis on cardiometabolic risks, few studies have revealed their causal link to ischemic heart disease (IHD). We prospectively investigated the combined effect of CKD in earlier stages and hepatic steatosis on incident IHD risk in large-scale, non-diabetic Koreans. Data were assessed from 16,531 participants without diabetes from the Health Risk Assessment Study (HERAS) and Korea Health Insurance Review and Assessment (HIRA) data. We divided the study population into four groups according to the existence of early CKD and hepatic steatosis: controls, early CKD only, hepatic steatosis only, and both early CKD and hepatic steatosis. We prospectively assessed hazard ratios (HRs) with 95% confidence intervals (CIs) for IHD using multivariate Cox proportional-hazard regression models over a 50-month period. During the follow-up period, 326 (2.0%) patients developed IHD. HRs of IHD in the four groups were 1.00 (controls), 1.26 (95% CI 0.72–2.19), 1.19 (95% CI 0.90–1.57) and 1.76 (95% CI 1.04–2.97), respectively, after adjusting for potential confounding variables. Even less than stage 3A, CKD could precede and predict IHD in patients with hepatic steatosis.
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Affiliation(s)
- Sung-Bum Lee
- Department of Health Check-up, Yongin Severance Hospital, Yongin-si 16995, Korea;
| | - Byoung-Jin Park
- Department of Family Medicine, Yongin Severance Hospital, Yongin-si 16995, Korea;
| | - Yong-Jae Lee
- Department of Family Medicine, Gangnam Severance Hospital, Seoul 06273, Korea;
| | - Dong-Hyuk Jung
- Department of Family Medicine, Yongin Severance Hospital, Yongin-si 16995, Korea;
- Correspondence:
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18
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Hsu CK, Lai TS, Chen YT, Tseng YJ, Lee CC, Chen CY, Hsu HJ, Pan HC, Chen LW, Chien CH, Lin CL, Chien RN, Wu IW. Renal function trajectories in hepatitis C infection: differences between renal healthy and chronic kidney disease individuals. Sci Rep 2021; 11:17197. [PMID: 34433887 PMCID: PMC8387367 DOI: 10.1038/s41598-021-96782-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Accepted: 08/17/2021] [Indexed: 02/07/2023] Open
Abstract
Associations between hepatitis C virus (HCV) and chronic kidney disease (CKD) have been reported; however, differences of renal progression between general and CKD population remain to be elucidated in prospective studies. A total of 1179 participants, who have tested for anti-HCV antibody, were enrolled and prospectively followed for 3 years. The risks associated with HCV infection, in terms of incidence of CKD, annual estimated glomerular filtration rate (eGFR) changes and 50% decline of eGFR at 3-year from baseline, were compared between normal renal function subjects and CKD patients. Overall, 111 of 233 (47.6%) CKD patients and 167 of 946 (17.7%) non-CKD subjects had HCV infection. The crude incidence rates of CKD were 226.9 per 1000 person-years and 14.8 per 1000 person-years in in HCV and non-HCV infected patients, respectively. The adjusted hazard ratio of HCV infection for incident CKD was 7.9 (95% CI 5-12.7). The HCV-infected normal renal function subjects were independently associated with increased risks of eGFR decline in the 1-year, 2-year and 3-year, respectively. The risk associations remained significant in 50% decline of eGFR at 3 years models and in different subgroup analyses. The increases of risks of eGFR decline were also notorious among overall HCV-infected CKD patients. However, the risk associations were less prominent in subgroup analyses (elderly, women and diabetic patients). The findings highlighted the importance of viral diagnosis with not only prognostic but also public health implications for preserving kidney function.
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Affiliation(s)
- Cheng-Kai Hsu
- Department of Nephrology, Chang Gung Memorial Hospital, 222, Mai-Chin Road, Keelung, 20401, Taiwan
| | - Tai-Shuan Lai
- Division of Nephrology, Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
| | - Yih-Ting Chen
- Department of Nephrology, Chang Gung Memorial Hospital, 222, Mai-Chin Road, Keelung, 20401, Taiwan
| | - Yi-Ju Tseng
- Department of Information Management, National Central University, Taoyüan, Taiwan
| | - Chin-Chan Lee
- Department of Nephrology, Chang Gung Memorial Hospital, 222, Mai-Chin Road, Keelung, 20401, Taiwan
| | - Chun-Yu Chen
- Department of Nephrology, Chang Gung Memorial Hospital, 222, Mai-Chin Road, Keelung, 20401, Taiwan
| | - Heng-Jung Hsu
- Department of Nephrology, Chang Gung Memorial Hospital, 222, Mai-Chin Road, Keelung, 20401, Taiwan
| | - Heng-Chih Pan
- Department of Nephrology, Chang Gung Memorial Hospital, 222, Mai-Chin Road, Keelung, 20401, Taiwan
| | - Li-Wei Chen
- Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Cheng-Hung Chien
- Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chih-Lang Lin
- Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Rong-Nan Chien
- Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - I-Wen Wu
- Department of Nephrology, Chang Gung Memorial Hospital, 222, Mai-Chin Road, Keelung, 20401, Taiwan.
- Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan.
- College of Medicine, Chang Gung University, Taoyüan, Taiwan.
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19
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Matías-García PR, Ward-Caviness CK, Raffield LM, Gao X, Zhang Y, Wilson R, Gào X, Nano J, Bostom A, Colicino E, Correa A, Coull B, Eaton C, Hou L, Just AC, Kunze S, Lange L, Lange E, Lin X, Liu S, Nwanaji-Enwerem JC, Reiner A, Shen J, Schöttker B, Vokonas P, Zheng Y, Young B, Schwartz J, Horvath S, Lu A, Whitsel EA, Koenig W, Adamski J, Winkelmann J, Brenner H, Baccarelli AA, Gieger C, Peters A, Franceschini N, Waldenberger M. DNAm-based signatures of accelerated aging and mortality in blood are associated with low renal function. Clin Epigenetics 2021; 13:121. [PMID: 34078457 PMCID: PMC8170969 DOI: 10.1186/s13148-021-01082-w] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2020] [Accepted: 04/18/2021] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND The difference between an individual's chronological and DNA methylation predicted age (DNAmAge), termed DNAmAge acceleration (DNAmAA), can capture life-long environmental exposures and age-related physiological changes reflected in methylation status. Several studies have linked DNAmAA to morbidity and mortality, yet its relationship with kidney function has not been assessed. We evaluated the associations between seven DNAm aging and lifespan predictors (as well as GrimAge components) and five kidney traits (estimated glomerular filtration rate [eGFR], urine albumin-to-creatinine ratio [uACR], serum urate, microalbuminuria and chronic kidney disease [CKD]) in up to 9688 European, African American and Hispanic/Latino individuals from seven population-based studies. RESULTS We identified 23 significant associations in our large trans-ethnic meta-analysis (p < 1.43E-03 and consistent direction of effect across studies). Age acceleration measured by the Extrinsic and PhenoAge estimators, as well as Zhang's 10-CpG epigenetic mortality risk score (MRS), were associated with all parameters of poor kidney health (lower eGFR, prevalent CKD, higher uACR, microalbuminuria and higher serum urate). Six of these associations were independently observed in European and African American populations. MRS in particular was consistently associated with eGFR (β = - 0.12, 95% CI = [- 0.16, - 0.08] change in log-transformed eGFR per unit increase in MRS, p = 4.39E-08), prevalent CKD (odds ratio (OR) = 1.78 [1.47, 2.16], p = 2.71E-09) and higher serum urate levels (β = 0.12 [0.07, 0.16], p = 2.08E-06). The "first-generation" clocks (Hannum, Horvath) and GrimAge showed different patterns of association with the kidney traits. Three of the DNAm-estimated components of GrimAge, namely adrenomedullin, plasminogen-activation inhibition 1 and pack years, were positively associated with higher uACR, serum urate and microalbuminuria. CONCLUSION DNAmAge acceleration and DNAm mortality predictors estimated in whole blood were associated with multiple kidney traits, including eGFR and CKD, in this multi-ethnic study. Epigenetic biomarkers which reflect the systemic effects of age-related mechanisms such as immunosenescence, inflammaging and oxidative stress may have important mechanistic or prognostic roles in kidney disease. Our study highlights new findings linking kidney disease to biological aging, and opportunities warranting future investigation into DNA methylation biomarkers for prognostic or risk stratification in kidney disease.
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Affiliation(s)
- Pamela R Matías-García
- TUM School of Medicine, Technical University of Munich, Munich, Germany.
- Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany.
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany.
- German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
| | - Cavin K Ward-Caviness
- Center for Public Health and Environmental Assessment, US Environmental Protection Agency, Chapel Hill, NC, USA
| | - Laura M Raffield
- Department of Genetics, University of North Carolina, Chapel Hill, NC, USA
| | - Xu Gao
- Laboratory of Precision Environmental Health, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Yan Zhang
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Rory Wilson
- Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany
| | - Xīn Gào
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Jana Nano
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Andrew Bostom
- Center For Primary Care and Prevention, Memorial Hospital of Rhode Island, Pawtucket, RI, USA
| | - Elena Colicino
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Adolfo Correa
- Departments of Medicine and Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA
| | - Brent Coull
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Charles Eaton
- Center For Primary Care and Prevention, Memorial Hospital of Rhode Island, Pawtucket, RI, USA
- Department of Family Medicine, Warren Alpert Medical School, Brown University, Providence, RI, USA
| | - Lifang Hou
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Allan C Just
- Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Sonja Kunze
- Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany
| | - Leslie Lange
- Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Ethan Lange
- Department of Medicine, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO, USA
| | - Xihong Lin
- Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
| | - Simin Liu
- Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA
| | | | - Alex Reiner
- Department of Epidemiology, University of Washington, Seattle, WA, USA
| | - Jincheng Shen
- Department of Population Health Sciences, School of Medicine, University of Utah, Salt Lake City, UT, USA
| | - Ben Schöttker
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Network Aging Research, University of Heidelberg, Heidelberg, Germany
| | - Pantel Vokonas
- Veterans Affairs Normative Aging Study, Veterans Affairs Boston Healthcare System, Department of Medicine, Boston University School of Medicine, Boston, MA, USA
| | - Yinan Zheng
- Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Bessie Young
- Nephrology, Hospital and Specialty Medicine and Center for Innovation for Veteran-Centered and Value Driven Care, Veterans Affairs Puget Sound Health Care System, Seattle, WA, USA
- Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, WA, USA
| | - Joel Schwartz
- Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Steve Horvath
- Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Ake Lu
- Department of Human Genetics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA, USA
| | - Eric A Whitsel
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
- Department of Medicine, School of Medicine, University of North Carolina, Chapel Hill, NC, USA
| | - Wolfgang Koenig
- German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
- Deutsches Herzzentrum München, Technische Universität München, Munich, Germany
- Institute of Epidemiology and Medical Biometry, University of Ulm, Ulm, Germany
| | - Jerzy Adamski
- Research Unit Molecular Endocrinology and Metabolism, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany
- Chair for Experimental Genetics, Technical University of Munich, Freising-Weihenstephan, Germany
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore
| | - Juliane Winkelmann
- Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany
- Chair Neurogenetics, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
- Institute of Human Genetics, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
- Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany
- Network Aging Research, University of Heidelberg, Heidelberg, Germany
| | - Andrea A Baccarelli
- Laboratory of Precision Environmental Health, Mailman School of Public Health, Columbia University, New York, NY, USA
| | - Christian Gieger
- Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany
| | - Annette Peters
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany
- German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Nora Franceschini
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
| | - Melanie Waldenberger
- Research Unit Molecular Epidemiology, Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany.
- Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Munich/Neuherberg, Germany.
- German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.
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20
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Scurt FG, Bose K, Canbay A, Mertens PR, Chatzikyrkou C. [Chronic kidney injury in patients with liver diseases - Reappraising pathophysiology and treatment options]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 59:560-579. [PMID: 33728618 DOI: 10.1055/a-1402-1502] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Abstract
Acute and chronic kidney disease concurs commonly with liver disease and is associated with a wide array of complications including dialysis dependency and increased mortality. Patients with liver disease or liver cirrhosis show a higher prevalence of chronic kidney disease. This is attributed to concomitant comorbidities, such as metabolic syndrome, chronic inflammation, hypercoagulability, hyperfibrinolysis, diabetes mellitus and dyslipidaemias. But chronic progressive kidney disease is not always due to hepatorenal syndrome. Beyond that, other diseases or disease entities should be considered. Among them are diabetic nephropathy, secondary IgA nephropathy, hepatitis C -associated membranoproliferative Glomerulonephritis (MPGN) and hepatitis B-associated membranous nephropathy.Coexisting diseases, similar underlying pathophysiologic mechanisms, or simultaneously concurring pathophysiological processes and overlapping clinical manifestations, impede the etiologic diagnosis and corresponding treatment of chronic kidney disease in the setting of chronic liver disease. In this review, we focus on common and rare pathologies, which can lead to chronic kidney disease in this particular patient group and try to summarize the most recent therapeutic modalities.
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Affiliation(s)
- Florian Gunnar Scurt
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany
| | - Katrin Bose
- Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany.,Universitätsklinik für Gastroenterologie, Hepatologie und Infektiologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland
| | - Ali Canbay
- Ruhr-Universität Bochum, Medizinische Klinik, Universitätsklinikum Knappschaftskrankenhaus Bochum GmbH, Bochum, Deutschland
| | - Peter R Mertens
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany
| | - Christos Chatzikyrkou
- Klinik für Nieren- und Hochdruckerkrankungen, Diabetologie und Endokrinologie, Medizinische Fakultät der Otto-von-Guericke-Universität, Magdeburg, Deutschland.,Health Campus Immunology, Infectiology and Inflammation, Otto von Guericke University, Magdeburg, Germany
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21
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Yagoglu AI, Dizdar OS, Erdem S, Akcakaya B, Gunal AI. The effect of linagliptin on renal progression in type-2 diabetes mellitus patients with chronic kidney disease: A prospective randomized controlled study. Nefrologia 2020; 40:664-671. [PMID: 32736891 DOI: 10.1016/j.nefro.2020.04.023] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2019] [Revised: 04/03/2020] [Accepted: 04/21/2020] [Indexed: 01/12/2023] Open
Abstract
BACKGROUND Linagliptin does not require dose adjustment in diabetes mellitus patients with chronic kidney disease (CKD). But, renal effects of linagliptin are not clear. Our aim was to examine the effect of linagliptin on renal disease progression in only insulin dependent type 2 diabetes mellitus (DM) patients with CKD. METHODS Stage 3-4 CKD patients were randomized into 2 groups in this prospective randomized controlled study. In the first group, linagliptin 5mg was added in addition to the background insulin therapy. In the second group, patients continued their insulin therapy. Patients were followed up at 3-month intervals for one year. RESULTS The study population consisted of 164 patients (90 patients in linagliptin group, 74 patients in other group) with a mean age of 67.5±8.8 years. eGFR significantly increased in linagliptin group (p=0.033), but decreased in other group (p=0.003). No significant change was observed in total insulin dose in linagliptin group (p=0.111), but in other group, total insulin dose significantly increased (p<0.001). Proteinuria levels decreased in both groups, but there was no significant change. In the multiple logistic regression analysis, male gender and proteinuria emerged as variables that showed significant association with increased risk and the use of linagliptin emerged as variable that showed significant association with decreased risk for CKD progression. CONCLUSION Linagliptin in DM patients with CKD was able to improve renal progression without significant effect on proteinuria and glucose control. With regard to treating diabetic nephropathy, linagliptin may offer a new therapeutic approach.
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Affiliation(s)
- Ali Ihsan Yagoglu
- Department of Internal Medicine, Kayseri City Training and Research Hospital, Kayseri, Turkey.
| | - Oguzhan Sıtkı Dizdar
- Department of Internal Medicine and Clinical Nutrition, Kayseri City Training and Research Hospital, Kayseri, Turkey
| | - Selahattin Erdem
- Department of Internal Medicine, Kayseri City Training and Research Hospital, Kayseri, Turkey
| | - Berkan Akcakaya
- Department of Internal Medicine, Kayseri City Training and Research Hospital, Kayseri, Turkey
| | - Ali Ihsan Gunal
- Department of Internal Medicine Division of Nephrology, Kayseri City Training and Research Hospital, Kayseri, Turkey
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22
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Steggerda JA, Mahendraraj K, Todo T, Noureddin M. Clinical considerations in the management of non-alcoholic steatohepatitis cirrhosis pre- and post-transplant: A multi-system challenge. World J Gastroenterol 2020; 26:4018-4035. [PMID: 32821068 PMCID: PMC7403794 DOI: 10.3748/wjg.v26.i28.4018] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Revised: 05/07/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic steatohepatitis (NASH) is the most common chronic liver disease worldwide, and the fastest growing indication for liver transplantation in the United States. NASH is now the leading etiology for liver transplantation in women, the second leading indication for men, and the most common cause amongst recipients aged 65 years and older. Patients with end-stage liver disease related to NASH represent a unique and challenging patient population due the high incidence of associated comorbid diseases, including obesity, type 2 diabetes (T2D), and hypertension. These challenges manifest in the pre-liver transplantation period with increased waitlist times and waitlist mortality. Furthermore, these patients carry considerable risk of morbidity and mortality both before after liver transplantation, with high rates of T2D, cardiovascular disease, chronic kidney disease, poor nutrition, and disease recurrence. Successful transplantation for these patients requires identification and management of their comorbidities in the face of liver failure. Multidisciplinary evaluations include a thorough pre-transplant workup with a complete cardiac evaluation, control of diabetes, nutritional support, and even, potentially, consultation with a bariatric surgeon. This article provides a comprehensive review of the conditions and challenges facing patients with NASH cirrhosis undergoing liver transplantation and provides recommendations for evaluation and management to optimize them before liver transplantation to produce successful outcomes.
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Affiliation(s)
- Justin A Steggerda
- Department of Surgery, Division of Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Krishnaraj Mahendraraj
- Department of Surgery, Division of Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Tsuyoshi Todo
- Department of Surgery, Division of Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
| | - Mazen Noureddin
- Division of Digestive and Liver Diseases, Comprehensive Transplant Center, Cedars-Sinai Medical Center, Los Angeles, CA 90048, United States
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23
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Fawzy MS, Abu AlSel BT, Al Ageeli E, Al-Qahtani SA, Abdel-Daim MM, Toraih EA. Long non-coding RNA MALAT1 and microRNA-499a expression profiles in diabetic ESRD patients undergoing dialysis: a preliminary cross-sectional analysis. Arch Physiol Biochem 2020; 126:172-182. [PMID: 30270667 DOI: 10.1080/13813455.2018.1499119] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2018] [Accepted: 07/08/2018] [Indexed: 01/22/2023]
Abstract
Background: Circulating non-coding RNAs (ncRNAs) have been implicated in health and disease. This study aimed to evaluate the serum expression profile of microRNA-499a (miR-499a) and its selected bioinformatically predicted partner long-ncRNA MALAT1 (metastasis-associated lung adenocarcinoma transcript 1) in diabetes-related end-stage renal disease (ESRD) patients and to correlate the expressions with the patients' clinicolaboratory data.Subjects and methods: Real-time quantitative polymerase chain reaction was applied in diabetics with and without ESRD (n = 90 for each).Results: Serum MALAT1 expression levels were increased in the ESRD group relative to diabetics without ESRD with median (quartile) values of 10.5 (1.41-126.7) (p < .001). However, miR-499a levels were decreased in more than half of ESRD patients with a median of 0.96 (0.13-3.14). Both MALAT1 and miR-499a expression levels were inversely correlated in the ESRD patient-group.Conclusions: MALAT1 up-regulation and miR-499 down-regulation might be involved in diabetic nephropathy-related ESRD pathogenesis. Functional validation studies are warranted to confirm the MALAT1/miR-499a partnership.
