Are cytotoxic agents beneficial in idiopathic membranous nephropathy? A meta-analysis of the controlled trials

Thomas Imperiale, S. Goldfarb, J. S. Berns

Research output: Contribution to journalArticle

63 Citations (Scopus)

Abstract

The use of cytotoxic agents for the treatment of idiopathic membranous nephropathy is controversial. Although several controlled trials have been published, both the comparison groups and the study findings have varied, resulting in clinical uncertainty. To explore this uncertainty, a meta-analysis of controlled trials of treatment with cyclophosphamide or chlorambucil was performed in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria. Patients in the control groups received only symptomatic treatment or corticosteroids. Descriptive and quantitative data from each trial were abstracted independently. Outcomes included effects of treatment on renal function and proteinuria, with a complete remission (CR) or partial remission (PR) defined as the complete or partial resolution of proteinuria without deterioration of renal function. For patients having either any response (CR or PR) or only a CR, both the relative risk (RR) and the number needed to be treated were calculated. The five trials that satisfied criteria for inclusion in the analysis were clinically and statistically homogeneous. There were no placebo-controlled trials that met the criteria for inclusion. Among the 228 patients in these studies, the RR of achieving any response with cytotoxic agents was 2.3 (95% confidence interval, 1.7 to 3.2) and the RR for a CR was 4.6 (95% confidence interval, 2.2 to 9.3), with respective numbers needed to be treated of 2.9 and 4.7, meaning that between three and five patients would need to be treated with cytotoxic agents to achieve one response. Exclusion of the only nonrandomized trial had no significant effect on the results. Both chlorambucil and cyclophosphamide showed similar beneficial effects. This meta-analysis demonstrates that treatment with cytotoxic agents benefits patients with idiopathic nephrotic syndrome due to membranous nephropathy by bringing about the resolution of nephrotic-range proteinuria. The published results of these five trials do not allow a conclusion to be drawn regarding the effects of cytotoxic drug therapy on renal function, highlighting the need for studies of the long-term benefits and risks of therapies for idiopathic membranous nephropathy.

Original languageEnglish (US)
Pages (from-to)1553-1558
Number of pages6
JournalJournal of the American Society of Nephrology
Volume5
Issue number8
StatePublished - 1995
Externally publishedYes

Fingerprint

Membranous Glomerulonephritis
Cytotoxins
Meta-Analysis
Proteinuria
Chlorambucil
Kidney
Cyclophosphamide
Uncertainty
Therapeutics
Confidence Intervals
Adrenal Cortex Hormones
Placebos
Drug Therapy
Control Groups

Keywords

  • immunosuppressive agents
  • membranous nephropathy
  • meta-analysis
  • nephrotic syndrome

ASJC Scopus subject areas

  • Nephrology

Cite this

Are cytotoxic agents beneficial in idiopathic membranous nephropathy? A meta-analysis of the controlled trials. / Imperiale, Thomas; Goldfarb, S.; Berns, J. S.

In: Journal of the American Society of Nephrology, Vol. 5, No. 8, 1995, p. 1553-1558.

Research output: Contribution to journalArticle

@article{9f606792d43947a79aaf1b0674177411,
title = "Are cytotoxic agents beneficial in idiopathic membranous nephropathy? A meta-analysis of the controlled trials",
abstract = "The use of cytotoxic agents for the treatment of idiopathic membranous nephropathy is controversial. Although several controlled trials have been published, both the comparison groups and the study findings have varied, resulting in clinical uncertainty. To explore this uncertainty, a meta-analysis of controlled trials of treatment with cyclophosphamide or chlorambucil was performed in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria. Patients in the control groups received only symptomatic treatment or corticosteroids. Descriptive and quantitative data from each trial were abstracted independently. Outcomes included effects of treatment on renal function and proteinuria, with a complete remission (CR) or partial remission (PR) defined as the complete or partial resolution of proteinuria without deterioration of renal function. For patients having either any response (CR or PR) or only a CR, both the relative risk (RR) and the number needed to be treated were calculated. The five trials that satisfied criteria for inclusion in the analysis were clinically and statistically homogeneous. There were no placebo-controlled trials that met the criteria for inclusion. Among the 228 patients in these studies, the RR of achieving any response with cytotoxic agents was 2.3 (95{\%} confidence interval, 1.7 to 3.2) and the RR for a CR was 4.6 (95{\%} confidence interval, 2.2 to 9.3), with respective numbers needed to be treated of 2.9 and 4.7, meaning that between three and five patients would need to be treated with cytotoxic agents to achieve one response. Exclusion of the only nonrandomized trial had no significant effect on the results. Both chlorambucil and cyclophosphamide showed similar beneficial effects. This meta-analysis demonstrates that treatment with cytotoxic agents benefits patients with idiopathic nephrotic syndrome due to membranous nephropathy by bringing about the resolution of nephrotic-range proteinuria. The published results of these five trials do not allow a conclusion to be drawn regarding the effects of cytotoxic drug therapy on renal function, highlighting the need for studies of the long-term benefits and risks of therapies for idiopathic membranous nephropathy.",
keywords = "immunosuppressive agents, membranous nephropathy, meta-analysis, nephrotic syndrome",
author = "Thomas Imperiale and S. Goldfarb and Berns, {J. S.}",
year = "1995",
language = "English (US)",
volume = "5",
pages = "1553--1558",
journal = "Journal of the American Society of Nephrology : JASN",
issn = "1046-6673",
publisher = "American Society of Nephrology",
number = "8",

}

TY - JOUR

T1 - Are cytotoxic agents beneficial in idiopathic membranous nephropathy? A meta-analysis of the controlled trials

AU - Imperiale, Thomas

AU - Goldfarb, S.

