A new study suggests that high-intensity, but not moderate-intensity, exercise may be associated with the development of RMC among individuals with sickle cell trait.

The study aimed to answer the question why some individuals with sickle cell trait are more likely to develop RMC. If additional strong risk factors were genetic then RMC cases would cluster in families in at least some cases. But this has practically never been observed, suggesting that non-genetic factors may be at play. Indeed, the driver event of RMC pathogenesis is thought to be renal medullary ischemia induced by the sickling of red blood cells in the setting of sickle cell trait. The longer length of the right renal artery can result in reduced blood flow in the right medulla vs the left, further exacerbating hypoxia predisposing to RMC thus accounting for the distinct predilection of RMC towards the right kidney. Moreover, epidemiological observations suggested that high-intensity exercise in individuals with sickle cell trait may increase the risk of adverse events due to red blood cell sickling including exertional rhabdomyolysis and sudden cardiac death. It is for this reason that National Collegiate Athletic Association adopted universal sickle cell trait screening for incoming Division I, II and III athletes. Conversely, moderate exercise has multiple long-term benefits in sickle cell trait.

The study hypothesized that red blood cell sickling due to high-intensity exercise may increase the risk of RMC. This hypothesis was then tested in a large dataset of patients with RMC and matched controls, as well as complementary animal models with sickle cell trait.

Whereas high-intensity exercise significantly exacerbated renal hypoxia in mice with sickle cell trait (but not wild-type mice), moderate-intensity exercise improved hypoxia levels consistent with the general recommendation that moderate exercise is beneficial for individuals with sickle cell trait. On the other hand, the hypoxia induced by high-intensity exercise was more prominent in the right kidney reflecting the distinct predilection of RMC toward the right kidney. Similarly to humans, the right renal artery of the mouse background strain used is known to be longer than the left.

The formal definition of moderate-intensity exercise is between 50 to 70 percent of the maximum heart rate for each individual. The maximum heart rate can be calculated by 220 minus the age of the individual. Thus, the maximum heart rate is 180 beats per minute for an individual that is 40 years old.

Individual performing moderate-intensity exercise can notice their breathing quicken but they will not be out of breath. They may develop a light sweat after about 5 to 10 minutes of activity, and can carry on a conversation while exercising but cannot sing.

The formal definition of high-intensity exercise is between 80 percent or more of the maximum heart rate for each individual. Individuals performing high-intensity exercise may notice their breathing being deep and rapid, may develop a sweat after just a few minutes of activity, and cannot say more than a few words without pausing for a breath.