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MESH Headings
- Adult
- Aged
- Base Pairing
- Base Sequence
- Cross-Sectional Studies
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/diagnosis
- Diabetes Mellitus, Type 2/genetics
- Diabetes Mellitus, Type 2/therapy
- Diabetic Nephropathies/diagnosis
- Diabetic Nephropathies/etiology
- Diabetic Nephropathies/genetics
- Diabetic Nephropathies/therapy
- Disease Progression
- Female
- Gene Expression Regulation
- Humans
- Kidney Failure, Chronic/diagnosis
- Kidney Failure, Chronic/etiology
- Kidney Failure, Chronic/genetics
- Kidney Failure, Chronic/therapy
- Male
- MicroRNAs/blood
- MicroRNAs/genetics
- Middle Aged
- RNA, Long Noncoding/blood
- RNA, Long Noncoding/genetics
- Renal Dialysis
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Affiliation(s)
- Manal S Fawzy
- Department of Biochemistry, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia
- Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt
| | - Baraah T Abu AlSel
- Department of Microbiology, Faculty of Medicine, Northern Border University, Arar, Saudi Arabia
| | - Essam Al Ageeli
- Department of Clinical Biochemistry (Medical Genetics), Faculty of Medicine, Jazan University, Jazan, Saudi Arabia
| | - Saeed Awad Al-Qahtani
- Department of Physiology, Faculty of Medicine, Taibah University, Almadinah Almunawwarah, Saudi Arabia
| | - Mohamed M Abdel-Daim
- Department of Pharmacology, Faculty of Veterinary Medicine, Suez Canal University, Ismailia, Egypt
| | - Eman A Toraih
- Department of Histology and Cell Biology (Genetics Unit), Faculty of Medicine, Suez Canal University, Ismailia, Egypt
- Center of Excellence of Molecular and Cellular Medicine, Suez Canal University, Ismailia, Egypt
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24
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Kim OH, Booth CJ, Choi HS, Lee J, Kang J, Hur J, Jung WJ, Jung YS, Choi HJ, Kim H, Auh JH, Kim JW, Cha JY, Lee YJ, Lee CS, Choi C, Jung YJ, Yang JY, Im SS, Lee DH, Cho SW, Kim YB, Park KS, Park YJ, Oh BC. High-phytate/low-calcium diet is a risk factor for crystal nephropathies, renal phosphate wasting, and bone loss. eLife 2020; 9:52709. [PMID: 32271147 PMCID: PMC7145417 DOI: 10.7554/elife.52709] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Accepted: 03/22/2020] [Indexed: 12/13/2022] Open
Abstract
Phosphate overload contributes to mineral bone disorders that are associated with crystal nephropathies. Phytate, the major form of phosphorus in plant seeds, is known as an indigestible and of negligible nutritional value in humans. However, the mechanism and adverse effects of high-phytate intake on Ca2+ and phosphate absorption and homeostasis are unknown. Here, we show that excessive intake of phytate along with a low-Ca2+ diet fed to rats contributed to the development of crystal nephropathies, renal phosphate wasting, and bone loss through tubular dysfunction secondary to dysregulation of intestinal calcium and phosphate absorption. Moreover, Ca2+ supplementation alleviated the detrimental effects of excess dietary phytate on bone and kidney through excretion of undigested Ca2+-phytate, which prevented a vicious cycle of intestinal phosphate overload and renal phosphate wasting while improving intestinal Ca2+ bioavailability. Thus, we demonstrate that phytate is digestible without a high-Ca2+ diet and is a risk factor for phosphate overloading and for the development of crystal nephropathies and bone disease.
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Affiliation(s)
- Ok-Hee Kim
- Department of Physiology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon, Republic of Korea
| | - Carmen J Booth
- Department of Comparative Medicine, Yale University School of Medicine, New Haven, United States
| | - Han Seok Choi
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Dongguk University Ilsan Hospital, Goyang, Republic of Korea
| | - Jinwook Lee
- Department of Physiology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon, Republic of Korea
| | - Jinku Kang
- Department of Physiology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon, Republic of Korea
| | - June Hur
- Department of Physiology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon, Republic of Korea
| | - Woo Jin Jung
- Department of Physiology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon, Republic of Korea
| | - Yun-Shin Jung
- Department of Physiology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon, Republic of Korea
| | - Hyung Jin Choi
- Department of Anatomy, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Hyeonjin Kim
- Department of Radiology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Joong-Hyuck Auh
- Department of Food Science and Technology, Chung-Ang University, Ansung, Republic of Korea
| | - Jung-Wan Kim
- Department of Biology, University of Incheon, Incheon, Republic of Korea
| | - Ji-Young Cha
- Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute Gachon University College of Medicine, Incheon, Republic of Korea
| | - Young Jae Lee
- Department of Biochemistry, Lee Gil Ya Cancer and Diabetes Institute Gachon University College of Medicine, Incheon, Republic of Korea
| | - Cheol Soon Lee
- Medical Health Research Center, Korea University Anam Hospital, Seoul, Republic of Korea
| | - Cheolsoo Choi
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea
| | - Yun Jae Jung
- Department of Mirobiolgy, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon, Republic of Korea
| | - Jun-Young Yang
- Department of Toxicological Evaluation and Research, Ministry of Food and Drug Safety, Cheongju-si, Republic of Korea
| | - Seung-Soon Im
- Department of Physiology, Keimyung University School of Medicine, Daegu, Republic of Korea
| | - Dae Ho Lee
- Department of Internal Medicine, Gachon University Gil Medical Center, Incheon, Republic of Korea
| | - Sun Wook Cho
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Young-Bum Kim
- Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, United States
| | - Kyong Soo Park
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Young Joo Park
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Byung-Chul Oh
- Department of Physiology, Lee Gil Ya Cancer and Diabetes Institute, Gachon University College of Medicine, Incheon, Republic of Korea
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25
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Maiwall R, Gupta M. Peri-transplant renal dysfunction in patients with non-alcoholic steatohepatitis undergoing liver transplantation. Transl Gastroenterol Hepatol 2020; 5:18. [PMID: 32258522 DOI: 10.21037/tgh.2019.10.11] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 10/15/2019] [Indexed: 12/11/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently the most common etiology of chronic liver disease (CLD) caused by an accumulation of fat in the liver and globally is the leading indication of liver transplantation. Emerging data has recognized an increased association of NAFLD with risk of other metabolic liver diseases like type 2 diabetes mellitus, chronic kidney disease (CKD) and cardiovascular diseases. Pathophysiologically, NAFLD patients have a state of low-grade systemic inflammation, insulin resistance and atherogenic dyslipidemia which causes renal dysfunction. Patients with NAFLD cirrhosis awaiting liver transplant (LT) face unique challenges and have a significantly higher requirement of simultaneous-liver-kidney transplant as compared to other etiologies. Further, NAFLD not only recurs but also occurs as a de novo manifestation post-LT. There is also a significantly higher risk of waiting list stagnation and dropouts due to burdensome cardiometabolic disorders in NAFLD patients. The current review aims to understand the prevalence and pathogenetic basis of renal dysfunction in NAFLD. Additionally, the review describes the choice of immunosuppression protocols and use of intraoperative renal replacement therapy in context of intra and post-operative renal dysfunction in NAFLD patients. Prospective controlled trials focusing on NAFLD and development of CKD are needed to assess the existence of a causal and/or a bidirectional relationship between NAFLD and CKD.
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Affiliation(s)
- Rakhi Maiwall
- Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India
| | - Manasvi Gupta
- Department of Internal Medicine, University of Connecticut School of Medicine, Hartford, CT, USA
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26
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Byrne CD, Targher G. NAFLD as a driver of chronic kidney disease. J Hepatol 2020; 72:785-801. [PMID: 32059982 DOI: 10.1016/j.jhep.2020.01.013] [Citation(s) in RCA: 277] [Impact Index Per Article: 55.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/09/2019] [Revised: 12/27/2019] [Accepted: 01/10/2020] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are worldwide public health problems, affecting up to 25-30% (NAFLD), and up to 10-15% (CKD) of the general population. Recently, it has also been established that there is a strong association between NAFLD and CKD, regardless of the presence of potential confounding diseases such as obesity, hypertension and type 2 diabetes. Since NAFLD and CKD are both common diseases that often occur alongside other metabolic conditions, such as type 2 diabetes or metabolic syndrome, elucidating the relative impact of NAFLD on the risk of incident CKD presents a substantial challenge for investigators working in this research field. A growing body of epidemiological evidence suggests that NAFLD is an independent risk factor for CKD and recent evidence also suggests that associated factors such as metabolic syndrome, dysbiosis, unhealthy diets, platelet activation and processes associated with ageing could also contribute mechanisms linking NAFLD and CKD. This narrative review provides an overview of the literature on: a) the evidence for an association and causal link between NAFLD and CKD and b) the underlying mechanisms by which NAFLD (and factors strongly linked with NAFLD) may increase the risk of developing CKD.
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Affiliation(s)
- Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, UK.
| | - Giovanni Targher
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
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27
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Liu HW, Liu JS, Kuo KL. Association of nonalcoholic fatty liver and chronic kidney disease: An analysis of 37,825 cases from health checkup center in Taiwan. Tzu Chi Med J 2020; 32:65-69. [PMID: 32110523 PMCID: PMC7015019 DOI: 10.4103/tcmj.tcmj_233_18] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2018] [Revised: 12/03/2018] [Accepted: 12/20/2018] [Indexed: 02/06/2023] Open
Abstract
OBJECTIVE Nonalcoholic fatty liver (NAFLD) and chronic kidney disease (CKD) share common pathogenic mechanisms and risk factors. The relationship between in NAFLD and CKD remains controversial. We aim to assess the association between NAFLD and CKD. MATERIALS AND METHODS A cross-sectional study was based on individuals who received physical checkups at the Taipei Tzu Chi Hospital from September 5, 2005, to December 31, 2016. Demographic and clinical characteristics of the study population were collected. NAFLD was defined by abdominal ultrasonography and excluded other liver disease. CKD was defined as estimated glomerular filtration rate ≤60 mL/min/1.73 m2 or the presence of proteinuria. The association between NAFLD and CKD was then analyzed using SAS software by using the multivariable logistic model. A higher prevalence of CKD was shown in individuals with NAFLD compared to those without NAFLD. RESULTS In univariate analysis, individuals with mild NAFLD and moderate-to-severe NAFLD were both significantly associated with CKD (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.13-1.33; OR, 1.66; CI, 1.49-1.85) when compared to individuals without NAFLD. After multivariate adjustment, individuals with moderate-to-severe NAFLD were still significantly more likely to have CKD (OR, 1.17, 95% CI, 1.03-1.33). CONCLUSIONS Our finding showed that the presence and severity of NAFLD was positively associated with CKD in unadjusted and adjusted analysis. Further follow-up studies may be needed to validate these associations.
