Protecting the residual renal function: which drugs of choice?

Diabetic nephropathy is a major cause of illness and premature death in diabetic patients, largely through accompanying cardiovascular disease and end-stage renal failure. Proteinuria heralds the clinical nephropathy, and the worsening of proteinuria parallels the progression of renal disease towards chronic renal failure. A large body of evidence has accumulated that emphasizes the role of elevated blood pressure in the progression of renal disease, as well as the clear benefit of antihypertensive treatment. However, the choice of antihypertensive drug to protect renal function was less clear in the past. In earlier studies, a reduction in the rate of progressive renal failure in hypertensive subjects has been shown with diuretics, beta-blockers, and vasodilators. However, there is now increasing evidence that angiotensin converting enzyme (ACE) inhibitors and some calcium antagonists produce a more beneficial effect on nephropathy in terms of reducing proteinuria and slowing progression to renal failure. These drugs are attributed nephroprotective capacity beyond their systemic blood pressure lowering effects, and initial clinical trials with combinations have revealed additive nephroprotective effects. Finally, ACE-inhibitors and calcium antagonists have no adverse effects on glycemic control or lipid levels and may even improve insulin sensitivity. This further promotes these antihypertensives to first-line drugs when treating subjects at risk of metabolic disorders or people with diabetes.