Optimizing the treatment of idiopathic membranous nephropathy.
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RU Radboud Universiteit Nijmegen, 29 november 2005
Promotor : Wetzels, J.F.M.
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SubjectUMCN 5.4: Renal disorders
Idiopathic membranous nephropathy (iMN) is a common cause of the nephrotic syndrome in adults. A nephrotic syndrome is a clinical syndrome consisting of proteinuria over 3.5 g/day, hypoalbuminemia, edema and hypercholesterolemia. Treatment of patients with membranous nephropathy consists of supportive treatment, mainly directed at reducing proteinuria and edema, and specific immunosuppressive therapy. The use of immunosuppressive therapy in patients with iMN is heavily debated. We propose a rational treatment strategy. We prefer treating only patients at highest risk for the development of end-stage renal disease (ESRD): patients with deteriorating renal function. We however question, if therapy can be safely delayed until renal function deteriorates. In this thesis we show that treatment with cyclophosphamide and steroids for patients with iMN and renal function deterioration is very effective and results in a remission rate (proteinuria < 2g/day) of over 80%. However, side effects are frequent and a relapse of the nephrotic syndrome occurs in 28% of the patients after 5 years. In non-responders or patients showing a relapse with deteriorating renal function, we show that re-treatment results in a gained dialysis-free survival time of >93 months. In search of less toxic therapy we report on the short-term efficacy of treatment with mycophenolate mofetil. In this thesis we further demonstrate the safety of our restrictive treatment strategy. In order to be able to start treatment earlier, we must be able to predict prognosis. In patients with normal renal function, risk for developing ESRD can be estimated by measuring urinary excretion of ß2-microglobulin or a1-microglobulin and IgG. The predictive value of these parameters was validated. For low-risk patients, a wait and see policy is advised. High-risk patients (urinary excretion of ß2-microglobulin > 0.5 æg/min and urinary excretion of IgG > 250 mg/24 hours) likely benefit from an early start of immunosuppressive therapy.
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