Efficacy and safety of adding mizoribine to standard treatment in patients with immunoglobulin A nephropathy: A randomized controlled trial

Hirai, Keiji; Ookawara, Susumu; Kitano, Taisuke; Miyazawa, Haruhisa; K, Ito; Ueda, Yuichirou; Kaku, Yoshio; Hoshino, Taro; Mori, Honami; Yokoyama, Izumi; Kubota, Kenji; Yamaji, Yasuyoshi; Takeda, Takeshi; Nakamura, Yoshikazu; Tabei, Kaoru; Morishita, Yoshiyuki

doi:10.23876/j.krcp.2017.36.2.159

Cited by 4 publications

(1 citation statement)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Immunoglobulin A (IgA) nephropathy is a primary glomerular disease characterized by the deposition of IgA in the mesangial region ( 1 , 2 ), and 10–20% of patients with IgA nephropathy develop end-stage renal disease within 10 years ( 3 ). Disease progression is often accompanied by a variety of complications, such as glomerulosclerosis, renal interstitial fibrosis, hypertension, proteinuria, and renal insufficiency ( 4 , 5 ).…”

Section: Introductionmentioning

confidence: 99%

Quantitative Comparison of the Clinical Efficacy of 6 Classes Drugs for IgA Nephropathy: A Model-Based Meta-Analysis of Drugs for Clinical Treatments

Luo

Zhu

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

IntroductionThere is a wide variety of drugs for the clinical treatment of immunoglobulin A (IgA) nephropathy; however, previous studies have failed to clarify the quantitative differences in the efficacy of various drugs. In this study, we aimed to quantitatively compare the clinical efficacy of 6 classes of drugs with different pharmacological mechanisms for the treatment of IgA nephropathy and to identify relevant influencing factors.MethodsClinical trials of drugs for the treatment of IgA nephropathy were obtained from public databases. The change in daily urinary protein excretion from baseline was used as the efficacy index, and the time–effect model was established using a model-based meta-analysis method. Based on the final model, the typical efficacy was simulated, and the differences in efficacy were compared.ResultsA total of 40 studies with 2288 subjects were included in this study. The results showed that the time–effect relationship of the placebo and 6 classes of drugs was consistent with the Emax model. The placebo reduced urinary protein excretion by up to 0.44 g/day, and it took more than 27 months to reach half of its maximum effect. The onset of the 6 classes of drugs were the same; they all reached half of their maximum effect after 5.59 months. More importantly, we found a significant influence of urinary protein baseline on drug efficacy, as indicated by an increase of 0.63 g/day in the theoretical maximum effect of drugs for every 1 g/day increase in urinary protein baseline. After correcting for the urinary protein baseline, the order of efficacy of the 6 classes of drugs was as follows: corticosteroids > immunosuppressants > other drugs > renin–angiotensin system blockers > antiplatelet agents > N-3 fatty acids.ConclusionThis study provides the first comprehensive quantitative analysis of the differences in the efficacy of 6 classes of drugs with different pharmacological mechanisms for treating IgA nephropathy. The results of this study provide an important reference for the rational clinical use of drugs for IgA nephropathy, and also provide a reliable efficacy standard for the development of new drugs for IgA nephropathy.

show abstract

Section: Introductionmentioning

confidence: 99%

Quantitative Comparison of the Clinical Efficacy of 6 Classes Drugs for IgA Nephropathy: A Model-Based Meta-Analysis of Drugs for Clinical Treatments

Luo

Zhu

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

show abstract

Immunosuppressive agents for treating IgA nephropathy

Natale

Palmer

Ruospo

et al. 2020

Cochrane Database of Systematic Reviews

View full text Add to dashboard Cite

show abstract

Efficacy and Safety of Immunosuppressive Treatment in IgA Nephropathy: A Meta-analysis of Randomized Controlled Trials

