Investigation of the role of FGF23/klotho expression profile in the pathogenesis of urolithiasis on renal tissue of hyperoxaluria induced rats

Purpose: Besides the high incidence and prevalence of urolithiasis, it is commonly seen in diseases like obesity, diabetes, hypertension, atherosclerosis and metabolic syndrome although association mechanisms is not fully understood. Systemic levels of FGF23 which has mainly phosphaturic effect and klotho which has renoprotective, anti-oxidant, anti-inflammatory properties in addition to its cofactor role for FGF23, are associated with these dieases. Evaluation of the roles of those proteins in the pathogenesis of urolithiasis may help explain the mechanism of association between urinary stone formation and systemic diseases. To our knowledge, there is not enough investigation to determine their roles in kidney stone formation except some genetic trials. Materials and Methods: A total of 35 male wistar rats which were included into the study are randomly divided into five groups equally in number (n=7). Group 1 remained as control group and was sacrificed after 24 hour follow up. Rats in all other groups were given ethylene glycol in drinking water for a period of 4 week to induce hyperoxaluria. Each group were also sacrificed at the end of each week; day 7 for group 2, day 14 for group 3, day 21 for group 4 and day 28 for group 5,respectively. Right kidneys of all rats that were sacrificed were extracted for histopathological evaluation. Immunhistochemistry was used for FGF23 and Klotho tissue expression. Results: Although FGF23 had a strong expression in cortical, medullary and glomerular sites at day 7, staining intensity decreased gradually at day 14 to day 21 and FGF23 expression level was statistically significantly lower than control group at day 28 (p<0,05). Klotho also had a strong expression in cortical and glomerular sites at day 7 similarly to FGF23 but staining density decreased gradually and expression level was statistically significantly lower than control group at day 28 (p<0,05). Although klotho had a weak expression in medullary region only at day 7 and other groups had close expression levels, it was not statistically significant (p>0,05). Conclusion: FGF23 and Klotho expressions had a strong inverse correlation with hyperoxaluria. This may show us their involvement in the pathogenesis of urolithiasis. It can be speculated that urolithiasis process has a causative aspect for diseases sharing oxidative damage in their pathogenesis as a common feature like obesity, diabetes, hypertension, atherosclerosis and metabolic syndrome especially when well-known decrement of klotho in those diseases considered.