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Kidney Week

Abstract: TH-PO462

TRPC6 Nephropathy: An International Registry of Prevalence and Outcome

Session Information

Category: Genetic Diseases of the Kidneys

  • 1202 Genetic Diseases of the Kidneys: Non-Cystic

Authors

  • McAnallen, Susan Marie, Beaumont Hospital, Dublin, Ireland
  • Elhassan, Elhussein Aamir Elzein, Beaumont Hospital, Dublin, Ireland
  • White, Eoghan, Beaumont Hospital, Dublin, Ireland
  • Kidd, Kendrah O., Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
  • Gbadegesin, Rasheed A., Duke University School of Medicine, Durham, North Carolina, United States
  • Bleyer, Anthony J., Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
  • Conlon, Peter J., Beaumont Hospital, Dublin, Ireland

Group or Team Name

  • TRPC6 Research Group.
Background

Monogenic forms of focal segmental glomerulosclerosis(FSGS)represent an important subset of patients with nephrotic syndrome.They often have an ominous clinical course reaching end-stage renal disease(ESRD)at a young age.
Variants in TRPC6(a non-selective calcium channel)have been described to cause autosomal dominant ESRD.Most have been described as “activating”variants,resulting in increased influx of calcium into the podocyte,precipitating the sclerosing process.TRPC6 is a rare disease with many cases reported to date arising from a large New Zealand kindred.Recently,a compound targetingTRPC6has entered clinical trial-making understanding the natural history all the more important.

Methods

We established aTRPC6collaborative research group&developed a questionnaire focusing on natural history,variability in phenotype&gene variants.This has been circulated internationally to professionals involved in inherited kidney disease,nephrologists worldwide&those who have previously published onTRPC6.

Results

To date,we have received responses involving38patients worldwide(Europe,UK,Asia,Australia,New Zealand,North America and Africa)from 21 families,identifying17variants.The majority are missense, with commonest variants located on exons 2&13.Average age of genetic testing-32 years old.
All but three patients experienced symptoms before the age of 40(six were 10 years old or younger).Presentation varied from microalbuminuria to anasarca&pre-eclampsia;most presenting with nephrotic syndrome,six presented with ESRD.Four patients were found to have hearing impairment.18patients underwent renal biopsy,14(78%)demonstrated FSGS.
19patients progressed to ESRD-median age of 29 years old.12 patients have undergone transplantation(10 of which are still functioning).Three patients have had recurrence of nephrotic syndrome,two of which still have graft function.The third patient lost graft function after two years,aged 28.One patient died from complications related to dialysis.To the best of our knowledge the remaining are alive with self-supporting renal function&varying degrees of CKD.

Conclusion

TRPC6 is a rare cause of monogenic ESRD presenting with nephrotic syndrome.The condition shows considerable variability in disease progression.New treatments are becoming available in effort to reduce immunosuppression burden.