ESPN 51th Annual Meeting

ESPN 2018


 
Response to Intensified Immunosuppression in genetically stratified SRNS patients predicts clinical outcome, and suggests distinct circulating factor mechanisms
ETNAN SEN AGNIESZKA BIERZYNSKA GAVIN WELSH MOIN SALEEM 1

1- UNIVERSITY OF BRISTOL, CHILDRENS RENAL UNIT
 
Introduction:

We previously showed that secondary steroid resistance is the most reliable predictor of circulating factor disease (CFD) that recurs post-transplantation (Ding et al J Am Soc Nephrol 2015). We aimed to advance this stratification, by determining if response to intensified immunosuppression (IIS) predicts progression and recurrence in SRNS

Material and methods:

Paediatric patients with SRNS were recruited via the United Kingdom NephroS registry. Complete response (CR) or partial response (PR) within 6 months of starting therapy was ascertained. Genetic analysis was achieved by whole exome sequencing or the Bristol SRNS extended gene panel.

Results:

177 genetically-sequenced patients were identified. 140 (72 male, median age at onset 4.4 years, 80 FSGS on first biopsy) received 298 IIS medications.

1. There was no overall difference in CR between all IIS treatments. When considering only first immunosuppressive treatments in non-genetic patients, there was CR to ciclosporin in 36.5% (19/52), to tacrolimus in 33.3% (9/27) and to cyclophosphamide in 11.5% (3/26).

2. Biopsy findings showed no correlation with either outcome, or response to IIS

3. 87.5% of patients with genetic disease showed no or partial response to IIS

3. In patients testing negative for genetic disease, those with secondary steroid resistance had a significantly higher response rate than those with primary steroid resistance (41.5 vs 21.8%), and the highest response rate was to Rituximab (66.7%)

4. Strikingly, 93% of patients who responded to 1st IIS showed no progression (ERF), after up to 10 years of follow-up.

5. 74.3% of non-responders progressed to established renal failure (ERF) within the follow up period, with 50% recurrence rate post-transplant

6. 50% of Rituximab non-responders relapsed post-transplant, and remain resistant to therapy

 

Conclusions:

This study stratifies non-genetic patients into responders and non-responders to IIS, with markedly different outcomes, and strongly suggests two distinct underlying immune mechanisms.