O52
INITIAL STEROID-SENSITIVITY IN CHILDREN WITH STEROID-RESISTANT
NEPHROTIC SYNDROME PREDICTS POST-TRANSPLANT RECURRENCE
Wen Y Ding1,2*, Ania Koziell4,5*, Hugh J McCarthy1,2, Agnieszka Bierzynska2, Murali K
Bhagavatula3, Jan A Dudley1, Carol D Inward1, Richard J Coward1,2, Jane Tizard1,
Christopher Reid4, Corinne Antignac6, Olivia Boyer6, Moin A Saleem1,2
1. Department of Paediatric Nephrology, Bristol Royal Hospital for Children
2. Academic Renal Unit, University of Bristol
3. Children’s Hospital for Wales
4. Department of Paediatric Nephrology, Evelina Children’s Hospital
5. Department of Experimental Immunobiology, King’s College London
6. Néphrologie Pédiatrique & INSERM U983, Hôpital Necker-Enfants Malades
*Joint first authors
INTRODUCTION: Steroid-resistant nephrotic syndrome (SRNS) is a disease with significant
morbidity where many affected children progress to end-stage renal failure (ESRF). 30-50% of
transplanted patients suffer from a recurrence of disease and as yet, we have no robust clinical
or biochemical indicators that predict recurrence. A proportion of SRNS is genetic, and studies
have shown that those with mutations are resistant to immunosuppression but have a low posttransplant recurrence rate of 0-3%. It is believed that an immunologically-derived circulating
factor underlies post-transplant recurrence of SRNS. We hypothesised that SRNS can be
broadly classified into 2 groups: those with a genetic mutation who are immunosuppression
resistant with low post-transplant recurrence rates; and those with a circulating factor who
initially respond to steroids with high post-transplant recurrence rates.
METHODS: We retrospectively reviewed 150 paediatric SRNS patients who received
transplants at the 3 large European paediatric nephrology centres. We collected data on clinical
characteristics including sex, race, age at diagnosis, time to ESRF, time on dialysis, age at
transplant, initial steroid-sensitivity at presentation, genetic mutations, family history, extrarenal abnormalities, recurrence, rejection, and graft loss.
RESULTS: 25/150 children had genetic or familial SRNS and none of these showed recurrence
post-transplant. Of the remaining 125 patients, 57/125 (45.6%) patients developed posttransplant recurrence. 26/29 (89.7%) patients with initial steroid-sensitivity recurred posttransplant while only 26/86 (30.2%) of those resistant from the outset recurred (p<0.0001;
OR=30, 95%CI=6.62 to 135.86). (Figure 1) We were unable to determine recurrence in 2
patients and 8 patients did not receive steroids.
CONCLUSION: Our data shows for the first time that initial steroid-sensitivity is highly
predictive for post-transplant disease recurrence. Steroid-resistance from the outset and/or
genetic mutation significantly diminished risk. We propose that initial steroid response is a
surrogate marker for circulating factor disease, and show that this progresses to posttransplantation recurrence in approaching 100% of patients. These findings will enable patients
to be counselled appropriately and targeted for intensive therapy in the earlier stages of their
disease as well as during the peri-transplant period.
Figure 1 Forest plot for odds ratios for recurrence
Age at Diagnosis<6 years
Time to ESRF<3 years
st
Age of 1 Transplant<12 years
Time on dialysis<2 years
African-European
Donor Type
Initial Steroid Sensitivity
0.1
1
10
Odds ratio for recurrence
100
1000