Treatment Of IgA Nephropathy Research Articles

Recurrence of glomerular diseases after kidney transplantation: What do we know new?

The recurrence of primary glomerulonephritis (GN) following kidney transplantation poses a significant threat to graft survival. To enhance kidney transplant outcomes, we must lessen the burden of recurrence. In recent years, there has been progress in understanding the incidence, risk factors for recurrence, pathophysiology, biomarkers, and therapeutics, making it worthwhile to conduct an update on primary glomerulonephritis that may recur following kidney transplantation. We conducted a narrative review of the literature on the novel discoveries of primary GN that can recur following kidney transplantation. To summarize, developing a broad consensus on recurrence diagnosis would greatly advance our understanding, and its development would be a valuable collaborative effort. The key risk factors for recurrence have been better understood, particularly in individuals with complement-related or monoclonal gammopathy-related recurrent membranoproliferative glomerulonephritis. Furthermore, we can identify better recurrent IgA nephropathy patients who are more likely to experience graft loss. New biomarkers for membranous nephropathy (anti-PLA2R-Ab) and focal and segmental glomerulosclerosis (anti-nephrin-Ab) can assist in identifying and monitoring patients at risk of recurrence. Regarding therapy, the focal and segmental glomerulosclerosis consensus will enhance recurrence treatment. Some complement inhibitors and anti-CD38 monoclonal antibodies are already promising in treating and healing recurrent C3 glomerulopathy and focal and segmental glomerulosclerosis, respectively. Finally, new drugs developed specifically to treat IgA nephropathy in the native kidney will also change the outcome of IgA nephropathy recurrence. Although there has been progress in understanding the recurrence of primary glomerulonephritis following kidney transplantation, a worldwide effort should be undertaken to gather research that will allow for improved diagnosis, monitoring, and management of these patients.

TACI Ig Fusion Protein Inhibits TLR4/MyD88/NF-κB Pathway Alleviates Renal Injury in IgA Nephropathy Rats.

To evaluate the impact of TACI fusion protein (TACI-Ig) on IgA nephropathy (IgAN) in rats, and to explore its mechanism and relationship with TLR4/MyD88/NF-κB pathway. Sprague Dawley(SD)rats were divided into six groups: control, model, TACI-Ig low dose (TACI-Ig-L), medium dose (TACI-Ig-M), high dose (TACI-Ig-H), and prednisone acetate (PAT) group. The control group and model group received physiological saline injections, while the TACI-Ig groups were administered doses of 7.18, 14.36, and 28.72 mg/kg of TACI-Ig, respectively. PAT group was pretreated with prednisone acetate. After 8 weeks, kidney weight/body weight ratios, 24-hour urine protein (24 h UP), serum creatinine (SCr), and blood urea nitrogen (BUN) levels were measured. Additionally, concentrations of B cell activating factor (BAFF), APRIL, and Gd-IgA1 were evaluated by using ELISA. Pathological changes in kidney tissues were scored, and TLR4, MyD88, NF-κB expression levels were detected through western blot (WB) and RT-qPCR. Results. Renal function assessments showed that the IgAN model group exhibited increased in 24 h UP, SCr, BUN, and elevated serum levels of BAFF, APRIL, Gd-IgA1, alongside higher TLR4/MyD88/NF-κB protein expression. TACI-Ig treatment significantly reduced proteinuria, SCr, BUN, levels of BAFF, APRIL, and Gd-IgA1 in IgAN rats. Pathologically, TACI-Ig ameliorated glomerular mesangial deposition and fibrosis. It also inhibited TLR4/MyD88/NF-κB protein expression, demonstrating anti-inflammatory and immune regulatory effects. TACI-Ig mitigates renal injury in IgAN rats by reducing inflammatory infiltration and IgA deposition and suppressing the pathway of TLR4/MyD88/NF-κB, offering data for developing effective treatments for IgAN.

Steps forward in the treatment of IgA nephropathy.

Steps forward in the treatment of IgA nephropathy.

