Limb ischemic per-conditioning ameliorated myocardial injury induced by renal ischemia/reperfusion in rats: the role of Klotho

Renal ischemic/reperfusion (I/R) injury leads to acute kidney injury with multiple organ damage. Klotho has anti-inflammatory and antioxidant capacities and protects the heart and kidneys against I/R injury. This study aimed to determine whether Klotho is involved in the cardioprotective effect of limb ischemic per-conditioning (LIPerC) during renal I/R injury. Sprague-Dawley rats were randomly divided into three groups: Sham, I/R underwent bilateral occlusions of the renal pedicles for 60 min followed by reperfusion for 24 h, and LIPerc + I/R, which underwent cyclic I/R of the left femoral artery performed during renal ischemia. After 24 h, plasma, urine, and kidney and heart tissue were collected. Renal and cardiac functional biomarkers, soluble Klotho, oxidative stress, and inflammatory mediators were assessed. Renal I/R injury caused a decrease in soluble Klotho and increased blood urea nitrogen, creatinine, troponin I, and LDH (p < 0.01). Moreover, it established oxidative stress and histopathological changes in the kidney and myocardium. The levels of TNF-α and NF-κB were upregulated, and Klotho (p < 0.01) was downregulated in the post-I/R cardiac tissue. LIPerC improved the histopathological changes and suppressed the oxidative status and inflammation. LIPerC could not compensate for the Klotho expression in the heart tissue. However, correlations between plasma levels and heart expression of Klotho with oxidative and inflammatory signals could confirm the role of Klotho in the healing effect of LIPerC on remote cardiac injury. LIPerC may potentially ameliorate the remote cardiac dysfunction induced by renal I/R injury by modulating oxidative and inflammatory signals associated with the Klotho protein.