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Kidney Week

Abstract: FR-PO0939

Autoantibodies Targeting Nephrin and CRB2 in Children with Nephrotic Syndrome

Session Information

Category: Pediatric Nephrology

  • 1800 Pediatric Nephrology

Authors

  • Robinson, Cal, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Leclerc, Simon, McGill University, Montreal, Quebec, Canada
  • Aman, Nowrin F., The Hospital for Sick Children, Toronto, Ontario, Canada
  • Aoudjit, Lamine, McGill University, Montreal, Quebec, Canada
  • Banh, Tonny Hue Minh, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Brooke, Josefina A., The Hospital for Sick Children, Toronto, Ontario, Canada
  • Bruno, Valentina, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Dhillon, Vaneet, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Garner, Mackenzie Alexander, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Licht, Christoph, The Hospital for Sick Children, Toronto, Ontario, Canada
  • McKay, Ashlene Maree, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Molinaro, Alessia Maria Carmela, McGill University, Montreal, Quebec, Canada
  • Noone, Damien Gerard, University of Alberta, Edmonton, Alberta, Canada
  • Pearl, Rachel Jane, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Radhakrishnan, Seetha, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Selvathesan, Nithiakishna, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Teoh, Chia Wei, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Vanos Hosick, Kristen, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Vasilevska-Ristovska, Jovanka, The Hospital for Sick Children, Toronto, Ontario, Canada
  • Takano, Tomoko, McGill University, Montreal, Quebec, Canada
  • Weins, Astrid, Mass General Brigham Inc, Boston, Massachusetts, United States
  • Parekh, Rulan S., Women's College Hospital, Toronto, Ontario, Canada
Background

Nephrotic syndrome is a common immune-mediated glomerular disorder among children. Autoantibodies targeting nephrin and CRB2 have been found among children and adults with nephrotic syndrome, although their pathophysiological role remains unclear. Our aims were to determine the prevalence of anti-nephrin and -CRB2 antibodies in childhood nephrotic syndrome and examine associations with outcomes and immunosuppression response.

Methods

We included children with primary nephrotic syndrome enrolled in a prospective Canadian cohort with specimens collected during relapse and remission. Anti-nephrin and -CRB2 antibodies were measured by ELISA. We evaluated associations between autoantibodies and steroid resistance, time-to-first relapse, frequent relapses or steroid dependence, relapse rate, and steroid-sparing immunosuppression response by regression analysis.

Results

Anti-nephrin and -CRB2 antibodies were measured in 298 samples from 149 children at median (IQR) 1.5 (0.5-4.5) years from nephrotic syndrome diagnosis. Anti-nephrin and -CRB2 antibodies were positive in 50 (33%) and 7 (5%) of relapse samples, respectively. Anti-nephrin and -CRB2 titers were significantly higher in relapse than remission (p<0.001). Positive anti-nephrin antibodies were more common in South, East, and Southeast Asian children (36-42%); those with frequent relapses or steroid dependence (42%); and minimal change disease (42%). Positive anti-CRB2 antibodies were more common in European children (7%) and those with focal segmental glomerulosclerosis (11%). There were no significant associations between anti-nephrin or -CRB2 antibody titer or positivity and time-to-first relapse or relapse rate (Table), or with sustained remission after initiating specific steroid-sparing immunosuppressive medications (all p>0.05).

Conclusion

Anti-nephrin and -CRB2 antibodies are found in less than one-third of children with nephrotic syndrome and titers correlate with relapses. Yet, we did not find evidence of associations with relapse rate or immunosuppression response. Thus, predictive utility in children remains uncertain.

Associations between autoantibodies and nephrotic syndrome relapses
AutoantibodyOutcomeAutoantibody titerUnadjusted estimate (95%CI)p-value
Antinephrin antibodies (in RU/mL)Time to first relapseQuartile 1 (<21.6)
Quartile 2 (21.6-70.8)
Quartile 3 (70.8-172.1)
Quartile 4 (>172.1)
Ref
HR 1.39 (0.80-2.40)
HR 0.93 (0.51-1.71)
HR 1.10 (0.62-1.97)
0.91 (trend)
Relapse rate throughout follow-upQuartile 1 (<21.6)
Quartile 2 (21.6-70.8)
Quartile 3 (70.8-172.1)
Quartile 4 (>172.1)
Ref
RR 1.22 (0.87-1.71)
RR 1.34 (0.96-1.87)
RR 1.26 (0.90-1.77)
0.14 (trend)
Anti-CRB2 antibodies (in µg/mL)Time to first relapseQuartile 1 (<10.7)
Quartile 2 (10.7-21.6)
Quartile 3 (21.6-33.3)
Quartile 4 (>33.3)
Ref
HR 1.00 (0.54-1.84)
HR 1.39 (0.78-2.49)
HR 1.21 (0.68-2.18)
0.33 (trend)
Relapse rate throughout follow-upQuartile 1 (<10.7)
Quartile 2 (10.7-21.6)
Quartile 3 (21.6-33.3)
Quartile 4 (>33.3)
Ref
RR 0.99 (0.72-1.35)
RR 0.85 (0.62-1.17)
RR 0.76 (0.55-1.05)
0.07 (trend)

Funding

  • Government Support – Non-U.S.