Induction and Maintenance Treatment of Proliferative Lupus Nephritis: A Meta-analysis of Randomized Controlled Trials

• Published in: American journal of kidney diseases Vol. 61; no. 1; pp. 74 - 87
• Main Authors: Henderson, Lorna K., MBChB, PhD, Masson, Philip, MBChB, Craig, Jonathan C., MBBS, PhD, Roberts, Matthew A., MBBS, Flanc, Robert S., MBBS, Strippoli, Giovanni F.M., MD, PhD, Webster, Angela C., MBChB, PhD
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.01.2013; Elsevier
• Subjects: Antibodies, Monoclonal, Murine-Derived - therapeutic use; Azathioprine - therapeutic use; Biological and medical sciences; cyclophosphamide (CYC); Cyclophosphamide - therapeutic use; Humans; Immunosuppressive Agents - therapeutic use; Kidneys; Lupus nephritis; Lupus Nephritis - drug therapy; Medical sciences; meta-analysis; mycophenolate mofetil (MMF); Mycophenolic Acid - analogs & derivatives; Mycophenolic Acid - therapeutic use; Nephrology; Nephrology. Urinary tract diseases; proliferative glomerulonephritis; Randomized Controlled Trials as Topic; Remission Induction; Rituximab; Sarcoidosis. Granulomatous diseases of unproved etiology. Connective tissue diseases. Elastic tissue diseases. Vasculitis; systematic review; systemic lupus erythematosus (SLE); Urinary system involvement in other diseases. Miscellaneous; systemic lupus erythematosus (SLE); cyclophosphamide (CYC); meta-analysis; proliferative glomerulonephritis; mycophenolate mofetil (MMF); Lupus nephritis; systematic review; Antineoplastic agent; Cell proliferation; Skin disease; Nephrology; Proliferative glomerulonephritis; Autoimmune disease; Review; Urology; Metaanalysis; Systemic lupus erythematosus; Maintenance treatment; Systemic disease; Kidney disease; Immunopathology; Connective tissue disease; Urinary system disease; Enzyme; IMP dehydrogenase; Enzyme inhibitor; Induction treatment; Randomized controlled trial; Immunomodulator; Alkylating agent; Oxazaphosphinane derivatives; Cyclophosphamide; Nitrogen mustard; Oxidoreductases; Immunosuppressive agent; Mycophenolate mofetil; Bibliographic review
• ISSN: 0272-6386; 1523-6838
• DOI: 10.1053/j.ajkd.2012.08.041

Background Lupus nephritis accounts for ∼1% of patients starting dialysis therapy. Treatment regimens combining cyclophosphamide with steroids preserve kidney function but have significant side effects. Newer immunosuppressive agents may have improved toxicity profiles. Study Design Systematic review and random-effects meta-analysis, searching MEDLINE (1966 to April 2012), EMBASE (1988-2011), and the Cochrane Renal Group Specialised Register. Setting & Population Patients with biopsy-proven proliferative lupus nephritis (classes III, IV, V+III, and V+IV). Selection Criteria Randomized controlled trials. Intervention Immunosuppressive treatment regimens used for induction and maintenance therapy of lupus nephritis. Outcomes Mortality, renal remission and relapse, doubling of creatinine level, proteinuria, incidence of end-stage kidney disease, ovarian failure, alopecia, leukopenia, infections, diarrhea, vomiting, malignancy, and bladder toxicity. Results 45 trials (2,559 participants) of induction therapy and 6 (514 participants) of maintenance therapy were included. In induction regimens comparing mycophenolate mofetil (MMF) with intravenous cyclophosphamide, there was no significant difference in mortality (7 studies, 710 patients; risk ratio [RR], 1.02; 95% CI, 0.52-1.98), incidence of end-stage kidney disease (3 studies, 231 patients; RR, 0.71; 95% CI, 0.27-1.84), complete renal remission (6 studies, 686 patients; RR, 1.39; 95% CI, 0.99-1.95), and renal relapse (1 study, 140 patients; RR, 0.97; 95% CI, 0.39-2.44). MMF-treated patients had significantly lower risks of ovarian failure (2 studies, 498 patients; RR, 0.15; 95% CI, 0.03-0.80) and alopecia (2 studies, 522 patients; RR, 0.22; 95% CI, 0.06-0.86). In maintenance therapy comparing azathioprine with MMF, the risk of renal relapse was significantly higher (3 studies, 371 patients; RR, 1.83; 95% CI, 1.24-2.71). Limitations Heterogeneity in interventions and definitions of remission and lack of long-term outcome reporting. Conclusions MMF is as effective as cyclophosphamide in achieving remission in lupus nephritis, but is safer, with a lower risk of ovarian failure. MMF is more effective than azathioprine in maintenance therapy for preventing relapse, with no difference in clinically important side effects.