Kidney disease in antiphospholipid antibody syndrome: Risk factors, pathophysiology and management

Abstract

Antiphospholipid antibody syndrome (APLS) is a rare autoimmune disease characterized by recurrent arterial and venous thromboembolic events, pregnancy related complications as well as the persistent detection of antiphospholipid antibodies at a 12 week interval. Renal complications tend to occur in 3% of APLS patients, with renal artery stenosis being the most common kidney related complication. Renal pathology may be subdivided into macro as well as microvascular thrombotic complications with stenosis, thrombosis and infarction representing the principle macrovascular events and APLS nephropathy representing the predominant microvascular complication. APLS related kidney disease may present with an array of heterogenous manifestations ranging from hematuria and non-nephrotic range proteinuria to hypertension or as part of a severe, life threatening and fulminant multiorgan failure disorder known as catastrophic antiphospholipid antibody syndrome (CAPS). Management of APLS related renal complications depends on the site of vascular injury, the thromboembolic risk profile based on the subtype, isotype and titer of the autoantibodies as well as the severity of the injury. Primary prophylaxis in these patients primarily revolves around the use of low dose aspirin, with prophylactic anticoagulation during events that increase thromboembolic like surgery and hospitalization. Anticoagulation is the cornerstone of treatment of APLS related kidney disease with INR targets varying depending on the associated venous or arterial thrombosis. Immunosuppression with the likes of rituximab, mTOR inhibitors, eculizumab and belimumab have been used with some success, but lack randomized control trial validation for their use. Pulsed corticosteroids with Plasmapheresis and intravenous immunoglobulins is the recommended treatment for CAPS.

Keywords: APLSN; Anticoagulation; Catastrophic antiphospholipid antibody syndrome; Eculizumab; Glomerulonephritis; Plasmapheresis; Rituximab; Systemic lupus erythematosus; Thrombotic microangiopathy.