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NPHS2 mutation associated with recurrence of proteinuria after transplantation

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Abstract

Mutations in the NPHS2 gene encoding podocin are associated with steroid-resistant nephrotic syndrome (SRNS) in childhood. Patients usually present with focal segmental glomerulosclerosis (FSGS). It is unclear to what extent SRNS due to NPHS2 mutations predisposes to recurrence of proteinuria/FSGS after renal transplantation (RTx). A 4-year-old girl with infantile SRNS was started on peritoneal dialysis because of end-stage renal disease due to FSGS. Mutational screening of the patient and her parents revealed a novel single nucleotide deletion in exon 8 of the NHPS2 gene (948delT), for which the patient was homozygous and her parents confirmed heterozygous asymptomatic carriers. At the age of 4.5 years the patient received a renal graft from her mother. On day 7 after RTx, the patient developed progressive proteinuria (urine protein/creatinine ratio 2.4 g/g), which responded within 1 week to prednisone pulse therapy, an increased cyclosporin A dosage, and ramipril therapy. The patient has maintained stable graft function and no further recurrence of proteinuria has been observed. In conclusion, patients with SRNS due to NPHS2 mutations are not protected from recurrence of proteinuria after RTx. The quick response to increased immunosuppression in our patient suggests an immune-mediated pathomechanism for recurrence of proteinuria.

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Authors and Affiliations

  1. Department of Pediatric Nephrology, Charité Hospital, Augustenburger Platz 1, 13353 Berlin, Germany

    Heiko Billing, Dominik Müller, Uwe Querfeld & Dieter Haffner

  2. Department of Pediatrics, University of Michigan, Ann Arbor, USA

    Rainer Ruf, Anne Lichtenberger & Friedhelm Hildebrandt

  3. Institute of Pathology, University of Münster, Germany

    Christian August

Authors
  1. Heiko Billing
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  2. Dominik Müller
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  3. Rainer Ruf
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  4. Anne Lichtenberger
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  5. Friedhelm Hildebrandt
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  6. Christian August
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  7. Uwe Querfeld
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  8. Dieter Haffner
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Correspondence to Dieter Haffner.

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Billing, H., Müller, D., Ruf, R. et al. NPHS2 mutation associated with recurrence of proteinuria after transplantation. Pediatr Nephrol 19, 561–564 (2004). https://doi.org/10.1007/s00467-003-1408-6

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  • DOI: https://doi.org/10.1007/s00467-003-1408-6

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