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Affiliation(s)
- Hao-Wen Liu
- Department of Family Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
| | - Jia-Sin Liu
- Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
| | - Ko-Lin Kuo
- Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei, Taiwan
- School of Medicine, Tzu Chi University, Hualien, Taiwan
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28
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Higher liver stiffness scores are associated with early kidney dysfunction in patients with histologically proven non-cirrhotic NAFLD. DIABETES & METABOLISM 2019; 46:288-295. [PMID: 31786360 DOI: 10.1016/j.diabet.2019.11.003] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/10/2019] [Revised: 11/03/2019] [Accepted: 11/09/2019] [Indexed: 12/18/2022]
Abstract
AIM The association between Liver fibrosis (LF), as assessed by either histology or Liver stiffness measurement (LSM), and the presence of Early kidney dysfunction (EKD) was investigated in this study, as was also the diagnostic performance of LSM for identifying the presence of EKD in patients with Non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS A total of 214 adults with non-cirrhotic biopsy-proven NAFLD were recruited from two independent medical centres. Their histological stage of LF was quantified using Brunt's criteria. Vibration-controlled Transient elastography (TE), using M-probe (FibroScan®) ultrasound, was performed in 154 patients and defined as significant when LSM was≥8.0kPa. EKD was defined as the presence of microalbuminuria with an estimated glomerular filtration rate≥60mL/min/1.73 m2. Logistic regression modelling was used to estimate the likelihood of having EKD with NAFLD (LSM-EKD model). RESULTS The prevalence of EKD was higher in patients with vs without LF on histology (22.14% vs 4.82%, respectively; P<0.001) and, similarly, EKD prevalence was higher in patients with LSM≥8.0kPa vs LSM<8.0kPa (23.81% vs 6.59%, respectively; P<0.05). The area under the ROC curve of the LSM-EKD model for identifying EKD was 0.80 (95% CI: 0.72-0.89). LF detected by either method was associated with EKD independently of established renal risk factors and potential confounders. CONCLUSION LF was independently associated with EKD in patients with biopsy-proven NAFLD. Thus, TE-measured LSM, a widely used technique for quantifying LF, can accurately identify those patients with NAFLD who are at risk of having EKD.
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Pallerla P, Bhumireddy SR, Lingampally SS, Ragi NC, Sripadi P. ESI-MS/MS analysis of protonated N-methyl amino acids and their immonium ions. JOURNAL OF MASS SPECTROMETRY : JMS 2019; 54:761-771. [PMID: 31412140 DOI: 10.1002/jms.4426] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/29/2019] [Revised: 07/28/2019] [Accepted: 08/05/2019] [Indexed: 06/10/2023]
Abstract
Methylation is one of the important posttranslational modifications of biological systems. At the metabolite level, the methylation process is expected to convert bioactive compounds such as amino acids, fatty acids, lipids, sugars, and other organic acids into their methylated forms. A few of the methylated amino acids are identified and have been proved as potential biomarkers for several metabolic disorders by using mass spectrometry-based metabolomics workstation. As it is possible to encounter all the N-methyl forms of the proteinogenic amino acids in plant/biological systems, it is essential to have analytical data of all N-methyl amino acids for their detection and identification. In earlier studies, we have reported the ESI-MS/MS data of all methylated proteinogenic amino acids, except that of mono-N-methyl amino acids. In this study, the N-methyl amino acids of all the amino acids (1-21; including one isomeric pair) were synthesized and characterized by ESI-MS/MS, LC/MS/MS, and HRMS. These data could be useful for detection and identification of N-methyl amino acids in biological systems for future metabolomics studies. The MS/MS spectra of [M + H]+ ions of most N-methyl amino acids showed respective immonium ions by the loss of (H2 O, CO). The other most common product ions detected were [MH-(NH2 CH3 ]+ , [MH-(RH)]+ (where R = side chain group) ions, and the selective structure indicative product ions due to side chain and N-methyl group. The isomeric/isobaric N-methyl amino acids could easily be differentiated by their distinct MS/MS spectra. Further, the MS/MS of immonium ions inferred side chain structure and methyl group on α-nitrogen of the N-methyl amino acids.
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Affiliation(s)
- Pavankumar Pallerla
- Centre for Mass Spectrometry, Analytical Department, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India
- Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India
| | - Sudarshana Reddy Bhumireddy
- Centre for Mass Spectrometry, Analytical Department, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India
| | - Sai Sachin Lingampally
- Centre for Mass Spectrometry, Analytical Department, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India
| | - Nagarjuna Chary Ragi
- Centre for Mass Spectrometry, Analytical Department, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India
- Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India
| | - Prabhakar Sripadi
- Centre for Mass Spectrometry, Analytical Department, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India
- Academy of Scientific and Innovative Research, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500007, India
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30
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Low levels of urinary epidermal growth factor predict chronic kidney disease progression in children. Kidney Int 2019; 96:214-221. [DOI: 10.1016/j.kint.2019.01.035] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2018] [Revised: 01/04/2019] [Accepted: 01/10/2019] [Indexed: 12/20/2022]
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Vlad CE, Foia L, Popescu R, Ivanov I, Luca MC, Delianu C, Toma V, Statescu C, Rezus C, Florea L. Apolipoproteins A and B and PCSK9: Nontraditional Cardiovascular Risk Factors in Chronic Kidney Disease and in End-Stage Renal Disease. J Diabetes Res 2019; 2019:6906278. [PMID: 31915710 PMCID: PMC6931031 DOI: 10.1155/2019/6906278] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Revised: 09/09/2019] [Accepted: 11/26/2019] [Indexed: 12/23/2022] Open
Abstract
PURPOSE Nontraditional cardiovascular risk factors as apolipoprotein A (ApoA), apolipoprotein B (ApoB), and the proprotein convertase subtilisin/kexin type 9 (PCSK9) increase the prevalence of cardiovascular mortality in chronic kidney disease (CKD) or in end-stage renal disease (ESRD) through quantitative alterations. This review is aimed at establishing the biomarker (ApoA, ApoB, and PCSK9) level variations in uremic patients, to identify the studies showing the association between these biomarkers and the development of cardiovascular events and to depict the therapeutic options to reduce cardiovascular risk in CKD and ESRD patients. METHODS We searched the electronic database of PubMed, Scopus, EBSCO, and Cochrane CENTRAL for studies evaluating apolipoproteins and PCSK9 in CKD and ESRD. Randomized controlled trials, observational studies (including case-control, prospective or retrospective cohort), and reviews/meta-analysis were included if reference was made to those keys and cardiovascular outcomes in CKD/ESRD. RESULTS 18 studies met inclusion criteria. Serum ApoA-I has been significantly associated with the development of new cardiovascular event and with cardiovascular mortality in ESRD patients. ApoA-IV level was independently associated with maximum carotid intima-media thickness (cIMT) and was a predictor for sudden cardiac death. The ApoB/ApoA-I ratio represents a strong predictor for coronary artery calcifications, cardiovascular mortality, and myocardial infarction in CKD/ESRD. Plasma levels of PCSK9 were not associated with cardiovascular events in CKD patients. CONCLUSIONS Although the "dyslipidemic status" in CKD/ESRD is not clearly depicted, due to different research findings, ApoA-I, ApoA-IV, and ApoB/ApoA-I ratio could be predictors of cardiovascular risk. Serum PCSK9 levels were not associated with the cardiovascular events in patients with CKD/ESRD. Probably in the future, the treatment of dyslipidemia in CKD/ESRD will be aimed at discovering new effective therapies on the action of these biomarkers.
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Affiliation(s)
- Cristiana-Elena Vlad
- Department of Nephrology, “Dr. C. I. Parhon” Clinical Hospital Iasi, Iasi, Romania
- Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
| | - Liliana Foia
- Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
| | - Roxana Popescu
- Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
| | - Iuliu Ivanov
- Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
| | | | - Carmen Delianu
- Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
| | - Vasilica Toma
- Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
| | | | - Ciprian Rezus
- Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
- Department of Cardiology, “Sf. Spiridon” Clinical Hospital Iasi, Iasi, Romania
| | - Laura Florea
- Department of Nephrology, “Dr. C. I. Parhon” Clinical Hospital Iasi, Iasi, Romania
- Grigore T. Popa University of Medicine and Pharmacy, Iasi, Romania
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Seija M, Nin M, Santiago J, Apaza L, Castaño A, Poggi L, Urioste I, Chiossoni A, Fernandez A, Navarrine N, Garau M, Astesiano R, Ferrari MS, Noboa O. Being Overweight Is Related to Faster Decline in Annual Glomerular Filtration Rate in Kidney Transplant. Transplant Proc 2018; 50:3392-3396. [PMID: 30577211 DOI: 10.1016/j.transproceed.2018.04.040] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2018] [Revised: 03/08/2018] [Accepted: 04/12/2018] [Indexed: 01/02/2023]
Abstract
Few studies have examined the relationship between non-immunological factors and glomerular filtration rate (GFR) decline in kidney transplant. Correcting these factors in native kidneys slows the progression of chronic kidney disease. The aim of this study was to analyze the association between the control of non-immunological factors and the annual decline of GFR. METHODS A single-center, retrospective study was performed. We included 128 patients who received kidney transplants between 2000 and 2015, with at least 1-year post-transplant follow-up. Clinical records were reviewed. GFR was estimated by CKD-EPI. Three groups were defined according to the annual change in eGFR (ΔGFR 2016-1015): non-progressors (> -1 mL/min/1.73 m2), slow progressors (> -1 and < -5 mL/min/1.73 m2), and fast progressors (< -5 mL/min/1.73 m2). Percentage of achievement of KDIGO target was also analyzed. RESULTS The mean GFR was 62.5 mL/min/1.73 m2. Glomerulonephritis was the most common cause of kidney failure (36%). When the fast progressor group was compared with the non-progressor group, they differed significantly in age-patients were younger (40 ± 12.3 vs 45 ± 13.1 years)-post-transplant body mass index (27.4 ± 5.6 vs 25.2 x ± 5.9 kg/m2), and serum uric acid, which was significantly higher (6.4 ± 1.7 vs 5.5 ± 1.58 mg/dL). There were no differences between the groups with regard to blood pressure, dyslipidemia, proteinuria, or venous bicarbonate. Target systolic blood pressure was achieved by 45% of patients. Biopsy-proven acute rejection was higher in the fast progression group, although this was not statistically significant (13 [24.5%] vs 8 [13.1%]). CONCLUSIONS High body mass index was associated with a faster decline in glomerular filtration rate in this study. Target blood pressure <140/90 mm Hg was achieved in less than 50% of cases.
