Crystalglobulin-induced nephropathy

Abstract

Crystalline nephropathy refers to renal parenchymal deposition of crystals leading to kidney damage. The most common forms of crystalline nephropathy encountered in renal pathology are nephrocalcinosis and oxalate nephropathy. Less frequent types include urate nephropathy, cystinosis, dihydroxyadeninuria, and drug-induced crystalline nephropathy (e.g., caused by indinavir or triamterene). Monoclonal proteins can also deposit in the kidney as crystals and cause tissue damage. This occurs in conditions such as light chain proximal tubulopathy, crystal-storing histiocytosis, and crystalglobulinemia. The latter is a rare complication of multiple myeloma that results from crystallization of monoclonal proteins in the systemic vasculature, leading to vascular injury, thrombosis, and occlusion. In this report, we describe a case of crystalglobulin-induced nephropathy and discuss its pathophysiology and the differential diagnosis of paraprotein-induced crystalline nephropathy.

Keywords: ARF; kidney biopsy; myeloma.

Figure 1.

Renal biopsy findings. (A) Photograph demonstrating nonblanchable, nonpalpable purpura of feet. The insert shows fingers with splinter hemorrhages. (B) Biopsy of the skin lesions shows occlusive vasculopathy. This small cutaneous arteriole shows intraluminal thrombosis without leukocytoclastic vasculitis (H&E). (C) This image of the kidney biopsy shows large extracellular bright red crystals within glomerular capillaries (long arrows) and arterioles (short arrows) with secondary vascular thrombosis (arrowhead) (trichrome stain). (D) The glomerular and arteriolar crystals (arrows) are light pink on silver stain. The depicted interlobular artery shows intimal and luminal fibrin deposition (arrowhead). (E) A large intraglomerular capillary electron dense crystal (electron microscopy) is shown. (F) On high magnification, the crystals exhibit a substructure characterized by parallel linear arrays (electron microscopy). (G and H) Large crystals in vessels and glomeruli stain brightly for IgG (G) and κ (H) by pronase immunofluorescence. H&E, hematoxylin and eosin. Original magnification, ×600 in B; ×400 in C; ×400 in D; ×13,000 in E; ×68,000 in F; ×200 in G and H.

Figure 2.

The pathomechanisms of crystalglobulinemia are still unclear. Crystallization of monoclonal protein potentially occurs due to Fc–Fc interactions of IgG-type monoclonal protein possibly owing to abnormal glycosylation of the light chain portion of monoclonal protein or through interactions with albumin. These interactions may be enhanced by cooling and/or stasis in the systemic microvasculature. Crystalglobulins may induce vascular endothelial injury and activation of coagulation cascade predisposing to thrombosis, occlusive changes and ischemic injury to kidney, skin, and other organs. LC, light chain; RBC, red blood cell.