Recurrence of focal segmental glomerulosclerosis after renal transplantation in patients with mutations of podocin.
BACKGROUND
Posttransplant recurrence of focal segmental glomerulosclerosis (FSGS) occurs in a relevant proportion of FSGS patients and represents an important clinical emergency. It is taken as a proof of the existence of circulating permeability plasma factor(s) that are also putative effectors of original proteinuria in these patients. Familial forms of FSGS do not recur, but the discovery of numerous patients with sporadic FSGS and mutations of podocin (NPHS2, that is actually an inherited disease) who received a renal graft require a re-evaluation of the problem.


METHODS
To evaluate the incidence of posttransplant recurrence of FSGS in patients with NPHS2, the authors screened for podocin mutations in 53 patients with the clinical and pathologic stigmata of FSGS who had renal failure and who had undergone renal transplantation.Results. Twelve children were found to carry a homozygous (n9) or a heterozygous (n4) mutation of podocin and were classified, according to current criteria, as patients with inherited FSGS. In 5 patients of this group (38%), proteinuria recurred after renal graft and in 2, renal biopsy results showed recurrence of FSGS. Prerecurrence serum of 3 patients of this cohort was tested for antipodocin antibodies with indirect immuno-Western utilizing human podocyte extracts and were found negative. The rate of FSGS recurrence was comparable in non-NPHS2-FSGS children (12 of 27) and adults (3 of 13). Also clinical outcome of recurrence and response to plasmapheresis and immunosuppressors were comparable, suggesting a common mechanism.


CONCLUSIONS
These data show a high rate of FSGS recurrence in patients with NPHS2 mutations that is comparable with idiopathic FSGS and describe the successful therapeutic approach. Recurrence of an apparently inherited disease should stimulate a critical review of the mechanisms of recurrence and of original proteinuria in these cases.
Bertelli
Roberta
R
Laboratory on Pathophysiology of Uremia, G. Gaslini Children's Hospital,Genoa, Italy.
Ginevri
Fabrizio
F
Caridi
Gianluca
G
Dagnino
Monica
M
Sandrini
Silvio
S
Di Duca
Marco
M
Emma
Francesco
F
Sanna-Cherchi
Simone
S
Scolari
Francesco
F
Neri
Tauro Maria
TM
Murer
Luisa
L
Massella
Laura
L
Basile
Giancarlo
G
Rizzoni
Gianfranco
G
Perfumo
Francesco
F
Ghiggeri
Gian Marco
GM
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000494:pharmacology / Q000627:therapeutic use; D000328:Adult; D019943:Amino Acid Substitution; D002463:Cell Membrane Permeability / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D004351:Drug Resistance; D005260:Female; D005838:Genotype; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000378:metabolism / Q000601:surgery / Q000628:therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D047908:Intracellular Signaling Peptides and Proteins; D016030:Kidney Transplantation; D008297:Male; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics* / Q000502:physiology; D008875:Middle Aged; D016254:Mutagenesis, Insertional; D020125:Mutation, Missense; D009404:Nephrotic Syndrome / Q000209:etiology / Q000601:surgery; D010956:Plasmapheresis; D011507:Proteinuria / Q000209:etiology; D012008:Recurrence; D017384:Sequence Deletion
D000305:Adrenal Cortex Hormones; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein