Recurrent Primary Focal Segmental Glomerulosclerosis Managed With Intensified Plasma Exchange and Concomitant Monitoring of Soluble Urokinase-Type Plasminogen Activator Receptor–Mediated Podocyte β3-integrin Activation
Autor: | Susanne Brakemeier, Jochen Reiser, Klemens Budde, Changli Wei, Hans-Hellmut Neumayer, Oliver Staeck, Torsten Slowinski, Danilo Schmidt, Birgit Rudolph, Ina Lieker, Fabian Halleck, Dmytro Khadzhynov, Kaiyin Wu |
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Rok vydání: | 2015 |
Předmět: |
Adult
Male medicine.medical_specialty urologic and male genital diseases Article Receptors Urokinase Plasminogen Activator Podocyte Focal segmental glomerulosclerosis Recurrence Internal medicine medicine Humans Kidney transplantation Monitoring Physiologic Retrospective Studies Urokinase Transplantation Plasma Exchange Glomerulosclerosis Focal Segmental Podocytes urogenital system business.industry Primary Focal Segmental Glomerulosclerosis Integrin beta3 Glomerulosclerosis medicine.disease female genital diseases and pregnancy complications Endocrinology medicine.anatomical_structure SuPAR Cancer research Female business Plasminogen activator Follow-Up Studies medicine.drug |
Zdroj: | Transplantation. 99:2593-2597 |
ISSN: | 0041-1337 |
Popis: | Primary focal segmental glomerulosclerosis (FSGS) often causes nephrotic proteinuria and frequently results in end-stage renal disease and recurrence after kidney transplantation. Recent studies describe soluble urokinase-type plasminogen activator receptor (suPAR) as a circulating factor implicated in FSGS.This single-center study included 12 adult patients with histologically proven primary FSGS (n = 2) or recurrent FSGS after transplantation (n = 10). The effect of plasma exchange (PE) on clinical outcome, suPAR levels, and in vitro podocyte β3-integrin activation was investigated over a median of 11 (6-18) sessions of PE.The course of treatment was monitored in a total of 70 sessions of PE, which partly eliminated suPAR, with a mean reduction of 37 ± 12% of serum concentration per session. However, a substantial rebound was observed between sessions, with suPAR levels reaching 99 ± 22% of the pretreatment levels after a median of 4 days. Podocyte β3-integrin activation dropped significantly after PE but rebounded within 4 days concomitant with a rising suPAR level. In 11 of 12 patients, multimodal treatment (including extensive PE) reduced proteinuria significantly (from 5.3 [2.0-7.8] to 1.0 [0.4-1.6] g/d), indicating clinical efficacy of the therapy. One patient suffered allograft loss due to FSGS recurrence. A persisting response was independent of a lasting reduction in the level of total suPAR because there was no sustained significant change in suPAR levels before and after the course of intensified treatment (3814 ± 908 to 3595 ± 521 pg/mL; P = 0.496).We conclude that multimodal therapy including extensive PE was associated with stabilization of recurrent FSGS and a temporary lowering of plasma suPAR as well as podocyte β3-integrin activation. Whether a sustained lowering of total suPAR results in further improved outcomes requires additional study. |
Databáze: | OpenAIRE |
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