Dataset Information

Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes.

ABSTRACT: Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics and immunohistochemistry were used to identify differentially expressed proteins and enriched pathways in glomeruli. During the median follow-up period of 24 months, 144 (45%) patients progressed to ESRD. In multivariable models, the Renal Pathology Society classification failed to predict ESRD, although the solidified glomerulosclerosis (score 1: HR 1.65, 95% confidence interval [CI] 1.04-2.60; score 2: HR 2.48, 95% CI 1.40-4.37) and extracapillary hypercellularity (HR 2.68, 95% CI 1.55-4.62) were identified as independent risk factors. Additionally, single glomerular proteomics, combined with immunohistochemistry, revealed that complement C9 and apolipoprotein E were highly expressed in solidified glomerulosclerosis. Therefore, solidified glomerulosclerosis and extracapillary hypercellularity predict diabetic ESRD in Chinese patients. Single glomerular proteomics identified solidified glomerulosclerosis as a unique pathological change that may be associated with complement overactivation and abnormal lipid metabolism.

SUBMITTER: Zhao L

PROVIDER: S-EPMC7907371 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes.

Zhao Lijun L Liu Fang F Li Lin L Zhang Junlin J Wang Tingli T Zhang Rui R Zhang Wei W Yang Xiaoyan X Zeng Xiaoxi X Wang Yiting Y Wu Yucheng Y Yang Hao H Wang Shisheng S Zhong Yi Y Xu Huan H Wang Shanshan S Guo Ruikun R Ren Honghong H Yang Lichuan L Su Baihai B Zhang Jie J Tong Nanwei N Zhou Xin J XJ Cooper Mark E ME

Scientific reports 20210225 1

Few histological prognostic indicators for end-stage renal disease (ESRD) have been validated in diabetic patients. This biopsy-based study aimed to identify nephropathological risk factors for ESRD in Chinese patients with type 2 diabetes. Histological features of 322 Chinese type 2 diabetic patients with biopsy-confirmed diabetic nephropathy (DN) were retrospectively analysed. Cox proportional hazards analysis was used to estimate the hazard ratio (HR) for ESRD. Single glomerular proteomics an ...[more]

PMID: 33633132

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Project description:IMPORTANCE:The established chronic kidney disease (CKD) progression end point of end-stage renal disease (ESRD) or a doubling of serum creatinine concentration (corresponding to a change in estimated glomerular filtration rate [GFR] of ?57% or greater) is a late event. OBJECTIVE:To characterize the association of decline in estimated GFR with subsequent progression to ESRD with implications for using lesser declines in estimated GFR as potential alternative end points for CKD progression. Because most people with CKD die before reaching ESRD, mortality risk also was investigated. DATA SOURCES AND STUDY SELECTION:Individual meta-analysis of 1.7 million participants with 12,344 ESRD events and 223,944 deaths from 35 cohorts in the CKD Prognosis Consortium with a repeated measure of serum creatinine concentration over 1 to 3 years and outcome data. DATA EXTRACTION AND SYNTHESIS:Transfer of individual participant data or standardized analysis of outputs for random-effects meta-analysis conducted between July 2012 and September 2013, with baseline estimated GFR values collected from 1975 through 2012. MAIN OUTCOMES AND MEASURES:End-stage renal disease (initiation of dialysis or transplantation) or all-cause mortality risk related to percentage change in estimated GFR over 2 years, adjusted for potential confounders and first estimated GFR. RESULTS:The adjusted hazard ratios (HRs) of ESRD and mortality were higher with larger estimated GFR decline. Among participants with baseline estimated GFR of less than 60 mL/min/1.73 m2, the adjusted HRs for ESRD were 32.1 (95% CI, 22.3-46.3) for changes of ?57% in estimated GFR and 5.4 (95% CI, 4.5-6.4) for changes of ?30%. However, changes of ?30% or greater (6.9% [95% CI, 6.4%-7.4%] of the entire consortium) were more common than changes of ?57% (0.79% [95% CI, 0.52%-1.06%]). This association was strong and consistent across the length of the baseline period (1 to 3 years), baseline estimated GFR, age, diabetes status, or albuminuria. Average adjusted 10-year risk of ESRD (in patients with a baseline estimated GFR of 35 mL/min/1.73 m2) was 99% (95% CI, 95%-100%) for estimated GFR change of ?57%, was 83% (95% CI, 71%-93%) for estimated GFR change of ?40%, and was 64% (95% CI, 52%-77%) for estimated GFR change of ?30% vs 18% (95% CI, 15%-22%) for estimated GFR change of 0%. Corresponding mortality risks were 77% (95% CI, 71%-82%), 60% (95% CI, 56%-63%), and 50% (95% CI, 47%-52%) vs 32% (95% CI, 31%-33%), showing a similar but weaker pattern. CONCLUSIONS AND RELEVANCE:Declines in estimated GFR smaller than a doubling of serum creatinine concentration occurred more commonly and were strongly and consistently associated with the risk of ESRD and mortality, supporting consideration of lesser declines in estimated GFR (such as a 30% reduction over 2 years) as an alternative end point for CKD progression.

