I came across a recent paper entitled “Exercise Capacity in Polycystic Kidney Disease” from a group in Brazil. I am not sure what I hoped to find, maybe an excuse for not doing much exercise myself, a promise that would relieve me of all guilt feelings when the word exercise is uttered.
As the authors begin, reports on exercise and PKD are scarce, most in the last ten years focus on exercise during dialysis, an interesting topic but something my current brain isn’t too keen on contemplating.
The Brazil paper describes a prospective controlled cohort study to evaluate exercise capacity, nitrous oxide (NO) levels and asymmetric dimethylarginine (ADMA) in normotensive patients with ADPKD. Yes, I have had to read that twice to work it out – essentially, they took 26 people in the early stages of ADPKD, walked them on a treadmill, took blood and urine tests and compared the results with 30 people without ADPKD. All 56 people had normal eGFR, were between 19 and 39 years of age and had resting BP less than 140/80mmHg. They excluded smokers, obese people and any with significant comorbidities.
I needed to do some reading around NO and ADMA. In a nutshell, NO makes peripheral blood vessels dilate I won’t go into the physiology of why this may be a good thing because here they are using it as in indicator of endothelial function. Vascular endothelium is the inner lining of blood vessels and has a role in control of blood pressure. In ADPKD part of the problem is high blood pressure and one of the mechanisms leading to this is endothelial dysfunction. In a normal individual exercise should trigger a rise in NO levels.
ADMA is another index of endothelial function. It is a chemical found in plasma as a result of protein turnover in many tissues, including the vascular endothelium. It blocks nitrous oxide synthase, an enzyme that takes part in making NO, and so interferes with NO-dependent vasodilation. In normal people ADMA is expected to fall during exercise.
Now these people in the study with ADPKD did not yet have high blood pressure or any macroscopic evidence of renal impairment. The first abnormality the researchers found was that as a group the ADPKD people had significantly lower aerobic capacity – their oxygen uptake peaked at around 22ml/kg/minute compared with the healthy group at 31ml/kg/minute. Low aerobic capacity is an independent cardiovascular risk factor. It is a risk that can be modified but all the same this indicates that although the ADPKD patients may have had normal observable parameters, there are underlying changes to the disease that come on earlier than hypertension. The measure of aerobic function is useful for predicting the ability of a person to sustain a given work rate for a prolonged period – in some instances it can be used to infer “fitness”.
In addition, results demonstrated that the post-exercise levels of NO did not rise in the ADPKD group as it did in the control group. If NO remains low then the blood vessels are not able to dilate so effectively -this will have several effects, muscles get less oxygen, blood pressure remains high and the heart has to work harder. Altogether not a good thing.
Thirdly, although the ADMA levels were expected to and did decrease after exercise in the controls, this drop was not seen in the ADPKD group. I am not sure if this is just another way of measuring or stating that the nitrous-oxide-vasodilation system is impaired or whether it has an impact in its own right, whether ADMA can precipitate other adverse reactions or is indicative of other ill-effects. It certainly supports their findings on nitrous oxide.
So, the authors conclude that this research shows an inadequate response of both NO and ADMA to aerobic exercise and suggests strongly the presence of early endothelial dysfunction in ADPKD.
This doesn’t sound like good news, so I searched PubMed for papers on what can be done to improve endothelial dysfunction. The answer, in rats at least, was that controlling dietary fat intake did have some benefits but a combination of diet-control and swimming was significantly effective in improving vascular endothelial action. That they used swimming as the exercise is also interesting because swimming and immersion in water has considerable effects on the renal and vascular systems, but that’s another post altogether.
What does this paper add?
It was already known that ADPKD patients tend to develop high blood pressure which means they are at risk from cardiovascular problems. What this research has shown is that even before the BP is elevated or markers of renal function change, there are likely to be effects from endothelial dysfunction that in themselves represent a risk for cardiovascular disease.
So it partly explains why ADPKD patients may have a lower exercise capacity but it is most definitely not an excuse of any sort!