First real-world evidence of sparsentan efficacy in patients with IgA nephropathy treated with SGLT2 inhibitors

Abstract Background Sparsentan, a dual-acting antagonist for both the angiotensin II receptor type 1 and the endothelin receptor type A, has emerged as a promising therapeutic agent for the treatment of IgA nephropathy (IgAN). Following the publication of the PROTECT trial, sparsentan recently received approval for the treatment of IgAN in Europe. However, it remains uncertain whether an additive effect can be observed in the context of existing treatment with sodium-glucose co-transporter 2 (SGLT2) inhibitors, given that the PROTECT study did not investigate this dual therapy approach. Methods A total of 23 patients with IgAN were treated with sparsentan via the Managed Access Programme between December 2023 and August 2024. The Patients were stable on maximum tolerated doses of renin-angiotensin system (RAS) and SGLT2 inhibitors, with an estimated glomerular filtration rate (eGFR) >30 ml/min/1.73 m² and a urine protein-creatinine ratio (UPCR) >0.75 g/g. Results Of the 23 patients, median (IQR) baseline eGFR (CKD-EPI) was 42 mL/min/1.73 m2 (32–63) and median baseline UPCR was 1.5 g/g (0.9–1.8). After initiation of sparsentan, UPCR significantly decreased (p < 0.0001) to a median of 0.85 g/g (0.42–1.15) in the 2-week follow-up and further declined (p = 0.001) to a median of 0.60 g/g (0.32–0.82) after 14 weeks, equivalent to a relative reduction in proteinuria up to 62% (45–74). A similar significant reduction was observed for the urine albumin-creatinine ratio (UACR). No drug-related serious adverse events were reported. Conclusions In this real-world setting, sparsentan shows a significant impact on proteinuria, leading to a relative reduction of 62% in UPCR after 14 weeks and beyond, even in patients already receiving SGLT2 inhibitors.

Post-transplant IgA nephropathy: a rapidly evolving field of kidney transplant medicine.

IgA nephropathy is the commonest pattern of primary glomerular disease in the world, with high rates of progression to kidney failure. As IgA nephropathy commonly causes kidney failure at a young age, kidney transplantation is commonly used to treat kidney failure. However, high rates of recurrent disease in the allograft remain a common management challenge. The prevalence of post-transplant recurrence approaches 15% at ten years post-transplant and is associated with poor allograft function and high rates of allograft loss. Post-transplant IgA nephropathy has also been described de novo in some case series. Treatment of recurrent IgA nephropathy has been challenging but with the rapid growth of new treatments for IgA nephropathy it is likely that many of these treatments will, over time, transition to the treatment of recurrent disease. In this narrative review, our aim is to evaluate post-transplant IgA nephropathy in terms of epidemiology, risk factors, underlying pathophysiology, diagnosis and management strategies.

Network Pharmacological Analysis of Hydroxychloroquine Intervention in the Treatment of Iga Nephropathy.

IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis globally and has a high propensity to develop into end-stage renal disease (ESRD). Hydroxychloroquine has been proven to reduce proteinuria in IgAN patients, but the precise mechanism remains unclear. Therefore, network pharmacology was used to investigate the mechanism. PubChem and SwissADME databases were utilized to acquire the structure of hydroxychloroquine. The SwissTargetPrediction, PharmMapper, DrugBank, TargetNet, and BATMAN-TCM databases were then utilized to obtain the targets. The target genes related to IgAN were then gathered from the databases, which included GeneCards, PHARMGKB, DrugBank, OMIM, and DisGeNET. Common targets were obtained by UniProt. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to define the main molecular mechanisms and pathways. Furthermore, a protein-protein interaction (PPI) network was constructed using the STRING tool, and the core targets were obtained by Cytoscape. Finally, molecular docking between the core targets and hydroxychloroquine was performed. 167 common target genes were acquired by overlapping. The core targets were TNF, ALB, IL1B, JUN, FOS, SRC, and MMP9. The GO and KEGG results showed the targets to be related to the production of inflammatory cytokines and chemokines and were engaged in the toll-like receptor (TLR) signaling pathway. At the same time, the molecular docking results showed that the core targets all combined with hydroxychloroquine closely. This study proved that hydroxychloroquine may treat IgAN through the TLR signaling pathway, and the restraint of TNF, TLR, IL1B, and JUN may be essential for the treatment.

Therapeutic Profile of IgA Nephropathy Regarding Pharyngeal Kidney Theory

IgA nephropathy (IgAN) is the most common glomerular disease, which is one of the main causes of chronic kidney disease. The course of this disease is prolonged, and the condition is often recurrent, and most of the disease changes after respiratory, gastrointestinal, and urinary infections, and respiratory infections are the most common of the three, which makes the treatment more difficult. In Chinese medicine, there is no direct name for this disease, but according to its symptoms, it can be categorized as "hematuria", "edema", "urolithiasis", "slow kidney wind" and other diseases. The disease is often caused by the recurrence of exogenous infections. For the recurrence of this disease due to exogenous infection, Chinese medicine treats IgA nephropathy from the pharynx according to the theory of "pharyngeal and renal correlation", which has achieved good clinical efficacy, and this point of view has received more and more attention nowadays. This article focuses on the treatment of IgA nephropathy from the pharyngeal-renal theory.

