Biomarkers of kidney involvement in paediatric IgA vasculitis: a systematic review and meta-analysis

BACKGROUND: IgA vasculitis nephritis (IgAVN) develops in 20-80% of patients with IgA vasculitis (IgAV), yet diagnosis is often delayed. Readily available biomarkers can help identify patients at risk earlier. OBJECTIVE: To conduct a systematic review and meta-analysis of all available serum and urinary biomarkers to evaluate their prognostic potential in predicting IgAVN in paediatric patients. DATA SOURCES: A comprehensive search was performed in PubMed, EMBASE and Cochrane Library on November 9, 2024, covering publications from inception. The search strategy included three domains: paediatric population, IgAV diagnosis and studied biomarkers. No language or additional restrictions were applied. STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS: We included original retrospective, prospective and cross-sectional studies that involved paediatric IgAV patients and reported biomarker levels in patients with and without nephritis. Two reviewers independently screened studies, and a third reviewer resolved conflicts. STUDY APPRAISAL AND SYNTHESIS METHODS: Data extraction was performed by two independent reviewers. A random-effects model was used for analysis. The review followed PRISMA guidelines, and study quality was assessed using the QUIPS tool. Outcomes were reported as mean or standardised mean differences with 95% confidence intervals (CI). Where possible, odds ratios (OR) and diagnostic performance measures were also evaluated. RESULTS: Of 10,611 records screened, 129 studies including 23,726 patients were included. The neutrophil-to-lymphocyte ratio (NLR) was significantly higher in patients with nephritis (0.48; 95% CI 0.04-0.93), with notable effects in the Turkish population (0.86; 95% CI 0.19-1.52) but not in the Chinese population (- 0.02; 95% CI - 0.75-0.72). The platelet-to-lymphocyte ratio (PLR) showed a similar pattern, being higher in the Turkish subgroup (21.9; 95% CI 9.64-34.16) and lower in the Chinese subgroup (- 6.75; 95% CI - 11.27-2.22). A positive faecal occult blood test (FOBT) was associated with increased odds of kidney involvement (OR 2.04; 95% CI 1.05-3.96). LIMITATIONS: This study has limitations, including the predominance of retrospective data, limited reporting of diagnostic accuracy metrics (e.g. sensitivity, specificity), and substantial inter-study heterogeneity in nephritis definitions, measurement methods and study populations, which restrict firm conclusions about biomarker performance. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: While statistically significant biomarker associations exist, clinically actionable predictors of IgAVN remain lacking. NLR, PLR and FOBT warrant prospective validation in multicentre cohorts with standardised protocols. SYSTEMATIC REVIEW REGISTRATION NUMBER: CRD42024593928.