A Systematic Review and Meta-Analysis of the Rate and Risk Factors for Post-transplant Disease Recurrence in Children With Steroid Resistant Nephrotic Syndrome

William Morello; Emanuele Proverbio; Giuseppe Puccio; Giovanni Montini

doi:10.1016/j.ekir.2022.10.030

A Systematic Review and Meta-Analysis of the Rate and Risk Factors for Post-transplant Disease Recurrence in Children With Steroid Resistant Nephrotic Syndrome

Kidney Int Rep. 2022 Nov 8;8(2):254-264. doi: 10.1016/j.ekir.2022.10.030. eCollection 2023 Feb.

Authors

William Morello¹, Emanuele Proverbio¹, Giuseppe Puccio¹, Giovanni Montini^{1

2}

Affiliations

¹ Pediatric Nephrology, Dialysis and Transplant Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milano, Italy.
² Department of Clinical Sciences and Community Health, University of Milan, Italy.

Abstract

Introduction: Posttransplant disease recurrence is a feared and severe complication in children with steroid resistant nephrotic syndrome (SRNS), but little is known about its incidence. Recent data suggest relapse is exceptional in patients with genetic SRNS, and initial steroid sensitivity may represent a risk factor for recurrence.

Methods: Systematic review and meta-analysis were performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to describe the post-transplant relapse rate among children with SRNS; as well as the association between recurrence and all potential risk factors, including the presence of causative genetic mutations, initial steroid sensitivity, underlying histology, and gender. The inclusion criteria were as follows: (i) children with SRNS who are undergoing kidney transplant, (ii) available data on post-transplant recurrence, (iii) no patient selection according to the underlying histology, (iv) available data on genetic testing, and (v) prospective or retrospective cohort design.

Results: Of the 5818 records identified, 8 studies including 581 children with SRNS met the inclusion criteria. Overall posttransplant recurrence rate was 39% (95% confidence interval [CI] 34%-44%). No genetic patient relapsed, whereas the recurrence rate in patients with no causative genetic mutation identified was 61% (95% CI 53%-69%). Children with initial steroid sensitivity were at a higher risk for recurrence with a 1.91 relative risk (RR) (95% CI 1.48-2.46) compared with those with primary SRNS (PSRNS). Gender and histology did not significantly affect relapse rate.

Conclusion: Post-transplant recurrence is a common event in children with idiopathic non-genetic SRNS, complicating the clinical course in over 60% of patients. The presence of a causative genetic mutation virtually excludes a recurrence. Initial steroid sensitivity is the only other significant risk factor, doubling the risk of relapse.

Keywords: children; genetic SRNS; kidney transplant; meta-analysis; posttransplant recurrence; steroid resistant nephrotic syndrome.