Research Viewpoints Early Renal Pathology in Diabetes

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Comai G, Malvi D, Angeletti A, Vasuri F, Valente S, Ambrosi F, Capelli I, Ravaioli M, Pasquinelli G, D’Errico A, Fornoni A, La Manna G: Histological evidence of diabetic kidney disease precede clinical diagnosis. Am J Nephrol DOI 10.1159/000500353

The microscopical anatomy of subjects with diabetes but exhibiting normal urinalyses and kidney function is largely unknown, as kidney biopsies are not presently indicated in these circumstances.

Comai and co-workers sought to remedy this deficiency by taking advantage of pre-implantation kidney biopsies of deceased donors with diabetes (mostly type 2) and protein excretion of <30mg/dL and eGFR >60ml/min/1.73m2 kidneys in the context of kidney transplantation. A total of 35 kidney biopsies from patients with diabetes (mean age 69.7 years, all white) were evaluated by light and electron microscopy. The mean urine protein-to-creatinine ratio (UPCR) was about 12mg/gm and the average eGFR was about 68ml/min/1.73m2. Hypertension was present in 69% and 22% were treated with renin-angiotensin system (RAS) inhibitors. No patient had diabetic retinopathy. Three had no evidence of diabetic kidney disease; 3 had stage 1; 22 had stage 2a; 3 had stage 2b, 4 had stage 3, and 0 had stage 4 diabetic kidney disease (assessed by the system of Tervaert, et al. , Tervaert TW et al. JASN, 2010). Additional histological parameters of glomerulosclerosis, tubular atrophy interstitial fibrosis, and vascular damage were assessed by the Karpinski score (Karpinski J, Transplantation, 1999).

These findings represent a good snapshot of renal histology of subjects with diabetes and normal renal function. The presence of hyper-filtration in the donors could not be excluded because no measured GFR were performed. The assessment of proteinuria did not include albuminuria to creatinine ratios. There was no comparison group of similarly aged non-diabetic donors so the significance of the Karpinski scores is very uncertain.

Despite these weaknesses, this study and other autopsy based descriptive analysis strongly support the notion that diabetes-related pathology precedes the development of overt clinical signs, such as proteinuria or reduced GFR. Whether this study justifies the broader application of kidney biopsy to foster earlier treatment of clinically lanthanic, diabetes-related lesion, as suggested by the authors, remains to be seen.