Risk Factors of Disease Progression in IgA Nephropathy: A Systematic Review and Meta‐Analysis

OBJECTIVE: IgA nephropathy (IgAN) is an important cause of chronic renal failure, and nearly all patients with IgAN are at risk of developing to end-stage renal disease (ESRD) during their lifetime. This meta-analysis aimed to identify and evaluate risk factors associated with the progression of IgAN patients. METHODS: Primary studies investigating the risk factors for predicting the progression of IgAN were included in this review. A comprehensive literature search was conducted across multiple electronic databases, including the Chinese Biological Medicine Database (CBM), China National Knowledge Infrastructure (CNKI), Cochrane Library, PubMed, Embase, Web of Science, and WANFANG, up to May 30, 2025. Two independent reviewers screened the literature based on the predefined inclusion and exclusion criteria, extracted the relevant data from the original studies, and assessed the quality of the included studies using the Newcastle-Ottawa Scale (NOS). Meta-analysis was performed on at least two studies reporting on a specific outcome, with pooled effect sizes expressed as hazard ratios (HRs) and 95% confidence intervals (CIs). Statistical analysis, including meta-analysis, subgroup analysis and sensitivity analysis, was conducted using the R software. Publication bias was evaluated using Egger's test in Stata12.0. RESULTS: A total of 53 studies, comprising 25,517 patients with IgAN, were included in the final analysis. This meta-analysis identified 10 clinical risk factors significantly associated with IgAN progression, including mean arterial pressure (MAP) (HR = 1.02, 95% CI: 1.01-1.03), diastolic blood pressure (DBP) (HR = 1.03, 95% CI: 1.01-1.05), systolic blood pressure (SBP) (HR = 1.03, 95% CI: 1.01-1.05), serum creatinine (SCr) (HR = 1.04, 95% CI: 1.03-1.06), triglyceride (HR = 1.11, 95% CI: 1.02-1.21), 24-h urinary protein excretion (UPE) (HR = 1.15, 95% CI: 1.12-1.18), low-density lipoprotein cholesterol (LDL-C) (HR = 1.37, 95% CI: 1.18-1.59), male sex (vs. female) (HR = 1.73, 95% CI: 1.16-2.59), complement C4 (C4) (HR = 1.81, 95% CI: 1.06-3.09), and hypertension (HR = 2.53, 95% CI: 1.92-3.33). The pathological features significantly predictive of IgAN progression including crescents (C1/C2) (vs. C0) (HR = 1.57, 95% CI: 1.24-1.99), C2 (vs. C0) (HR = 2.87, 95% CI: 1.65-5.01), endocapillary hypercellularity (E1) (vs. E0) (HR = 1.17, 95% CI: 1.02-1.35), segmental glomerulosclerosis (S1) (vs. S0) (HR = 2.23, 95% CI: 1.78-2.79), and tubular atrophy (T1/T2) (vs. T0) (HR = 5.12, 95% CI: 3.56-7.36), when analyzed individually, T1 (vs. T0) showed an HR = 4.59 (95% CI: 3.24-6.51), and T2 (vs. T0) showed an HR = 16.40 (95% CI: 9.65-27.87). In contrast, C1 (vs. C0) (HR = 1.41, 95% CI: 0.81-2.45) was not significantly associated with progression risk. Protective factors against lgAN progression included higher level of albumin (Alb) (HR = 0.95, 95% CI: 0.93-0.98), estimated glomerular filtration rate (eGFR) (HR = 0.96, 95% CI: 0.95-0.97), hemoglobin (Hb) (HR = 0.98, 95% CI: 0.97-0.99), complement C3 (C3) (HR = 0.97, 95% CI: 0.95-0.99). Additionally, female sex was associated with a lower risk of disease progression, with HR = 0.69 (95% CI: 0.57-0.84) and when compared directly with male HR = 0.55 (95% CI: 0.45-0.67). CONCLUSION: This meta-analysis indicates that MAP, DBP, SBP, SCr, triglyceride, 24-h UPE, LDL-C, male sex (vs. female), C4, hypertension, C-lesions, M-lesions, S-lesions, and T-lesions in Oxford classification are significantly associated with an increased risk of IgAN progression. In contrast, higher levels of Alb, eGFR, Hb, C3, as well as female sex (both as an independent variable and compared with males), are identified as protective factors in patients with IgAN.