Antiphospholipid Syndrome Nephropathy: From Pathogenesis to Treatment

Abstract

Kidney damage is a well-recognized complication of the antiphospholipid syndrome (APS), either primary or systemic lupus erythematosus (SLE)-associated APS. Kidney involvement in APS involves a variety of manifestations, such as renal artery thrombosis or stenosis, renal vein thrombosis, allograft loss due to thrombosis after kidney transplantation, and injury to the renal microvasculature, also known as APS nephropathy. Biopsy in patients with APS nephropathy includes acute thrombotic microangiopathy lesions and chronic intrarenal vascular lesions such as interlobular fibrous intimal hyperplasia, arterial and arteriolar recanalizing thrombosis, fibrous arterial occlusion, and focal cortical atrophy. The most frequent clinical features are hypertension, microscopic hematuria, proteinuria (ranging from mild to nephritic levels), and renal insufficiency. It is uncertain whether antiphospholipid antibodies or other factors are implicated in the development of APS nephropathy, and whether it is driven mainly by thrombotic or by inflammatory processes. Experimental models and clinical studies of thrombotic microangiopathy lesions implicate activation of the complement cascade, tissue factor, and the mTORC pathway. Currently, the management of APS nephropathy relies on expert opinion, and consensus is lacking. There is limited evidence about the effect of anticoagulants, and their use remains controversial. Treatment approaches in patients with APS nephropathy lesions may include the use of heparin based on its role on complement activation pathway inhibition or the use of intravenous immunoglobulin and/or plasma exchange. Targeted therapies may also be considered based on potential APS nephropathy pathogenetic mechanisms such as B-cell directed therapies, complement inhibition, tissue factor inhibition, mTOR pathway inhibition, or anti-interferon antibodies, but prospective multicenter studies are needed to address their role.

Keywords: antiphospholipid antibodies; antiphospholipid syndrome; nephropathy; pathogenesis; treatment.

Figure 1

Antiphospholipid syndrome nephropathy histologic lesions. (A) Luminal narrowing due to circumferential myointimal thickening of the wall of one arteriole and one interlobular artery. Glomerulus exhibiting ischemic features with wrinkling of the glomerular capillary basement membranes (PAS 200×). (B) An interlobular artery and an arteriole showing luminal narrowing due to pale mucoid intimal thickening and myointimal cellular proliferation. Additionally, the arteriole reveals fibrin insudation within the wall (black arrows) (Masson trichrome 400×). (C) Arteriole showing luminal thrombus (HE 400×). (D) Arteriole showing TMA with platelet-fibrin thrombus occluding the lumen and nuclear debris in the arterial wall (HE 400×).