Morphologic Features of Declining Renal Function in Type 1 Diabetes

Progressive renal dysfunction is a major complication of type 1 diabetes. Studying relationships between evolution of diabetic nephropathy lesions and renal functional alterations (structural-functional relationships) helps to better understand the natural history of diabetic nephropathy. The focus of this review is our current understanding of the interplay between morphologic changes of diabetic nephropathy and glomerular filtration rate (GFR) loss. These morphologic changes often may not progress in parallel to each other or to the decline in GFR or increase in albumin excretion rate (AER). Quantitative measures of renal (mainly glomerular) structural changes can predict a substantially larger fraction of AER variability compared with that of GFR, especially using linear correlation analyses. However, nonlinear models better fit the structural-functional relationships across a wide range of GFRs and AERs. Currently, there are insufficient longitudinal data to show which structural changes predict the slope of GFR decline in type 1 diabetic patients. Based on cross-sectional studies, however, such a predictor would be about 10% more robust in patients whose GFR was 45 mL/min/1.73 m2 or greater if comprised of a composite of glomerular, tubular, and interstitial parameters versus glomerular changes alone. For a slowly progressive disease, such as diabetic nephropathy, in which, especially in the earlier stages, it takes a long time for GFR to decline substantially, such predictors are much needed and, if sufficiently precise, could potentially serve as a surrogate of renal functional decline in clinical trials.