Acute alloxan toxicity causes granulomatous tubulointerstitial nephritis with severe mineralization

Abstract

Alloxan had been recognized as having a direct nephrotoxic effect different from its diabetogenic action. We encountered previously unreported granulomatous tubulointerstitial nephritis with severe luminal and interstitial mineralization in one diabetic rat after one week of alloxan administration. Histopathologically, many dilated and occluded proximal and distal tubules were segmentally observed in the cortex and outer medulla. The tubular lumen contained minerals and cell debris. Tubular epithelial cells were degenerated and piled up, and they protruded into the lumen, where they enveloped minerals. Mineralization was observed mainly in the tubular lumen, and to some extent in the subepithelium and interstitium. The mineralization beneath the tubular epithelium was often continuous from the subepithelium to the interstitium. In these lesions, the tubular basement membrane was disrupted by mineralization, and a granuloma with multinuclear foreign-body giant cells was formed in the interstitial areas.

Acute alloxan renal toxicity in the rat initially causes degeneration of thick ascending limbs of Henle

“…Glycogen accumulation in distal renal tubules, so-called Ebstein-Armanni lesions, reportedly appears in the kidney of AL-induced diabetic rats and mice with prolonged hyperglycemia. Prior to inducing a prolonged diabetic state, AL induces acute tubulointerstitial nephritis, consequently resulting in nephrotoxicity 1 , 2 , 3 , 4 . Renal changes, varying from swelling to necrosis, occur predominantly in the epithelia of the proximal convoluted tubules (PCT) 1 , 2 , 5 .…”