As life expectancy increases, the impact of advanced age on renal health and function is becoming an increasingly important medical and socioeconomic factor. It is estimated that the glomerular filtration rate decreases by 0.8% − 1.0% per year after the age of 40 (12, 13). With increasing age, the size and number of total renal units decrease, tubulointerstitial changes occur, the glomerular basement membrane thickens, and glomerulosclerosis increases. This age-related histologic manifestation is often described as nephrosclerosis (14, 15). In this study, we found that more than 300 minutes per week of MPA or VPA was a protective factor for renal function. To some extent, these findings suggest that renal aging can be slowed by PA. Aging is characterized by progressive renal tubular dysfunction and changes in renal vascular structure and function(16, 17). CKD progression is associated with a decreased ability of β-oxidation to utilize free fatty acids and results in a shift of accumulated fatty acids to complex lipids such as TG. Improving lipid abnormalities may therefore help prevent CKD progression.(18) The diabetes-related decrease in eGFR is triggered by disturbances in glucose metabolism secondary to hemodynamic, inflammatory, and fibrotic processes (19). UA is a potential risk factor for renal injury because it induces activation of the immune system and alters the properties of resident renal cells, such as tubular epithelial cells, endothelial cells, and vascular smooth muscle cells, leading to proinflammatory and profibrotic states (20). Renal insufficiency in hypertensive patients is considered to be the manifestation of renal microangiopathy, which is characterized by the involvement of small preglomerular arteries and tubulointerstitial changes (21). PA has been demonstrated to improve hyperglycemia, hyperuricemia, hypertension, and dyslipidemia (22–24). Interestingly, this study revealed that PA affected the kidneys independently of blood glucose, blood lipids, hypertension, and blood uric acid, demonstrating that there is a unique mechanism by which PA benefits the kidneys.
The inhibition of inflammatory processes has been found to protect the kidney in experimental models of acute kidney failure (AKI) and CKD (25, 26). Exercise exerts systemic anti-inflammatory effects by reducing visceral lipids (27). Renal fibers are associated with persistent inflammatory stimulation(28). Six weeks of moderate-intensity treadmill training attenuated the infiltration of interleukin-1β, monocyte chemoattractant protein-1, and macrophages in the kidneys, thereby alleviating renal injury (29). In a sepsis-induced AKI model, high-intensity running improved renal function in mice while decreasing interleukin-6 and interleukin-10 levels (30). Eight weeks of aerobic exercise reduced nuclear factor-kappa B (NF-κB) expression and immune cell infiltration in the renal tissues of CKD rats (31). Amaral et al. demonstrated that initiating aerobic training prior to the onset of diabetes was more effective at reducing NF-κB activation in renal tissues than initiating it after the onset of diabetes (26). Studies in the CKD population have shown that walking for 6 months reduces plasma concentrations of interleukin-6 in predialysis patients (32). Irisin likely mediates the link between skeletal muscle and the kidney (33). Formigari et al. suggested that 8 weeks of aerobic training attenuated localized inflammation in the kidney by inhibiting AMP-activated protein kinase (AMPK) activation via irisin (33). In addition to its anti-inflammatory effects, the whole-body antioxidant effects of aerobic exercise are also widely recognized (34). Exercise-mediated antioxidant mechanisms are associated with the upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling (35). In AKI, moderate aerobic exercise may exert local antioxidant effects to protect the kidney by activating the Nrf2 signaling pathway (36). Clinical studies in humans have also shown that aerobic exercise training reduces serum malondialdehyde levels and increases the levels of the antioxidant enzymes superoxide dismutase and glutathione peroxidase and the total antioxidant capacity in CKD patients (37). Multiple apoptotic signaling pathways are involved in the pathophysiological events of AKI and CKD (38). Miyagi et al. observed a decrease in apoptotic cells in kidney tissue after 8 weeks of treadmill exercise in AKI mice (39). Reduced caspase-3 and increased Bcl-2 and Bcl-XL proteins in the kidneys of streptozotocin-induced DKD rats under moderate exercise (40). This evidence suggests that exercise training can exert a nephroprotective effect through the regulation of apoptosis in AKI and CKD patients. During the pathogenesis of CKD, fibrosis is one of the mechanisms leading to loss of renal function. Exercise training has emerged as a potential antifibrotic treatment strategy. Moderate light treadmill training reduces transforming growth factor β (TGF-β) and Smad levels in the kidney tissue of CKD rats (41). The antifibrotic effects of exercise training may be associated with increased NO bioavailability (42). In addition, Formigari et al. demonstrated that exercise training exerted an antifibrotic effect on the kidneys of CKD rats through activation of the irisin/AMPK pathway, leading to a decrease in the expression of TGF-β, fibronectin and type IV collagen (33). Autophagy plays an important role in maintaining renal homeostasis and is positively regulated in AKI (43). The autophagy pathway in AKI can lead to maladaptive repair and subsequent progression to CKD, such as glomerulosclerosis, vascular sclerosis, and tubulointerstitial fibrosis (44). Lima et al. reported that moderate exercise upregulated autophagy and simultaneously improved renal function in AKI patients (45). Experimental models of CKD suggest that aerobic exercise can restore autophagy activity by activating the AMPK pathway and subsequently inhibiting the mechanistic target of the rapamycin pathway, at least in part, to attenuate histological and functional damage (46). In conclusion, exercise training exerts a renoprotective effect against AKI and CKD through its antioxidant, anti-inflammatory, and antiapoptotic effects, in addition to regulating fibrosis and autophagy processes.
The World Health Organization (WHO) recommends that adults can improve all-cause mortality, cardiovascular disease mortality, and new-onset type 2 diabetes through 150–300 minutes or more of MPA per week, 75–150 minutes or more of VPA, or a combination of equal amounts of MPA and VPA (47). However, the WHO guidelines do not mention the effect of PA on renal outcomes. Current evidence on the renal benefits of physical activity focuses on chronic kidney disease (CKD) populations. PA in patients with chronic kidney disease has health benefits, such as improved survival, and may even slow the decline in kidney function (48, 49). However, it is not clear whether physical activity in the general population protects renal function. This study revealed that a duration of more than 300 minutes of MPA and VPA per week was a protective factor for renal function and was independent of factors such as blood glucose, blood lipids, and blood pressure. Therefore, we recommend more than 300 minutes of MPA and VPA per week to avoid sedentary behavior.
However, there are some limitations to this study. Our observations of exercise duration and intensity are based on questionnaires, and subjective bias is inevitable. Therefore, future randomized controlled trials are needed to validate the results of this study. Subgroup analyses were not performed in this study because the results were unreliable due to the small sample size.