Zhang

Yang

Jiang

et al. 2019

Preprint

View full text Add to dashboard Cite

25 Background: There is some controversy regarding the efficacy and safety of 26 immunosuppressive agents for the treatment of kidney diseases. The recent STOP-IgAN and 27 TESTING studies have focused attention on the application of immunosuppressive agents in 28 IgA nephropathy (IgAN). This study investigated the benefits and risks of 29 immunosuppressive agents in IgAN.30 Methods: MEDLINE, EMBASE, the Cochrane Library, and article reference lists were 31 searched for randomized controlled trials (RCTs) comparing immunosuppressive agents with 32 any other non-immunosuppressive agents for treating IgAN. A meta-analysis was performed 33 on the outcomes of proteinuria, creatinine (Cr), estimated glomerular filtration rate (eGFR), 34 and adverse events in patients with IgAN, and trial sequential analyses were also performed 35 for outcomes. 36 Results: Twenty-nine RCTs (1957 patients) that met our inclusion criteria were identified. 37 Steroids (weighted mean difference [WMD] -0.70, 95% confidence interval [CI] -1.2 to 38 -0.20), non-steroidal immunosuppressive agents (NSI) (WMD -0. 43, 95% CI -0.55 to 39 -0.31), and combined steroidal and non-steroidal immunosuppressive agents (S&NSI) 40 (WMD -1.46, 95% CI -2.13 to -0.79) therapy significantly reduced proteinuria levels in 41 patients with IgAN. Steroid treatment significantly reduced the risk for end-stage renal 42 disease (ESRD) (relative risk [RR] 0.39, CI 0.19 to 0.79). The immunosuppressive therapy 43 group showed significant increases in gastrointestinal, hematological, dermatological, and 44 genitourinary side effects, as well as impaired glucose tolerance or diabetes. Hyperkalemia 45 was more common in the control group.46 Conclusion: Immunosuppressive therapy can significantly reduce proteinuria and ESRD risk 3 47 in patients with IgAN, but with a concomitant increase in adverse reactions. Therefore, care 48 is required in the application of immunosuppressive agents in IgAN. 49 50 Introduction 51 IgA nephropathy (IgAN) is one of the most common primary glomerular diseases (1). A 52 systematic review demonstrated an overall population incidence of IgAN of 2.5/100000/year 53 (2). There is still no uniform standard of treatment for IgAN. The 2012 Kidney Disease: 54 Improving Global Outcomes (KDIGO) guidelines (3) for IgAN recommend treatment with a 55 renin-angiotensin system (RAS) blocker, such as angiotensin-converting enzyme inhibitors 56 (ACEIs) and angiotensin II receptor blockers (ARBs), in patients with proteinuria with 57 protein excretion > 1 g/day. Corticosteroid therapy can be considered in patients with 58 proteinuria > 1 g/day after 3-6 months of best supportive treatment and without renal failure. 59 Intensive immunosuppression is reserved for patients with crescents in more than half the 60 glomeruli and a rapid decline in renal function. 61 The publication of the Supportive versus Immunosuppressive Therapy of Progressive IgA 62 Nephropathy (STOP-IgAN) trial in 2015 and Therapeutic Evaluation of Steroids in IgA 63 Nephropathy Global (TESTING) t...

show abstract

Efficacy and safety of adding mizoribine to standard treatment in patients with immunoglobulin A nephropathy: A randomized controlled trial

Cited by 4 publications

References 25 publications

Quantitative Comparison of the Clinical Efficacy of 6 Classes Drugs for IgA Nephropathy: A Model-Based Meta-Analysis of Drugs for Clinical Treatments

Quantitative Comparison of the Clinical Efficacy of 6 Classes Drugs for IgA Nephropathy: A Model-Based Meta-Analysis of Drugs for Clinical Treatments

Immunosuppressive agents for treating IgA nephropathy

Efficacy and Safety of Immunosuppressive Treatment in IgA Nephropathy: A Meta-analysis of Randomized Controlled Trials

Contact Info

Product

Resources

About