New insights about post‐exercise albuminuria in hypertensive patients

Based on office blood pressure (BP), the global prevalence of hypertension was estimated to be 1.13 billion in 2015.1 Regular physical activity is one of the recommended lifestyle measures that can contribute to reducing elevated BP effectively.2 Epidemiological studies suggest that regular aerobic exercises may be advantageous for the prevention and treatment of hypertension and reduction of cardiovascular risk and mortality. The World Health Organization (WHO) advises that healthy adults, aged 18-64, should do at least 150 minutes of moderate-intensity aerobic physical activity or 75 minutes of vigorous-intensity aerobic physical activity throughout the week, or an equivalent combination of moderate- and vigorous-intensity activity.3 The general health recommendation to perform moderate- or high-intensity exercise (>40%–60% maximum) for at least 30 minutes on most days per week to achieve a total of at least 150 minutes per week is likely to have a beneficial impact on BP lowering.4, 5 Indeed, these recommendations are in line with the American College of Sports Medicine position on exercise and hypertension.6 According to these definitions, the authors categorized the participants based on their reported lifestyle. Non-active participantshad no regular sport activity, less-active individuals were defined as exercising <2.5 hours (150 min) per week, and active ones were those who exercised ≥2.5 hours weekly. As expected, hypertensive participants demonstrated increased albumin excretion at rest.7 Furthermore, post-exercise albuminuria was higher in the hypertensive compared with the normotensive cohort. Post-exercise albuminuria is often observed, and its magnitude varies significantly between individuals. The causes of post-exercise albuminuria have not been conclusively established, but one likely mechanism encompasses renal hemodynamic changes.8 Scrutinizing their results, after adjustments for age, body mass index (BMI), metabolic equivalents of task (METS), diabetes mellitus, and use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, it becomes apparent that at rest both low-active and active patients with hypertension benefited from regular exercises, as they excreted less albumin in comparison with sedentary patients. Intriguingly, and independent of gender, only active hypertensive participants showed a lower albumin excretion. However, normotensive individuals did not present with such a trend. Albumin excretion in normotensive participants was associated with increased BMI and diabetes, while in hypertensive patients, it was also related to advanced age. Conversely, only for hypertensive patients, an active lifestyle was associated with reduced albuminuria. While the authors state that most of the participants in their study had normal kidney function, including normal range albumin excretion, the hypertensive population at baseline had a median albumin/creatinine ratio (ACR) at rest that was higher than that of their normotensive counterpart (3.6 vs 2.8 mg/g, respectively, P < 0.001). In addition, more patients had evidence of CKD (P = 0.002), and they were not included in the multivariate regression analysis. Peculiarly, individuals with hypertension also presented a higher mean fasting glucose (P < 0.001), but the difference of diabetic patients between groups was not displayed. It also needs to be noted that data on median time (~20 min) post-exercise urine samples were available for only 710 out of the 3931 enrolled participants, which may have had implications on individuals' oral hydration status. Of note, data regarding oral hydration during or post-exercise were not provided but could be relevant as Geardinie and colleagues demonstrated that rehydration during karate training could decrease albuminuria after exercise.9 Albuminuria is a well-known independent cardiovascular risk factor10 with the relationship being evident even at the lowest levels of albuminuria (<30 mg/g) regardless of chronic kidney disease (CKD) stage.11, 12 Increased sympathetic tone, a well-known risk factor for cardiovascular diseases, is also frequently present in patients with essential hypertension and those with CKD.13 In both hypertension and renal impairment, the mechanisms of the hyperadrenergic state are manifold and include reflex and neurohumoral pathways.13, 14 Sympathetic overactivity is present in the early stages of both conditions, showing a direct association with their severity.14, 15 A correlation between albuminuria and hemodynamic alterations resulting in an increased filtration fraction and glomerular hypertension has been observed in some diseases. Albuminuria accompanying glomerular hypertension provoking hyperfiltration has been described in diabetic16 and obese patients.17 Recently, endurance training has revealed a sympatho-inhibitory effect in states of sympathoexcitation.18, 19 In contrast to other types of exercise, endurance training is more efficient in lowering BP in hypertensive individuals (8.3/5.2 mm Hg). Regular activities of lower intensity and duration reduce BP less than moderate-intensity or high-intensity exercise, and it is associated with at least a 15% decrease in mortality in cohort studies.20, 21 In healthy individuals, intense endurance training has a more pronounced effect on autonomic balance,22 and longer duration interventions (≥4 months) have been more effective in lowering sympathetic activity.23 It is conceivable that hypertensive participants may have benefited more than the normotenisve ones, owing to the blunting of their increased sympathetic tone, which could reduce the activation of their renin-angiotensin-aldosterone (RAA) system, lowered renal blood flow, glomerular podocyte injury, endothelial dysfunction, and therefore their albumin excretion. Glomerular pressure reduction through RAA system blockade alleviates albuminuria and is considered to exert a nephroprotective critical role in nephropathies with albuminuria.24 During physical activities, the filtration rate increases at least in part due to alterations in renal blood flow.8, 25 These modifications are associated with activation of both the sympathetic nervous system and the RAA system.8, 25 Some data revealed that changes in renal hemodynamics could contribute to albuminuria.9, 25 A recent study described that in type 2 diabetic patients, who were mostly hypertensive (62%), light-moderate exercise, similar to that of normal daily activity, induced albuminuria.26 In this context, the authors also described that hypertensive individuals had increased albumin excretion post-exercise, compared with normotensive participants. Nonetheless, they revealed that in hypertensive patients, any regular sport activity could ameliorate rest ACR, and an active lifestyle may substantially impact on albuminuria reduction after exercise. This is a clinically relevant finding and demonstrates that an active lifestyle may serve as a potential protective factor to reduce post-exercise albuminuria and clearly support current recommendations of lifestyle modification as a valid basis for antihypertensive and cardio- and reno-protective therapeutic approaches. MGK, SC, and RC declare that they have no conflict of interest. MPS is supported by an NHMRC Research Fellowship and has received consulting fees, and/or travel and research support from Medtronic, Abbott, Novartis, Servier, Pfizer, and Boehringer-Ingelheim.