#PathPointer: Renal Thrombotic Microangiopathy in Systemic Lupus Erythematosus

PathPointers highlight important everyday teaching points when reviewing kidney histology. These brief and easy-to-read blog posts include real clinical images to demonstrate various biopsy findings.

The typical renal lesion in systemic lupus erythematosus (SLE) is immune complex glomerulonephritis. However, it is well recognized that renal lesions in SLE may involve all three compartments: glomerular, tubular, and vascular. In fact, renal vascular lesions are not rare in SLE, and this Pathpointer will highlight these findings. Four different types of vascular lesions are recognized in the setting of SLE: uncomplicated vascular immune deposit, non-inflammatory lupus vasculopathy, thrombotic microangiopathy (TMA), and vasculitis, the latter being the least frequent. Renal vascular lesions are essential to recognize as they adversely affect renal outcomes and overall survival and may also influence the therapeutic choice. This is particularly true for TMA.

TMA may be the sole manifestation of SLE and can also be an unusual presentation mode of SLE. The presence of TMA on a renal biopsy of a SLE patient is associated with more severe clinical manifestations and worse kidney function outcomes. TMA doesn’t always present with systemic symptoms and may be limited to the kidney, and thrombocytopenia and hemolytic anemia are inconstant findings. SLE patients with TMA have higher creatinine and more frequent and severe hypertension compared to patients with lupus nephritis (LN). Patients with TMA and LN have higher rate of oliguria and higher proteinuria in comparison to patients with LN without TMA. Histologically, TMA lesions in SLE are identical to TMA lesions from other causes (see figure below).

Thrombotic microangiopathy in SLE. (A) Glomeruli showing endothelial cell swelling and mesangiolysis (Jones, 20x) without associated lupus nephritis, (B) on the same biopsy, a glomerulus with endotheliosis and an arteriole showing fibrinoid necrosis (arrow)(HE, 40x). (C) TMA associated with lupus nephritis with hypercellular glomeruli (Jones 10x), (D) the vascular pole of one glomerulus is occluded by a large fibrin thrombus (arrow) (PAS, 20x).

TMA may occur with or without associated immune complex-related LN. Patients with LN and TMA tend to have higher lupus activity and chronicity indices compared to LN alone. TMA may not be easily distinguished from non-inflammatory lupus vasculopathy. The presence of glomerular alterations such as endothelial cell swelling, mesangiolysis, glomerular fibrin thrombi by light microscopy, and subendothelial widening by electron microscopy favor a diagnosis of TMA over lupus vasculopathy. Also, vascular immune deposits by immunofluorescence are not characteristic of TMA and are usually seen in lupus vasculopathy.

In SLE patients, antiphospholipid antibodies are an important mechanism of renal TMA, but their presence is not essential. Other mechanisms involve complement dysregulation of both the classical and alternative pathways. Immunodetection of glomerular C4d deposition in renal biopsy has been associated with a higher risk of TMA in LN, suggesting a role of the classical pathway. Alternative pathway proteins defects, such as reduced factor H level, may contribute to the endothelial cell damage leading to TMA in SLE. A  few successfully treated cases with complement inhibition therapy have been reported. Other possible causes or contributors to TMA include hypertension, drugs, malignancy, pregnancy, and infection.

Although the current ISN/RPS lupus classification does not include the evaluation of vascular lesions, the authors suggest reporting vascular lesions with a “standardized approach and terminology.” The recognition and reporting of TMA and other vascular lesions is crucial as it impacts kidney outcomes and overall survival in patients with SLE.

– Post prepared by Virginie Royal, AJKDBlog Contributor. Follow her @virginieroyal.

 

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