Diuretics, ACEIs, ARBs, and NSAIDs: A Nephrotoxic Combination This triple therapy can increase the risk of acute renal failure.

Diuretics, ACEIs, ARBs, and NSAIDs: A Nephrotoxic Combination

This triple therapy can increase the risk of acute renal failure.

Mechanism of the Interaction

Diuretics can reduce plasma volume leading to reduced renal blood flow. This may lead to increased serum creatinine concentrations. The kidney can compensate via the renin-angiotensin system by constricting the efferent renal arteriole to increase glomerular filtration pressure and favor water and sodium retention. ACEIs and ARBs inhibit efferent renal arteriolar vasoconstriction that lowers glomerular filtration pressure. NSAIDs, by inhibition of prostaglandins and bradykinin, produce vasoconstriction of the afferent renal arteriole and reduce the ability of the kidney to regulate (increase) glomerular blood flow. The administration of an NSAID plus diuretic or ACEI or ARB may reduce the hypotensive effect of the antihypertensive agent but does not commonly lead to acute renal failure. When triple therapy with an NSAID plus diuretic and an ACEI or ARB is administered, the kidney is unable to use its normal compensatory mechanisms and may suffer an acute reduction in glomerular filtration that is marked by a rising serum creatinine.

Management

Patients receiving NSAIDs chronically in combination with diuretics, ACEIs, or ARB, are at risk for diminished hypotensive response, elevated serum creatinine, and acute kidney injury. They should be monitored for altered blood pressure and serum creatinine, particularly during the first few months of combination therapy. While it appears that alternative hypotensive agents (eg, calcium channel blockers, centrally acting agents) are less affected by NSAIDs, similar data are not available for the risk of renal injury.