Scleroderma renal crisis: a pathology perspective

Abstract

Scleroderma renal crisis (SRC) is an infrequent but serious complication of systemic sclerosis (SSc). It is associated with increased vascular permeability, activation of coagulation cascade, and renin secretion, which may lead to the acute renal failure typically associated with accelerated hypertension. The histologic picture of SRC is that of a thrombotic microangiopathy process with prominent small vessel involvement manifesting as myxoid intimal changes, thrombi, onion skin lesions, and/or fibrointimal sclerosis. Renal biopsies play an important role in confirming the clinical diagnosis, excluding overlapping/superimposed diseases that might lead to acute renal failure in SSc patients, helping to predict the clinical outcome and optimizing patient management. Kidney transplantation may be the only treatment option available for a subset of SRC patients who develop end-stage renal failure despite aggressive angiotensin-converting enzyme inhibitor therapy. However, the posttransplant outcome for SSc patients is currently suboptimal compared to the general renal transplant population.

Figure 1

Arterial thrombosis associated with prominent glomerular ischemic collapse in a patient with scleroderma renal crisis (Methenamine silver stain; original magnification x100).

Figure 2

Prominent arterial onion skin lesion in a patient with scleroderma renal crisis. Such lesions often cause severe vascular narrowing leaving only a pinpoint open lumen (Methenamine silver stain; original magnification x400).

Figure 3

Glomerular capillary thrombosis in a patient with scleroderma renal crisis. This finding is rather infrequent in scleroderma renal crisis and is more commonly observed in hemolytic uremic anemia and thrombotic thrombocytopenic purpura (Methenamine silver stain; original magnification x600).

Figure 4

Prominent juxtaglomerular apparatus containing sparse silver positive renin granules in a patient with scleroderma renal crisis (Methenamine silver stain; original magnification x400).

Figure 5

Electron microscopy from a patient with scleroderma renal crisis reveals detachment of the endothelium and prominent electron lucent fluffy material (Electron microscopy; original magnification x5600).

Figure 6

Prominent arterial adventitial fibrosis in a patient with scleroderma renal crisis. Note that the arteries also have mild intimal accumulation of myxoid material. (Methenamine silver stain; original magnification x100).

Figure 7

Two renal allograft biopsies with histologic features suspicious for recurrence of scleroderma. Note the prominent myxoid changes in the artery in biopsy (a) as well as the severe intimal thickening of blood vessels, which is accompanied by thrombosis and schistocytes within the arteriole wall in biopsy (b). The differential diagnosis includes acute antibody-mediated rejection and acute calcineurin inhibitor toxicity. Clinical correlation with the presence of C4d stain, detection of circulating donor-specific antibodies, and calcineurin inhibitor levels are usually warranted to achieve a correct diagnosis [(a) H&E; original magnification x200 and (b) Methenamine silver stain; original magnification x400].