Systematic Review of Kidney Involvement in Antisynthetase Syndrome

Introduction Antisynthetase syndrome (ASyS) is a rare autoimmune disorder characterized by autoantibodies targeting aminoacyl-tRNA synthetases. Kidney involvement has been historically regarded as uncommon and remains poorly characterized. Methods We conducted a systematic review according to PRISMA 2020 guidelines (PROSPERO: CRD420261282317). MEDLINE, Scopus, Web of Science, and Google Scholar were searched from inception to January 2026. We included adults with biopsy-proven or clinically defined kidney involvement in ASyS. Risk of bias was assessed using Joanna Briggs Institute tools; certainty of evidence was evaluated with GRADE. Results Thirty-eight articles comprising 52 patients were included. Kidney disease presented with or following interstitial lung disease in 81% of cases. Among 35 biopsied patients, membranous nephropathy (29%), pauci-immune crescentic glomerulonephritis (23%), acute tubular necrosis (17%), and tubulointerstitial nephritis (11%) were identified. Non-Jo1 antibodies predominated in vasculitic phenotypes and were associated with higher peak creatinine than anti-Jo1 (4.7 vs 2.3 mg/dl; P=0.01). Corticosteroid monotherapy achieved complete recovery in 48% of mild disease, while rituximab was effective in 6 of 8 refractory cases. At median 18-month follow-up, 13% progressed to chronic kidney disease stages 4-5. Conclusions Kidney involvement in ASyS carries substantial clinical significance. Non-Jo1 serotype may predict worse kidney outcomes, though this association requires confirmation in prospective cohorts with multivariable adjustment. Routine kidney surveillance and early antibody-guided immunosuppression may improve outcomes, pending validation.