Non-immunosuppressive treatment for IgA nephropathy

Key messages

Treatment with renin-angiotensin system (RAS) inhibition, namely angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, is the most common first-line, non-immunosuppressive therapy used for managing patients with IgA nephropathy (IgAN).

The role of other non-immunosuppressive treatments in managing IgAN is unclear and warrants further clinical studies.

Why treat IgA nephropathy with non-immunosuppressive therapies?

IgAN is one of the most common kidney diseases, leading to reduced kidney function and kidney failure for about 20% to 40% of patients within 20 to 25 years. The cause of IgAN is not widely understood, but most people have an abnormality in their immune system that leads to damage to the kidney. However, other non-immune functions play a role in the disease's impact on the kidney.

What did we want to find out?

We wanted to find out if non-immunosuppressive treatments (e.g. antihypertensive agents, anticoagulants, fish oil, tonsillectomy, herbal medicine) improved kidney function in adults and children with IgAN.

What did we do?

We searched for all trials that assessed the benefits and harms of randomly allocated non-immunosuppressive treatment in people with IgAN. We compared and summarised the results of the trials and rated our confidence in the information based on factors such as trial methods and sizes.

What did we find?

We included 80 studies involving 4856 people with IgAN treated with a diverse collection of non-immunosuppressive treatments. Patients in studies were given various therapies, including blood pressure lowering agents (antihypertensives), removal of participant's tonsils (tonsillectomy), antimalarials, traditional Chinese medicine, dietary supplements (e.g. fish oil), and vitamin D receptor agonists. Antihypertensive medication aimed at inhibiting the RAS appears to slow damage to the kidney with minimal side effects. However, its impact in preventing people from progressing to kidney failure is unclear. Other interventions, such as tonsillectomy, antimalarial medication, and low-calorie restricted diets role in treating patients are still unclear.

What are the limitations of the evidence?

The small number of studies per comparison and the small size of the studies were limitations in this review. Not all the studies provided data about the outcomes we were interested in. We are unsure about the results.

How up to date is the evidence?

The evidence is up to date as of December 2023.

Authors' conclusions: 

Available RCTs focused on a diverse range of interventions. They were few, small, and of insufficient duration to determine potential long-term benefits on important kidney and cardiovascular outcomes and harms of treatment. Antihypertensive agents appear to be the most beneficial non-immunosuppressive intervention for IgAN. The antihypertensives examined were predominantly angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. The benefits of RAS inhibition appear to outweigh the harms in patients with IgAN. The certainty of the evidence of RCTs demonstrating a benefit of tonsillectomy to patients with Japanese patients with IgAN was low. In addition, these findings are inconsistent across observational studies in people with IgAN of other ethnicities; hence, tonsillectomy is not widely recommended, given the potential harm of therapy. The RCT evidence is insufficiently robust to demonstrate efficacy for the other non-immunosuppressive treatments evaluated here.

Read the full abstract...

IgA nephropathy (IgAN) is the most common primary glomerular disease, with approximately 20% to 40% of patients progressing to kidney failure within 25 years. Non-immunosuppressive treatment has become a mainstay in the management of IgAN by improving blood pressure (BP) management, decreasing proteinuria, and avoiding the risks of long-term immunosuppressive management. Due to the slowly progressive nature of the disease, clinical trials are often underpowered, and conflicting information about management with non-immunosuppressive treatment is common. This is an update of a Cochrane review, first published in 2011.


To assess the benefits and harms of non-immunosuppressive treatment for treating IgAN in adults and children. We aimed to examine all non-immunosuppressive therapies (e.g. anticoagulants, antihypertensives, dietary restriction and supplementation, tonsillectomy, and herbal medicines) in the management of IgAN.

Search strategy: 

We searched the Cochrane Kidney and Transplant Register of Studies up to December 2023 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal and

Selection criteria: 

Randomised controlled trials (RCTs) and quasi-RCTs of non-immunosuppressive agents in adults and children with biopsy-proven IgAN were included.

Data collection and analysis: 

Two authors independently reviewed search results, extracted data and assessed study quality. Results were expressed as mean differences (MD) for continuous outcomes and risk ratios (RR) for dichotomous outcomes with 95% confidence intervals (CI) using random-effects meta-analysis. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.

Main results: 

This review includes 80 studies (4856 participants), of which 24 new studies (2018 participants) were included in this review update. The risk of bias within the included studies was mostly high or unclear for many of the assessed methodological domains, with poor reporting of important key clinical trial methods in most studies.

Antihypertensive therapies were the most examined non-immunosuppressive therapy (37 studies, 1799 participants). Compared to placebo or no treatment, renin-angiotensin system (RAS) inhibition probably decreases proteinuria (3 studies, 199 participants: MD - 0.71 g/24 h, 95% CI -1.04 to -0.39; moderate certainty evidence) but may result in little or no difference to kidney failure or doubling of serum creatinine (SCr), or complete remission of proteinuria (low certainty evidence). Death, remission of haematuria, relapse of proteinuria or > 50% increase in SCr were not reported. Compared to symptomatic treatment, RAS inhibition (3 studies, 168 participants) probably decreases proteinuria (MD -1.16 g/24 h, 95% CI -1.52 to -0.81) and SCr (MD -9.37 µmol/L, 95% CI -71.95 to -6.80) and probably increases creatinine clearance (2 studies, 127 participants: MD 23.26 mL/min, 95% CI 10.40 to 36.12) (all moderate certainty evidence); however, the risk of kidney failure is uncertain (1 study, 34 participants: RR 0.20, 95% CI 0.01 to 3.88; very low certainty evidence). Death, remission of proteinuria or haematuria, or relapse of proteinuria were not reported. The risk of adverse events may be no different with RAS inhibition compared to either placebo or symptomatic treatment (low certainty evidence).

In low certainty evidence, tonsillectomy in people with IgAN in addition to standard care may increase remission of proteinuria compared to standard care alone (2 studies, 143 participants: RR 1.90, 95% CI 1.45 to 2.47) and remission of microscopic haematuria (2 studies, 143 participants: RR 1.93, 95% CI 1.47 to 2.53) and may decrease relapse of proteinuria (1 study, 73 participants: RR 0.70, 95% CI 0.57 to 0.85) and relapse of haematuria (1 study, 72 participants: RR 0.70, 95% CI 0.51 to 0.98). Death, kidney failure and a > 50% increase in SCr were not reported. These trials have only been conducted in Japanese people with IgAN, and the findings' generalisability is unclear.

Anticoagulant therapy, fish oil, and traditional Chinese medicines exhibited small benefits to kidney function in patients with IgAN when compared to placebo or no treatment. However, compared to standard care, the kidney function benefits are no longer evident. Antimalarial therapy compared to placebo in one study reported an increase in a > 50% reduction of proteinuria (53 participants: RR 3.13 g/24 h, 95% CI 1.17 to 8.36; low certainty evidence). Although, there was uncertainty regarding adverse events from this study due to very few events.