Immunoglobulin A Nephropathy Associated with Systemic Disease: Clinical Spectrum and Long-Term Kidney Outcomes in a Single-Center Cohort

Immunoglobulin A nephropathy diagnosed in a patient who already has a chronic systemic illness is conventionally reported as secondary disease, although for most associations the evidence for causation is limited and the clinical course is poorly characterized. We examined which systemic diseases accompany the nephropathy and how far they relate to long-term outcome. We reviewed 46 adults with biopsy-proven immunoglobulin A nephropathy and a systemic disease documented at or before biopsy at a single center between 1992 and 2023, grouped as gastrointestinal/liver, infection, rheumatologic or malignancy. The primary outcome was kidney replacement therapy. Median age was 40 years and median follow-up 10 years. Psoriasis was the most frequent associated diagnosis (12 patients, 26.1%); no difference from the rest of the cohort could be demonstrated in presentation, histology or outcome (KRT 4/12 vs 11/34, p=1.000; composite outcome 7/12 vs 17/34, p=0.742), although with 12 patients these estimates are imprecise. Patients with malignancy had a much lower estimated glomerular filtration rate (29.0 vs 90.0 mL/min/1.73 m2, p<0.001), more nephritic syndrome (90.0% vs 13.0%, p<0.001) and more crescents (40.0% vs 8.7%, p=0.053). Overall, 15 patients (32.6%) required KRT, 10 (21.7%) died and 24 (52.2%) met the composite outcome. The 10-year cumulative incidence of KRT was 65.0% in the malignancy group against 4.3% in the rheumatologic group (p=0.016). Patients with psoriasis did not show more favorable outcomes than the rest of the cohort, although the size of this subgroup precludes a firm conclusion; since these patients are followed largely outside nephrology, periodic urinalysis might be considered, a suggestion drawn from a small single-center cohort rather than from tested evidence. The worst outcomes occurred in older patients presenting with advanced kidney impairment, most of whom had a malignancy, a group that may warrant closer nephrological follow-up.