Changes in albuminuria but not GFR are associated with early changes in kidney structure in type 2 diabetes

Background: In type 1 diabetes, changes in theGFR and urine albumin-to-creatinine ratio (ACR) are related to changes in kidney structure that reflect disease progression. However, such changes have not been studied in type 2 diabetes. Methods: Participants were American Indians with type 2 diabetes enrolled in a clinical trial of losartan versus placebo. We followed a subset who underwent kidney biopsy at the end of the 6-year trial, with annual measurements of GFR (by urinary clearance of iothalamate) and ACR. Participants had a second kidney biopsy after a mean follow-up of 9.3 years. We used quantitative morphometric analyses to evaluate both biopsy specimens. Results: Baseline measures for 48 participants (12 men and 36 women, mean age 45.6 years) who completed the study included diabetes duration (14.6 years), GFR (156 ml/min), and ACR (15 mg/g). During follow-up, glomerular basement membrane (GBM) width, mesangial fractional volume, and ACR increased, and surface density of peripheral GBM and GFR decreased. After adjustment for sex, age, ACR, and each morphometric variable at baseline, an increase in ACR during follow-up was significantly associated with increases in GBM width, mesangial fractional volume, and mean glomerular volume, and a decrease in surface density of peripheral GBM. Decline in GFR was not associated with changes in these morphometric variables after additionally adjusting for baseline GFR. Conclusions: In American Indians with type 2 diabetes and preserved GFR at baseline, increasing ACR reflects the progression of earlier structural glomerular lesions, whereas early GFR decline may not accurately reflect such lesions.