Primary antiphospholipid syndrome and the kidney: biopsy-proven insights from two referral Italian centres

Objectives To investigate the prevalence, clinical features, histological spectrum and outcomes of intra-renal involvement in patients with primary APS (PAPS), with particular attention to both aPL nephropathy (aPL-N) and non-aPL-N renal lesions.Methods This multicentric retrospective case-control study included 258 PAPS patients followed between 1984 and 2023 at two Italian referral centres. Patients with a biopsy-proven intra-renal involvement (n = 17) were compared with those without renal manifestations. Histologic classification followed the updated aPL-N criteria. Clinical, laboratory, therapeutic features, and 12-month renal responses were assessed.Results Seventeen of 258 (7%) patients underwent renal biopsy. Two out of 17 (12%) presented with acute kidney injury, 5/17 (29%) with nephrotic syndrome and 5/17 (29%) had isolated urinary abnormalities; the remaining 5 patients presented with different combination of signs/symptoms. Six (2.3%) were diagnosed with aPL-N, while 11 (4.2%) exhibited alternative glomerular lesions (e.g. membranous nephropathy, focal segmental glomerulosclerosis). Compared with controls, patients with intra-renal involvement had higher frequencies of CAPS (18% vs 0.4%, P = 0.001), thrombocytopenia (35% vs 10%, P = 0.006), epilepsy (24% vs 5%, P = 0.018) and LA positivity (100% vs 62%, P = 0.002). At 12 months, partial renal response was observed in most cases, with a worse prognosis in those with aPL-N despite anti-thrombotic treatment. All non-aPL-N patients had aPL-related events, including thrombotic, obstetric and non-thrombotic manifestations, with non-aPL-N renal disease preceding these events in 45%.Conclusion Intra-renal involvement in PAPS is rare but heterogeneous, encompassing both vascular and glomerular pathologies. These findings support the need for heightened renal surveillance in PAPS, even in the absence of classic thrombotic manifestations, and highlight the importance of histologic assessment to guide tailored therapy. From a nephrologist's perspective, routine screening for aPL in glomerular disease assessment may be relevant, particularly by providing prognostic value for subsequent aPL-related events.