Renal protection in diabetes: is it affected by glucose control or inhibition of the renin-angiotensin pathway?

BACKGROUND: Recent reports indicate increased risk of renal failure with long-term use of angiotensin-converting enzyme inhibitors (ACEI) in diabetes. End-stage renal disease (ESRD) in diabetes has increased despite ACEI and angiotensin receptor blocker (ARB) use. This study questions renal protection by ACEI or ARB. Our hypothesis is that uncontrolled hyperglycemia is central to diabetic ESRD while tight glucose control is renoprotective. Cultured endothelial cells show morphological damage that increases with duration of exposure to high glucose and is prevented by insulin and more so by a combination of insulin and heparin.
METHODS: Findings from individual patients are compared to clinical trial results wherein ACEI or ARB was emphasized as the prime therapy to prevent progression of diabetic nephropathy to ESRD. Serum creatinine (Scr) changes were the main indicator of renoprotective effects in clinical trials. Creatinine clearance (Ccl), an important marker of glomerular filtration rate, was seldom reported.
RESULTS: Our observations show that ACEI-treated patients develop progressive renal failure, whereas renal function remains stable with optimum glucose control. Clinical trials showed that reduction of proteinuria, with ACEI, reduces the risk of ESRD. Our studies show that reduction of proteinuria with use of ACEI or ARB parallels a reduction in Ccl, suggesting that a change in proteinuria is related to Ccl changes. Scr changes are small, giving a deceptive view of renal protection.
CONCLUSIONS: Our observations find no evidence of renal protection with ACEI or ARB use in diabetes. Laboratory studies and clinical observations suggest that adequate glucose control is the key to renal protection in diabetes.