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

MedStar author(s):
Citation: Transplantation. 96(7):649-56, 2013 Oct 15.PMID: 23842190Institution: MedStar Union Memorial HospitalDepartment: MedicineForm of publication: Journal ArticleMedline article type(s): Journal Article | Research Support, N.I.H., Extramural | Research Support, Non-U.S. Gov'tSubject headings: *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 AdultYear: 2013Local holdings: Available online from MWHC library: 1996 - present, Available in print through MWHC library: 1999 - 2006ISSN:
  • 0041-1337
Name of journal: TransplantationAbstract: 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.All authors: Alachkar N, Arend LJ, Burke G, Estrella MM, Fornoni A, Jackson AM, Kakkad K, Rabb H, Racusen LC, Reiser J, Wei CFiscal year: FY2014Digital Object Identifier: Date added to catalog: 2016-07-15
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Item type Current library Collection Call number Status Date due Barcode
Journal Article MedStar Authors Catalog Article 23842190 Available 23842190

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.

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