From Despair to Promise: The Dawn of Novel Treatment in IgA Nephropathy.

From Despair to Promise: The Dawn of Novel Treatment in IgA Nephropathy.

Integrative multi-omics and network pharmacology reveal the mechanisms of Fangji Huangqi Decoction in treating IgA nephropathy

Ethnopharmacological relevanceFangji Huangqi Decoction (FJHQD), a classical Chinese herbal formulation, has demonstrated significant clinical efficacy in the treatment of IgA nephropathy (IgAN), although its mechanisms remain poorly understood. Aim of the studyThis study aims to investigate the renal protective mechanisms of FJHQD using an integrated approach that combines transcriptomics, proteomics, and network pharmacology. MethodsRenal glomerular structure changes were assessed via hematoxylin and eosin (H&E) and Masson staining. IgA expression in the glomeruli was quantified using immunofluorescence. Furthermore, the potential mechanisms underlying the effects of FJHQD were explored through a combined strategy of network pharmacology, transcriptomics, and proteomics. The expression of signaling pathway-related proteins was detected using Western blot. ResultsFJHQD inhibited mesangial cell proliferation and renal interstitial fibrosis, and significantly reduced excessive IgA deposition in the glomerular mesangium. Network pharmacology identified 113 important active components and 8 common active components in FJHQD, with quercetin, isorhamnetin, jaranol, and kaempferol having the highest number of target interactions. Integration of network pharmacology with multi-omics approaches revealed that 44 active components regulated numerous immune and inflammatory signaling pathways through 17 hub targets. These pathways include the Calcium signaling pathway, cAMP signaling pathway, Ras signaling pathway, MAPK signaling pathway, and PI3K-AKT signaling pathway. Subsequent in vivo experiments demonstrated that FJHQD effectively regulates the identified pathways in IgAN mice. Ultimately, molecular docking results further validated the reliability of the network pharmacology combined with multi-omics analyses. ConclusionThe findings suggest that FJHQD exerts a renal protective effect, potentially through modulation of the Calcium signaling pathway, cAMP signaling pathway, Ras signaling pathway, MAPK signaling pathway, and PI3K-AKT signaling pathway. These insights offer valuable support for the clinical use of FJHQD and open new avenues for exploring the active compounds and molecular mechanisms of Traditional Chinese Medicines (TCMs).

Combination treatment with telitacicept, mycophenolate mofetil and glucocorticoids for immunoglobulin A nephropathy: A case report

BACKGROUND Telitacicept reduces B cell activation and abnormal immunoglobulin A (IgA) antibody production by inhibiting the activity of B lymphocyte stimulator (BLyS) and a proliferation-inducing ligand (APRIL), thereby decreasing IgA deposition in the glomeruli and local inflammatory response. This ultimately protects the kidneys from damage. This mechanism suggests that Telitacicept has potential efficacy in the treatment of IgA nephropathy. CASE SUMMARY We present the case of a 24-year-old female who was diagnosed with IgA nephropathy due to significant proteinuria and mild renal impairment. Pathologically, she exhibited focal proliferative glomerulonephritis. Treatment with angiotensin II receptor blocker, hormones, and mycophenolate mofetil did not lead to a significant improvement in her condition. However, upon the addition of telitacicept, the patient’s renal function recovered and her proteinuria rapidly reduced. Hormones were swiftly tapered and discontinued, with no occurrence of severe infections or related complications. CONCLUSION Telitacicept combined with hormones and mycophenolate mofetil may be a safe and effective induction therapy for IgA nephropathy.

Follow-Up Kidney Biopsy Might Be a Mandatory Procedure after Treatment in IgA Nephropathy

Follow-Up Kidney Biopsy Might Be a Mandatory Procedure after Treatment in IgA Nephropathy

New Insights and Future Perspectives of APRIL in IgA Nephropathy.

