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

Abstract

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...

A Novel Scoring System Based on Oxford Classification Indicating Steroid Therapy Use for IgA Nephropathy

“…1 Since then, the beneficial effects of treatment strategies for the prevention of progression to end-stage renal disease (ESRD) have been reported. [2][3][4][5][6] Indications for these therapies are generally decided based on disease activity, such as proteinuria and haematuria levels, renal function, and the patient's background, including age, presence of hypertension, and comorbidities. [7][8][9] Histological findings should also be considered, and several validation and classification systems that predict the renal prognosis have been reported.…”

Immunosuppressants or corticosteroids compared with supportive therapy: a systematic review and meta-analysis on the efficacy and safety for IgA nephropathy treatment

“…Moreover, our results also showed that the 2 treatment regimens had a similar risk of adverse events, which was different from the results of other studies. The metaanalyses using non-immunosuppressants/corticosteroids as a reference showed that immunosuppressants/ corticosteroids significantly increased the incidence of adverse events (30,31). The possible reason may be that our reference objects were patients receiving a single supportive treatment, and the types of adverse events in this study were diverse and mainly mild with good tolerance, including diarrhea, gastrointestinal discomfort, cough, insomnia, nausea, and mild hair loss.…”

Literature Review: The Efficacy of Glucocorticoids in IgA Nephropathy Patients

“…Initially, the malady was believed to be the uncommon and benign cause of rehashed hematuria. Be that as it may, it has since gotten to be clear that IgAN is neither rare nor benign [1] and is the frequent cause of primary glomerulonephritis around the world [1,2]. IgAN in up to 15-20% of patients within 10 years from the malady onset which leads to end-stage renal disease (ESRD) and 30-40% within 20 years [2].…”