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The Role of Glomerular Epithelial Injury in Kidney Function Decline in Patients With Diabetic Kidney Disease in the TRIDENT Cohort.

ABSTRACT:

Introduction

Although diabetic kidney disease (DKD) is responsible for more than half of all chronic and end-stage kidney disease (ESKD), the association of light (LM) and electron microscopic (EM) structural changes with clinical parameters and prognosis in DKD is incompletely understood.

Methods

This is an interim analysis of 62 patients diagnosed with biopsy-confirmed DKD from the multicenter TRIDENT (Transformative Research in Diabetic Nephropathy) study. Twelve LM and 8 EM descriptors, representing changes in glomeruli, tubulointerstitium, and vasculature were analyzed for their relationship with clinical measures of renal function. Patients were followed every 6 months.

Results

Multivariable linear regression analysis revealed that estimated glomerular filtration rate (eGFR) upon enrollment correlated the best with interstitial fibrosis. On the other hand, the rate of kidney function decline (eGFR slope) correlated the most with glomerular lesions including global glomerulosclerosis and mesangiolysis. Unbiased clustering analysis based on histopathologic data identified 3 subgroups. The first cluster, encompassing subjects with the mildest histologic lesions, had the most preserved kidney function. The second and third clusters had similar degrees of kidney dysfunction and structural damage, but differed in the degree of glomerular epithelial cell and podocyte injury (podocytopathy DKD subtype). Cox proportional hazard analysis showed that subjects in cluster 2 had the highest risk to reach ESKD (hazard ratio: 17.89; 95% confidence interval: 2.13-149.79). Glomerular epithelial hyperplasia and interstitial fibrosis were significant predictors of ESKD in the multivariate model.

Conclusion

The study highlights the association between fibrosis and kidney function and identifies the role of glomerular epithelial changes and kidney function decline.

SUBMITTER: Palmer MB

PROVIDER: S-EPMC8071659 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Rationale & objectivePatients with kidney failure have poor physical performance, but its trajectory is less clear. We examined physical function over the course of kidney disease, including the transition to dialysis.Study designObservational cohort.Setting & participantsCommunity-dwelling adults aged ≥45 years in the Brain in Kidney Disease (BRINK) cohort study.PredictorsEstimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR).OutcomesChange in physical performance using the Short Physical Performance Battery (SPPB) (primary) and gait speed (secondary).Analytical approachLinear mixed effects regression models.ResultsThe analytical cohort included 562 participants with mean age of 69.3 (SD, 9.8) years followed for up to 63 months. In total, 49.8% were women. In addition, 79.9% self-identified as White, and 15.3% self-identified as Black. In total, 48.8% had diabetes. Mean eGFR at baseline was 48.1 (SD, 24.3) mL/min/1.73 m2. In unadjusted analysis, lower eGFR was associated with greater decline in SPPB score (P trend < 0.001). The decline in SPPB score was larger among participants with lower eGFR, with a gradient from -0.15 (95% CI, -0.23 to -0.07) points per year for participants with eGFR ≥60 mL/min/1.73 m2 to -0.56 (95% CI, -0.84 to -0.27) for participants with eGFR <15 mL/min/1.73 m2 and -0.61 (95% CI, -0.90 to -0.33) after dialysis initiation. In covariate-adjusted models, SPPB did not continue to decline after dialysis initiation. In secondary analyses evaluating change in gait speed, gait speed continued to decline after dialysis initiation. Higher UACR was also associated with a greater decline in SPPB score and gait speed in unadjusted and adjusted models.LimitationsSmall number of participants started dialysis.ConclusionsWe found a graded association of chronic kidney disease stage and albuminuria with decline in physical performance. The decline in SPPB was not accelerated after dialysis initiation in covariate-adjusted models, whereas gait speed continued to decline.