Serum Uric Acid as a New Player in the Development of Diabetic Nephropathy

The pathogenesis of diabetic nephropathy is complex and still not fully elucidated. Uric acid has been associated with renal disease, even though hyperuricemia may be a marker of or by itself be responsible for microvascular disease in diabetes. In animal models, elevated level of uric acid can lead to arteriolopathy of preglomerular vessels, impaired autoregulation, glomerular hypertension, as well as endothelial dysfunction. Kidney damage in hyperuricemic rats is not dependent on blood pressure, and instead involves the renin-angiotensin system. In patients with diabetes, serum uric acid early in the course of diabetes is significantly, and independent of confounders, associated with later development of persistent macroalbuminuria. Therefore, uric acid may be a novel and important player in the pathogenesis of microvascular complications in diabetes. A dose-response relationship between serum uric acid and early decline in renal function has recently been demonstrated in patients with type-1 diabetes. Randomized controlled trials on drugs that lower uric acid need to be conducted to evaluate the causal relationship between serum uric acid and development and progression of diabetic kidney disease; in addition, large scale long-term treatment trials need to be performed, as they are still lacking.