Chronic kidney disease (CKD)

CKD is a clinical condition characterized by gradual and progressive loss of kidney function that decreases the quality and quantity of body fluids, the production of substances with hormonal action, as well as the acid-base function of the body.

Among the most common CKD causes are:

Glomerulonephritis
Diabetic Nephropathy
Pyelonephritis or interstitial nephritis
Various systemic diseases, such as collagen diseases, polycystic and renal disease, obstructive renal disease kidney disease that occurs from drugs consumption etc.

The decrease of kidney’s glomerular filtration capacity gradually leads to dysfunction of all body organs and to the onset of various symptoms. A large percentage of the disorders that occur in the context of uremic syndrome are responsible for certain toxic substances (uremic toxins), such as urea, creatinine, parathormone, which are accumulated in the patients’ blood and spread to the tissues.

These uremic toxins are blamed for multiple complications from musculoskeletal, nervous, hematopoietic and circulatory systems, for disorders of the metabolism of carbohydrates and fats, as well as for other problems. Patients with End stage renal disease (ESRD) (GFR <15 ml / min / 1.73 m2) must undertake renal treatment, such as hemodialysis, continuous portable peritoneal dialysis (CAPD) or kidney transplantation. Because of modern methods of treatment, ESRD patients’ life expectancy has been increased significantly in the last twenty-five years. However, the survival’s extension is not associated with treatment of various problems of chronic uremia, in patients that are undergoing hemodialysis or peritoneal dialysis.

Thus, one of the most major problems is the fact that patients with CKD show particularly reduced physical activity levels, which also limits their ability to do physical exercise. More specifically, VO2 peak values range to 15-25 ml kg-1 min-1 and their maximum functional adequacy is less than 3.5 METs. These low physical activity levels are present even when the patient is undergoing dialysis.

Many researchers have shown that only 60% of non-diabetic and 23% of diabetic patients with CKD who undergo periodic dialysis are able to do daily physical activity. In fact, there is a characteristic linear correlation between the degree of renal insufficiency and the maximum ability to exercise.

Moreover, 70-80% of dialysis patients and 45% of transplanted patients are usually complaining about fatigue and muscle cramps. Thus, only about half of CKD dialysis patients can participate in moderate to high physical activity on daily base, while the rest of the patients have limited physical ability, even for low-intensity physical activity, such as walking or climbing stairs.

The reduced physical adequacy leads ERSD patients to physical work inability, social isolation, increases their psychological problems, such as depression, stress, low self-esteem, and leads to decreased quality of life.

However, reduced physical activity significantly deteriorates the complications that occur as a result of CKD and / or dialysis in the various body systems.

Thus, accelerates the development of atherosclerosis of blood vessels and
the occurrence of coronary heart disease.
reduces their aerobic capacity exacerbates muscle atrophy
osteoporosis and
degenerative lesions of the joints
One of the most important causes of decreased physical activity in ERSD patients is anemia.

It has been found that by using erythropoietin, there is a significant improvement (approximately 20%) in patients’ functional capacity for exercise workload. However, aerobic capacity remains in lower levels, at about 50%, than normal values.

Other factors that are responsible for reduced physical activity in CKD are:

left ventricular dysfunction, which limits the satisfactory increase in pulse volume during exercise,
autonomic nervous system’ s disorders, which limit the heart rate to reach the expected levels according to the intensity of physical effort,
disturbances in pulmonary ventilation and gas diffusion,
problems occurring in the metabolism and functional performance of skeletal muscle due to uremic neuropathy and myopathy.

Moreover, successful kidney transplantation has beneficial effects on the effects of chronic uremia and it significantly improves the physical activity level of ERSD patients. On the other side, patients undergoing renal function replacement, improvements in their physical activity can be significantly achieved by increasing physical activity, usually in the form of regular exercise.

Exercise in CKD patients

Exercise in patients with CKD encounters several difficulties, due to the specificity of the treatment, as dialysis patients spend about half a day a week in the hospital. The coexistence of many health problems in those patients, especially from the circulatory system, requires special attention and constant monitoring of patients in the initial stage at least of exercise programs.

