NDT Advance Access originally published online on February 7, 2009
Nephrology Dialysis Transplantation 2009 24(7):2144-2150; doi:10.1093/ndt/gfn771
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Inhibition of tumour necrosis factor alpha in idiopathic membranous nephropathy: a pilot study
1 Department of Nephrology & Transplantation Center, Laiko Hospital, Athens, Greece 2 Department of Nephrology, School of Medicine, University of Ioannina, Ioannina, Greece 3 Department of Rheumatology, Clinical Immunology, and Allergy, School of Medicine, University of Crete, Heraklion, Greece
Correspondence and offprint requests to: Sofia Lionaki; E-mail: Sofia.Lionaki{at}gmail.com
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Abstract |
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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-
) 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-, 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-, 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.
Keywords: etanercept; membranous nephropathy; tumour necrosis factor alpha
* equal contribution
Received for publication: 26. 5.08
Accepted in revised form: 24.12.08