Renal involvement as a unique manifestation of hemophagocytic syndrome

Abstract

Renal-limited hemophagocytic syndrome (HPS) is a rare clinical setting characterized by abnormal activation of the immune system. Fever associated with pancytopenia, hepatosplenomegaly with liver dysfunction, and hypofibrinogenemia are usually observed in HPS. From a histological level, the presence of non-malignant macrophages infiltrating bone marrow and organs represents the hallmark of this condition. Non-malignant macrophages are associated with phagocytizing activities involving other blood cells. While primary HPS is usually associated with inherited dysregulation of the immune system, secondary HPS usually occurs in the context of infection or is linked to a neoplastic process. Clinical presentation varies and can potentially lead to life-threatening settings. While renal involvement has frequently been reported, however, detailed descriptions of the kidney manifestations of HPS are lacking. More critically, the diagnosis of HPS is rarely supported by renal biopsy specimens. We report four rare cases of biopsy-proven renal-limited HPS in patients presenting with acute kidney injury (AKI). The available evidence on this topic is critically discussed in light of the possible emergence of an autonomous entity characterized by an isolated kidney involvement.

Keywords: acute kidney injury; autoinflammatory diseases; hemophagocytic lymphohistiocytosis; hemophagocytic syndrome; macrophage activation syndrome.

Figure 1

Exemplary features of renal biopsy samples from patients with hemophagocytic syndrome (HPS). (A,B) Diffuse thickening of the glomerular basement membrane (GBM) with double contours and capillary lumina occluded by mononuclear cells with foamy cytoplasm. (C,D) Immunohistochemistry shows mononuclear cells to be CD68-positive, consistent with monocyte/macrophages. (E) Capillary lumina occluded by vacuolized mononuclear cells. (F) Immunohistochemistry CD68-positive for monocyte/macrophages. (G,H) Capillary lumina occluded by monocyte/macrophages. (I,J) Features of hemophagocytosis at electron microscopy.