AU - Berns, J. S.

PY - 1995

Y1 - 1995

N2 - The use of cytotoxic agents for the treatment of idiopathic membranous nephropathy is controversial. Although several controlled trials have been published, both the comparison groups and the study findings have varied, resulting in clinical uncertainty. To explore this uncertainty, a meta-analysis of controlled trials of treatment with cyclophosphamide or chlorambucil was performed in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria. Patients in the control groups received only symptomatic treatment or corticosteroids. Descriptive and quantitative data from each trial were abstracted independently. Outcomes included effects of treatment on renal function and proteinuria, with a complete remission (CR) or partial remission (PR) defined as the complete or partial resolution of proteinuria without deterioration of renal function. For patients having either any response (CR or PR) or only a CR, both the relative risk (RR) and the number needed to be treated were calculated. The five trials that satisfied criteria for inclusion in the analysis were clinically and statistically homogeneous. There were no placebo-controlled trials that met the criteria for inclusion. Among the 228 patients in these studies, the RR of achieving any response with cytotoxic agents was 2.3 (95% confidence interval, 1.7 to 3.2) and the RR for a CR was 4.6 (95% confidence interval, 2.2 to 9.3), with respective numbers needed to be treated of 2.9 and 4.7, meaning that between three and five patients would need to be treated with cytotoxic agents to achieve one response. Exclusion of the only nonrandomized trial had no significant effect on the results. Both chlorambucil and cyclophosphamide showed similar beneficial effects. This meta-analysis demonstrates that treatment with cytotoxic agents benefits patients with idiopathic nephrotic syndrome due to membranous nephropathy by bringing about the resolution of nephrotic-range proteinuria. The published results of these five trials do not allow a conclusion to be drawn regarding the effects of cytotoxic drug therapy on renal function, highlighting the need for studies of the long-term benefits and risks of therapies for idiopathic membranous nephropathy.

AB - The use of cytotoxic agents for the treatment of idiopathic membranous nephropathy is controversial. Although several controlled trials have been published, both the comparison groups and the study findings have varied, resulting in clinical uncertainty. To explore this uncertainty, a meta-analysis of controlled trials of treatment with cyclophosphamide or chlorambucil was performed in patients with idiopathic membranous nephropathy and nephrotic-range proteinuria. Patients in the control groups received only symptomatic treatment or corticosteroids. Descriptive and quantitative data from each trial were abstracted independently. Outcomes included effects of treatment on renal function and proteinuria, with a complete remission (CR) or partial remission (PR) defined as the complete or partial resolution of proteinuria without deterioration of renal function. For patients having either any response (CR or PR) or only a CR, both the relative risk (RR) and the number needed to be treated were calculated. The five trials that satisfied criteria for inclusion in the analysis were clinically and statistically homogeneous. There were no placebo-controlled trials that met the criteria for inclusion. Among the 228 patients in these studies, the RR of achieving any response with cytotoxic agents was 2.3 (95% confidence interval, 1.7 to 3.2) and the RR for a CR was 4.6 (95% confidence interval, 2.2 to 9.3), with respective numbers needed to be treated of 2.9 and 4.7, meaning that between three and five patients would need to be treated with cytotoxic agents to achieve one response. Exclusion of the only nonrandomized trial had no significant effect on the results. Both chlorambucil and cyclophosphamide showed similar beneficial effects. This meta-analysis demonstrates that treatment with cytotoxic agents benefits patients with idiopathic nephrotic syndrome due to membranous nephropathy by bringing about the resolution of nephrotic-range proteinuria. The published results of these five trials do not allow a conclusion to be drawn regarding the effects of cytotoxic drug therapy on renal function, highlighting the need for studies of the long-term benefits and risks of therapies for idiopathic membranous nephropathy.

KW - immunosuppressive agents

KW - membranous nephropathy

KW - meta-analysis

KW - nephrotic syndrome

UR - http://www.scopus.com/inward/record.url?scp=0028998429&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028998429&partnerID=8YFLogxK

M3 - Article

C2 - 7756587

AN - SCOPUS:0028998429

VL - 5

SP - 1553

EP - 1558

JO - Journal of the American Society of Nephrology : JASN

JF - Journal of the American Society of Nephrology : JASN

SN - 1046-6673

IS - 8

ER -