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Renal histology in diabetic nephropathy predicts progression to end-stage kidney disease but not the rate of renal function decline.

ABSTRACT: BACKGROUND:While histopathologic changes correlate with functional impairment in cross-sectional studies of diabetic nephropathy (DN), whether these findings predict future rate of kidney function loss remains uncertain. We thus sought to examine the relationship between kidney histopathology, incidence of end-stage kidney disease (ESKD), and rate of estimated glomerular filtration rate (eGFR) loss in DN. METHODS:In this longitudinal cohort study, we studied 50 adults diagnosed with biopsy-proven DN. We analyzed the histopathologic parameters of each patient's kidney biopsy, as defined by the Renal Pathology Society classification system for DN, and tracked all available eGFR measurements post-biopsy. We additionally collected baseline clinical parameters (at the time of biopsy), including eGFR, albumin-to-creatinine ratio (ACR), and hemoglobin A1c. Multivariable linear regression was used to assess the relationship between histologic and clinical parameters at the time of the biopsy and eGFR slope. Kaplan-Meier curves and Cox regression were used to evaluate the association between histologic and clinical parameters and ESKD incidence. RESULTS:Progression to ESKD was associated with worsening interstitial fibrosis score (p?=?0.05), lower baseline eGFR (p?=?0.02), higher ACR (p?=?0.001), and faster eGFR decline (p?

SUBMITTER: Misra PS

PROVIDER: S-EPMC7368674 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Renal histology in diabetic nephropathy predicts progression to end-stage kidney disease but not the rate of renal function decline.

Misra Paraish S PS Szeto Stephen G SG Krizova Adriana A Gilbert Richard E RE Yuen Darren A DA

BMC nephrology 20200718 1

<h4>Background</h4>While histopathologic changes correlate with functional impairment in cross-sectional studies of diabetic nephropathy (DN), whether these findings predict future rate of kidney function loss remains uncertain. We thus sought to examine the relationship between kidney histopathology, incidence of end-stage kidney disease (ESKD), and rate of estimated glomerular filtration rate (eGFR) loss in DN.<h4>Methods</h4>In this longitudinal cohort study, we studied 50 adults diagnosed wi ...[more]

PMID: 32682403

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Project description:Data on risk factors predicting rapid progression to end-stage renal disease (ESRD) or short-term kidney function decline (i.e., within 1 year) in chronic kidney disease (CKD) are rare but urgently needed to plan treatment. This study describes the association and predictive value of urinary uromodulin (uUMOD) for rapid progression of CKD.We assessed uUMOD, demographic/treatment parameters, estimated glomerular filtration rate (eGFR), and proteinuria in 230 CKD patients stage I-V. ESRD and 25% decline of eGFR was documented at the end of follow-up period and used as a composite endpoint. Association between logarithmic uUMOD and eGFR/proteinuria was calculated using linear regression analysis, adjusting for age, gender, and body mass index. We performed multivariable Cox proportional hazard regression analysis to evaluate the association of uUMOD with the composite endpoint. Therefore, patients were categorized into quartiles. The predictive value of uUMOD for the above outcomes was assessed using receiver-operating characteristic (ROC) curve analysis.Follow-up was 57.3?±?18.7 weeks, baseline age was 60 (18;92) years, and eGFR was 38 (6;156) mL/min/1.73?m. Forty-seven (20.4%) patients reached the composite endpoint. uUMOD concentrations were directly associated with eGFR and inversely associated with proteinuria (??=?0.554 and ??=?-0.429, P?<?.001). In multivariable Cox regression analysis, the first 2 quartiles of uUMOD concentrations had a hazard ratio (HR) of 3.589 [95% confidence interval (95% CI) 1.002-12.992] and 5.409 (95% CI 1.444-20.269), respectively, in comparison to patients of the highest quartile (?11.45??g/mL) for the composite endpoint. In ROC-analysis, uUMOD predicted the composite endpoint with good sensitivity (74.6%) and specificity (76.6%) at an optimal cut-off at 3.5??g/mL and area under the curve of 0.786 (95% CI 0.712-0.860, P?<?.001).uUMOD was independently associated with ESRD/rapid loss of eGFR. It might serve as a robust predictor of rapid kidney function decline and help to better schedule arrangements for future treatment.

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:This study was performed to develop and validate a predictive model for the risk of end-stage renal disease (ESRD) inpatients with diabetic nephropathy (DN) confirmed by renal biopsy. We conducted a retrospective study with 968 patients with T2DM who underwentrenal biopsy for the pathological confirmation of DNat the First Affiliated Hospital of Zhengzhou University from February 2012 to January 2015; the patients were followed until December 2018. The outcome was defined as a fatal or nonfatal ESRD event (peritoneal dialysis or hemodialysis for ESRD, renal transplantation, or death due to chronic renal failure or ESRD). The dataset was randomly split into development (75%) and validation (25%) cohorts. We used stepwise multivariablelogistic regression to identify baseline predictors for model development. The model's performance in the two cohorts, including discrimination and calibration, was evaluated by the C-statistic and the P value of the Hosmer-Lemeshow test. During the 3-year follow-up period, there were 225 outcome events (47.1%) during follow-up. Outcomes occurred in 187 patients (52.2%) in the derivation cohort and 38 patients (31.7%) in the validation cohort. The variables selected in the final multivariable logistic regression after backward selection were pathological grade, Log Urinary Albumin-to-creatinine ratio (Log ACR), cystatin C, estimated glomerular filtration rate (eGFR) and B-type natriuretic peptide (BNP). 4 prediction models were created in a derivation cohort of 478 patients: a clinical model that included cystatin C, eGFR, BNP, Log ACR; a clinical-pathological model and a clinical-medication model, respectively, also contained pathological grade and renin-angiotensin system blocker (RASB) use; and a full model that also contained the pathological grade, RASB use and age. Compared with the clinical model, the clinical-pathological model and the full model had better C statistics (0.865 and 0.866, respectively, vs. 0.864) in the derivation cohort and better C statistics (0.876 and 0.875, respectively, vs. 0.870) in the validation cohort. Among the four models, the clinical-pathological model had the lowest AIC of 332.53 and the best P value of 0.909 of the Hosmer-Lemeshow test. We constructed a nomogram which was a simple calculator to predict the risk ratio of progression to ESRD for patients with DN within 3 years. The clinical-pathological model using routinely available clinical measurements was shown to be accurate and validated method for predicting disease progression in patients with DN. The risk model can be used in clinical practice to improve the quality of risk management and early intervention.

Dataset Information

Renal histology in diabetic nephropathy predicts progression to end-stage kidney disease but not the rate of renal function decline.

Publications

Renal histology in diabetic nephropathy predicts progression to end-stage kidney disease but not the rate of renal function decline.

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