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Affiliation(s)
- M Seija
- Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, UdeLaR, Montevideo, Uruguay; Departamento de Fisiopatología, Hospital de Clínicas, Facultad de Medicina, UdeLaR, Montevideo, Uruguay.
| | - M Nin
- Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, UdeLaR, Montevideo, Uruguay
| | - J Santiago
- Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, UdeLaR, Montevideo, Uruguay
| | - L Apaza
- Hospital Obrero N°1, La Paz, Bolivia
| | - A Castaño
- Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, UdeLaR, Montevideo, Uruguay
| | - L Poggi
- Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, UdeLaR, Montevideo, Uruguay
| | - I Urioste
- Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, UdeLaR, Montevideo, Uruguay
| | - A Chiossoni
- Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, UdeLaR, Montevideo, Uruguay
| | - A Fernandez
- Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, UdeLaR, Montevideo, Uruguay
| | - N Navarrine
- Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, UdeLaR, Montevideo, Uruguay
| | - M Garau
- Departamento de Métodos Cuantitativos, Facultad de Medicina, UdeLaR, Montevideo, Uruguay
| | - R Astesiano
- Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, UdeLaR, Montevideo, Uruguay
| | - M S Ferrari
- Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, UdeLaR, Montevideo, Uruguay
| | - O Noboa
- Centro de Nefrología, Hospital de Clínicas, Facultad de Medicina, UdeLaR, Montevideo, Uruguay
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Pácal L, Chalásová K, Pleskačová A, Řehořová J, Tomandl J, Kaňková K. Deleterious Effect of Advanced CKD on Glyoxalase System Activity not Limited to Diabetes Aetiology. Int J Mol Sci 2018; 19:ijms19051517. [PMID: 29783710 PMCID: PMC5983829 DOI: 10.3390/ijms19051517] [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: 04/24/2018] [Revised: 05/14/2018] [Accepted: 05/16/2018] [Indexed: 11/17/2022] Open
Abstract
Methylglyoxal production is increased in diabetes. Methylglyoxal is efficiently detoxified by enzyme glyoxalase 1 (GLO1). The aim was to study the effect of diabetic and CKD milieu on (a) GLO1 gene expression in peripheral blood mononuclear cells; (b) GLO1 protein levels in whole blood; and (c) GLO1 activity in RBCs in vivo in diabetic vs. non-diabetic subjects with normal or slightly reduced vs. considerably reduced renal function (CKD1-2 vs. CKD3-4). A total of 83 subjects were included in the study. Gene expression was measured using real-time PCR, and protein levels were quantified using Western blotting. Erythrocyte GLO1 activity was measured spectrophotometrically. GLO1 gene expression was significantly higher in subjects with CKD1-2 compared to CKD3-4. GLO1 protein level was lower in diabetics than in non-diabetics. GLO1 activity in RBCs differed between the four groups being significantly higher in diabetics with CKD1-2 vs. healthy subjects and vs. nondiabeticsfig with CKD3-4. GLO1 activity was significantly higher in diabetics compared to nondiabetics. In conclusion, both diabetes and CKD affects the glyoxalase system. It appears that CKD in advanced stages has prevailing and suppressive effects compared to hyperglycaemia. CKD decreases GLO1 gene expression and protein levels (together with diabetes) without concomitant changes of GLO1 activity.
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Affiliation(s)
- Lukáš Pácal
- Department of Pathophysiology, Faculty of Medicine, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
| | - Katarína Chalásová
- Department of Pathophysiology, Faculty of Medicine, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
| | - Anna Pleskačová
- Department of Pathophysiology, Faculty of Medicine, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
- Department of Biochemistry, Faculty of Medicine, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
| | - Jitka Řehořová
- Department of Gastroenterology, University Hospital Brno, Jihlavská 20, 625 00 Brno, Czech Republic.
| | - Josef Tomandl
- Department of Biochemistry, Faculty of Medicine, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
| | - Kateřina Kaňková
- Department of Pathophysiology, Faculty of Medicine, Masaryk University Brno, Kamenice 5, 625 00 Brno, Czech Republic.
- Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Zluty kopec 7, 656 53 Brno, Czech Republic.
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Jang HR, Kang D, Sinn DH, Gu S, Cho SJ, Lee JE, Huh W, Paik SW, Ryu S, Chang Y, Shafi T, Lazo M, Guallar E, Cho J, Gwak GY. Nonalcoholic fatty liver disease accelerates kidney function decline in patients with chronic kidney disease: a cohort study. Sci Rep 2018; 8:4718. [PMID: 29549269 PMCID: PMC5856790 DOI: 10.1038/s41598-018-23014-0] [Citation(s) in RCA: 55] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 03/05/2018] [Indexed: 02/06/2023] Open
Abstract
This study aimed to investigate the association of nonalcoholic fatty liver disease (NAFLD) and its severity with the decline in kidney function in patients with chronic kidney disease (CKD). We conducted a cohort study of 1,525 CKD patients who underwent repeated health check-up examinations from January 2003 through December 2013. NAFLD was diagnosed by ultrasonography and its severity was assessed by the NAFLD fibrosis score. At baseline, the prevalence of NAFLD was 40.9%, and the mean estimated glomerular filtration rate (eGFR) was 59.1 ml/min/1.73 m2. The average follow-up was 6.5 years. The age- and sex-adjusted decline in eGFR was greater in patients with NAFLD (-0.79% per year, 95% CI -1.31%, -0.27%) compared to those without it (0.30%, 95% CI -0.14%, 0.76%; p = 0.002). In multivariable adjusted models, the average difference in annual percent change in decline in eGFR comparing patients with NAFLD to those without NAFLD was -1.06% (-1.73%, -0.38%; p = 0.002). The decline in eGFR associated with NAFLD was greater in patients with higher NAFLD fibrosis score, in those with proteinuria or with low eGFR at baseline ( <45 ml/min/1.73 m2), and in those who were smokers and hypertensive. Therefore, NAFLD is independently associated with CKD progression.
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Affiliation(s)
- Hye Ryoun Jang
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, South Korea
| | - Danbee Kang
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Kangbuk Samsung Hospital, Seoul, South Korea
| | - Dong Hyun Sinn
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, South Korea
| | - Seonhye Gu
- Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Kangbuk Samsung Hospital, Seoul, South Korea
| | - Soo Jin Cho
- Center for Health Promotion, Samsung Medical Center, Kangbuk Samsung Hospital, Seoul, South Korea
| | - Jung Eun Lee
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, South Korea
| | - Wooseong Huh
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, South Korea
- Department of Clinical Pharmacology and Therapeutics, Samsung Medical Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, South Korea
| | - Seung Woon Paik
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, South Korea
| | - Seungho Ryu
- Center for Total Health Studies, Kangbuk Samsung Hospital, Seoul, South Korea
| | - Yoosoo Chang
- Center for Total Health Studies, Kangbuk Samsung Hospital, Seoul, South Korea
| | - Tariq Shafi
- Division of Nephrology, Department of Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
- Departments of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Mariana Lazo
- Departments of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Eliseo Guallar
- Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Kangbuk Samsung Hospital, Seoul, South Korea
- Departments of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA
| | - Juhee Cho
- Department of Clinical Research Design and Evaluation, SAIHST, Sungkyunkwan University, Kangbuk Samsung Hospital, Seoul, South Korea.
- Center for Clinical Epidemiology, Samsung Medical Center, Sungkyunkwan University, Kangbuk Samsung Hospital, Seoul, South Korea.
- Departments of Epidemiology and Medicine and Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
| | - Geum-Youn Gwak
- Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Kangbuk Samsung Hospital, Seoul, South Korea.
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Futrakul N, Futrakul P. Biomarker for early renal microvascular and diabetic kidney diseases. Ren Fail 2017; 39:505-511. [PMID: 28494191 PMCID: PMC6014362 DOI: 10.1080/0886022x.2017.1323647] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2016] [Revised: 02/20/2017] [Accepted: 04/23/2017] [Indexed: 12/20/2022] Open
Abstract
Recognition of early stage of diabetic kidney disease, under common practice using biomarkers, namely microalbuminuria, serum creatinine level above 1 mg/dL and accepted definition of diabetic kidney disease associated with creatinine clearance value below 60 mL/min/1.73 m2, is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis. Other alternative biomarkers related to the state of microalbuminuria is not sensitive to screen for early diabetic kidney disease (stages I, II). In this regard, a better diagnostic markers to serve for this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg), cystatin C. Recently, renal microvascular disease and renal ischemia have been demonstrated to correlate indirectly with the development of diabetic kidney disease and its function. Among these are angiogenic and anti-angiogenic factors, namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to therapeutic prevention, implementation of treatment at early stage of diabetic and nondiabetic kidney disease is able to restore renal perfusion and function.
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Affiliation(s)
- Narisa Futrakul
- Department of Physiology, Faculty of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
| | - Prasit Futrakul
- Academy of Science, The Royal Institute of Thailand and Bhumirajanagarindra Kidney Institute, Bangkok, Thailand
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Lai TS, Lee MH, Yang HI, You SL, Lu SN, Wang LY, Yuan Y, L'Italien G, Chien KL, Chen CJ. Hepatitis C viral load, genotype, and increased risk of developing end-stage renal disease: REVEAL-HCV study. Hepatology 2017; 66:784-793. [PMID: 28370058 DOI: 10.1002/hep.29192] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2016] [Revised: 03/16/2017] [Accepted: 03/23/2017] [Indexed: 12/18/2022]
Abstract
UNLABELLED The association between hepatitis C virus (HCV) infection and end-stage renal disease (ESRD) remains controversial without considering the role of HCV viral load and genotype. This study aimed to determine whether HCV RNA level and genotype affect the risk of developing ESRD. Between 1991 and 1992, 19,984 participants aged 30-65 years were enrolled in a community-based prospective cohort study in Taiwan. Chronic HCV infection was defined by detectable HCV viral load. ESRD was determined as the need for chronic dialysis or renal transplantation. Conventional Cox proportional hazard and competing risk models were used to determine the hazard ratio (HR) for ESRD. After a median follow-up of 16.8 years, 204 cases were detected during 319,474 person-years. The incidence rates of ESRD for nonchronically HCV-infected and chronically HCV-infected patients were 60.2 and 194.3 per 100,000 person-years, respectively. The multivariable HR was 2.33 (95% confidence interval [CI] 1.40-3.89) when comparing patients with and without chronic HCV infection. Patients with low and high HCV RNA levels were at higher risk of ESRD than those who were nonchronically HCV-infected (HR, 2.11, 95% CI 1.16-3.86, and HR, 3.06, 95% CI 1.23-7.58; Ptrend < 0.001). This association remained robust after taking pre-ESRD death as a competing event for ESRD. Patients with HCV genotype 1 tended to have a higher risk of developing ESRD (HR, 3.60 95% CI 1.83-7.07) compared with nonchronically HCV-infected subjects. CONCLUSIONS This study reveals that chronic HCV infection is associated with an increased risk of developing ESRD and suggests that elevated serum levels of HCV RNA (>167,000 IU/mL) and HCV genotype 1 are strong predictors of ESRD, indicating clinical implications for the management of chronic HCV. (Hepatology 2017;66:784-793).
