Growth in children with nephrotic syndrome: a post hoc analysis of the NEPTUNE study

Aesha Maniar; Debbie S Gipson; Tammy Brady; Tarak Srivastava; David T Selewski; Larry A Greenbaum; Katherine M Dell; Frederick Kaskel; Susan Massengill; Cheryl Tran; Howard Trachtman; Richard Lafayette; Salem Almaani; Sangeeta Hingorani; Chia-Shi Wang; Kimberly Reidy; Gabriel Cara-Fuentes; Rasheed Gbadegesin; Kevin Myers; Christine B Sethna; Members of the Nephrotic Syndrome Study Network (NEPTUNE)

doi:10.1007/s00467-024-06375-9

Growth in children with nephrotic syndrome: a post hoc analysis of the NEPTUNE study

Pediatr Nephrol. 2024 Apr 26. doi: 10.1007/s00467-024-06375-9. Online ahead of print.

Authors

Aesha Maniar¹, Debbie S Gipson², Tammy Brady³, Tarak Srivastava⁴, David T Selewski⁵, Larry A Greenbaum⁶, Katherine M Dell⁷, Frederick Kaskel⁸, Susan Massengill⁹, Cheryl Tran¹⁰, Howard Trachtman², Richard Lafayette¹¹, Salem Almaani¹², Sangeeta Hingorani¹³, Chia-Shi Wang⁶, Kimberly Reidy⁸, Gabriel Cara-Fuentes¹⁴, Rasheed Gbadegesin¹⁵, Kevin Myers¹⁶, Christine B Sethna¹⁷; Members of the Nephrotic Syndrome Study Network (NEPTUNE)

Collaborators

Members of the Nephrotic Syndrome Study Network (NEPTUNE):
M Schachere, J Negrey, J Scott, S Morrison, M Pfaiff, P Canetta, A Pradhan, E Yun, S Adler, J LaPage, A Athavale, M Itteera, M Atkinson, T Dell, F Fervenza, M Hogan, J Lieske, G Hill, M Ross, P Flynn, J Kopp, L Malaga-Dieguez, O Zhdanova, F Modersitzki, L Pehrson, B Yeung, I Lee, S Quinn-Boyle, H Reich, M Hladunewich, P Ling, M Romano, A Fornoni, C Bidot, C Klida, V Derebail, K Gibson, A Froment, F Ochoa-Toro, K Meyers, K Kallem, A Swenson, K Sambandam, K Aleman, M Rogers, A Jefferson, K Tuttle, L Manahan, E Pao, A Copper, J J Lin, Stefanie Baker, M Kretzler, L Barisoni, C Gadegbeku, B Gillespie, L Holzman, L Mariani, M Sampson, J Sedor, J Zee, G Alter, H Desmond, S Eddy, D Fermin, M Larkina, S Li, S Li, C C Lienczewski, T Mainieri, R Scherr, A Smith, A Szymanski, A Williams, Carmen Avila-Casado, Serena Bagnasco, Joseph Gaut, Stephen Hewitt, Jeff Hodgin, Kevin Lemley, Matthew Palmer, Avi Rosenberg, Virginie Royal, David Thomas, Cynthia Nast

Affiliations

¹ Division of Nephrology, Department of Pediatrics, Stanford University, Palo Alto, CA, USA.
² Division of Nephrology, Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA.
³ Division of Nephrology, Department of Pediatrics, Johns Hopkins, Baltimore, MD, USA.
⁴ Division of Nephrology, Children's Mercy Hospital and University of Missouri at Kansas City, Kansas City, MO, USA.
⁵ Division of Pediatric Nephrology, Department of Pediatrics, Medical University of South Carolina, Charleston, SC, USA.
⁶ Division of Nephrology, Department of Pediatrics, Emory University and Children's Healthcare of Atlanta, Atlanta, GA, USA.
⁷ Center for Pediatric Nephrology and Hypertension, Cleveland Clinic Children's, Department of Pediatrics, Case Western Reserve University, Cleveland, OH, USA.
⁸ Division of Nephrology, Department of Pediatrics, Children's Hospital at Montefiore, Bronx, NY, USA.
⁹ Division of Nephrology, Department of Pediatrics, Levine Children's Hospital, Charlotte, NC, USA.
¹⁰ Division of Nephrology, Department of Pediatrics, Mayo Clinic, Rochester, MN, USA.
¹¹ Division of Nephrology, Department of Medicine, Stanford University, Palo Alto, CA, USA.
¹² Division of Nephrology, Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
¹³ Division of Nephrology, Department of Pediatrics, University of Washington, Seattle, WA, USA.
¹⁴ Division of Nephrology, Department of Pediatrics, Children's Hospital Colorado, Aurora, CO, USA.
¹⁵ Division of Nephrology, Duke School of Medicine, Durham, NC, USA.
¹⁶ Division of Nephrology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
¹⁷ Division of Pediatric Nephrology, Northwell, Cohen Children's Medical Center, 2000 Marcus Ave, Suite 300, New Hyde Park, Northwell, NY, 11042-1069, USA. csethna@northwell.edu.

PMID: 38671228
DOI: 10.1007/s00467-024-06375-9

Abstract

Background: Steroids, the mainstay of treatment for nephrotic syndrome in children, have multiple adverse effects including growth suppression.

Methods: Anthropometric measurements in children < 18 years enrolled in the Nephrotic Syndrome Study Network (NEPTUNE) were collected. The longitudinal association of medication exposure and nephrotic syndrome characteristics with height z-score and growth velocity was determined using adjusted Generalized Estimating Equation regression and linear regression.

Results: A total of 318 children (57.2% males) with a baseline age of 7.64 ± 5.04 years were analyzed. The cumulative steroid dose was 216.4 (IQR 61.5, 652.7) mg/kg (N = 233). Overall, height z-scores were not significantly different at the last follow-up compared to baseline (- 0.13 ± 1.21 vs. - 0.23 ± 1.71, p = 0.21). In models adjusted for age, sex, and eGFR, greater cumulative steroid exposure (β - 7.5 × 10^-6, CI - 1.2 × 10^-5, - 3 × 10^-6, p = 0.001) and incident cases of NS (vs. prevalent) (β - 1.1, CI - 2.22, - 0.11, p = 0.03) were significantly associated with lower height z-scores over time. Rituximab exposure was associated with higher height z-scores (β 0.16, CI 0.04, 0.29, p = 0.01) over time.

Conclusion: Steroid dose was associated with lower height z-score, while rituximab use was associated with higher height z-score.

Keywords: Body mass index (BMI); Height; Nephrotic syndrome; Steroids; Weight.