title: Initial steroid sensitivity in children with steroid-resistant nephrotic syndrome predicts post-transplant recurrence.
abstract: Of children with idiopathic nephrotic syndrome, 10%-20% fail to respond to steroids or develop secondary steroid resistance (termed initial steroid sensitivity) and the majority progress to transplantation. Although 30%-50% of these patients suffer disease recurrence after transplantation, with poor long-term outcome, no reliable indicator of recurrence has yet been identified. Notably, the incidence of recurrence after transplantation appears reduced in patients with steroid-resistant nephrotic syndrome (SRNS) due to monogenic disorders. We reviewed 150 transplanted patients with SRNS to identify biomarkers that consistently predict outcome of SRNS after transplantation. In all, 25 children had genetic or familial SRNS and did not experience post-transplant recurrence. We reviewed phenotypic factors, including initial steroid sensitivity, donor type, age, ethnicity, time to ESRD, and time on dialysis, in the remaining 125 children. Of these patients, 57 (45.6%) developed post-transplant recurrence; 26 of 28 (92.9%) patients with initial steroid sensitivity recurred after transplantation, whereas only 26 of 86 (30.2%) patients resistant from the outset recurred (odds ratio, 30; 95% confidence interval, 6.62 to 135.86; P<0.001). We were unable to determine recurrence in two patients (one with initial steroid sensitivity), and nine patients did not receive initial steroids. Our data show that initial steroid sensitivity is highly predictive of post-transplant disease recurrence in this pediatric patient population. Because a pathogenic circulating permeability factor in nephrotic syndrome remains to be confirmed, we propose initial steroid sensitivity as a surrogate marker for post-transplant recurrence.
authors: Department of Paediatric Nephrology, Bristol Royal Hospital for Children, Bristol, United Kingdom; Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, United Kingdom;
authors: Wen Y
authors: WY
authors: Ding
authors: Department of Paediatric Nephrology, Evelina Children's Hospital, London, United Kingdom; Department of Experimental Immunobiology, King's College London, Guy's Hospital, London, United Kingdom;
authors: Ania
authors: A
authors: Koziell
authors: Department of Paediatric Nephrology, Bristol Royal Hospital for Children, Bristol, United Kingdom; Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, United Kingdom;
authors: Hugh J
authors: HJ
authors: McCarthy
authors: Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, United Kingdom;
authors: Agnieszka
authors: A
authors: Bierzynska
authors: Children's Hospital for Wales, Cardiff, United Kingdom; and.
authors: Murali K
authors: MK
authors: Bhagavatula
authors: Department of Paediatric Nephrology, Bristol Royal Hospital for Children, Bristol, United Kingdom;
authors: Jan A
authors: JA
authors: Dudley
authors: Department of Paediatric Nephrology, Bristol Royal Hospital for Children, Bristol, United Kingdom;
authors: Carol D
authors: CD
authors: Inward
authors: Department of Paediatric Nephrology, Bristol Royal Hospital for Children, Bristol, United Kingdom; Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, United Kingdom;
authors: Richard J
authors: RJ
authors: Coward
authors: Department of Paediatric Nephrology, Bristol Royal Hospital for Children, Bristol, United Kingdom;
authors: Jane
authors: J
authors: Tizard
authors: Department of Paediatric Nephrology, Evelina Children's Hospital, London, United Kingdom;
authors: Christopher
authors: C
authors: Reid
authors: Pediatric Nephrology, French Institute of Health and Medical Research Unit 983, Necker Hospital for Sick Children, Paris, France.
authors: Corinne
authors: C
authors: Antignac
authors: Pediatric Nephrology, French Institute of Health and Medical Research Unit 983, Necker Hospital for Sick Children, Paris, France.
authors: Olivia
authors: O
authors: Boyer
authors: Department of Paediatric Nephrology, Bristol Royal Hospital for Children, Bristol, United Kingdom; Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, United Kingdom; m.saleem@bristol.ac.uk.
authors: Moin A
authors: MA
authors: Saleem
mesh_terms: D000293:Adolescent; D017677:Age Distribution; D017668:Age of Onset; D015415:Biomarkers / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance; D005260:Female; D006801:Humans; D007223:Infant; D007676:Kidney Failure, Chronic / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000601:surgery*; D016030:Kidney Transplantation; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000453:epidemiology / Q000235:genetics / Q000601:surgery*; D012008:Recurrence; D006435:Renal Dialysis; D012307:Risk Factors; D013256:Steroids / Q000627:therapeutic use*; D059467:Transcriptome
chemical_list: D015415:Biomarkers; D013256:Steroids