Interplay Between Klotho and IL-6 in Diabetic Kidney Disease: Inflammation, Mineral Dysregulation, and Renal Dysfunction

Abstract

Diabetic kidney disease is a serious complication of diabetes mellitus, often leading to chronic kidney disease and ultimately end-stage renal disease. Inflammation, besides deranged mineral metabolism, plays a role in the pathophysiology of diabetic kidney disease. The present study investigated the relationship between IL-6 an important pro-inflammatory cytokine, and Klotho an anti-aging protein with renoprotective function in diabetic kidney disease progression. A study was carried out on 60 patients with ESRD caused by diabetic kidney disease on maintenance hemodialysis and 40 apparently healthy control individuals. IL-6 and Klotho serum levels were measured using the enzyme-linked immunosorbent assay method. Some biochemical indicators, such as intact parathyroid hormone, 1.25-dihydroxyvitamin D₃, blood urea, and creatinine, were also measured. The main findings (mean ± SE) showed that the levels of IL-6 and iPTH levels were considerably higher in DKD patients (18.360 ± 2.323 pg/mL; 239.222 ± 24.073 pg/dL) than in controls (4.341 ± 0.393 pg/mL; 26.077 ± 1.609 pg/dL), indicating persistent inflammation and secondary hyperparathyroidism. Conversely, serum 1.25(OH)₂D₃ and Klotho levels were considerably lower in the DKD group (14.911 ± 0.991 ng/dL and 213.500 ± 25.905 pg/mL, respectively) than in controls (29.125 ± 1.195 ng/dL and 453.587 ± 33.797 pg/mL), indicating kidney function impairment and mineral metabolism disturbance. There was a notable weak inverse relationship between IL-6 and Klotho (r = –0.271, p = 0.036). This suggests that Klotho low levels may increase inflammatory responses and adversely affect renal function. In conclusion, the research demonstrates how IL-6 and Klotho affect one another in diabetic kidney disease. This suggests their application as potential biomarkers for disease progression and targets for therapy in preventing inflammation and maintaining kidney function.