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. 2018 Jan;33(1):139-146.
doi: 10.1007/s00467-017-3763-8. Epub 2017 Aug 4.

Effect of renal function on antihypertensive drug safety and efficacy in children

Kevin M Watt  1   2 , Debbie Avant  3 , Jennifer Sherwin  4 , Daniel K Benjamin  5 , Christoph Hornik  4   6 , Daniel K Benjamin Jr  4   6 , Jennifer S Li  4   6 , P Brian Smith  4   6
Affiliations

Effect of renal function on antihypertensive drug safety and efficacy in children

Kevin M Watt et al. Pediatr Nephrol. 2018 Jan.

Abstract

Background: Hypertension and chronic kidney disease (CKD) are common comorbidities. Guidelines recommend treating hypertension in children with CKD because it is a modifiable risk factor for subsequent cardiovascular disease. Children with CKD are frequently excluded from antihypertensive drug trials. Consequently, safety and efficacy data for antihypertensive drugs are lacking in children with CKD.

Methods: We determined the incidence of adverse events in 10 pediatric antihypertensive trials to determine the effect of renal function on antihypertensive safety and efficacy in children. These trials were submitted to the US Food and Drug Administration from 1998 to 2005. We determined the number and type of adverse events reported during the trials and compared these numbers in participants with normal renal function and those with decreased function (defined as an estimated glomerular filtration rate [eGFR] <90 mL/min/1.73 m2 calculated using the original Schwartz equation).

Results: Among the 1,703 children in the 10 studies, 315 had decreased renal function. We observed no difference between the two cohorts in the incidence of adverse events or adverse drug reactions related to study drug. Only 5 participants, all with decreased renal function, experienced a serious adverse event; none was recorded by investigators to be study drug-related. Among treated participants, children with decreased renal function who received a high dose of study drug had a significantly larger drop in diastolic blood pressure compared with children with normal renal function.

Conclusions: These data show that antihypertensive treatment in children with renal dysfunction can be safe and efficacious, and consideration should be given to their inclusion in selected drug development programs.

Keywords: Antihypertensive drugs; Chronic kidney disease; Hypertension; Pediatrics.

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Conflict of interest statement

CONFLICT OF INTEREST

The work of KMW was supported under an Intergovernmental Personnel Agreement (IPA) between the U.S. Food and Drug Administration and Duke University.

K.M.W. receives support from the National Institute of Child Health and Human Development (NICHD) (1K23HD075891, 5K12HD047349) and the Thrasher Research Fund for his work in pediatric clinical pharmacology. D.K.B. Jr. receives support from the National Institutes of Health (NIH) (award 2K24HD058735-06, National Center for Advancing Translational Sciences (NCATS)award UL1TR001117, NICHD contract HSN275201000003I, and National Institute of Allergy and Infectious Diseases [NIAID] contract HHSN272201500006I); he also receives research support from Cempra Pharmaceuticals (subaward to HHSO100201300009C) and industry for neonatal and pediatric drug development (www.dcri.duke.edu/research/coi.jsp).

P.B.S. receives salary support for research from the NIH and the NCATS of the NIH (UL1TR001117), the NICHD (HHSN275201000003I and 1R01-HD081044-01), and the Food and Drug Administration (FDA) (1R18-FD005292-01); he also receives research support from Cempra Pharmaceuticals (subaward to HHS0100201300009C) and industry for neonatal and pediatric drug development (www.dcri.duke.edu/research/coi.jsp). The remaining authors have no disclosures. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Figures

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Figure 1
Trial Designs
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