DARNLEY, M. J., N. M. DIMARCO, and H. M. AUKEMA. Safety of chronic exercise in a rat model of kidney disease. Med. Sci. Sports Exerc., Vol. 32, No. 3, pp. 576–580, 2000.
Purpose: The objective of this study was to determine the effect of treadmill running on polycystic kidney disease (PKD) progression and bone mineral density in Han:SPRD-cy rats, an animal model of PKD.
Methods: Using a 2 × 2 design, normal and polycystic male rats were divided randomly into exercise and sedentary groups at 4 wk of age. The exercising group performed treadmill exercise (14 m·min−1) for 30 min 3 d·wk−1 for 6 wk, whereas the control group remained sedentary. This 6-wk period represents the period of greatest cyst growth in this model.
Results: Both exercised and sedentary polycystic animals had significantly greater kidney weights, as well as greater concentrations of serum urea nitrogen and serum creatinine than control animals. Exercise did not alter these parameters in either normal or polycystic animals. In addition, bone mineral density and bone mineral content, determined by dual-energy x-ray absorptiometry, were not altered by exercise in these animals. Bone mineral content, however, was marginally lower in polycystic animals.
Conclusions: These results support the safety of moderate exercise in PKD. Additional research in this area is needed since there may be other benefits that are derived from exercise in this population.
Kidney disease affects over 3.5 million Americans, resulting in annual healthcare costs that exceed $10 billion. Autosomal dominant polycystic kidney disease (PKD) is the most common inherited nephropathy, affecting over 600,000 people in the United States and 12 million people worldwide (32). The incidence of PKD is greater than the combined occurrences of cystic fibrosis, multiple sclerosis, muscular dystrophy, sickle cell anemia, and hemophilia. In addition, renal cysts are frequently seen in dialysis patients (17) and are a common feature of the aging kidney (20). As PKD progresses, kidney weight increases with cyst enlargement. Encroachment upon normal tissue ultimately leads to the deterioration of renal function, with uremia developing in the latter stages of the disease as concentrations of serum urea nitrogen (SUN) and creatinine increase.
The severity and rates of disease progression of various kidney diseases can be influenced by exercise, and the benefits of aerobic exercise are well established in dialysis patients. In dialysis patients, regular exercise potentially improves the effectiveness of dialysis, improves coronary risk factors and anemia (9–11) and appears to be safe for patients without electrocardiographic evidence of coronary artery disease (8,25).
During chronic renal disease, an improvement in renal function in response to exercise has been demonstrated in several animal models. Aerobic exercise training for 8 wk in partially nephrectomized rats resulted in higher glomerular filtration rates (GFR) and less proteinuria in exercised compared with sedentary animals (15). Osato et al. (24) reported lower serum creatinine concentration and higher inulin clearance in adriamycin-treated rats (a model of chronic progressive renal dysfunction) that were exercised aerobically and fed a restricted amount of food for 20 wk compared with controls.
It also has been suggested, however, that exercise could have a detrimental effect during moderate renal impairment. Even in normal animals, intense and prolonged aerobic exercise results in transient decreases in renal blood flow, proteinuria, and increased production of urea and uric acid (26,27). Humans with moderately impaired renal function can have a significant decline in GFR with acute bouts of physical activity and lose the ability to conserve water (30). Albumin excretion is observed during exercise even in early diabetes (3–17 yr duration of disease) and indicates a potential negative effect of exercise in this population at risk for nephropathy (31). Cornacoff et al. (4) found that rabbits with immune complex-mediated glomerulonephritis had higher levels of SUN and more albuminuria when aerobically trained animals were compared with sedentary controls.
Renal disease also affects bone metabolism by depressing the kidney-dependent hydroxylation of 25-hydroxycholecalciferol to 1,25-hydroxycholecalciferol (the active hormonal form of vitamin D). Renal osteodystrophy is a frequent complication in chronic renal failure patients, and bone metabolism can be affected early in the disease process (33). There is an inverse linear correlation between blood urea nitrogen, serum creatinine, and serum markers of bone formation, such as alkaline phosphatase in renal patients (12). Chronic running exercise in the early stages of the disease may benefit bone formation. Kannus et al. (18) have shown that seven weeks of aerobic treadmill running increases bone mineral content in previously immobilized rats. In PKD, renal osteodystrophy is common in the latter stages of the disease and also has been observed in the older Han:SPRD-cy rat model of PKD (19).
In contrast to research on the feasibility of exercise during the latter stages of kidney disease, there is a paucity of research on the effect of chronic exercise during moderate renal impairment in the early stages of the disease. With respect to PKD, specifically, the effect of exercise on disease progression and bone formation and the effect of renal cystic disease on bone formation has not been examined in the early stages of PKD. The purpose of this study, therefore, was to determine potential benefits and/or risks of a 6-wk period of chronic exercise on early disease progression and bone density in the Han:SPRD-cy rat model of PKD.