Discontinuation of renin-angiotensin-aldosterone system inhibition (RAASi) in children with chronic kidney disease (CKD) may accelerate kidney function decline, according to new research.

In the Cardiovascular Comorbidity in Children with CKD study, 69 patients aged 6 to 17 years with an estimated glomerular filtration rate (eGFR) of 10 to 60 mL/min/1.73 m2 were assessed before and after RAASi discontinuation. Physicians commonly discontinued RAASi in patients due to increased serum creatinine (33%), hyperkalemia (23%), and hypotension (17%). RAASi was immediately replaced by other antihypertensive medications in 20% of children.

Results showed that eGFR declined faster after RAASi discontinuation than before: -3.9 vs -1.5 mL/min/1.73 m2 per year before discontinuation, Sophie M. van den Belt, MD, PhD, of the University Medical Center Groningen in The Netherlands, and colleagues reported in the Clinical Journal of the American Society of Nephrology. (Similar trends were observed in subgroup analyses by reason for discontinuation.) A propensity-score matched cohort that continued RAASi experienced no meaningful change in eGFR over the same time period: -1.8 vs -1.2 mL/min/1.73 m2 per year.

After discontinuation of RAASi, albuminuria initially increased significantly by 115% and systolic blood pressure nonsignificantly by 2.8 mm Hg. A spike in albuminuria was associated with double the risks for the composite kidney end point, a sustained 50% reduction in eGFR or progression to end-stage kidney disease.


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“These results are consistent with the notion that RAASi is important for kidney protection in advanced pediatric CKD, and that clinicians should consider the possible adverse effect on long-term kidney function when discontinuing RAASi,” Dr van den Belt’s team wrote.

With respect to hyperkalemia, serum potassium significantly decreased by 0.17 meq/L with RAASi discontinuation, but that reduction may not be clinically meaningful.

In an accompanying editorial, Marie-Michéle Gaudreault-Tremblay, MD, and Bethany J. Foster, MD, MSCE, of Montreal Children’s Hospital at McGill University Health Centre in Montreal, Canada, said that stopping RAASi remains a reasonable response to hyperkalemia in patients with advanced CKD, but if this fails to improve potassium, the new findings suggest that reinitiation of RAASi should be considered. “With the advent of newer potassium-binding medications, such as patiromer and sodium zirconium cyclosilicate, addition of these medications may allow RAASi to be prolonged,” they wrote.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

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References

van den Belt SM, Heerspink HJL, Kirchner M, et al. Discontinuation of RAAS inhibition in children with advanced CKD [published online April 6, 2020]. Clin J Am Soc Nephrol. doi: 10.2215/CJN.09750819

Gaudreault-Tremblay MM and Foster BJ. Benefits of continuing RAAS inhibitors in advanced CKD [published online April 6, 2020]. Clin J Am Soc Nephrol. doi: 10.2215/CJN.02920320