The effect of calcineurin inhibitors in the treatment of IgA nephropathy

Abstract

Background:Immunoglobin A nephropathy (IgAN), the most prevalent form of primary glomerulonephritis, represents the leading cause of kidney failure among East Asian populations. Immunosuppressive treatment regimen, except for a 6-month trial of corticosteroids, has not been approved by the KDIGO guideline yet. Specific and effective treatment is still lacking. We decided to evaluate the efficacy and safety of the calcineurin inhibitors (CNIs) in the treatment of IgAN.Methods:Database from the Cochrane library, PubMed, Embase, CBM, CNKI, and CENTRAL databases were searched and reviewed up to March 2016. Literature was screened by 2 independent reviewers accordingly. Clinical trials were analyzed using Stata 12.0.Results:Five random control trials and 2 nonrandomized concurrent control trials were selected and included in this study according to our inclusion and exclusion criteria. The rates of complete remission in patients with IgAN were significantly increased in the group of CNIs (RR 1.56, P = 0.002). No statistical difference was observed in the rates of partial remission, or response between the CNIs and steroids alone. Additionally, CNIs resulted in a significant reduction in urinary protein (WMD 0.34, P = 0.002) and increase in serum albumin level (WMD 1.89, P = 0.013). No differences were found in the serum creatinine, estimated glomerular filtration rate, and rates of adverse effects including infection, hyperglycemia, and liver dysfunction.Conclusion:With present evidence, CNIs may be promising immunosuppressive agents for IgAN in future. However, large, long-term, multicenter trials are required to confirm our findings.

Efficacy and safety of tacrolimus combined with glucocorticoid treatment for IgA nephropathy: a meta-analysis

“…Our results are similar to those of a previous study showing that patients with IgAN may experience significant improvement in proteinuria and hypoalbuminemia during TAC treatment. 43 Moreover, this meta-analysis concluded that there is no significant difference in the relative risk of adverse events at the end of treatment or during follow-up. IgAN patients who achieved remission had far better outcomes than those who did not.…”

A comparison of the effectiveness of cyclophosphamide, leflunomide, corticosteroids, or conservative management alone in patients with IgA nephropathy: a retrospective observational study

“…It is a relatively benign disease, however, the long term prognosis should not be considered mild, because, after 20 years of disease progression, 20–50% of the patients reach end stage renal disease 3 – 6 . A number of immunosuppressive agents have been used for treatment of IgAN, including calcineurin inhibitors 7 , 8 , azathioprine 9 , mycophenolate mofetil 10 , 11 , cyclophosphamide 11 , 12 , leflunomide 13 , 14 , corticosteroids 12 , 15 – 17 , etc. Many studies have only compared two treatment regimens for a relatively small sample size.…”

Combined Immunosuppressive Treatment May Improve Short-Term Renal Outcomes in Chinese Patients with Advanced IgA Nephropathy

“…However, no recommendation was made for patients with eGFR < 45 ml/min/1.73m 2 . Given that some studies supported the use of steroids or immunosuppressants [7][8][9] for these patients, which is also widely applied clinically, thus we conducted this study to explore whether corticosteroids or immunosuppressant therapies could improve the renal outcome of patients with advanced IgAN (eGFR < 45 mL/min/1.73 m 2 and mean proteinuria > 1 g/24h).…”