Journal of the American Society of Nephrology
Clinical Research
Initial Steroid Sensitivity in Children with Steroid-Resistant Nephrotic Syndrome Predicts Post-Transplant Recurrence
Ding, Wen Y.*,†; Koziell, Ania‡,§; McCarthy, Hugh J.*,†; Bierzynska, Agnieszka†; Bhagavatula, Murali K.‖; Dudley, Jan A.*; Inward, Carol D.*; Coward, Richard J.*,†; Tizard, Jane*; Reid, Christopher‡; Antignac, Corinne¶; Boyer, Olivia¶; Saleem, Moin A.*,†
*Department of Paediatric Nephrology, Bristol Royal Hospital for Children, Bristol, United Kingdom;
†Academic Renal Unit, University of Bristol, Southmead Hospital, Bristol, United Kingdom;
‡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;
‖Children’s Hospital for Wales, Cardiff, United Kingdom; and
¶Pediatric Nephrology, French Institute of Health and Medical Research Unit 983, Necker Hospital for Sick Children, Paris, France
W.Y.D. and A.K. contributed equally to this work.
Correspondence: Dr. Moin Saleem, Academic Renal Unit, University of Bristol, Second Floor, Learning and Research, Southmead Hospital, Bristol BS10 5NB, UK. Email: [email protected]
Received August 10, 2013
Accepted October 8, 2013
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.