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Abstract: TH-OR119

Response to Intensified Immunosuppression in Genetically-Stratified SRNS Patients Predicts Outcomes and Indicates Distinct Underlying Mechanisms

Session Information

Category: Pediatric Nephrology

  • 1700 Pediatric Nephrology

Authors

  • Saleem, Moin, University of Bristol, Bristol, United Kingdom
  • Mason, Anna E., University of Bristol, Bristol, United Kingdom
  • Sen, Ethan S., University of Bristol, Bristol, United Kingdom
  • Bierzynska, Agnieszka, University of Bristol, Bristol, United Kingdom
  • Colby, Liz, University of Bristol, Bristol, United Kingdom
  • Afzal, Maryam, University of Bristol, Bristol, United Kingdom
  • Koziell, Ania B., Kings College London, London, United Kingdom
  • Boyer, Olivia, Hopital Necker - Enfants Malades, Paris, France
  • Welsh, Gavin Iain, University of Bristol, Bristol, United Kingdom
Background

We previously showed that secondary steroid resistance (SSR) in nephrotic syndrome is a reliable predictor of circulating factor disease that recurs post-transplantation. This follow-up study aimed to improve disease stratification by determining if response to intensified immunosuppression (IIS) in genetically-screened SRNS predicts disease progression and/or recurrence.

Methods

Paediatric patients with steroid resistant nephrotic syndrome (SRNS) were recruited via the United Kingdom RaDaR registry. 274 patients were whole genome, whole exome or SRNS-gene-panel sequenced. Complete response (CR) or partial response within six months of starting IIS was ascertained.

Results

Of 274 patients, 180 (93 male, median onset age 4.7 years, 99 focal segmental glomerulosclerosis) received IIS medications with responses available. 3.8% of monogenic disease patients showed CR, compared to 25.2% of genetic-testing negative (GTN) patients (p=0.018). None of the former recurred post-transplantation. In GTN patients, 97.4% with CR to first IIS showed no progression, whereas 43.2% of non-responders developed renal failure with 73.1% recurrence post-transplant. SSR had a higher CR rate than primary/presumed resistance (42.5% vs 23.0%, p=0.0014). Highest CR rate was to Rituximab (64.3%). Biopsy findings showed no correlation with response to IIS or outcome.

Conclusion

This stratifies SRNS into three subgroups of prognostic utility based on genotype-phenotype correlation: monogenic disease responds poorly to IIS but doesn’t recur, GTN SRNS that responding early to IIS with good long-term outcome, and multi-drug resistant GTN SRNS with poor renal survival and high post-transplant recurrence risk. This supports at least two different underlying immune mechanisms in non-genetic SRNS, able to determine disease outcome.