Background/Purpose: Antiphospholipid antibodies nephropathy (aPL-N) is defined by thrombotic microangiopathy (TMA) early lesions and late lesions such fibro-intimal hyperplasia with luminal obliteration/organized thrombi, fibrous arterial/arteriolar occlusion and focal cortical atrophy¹.Beyon d these distinct microvascular lesions, other glomerular conditions (membranous nephropathy, MN; focal segmental glomerulosclerosis, FSGS), were reported in primary APS (PAPS) patients, even without aPL-related vascular lesions. Aim: 1) To evaluate clinical/laboratory features associated to intra-renal involvement in PAPS patients; 2) to clinically and histologically characterize PAPS patients with a) aPL-N and b) non-aPL-N intra-renal involvement.

Methods: Observational multicentric study including PAPS patients regularly followed (1984-2023). 1) Case-control study: PAPS patients with intra-renal involvement histologically confirmed vs PAPS patients without renal involvement signs. 2) Separate analysis according to renal histologic findings: a) aPL-N and b) non-aPL-N.

Results: Among 258 PAPS patients (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. It was the first disease manifestation in 10/17 (59%) patients, the main presentation was with isolated urinary abnormalities (IUAs) in 53% of the cases. At renal biopsy 35% had classic aPL-N injuries while 65% showed non-aPL-N intra-renal lesions. 1) Patients with intra-renal involvement suffered less macrovascular thrombotic events and more catastrophic APS (CAPS), thrombocytopenia, epilepsy, and lupus anticoagulant (LA)+ (Table 1). 2a) aPL-N was the first manifestation of APS in 5/6 (83%) cases, presenting with severe arterial hypertension in 17%, CAPS in 33% and IUAs in 50%. Despite therapy with anticoagulant (60%) or antiplatelet (40%) drugs in most patients, the 12-months renal response was complete in only 1/3 of the cases; half of the patients suffered subsequent aPL-related events (3/6 thrombocytopenia; 2/6 thrombotic events).  

2b) PAPS patients with non-aPL-N intra-renal lesions had MN in 6/11 and FSGS in 5/11 cases, with some degree of non-specific vascular injury in 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/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 45% cases were preceded by the renal disease.

Conclusion: The present work highlights the importance of conducting appropriate renal study in PAPS patients with renal biopsy, if needed, even in presence of mild IUAs. It underscores that aPL-N, being part of the peculiar microvascular APS subset, may require a treatment strategy beyond anticoagulation². From 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. 

« Back to ACR Convergence 2024

ACR Meeting Abstracts - https://acrabstracts.org/abstract/intra-renal-involvement-in-primary-antiphospholipid-antibodies-syndrome-data-from-two-italian-centers/