IgA nephropathy (IgAN) is characterized by immune-mediated glomerulonephritis, with the accumulation of galactose-deficient IgA1 (Gd-IgA1) in the glomeruli and increased levels of circulating Gd-IgA1 and Gd-IgA1-containing immune complexes. An incomplete understanding of the underlying mechanisms and differences in clinical and pathological features between individuals and ethnicities has contributed to the lack of established treatments for IgAN. A tumor necrosis factor (TNF) family member, a proliferation-inducing ligand (APRIL), is a crucial cytokine essential for the generation and survival of plasma cells. Recent studies demonstrated that APRIL is a pivotal mediator in the production of Gd-IgA1 in IgAN. As our understanding of the autoimmune pathogenesis underlying IgAN has improved, various pharmacological therapeutic targets, including APRIL antagonists, have emerged. Preliminary results showed that APRIL-targeting agents effectively reduced proteinuria and Gd-IgA1 levels without significantly increasing adverse events, indicating their potential as novel therapeutic agents for IgAN. In the present review, we discuss the current understanding of the role of APRIL in the pathogenesis of IgAN and novel therapeutic strategies focusing on APRIL-targeting agents for IgAN. APRIL inhibitors may offer new hope to patients with IgAN.

Efficacy and safety of telitacicept, a BLyS/APRIL dual inhibitor, in the treatment of IgA nephropathy: a retrospective case-control study.

Telitacicept, a B lymphocyte stimulator/A proliferation-inducing ligand dual-target fusion protein, has recently been used in autoimmune diseases. We assessed the efficacy and safety of telitacicept in immunoglobulin A nephropathy (IgAN) patients. This study included 42 IgAN patients who received telitacicept treatment, forming the 'whole telitacicept group'. Among them, 20 patients who had not previously received corticosteroid (CS) therapy or immunosuppressive (IS) agents were categorized as the 'newly treated telitacicept subgroup'. Additionally, 28 patients who were selected to match historical controls received conventional IS therapy (CS therapy with/without IS agents) and were classified as the 'conventional IS group'. Telitacicept was partially used in combination with conventional IS therapy, including initial CS in different doses. Various indicators were compared at 4-week intervals up to 24weeks among the three groups. After 24weeks of treatment, the 24-hour proteinuria decreased from 1.70g [interquartile range (IQR) 1.05-2.58] to 0.21g (IQR 0.39-0.13) (P=.043) in the newly treated telitacicept subgroup, from 1.78g (IQR 0.97-2.82) to 0.44g (IQR 1.48-0.16) (P=.001) in the conventional IS group and from 1.07g (IQR 0.66-1.99) to 0.26g (IQR 0.59-0.17) (P=.028) in the whole telitacicept group. The estimated glomerular filtration rate (eGFR) increased from 76.58±30.26ml/min/1.73m2 to 80.30±26.76ml/min/1.73m2 (P=.016) in the newly treated telitacicept subgroup, from 72.73±33.41ml/min/1.73m2 to 84.08±26.81ml/min/1.73m2 (P=.011) in the conventional IS group and from 70.10±32.88ml/min/1.73m2 to 71.21±31.49ml/min/1.73m2 (P=.065) in the whole telitacicept group. During follow-up periods, the efficacy rates of the three groups did not show statistically significant differences and no serious adverse events were observed. Telitacicept may be a safe and effective treatment for IgAN, offering reductions in proteinuria and increases in eGFR similar to conventional IS therapy. After a 24-week follow-up, the incidence of adverse events was lower for telitacicept than for conventional IS therapy.

IgA Nephropathy – Current and Future Perspectives in Treatment

Abstract Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulopathy in our adult population and is associated with a high lifetime risk of kidney failure. Recent years have succeeded in describing the pathogenesis of IgAN at the molecular level, where immune complexes containing specific galactose deficient IgA1 play an essential role. The gold standard in the diagnosis of IgAN remains renal biopsy followed by determination of a prognostic score using the Oxford classification. A fundamental goal in the management of patients with IgAN is to optimize supportive therapy involving active lifestyle modification and renoprotective medications. The reno-protective drug menu has recently been expanded to include effective sodium-glucose cotransporter 2 inhibitors (SGLT2i), and additional agents are on the way. However, despite maximal supportive therapy, a wide range of patients remain at high risk of disease progression and require the deployment of immunomodulatory drugs. To date, however, we do not have high potency agents that are well tolerated and safe. This has led to the initiation of many studies to target the inflammatory process at different pathogenetic levels. In this article, we summarize the current standards in the treatment of IgAN and present new promising options in the management of this disease.

IgA Nephropathy: Significance of IgA1-Containing Immune Complexes in Clinical Settings.

