SynthesisFrontiers in immunology2026
Renal involvement in hypereosinophilic syndrome: a systematic review with narrative synthesis of pathology, diagnosis, and therapy.
Synthesis in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Authors and funding
5 authors.
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Abstract
Background: Renal involvement in hypereosinophilic syndrome (HES) occurs in 5-10% of patients but remains poorly characterized. Diagnostic overlap with IgG4-related kidney disease (IgG4-RKD) presents clinical challenges. Objective: To characterize the clinicopathologic spectrum of histologically confirmed HES-related kidney disease, examine diagnostic differentiation from IgG4-RKD, and appraise therapeutic evidence. Methods: Systematic review with narrative synthesis following PROSPERO-registered protocol (CRD420261307200). Six databases were searched from inception to February 27, 2026. Dual independent screening and domain-specific GRADE assessment were performed. Due to uncontrolled study designs and high heterogeneity, narrative synthesis was conducted rather than quantitative meta-analysis. Results: From 2, 247 records, 37 studies (42 cases) met inclusion criteria. Acute eosinophilic interstitial nephritis predominated (54.8%, 23/42), followed by thrombotic microangiopathy (19.0%, 8/42), chronic interstitial fibrosis (11.9%, 5/42), and glomerular lesions (14.3%, 6/42). Nine cases (21.4%) exhibited IgG4-RKD-like features with IgG4+/IgG+ ratios below 40% (median 21%, IQR 14-30%). However, substantial technical heterogeneity limits clinical applicability. Fourteen cases received anti-IL-5/IL-5Rα biologics; all reported improvement with no documented failures, suggesting publication bias. No randomized controlled trials exist for HES-related kidney disease. Certainty of evidence: Descriptive pathology findings were rated low certainty (downgraded for selection bias from biopsy requirement). IgG4/IgG ratio observations were very low certainty (downgraded for risk of bias, inconsistency, and indirectness). Treatment efficacy conclusions were very low certainty (downgraded for all GRADE domains, with publication bias and indirectness being most critical). Conclusion: This systematic review provides hypothesis-generating observations on HES-related kidney disease with low to very low certainty evidence. The 40% IgG4/IgG ratio remains unvalidated and should not be used diagnostically. International prospective registries and individual patient data meta-analyses are needed to establish evidence-based management. These findings require prospective validation before clinical application.
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