BACKGROUND: Tumour necrosis alpha has been implicated in the pathogenesis of autoimmune disorders was to evaluate the safety, tolerability and potential efficacy of the tumour necrosis factor alpha (TNF-alpha) inhibitor, etanercept (ET), in patients with idiopathic membranous nephropathy (MN). METHODS: Patients with biopsy-proven MN, nephrotic-range proteinuria and clearance of creatinine 50 ml/min or more were included in the study. Exclusion criteria were treatment with steroids or cyclosporine during the previous 3 months, or cytotoxic agents within 6 months prior to entry. ET was administered subcutaneously, 25 mg twice per week for 3 months. Plasma levels of TNF-alpha, interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), soluble intercellular adhesion molecule type 1 (sICAM-1), E-selectin, and the soluble form of tumour necrosis factor receptor-55 (sTNFR-55) were measured on entry and at Months 3, 6, and 9 after commencing therapy. RESULTS: Twelve patients were entered in the study (four females/eight males, mean time from diagnosis 8.3 months). The therapy was well tolerated; no infections or other adverse events were recorded by the end of follow-up. Two patients exhibited complete remission of proteinuria for at least 4 years. No significant change was found in the levels of TNF-alpha, IL-1, IL-6, IL-8 and IL-10 during the study. Similarly the levels of E-selectin and sICAM-1 were not significantly altered by therapy. Although we found no change in sTNFR-55 at 3 and 6 months, the levels of sTNFR-55 were found significantly decreased 9 months after therapy (mean difference from baseline: 334 +/- 527 pg/ml, P = 0.028). CONCLUSION: Short-term use of ET in a small series of patients reduced sTNFR-55 levels but did not exhibit any significant clinical effect in the majority of patients.
BACKGROUND:Tumour necrosis alpha has been implicated in the pathogenesis of autoimmune disorders was to evaluate the safety, tolerability and potential efficacy of the tumour necrosis factor alpha (TNF-alpha) inhibitor, etanercept (ET), in patients with idiopathic membranous nephropathy (MN). METHODS:Patients with biopsy-proven MN, nephrotic-range proteinuria and clearance of creatinine 50 ml/min or more were included in the study. Exclusion criteria were treatment with steroids or cyclosporine during the previous 3 months, or cytotoxic agents within 6 months prior to entry. ET was administered subcutaneously, 25 mg twice per week for 3 months. Plasma levels of TNF-alpha, interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-10 (IL-10), soluble intercellular adhesion molecule type 1 (sICAM-1), E-selectin, and the soluble form of tumour necrosis factor receptor-55 (sTNFR-55) were measured on entry and at Months 3, 6, and 9 after commencing therapy. RESULTS: Twelve patients were entered in the study (four females/eight males, mean time from diagnosis 8.3 months). The therapy was well tolerated; no infections or other adverse events were recorded by the end of follow-up. Two patients exhibited complete remission of proteinuria for at least 4 years. No significant change was found in the levels of TNF-alpha, IL-1, IL-6, IL-8 and IL-10 during the study. Similarly the levels of E-selectin and sICAM-1 were not significantly altered by therapy. Although we found no change in sTNFR-55 at 3 and 6 months, the levels of sTNFR-55 were found significantly decreased 9 months after therapy (mean difference from baseline: 334 +/- 527 pg/ml, P = 0.028). CONCLUSION: Short-term use of ET in a small series of patients reduced sTNFR-55 levels but did not exhibit any significant clinical effect in the majority of patients.
Authors: Melanie S Joy; Debbie S Gipson; Leslie Powell; Jacqueline MacHardy; J Charles Jennette; Suzanne Vento; Cynthia Pan; Virginia Savin; Allison Eddy; Agnes B Fogo; Jeffrey B Kopp; Daniel Cattran; Howard Trachtman Journal: Am J Kidney Dis Date: 2009-11-22 Impact factor: 8.860