Optimizing the treatment of idiopathic membranous nephropathy.

Contains fulltext : 27028.pdf (publisher's version ) (Open Access)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 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.RU Radboud Universiteit Nijmegen, 29 november 2005Promotor : Wetzels, J.F.M.175 p

Recovery of dialysis patients with COVID-19 : health outcomes 3 months after diagnosis in ERACODA

Background. Coronavirus disease 2019 (COVID-19)-related short-term mortality is high in dialysis patients, but longer-term outcomes are largely unknown. We therefore assessed patient recovery in a large cohort of dialysis patients 3 months after their COVID-19 diagnosis. Methods. We analyzed data on dialysis patients diagnosed with COVID-19 from 1 February 2020 to 31 March 2021 from the European Renal Association COVID-19 Database (ERACODA). The outcomes studied were patient survival, residence and functional and mental health status (estimated by their treating physician) 3 months after COVID-19 diagnosis. Complete follow-up data were available for 854 surviving patients. Patient characteristics associated with recovery were analyzed using logistic regression. Results. In 2449 hemodialysis patients (mean ± SD age 67.5 ± 14.4 years, 62% male), survival probabilities at 3 months after COVID-19 diagnosis were 90% for nonhospitalized patients (n = 1087), 73% for patients admitted to the hospital but not to an intensive care unit (ICU) (n = 1165) and 40% for those admitted to an ICU (n = 197). Patient survival hardly decreased between 28 days and 3 months after COVID-19 diagnosis. At 3 months, 87% functioned at their pre-existent functional and 94% at their pre-existent mental level. Only few of the surviving patients were still admitted to the hospital (0.8-6.3%) or a nursing home (∼5%). A higher age and frailty score at presentation and ICU admission were associated with worse functional outcome. Conclusions. Mortality between 28 days and 3 months after COVID-19 diagnosis was low and the majority of patients who survived COVID-19 recovered to their pre-existent functional and mental health level at 3 months after diagnosis

Treatment-related changes in urinary excretion of high and low molecular weight proteins in patients with idiopathic membranous nephropathy and renal insufficiency.

Item does not contain fulltextBACKGROUND: In patients with idiopathic membranous nephropathy, an increased urinary excretion of high (IgG) and low [beta(2)-microglobulin (beta(2)M), alpha(1)-microglobulin (alpha(1)M)] molecular weight proteins predicts prognosis and precedes renal insufficiency. We have studied the changes in the urinary excretion of these proteins in patients with idiopathic membranous nephropathy and renal insufficiency during and after treatment with cyclophosphamide and steroids, and investigated their value in predicting long-term outcome. METHODS: Standardized measurements of urinary IgG, albumin, beta(2)M and alpha(1)M were performed at 0, 2, 6 and 12 months in 11 patients, at 12 months in 25 patients and in 17 of these last patients after 2-5 years. RESULTS: We observed a rapid improvement of glomerular permselectivity and tubular protein reabsorption within 2 months after the start of therapy. Despite a partial remission of proteinuria within 12 months in most patients, evidence of tubulo-interstitial injury remained apparent. Neither absolute levels of urinary IgG, beta(2)M or alpha(1)M at baseline or at 12 months nor the percentage reduction between baseline and 12 months clearly predicted the occurrence of a remission or a relapse to nephrotic range proteinuria. In the case of a persistent stable remission, we observed a gradual decrease of urinary beta(2)M towards normal values. CONCLUSIONS: In patients with idiopathic membranous nephropathy and renal insufficiency, treatment with cyclophosphamide and steroids resulted in an improvement of glomerular permeability and tubular proteinuria. Tubular proteinuria remained present for many years, even in patients with stable remission of proteinuria. Measurements of urinary proteins at 12 months after treatment start lacked predictive accuracy

Idiopathic membranous nephropathy: outline and rationale of a treatment strategy.

