Heterogeneity in the relationships between albuminuria and glomerular structure in type 1 and type 2 diabetes.

Abstract

Kidney structural-functional relationship studies have been critical in understanding diabetic kidney disease (DKD) evolution. However, most such studies were performed in persons with type 1 diabetes, where diabetic glomerular lesions are strongly associated with albumin excretion rate (AER). Here, we compare DKD structural-functional relationships in type 1 and type 2 diabetes. To better understand the evolution of DKD in type 2 diabetes, analyses of glomerular structure/albuminuria relationships were performed in 133 research volunteers with type 2 and 161 with type 1 diabetes matched for AER compared to 95 living donor kidney biopsies as controls. Morphometric measures of DKD glomerular lesions were more advanced and showed stronger relationships with AER in persons with type 1 vs type 2 diabetes. K-means cluster analysis based on distance from a structural-functional relationship model derived from data of research participants with type 1 diabetes yielded two clusters: 74% of participants with type 2 diabetes were in Cluster 1, which also included most participants with type 1 diabetes, while 26% of participants with type 2 diabetes (39% of type 2 cases with increased AER) were in Cluster 2 and showed greater AER than predicted by their DKD glomerular lesions based on the model. Among those with type 2 diabetes, despite excessive AER in Cluster 2, DKD glomerular lesions and podocyte structural parameters were similar between the two clusters. However, adjusted for AER, individuals with type 2 diabetes in Cluster 1 had more severe DKD lesions and approximately four-fold greater rates of glomerular filtration rate decline over nine to ten years follow up than those in Cluster 2. Kidney structural-functional relationships are heterogeneous in individuals with type 2 diabetes, and this heterogeneity is linked to glomerular filtration rate loss over time. Our investigation calls for further studies to better understand factors involved in this heterogeneity.