Journal
TRANSPLANTATION
Volume 96, Issue 7, Pages 649-656Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/TP.0b013e31829eda4f
Keywords
Kidney transplant; Podocyte effacement; FSGS; suPAR; Rituximab
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Funding
- National Institutes of Health (NIH) [DK073495, DK089394]
- NIH/National Institute of Diabetes and Digestive and Kidney Diseases [R01DK090316, 1K23DK081317]
- Nephcure Foundation
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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. 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. 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.
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