Abstract
BackgroundIgA nephropathy is the most common progressive glomerular disease to end stage renal failure worldwide. Calcineurin inhibitors (CNIs) is a selective immunosuppressant widely used in organ transplantation. The efficacy and safety of calcineurin inhibitors for the treatment of IgA nephropathy remain uncertain.MethodsWe performed a systematic literature search using the PubMed, Embase, Science Citation Index, Ovid evidence-based medicine, Chinese Biomedical Literature (CBM) and Chinese science and technology periodicals (CNKI, VIP, and Wan Fang) for randomized, controlled trials of CNIs therapy of IgA nephropathy. Complete remission rate (CR) was defined as proteinuria less than 0.5 or 0.3 g/d. Partial remission rate (PR) was defined as proteinuria reduced to at least half of the baseline measurement and an absolute value of >0.5 or 0.3 g/d.ResultsSeven relevant trials were conducted with 374 patients enrolled. CNIs plus medium/low-dose steroid had a higher CR (RR = 2.51 [95% CI,1.25 to 5.04], P = 0.02) compared to therapy with steroid alone or placebo, but were not significant on PR (RR = 0.87 [95% CI,0.32 to 2.38]; P = 0.78). Also, significant alterations were observed in proteinuria (weighted mean difference, −0.46 g/d,[95% CI:-0.55 to −0.24], P < 0.01) with no differences were found in serum creatinine (SCr) (weighted mean difference, 0.57,95% CI:-4.05 to 5.19; P = 0.78) and estimated glomerular filtration rate (eGFR) (weighted mean difference, 1.13,95% CI:-4.05 to 6.32; P = 0.34) level between the two groups. CNI therapy was associated with an increased risk for adverse events (RR = 2.21,95% CI:1.52 to 3.21, P < 0.01), such as gastrointestinal and neurological symptoms or hirsutism.ConclusionsCNIs might provide renal protection in patients with IgAN, but at an increased risk of adverse events. Reliably defining the efficacy and safety of CNIs in IgAN requires a high-quality trial with a large sample size.
Highlights
IgA nephropathy is the most common progressive glomerular disease to end stage renal failure worldwide
IgA patients who achieved remission had far better outcomes than those who never achieved remission [34, 35]. These findings suggest that achieving remission, whether Complete remission rate (CR) or Partial remission rate (PR), is important in IgA patients to improve renal survival, irrespective of glomerular disease type
The fear of increase in serum creatinine (Scr) seems to have prevented the researchers from designing clinical trials to study this valuable immunosuppressive agent in the treatment of Immunoglobulin A nephropathy (IgAN), and we suggest starting such trials for a better long-term judgment
Summary
IgA nephropathy is the most common progressive glomerular disease to end stage renal failure worldwide. The efficacy and safety of calcineurin inhibitors for the treatment of IgA nephropathy remain uncertain. Due to the lack of controlled clinical trials, the benefit and risk of CNIs in the treatment of IgAN remained uncertain [5,6,7,8]. There are a few other studies that have successfully used CNIs in resistant IgAN patients, which demonstrated that CNIs could decrease proteinuria in IgAN patients who showed resistance to steroids and/or other immunosuppressants [9]
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