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

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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.

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Authors and Affiliations

  1. Department of Pediatrics, Duke University, Durham, NC, USA

    Kevin M. Watt, Jennifer Sherwin, Christoph Hornik, Daniel K. Benjamin Jr, Jennifer S. Li & P. Brian Smith

  2. Duke Clinical Research Institute, Durham, NC, USA

    Kevin M. Watt, Christoph Hornik, Daniel K. Benjamin Jr, Jennifer S. Li & P. Brian Smith

  3. Office of Pediatric Therapeutics, Office of the Commissioner, U.S. Food and Drug Administration, Silver Spring, MD, USA

    Debbie Avant

  4. Department of Economics, Clemson University, Clemson, SC, USA

    Daniel K. Benjamin

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  1. Kevin M. Watt
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Corresponding author

Correspondence to Kevin M. Watt.

Ethics declarations

Ethics

All trials were approved by the institutional review boards of the participating sites. Because the datasets obtained from DARRTS and the EDR contained no patient identifiers, we received a waiver of review from the Duke University Medical Center Institutional Review Board and a letter of exempt status from the FDA Research Involving Human Subjects Committee.

Funding

This study was funded by a grant from the Duke University O’Brien Center for Kidney Research, which is supported by a grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and by the Duke University School of Medicine and Department of Medicine.

Conflicts of interest

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

KMW 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. DKB 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 (http://www.dcri.duke.edu/research/coi.jsp). PBS 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.

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Watt, K.M., Avant, D., Sherwin, J. et al. Effect of renal function on antihypertensive drug safety and efficacy in children. Pediatr Nephrol 33, 139–146 (2018). https://doi.org/10.1007/s00467-017-3763-8

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  • DOI: https://doi.org/10.1007/s00467-017-3763-8

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