Diabetic renal disease: An overview with therapeutic implications

In the United States, diabetic nephropathy is now the leading cause of end-stage renal disease (ESRD) leading to kidney transplant. In insulin-dependent diabetes mellitus (IDDM), the evolution of renal disease follows five characteristic stages: glomerular hyperfiltration and nephromegaly are observed at the time of diagnosis (stage 1). This is followed by a clinically silent phase of developing structural injury (stage 2). “Incipient” diabetic nephropathy follows with microalbuminuria (stage 3). Overt nephropathy (stage 4) leads to ESRD (stage 5). Much less is known about renal disease in patients with non-insulin-dependent diabetes mellitus. Recent studies, however, indicate that the process is functionally and structurally analogous to that in IDDM. Experimental and clinical studies have improved our understanding of the pathophysiology of diabetic renal disease. The most promising interventions appear to be optimal glycemic control, dietary protein restriction, and antihypertensive therapy. Efficacy varies with stage of disease. Current evidence suggests that during stages 1 and 2 the rate of progression of microalbuminuria and the decline in glomerular filtration rate can be reduced by maintaining near-normoglycemia and, possibly, with angiotensin-converting enzyme inhibitor (CEI) administration. Following the appearance of persistent protein-uria, progression to ESRD can be delayed by aggressive antihypertensive therapy and restriction of dietary protein intake. Recent studies suggest that CEI may be better than other antihypertensive agents. Therapies have been identified that can slow the progression of diabetic renal disease and delay the appearance of ESRD.