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Interventions for renal vasculitis in adults.

AbstractBACKGROUND:
Renal vasculitis presents as rapidly progressive glomerulonephritis which comprises of a group of conditions characterised by acute kidney injury (AKI), haematuria and proteinuria. Treatment of these conditions comprises steroid and non-steroid agents in combination with plasma exchange. Although immunosuppression overall has been very successful in treatment of these conditions, many questions remain unanswered in terms of dose and duration of therapy, the use of plasma exchange and the role of new therapies. This an update of a review first published in 2008.
OBJECTIVES:
To evaluate the benefits and harms of any intervention used for the treatment of renal vasculitis in adults.
SEARCH METHODS:
We searched the Cochrane Kidney and Transplant Specialised Register up to 27 July 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA:
Randomised controlled trials investigating any intervention for the treatment of renal vasculitis in adults.
DATA COLLECTION AND ANALYSIS:
Two authors independently assessed study quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes or mean difference (MD) for continuous outcomes.
MAIN RESULTS:
Thirty one studies (2217 patients) were included. Studies conducted earlier tended to have a higher risk of bias due to poor (or poorly reported) study design, broad inclusion criteria, less well developed disease definitions and low patient numbers. Later studies tend to have improved in all areas of quality, aided by the development of large transnational study groups.Plasma exchange as adjunctive therapy significantly reduces the risk of end-stage kidney disease at three months (2 studies: RR 0.43, 95% CI 0.23 to 0.78) and 12 months (6 studies: RR 0.45, 95% CI 0.29 to 0.72). Four studies (300 patients) compared the use of pulse and continuous administration of cyclophosphamide. Remission rates were equivalent but pulse treatment causes an increased risk of relapse (4 studies: RR 1.79, 95% CI 1.11 to 2.87) compared with continuous cyclophosphamide. Azathioprine has equivalent efficacy as a maintenance agent to cyclophosphamide with fewer episodes of leucopenia. Mycophenolate mofetil may be equivalent to cyclophosphamide as an induction agent but resulted in a higher relapse rate when tested against azathioprine in remission maintenance. Rituximab is an effective remission induction agent. Methotrexate or leflunomide are potential choices in remission maintenance therapy. Oral co-trimoxazole did not reduce relapses significantly in granulomatosis with polyangiitis.
AUTHORS' CONCLUSIONS:
Plasma exchange was effective in patients with severe AKI secondary to vasculitis. Pulse cyclophosphamide results in an increased risk of relapse when compared to continuous oral use but a reduced total dose. Whilst cyclophosphamide is standard induction treatment, rituximab and mycophenolate mofetil were also effective. Azathioprine, methotrexate and leflunomide were effective as maintenance therapy. Further studies are required to more clearly delineate the appropriate place of newer agents within an evidence-based therapeutic strategy.
AuthorsGiles Walters, Narelle S Willis, Jonathan C Craig
JournalThe Cochrane database of systematic reviews (Cochrane Database Syst Rev) Issue 9 Pg. CD003232 (Sep 24 2015) ISSN: 1469-493X [Electronic] England
PMID26400765 (Publication Type: Journal Article, Meta-Analysis, Review, Systematic Review)
Chemical References
  • Immunosuppressive Agents
  • Cyclophosphamide
  • Azathioprine
Topics
  • Acute Kidney Injury (therapy)
  • Adult
  • Azathioprine (therapeutic use)
  • Cyclophosphamide (therapeutic use)
  • Glomerulonephritis (complications)
  • Humans
  • Immunosuppressive Agents (therapeutic use)
  • Kidney (blood supply)
  • Kidney Diseases (therapy)
  • Kidney Failure, Chronic (prevention & control)
  • Plasma Exchange
  • Randomized Controlled Trials as Topic
  • Vasculitis (therapy)

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