Discontinuation of RAAS Inhibition in Children with Advanced CKD

Abstract

Background and objectives: Although renin-angiotensin-aldosterone system inhibition (RAASi) is a cornerstone in the treatment of children with CKD, it is sometimes discontinued when kidney function declines. We studied the reasons of RAASi discontinuation and associations between RAASi discontinuation and important risk markers of CKD progression and on eGFR decline in the Cardiovascular Comorbidity in Children with CKD study.

Design, setting, participants, & measurements: In this study, 69 children with CKD (67% male, mean age 13.7 years, mean eGFR 27 ml/min per 1.73 m²) who discontinued RAASi during prospective follow-up were included. Initial change in BP, albuminuria, and potassium after discontinuation were assessed (median time 6 months). Rate of eGFR decline (eGFR slope) during a median of 1.9 years before and 1.2 years after discontinuation were estimated using linear mixed effects modeling.

Results: Physician-reported reasons for RAASi discontinuation were increase in serum creatinine, hyperkalemia, and symptomatic hypotension. After discontinuation of RAASi, BP and albuminuria increased, whereas potassium decreased. eGFR declined more rapidly after discontinuation of RAASi (-3.9 ml/min per 1.73 m² per year; 95% confidence interval, -5.1 to -2.6) compared with the slope during RAASi treatment (-1.5 ml/min per 1.73 m² per year; 95% confidence interval, -2.4 to -0.6; P=0.005). In contrast, no change in eGFR slope was observed in a matched control cohort of patients in whom RAASi was continued.

Conclusions: Discontinuation of RAASi in children with CKD is associated with an acceleration of kidney function decline, even in advanced CKD.

Keywords: Acceleration; Blood Pressure Determination; Cohort Studies; Comorbidity; Follow-Up Studies; Hyperkalemia; Potassium; Prospective Studies; RAAS inhibition; Renal Insufficiency, Chronic; Renin-Angiotensin System; albuminuria; blood pressure; chronic renal disease; creatinine; glomerular filtration rate; hypotension; pediatric nephrology.