Creatinine Rises After RAS Inhibitor Initiation Tied to Worse Outcomes – Renal and Urology News

Although guidelines permit up to a 30% acute increase in creatinine following initiation of renin angiotensin system inhibitors (RASi), new evidence published in the Clinical Journal of the American Society of Nephrology associates creatinine rises of 10% or more with increased risks for death, cardiovascular events, and end-stage renal disease (ESRD).

Using data from theStockholm Creatinine Measurements (SCREAM) project, researchers identified 31,951patients initiating RASi during 2007 to 2011. Creatinine increases exceeding10% within 2 months of RASi initiation were consistently associated withgreater risks over a median 3.5 years, Edouard L. Fu, MD, a PhD candidate atLeiden University in The Netherlands, and colleagues reported. The risk forall-cause mortality significantly increased by 15%, 22%, and 55% withcreatinine rises of 10% to 19%, 20% to 29%, and 30% or more, respectively,compared with a reference creatinine rise of less than 10%. Heart failure risk significantlyincreased by 14%, 23%, and 41%, respectively. Myocardial infarction risk rose by5%, 32%, and 29%, respectively, but the increases were not significant. Lastly,ESRD risk increased significantly by 3-, 3-, and 8-fold, respectively. Patientswith CKD stages 4 and 5 were previously excluded from study.

Findings from the currentstudy differ somewhat from results from several trials, such as TRANSCEND, but thetendencies and effects in these studies are in the direction of the effects thatwe observed, Dr Lus team observed.

The investigators pointedout that these findings do not necessarily mean RASi should be discontinuedafter acute creatinine increases. Additional studies are needed to clarify optimalthresholds for discontinuation.

Because reanalyses of TRANSCENDand ADVANCE found no evidence for modification of the benefit of RASi by levelof creatinine increase, we speculate that creatinine increases may therefore bea risk marker of disease rather than directly leading to adverse outcomes, DrLu and his colleagues stated.

Monitoring creatininebefore and after initiation of RASi identifies patients at high risk forsubsequent adverse outcomes, they added.

Among the studyslimitations, the researchers could not determine the persistence of acute creatininerises and lacked information on blood pressure and proteinuria.

Reference

Fu EL, Trevisan M, Clase CM, et al. Associationof acute increases in plasma creatinine after renin-angiotensin blockade with subsequentoutcomes. Clin J Am Soc Nephrol. 14:13361345,2019. doi:10.2215/CJN.03060319

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Creatinine Rises After RAS Inhibitor Initiation Tied to Worse Outcomes - Renal and Urology News