Long-Term Risk of Cancer in Membranous Nephropathy Patients

Bjørneklett, Rune; Vikse, Bjørn Egil; Svarstad, Einar; Aasarød, Knut; Bostad, Leif; Langmark, Frøydis; Iversen, Bjarne M.

doi:10.1053/j.ajkd.2007.06.003

Cited by 81 publications

(67 citation statements)

References 29 publications

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“…However, our data compared favorably to the 5-year mortality rate of 6%-26% reported in other iMN cohorts. 8,24,25 A limitation of the present study is its observational nature. No causal inferences about the efficacy of the strategy or about the efficacy of individual drugs can be made with the current design.…”

Section: Discussionmentioning

confidence: 95%

Long-Term Outcomes in Idiopathic Membranous Nephropathy Using a Restrictive Treatment Strategy

Brand

Dijk

Hofstra

et al. 2014

Journal of the American Society of Nephrology

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Recently published Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend limiting the use of immunosuppressive drugs in idiopathic membranous nephropathy to patients at the highest risk of kidney failure. However, recommendations are based on natural history rather than direct assessment of a restrictive treatment strategy. Here, we describe the long-term outcomes of treating a large cohort of patients with idiopathic membranous nephropathy according to a restrictive treatment policy. We analyzed data for 254 patients who visited our outpatient clinic between 1995 and 2009. All patients were treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Immunosuppressive therapy was recommended in cases of deteriorating renal function or untreatable nephrotic syndrome. Primary outcomes for the present study were renal replacement therapy and death. Secondary outcomes included adverse events during follow-up and remission of proteinuria. In total, 124 patients (49%) received immunosuppressive therapy, which predominantly consisted of cyclophosphamide combined with steroids. Ten-year cumulative incidence rates were 3% for renal replacement therapy and 10% for death. Partial remission rates were 39%, 70%, and 83% after 1, 3, and 5 years, respectively; complete remission rates were 5%, 24%, and 38% at 1, 3, and 5 years, respectively. A serious adverse event occurred in 23% of all patients. The most notable complications were infections (17%), leukopenia (18%), cardiovascular events (13%), and malignancies (8%). In conclusion, the use of a restrictive treatment strategy in this cohort of patients with idiopathic membranous nephropathy yielded favorable outcomes while limiting the number of patients exposed to toxic drugs. These results support current KDIGO guidelines. 25: 150-158, 201425: 150-158, . doi: 10.1681 Idiopathic membranous nephropathy (iMN) is the most common cause of adult-onset nephrotic syndrome in whites. Recent data show that iMN is an autoimmune disease, with antibodies against M-type phospholipase A 2 receptor present in about 70% of patients. 1 The natural course of the disease varies, with spontaneous remission occurring in 30%-50% of patients, whereas another 30%-50% show progressive renal failure. 2,3 To avoid progression to ESRD, patients can be treated with immunosuppressive drugs. Two randomized, controlled trials evaluated the efficacy of the alkylating agents chlorambucil and cyclophosphamide. 4,5 These trials included patients with iMN of recent onset, with normal renal function and nephrotic-range proteinuria, and showed increased remission rates and improved renal survival in treated patients. However, outcome was favorable in 60%-65% of the untreated patients. Because most physicians are reluctant to use a treatment schedule that exposes many patients to unneeded, toxic therapy, the use of immunosuppressive therapy in iMN is heavily J Am Soc Nephrol

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Section: Discussionmentioning

confidence: 95%

Long-Term Outcomes in Idiopathic Membranous Nephropathy Using a Restrictive Treatment Strategy

Brand

Dijk

Hofstra

et al. 2014

Journal of the American Society of Nephrology

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“…Compared with age-and sex-adjusted general population, the standardized incidence ratio of cancer in patients with MN is 2.25; the annual incidence continues to increase for more than 5 years after the histologic diagnosis of nephropathy (13). The malignancies most frequently associated with MN are solid tumors, including lung, gastrointestinal, and prostate carcinomas (8,10,11,13). Not surprisingly, age and heavy smoking increase the likelihood of malignancy in MN patients.…”

Section: Carcinoma-associated Paraneoplastic Glomerulopathies Membranmentioning

confidence: 99%

“…Not surprisingly, age and heavy smoking increase the likelihood of malignancy in MN patients. Patients with MN plus malignancy have a poorer prognosis than those without cancer (13).…”

