Abstract: FR-OR024

Response to Second-Line Immunosuppressive Treatments in Genetically Stratified Steroid-Resistant Nephrotic Syndrome

Session Information

Category: Glomerular

  • 1005 Clinical Glomerular Disorders

Authors

  • Sen, Ethan S, University of Bristol, Bristol, United Kingdom
  • Bierzynska, Agnieszka, University of Bristol, Bristol, United Kingdom
  • Welsh, Gavin Iain, University of Bristol, Bristol, United Kingdom
  • Saleem, Moin, University of Bristol, Bristol, United Kingdom
Background

Steroid-resistant nephrotic syndrome (SRNS) is a heterogeneous condition with significant numbers of patients progressing to end-stage renal failure. Response to second-line immunosuppression is variable. This study aimed to evaluate effectiveness of second-line treatment according to genetic aetiology and pattern of steroid resistance.

Methods

Paediatric patients with SRNS were recruited into the United Kingdom Renal Registry. We have previously reported whole exome sequencing of these patients (Bierzynska et al. KI 2017;91:937-947). The current study included subjects from this group with available data on response to immunosuppression. Complete response (CR) was defined as urine protein:creatinine ratio (PCR) < 20mg/mmol or negative/trace dipstick proteinuria within 6 months of starting therapy. Partial response (PR) was PCR > 20mg/mmol or dipstick ≥ 1+ but plasma albumin > 25g/L.

Results

Of 177 genetically-sequenced patients, 140 (72 male, median age at onset 4.4 years, 80 FSGS on first biopsy) received 298 second-line medications. These included ciclosporin in 64%, tacrolimus 51%, cyclophosphamide 33%, mycophenolate mofetil 29% and rituximab 27%. In 21 monogenic patients (33 treatments), overall CR was 9.1% and PR was 36.4% compared with 31.4% and 25.2% respectively in 119 non-genetic patients (242 treatments). Within the non-genetic group, among 92 patients with presumed or primary steroid resistance (SR) (178 treatments), overall CR was 27.0% and PR was 26.4% compared with 43.3% and 21.7% respectively in 25 patients with secondary SR (60 treatments). Fifteen patients suffered post-transplant disease recurrence among whom pre-transplant CR and PR were both 5.9% (34 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).

Conclusion

CR occurred most frequently in patients with secondary SR, followed by non-genetic primary SR and then patients with genetic disease. Subjects retrospectively identified as having circulating factor disease based on post-transplant recurrence had a particularly poor response to immunosuppression.

Funding

  • Private Foundation Support