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.

Chronic thrombotic microangiopathy secondary to antiphospholipid syndrome, presenting with severe hypertension and chronic renal impairment

“…This results in post-thrombotic lesions in arterioles and glomeruli, as well as focal cortical atrophy with interstitial fibrosis on renal biopsy. The severity of APS nephropathy can range from mild chronic renal impairment with variable degrees of proteinuria and haematuria to acute renal failure with associated multiorgan involvement 13 14. Hypertension is highly prevalent in APS nephropathy and has been described as the hallmark feature of the disease.…”

The antiphospholipid syndrome – often overlooked cause of vascular occlusions?

“…In the kidneys, aPL‐associated nephropathy (APLN) comprises acute conditions such as thrombotic microangiopathy (TMA) and more chronic lesions with vascular damage that are often difficult to delineate from kidney damage caused by hypertension. APLN was recently reviewed , and notably, this condition is similar in SLE and pAPS, but cannot from the clinical presentation be distinguished from lupus nephritis, unless a biopsy is performed. Tektonidou et al demonstrated that these lesions are common in SLE patients with aPL and that they are associated with hypertension and impaired renal function .…”

Catastrophic Antiphospholipid Syndrome–Associated Nephropathy in a Systemic Lupus Erythematosus Patient Without Lupus Nephritis

“…Electron microscopy (original magnification × 4,800) revealed a glomerulus with mesangial matrix collapse and resultant capillary loop collapse ( CL b in D ), along with subendothelial electron‐lucent widening ( dashed arrow in D )—classic ultrastructural features of acute TMA and mesangiolysis (urinary space [ US ], mesangial cell nucleus [ MCN ], podocyte [ P ], and a normal capillary loop [ CL a ] are also seen in D ). Antiphospholipid antibody–associated nephropathy as pure TMA without concurrent lupus nephritis is rarely described in the literature . Further evaluation revealed mitral valvulitis with mitral regurgitation; right atrial thrombus; and thrombi in jugular, basilic, and brachial veins.…”

“…. Antiphospholipid antibody-associated nephropathy as pure TMA without concurrent lupus nephritis is rarely described in the literature (2,3). Further evaluation revealed mitral valvulitis with mitral regurgitation; right atrial thrombus; and thrombi in jugular, basilic, and brachial veins.…”