Serum Creatinine Elevations After Starting Angiotensin-Renin Blockade Signal High Risk

April 25, 2017

Serum Creatinine Elevations After Starting Angiotensin-Renin Blockade Signal High Risk

  1. Paul S. Mueller, MD, MPH, FACP

Patients whose levels rose after starting angiotensin-converting–enzyme inhibitors or angiotensin-receptor had worse outcomes.

  1. Paul S. Mueller, MD, MPH, FACP

National Kidney Foundation guidelines recommend stopping angiotensin-converting–enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs) if serum creatinine increases by ≥30% after starting treatment. However, the rationale for this 30% threshold is unclear. In this cohort study of 122,000 U.K. adults, researchers assessed outcomes associated with rises in serum creatinine concentrations during the first 2 months after beginning ACE inhibitor or ARB treatment.

About 2100 patients (1.7%) had serum creatinine increases of ≥30% after starting treatment. Compared with patients in whom creatinine increased by <30%, those with larger increases were more likely to die (adjusted incident rate ratio, 1.84) or to develop end-stage kidney disease (IRR, 3.43), heart failure (IRR, 1.37), or myocardial infarction (IRR, 1.46) during about 10 years of follow-up. Moreover, dose-response relations between serum creatinine and these outcomes were observed even when creatinine rose by 10% to 19% or 20% to 29% following ACE inhibitor or ARB initiation.

Comment

In this real-world study, which was subject to residual confounding, any increase in serum creatinine after starting ACE inhibitor or ARB treatment was associated with higher risks for death, end-stage kidney disease, heart failure, and myocardial infarction — with no distinct cutoff at 30%. Whether ACE inhibitors or ARBs directly cause adverse outcomes or just unmask underlying pathophysiology are unknown. Nonetheless, patients with increases in serum creatinine after starting these drugs should be recognized as a high-risk group and monitored closely.

Editor Disclosures at Time of Publication

  • Disclosures for Paul S. Mueller, MD, MPH, FACP at time of publication Consultant / advisory board Boston Scientific (Patient Safety Advisory Board) Editorial boards Medical Knowledge Self-Assessment Program (MKSAP 17 General Internal Medicine Committee); MKSAP 17 General Internal Medicine (author/contributor) Leadership positions in professional societies American Osler Society (Vice President)

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