Abstract
The present study aimed at evaluating the relationship between Klotho levels and insulin resistance and albumin-to-creatinine ratio (ACR) in type 2 diabetic patients with CKD. We conducted an observational, cross-sectional study in our outpatient diabetic nephropathy clinic from 2014 to 2016, enrolling a total of 107 type 2 diabetic patients with stage 2-3 CKD, with a mean age of 59years. Several clinical and laboratorial parameters were evaluated, including those related to mineral and carbohydrate metabolism. The mean eGFR at baseline was 53.2mL/min, and the mean levels of ACR and Klotho were 181.9µg/mg and 331.1pg/m, respectively. In the simple linear regression model, Klotho levels were correlated with age, phosphorus, PTH, ACR, HOMA, IL-6, FGF-23, OxLDL, eGFR and vitamin D levels. Applying a multivariate linear regression model, only the ACR, HOMA-IR, FGF-23 and vitamin D independently influenced the Klotho levels. In the generalized linear model, only the Klotho groups were statistically significant as independent variable (p=0.007). The results show that the group 1 (<268) compared with group 3 (>440) had higher odds in the higher ACR (≥181), ORa=3.429, p=0.014. There were no statistically significant differences between Klotho groups 2 and 3, and the HOMA-IR obtained showed that group 1 (<268) had greater odds of HOMA-IR ≥2 when compared with group 3 (>440), ORa=21.59, p=0.017. Our results showed that Klotho levels are influenced by FGF23, vitamin D and insulin resistance. This suggests that Klotho levels might be affected by renal function as well as having a relevant role on insulin metabolism and ACR homeostasis.
Highlights
Klotho is a protein expressed in several organs and tissues, with greater predominance in the kidney and brain
Results showed that Klotho levels were correlated with FGF23, vitamin D and insulin resistance, suggesting that Klotho levels might be affected by renal function
This seems to be in accordance with most of the studies that describe chronic kidney disease (CKD) as a state of FGF-23 resistance caused by the deficiency of Klotho [16]
Summary
Klotho is a protein expressed in several organs and tissues, with greater predominance in the kidney and brain. It has been implicated in multiple organic processes, being able to regulate growth factors signaling pathways, ion channels and transporters [1]. Klotho plays a relevant role within the bonekidney endocrine axis. In association FGF-23, it mediates the phosphate excretion and homeostasis through the inhibition of 1.25(OH) vitamin D3 synthesis and the induction of phosphaturia [2]. Klotho seems to play a renoprotective role through its anti-oxidation properties: protection of vasculature, promotion of vascularization and inhibition of fibrinogenesis [6]. It appears reasonable to consider Klotho as a potential surrogate
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