Recurrence of nephrotic syndrome following kidney transplantation is associated with initial native kidney biopsy findings

• Type of Material: Article
• Authors: Jonathan H. Pelletier, Duke University; Karan R. Kumar, Duke University; Rachel Engen, Ann & Robert H. Lurie Children’s Hospital of Chicago; Adam Bensimhon, Duke University; Jennifer D. Varner, Duke University; Michelle N. Rheault, University of Minnesota; Tarak Srivastava, Children's Mercy Hospital; Caroline Straatmann, Louisiana State University; Cynthia Silva, Connecticut Children's Medical Center; T. Keefe Davis, St. Louis Children's Hospital; Scott E. Wenderfer, Texas Children's Hospital; Keisha Gibson, North Carolina Children's Hospital; David Selewski, C.S. Mott Children’s Hospital; John Barcia, University of Virginia; Patricia Weng, University of California, Los Angeles; Christoph Licht, Hospital for Sick Children; Natasha Jawa, Hospital for Sick Children; Mahmoud Kallash, Nationwide Children’s Hospital; John W. Foreman, Duke University; Delbert R. Wigfall, Duke University; Annabelle N. Chua, Duke University; Eileen Chambers, Duke University; Christoph P. Hornik, Duke University; Eileen D. Brewer, Texas Children’s Hospital; Shashi K. Nagaraj, Duke University; Larry Greenbaum, Emory University; Rasheed A. Gbadegesin, Duke University
• Language: English
• Date: 2018-10-01
• Publisher: Springer Verlag (Germany)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2018, IPNA.
• Final Published Version (URL): http://dx.doi.org/10.1007/s00467-018-3994-3
• Title of Journal or Parent Work: Pediatric Nephrology
• ISSN: 0931-041X
• Volume: 33
• Issue: 10
• Start Page: 1773
• End Page: 1780
• Grant/Funding Information: JHP, KK and AB are supported by the Duke Pediatric Research Scholar (DPRS) program.; RG and JDV are recipients of the Doris Duke Clinical Research Mentorship grant award.; National Institute of Health (NIH) and National Institute of Diabetes, Digestive and Kidney Disease (NIDDK) 5R01DK098135 and 5R01DK094987 to RG.
• Keywords: INFANTS; Life Sciences & Biomedicine; VOIDING CYSTOURETHROGRAPHY; Focal segmental glomerulosclerosis; Nephrosis; VESICOURETERAL REFLUX; Science & Technology; ULTRASOUND; FETAL HYDRONEPHROSIS; DETECTED HYDRONEPHROSIS; Urology & Nephrology; ANTENATAL HYDRONEPHROSIS; Transplantation; URINARY-TRACT-INFECTION; Lipoid; Pediatrics; DILATION; Nephrotic syndrome; SYSTEM; Immunosuppression
• Research Categories: Health Sciences, Medicine and Surgery

Abstract

Background and objectives: Steroid-resistant nephrotic syndrome (SRNS) due to focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD) is a leading cause of end-stage kidney disease in children. Recurrence of primary disease following transplantation is a major cause of allograft loss. The clinical determinants of disease recurrence are not completely known. Our objectives were to determine risk factors for recurrence of FSGS/MCD following kidney transplantation and factors that predict response to immunosuppression following recurrence. Methods: Multicenter study of pediatric patients with kidney transplants performed for ESKD due to SRNS between 1/2006 and 12/2015. Demographics, clinical course, and biopsy data were collected. Patients with primary-SRNS (PSRNS) were defined as those initially resistant to corticosteroid therapy at diagnosis, and patients with late-SRNS (LSRNS) as those initially responsive to steroids who subsequently developed steroid resistance. We performed logistic regression to determine risk factors associated with nephrotic syndrome (NS) recurrence. Results: We analyzed 158 patients; 64 (41%) had recurrence of NS in their renal allograft. Disease recurrence occurred in 78% of patients with LSRNS compared to 39% of those with PSRNS. Patients with MCD on initial native kidney biopsy had a 76% recurrence rate compared with a 40% recurrence rate in those with FSGS. Multivariable analysis showed that MCD histology (OR; 95% CI 5.6; 1.3–23.7) compared to FSGS predicted disease recurrence. Conclusions: Pediatric patients with MCD and LSRNS are at higher risk of disease recurrence following kidney transplantation. These findings may be useful for designing studies to test strategies for preventing recurrence.