Podocin-related mechanisms in posttransplant [corrected] recurrence of focal segmental glomerulosclerosis [corrected].
Posttransplantation recurrence of focal segmental glomerulosclerosis (FSGS) is one of the most disarming events in human pathology with important social and psychological consequences. It usually occurs in 30% to 50% of patients affected by the primary form of the disease with an abrupt onset in the majority of cases occurring within 1 month of the transplantation. Prediction of recurrent cases and early therapy with plasmapheresis are the main goals of the therapy. Although the mechanism of posttransplantation recurrence is still obscure, it has been proposed to be of a multifactorial origin, in which plasma factors determine the shedding of proteins of the slit-diaphragm, such as nephrin and podocin, with structural alterations of the ultra-filtering unit of the glomerulus. Low resynthesis of podocin and/or haplo-insufficiency due to heterozygous mutations should represent significant predisposing factors to proteinuria. In this review, the role of podocin in posttransplantation recurrence will be evaluated focusing on the possibility that resynthesis of the protein could represent a key step also for stable normalization of the renal filter. The recent characterization of the podocin promoter cis- and trans- acting elements and the possibility to characterize low- and high-podocin producer haplotypes offer opportunities to evaluate the capacity for podocin resynthesis in the donor kidney. A review of the literature on posttransplantation recurrence of FSGS in patients originally carrying homozygous and/or heterozygous NPHS2 mutations supports the general idea of a multifactorial origin of the primary disease that can be extended to the pathogenesis of posttransplantation recurrence.
Caridi
G
G
Laboratory on Pathophysiology of Uremia, Istituto Giannina Gaslini, Genova, Italy.
Dagnino
M
M
Sanna-Cherchi
S
S
Perfumo
F
F
Ghiggeri
G M
GM
D006580:Genetic Carrier Screening; D005923:Glomerulosclerosis, Focal Segmental / Q000235:genetics* / Q000473:pathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D016030:Kidney Transplantation / Q000473:pathology*; D008565:Membrane Proteins / Q000235:genetics*; D009154:Mutation; D011183:Postoperative Complications / Q000175:diagnosis*; D012008:Recurrence
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C407223:NPHS2 protein