Op0297 Intra-Renal Involvement in Primary Antiphospholipid Antibodies Syndrome: Data From Two Italian Centers

Background: The definition of antiphospholipid antibodies nephropathy (aPL-N) was recently updated1 and encompasses early lesions with features of thrombotic microangiopathy (TMA) along with late lesions displaying fibro-intimal hyperplasia with luminal obliteration and organized thrombi, fibrous arterial or arteriolar occlusion and focal cortical atrophy. Apart from the distinct microvascular lesions characterizing aPL-N, various glomerular conditions, especially membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS), have been reported in primary APS (PAPS) patients, even without evidence of aPL-related vascular lesions. Objectives: i) To evaluate clinical and laboratory features associated to intra-renal involvement in PAPS patients; secondly, to clinically and histologically characterize PAPS patients with ii) aPL-N and iii) non-aPL-N intra-renal involvement. Methods: An observational retrospective multicentric study was conducted including all PAPS patients regularly and prospectively followed in the participating Centers (1984-2023). i) A case-control study was performed by comparing PAPS patients with intra-renal involvement histologically confirmed vs PAPS patients without signs of renal involvement. Patients with intra-renal involvement were separately analyzed according to the main renal histologic findings: ii) aPL-N and iii) non-aPL-N. Results: Among the 258 PAPS patients evaluated (78% females, median age at onset: 32 years, 67% thrombotic phenotype, 54% obstetric phenotype, 41% triple aPL+), 17 (7%) had histologically confirmed intra-renal involvement that was the first disease manifestation in 10/17 (59%) patients. The main presentation was with isolated urinary abnormalities (IUAs), in 9/17 (53%) cases. At renal biopsy 6/17 (35%) had classic aPL-N injuries while 11/17 (65%) showed non-aPL-N intra-renal lesions. i)As compared to patients without intra-renal involvement (Table 1), they suffered less macrovascular thrombotic events but more catastrophic APS (CAPS), and exhibited more thrombocytopenia, epilepsy, and lupus anticoagulant (LA) positivity. ii)Among the 6 patients with aPL-N, it was the manifestation of APS onset in 5/6 (83%) cases presenting with severe arterial hypertension in 1/6 (17%), CAPS in 2/6 (33%) and IUAs in 3/6 (50%) cases. Despite all the patients were treated with anticoagulants (60%) or antiplatelets (40%), the 12-months renal response was complete in only one third of the cases, and half of the patients suffered subsequent aPL-related events (3/6 thrombocytopenia; 2/6 thrombotic events). iii)The 11 PAPS patients with non-aPL-N intra-renal lesions had MN in 6/11 (55%) and FSGS in 5/11 (45%) cases, with some degree of non-specific vascular injury (glomerular basement membrane wrinkling, mild hyaline plaques) in 7/11 (64%). As compared to patients with aPL-N, they presented more frequently normal serum creatinine and higher 24h-proteinuria levels (Figure 1) but no differences in systemic autoantibodies or complement levels. All the patients belonging to this subgroup experienced aPL-related events (8/11 thrombotic events, 5/6 obstetric events, 3/11 epilepsy, 2/11 heart valve lesions, 1/11 thrombocytopenia), that in 5/11 (45%) of the cases were preceded by the renal disease. Conclusion: The present work highlights the importance of conducting appropriate renal study and, when necessary, renal biopsy in PAPS patients, even in presence of mild urinary alterations. Furthermore, it underscores that aPL-N, being part of the peculiar microvascular APS subset, may require a treatment strategy beyond anticoagulation2. On the other hand, from the nephrologists' perspective, routinary screening for aPL during the assessment of glomerulopathies could be relevant, given the aPL prognostic role in the development of subsequent related events. REFERENCES: 1 Barbhaiya M et al. J Rheumatol 2023. 2Erkan D et al. Arthritis Rheumatol 2021. Acknowledgements: NIL. Disclosure of Interests: None declared.