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Determinants of medication adherence in childhood nephrotic syndrome and associations of adherence with clinical outcomes

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Pediatric patients with nephrotic syndrome take medications long-term with significant toxicity and complex regimens, yet data on medication adherence are limited.


In a multicenter observational study of patients with nephrotic syndrome, NEPTUNE (NCT01209000), we surveyed caregivers of patients <19 years old and adolescent patients on medication adherence during longitudinal follow-up beginning in June 2015. Data extraction was in October 2020. We described the proportion of nonadherent patients at first survey. Participant social and economic factors, condition-related factors, therapy-related factors, and patient-related factors were examined for relationships with nonadherence by generalized linear mixed models using the longitudinal data. In exploratory fashion, we assessed the relationship between adherence and subsequent steroid response classification by binary logistic regression and adherence with healthcare utilization by Poisson regression.


A total of 225 participants completed a median of 3 surveys during follow-up (IQR, 2–5), with a total of 743 surveys. Overall, 80 (36%) reported nonadherence with medications. In adjusted analysis, older age (per 1 year; OR 1.08; 95% CI, 1.03 1.12), lower maternal educational level (≥ high school vs. < high school; OR 0.47; 95% CI 0.25 to 0.89), and increased parent and self-identification of medications barriers (per 1 point; OR 1.57; 95% CI, 1.15–2.15) were significantly associated with nonadherence. No relationship between nonadherence and subsequent frequency of healthcare utilization was observed. A trend toward increased subsequent steroid resistance classification was seen with nonadherence, though not statistically significant.


Medication nonadherence is common in pediatric nephrotic syndrome. Investigations into the use of surveys in the clinic setting to identify at-risk patients and ways to support families over time are needed.

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Data availability

Datasets generated and/or analyzed during the current study are available in the NEPTUNE data repository. Interested researchers can contact NEPTUNE at studies for data access.


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We are indebted to the patients and families who graciously participated in this research study. We would also like to thank all members of the NEPTUNE consortium listed below:

Members of the Nephrotic Syndrome Study Network (NEPTUNE)

NEPTUNE Enrolling Centers

Cleveland Clinic, Cleveland, OH: K Dell*, J Sedor**, M Schachere#, J Negrey#

Children’s Hospital, Los Angeles, CA: K Lemley*, B Silesky#

Children’s Mercy Hospital, Kansas City, MO: T Srivastava*, A Garrett#

Cohen Children’s Hospital, New Hyde Park, NY: C Sethna*, O Bullaro #

Columbia University, New York, NY: P Canetta*, A Pradhan#

Emory University, Atlanta, GA: L Greenbaum*, C Wang**, C Kang#

Harbor-University of California Los Angeles Medical Center: S Adler*, J LaPage#

John H Stroger Jr. Hospital of Cook County, Chicago, IL: A Athavale*, M Itteera

Johns Hopkins Medicine, Baltimore, MD: M Atkinson*, T Dell#

Mayo Clinic, Rochester, MN: F Fervenza*, M Hogan**, J Lieske*, V Chernitskiy#

Montefiore Medical Center, Bronx, NY: F Kaskel*, M Ross*, P Flynn#

NIDDK Intramural, Bethesda MD: J Kopp*, J Blake#

New York University Medical Center, New York, NY: H Trachtman*, O Zhdanova**, F Modersitzki#, S Vento#

Stanford University, Stanford, CA: R Lafayette*, K Mehta#

Temple University, Philadelphia, PA: C Gadegbeku*, S Quinn-Boyle#

University Health Network, Toronto: M Hladunewich**, H Reich**, P Ling#, M Romano#

University of Miami, Miami, FL: A Fornoni*, C Bidot#

University of Michigan, Ann Arbor, MI: M Kretzler*, D Gipson*, A Williams#, C Klida#

University of North Carolina, Chapel Hill, NC: V Derebail*, K Gibson*, E Cole#, J Ormond-Foster#

University of Pennsylvania, Philadelphia, PA: L Holzman*, K Meyers**, K Kallem#, A Swenson#