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Affiliation(s)
- Tai-Shuan Lai
- Department of Internal Medicine, National Taiwan University Hospital, Bei-Hu Branch, Taipei, Taiwan.,Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - San-Lin You
- School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan.,Big Data Research Center, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Sheng-Nan Lu
- Department of Gastroenterology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Li-Yu Wang
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Yong Yuan
- Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ
| | - Gilbert L'Italien
- Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, NJ.,Yale University School of Medicine, New Haven, CT
| | - Kuo-Liong Chien
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Chien-Jen Chen
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.,Genomics Research Center, Academia Sinica, Taipei, Taiwan
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Gai Z, Chu L, Xu Z, Song X, Sun D, Kullak-Ublick GA. Farnesoid X receptor activation protects the kidney from ischemia-reperfusion damage. Sci Rep 2017; 7:9815. [PMID: 28852062 PMCID: PMC5575310 DOI: 10.1038/s41598-017-10168-6] [Citation(s) in RCA: 68] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2016] [Accepted: 06/16/2017] [Indexed: 02/06/2023] Open
Abstract
Farnesoid X receptor (FXR) activation has been reported to reduce inflammation and oxidative stress. Because both inflammation and oxidative stress are critical for tissue destruction during kidney ischemia reperfusion (I/R) injury, we investigated the protective role of FXR against kidney damage induced by I/R in mice. Mice undergoing renal I/R developed the typical features of acute kidney injury (AKI): increased creatinine, albuminuria, tubular necrosis and apoptosis. Inflammatory cytokine production and oxidative stress were also markedly increased. In mice pretreated with 6-ethyl-chenodeoxycholic acid (6-ECDCA), a selective FXR agonist, I/R induced changes were prevented and renal function and structure were improved. Moreover, FXR activation also effectively prevented the subsequent progression of AKI to chronic kidney disease (CKD) by ameliorating glomerulosclerosis and interstitial fibrosis and by suppressing fibrogenic gene expression. FXR mRNA levels were inversely correlated with the progression to CKD in mice and with the degree of interstitial fibrosis in human biopsies. In further experiments administering 6-ECDCA to renal proximal tubular cells cultured under hypoxia, the renoprotective effects of FXR activation were associated with inhibition of oxidative and ER stress and with increased antioxidant activity. In conclusion, FXR agonists may have a therapeutic role in conditions associated with ischemic kidney damage.
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Affiliation(s)
- Zhibo Gai
- Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Lei Chu
- Department of Urology, Tengzhou Central People's Hospital, Zaozhuang, People's Republic of China
| | - Zhenqiang Xu
- Department of Cardiovascular Surgery, Shandong Provincial Hospital affiliated to Shandong University, Jinan, People's Republic of China
| | - Xiaoming Song
- Department of Thoracic Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, People's Republic of China
| | - Dongfeng Sun
- Department of Thoracic Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, People's Republic of China.
| | - Gerd A Kullak-Ublick
- Department of Clinical Pharmacology and Toxicology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
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Afrin MR, Arumugam S, Rahman MA, Karuppagounder V, Harima M, Suzuki H, Miyashita S, Suzuki K, Ueno K, Yoneyama H, Watanabe K. Curcumin reduces the risk of chronic kidney damage in mice with nonalcoholic steatohepatitis by modulating endoplasmic reticulum stress and MAPK signaling. Int Immunopharmacol 2017; 49:161-167. [DOI: 10.1016/j.intimp.2017.05.035] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2016] [Revised: 05/16/2017] [Accepted: 05/29/2017] [Indexed: 12/26/2022]
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Wong F, O'Leary JG, Reddy KR, Garcia-Tsao G, Fallon MB, Biggins SW, Subramanian RM, Thuluvath PJ, Kamath PS, Patton H, Maliakkal B, Tandon P, Vargas H, Thacker L, Bajaj JS. Acute Kidney Injury in Cirrhosis: Baseline Serum Creatinine Predicts Patient Outcomes. Am J Gastroenterol 2017; 112:1103-1110. [PMID: 28440305 DOI: 10.1038/ajg.2017.122] [Citation(s) in RCA: 69] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2016] [Accepted: 03/02/2017] [Indexed: 02/07/2023]
Abstract
OBJECTIVES The International Ascites Club (IAC) recently defined Stage 1 acute kidney injury (AKI) for cirrhosis as an acute increase in serum creatinine (SCr) by ≥0.3 mg/dl or by ≥50% in <48 h from a stable value within 3 months. The baseline SCr may influence AKI risk and patient outcomes. The objective of this study is to determine in cirrhosis whether the baseline SCr has any effect on the in-hospital AKI course and patient survival. METHODS North American Consortium for the Study of End-Stage Liver Disease is a consortium of tertiary-care hepatology centers prospectively enroling non-elective cirrhotic inpatients. Patients with different baseline SCr levels (≤0.5, 0.51-1.0, 1.01-1.5, >1.5 mg/dl) were evaluated for the development of AKI, and compared for AKI outcomes and 30-day survival. RESULTS 653 hospitalized cirrhotics (56.7±10years, 64% men, 30% with infection) were included. The incidence of AKI was 47% of enrolled patients. Patients with higher baseline SCr were more likely to develop AKI, with significantly higher delta and peak SCr (P<0.001) than the other groups, more likely to have a progressive AKI course (P<0.0001), associated with a significantly reduced 30-day survival (P<0.0001). Multivariate logistic regression showed that the delta SCr during an AKI episode to be the strongest factor impacting AKI outcomes and survival (P<0.001), with a delta SCr of 0.70 mg/dl having a 68% sensitivity and 80% specificity for predicting 30-day mortality. CONCLUSIONS Admitted cirrhotic patients with higher baseline SCr are at higher risk for in-hospital development of AKI, and more likely to have AKI progression with reduced survival. Therefore, such patients should be closely monitored and treated promptly for their AKI.
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Affiliation(s)
- F Wong
- University of Toronto, Toronto, Ontario, Canada
| | - J G O'Leary
- Baylor University Medical Center, Dallas, Texas, USA
| | - K R Reddy
- University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | | | - M B Fallon
- Health Science Center, University of Texas, Houston, Texas, USA
| | - S W Biggins
- University of Colorado Denver, Denver, Colorado, USA
| | | | - P J Thuluvath
- Mercy Medical Center &University of Maryland School of Medicine, Baltimore, Maryland, USA
| | | | - H Patton
- University of California San Diego, San Diego, California, USA
| | - B Maliakkal
- University of Rochester, Rochester, New York, USA
| | - P Tandon
- University of Alberta, Edmonton, Alberta, Canada
| | - H Vargas
- Mayo Clinic, Scottsdale, Arizona, USA
| | - L Thacker
- Biostatisitcs, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
| | - J S Bajaj
- Medicine, Virginia Commonwealth University and McGuire VA Medical Center, Richmond, Virginia, USA
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Lai TS, Lee MH, Yang HI, You SL, Lu SN, Wang LY, Yuan Y, L'Italien G, Chien KL, Chen CJ. High hepatitis C viral load and genotype 2 are strong predictors of chronic kidney disease. Kidney Int 2017; 92:703-709. [PMID: 28532708 DOI: 10.1016/j.kint.2017.03.021] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2016] [Revised: 03/04/2017] [Accepted: 03/09/2017] [Indexed: 01/07/2023]
Abstract
Associations between chronic hepatitis C virus (HCV) infection and chronic kidney disease (CKD) remain controversial. Here we aimed to clarify the association between HCV viral load, genotype, and CKD in 13,805 participants aged 30-65 years enrolled in the REVEAL-HCV Study, a community-based prospective study conducted in 1991-1992. CKD was defined by consecutive proteinuria or an estimated glomerular filtration rate (eGFR) under 60 mL/min/1.73 m2. Chronic HCV infection was defined by detectable HCV viral load. Logistic regression models were used to estimate prevalence odds ratio of CKD for chronic HCV infection after adjusting for other risk factors. Compared to non-chronically HCV-infected participants, the adjusted prevalence odds ratio (95% confidence interval) for CKD was significantly increased to 1.91 (1.27-2.88) for chronically HCV-infected participants. Compared to non-chronically HCV-infected participants, the adjusted prevalence odds ratio of CKD was 1.21 (0.54-2.70), 1.40 (0.66-3.00) and 3.44 (1.92-6.14) for chronically HCV-infected participants with low to high tertiles of serum HCV RNA, respectively. The adjusted prevalence odds ratios of CKD were 0.54 (0.17-1.75) for participants with low HCV RNA and genotype 1, 1.80 (0.84-3.87) for those with low HCV RNA and genotype 2, 2.62 (1.11-6.17) for those with high HCV RNA and genotype 1 and 4.99 (2.25-11.06) for those with high HCV RNA and genotype 2, compared with non-chronically HCV-infected participants. Thus, chronic HCV infection is associated with an increased risk of CKD. High HCV viral load and HCV genotype 2 are strong CKD predictors.
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MESH Headings
- Adult
- Female
- Genotype
- Glomerular Filtration Rate
- Hepacivirus/physiology
- Hepatitis C, Chronic/blood
- Hepatitis C, Chronic/epidemiology
- Hepatitis C, Chronic/urine
- Hepatitis C, Chronic/virology
- Humans
- Liver Function Tests
- Logistic Models
- Male
- Middle Aged
- Odds Ratio
- Prevalence
- Prospective Studies
- Proteinuria/urine
- RNA, Viral/blood
- RNA, Viral/isolation & purification
- Renal Insufficiency, Chronic/blood
- Renal Insufficiency, Chronic/epidemiology
- Renal Insufficiency, Chronic/urine
- Renal Insufficiency, Chronic/virology
- Risk Factors
- Taiwan/epidemiology
- Viral Load
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Affiliation(s)
- Tai-Shuan Lai
- Department of Internal Medicine, National Taiwan University Hospital, Bei-Hu branch, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Hwai-I Yang
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - San-Lin You
- School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan; Big Data Research Center, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Sheng-Nan Lu
- Department of Gastroenterology, Kaohsiung Chang-Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Li-Yu Wang
- Department of Medicine, Mackay Medical College, New Taipei City, Taiwan
| | - Yong Yuan
- Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, New Jersey, USA
| | - Gilbert L'Italien
- Global Health Economics and Outcomes Research, Bristol-Myers Squibb, Princeton, New Jersey, USA; Yale University School of Medicine, New Haven, Connecticut, USA
| | - Kuo-Liong Chien
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan.
| | - Chien-Jen Chen
- Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Genomics Research Center, Academia Sinica, Taipei, Taiwan.