The patients’ inclusion in exercise programs should be based on medical examination and assessment of their hemodynamic response to fatigue. It is therefore recommended firstly to apply a fatigue test or an ergospirometry test, in order to be included in an exercise program. Secondly, the patients’ functional capacity evaluation, either with laboratory tests or with simple field tests, contributes to the appropriate design of the program.

There are three methods of exercise that can be applied to hemodialysis patients:

A. The implementation of an exercise program in an organized rehabilitation center on non-dialysis days, three times per week, 60-90 min each time. Based on age, gender, day of dialysis, but also and on their personal obligations, patients should be divided into small groups.

The exercise training is suggested to be interval and comprises mainly aerobic exercises, as well as flexibility exercises and stretching, under the constant supervision and qualified staff instructions. After the first months, isotonic muscle strengthening exercises should be added, first with on the body weight and then with rubber bands or small weights adapted to their ends. In patients undergoing continuous ambulatory peritoneal dialysis, exercise should be done with their peritoneal cavity empty, while in transplant patients, exercise should start early after the transplantation surgery.

Despite the significant benefits of exercise on non-dialysis days, the total number of patients that participating is quite small. Lack of free time, since several hours are spent during the dialysis procedure at the Hospital, mobility difficulties and the coexistence of medical problems are the main reasons for reducing the number of patients participating in exercise or maintenance programs until their end. To solve the problem of limited participation, other ways of training were sought.

B. Systematic exercise in patients’ homes, about four to five times a week, lasting 30 minutes each time. This type of exercise mainly includes cycling on a stationary bike and performance of simple flexibility and stretching exercises after their cycling training. Occasionally simple tests of the exercises results should be made, as well as gradual modification of the exercise and its overall burden. In clinical practice, home based exercise was not found to have supporters, as patients did not appear to be involved. Most of them show indifference and constantly need motivation and encouragement in order to keep on going.

C. Exercise in the artificial kidney unit three times per week, 60 minutes per session, during the first two hours in patients undergoing dialysis. In Greece, the Sports Medicine Laboratory of TEFAA AUTH, implements from 1997 until today exercise programs during dialysis in the Artificial Kidney unit of the University Hospital AHEPA. The exercise is done mainly with special bicycles that adapt to the patient’s bed and it can be done either active or passive, while the patients remain in a reclining or sitting position. After the first months, exercise programs are added with isotonic muscle strengthening exercises, flexibility exercises and stretching exercises, under the constant supervision and instructions of specialized personnel. This method produces satisfactory results and has spread all over the world, mainly because the exercise is applied when the patients is already in the hospital for dialysis session and does not require extra time from them. However, this method has also some disadvantages, as the program is performed in the artificial kidney unit and the exercise is done individually for everyone, it is monotonous and there are limited exercise types that can be used. Due to the patient’s limitations with movement during dialysis, the exercise is mainly done with the lower extremities.

It is noteworthy that all the exercise programs start with a warm-up and end with a recovery.

Progress tests are regularly carried out, whose role is two-fold. On one hand, it gives the opportunity to check the condition of each patient and modify the type of exercise according to their needs. On the other hand, the patients themselves feel confident and satisfied seeing in practice the benefits of exercise, while maintaining the interest to continue participating in the program.

Exercise benefits in ESRD patients

The benefits of the exercise programs begin to appear 4-6 weeks after the beginning of these programs and mainly concern the improvement of patients’ functional capacity. According to studies that focus on the effects of systematic exercise on the morphology and function of the various organs on patients with CKD, safe conclusions can be drawn about the beneficial effect of exercise on key parameters, such as increasing cardiorespiratory fitness and overall physical function, better function of the autonomic nervous system, increased muscle strength, improved lipid and glucose metabolism, better control of hypertension, reduced cardiovascular risk, improved uremic myopathy and neuropathy, supporting the psychological state of patients, as well as improving their quality of life.