IgA nephropathy (IgAN) is considered to be an autoimmune disease characterized by the formation of IgA1-containing immune complexes in the circulation and glomerular immunodeposits. Extensive research has identified multiple genetic, immunological, and environmental factors contributing to disease development and progression. The pathogenesis of IgAN is considered a multifactorial process involving the formation of immune complexes wherein aberrantly O-glycosylated IgA1 is recognized as an autoantigen. Consequently, the clinical presentation of IgAN is highly variable, with a wide spectrum of manifestations ranging from isolated microscopic hematuria or episodic macroscopic hematuria to nephrotic-range proteinuria. Whereas some patients may exhibit a slowly progressive form of IgAN, others may present with a rapidly progressive glomerulonephritis leading to kidney failure. Development of the treatment for IgAN requires an understanding of the characteristics of the pathogenic IgA1-containing immune complexes that enter the glomerular mesangium and induce kidney injury. However, not all details of the mechanisms involved in the production of galactose-deficient IgA1 and immune-complex formation are fully understood. Here, we review what we have learned about the characteristics of nephritogenic IgA1 in the half-century since the first description of IgAN in 1968.

Advances in primary glomerulonephritis.

Primary glomerulonephritis comprises several renal-limited diseases that can cause haematoproteinuria, chronic kidney disease, nephrosis and end stage kidney disease. The most common of these are IgA nephropathy (IgAN), primary membranous nephropathy (PMN), Focal Segmental Glomerulosclerosis (FSGS) and Minimal Change Disease (MCD). Although rare, these diseases cause a significant burden to health care systems, given the high cost of treating End Stage Kidney Disease (ESKD) with dialysis or transplantation. Until recently, the pathogenesis of primary gloerulonephritis has remained obscure. However, recent advances in understanding of how these diseases evolve has led to the introduction of novel therapeutic agents. Trials are underway or have recently completed that have huge implications for the standard of care for the primary glomerulonephritidies, and should dramatically reduce the number of patients who progress onto end stage kidney disease. This article reviews the international Kidney Disease Improving Global Outcomes (KDIGO) guidelines for the treatment of IgAN, PMN, FSGS and MCD, as well as recent research on pathogenesis and treatment.

Effectiveness and Safety of Spironolactone in the Treatment of IgA Nephropathy: A Retrospective Self-Controlled Study

Introduction: It is crucial to utilize combination therapy for immunoglobulin A nephropathy (IgAN) patients to reduce proteinuria and maintain stable kidney function. We demonstrate the safety and efficacy of low-dose spironolactone in the management of IgAN patients. Methods: Adult IgAN patients treated with spironolactone were evaluated. Patients were separated into two categories according to whether 24-h proteinuria was reduced by more than 20% after 2 months of spironolactone treatment compared to baseline levels. Results: Eighty-eight patients were analyzed and 24-h proteinuria decreased from 0.93 g to 0.70 g (p < 0.001) after 2 months of treatment with spironolactone, accompanied by a slight decrease in eGFR from 75.7 to 73.9 mL/min/1.73 m2 (p = 0.033). Intriguingly, 47 patients in the effective mineralocorticoid receptor antagonist (MRA) group showed less endocapillary hypercellularity (p = 0.040). In the ineffective group, 18 patients discontinued MRA treatment because 24-h proteinuria increased from 0.83 g to 1.04 g, while the other 23 patients continued with spironolactone and proteinuria decreased to 0.57 g in the sixth month (p = 0.001). Furthermore, 12 patients with persistent high proteinuria during prednisone therapy were added with spironolactone. 24-proteinuria was dropped from 0.95 g to 0.73 g at the second month and to 0.50 g at the sixth month. Conclusions: In our study, we confirmed spironolactone’s efficacy in reducing urine protein excretion in IgA nephropathy patients within 2 months of treatment. However, response varied among patients, with those showing endocapillary proliferation (E1) in renal biopsies having poor spironolactone responsiveness. Administering MRAs to patients with eGFR over 30 mL/min did not result in hyperkalemia, indicating the treatment’s safety.

Current understanding and new insights in the treatment of IgA nephropathy.

IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, and almost all patients are at risk of progression to end-stage kidney disease within their lifetime. The mechanisms responsible for the presentation and development of IgAN are required for the development of highly targeted therapies for this disease. In this review, we first demonstrate the current treatment strategy of IgAN recommended by the 2021 KDIGO guideline. Then, we update the new insights into disease pathogenesis based on the well acknowledged 'multiple-hit hypothesis' and provide the potential therapeutic targets involved in the upstream production of pathogenic IgA1 and the downstream complement activation. Finally, the recent large randomized controlled trials focusing on these novel targets have been summarized, among which Nefecon and Sparsentan have received approval and Telitacicept have been used off-label for IgAN. In the future, emerging treatment approaches for IgAN is likely to evolve, which will signify a shift in the management of the IgAN from traditional immunosuppressive approaches to an era of targeted treatment based on the understanding of the pathogenic mechanisms.

