Exercise Effect on Progression of Chronic Kidney Disease

Abstract

Chronic kidney disease （CKD） is a worldwide health burden that afflicts approximately 10,000,000 people even only in Japan. The unsolved issues around CKD lie not only in high, mainly cardiovascular, mortality of patients with end stage kidney disease but also in substantial expenditure for maintenance dialysis therapy. Unfortunately, effective remedies against CKD have not been well established although recent clinical trials casted light on several pharmaceutical agents for diabetes and hypertension such as renin-angiotensin-aldosterone （RAA） system inhibitors and sodium/glucose cotransporter 2 （SGLT-2） inhibitors. Since aerobatic exercise benefit on CKD progression is controversial, we designed animal experiments in which two different, immunologic and metabolic, renal injury models were conducted to mice which were concurrently subject to treadmill running test for 1 hour per day, 5 times per week. First, the exercise for 1 week prior to disease induction had no effect on albuminuria 8 hours after the induction, of mice with acute passive nephrotoxic serum induced glomerulonephritis. Secondly, we focused on diet-dependent renal injury and confirmed that high fat diet for only 8 weeks conferred to a significant amount of albuminuria in mice. Interestingly, the treadmill test for 8 weeks reduced albuminuria in mice fed with high fat diet as well as suppression of body weight gain. This result indicating that metabolic disorder based renal damage more than immunological renal damage may be able to receive benefits of the aerobatic exercise, raises a possibility that aerobatic exercise may prevent dyslipidemia-mediated CKD progression in a clinical setting. As to mechanistic process, in addition to improvement of systemic lipid and diabetic profile by skeletal activity, mitigation of renal lipotoxicity or enhancement of myokine action may also be contributory. Further study is needed to elucidate the underlying mechanism of the exercise effect on different animal CKD models.