Increased oxidative stress in diabetic nephropathy and its relationship with soluble Klotho levels

Background: In the present study, we aimed to assess the relationship between the levels of soluble Klotho (s-Klotho) and oxidative stress markers in diabetic nephropathy patients with different stages of chronic kidney disease (CKD) and albuminuria levels.

Methods: We enrolled 109 patients with type 2 diabetes (mean age, 61.63 ± 9.77 years) and 32 healthy controls (mean age, 49.53 ± 7.32 years) between January and June 2014. Patients were classified into three groups based on their urinary albumin/creatinine ratio (UACR). Blood samples were collected to measure the levels of s-Klotho, serum creatinine, calcium, phosphorus, 25-hydroxyvitamin D3, and parathyroid hormone (PTH). We used the total oxidant status (TOS), total antioxidant status (TAS), ischemia-modified albumin (IMA), and ischemia-modified albumin ratio (IMAR) values to measure the oxidative status. Moreover, the oxidative stress index (OSI) was estimated as the percentage ratio of TOS/TAS values.

Results: The TOS, TAS, and OSI values were significantly greater in the diabetic nephropathy patients compared to controls (p <0.001). When patients were classified based on their UACR, we noted that the TOS, OSI, and IMA values did not significantly differ, although the TAS (p <0.001), and IMAR (p =0.002) values significantly differed between the groups. The s-Klotho levels also significantly differed (p =0.031) between the groups. These s-Klotho levels exhibited a significant positive correlation with TOS (r =0.186, p =0.034) and OSI (r =0.207 p =0.018), but showed no correlation with the estimated glomerular filtration rate; UACR; HbA1c, calcium, phosphorus, and PTH levels; and TAS, IMA, and IMAR values.

Conclusion: Oxidative stress is greater in patients with diabetic nephropathy, and the TOS was positively correlated with s-Klotho levels in diabetic patients. The therapeutic reduction of oxidative stress in patients with diabetic nephropathy could improve the renal and cardiovascular outcomes. Hippokratia 2016, 20(3): 198-203.