Recurrence of proteinuria 10 years post-transplant in NPHS2-associated focal segmental glomerulosclerosis after conversion from cyclosporin A to sirolimus

• Published in: Pediatric nephrology (Berlin, West) West), 2006-10, Vol.21 (10), p.1476-1479
• Main Authors: Höcker, Britta, Knüppel, Tanja, Waldherr, Rüdiger, Schaefer, Franz, Weber, Stefanie, Tönshoff, Burkhard
• Format: Article
• Language: English
• Subjects: Adolescent; Case studies; Complications and side effects; Cyclosporine; Cyclosporine - adverse effects; Cyclosporine - therapeutic use; Dosage and administration; Drug therapy; Female; Gene mutations; Glomerulosclerosis, Focal Segmental - etiology; Glomerulosclerosis, Focal Segmental - genetics; Glomerulosclerosis, Focal Segmental - pathology; Graft Rejection - pathology; Graft Rejection - prevention & control; Humans; Immunosuppressive Agents - adverse effects; Immunosuppressive Agents - therapeutic use; Intracellular Signaling Peptides and Proteins - genetics; Kidney Transplantation - immunology; Kidney Transplantation - pathology; Living Donors; Membrane Proteins - genetics; Mutation; Nephrotic syndrome; Nephrotic Syndrome - etiology; Nephrotic Syndrome - genetics; Nephrotic Syndrome - pathology; Proteinuria - etiology; Proteinuria - genetics; Proteinuria - pathology; Recurrence; Renal Insufficiency - surgery; Risk Factors; Sirolimus - therapeutic use; Time Factors
• ISSN: 0931-041X; 1432-198X
• DOI: 10.1007/s00467-006-0148-9

Mutations in the NPHS2 gene, which encodes podocin, are associated with steroid-resistant nephrotic syndrome in childhood. Renal histology frequently presents focal segmental glomerulosclerosis (FSGS). Post-transplant recurrence of proteinuria in patients affected by homozygous or compound heterozygous NPHS2 mutation is encountered rarely (1-2%) compared to 30% recurrence in nonhereditary FSGS. We report on a pediatric kidney transplant recipient with NPHS2-associated nephrotic syndrome and FSGS, who developed biopsy-proven recurrence of FSGS 10 years post-transplant in temporal association with conversion from cyclosporin A (CsA)- to sirolimus (SRL)-based immunosuppression, due to histological evidence of severe CsA-induced nephrotoxicity. Reswitch of the immunosuppressive regimen from SRL to CsA led to a noticeable decrease of proteinuria and to stabilization of graft function. We conclude that patients with hereditary FSGS are not entirely protected from post-transplant recurrence of proteinuria, even in the long term. The close temporal relationship of FSGS recurrence with CsA withdrawal and conversion to SRL suggests that caution should be exercised in the use of CsA-free immunosuppression also in patients with NPHS2-associated FSGS.