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41
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Applying the Temporal Abstraction Technique to the Prediction of Chronic Kidney Disease Progression. J Med Syst 2017; 41:85. [PMID: 28401396 DOI: 10.1007/s10916-017-0732-5] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Accepted: 04/03/2017] [Indexed: 01/05/2023]
Abstract
Chronic kidney disease (CKD) has attracted considerable attention in the public health domain in recent years. Researchers have exerted considerable effort in attempting to identify critical factors that may affect the deterioration of CKD. In clinical practice, the physical conditions of CKD patients are regularly recorded. The data of CKD patients are recorded as a high-dimensional time-series. Therefore, how to analyze these time-series data for identifying the factors affecting CKD deterioration becomes an interesting topic. This study aims at developing prediction models for stage 4 CKD patients to determine whether their eGFR level decreased to less than 15 ml/min/1.73m2 (end-stage renal disease, ESRD) 6 months after collecting their final laboratory test information by evaluating time-related features. A total of 463 CKD patients collected from January 2004 to December 2013 at one of the biggest dialysis centers in southern Taiwan were included in the experimental evaluation. We integrated the temporal abstraction (TA) technique with data mining methods to develop CKD progression prediction models. Specifically, the TA technique was used to extract vital features (TA-related features) from high-dimensional time-series data, after which several data mining techniques, including C4.5, classification and regression tree (CART), support vector machine, and adaptive boosting (AdaBoost), were applied to develop CKD progression prediction models. The results revealed that incorporating temporal information into the prediction models increased the efficiency of the models. The AdaBoost+CART model exhibited the most accurate prediction among the constructed models (Accuracy: 0.662, Sensitivity: 0.620, Specificity: 0.704, and AUC: 0.715). A number of TA-related features were found to be associated with the deterioration of renal function. These features can provide further clinical information to explain the progression of CKD. TA-related features extracted by long-term tracking of changes in laboratory test values can enable early diagnosis of ESRD. The developed models using these features can facilitate medical personnel in making clinical decisions to provide appropriate diagnoses and improved care quality to patients with CKD.
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Targher G, Byrne CD. Non-alcoholic fatty liver disease: an emerging driving force in chronic kidney disease. Nat Rev Nephrol 2017; 13:297-310. [PMID: 28218263 DOI: 10.1038/nrneph.2017.16] [Citation(s) in RCA: 229] [Impact Index Per Article: 28.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is caused by an accumulation of fat in the liver; the condition can progress over time to increase the risk of developing cirrhosis, end-stage liver disease and hepatocellular carcinoma. The prevalence of NAFLD is increasing rapidly owing to the global epidemics of obesity and type 2 diabetes mellitus (T2DM), and NAFLD has been predicted to become the most important indication for liver transplantation over the next decade. It is now increasingly clear that NAFLD not only affects the liver but can also increase the risk of developing extra-hepatic diseases, including T2DM, cardiovascular disease and chronic kidney disease (CKD), which have a considerable impact on health-care resources. Accumulating evidence indicates that NAFLD exacerbates insulin resistance, predisposes to atherogenic dyslipidaemia and releases a variety of proinflammatory factors, prothrombotic factors and profibrogenic molecules that can promote vascular and renal damage. Furthermore, communication or 'crosstalk' between affected organs or tissues in these diseases has the potential to further harm function and worsen patient outcomes, and increasing amounts of evidence point to a strong association between NAFLD and CKD. Whether a causal relationship between NAFLD and CKD exists remains to be definitively established.
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Affiliation(s)
- Giovanni Targher
- Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Piazzale Stefani 1, 37126 Verona, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton.,Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK
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43
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AT1 receptor antagonism before ischemia prevents the transition of acute kidney injury to chronic kidney disease. Kidney Int 2017; 89:363-73. [PMID: 26509589 DOI: 10.1038/ki.2015.320] [Citation(s) in RCA: 76] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2015] [Revised: 08/21/2015] [Accepted: 08/27/2015] [Indexed: 12/29/2022]
Abstract
Despite clinical recovery of patients from an episode of acute kidney injury (AKI), progression to chronic kidney disease (CKD) is possible on long-term follow-up. However, mechanisms of this are poorly understood. Here, we determine whether activation of angiotensin-II type 1 receptors during AKI triggers maladaptive mechanisms that lead to CKD. Nine months after AKI, male Wistar rats develop CKD characterized by renal dysfunction, proteinuria, renal hypertrophy, glomerulosclerosis, tubular atrophy, and tubulointerstitial fibrosis. Renal injury was associated with increased oxidative stress, inflammation, α-smooth muscle actin expression, and activation of transforming growth factor β; the latter mainly found in epithelial cells. Although administration of losartan prior to the initial ischemic insult did not prevent or reduce AKI severity, it effectively prevented eventual CKD. Three days after AKI, renal dysfunction, tubular structural injury, and elevation of urinary biomarkers were present. While the losartan group had similar early renal injury, renal perfusion was completely restored as early as day 3 postischemia. Further, there was increased vascular endothelial growth factor expression and an early activation of hypoxia-inducible factor 1 α, a transcription factor that regulates expression of many genes that help reduce renal injury. Thus, AT1 receptor antagonism prior to ischemia prevented AKI to CKD transition by improving early renal blood flow recovery, lesser inflammation, and increased hypoxia-inducible factor 1 α activity.
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Karathanasis SK, Freeman LA, Gordon SM, Remaley AT. The Changing Face of HDL and the Best Way to Measure It. Clin Chem 2016; 63:196-210. [PMID: 27879324 DOI: 10.1373/clinchem.2016.257725] [Citation(s) in RCA: 84] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Accepted: 10/26/2016] [Indexed: 01/08/2023]
Abstract
BACKGROUND HDL cholesterol (HDL-C) is a commonly used lipid biomarker for assessing cardiovascular health. While a central focus has been placed on the role of HDL in the reverse cholesterol transport (RCT) process, our appreciation for the other cardioprotective properties of HDL continues to expand with further investigation into the structure and function of HDL and its specific subfractions. The development of novel assays is empowering the research community to assess different aspects of HDL function, which at some point may evolve into new diagnostic tests. CONTENT This review discusses our current understanding of the formation and maturation of HDL particles via RCT, as well as the newly recognized roles of HDL outside RCT. The antioxidative, antiinflammatory, antiapoptotic, antithrombotic, antiinfective, and vasoprotective effects of HDL are all discussed, as are the related methodologies for assessing these different aspects of HDL function. We elaborate on the importance of protein and lipid composition of HDL in health and disease and highlight potential new diagnostic assays based on these parameters. SUMMARY Although multiple epidemiologic studies have confirmed that HDL-C is a strong negative risk marker for cardiovascular disease, several clinical and experimental studies have yielded inconsistent results on the direct role of HDL-C as an antiatherogenic factor. As of yet, our increased understanding of HDL biology has not been translated into successful new therapies, but will undoubtedly depend on the development of alternative ways for measuring HDL besides its cholesterol content.
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Affiliation(s)
| | - Lita A Freeman
- Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD
| | - Scott M Gordon
- Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD
| | - Alan T Remaley
- Lipoprotein Metabolism Section, Cardiovascular-Pulmonary Branch, National Heart, Lung, and Blood Institute, NIH, Bethesda, MD.
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45
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Mikolasevic I, Milic S, Turk Wensveen T, Grgic I, Jakopcic I, Stimac D, Wensveen F, Orlic L. Nonalcoholic fatty liver disease - A multisystem disease? World J Gastroenterol 2016; 22:9488-9505. [PMID: 27920470 PMCID: PMC5116593 DOI: 10.3748/wjg.v22.i43.9488] [Citation(s) in RCA: 133] [Impact Index Per Article: 14.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2016] [Revised: 08/30/2016] [Accepted: 10/19/2016] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is one of the most common comorbidities associated with overweight and metabolic syndrome (MetS). Importantly, NAFLD is one of its most dangerous complications because it can lead to severe liver pathologies, including fibrosis, cirrhosis and hepatic cellular carcinoma. Given the increasing worldwide prevalence of obesity, NAFLD has become the most common cause of chronic liver disease and therefore is a major global health problem. Currently, NAFLD is predominantly regarded as a hepatic manifestation of MetS. However, accumulating evidence indicates that the effects of NAFLD extend beyond the liver and are negatively associated with a range of chronic diseases, most notably cardiovascular disease (CVD), diabetes mellitus type 2 (T2DM) and chronic kidney disease (CKD). It is becoming increasingly clear that these diseases are the result of the same underlying pathophysiological processes associated with MetS, such as insulin resistance, chronic systemic inflammation and dyslipidemia. As a result, they have been shown to be independent reciprocal risk factors. In addition, recent data have shown that NAFLD actively contributes to aggravation of the pathophysiology of CVD, T2DM, and CKD, as well as several other pathologies. Thus, NAFLD is a direct cause of many chronic diseases associated with MetS, and better detection and treatment of fatty liver disease is therefore urgently needed. As non-invasive screening methods for liver disease become increasingly available, detection and treatment of NAFLD in patients with MetS should therefore be considered by both (sub-) specialists and primary care physicians.
