Intranasal administration of sugarcane ash causes chronic kidney disease in rats

Abstract

Silica nanoparticles found in sugarcane ash have been postulated to be a toxicant contributing to chronic kidney disease (CKD) of unknown etiology. However, although the administration of manufactured silica nanoparticles is known to cause chronic tubulointerstitial disease in rats, the effect of administering sugarcane ash on kidney pathology remains unknown. Here, we investigated whether sugarcane ash can induce CKD in rats. Sugarcane ash was administered for 13 wk into the nares of rats (5 mg/day for 5 days/wk), and blood, urine, and kidney tissues were collected at 13 wk (at the end of ash administration) and in a separate group of rats at 24 wk (11 wk after ash administration was stopped). Kidney histology was evaluated, and inflammation and fibrosis (collagen deposition) were measured. Sugarcane ash exposure led to the accumulation of silica in the kidneys, lungs, liver, and spleen of rats. Mild proteinuria developed, although renal function was largely maintained. However, biopsies showed focal glomeruli with segmental glomerulosclerosis as well as tubulointerstitial inflammation and fibrosis that tended to worsen even after the ash administration had been stopped. Staining for the lysosomal marker lysosomal associated membrane protein-1 showed decreased staining in ash-administered rats consistent with lysosomal activation. In conclusion, sugarcane ash containing silica nanoparticles can cause CKD in rats. NEW & NEWSWORTHY Epidemics of chronic kidney disease of unknown etiology have been reported in many areas of the world. In Central America, it occurs most commonly in sugarcane workers. Although heat stress is a major risk factor, there is some evidence that there may be a toxin. Here we show that sugarcane ash containing silica nanoparticles can induce chronic kidney disease in rats with similar features as observed in humans.