Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in chronic renal disease: safety issues

Abstract 

Reducing the actions of the renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) slows nephropathy progression in patients with or without diabetes. These drug classes have proven therapeutic benefits, particularly in patients with renal insufficiency (ie, serum creatinine level 133–265 μmol/L [1.5–3.0 mg/dL]). This class of drugs could also provide renoprotective effects that are nonblood pressure-dependent when used as part of combination antihypertensive therapy in patients with more advanced renal disease. Although many studies demonstrate the use of ACE inhibitors and ARBs to delay the decline in renal function and reduce proteinuria, many physicians fail to use these drug classes in patients with renal insufficiency for fear that either serum creatinine or potassium levels will rise. Thus, because of these issues, patients are deprived of known strategies that delay progression of renal disease. A strong association exists between acute increases in serum creatinine of up to 30% to 35% after initiating ACE inhibitor therapy and long-term preservation of renal function. This association is predominantly present in people with a baseline serum creatinine of up to 3 mg/dL and usually stablizes within 2 to 3 months of therapy given blood pressure is reduced to goal. Moreover, the appropriate use of diuretics mitigates against profound increases in serum potassium. Thus, withdrawal of an ACE inhibitor in such patients should occur only when the rise in creatinine exceeds this threshold over a shorter period of time or hyperkalemia develops, ie, serum potassium level of 5.6 mmol/L or greater.