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10.1681/ASN.2014070640

http://scihub22266oqcxt.onion/10.1681/ASN.2014070640
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suck abstract from ncbi


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pmid25804280      J+Am+Soc+Nephrol 2015 ; 26 (10): 2545-58
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  • Anti-Phospholipase A2 Receptor Antibody Titer Predicts Post-Rituximab Outcome of Membranous Nephropathy #MMPMID25804280
  • Ruggenenti P; Debiec H; Ruggiero B; Chianca A; Pelle T; Gaspari F; Suardi F; Gagliardini E; Orisio S; Benigni A; Ronco P; Remuzzi G
  • J Am Soc Nephrol 2015[Oct]; 26 (10): 2545-58 PMID25804280show ga
  • Rituximab induces nephrotic syndrome (NS) remission in two-thirds of patients with primary membranous nephropathy (MN), even after other treatments have failed. To assess the relationships among treatment effect, circulating nephritogenic anti-phospholipase A2 receptor (anti-PLA2R) autoantibodies and genetic polymorphisms predisposing to antibody production we serially monitored 24-hour proteinuria and antibody titer in patients with primary MN and long-lasting NS consenting to rituximab (375 mg/m(2)) therapy and genetic analyses. Over a median (range) follow-up of 30.8 (6.0-145.4) months, 84 of 132 rituximab-treated patients achieved complete or partial NS remission (primary end point), and 25 relapsed after remission. Outcomes of patients with or without detectable anti-PLA2R antibodies at baseline were similar. Among the 81 patients with antibodies, lower anti-PLA2R antibody titer at baseline (P=0.001) and full antibody depletion 6 months post-rituximab (hazard ratio [HR], 7.90; 95% confidence interval [95% CI], 2.54 to 24.60; P<0.001) strongly predicted remission. All 25 complete remissions were preceded by complete anti-PLA2R antibody depletion. On average, 50% anti-PLA2R titer reduction preceded equivalent proteinuria reduction by 10 months. Re-emergence of circulating antibodies predicted disease relapse (HR, 6.54; 95% CI, 1.57 to 27.40; P=0.01), whereas initial complete remission protected from the event (HR, 6.63; 95% CI, 2.37 to 18.53; P<0.001). Eighteen patients achieved persistent antibody depletion and complete remission and never relapsed. Outcome was independent of PLA2R1 and HLA-DQA1 polymorphisms and of previous immunosuppressive treatment. Therefore, assessing circulating anti-PLA2R autoantibodies and proteinuria may help in monitoring disease activity and guiding personalized rituximab therapy in nephrotic patients with primary MN.
  • |Autoantibodies/*blood[MESH]
  • |Female[MESH]
  • |Glomerulonephritis, Membranous/*blood/*drug therapy[MESH]
  • |Humans[MESH]
  • |Immunologic Factors/*therapeutic use[MESH]
  • |Longitudinal Studies[MESH]
  • |Male[MESH]
  • |Middle Aged[MESH]
  • |Predictive Value of Tests[MESH]
  • |Receptors, Phospholipase A2/*immunology[MESH]
  • |Remission Induction[MESH]
  • |Rituximab/*therapeutic use[MESH]


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