Structural Predictors of Loss of Renal Function in American ... : Clinical Journal of the American Society of Nephrology (original) (raw)

Original Articles

Structural Predictors of Loss of Renal Function in American Indians with Type 2 Diabetes

Fufaa, Gudeta D.*; Weil, E. Jennifer*; Lemley, Kevin V.†; Knowler, William C.*; Brosius, Frank C. 3rd‡; Yee, Berne§; Mauer, Michael‖; Nelson, Robert G.*

*Diabetes Epidemiology and Clinical Research Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Phoenix, Arizona;

†Department of Pediatrics, University of Southern California Keck School of Medicine, Children’s Hospital Los Angeles, Los Angeles, California;

‡Division of Nephrology, University of Michigan, Ann Arbor, Michigan;

§Southwest Kidney Institute, Phoenix, Arizona; and

‖Department of Pediatrics and Medicine, University of Minnesota, Minneapolis, Minnesota

Correspondence: Dr. Robert G. Nelson, National Institutes of Health, 1550 East Indian School Road, Phoenix, AZ 85014-4972. Email: [email protected]

Received May 27, 2015

Accepted October 14, 2015

Abstract

Background and objectives

Diabetes is the leading cause of kidney failure in the United States, but early structural determinants of renal function loss in type 2 diabetes are poorly defined. We examined the association between morphometrically determined renal structural variables and loss of renal function in 111 American Indians with type 2 diabetes who volunteered for a research kidney biopsy at the end of a 6-year clinical trial designed to test the renoprotective efficacy of losartan versus placebo. Participants were subsequently followed in an observational study, in which annual measurements of GFR (iothalamate) initiated during the clinical trial were continued.

Design, setting, participants, & measurements

Renal function loss was defined as ≥40% loss of GFR from the research examination performed at the time of kidney biopsy. Associations with renal function loss were evaluated by Cox proportional hazards regression. Hazard ratios (HRs) were reported per 1-SD increment for each morphometric variable.

Results

Of 111 participants (82% women; baseline mean [±SD] age, 46 years old [±10]; diabetes duration, 16 years [±6]; hemoglobin A1c =9.4% [±2.2]; GFR=147 ml/min [±56]; median albumin-to-creatinine ratio, 41 mg/g [interquartile range, 13–158]), 51 (46%) developed renal function loss during a median follow-up of 6.6 years (interquartile range, 3.1–9.0). Fourteen had baseline GFR <90 ml/min, and three had baseline GFR <60 ml/min. Higher mesangial fractional volume (HR, 2.27; 95% confidence interval [95% CI], 1.58 to 3.26), percentage of global glomerular sclerosis (HR, 1.63; 95% CI, 1.21 to 2.21), nonpodocyte cell number per glomerulus (HR, 1.50; 95% CI, 1.10 to 2.05), glomerular basement membrane width (HR, 1.48; 95% CI, 1.05 to 2.08), mean glomerular volume (HR, 1.42; 95% CI, 1.02 to 1.96), and podocyte foot process width (HR, 1.28; 95% CI, 1.03 to 1.60); lower glomerular filtration surface density (HR, 0.62; 95% CI, 0.41 to 0.94); and fewer endothelial fenestrations (HR, 0.68; 95% CI, 0.48 to 0.95) were each associated with GFR decline after adjustment for baseline age, sex, duration of diabetes, hemoglobin A1c, GFR, and treatment assignment during the clinical trial.

Conclusions

Quantitative measures of glomerular structure predict loss of renal function in type 2 diabetes.