Section: Carcinoma-associated Paraneoplastic Glomerulopathies Membranmentioning

confidence: 99%

“…Malignancy is usually found within 12 months of the diagnosis of MN, and most (80%) cases are discovered before or at the time of the renal diagnosis (7,12). Compared with age-and sex-adjusted general population, the standardized incidence ratio of cancer in patients with MN is 2.25; the annual incidence continues to increase for more than 5 years after the histologic diagnosis of nephropathy (13). The malignancies most frequently associated with MN are solid tumors, including lung, gastrointestinal, and prostate carcinomas (8,10,11,13).…”

Section: Carcinoma-associated Paraneoplastic Glomerulopathies Membranmentioning

confidence: 99%

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Onco-Nephrology

Cambier

Ronco

2012

Clinical Journal of the American Society of Nephrology

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SummaryGlomerular diseases occurring in the course of malignancies remain rare. Diverse glomerular lesions can be observed in a variety of neoplasms and involve different pathophysiologic links between the glomerulopathy and the cancer. The pathophysiology of solid tumor-associated glomerulopathies remains obscure, whereas in hematologic malignancy-induced paraneoplastic glomerulopathies, a molecular link can usually be demonstrated. The aim of this review is to provide an update on glomerular diseases associated with carcinoma and hematologic malignancies, covering epidemiology, pathophysiology, clinical presentation, and therapy. Special emphasis will be placed on the potential usefulness of novel biomarkers, such as antiphospholipase A2 receptor antibodies, for the diagnosis of membranous nephropathy, and on new associations and recent entities, including (proliferative) GN with nonorganized monoclonal immunoglobulin deposits and myeloproliferative neoplasmrelated glomerulopathy.

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“…However, many physicians and patients are reluctant to use cyclophosphamide because of the increased risk of cancer after cyclophosphamide therapy in patients with granulomatosis with polyangiitis (formerly Wegener's granulomatosis), rheumatoid arthritis, and non-Hodgkin's lymphoma (2)(3)(4). Ascertaining the association between cyclophosphamide therapy and malignancy in iMN is challenging because of the concomitant immunosuppressive therapy, the relative rarity of malignancies, and the fact that membranous nephropathy may occur secondary to cancer (5,6). As a result, data on cancer risk in cyclophosphamidetreated iMN patients are sparse.…”

Section: Introductionmentioning

confidence: 99%

Cancer Risk after Cyclophosphamide Treatment in Idiopathic Membranous Nephropathy

Brand

Dijk

Hofstra

et al. 2014

Clinical Journal of the American Society of Nephrology

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Background and objectives Cyclophosphamide treatment improves renal survival in patients with idiopathic membranous nephropathy. However, use of cyclophosphamide is associated with cancer. The incidence of malignancies in patients with idiopathic membranous nephropathy was evaluated, and the cancer risk associated with cyclophosphamide use was estimated.Design, setting, participants, & measurements Patients who attended the clinic were included prospectively from 1995 on. A crude incidence ratio for the occurrence of malignancy was calculated. Incidence ratios were subsequently standardized to potential confounders. Latency between cyclophosphamide therapy and the occurrence of cancer was estimated by stratifying for time since the start of treatment. Finally, Poisson regression was used to obtain a multiple adjusted incidence ratio and investigate the dose-response relationship between cyclophosphamide and cancer.Results Data were available for 272 patients; the mean age was 51 years, and 70% of the patients were men. Median follow-up was 6.0 years (interquartile range=3.6-9.5), and 127 patients were treated with cyclophosphamide. Cancer incidence was 21.2 per 1000 person-years in treated patients compared with 4.6 per 1000 personyears in patients who did not receive cyclophosphamide, resulting in crude and adjusted incidence ratios of 4.6 (95% confidence interval, 1.5 to 18.8) and 3.2 (95% confidence interval, 1.0 to 9.5), respectively.Conclusion Cyclophosphamide therapy in idiopathic membranous nephropathy gives a threefold increase in cancer risk. For the average patient, this finding translates into an increase in annual risk from approximately 0.3% to 1.0%. The increased risk of malignancy must be balanced against the improved renal survival.

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Long-Term Risk of Cancer in Membranous Nephropathy Patients

Cited by 81 publications

References 29 publications

Long-Term Outcomes in Idiopathic Membranous Nephropathy Using a Restrictive Treatment Strategy

Long-Term Outcomes in Idiopathic Membranous Nephropathy Using a Restrictive Treatment Strategy

Onco-Nephrology

Cancer Risk after Cyclophosphamide Treatment in Idiopathic Membranous Nephropathy

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