Research Progress of Traditional Chinese Medicine in the Treatment of IgA Nephropathy

The treatment of IgA nephropathy (IgAN) is difficult, and modern medicine is still not clear about its etiology and pathogenesis. Traditional Chinese medicine(TCM) plays an important role in the treatment of IgAN, the use of "poison damage of renal collaterals", from the wind treatment, general use, "mediation trijiao", treating IgAN from the pharynx, spleen and kidney, intelligent door as well as five zang-organs make , the selection of Zhuling decoction, Banxia-xiexin decoction, Shenqi-Dihuang Decoction, Guben-Tongluo Decoction and other classic and experience prescriptions, trijiao acupuncture, invigorating spleen and kidney acupuncture treatment, etc. TCM such as diet therapy can control clinical symptoms such as hematuria, proteinuria and hypertension caused by IgAN, and further control and delay the progress of IgAN.

Immunosuppressive therapy for IgA nephropathy in children.

IgA nephropathy (IgAN) is the most common cause of primary glomerulonephritis. It is a heterogeneous disease with different presentations and high morbidity. Thirty per cent of adults and 20% of children (followed into adulthood) will have a 50% decline in kidney function or develop kidney failure after 10 years. To determine the benefits and harms of immunosuppressive therapy for the treatment of IgAN in children. We contacted the Information Specialist and searched the Cochrane Kidney and Transplant Register of Studies up to 03 October 2023 using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Registry Platform (ICTRP) Search Portal, and ClinicalTrials.gov. We included randomised controlled trials (RCTs) and non-randomised studies of interventions (NRSIs) investigating the treatment of IgAN in children with immunosuppressive therapies compared to placebo, no treatment, supportive care, standard therapy (Japanese protocol), other immunosuppressive therapies or non-immunosuppressive therapies. Two authors independently extracted data and assessed the risk of bias. Random effects meta-analyses were used to summarise estimates of treatment effects. Treatment effects were expressed as risk ratios (RR) and 95% confidence intervals (CI) for dichotomous outcomes, and the mean difference (MD) and 95% CI for continuous outcomes. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs and the ROBIN-I tool for NRSIs. The certainty of the evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). This review included 13 studies with 686 participants. Ten RCTs included 334 children and 191 adults, and three NRSIs included 151 participants, all children. Most participants had mild kidney disease. The risk of bias was unclear for most of the domains relating to allocation concealment, blinding of participants, personnel, and outcome assessment. In children with IgAN, it is uncertain if corticosteroid (steroid) therapy, compared to placebo reduces proteinuria (1 study, 64 children and young adults: RR 0.47, 95% CI 0.13 to 1.72; low certainty evidence) or the decline in estimated glomerular filtration rate (eGFR) (1 study, 64 children and young adults: RR 0.47, 95% CI 0.09 to 2.39; low certainty evidence). It is uncertain if steroids reduce proteinuria compared to supportive care (2 studies, 61 children: RR 0.04, 95% CI -0.83 to 0.72; low certainty evidence). Adverse events associated with steroid therapy were not assessed due to heterogeneity in steroid protocols, including dose and duration, and lack of systematic assessment for adverse events in the included studies. Azathioprine, mycophenolate mofetil, mizoribine, or cyclophosphamide alone or in combination with steroid therapy had uncertain effects on improving proteinuria or preventing eGFR decline in children with IgAN. Fish oil, vitamin E and tonsillectomy had uncertain effects on improving proteinuria or preventing eGFR decline. Effects of other immunosuppressive therapies, secondary outcomes and adverse events were not assessed due to insufficient data. There is a lack of high-quality evidence to guide the management of IgAN in children. There is no evidence to indicate that steroids, other immunosuppressive therapies, or tonsillectomy, when added to optimal supportive care, prevent a decline in eGFR or proteinuria in children with IgAN. Available studies were few, with small numbers, low-quality evidence, high or uncertain risk of bias, did not systematically assess harms associated with treatment, or report net benefits or harms. Severe cases and atypical presentations of IgAN were not included in the reviewed studies, and our findings cannot be generalised to these situations.