Back
Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by persistently positive antiphospholipid antibodies (aPL) associated with thrombosis (arterial or venous) or recurrent pregnancy loss. Clinical presentation spectrum ranges from venous thrombosis to multiorgan involvement in catastrophic antiphospholipid syndrome (CAPS), with a minority of patients experiencing microvascular thrombosis. Thrombosis risk increases based on the subtype and number of APS present, with "triple positivity" conferring higher risk of initial or recurrent thrombosis. Prevalence of renal involvement has been reported up to 25%, with isolated thrombotic microangiopathy (TMA) being an unusual finding in both SAAF and concurrent systemic lupus erythematosus (SLE).
We present a case of graft dysfunction due to TMA in a patient with coexisting SLE - APS and response to belimumab treatment.
48-year-old male with APS (triple-positive markers; history of thrombotic event on anticoagulation and CAPS), SLE (lupus nephritis IV+V and end-stage renal disease on renal replacement therapy). Deceased-donor kidney transplant, receiving immunosuppression with thymoglobulin, steroids, antiproliferative agent, and calcineurin inhibitor according to local transplant protocol. Early initiation of anticoagulation (enoxaparin) due to a history of APS. During outpatient surveillance inadequate decrease in azotemia, with creatinine (Cr) level persistently >4 mg/dL. Graft ultrasound with appropriate resistance index and tacrolimus levels within range. Renal graft biopsy performed on day 21 post-transplant. Cr at admission 3.89 mg/dL, with no other relevant findings in laboratory tests. Histopathology reveals active thrombotic microangiopathy (TMA) in glomeruli and arterioles, negative Cd4. Due to histopathological findings anticoagulation dose is increased and weekly belimumab treatment (200 mg) is started in accord with rheumatology. Follow-up shows a 27% decrease in Cr levels (2.83 mg/dL).
Antiphospholipid syndrome nephropathy (APSN) encompasses various degrees of thrombotic microangiopathy, proliferative and fibrotic intrarenal vascular lesions, and changes consequent to renal parenchymal ischemia. Complement activation is proposed to play a central role in aPL-related pathogenic mechanisms, inflammation and vascular activation. In patients with APS, higher serum levels of B-Cell activating factor (BAFF) correlate with lupus anticoagulant positivity and higher risk of clinical events. Lupus anticoagulant positivity is linked to worse outcomes post-renal transplant, with a higher incidence of intra and extrarenal thrombosis. There is no consensus regarding the management of APSN in post-transplant patients, however better graft survival has been observed with the use of anticoagulation, with vitamin K antagonists being recommended. Research in murine models has demonstrated that blocking BAFF delays the development of nephropathy and provides benefits in managing other manifestations of APS. Notwithstanding, there are currently no studies on its potential benefits in APSN. This abstract was also submitted for the 70th International Congress of Nephrology by the Mexican Institute of Nephrological Research.