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46
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Umbro I, Tinti F, Scalera I, Evison F, Gunson B, Sharif A, Ferguson J, Muiesan P, Mitterhofer AP. Acute kidney injury and post-reperfusion syndrome in liver transplantation. World J Gastroenterol 2016; 22:9314-9323. [PMID: 27895419 PMCID: PMC5107695 DOI: 10.3748/wjg.v22.i42.9314] [Citation(s) in RCA: 42] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2016] [Revised: 09/10/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023] Open
Abstract
In the past decades liver transplantation (LT) has become the treatment of choice for patients with end stage liver disease (ESLD). The chronic shortage of cadaveric organs for transplantation led to the utilization of a greater number of marginal donors such as older donors or donors after circulatory death (DCD). The improved survival of transplanted patients has increased the frequency of long-term complications, in particular chronic kidney disease (CKD). Acute kidney injury (AKI) post-LT has been recently recognized as an important risk factor for the occurrence of de novo CKD in the long-term outcome. The onset of AKI post-LT is multifactorial, with pre-LT risk factors involved, including higher Model for End-stage Liver Disease score, more sever ESLD and pre-existing renal dysfunction, either with intra-operative conditions, in particular ischaemia reperfusion injury responsible for post-reperfusion syndrome (PRS) that can influence recipient’s morbidity and mortality. Post-reperfusion syndrome-induced AKI is an important complication post-LT that characterizes kidney involvement caused by PRS with mechanisms not clearly understood and implication on graft and patient survival. Since pre-LT risk factors may influence intra-operative events responsible for PRS-induced AKI, we aim to consider all the relevant aspects involved in PRS-induced AKI in the setting of LT and to identify all studies that better clarified the specific mechanisms linking PRS and AKI. A PubMed search was conducted using the terms liver transplantation AND acute kidney injury; liver transplantation AND post-reperfusion syndrome; acute kidney injury AND post-reperfusion syndrome; acute kidney injury AND DCD AND liver transplantation. Five hundred seventy four articles were retrieved on PubMed search. Results were limited to title/abstract of English-language articles published between 2000 and 2015. Twenty-three studies were identified that specifically evaluated incidence, risk factors and outcome for patients developing PRS-induced AKI in liver transplantation. In order to identify intra-operative risk factors/mechanisms specifically involved in PRS-induced AKI, avoiding confounding factors, we have limited our study to “acute kidney injury AND DCD AND liver transplantation”. Accordingly, three out of five studies were selected for our purpose.
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Lin L, Lu J, Huang X, Ding L, Huang Y, Wang P, Peng K, Zhang D, Xu Y, Xu M, Chen Y, Bi Y, Wang W, Xu Y. Nonalcoholic fatty liver disease is associated with low-grade albuminuria in Chinese adults (change not displayed). QJM 2016; 109:737-743. [PMID: 27317608 DOI: 10.1093/qjmed/hcw070] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2015] [Revised: 03/24/2016] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND Nonalcoholic fatty liver disease (NAFLD) was associated with higher risk of cardiovascular disease (CVD). Low-grade albuminuria was recognized as an early indicator of CVD. Epidemiological studies investigating the association between NAFLD and low-grade albuminuria were limited. AIM To determine whether NAFLD is independently associated with the presence of low-grade albuminuria in Chinese adults. DESIGN A cross-sectional community-based population study was performed in 8270 Chinese adults aged 40 years or older. METHODS A first-voided early morning spot urine sample was obtained for urinary albumin and creatinine measurements. The highest quartile of urinary albumin-to-creatinine ratio was defined as low-grade albuminuria, after excluding the participants with micro- or macroalbuminuria. NAFLD was diagnosed by using ultrasonography findings after the exclusion of alcohol abuse and other liver diseases. RESULTS The prevalence of low-grade albuminuria was significantly higher in participants with NAFLD than in those without NAFLD (33.6% vs. 21.3% in men and 30.4% vs. 22.8% in women, respectively). Multivariate-adjusted logistic regression analysis revealed that NAFLD was significantly associated with increased odds ratio of low-grade albuminuria in men (odds ratio, 1.47; 95% CI, 1.16-1.87) after adjusting for multiple confounders. The significant association was not detected in women. CONCLUSIONS NAFLD was significantly associated with an increased risk of present low-grade albuminuria in middle-aged and elderly Chinese men.
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Affiliation(s)
- L Lin
- From the State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - J Lu
- From the State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - X Huang
- From the State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - L Ding
- From the State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - Y Huang
- From the State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - P Wang
- From the State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - K Peng
- From the State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - D Zhang
- From the State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - Y Xu
- From the State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - M Xu
- From the State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - Y Chen
- From the State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - Y Bi
- From the State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - W Wang
- From the State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
| | - Y Xu
- From the State Key Laboratory of Medical Genomics, National Clinical Research Center for Metabolic Diseases, Collaborative Innovation Center of Systems Biomedicine, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrine and Metabolic Diseases Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
- Department of Research and Development, Rui-Jin Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai 200025, China
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Martínez-Lara E, Peña A, Calahorra J, Cañuelo A, Siles E. Hydroxytyrosol decreases the oxidative and nitrosative stress levels and promotes angiogenesis through HIF-1 independent mechanisms in renal hypoxic cells. Food Funct 2016; 7:540-8. [PMID: 26608793 DOI: 10.1039/c5fo00928f] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
In the kidney, tissue oxygen tension is comparatively low and this renders this organ more prone to hypoxic injury. In fact, hypoxia has a central role in the development and progression of renal disease. The recovery from this situation is dependent on the degree to which sublethally damaged cells restore normal function. The master regulator of the hypoxic response is hypoxia-inducible factor-1 (HIF-1). HIF-1 activity depends on the HIF-1α subunit level which is regulated by oxygen, nitric oxide (NO), reactive oxygen species and mTOR. Given the antioxidant and antinitrosative properties ascribed to hydroxytyrosol (HT), this study evaluates the impact of this olive oil polyphenol on the response to hypoxia in kidney cells. For this purpose, the human embryonic kidney HEK293T cell line was treated with HT and cultured under sublethal hypoxic conditions. Our results demonstrate that HT treatment decreases both, post-hypoxic reactive oxygen species and NO levels and, consequently, HIF-1α accumulation. However, HT does not affect mTOR activation or the factor inhibiting HIF level but promotes the expression of angiogenic proteins, suggesting that HT activates an adaptive response to hypoxia in a HIF-1α-independent pathway. In fact, this effect could be ascribed to the up-regulation of estrogen-related receptor α. In conclusion, our results suggest that in renal hypoxia, HT treatment might act as an effective preventive therapeutic approach to decrease stress and to improve the adaptive response to this pathological situation.
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Affiliation(s)
- Esther Martínez-Lara
- Department of Experimental Biology, University of Jaén, Paraje Las Lagunillas s/n, 23071-Jaén, Spain.
| | - Ana Peña
- Department of Experimental Biology, University of Jaén, Paraje Las Lagunillas s/n, 23071-Jaén, Spain.
| | - Jesús Calahorra
- Department of Experimental Biology, University of Jaén, Paraje Las Lagunillas s/n, 23071-Jaén, Spain.
| | - Ana Cañuelo
- Department of Experimental Biology, University of Jaén, Paraje Las Lagunillas s/n, 23071-Jaén, Spain.
| | - Eva Siles
- Department of Experimental Biology, University of Jaén, Paraje Las Lagunillas s/n, 23071-Jaén, Spain.
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Ochoa-Callejero L, Pozo-Rodrigálvarez A, Martínez-Murillo R, Martínez A. Lack of adrenomedullin in mouse endothelial cells results in defective angiogenesis, enhanced vascular permeability, less metastasis, and more brain damage. Sci Rep 2016; 6:33495. [PMID: 27640364 PMCID: PMC5027589 DOI: 10.1038/srep33495] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2016] [Accepted: 08/26/2016] [Indexed: 12/28/2022] Open
Abstract
Adrenomedullin (AM) is a vasodilating peptide involved in the regulation of circulatory homeostasis and in the pathophysiology of certain cardiovascular diseases. AM plays critical roles in blood vessels, including regulation of vascular stability and permeability. To elucidate the autocrine/paracrine function of AM in endothelial cells (EC) in vivo, a conditional knockout of AM in EC (AM(EC-KO)) was used. The amount of vascularization of the matrigel implants was lower in AM(EC-KO) mice indicating a defective angiogenesis. Moreover, ablation of AM in EC revealed increased vascular permeability in comparison with wild type (WT) littermates. In addition, AM(EC-KO) lungs exhibited significantly less tumor growth than littermate WT mice using a syngeneic model of metastasis. Furthermore, following middle cerebral artery permanent occlusion, there was a significant infarct size decrease in animals lacking endothelial AM when compared to their WT counterparts. AM is an important regulator of EC function, angiogenesis, tumorigenesis, and brain response to ischemia. Studies of AM should bring novel approaches to the treatment of vascular diseases.
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Affiliation(s)
- Laura Ochoa-Callejero
- Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), C/Piqueras 98, 26006-Logroño. Spain
| | - Andrea Pozo-Rodrigálvarez
- Neurovascular Research Group, Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, Av. Doctor Arce 37, 28002-Madrid. Spain
| | - Ricardo Martínez-Murillo
- Neurovascular Research Group, Department of Molecular, Cellular and Developmental Neurobiology, Cajal Institute, Av. Doctor Arce 37, 28002-Madrid. Spain
| | - Alfredo Martínez
- Oncology Area, Center for Biomedical Research of La Rioja (CIBIR), C/Piqueras 98, 26006-Logroño. Spain
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Yu XY, Zhao SS. Renal dysfunction in initially treated patients with chronic hepatitis B: Rate and risk factors. Shijie Huaren Xiaohua Zazhi 2016; 24:3026-3031. [DOI: 10.11569/wcjd.v24.i19.3026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the rate of and risk factors for renal dysfunction in initially treated patients with chronic hepatitis B.
METHODS: Patients with chronic hepatitis B treated at our hospital from November 2013 to October 2015 were divided into a chronic hepatitis B group, a compensated liver cirrhosis group, and a decompensated liver cirrhosis group. The simplified Modification of Diet in Renal Disease Study Equation was used to estimate the glomerular filtration rate (e-GFR) to calculate the rate of renal dysfunction [e-GFR < 90 mL/(min•1.73 m2)]. The risk factors for renal dysfunction were analyzed by univariate and multivariate binary logistic regression analyses.
RESULTS: This study collected a total of 358 cases, of which 15.9% had renal dysfunction. The rate of renal dysfunction was 9.5% for the chronic hepatitis B group, 7.9% for the compensated liver cirrhosis group, and 25.2% for the decompensated group (χ2 = 16.726, P = 0.000). Multivariate binary logistic regression analysis showed that age, sex, disease progression, and kidney stones were independent risk factors for renal dysfunction.
CONCLUSION: Disease progression is an independent risk factor for abnormal renal function in initially treated patients with chronic hepatitis B. Clinicians should make the best decision based on the specific condition of the patient.
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