Are drugs that block the renin-angiotensin system effective and safe in patients with renal insufficiency?

Extensive clinical experience with angiotensin-converting enzyme (ACE) inhibitors in patients with renal disease has demonstrated efficacy in reducing blood pressure, proteinuria, and the rate of progression of renal disease. This is evident in both diabetic and nondiabetic nephropathy, particularly that associated with proteinuria. The ability of ACE inhibitors to stabilize renal function is not attenuated by more severe renal insufficiency, but greater caution with these drugs is necessary, as there may be drug accumulation and a greater propensity for an increase in serum potassium and creatinine levels. Both of these effects are self-limited and rarely require discontinuation of the drug. Increases in creatinine up to 20% are expected; greater increases are indicative of volume depletion or anatomic renal artery disease. Angiotensin II receptor blockers reduce blood pressure to a degree comparable to that achieved with ACE inhibitors, and like ACE inhibitors, they reduce proteinuria to an extent greater than what would be expected by blood pressure reduction alone. Angiotensin II receptor blockers are currently being evaluated in comparison with other therapies in two large clinical trials of non-insulin-dependent diabetic nephropathy with proteinuria to assess impact on the rate of progression of renal disease. Because of their antihypertensive/ antiproteinuric properties, it is likely they will provide some advantages over conventional drugs in protecting renal function. Early clinical experience with these drugs in patients with renal disease suggests that there might be a lesser incidence of functional renal insufficiency and hyperkalemia compared with ACE inhibitors.