Biochemical and histopathological changes in Wistar rats after consumption of boiled and un-boiled water from high and low disease prevalent areas for chronic kidney disease of unknown etiology (CKDu) in north Central Province (NCP) and its comparison with low disease prevalent Colombo, Sri Lanka

Abstract

Background: Chronic Kidney Disease of unknown etiology (CKDu) is prevalent in North Central Province (NCP) of Sri Lanka. Consumption of un-boiled dug well water has been identified as one of the causative factors. This in-vivo study was performed to investigate some of the suspected factors associated with the pathogenesis of CKDu mediated via ground water.

Method: Rats were given water, collected from high and low disease prevalent areas from the NCP of Sri Lanka and the results compared with those obtained from previously identified low disease prevalent area; Colombo. Blood Urea Nitrogen, creatinine, urinary microalbumin:creatinine ratio together with ALT and AST levels were analyzed and results were compared using one-way ANOVA and paired t-Test. Histopathology was analyzed using non-parametric method.

Results: Rats that ingested water from New Town Medirigiriya (NTM) from high disease prevalent NCP reported significantly elevated microalbumin:creatinine ratios compared to other water sources after 8 months, whilst boiled water from NTM had been able to significantly reduce it. Histopathological findings after the 14 months experimental period revealed significantly high tubular lesion index in rats that ingested water from NCP compared to Colombo. Rats that ingested water from high disease prevalent Divuldamana (DD) from NCP showed the highest kidney lesion index though the fluoride content was relatively low in this area compared to other water sources from high disease prevalent NCP. Rats that ingested boiled and un-boiled water from NTM also developed severe lesions whilst the group from Colombo reported the lowest. Low disease prevalent area from NCP, Huruluwewa (HW) also reported elevated liver enzymes and altered renal histopathology. Association of Na⁺:Ca²⁺ ratio in the disease progression was not reflected by the current study. Compared to Colombo, high fluoride, calcium and sodium contents were observed in water from high disease prevalent areas. All the water samples were negative for heavy metals.

Conclusions: Though Fluoride is a known kidney toxic agent it cannot be the sole reason for CKDu in NCP, Sri Lanka. Various toxic elements present in NCP water may contribute to different grade of kidney and liver lesions in Wistar rats.

Keywords: BUN; CKDu; Microalbumin:creatinine; NCP.

Fig. 1

Chronic inflammatory cell infiltrates around the kidney tubules with tubular degeneration. Kidney tubules of rat tissue under (H&E) stain with (10 × 40) magnification

Fig. 2

Chronic inflammatory cell infiltrates around the kidney tubules with tubular degeneration and regeneration. Degenerated kidney tubules of rat tissue under (H&E) stain with (10 × 40) magnification

Fig. 3

Degenerated kidney tubules with chronic inflammatory cell infiltrates. Peritubular chronic cell infiltrations with prominent tubular destruction under (H&E) stain with (10 × 40) magnification

Fig. 4

Areas with tubular regeneration. Rat kidney tubules with tubular regeneration under H&E stain (10 × 40)

Fig. 5

Chronic Inflammatory cell infiltrates around the portal tracts in liver sections. Chronic inflammatory cell infiltrates around the portal tracts under (H&E) stain and (10 × 4)

Fig. 6

Inflammatory cell foci in liver parenchyma. Mild chronic inflammatory foci in the liver parenchyma under H&E stain and (10 × 4) magnification