Abstract
BackgroundAs 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.ResultsSerum 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 alpha-klotho 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.ConclusionsUrKl/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.
Highlights
As a co-receptor for fibroblast growth factor 23, klotho plays a pivotal role in phosphate metabolism
The significantly lower UrKl/Urine klotho-to-creatinine ratio (Cr) in dogs with progressed chronic kidney disease (CKD) and its correlation with various parameters reflecting either kidney function or the severity of kidney disease suggests that klotho is associated with CKD and the development of its clinical consequences in dogs
It showed a negative correlation to serum symmetric dimethylarginine (sSDMA), blood urea nitrogen (BUN), creatinine and phosphorus concentrations
Summary
As a co-receptor for fibroblast growth factor 23, klotho plays a pivotal role in phosphate metabolism. Previous studies in human participants showed that the concentration of soluble alpha-klotho in serum and urine decreased in chronic kidney disease (CKD) patients. 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. The term “chronic kidney disease-mineral bone disorder” (CKD-MBD) has been used in humans and animals to describe a condition characterized by renal osteodystrophy and abnormal mineral metabolism with high levels of serum phosphate, fibroblast growth factor (FGF)-23, and parathyroid hormone (PTH) [4,5,6]. Klotho deficiency was suggested to be associated with or even induce these abnormal metabolic consequences [7,8,9,10,11]
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