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Antihypertensive medication nonadherence and target organ damage in children with chronic kidney disease

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Abstract

Background

Nonadherence is common in children with chronic kidney disease (CKD). This may contribute to inadequate blood pressure control and adverse outcomes. This study examined associations between antihypertensive medication nonadherence, ambulatory blood pressure monitoring (ABPM) parameters, kidney function, and cardiac structure among children with CKD.

Methods

We performed secondary analyses of data from the CKD in Children (CKiD) study, including participants with treated hypertension who underwent ABPM, laboratory testing, and echocardiography biannually. Nonadherence was defined by self-report of any missed antihypertensive medication 7 days prior to the study visit. Linear regression and mixed-effects models were used to assess the association of nonadherence with baseline and time-updated ABPM profiles, estimated glomerular filtration rate (eGFR), urine protein to creatinine ratio (UPCR), and left ventricular mass index (LVMI).

Results

Five-hundred and eight participants met inclusion criteria, followed for a median of 2.9 years; 212 (42%) were female, with median age 13 years (IQR 10–16), median baseline eGFR 49 (33–64) ml/min/1.73 m2 and median UPCR 0.4 (0.1–1.0) g/g. Nonadherence occurred in 71 (14%) participants. Baseline nonadherence was not significantly associated with baseline 24-h ABPM parameters (for example, mean 24-h SBP [β − 0.1, 95% CI − 2.7, 2.5]), eGFR (β 1.0, 95% CI − 0.9, 1.2), UCPR (β 1.1, 95% CI − 0.8, 1.5), or LVMI (β 0.6, 95% CI − 1.6, 2.9). Similarly, there were no associations between baseline nonadherence and time-updated outcome measures.

Conclusions

Self-reported antihypertensive medication nonadherence occurred in 1 in 7 children with CKD. We found no associations between nonadherence and kidney function or cardiac structure over time.

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Data availability

The datasets generated during and/or analyzed during the current study are available in the NIDDK Central repository (https://repository.niddk.nih.gov/home/).

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Acknowledgements

Data in this manuscript were collected by the Chronic Kidney Disease in children prospective cohort study (CKiD) with clinical coordinating centers (Principal Investigators) at Children’s Mercy Hospital and the University of Missouri–Kansas City (Bradley Warady, MD) and Children’s Hospital of Philadelphia (Susan Furth, MD, PhD), Central Biochemistry Laboratory (George Schwartz, MD) at the University of Rochester Medical Center, and data coordinating center (Alvaro Muñoz, PhD and Derek Ng, PhD) at the Johns Hopkins Bloomberg School of Public Health. The CKiD Study is funded by the National Institute of Diabetes and Digestive and Kidney Diseases, with additional funding from the National Institute of Child Health and Human Development, and the National Heart, Lung, and Blood Institute (U01-DK-66143, U01-DK-66174, U24-DK-082194, and U24-DK-66116). The CKID website is located at https://statepi.jhsph.edu/ckid, and a list of CKiD collaborators can be found at https://statepi.jhsph.edu/ckid/site-investigators/.

Funding

RB was supported by the National Institutes of Health (T32DK007006-48S1). JBC is supported by the National Institutes of Health (R01-HL153646, R01-HL157108, R01-HL155599, R01-HL157264, U01-HL160277, U24-DK060990, and R01-AG074989), and an American Heart Association Bugher Award. IK receives support from the National Heart, Lung, and Blood Institute (R01 HL152699) and the National Institute on Minority Health and Health Disparities (P50 MD017431). SF receives support from the NIDDK for the CKiD Study (U01DK066174) and the Pediatric Center of Excellence in Nephrology (P50DK114786). SA was supported by NIDDK (R01 DK110749, R01 DK120886) and NICHD (R01 HD091185).

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Authors and Affiliations

  1. Division of Pediatric Nephrology and Hypertension, Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, 622 West 168th Street, PH17-102E, NY, 10032, New York, USA

    Rushelle L. Byfield

  2. Division of Nephrology, Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Rushelle L. Byfield, Susan L. Furth & Sandra Amaral

  3. Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Rui Xiao, Susan L. Furth, Sandra Amaral & Jordana B. Cohen

  4. Columbia Hypertension Center, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA

    Daichi Shimbo

  5. Center for Behavioral Cardiovascular Health, Columbia University Irving Medical Center, New York, NY, USA

    Ian M. Kronish

  6. Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Jordana B. Cohen

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  1. Rushelle L. Byfield
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  2. Rui Xiao
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Contributions

RB, JBC, and SA contributed to research idea and study design. RB, JBC, and RX contributed to data analysis/interpretation. JBC, SF, DS, and IK contributed to supervision or mentorship. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for the individual’s own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. RB wrote the initial draft of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Rushelle L. Byfield.

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Ethics approval

This research study was conducted retrospectively from data previously obtained for multicenter observational cohort study. We consulted extensively with the IRB of Children’s Hospital of Philadelphia and the University of Pennsylvania who determined that our study did not need ethical approval. An IRB official waiver of ethical approval was granted from the IRB of Children’s Hospital of Philadelphia and University of Pennsylvania.

Competing interests

The authors declare no competing interests.

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Byfield, R.L., Xiao, R., Shimbo, D. et al. Antihypertensive medication nonadherence and target organ damage in children with chronic kidney disease. Pediatr Nephrol 39, 221–231 (2024). https://doi.org/10.1007/s00467-023-06059-w

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