Project description:Background/objectiveRAC1 gene could influence susceptibility to renal failure by altering the activity and expression of Rac1, which is a member of the Rho family of small GTP-binding proteins. In clinical practice, renal transplantation provides the optimal treatment for people with end-stage renal disease (ESRD). The objective of this present study was to determine whether the RAC1 gene polymorphisms were associated with primary ESRD susceptibility in Chinese renal recipients.MethodsSix single nucleotide polymorphisms (SNPs) of RAC1 gene, including rs836488 T>C, rs702482 A>T, rs10951982 G>A, rs702483 A>G, rs6954996 G>A, and rs9374 G>A, were genotyped in 300 renal transplant recipients (cases) and 998 healthy Chinese subjects (controls) by using TaqMan SNP genotyping assay. Allele, genotype, and haplotype frequencies of the six SNPs were compared between cases and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in logistic regression models to evaluate the associations of the six SNPs with ESRD risk.ResultsThe genotype distributions for the six SNPs in controls were consistent with Hardy-Weinberg equilibrium (P > 0.05). Association analysis revealed that three SNPs were significantly associated with ESRD risk. Positive associations with ESRD risk were found for the rs836488, rs702482, and rs702483 in the co-dominant model (minor allele homozygotes versus major allele homozygotes); specifically, the frequencies of the minor allele homozygotes and the minor allele for the three SNPs were higher in the cases than in the controls. In addition, these three SNPs also had associations with increased ESRD risk under the additive model (P < 0.05), and positive associations were also found for the rs836488 in the dominant model (P < 0.05) and for the rs702483 in the recessive model (P < 0.05). All these associations were independent of confounding factors. The other three SNPs (rs10951982, rs6954996, and rs9374), in all comparison models, were not associated with ESRD risk (P > 0.05). In haplotype analysis, carriers with "C-T-G-G-G-G" haplotype had a significantly higher risk of ESRD compared with the most common haplotype "T-A-G-A-G-G" (P = 0.011, OR = 1.46, 95% CI = 1.09-1.94).ConclusionThis study suggested that polymorphisms of RAC1 gene might influence the susceptibility to ESRD in Chinese Han population. Further studies are necessary to confirm our findings.

Project description:Background and Objectives The study aimed to evaluate the performance of a predictive model using the kidney failure risk equation (KFRE) for end-stage renal disease (ESRD) in diabetes and to investigate the impact of glomerular filtration rate (GFR) as estimated by different equations on the performance of the KFRE model in diabetes. Design, Setting, Participants, and Measurements A total of 18,928 individuals with diabetes without ESRD history from the UK Biobank, a prospective cohort study initiated in 2006–2010, were included in this study. Modification of diet in renal disease (MDRD), chronic kidney disease epidemiology collaboration (CKD-EPI) or revised Lund–Malmö (r-LM) were used to estimate GFR in the KFRE model. Cox proportional risk regression was used to determine the correlation coefficients between each variable and ESRD risk in each model. Harrell’s C-index and net reclassification improvement (NRI) index were used to evaluate the differentiation of the models. Analysis was repeated in subgroups based on albuminuria and hemoglobin A1C (HbA1c) levels. Results Overall, 132 of the 18,928 patients developed ESRD after a median follow-up of 12 years. The Harrell’s C-index based on GFR estimated by CKD-EPI, MDRD, and r-LM was 0.914 (95% CI = 0.8812–0.9459), 0.908 (95% CI = 0.8727–0.9423), and 0.917 (95% CI = 0.8837–0.9496), respectively. Subgroup analysis revealed that in diabetic patients with macroalbuminuria, the KFRE model based on GFR estimated by r-LM (KFRE-eGFRr-LM) had better differentiation compared to the KFRE model based on GFR estimated by CKD-EPI (KFRE-eGFRCKD-EPI) with a KFRE-eGFRr-LM C-index of 0.846 (95% CI = 0.797–0.894, p = 0.025), while the KFRE model based on GFR estimated by MDRD (KFRE-eGFRMDRD) showed no significant difference compared to the KFRE-eGFRCKD-EPI (KFRE-eGFRMDRD C-index of 0.837, 95% CI = 0.785–0.889, p = 0.765). Subgroup analysis of poor glycemic control (HbA1c >8.5%) demonstrated the same trend. Compared to KFRE-eGFRCKD-EPI (C-index = 0.925, 95% CI = 0.874–0.976), KFRE-eGFRr-LM had a C-index of 0.935 (95% CI = 0.888–0.982, p = 0.071), and KFRE-eGFRMDRD had a C-index of 0.925 (95% CI = 0.874–0.976, p = 0.498). Conclusions In adults with diabetes, the r-LM equation performs better than the CKD-EPI and MDRD equations in the KFRE model for predicting ESRD, especially for those with macroalbuminuria and poor glycemic control (HbA1c >8.5%).

Dataset Information

Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes.

Publications

Solidified glomerulosclerosis, identified using single glomerular proteomics, predicts end-stage renal disease in Chinese patients with type 2 diabetes.

Similar Datasets

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