Investigation on urinary and serum alpha klotho in dogs with chronic kidney disease

Abstract

Background: As a co-receptor for fibroblast growth factor 23, klotho plays a pivotal role in phosphate metabolism. The kidney is known to be the main source of soluble alpha-klotho and the principal regulator of its concentration. Previous studies in human participants showed that the concentration of soluble alpha-klotho in serum and urine decreased in chronic kidney disease (CKD) patients. However, no previous study has assessed soluble alpha-klotho levels in dogs. This study aimed to measure serum and urinary alpha-klotho levels in CKD dogs and identify their associations with International Renal Interest Society (IRIS) CKD stages and other parameters known to be associated with CKD. Results: Serum and urinary alpha klotho concentrations were measured by a commercially available canine-specific sandwich enzyme-linked immunosorbent assay kit and compared between groups by a nonparametric Kruskal-Wallis test. Spearman's correlation coefficient was used to evaluate the relationships between variables. A stepwise multiple regression analysis was performed to estimate the effects of independent predictors on klotho concentrations. The urine klotho-to-creatinine ratio (UrKl/Cr) was significantly lower in stage 3 dogs than the control group and was significantly lower in dogs with stage 3 and 4 CKD than in those with stage 1 and 2 disease. UrKl/Cr was negatively correlated with serum symmetric dimethylarginine (sSDMA), blood urea nitrogen (BUN), creatinine, and phosphorus concentration. Serum alpha-klotho concentration in dogs with stages 2 and 3 CKD was significantly lower than those in the control group. There was no significant correlation between serum alphaklotho and BUN, creatinine, and phosphorus concentrations. No statistically significant differences were observed in UrKl/Cr and serum alpha-klotho concentration between groups based on sex, age, urine protein-to-creatinine ratio (UPC), or blood pressure. Conclusions: UrKl/Cr decreased in dogs with advanced CKD, and it was negatively correlated with sSDMA, BUN, creatinine, and phosphorus concentrations. Thus, klotho is associated with CKD and its clinical consequences, including CKD-mineral bone disorder, in dogs. Although serum klotho concentration was negatively correlated with sSDMA levels, it was not apparently related to IRIS CKD stage or other parameters known to be associated with CKD.

METTL14 promotes glomerular endothelial cell injury and diabetic nephropathy via m6A modification of α-klotho

“…According to the literature, the expression of α-klotho in serum and urine klotho-to-creatinine ratio of patients with kidney disease is down regulated (Yi et al 2020), such as renal fibrosis and podocyte injury (Cho et al 2018), acute kidney injury (Qian et al 2019), DN (Kacso et al 2012), etc. α-klotho was found to be decreased during DN progress.…”

Investigation of α-Klotho Concentrations in Serum of Cats Affected by Hypertrophic Cardiomyopathy

“…While there are several approaches for addressing Klotho and cardiovascular diseases in experimental and clinical contexts, as well as two studies dealing with Klotho in dogs, this study investigated α-Klotho in cats with HCM. A study by Yi et al [20] also examined α-Klotho in serum using an ELISA, though this study was on dogs with CKD. This analysis found a difference in the median values between the control group and the CKD group, and the range of values was wider than the one in our study.…”

“…Olejnik et al [16] even linked Klotho to therapy options for cardiovascular disease by referring to its ability to positively influence pathological alterations in the heart. In veterinary medicine, Klotho has been described in canine patients with CKD [20] and mammary gland tumours [21] so far. Klotho seems to be a promising parameter in the context of cardiovascular diseases.…”

Serum Analytes of American Mink (Neovison Vison) Challenged with Aleutian Mink Disease Virus

“…The means of the values of the two groups in that study were calculated as 6.89 and 21.35 mmol/L (19.27 and 59.5 mg/dL), respectively, showing 210% higher value for those which showed signs of AD. The concentration of BUN is also positively and significantly associated with the degree of severity of chronic kidney disease in dogs based on IRIS classification [ 78 ].…”

“…The overall mean PHOS concentration in the current study (2.08 mmol/L) was close to the reported values for non-infected mink (1.30 to 2.78 mmol/L), except in one report of a high value (5.9 mmol/L) for lactating mink [ 79 ]. Although impaired kidney function increased serum PHOS concentration in dogs [ 77 , 78 ], AMDV infection only non-significantly elevated serum PHOS concentration in mink [ 33 ], thus, suggesting that the serum PHOS concentration is not an accurate measure of tolerance in AMDV infected mink. Ca concentration in the current study (2.24 mmol/L) was lower than the values in three reports for non-infected mink (2.36 to 2.70 mmol/L).…”