Item does not contain fulltextIdiopathic membranous nephropathy is a common cause of nephrotic syndrome. The treatment of patients with idiopathic membranous nephropathy is heavily debated. Based on literature data and our own experience, we propose a rational treatment strategy. Patients with renal insufficiency (serum creatinine level > 1.5 mg/dL [> 135 micromol/L]) are at greatest risk for the development of end-stage renal disease and should receive immunosuppressive therapy. In patients with normal renal function (serum creatinine level < 1.5 mg/dL [< 135 micromol/L]), risk for developing end-stage renal disease can be estimated by measuring urinary excretion of beta2-microglobulin or alpha1-microglobulin and immunoglobulin G. For low-risk patients, a wait-and-see policy is advised. High-risk patients likely benefit from immunosuppressive therapy. Currently, combinations of steroids with chlorambucil or cyclophosphamide are the best studied. We prefer cyclophosphamide in view of its fewer side effects. Cyclosporine may be an alternative option in patients with well-preserved renal function, although long-term data are lacking. Other immunosuppressive agents, such as mycophenolate mofetil or rituximab, currently are under study; however, data are insufficient to support their routine use

Mycophenolate mofetil in idiopathic membranous nephropathy: a clinical trial with comparison to a historic control group treated with cyclophosphamide.

Item does not contain fulltextBACKGROUND: Cyclophosphamide can decrease proteinuria and improve renal function in patients with idiopathic membranous nephropathy, but has a high risk of side effects. We studied whether mycophenolate mofetil (MMF) could be a reasonable alternative with fewer side effects. STUDY DESIGN: Clinical trial with historic controls. SETTINGS & PARTICIPANTS: 32 cases and 32 controls with idiopathic membranous nephropathy and renal insufficiency at multiple centers. For comparison, we selected matched historic controls treated with cyclophosphamide. INTERVENTION: MMF, 1 g twice daily, for 12 months versus cyclophosphamide, 1.5 mg/kg/d, for 12 months. Both groups also received intermittent methylprednisolone and alternate-day prednisone. OUTCOMES & MEASUREMENTS: Serum creatinine, proteinuria, and side effects during and after treatment. RESULTS: Median follow-up was 23 months (range, 11 to 46 months). Median serum creatinine levels were 1.8 mg/dL (159 micromol/L) in both groups at baseline and 1.4 mg/dL (124 micromol/L) in the MMF group versus 1.3 mg/dL (115 micromol/L) in the cyclophosphamide group at 12 months (P = 0.4). Proteinuria values at baseline and 12 months were protein of 8.40 and 1.41 g/d in the MMF group versus 9.19 and 1.13 g/d in the cyclophosphamide group (P = 0.5 at 12 months), respectively. Cumulative incidences of remission of proteinuria at 12 months were 66% in the MMF group versus 72% in the cyclophosphamide group (P = 0.3). Five patients (16%) in the MMF group versus none in the cyclophosphamide group had disease that did not respond to therapy (P = 0.05). Twelve patients (38%) experienced a relapse and 9 patients (31%) were re-treated in the MMF group compared with 4 (13%) and 2 patients (6%) in the cyclophosphamide group (P < 0.01 and P = 0.024, respectively). Side effects occurred in 24 patients (75%) in the MMF group and 22 patients (69%) in the cyclophosphamide group (P = 0.6). LIMITATIONS: Nonrandomized control group, short duration of follow-up. CONCLUSIONS: A 12-month course of MMF decreased proteinuria and improved renal function in the majority of patients, but did not appear as effective or better tolerated than cyclophosphamide. Long-term data and randomized controlled trials are needed to ascertain the efficacy of MMF in patients with idiopathic membranous nephropathy

Skin vasomotor reflexes during inspiratory gasp: standardization by spirometric control does not improve reproducibility

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Reply to letter to the editor of J.H. van Loenhout-Rooyackers [published in the September issue of The Netherlands Journal of Medicine (1999;55:163)]

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