title: Non-immunosuppressive treatment for IgA nephropathy.
abstract: BACKGROUND
  IgA nephropathy (IgAN) is the most common primary glomerular disease with approximately 30% to 40% of patients progressing to end-stage kidney disease (ESKD) within 20 years. The most common regimens include immunosuppressive agents, however the risks of long-term treatment often outweigh the potential benefits. Non-immunosuppressive options, including fish oils, anticoagulants, antihypertensive agents and tonsillectomy have also been examined but not reviewed systematically.
  
  
  OBJECTIVE
  To assess the benefits and harms of non-immunosuppressive treatments for treating IgAN in adults and children.
  
  
  METHODS
  In July 2010 we searched the Cochrane Renal Group's specialised register, CENTRAL (in The Cochrane Library), MEDLINE (from 1966) and EMBASE (from 1980). We also searched reference lists of included studies, review articles and contacted local and international experts.
  
  
  METHODS
  Randomised controlled trials (RCTs) of non-immunosuppressive agents in adults and children with biopsy-proven IgAN were included.
  
  
  METHODS
  Two authors independently reviewed search results, extracted data and assessed study quality. Results were expressed as mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI) using a random-effects model.
  
  
  RESULTS
  We included 56 studies (2838 participants). Antihypertensive agents were the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined were predominantly angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB) or combinations of both, versus other antihypertensives and other agents. The benefits of antihypertensive agents, particularly inhibitors of the renin angiotensin system, appear to potentially outweigh the harms in patients with IgAN. The benefits are largely manifest as a reduction in proteinuria, a surrogate outcome. There is no evidence that treatment with any of the antihypertensive agents evaluated affect major renal and/or cardiovascular endpoints or long-term mortality risk beyond the benefit that arises from controlling hypertension in patients with IgAN. The RCT evidence is insufficiently robust to demonstrate efficacy for any of the other non-immunosuppressive therapies evaluated here.
  
  
  CONCLUSIONS
  IgAN remains a disease in search of adequately powered RCTs to reliably inform clinical practice. More and better evidence is needed to understand the magnitude of benefit and the possible risks of anti-hypertensive or more specifically of ACEi/ARB therapy alone or in combination and which specific types of patients with the IgAN might have the greatest potential for benefit. For other non-immunosuppressive therapies, where neither benefit nor significant harm has yet to be demonstrated, there remains some justification for further exploration of the potential benefits.
authors.affiliation: Sydney School of Public Health, University of Sydney, Edward Ford Building (A27), Room 301C, Sydney, NSW, Australia, 2006.
authors.forename: Sharon
authors.initials: S
authors.lastname: Reid
authors.forename: Peggy M
authors.initials: PM
authors.lastname: Cawthon
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Craig
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Samuels
authors.forename: Donald A
authors.initials: DA
authors.lastname: Molony
authors.forename: Giovanni Fm
authors.initials: GF
authors.lastname: Strippoli
mesh_terms: D000328:Adult; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000925:Anticoagulants / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002648:Child; D003131:Combined Modality Therapy / Q000379:methods; D005395:Fish Oils / Q000627:therapeutic use*; D005922:Glomerulonephritis, IGA / Q000628:therapy*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D010672:Phenytoin / Q000627:therapeutic use; D008517:Phytotherapy; D028321:Plant Preparations / Q000627:therapeutic use; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D011507:Proteinuria / Q000517:prevention & control; D016032:Randomized Controlled Trials as Topic; D014068:Tonsillectomy
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000925:Anticoagulants; D000959:Antihypertensive Agents; D005395:Fish Oils; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D028321:Plant Preparations; D010975:Platelet Aggregation Inhibitors; D010672:Phenytoin