Podocyte effacement closely links to suPAR levels at time of posttransplantation focal segmental glomerulosclerosis occurrence and improves with therapy. - 2013

Available online from MWHC library: 1996 - present, Available in print through MWHC library: 1999 - 2006

BACKGROUND: Focal segmental glomerulosclerosis (FSGS) recurs after kidney transplantation in more than 30% of cases and can lead to allograft loss. Serum soluble urokinase-type plasminogen activator receptor (suPAR) is implicated in the pathogenesis of native and recurrent FSGS. CONCLUSIONS: Podocyte effacement is the first pathologic manifestation of FSGS after transplantation. The degree of podocyte effacement correlates with suPAR levels at time of diagnosis. Response to therapy results in significant reduction of suPAR levels and complete or significant improvement of podocyte effacement. METHODS: We conducted a retrospective study of 25 adults with posttransplantation FSGS. We investigated the relationship between suPAR levels and podocyte changes and the impact of therapy on podocyte structure. We assessed response to therapy by improvement in proteinuria, allograft function, and resolution of histologic changes. RESULTS: A median (interquartile range) of 15 (10-23) plasmapheresis sessions was administered; 13 of the subjects also received rituximab. Median pretreatment suPAR levels were higher among those with severe (>75%) versus those with mild (<25%) podocyte foot process effacement (13,030 vs. 4806 pg/mL; P=0.02). Overall, mean+/-SD of proteinuria improved from 5.1+/-3.8 to 2.1+/-2.8 mg/dL (P=0.003), mean podocyte effacement decreased from 57%+/-33% to 22%+/-22% (P=0.0001), estimated glomerular filtration rates increased from median (interquartile range) of 32.9 (20.6-44.2) to 39.3 (28.8-63.4; P<0.0001), and suPAR levels decreased from a median of 6.781 to 4.129 pg/mL (P=0.02) with therapy.


English

0041-1337


*Glomerulosclerosis, Focal Segmental/su [Surgery]
*Kidney Transplantation/ae [Adverse Effects]
*Podocytes/pa [Pathology]
*Receptors, Urokinase Plasminogen Activator/bl [Blood]
Adult
Antibodies, Monoclonal, Murine-Derived/tu [Therapeutic Use]
Biomarkers/bl [Blood]
Biopsy
C-Reactive Protein/me [Metabolism]
Female
Glomerular Filtration Rate
Glomerulosclerosis, Focal Segmental/bl [Blood]
Glomerulosclerosis, Focal Segmental/pa [Pathology]
Glomerulosclerosis, Focal Segmental/pp [Physiopathology]
Humans
Immunosuppressive Agents/tu [Therapeutic Use]
Male
Middle Aged
Plasmapheresis
Podocytes/de [Drug Effects]
Proteinuria/bl [Blood]
Proteinuria/pa [Pathology]
Proteinuria/th [Therapy]
Recurrence
Retrospective Studies
Rituximab
Time Factors
Treatment Outcome
Young Adult


MedStar Union Memorial Hospital


Medicine


Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't