title: NPHS2 mutation associated with recurrence of proteinuria after transplantation.
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.
authors.affiliation: Department of Pediatric Nephrology, Charité Hospital, Augustenburger Platz 1, 13353 Berlin, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Billing
authors.forename: Dominik
authors.initials: D
authors.lastname: Müller
authors.forename: Rainer
authors.initials: R
authors.lastname: Ruf
authors.forename: Anne
authors.initials: A
authors.lastname: Lichtenberger
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
authors.forename: Christian
authors.initials: C
authors.lastname: August
authors.forename: Uwe
authors.initials: U
authors.lastname: Querfeld
authors.forename: Dieter
authors.initials: D
authors.lastname: Haffner
mesh_terms: D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D004247:DNA / Q000096:biosynthesis / Q000302:isolation & purification; D005260:Female; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications / Q000601:surgery; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007676:Kidney Failure, Chronic / Q000209:etiology / Q000601:surgery; D016030:Kidney Transplantation / Q000502:physiology*; D008565:Membrane Proteins / Q000235:genetics*; D008775:Methylprednisolone / Q000627:therapeutic use; D009154:Mutation; D009404:Nephrotic Syndrome / Q000150:complications / Q000601:surgery; D011507:Proteinuria / Q000188:drug therapy / Q000235:genetics*; D012008:Recurrence
chemical_list: D000893:Anti-Inflammatory Agents; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein; D004247:DNA; D008775:Methylprednisolone