Biochemical,inflammatory, and histopathological changes in wistar rats given dug well water from high and low disease prevalent villages for chronic kidney disease of unknown etiology (CKDu) in north central province of Sri Lanka

Abstract

Chronic Kidney Disease of unknown etiology (CKDu) is prevalent in the North Central Province (NCP) of Sri Lanka. Ingestion of groundwater is identified as one of the causative factors. The einfonley of the population consumes un-boiled dug well water. The objectives of the study were to find out the biochemical, haematological, and immunological changes in Wistar rats that ingested dug well water from high and low disease prevalent areas from the NCP and low disease prevalent Colombo and correlate the findings with their histopathological changes. Sex balance 3 months old Wistar rats (n=60) were used for the study. Their WBC/ DC, cpt CD** gerum cytokines, creatinine, ALT, AST, BUN levels and Microalbumin: creatinine ratios were measured. Rats were randomly divided into 6 groups by assigning 10 rats per group. Groups 1, 2, and 3 were given water from high disease prevalent New Town Medirigiriya (NTM), Bisobandaragama (BB), and Divuldamana (DD) respectively. Group 4 was given boiled water from NTM (NTMB). Groups 5 and 6 were given water from low disease prevalent Huruluwewa (HW) from NCP and tap water from low disease prevalent Colombo (CO) adlibitum quantity. Serum cytokines (IL1β; IL6, TNFα) were measured after 8 months and CD 4+ and CD 8+ counts were measured after 14 months. Histopathology was performed in kidney and liver tissues. Serum TNFα levels were significantly elevated in rats from DD and BB (p<0.05) but hepatic TNFα levels were significantly elevated only in rats from DD (p<0.05)). Rats from high disease prevalent NTM had significantly high CD4+ and CD8+ cells than those from low disease prevalent HW and CO. Immunological findings. were correlated with the histopathological changes. There was a correlation between the kidney Tubular Interstitial (TI) Lesion index and liver lesions. Serum TNFα and CD4+ and CD8+ lymphocytes were closely correlated with renal damage. Rats with severe TI lesions reported a high percentage of portal tracts and parenchymal lesions in the liver and this expression was minimum in CO. It was evident that boiling water was effective against liver damage but not renal damage. The present study is supportive of an immune therapy targeting the CD4+ and CD8+, and TNFα in reducing renal damage in the early stages of the disease. In conclusion, peritubular nonsuppurative interstitial cell infiltrations in kidney tissues were common in all the experimental groups irrespective of the toxicant sicient in water bodies. Observed kidney damage may mediate via cytokine triggered immune response by high sodium, fluoride, calcium and some other unmeasured toxic agents present in NCP water. anid toxicant present in DD from NCP can directly damage the kidney tubules leading to fibrosis.