University of Texas Southwestern, Dallas, TX: K Sambandam*, Z Wang#, M Rogers#

University of Washington, Seattle, WA: A Jefferson*, S Hingorani**, K Tuttle**§, M Bray #, E Pao#, A Cooper

Wake Forest University Baptist Health, Winston-Salem, NC: JJ Lin*, Stefanie Baker#

Data Analysis and Coordinating Center: M Kretzler*, L Barisoni**, J Bixler, H Desmond, S Eddy, D Fermin, C Gadegbeku**, B Gillespie**, D Gipson**, L Holzman**, V Kurtz, M Larkina, S Li, S Li, CC Lienczewski, J Liu, T Mainieri, L Mariani**, M Sampson**, J Sedor**, A Smith, A Williams, J Zee.

Digital Pathology Committee: Carmen Avila-Casado (University Health Network, Toronto), Serena Bagnasco (Johns Hopkins University), Joseph Gaut (Washington University in St Louis), Stephen Hewitt (National Cancer Institute), Jeff Hodgin (University of Michigan), Kevin Lemley (Children’s Hospital of Los Angeles), Laura Mariani (University of Michigan), Matthew Palmer (University of Pennsylvania), Avi Rosenberg (Johns Hopkins University), Virginie Royal (University of Montreal), David Thomas (University of Miami), Jarcy Zee (University of Pennsylvania). Co-Chairs: Laura Barisoni (Duke University) and Cynthia Nast (Cedar Sinai).

*Principal Investigator, **Co-investigator, #Study Coordinator

§Providence Medical Research Center, Spokane, WA


The Nephrotic Syndrome Study Network Consortium (NEPTUNE), U54-DK-083912, is a part of the National Institutes of Health (NIH) Rare Disease Clinical Research Network (RDCRN), supported through a collaboration between the Office of Rare Diseases Research, National Center for Advancing Translational Sciences and the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK). Additional funding and/or programmatic support for this project has also been provided by the University of Michigan, the NephCure Kidney International and the Halpin Foundation. Chia-shi Wang is supported by the NIH-NIDDK under Award Number K23DK118189. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Jonathan Troost was supported in part by the National Center for Advancing Translational Sciences (NCATS) for the Michigan Institute for Clinical and Health Research (UL1TR002240).

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Authors and Affiliations



All authors contributed to the study conception and design. Material preparation and data collection and analysis were performed by Chia-shi Wang, Jonathan P. Troost, Yujie Wang, Larry A Greenbaum, and Debbie S. Gipson. The first draft of the manuscript was written by Chia-shi Wang and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Chia-shi Wang.

Ethics declarations

Ethics approval

Institutional review board (IRB) approval for this study was obtained via the single IRB of record at the University of Michigan.

Consent to participate

Consent for study participation was obtained at NEPTUNE enrollment from the legal guardians of the minor participants. Assent was obtained where applicable according to single and local IRB guidelines.

Conflict of interest/Competing interest

Tarak Srivastava has received research funding from Bristol-Myers-Squibb, Retrophin, Mallinckrodt, and Alexion, and has consulted for Alnylam. Larry A. Greenbaum receives research support from Reata Pharmaceuticals and Vertex. He also serves as a consultant for Travere. Howard Trachtman has consultancy agreements through NYU Grossman School of Medicine with Travere Therapeurtics and Goldfinch Bio. He is a consultant to Otsuka and Chemocentryx as member of study data monitoring committees. Debbie S Gipson receives research support from Goldfinch Bio, Novartis, Travere, and Reata. She is a scientific advisor through the University of Michigan with Vertex and AstraZeneca. Kimberly Reidy is a site investigator for Advicienne- and Travere-sponsored clinical trials. Katherine Dell is a site investigator for Travere and AMGEN- sponsored clinical trials and has a consultancy agreement with Sanofi Genzyme.

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Wang, Cs., Troost, J.P., Wang, Y. et al. Determinants of medication adherence in childhood nephrotic syndrome and associations of adherence with clinical outcomes. Pediatr Nephrol 37, 1585–1595 (2022).

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