Nada Alachkar1, Changli Wei, Lois J Arend, Annette M Jackson, Lorraine C Racusen, Alessia Fornoni, George Burke, Hamid Rabb, Kavita Kakkad, Jochen Reiser, Michelle M Estrella. 1. 1 Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. 2 Department of Medicine, Rush University Medical Center, Chicago, IL. 3 Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD. 4 Department of Medicine, University of Miami Miller School of Medicine, Miami, FL. 5 Department of Surgery, University of Miami Miller School of Medicine, Miami, FL. 6 Department of Medicine, Union Memorial Hospital, Baltimore, MD. 7 Address correspondence to: Nada Alachkar, M.D., Department of Medicine, Johns Hopkins University School of Medicine, 720 Rutland Avenue, Ross 971, Baltimore, MD 21205 and Jochen Reiser, M.D., Ph.D., Department of Medicine, Rush University Medical Center, Cohn Research Building, Suite 724, 1735 W. Harrison Street, Chicago, IL 60612.
Abstract
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.
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.
Authors: K C Abbott; E S Sawyers; J D Oliver; C W Ko; A D Kirk; P G Welch; T G Peters; L Y Agodoa Journal: Am J Kidney Dis Date: 2001-02 Impact factor: 8.860
Authors: V J Savin; R Sharma; M Sharma; E T McCarthy; S K Swan; E Ellis; H Lovell; B Warady; S Gunwar; A M Chonko; M Artero; F Vincenti Journal: N Engl J Med Date: 1996-04-04 Impact factor: 91.245