Specifically, it was found that the implementation of regular exercise programs causes:

Increase in the overall capacity for work, as assessed by improved cardiorespiratory capacity as well as fatigue time. The benefits of exercise related to the cardiorespiratory capacity of patients with CKD appear to be dose dependent. This improvement is attributed both to central favorable adaptations, i.e. to the increase of cardiac output, and mainly to peripheral adaptations that occur with exercise in skeletal muscles. Long-term exercise programs are particularly effective in improving patients’ functional capacity. Of course, exercise on non-dialysis days in an organized center seems to be the most effective method of exercise to improve the overall performance of patients.
Significant recovery of skeletal muscle atrophy. From the morphometric examination of muscle biopsies in hemodialysis patients, a significant percentage of the diameter of the muscle fibers the normal structure of the Z disks were restored, in the presence of satellite cells, as well as myoblasts and muscle filaments in different stages of regeneration and regeneration. Also found morphological restoration of cores and increased number of muscle fibers in the ribosome, which are indicative signs of increased protein production in them. At the same time, restoration of the normal structure of muscles mitochondria and blood capillaries was found. These morphological adaptations of skeletal muscle due to exercise also lead to an improvement in muscle strength and endurance and the conduction velocity of nerve stimulation.
Improvement of heart function in both calm and fatigue phase. This increase in the functional efficiency of the left ventricle is attributed to the increase in its end-diastolic volume, i.e. to the activation of the Frank-Starling mechanism, and to the decrease in the end-systolic volume, i.e. to the increase in endogenous myocardial contractility.
Increase in the tone action of the heart’s parasympathetic nervous system and decrease the corresponding of the sympathetic in the calm phase, thus restoring to a sufficient degree the dysfunction of the autonomic nervous system. This beneficial effect of exercise leads to a reduction in resting heart rate and the incidence rate of arrhythmias.
Prevention or slowing down the course of atherosclerosis, both by direct and indirect mechanisms (reduction of risk factors). The immediate mechanisms include the improvement of the lipid profile, but also the favorable effect of exercise on endothelial dysfunction. The wall tension caused by exercise on the arteries reduces the secretion of vasoconstrictors and promotes vasodilation. Systematic exercise has also been found to have a positive effect on vascular function, improving pulse wave velocity (PWV), which is an indicator of vascular elasticity, as well as pulse wave enhancement (AI).
Significant reduction in both systolic and diastolic blood pressure. The reduction of blood pressure in hypertensive patients with CKD after systematic exercise may be due to a reduction in circulating plasma volume, to direct beneficial effects of exercise on peripheral blood vessels (reduction of peripheral vascular resistance), as well as to suppression of sympathetic nervous system and renin-angiotensin system actions. The result of this reduction is a reduction in the dosage of antihypertensive therapy in some patients.
Improvement of the adequacy of dialysis, helping to faster clearance of substances such as urea.
Improvement of their psychosocial status. Systematic exercise in CKD patients reduces depression, enhances the feeling of self-confidence and self-esteem, helps social reintegration and, ultimately, leads to improved quality of life indicators. The increase in physical fitness level, the feeling of well-being and the psychological support provided by exercise, make them more able to cope successfully with their daily activities.
Increase in the capacity for physical work and improving their psychosocial status, helps them in their professional activity and social reintegration, mainly through the development of interpersonal relationships with the result of improving their quality of life.

Studies have shown that the physical activity level of CKD patients is a prognostic indicator of survival, as patients with aerobic capacity ≤17.5 ml/kg/min have a worse prognosis. Improving aerobic capacity through regular exercise also improves patient survival.

Thus, the implementation of special exercise programs for CKD patients is important for their social and psychological support and should be applied in all dialysis units in each country with the participation of properly trained physical education professors in collaboration with the medical staff.

Bibliography

Exercise Renal Rehabilitation Program: Psychosocial Effects
E Kouidi 1, A Iacovides, P Iordanidis, S Vassiliou, A Deligiannis, C Ierodiakonou, A Tourkantonis

The Effects of Exercise Training on Muscle Atrophy in Haemodialysis Patients
E Kouidi 1, M Albani, K Natsis, A Megalopoulos, P Gigis, O Guiba-Tziampiri, A Tourkantonis, A Deligiannis

Effects of Physical Training on Heart Rate Variability in Patients on Hemodialysis
A Deligiannis 1, E Kouidi, A Tourkantonis

Exercise Training in Patients With End-Stage Renal Disease on Hemodialysis: Comparison of Three Rehabilitation Programs
Erasmia Konstantinidou 1, Georgia Koukouvou, Evangelia Kouidi, Asterios Deligiannis, Achilleas Tourkantonis

Central and Peripheral Adaptations to Physical Training in Patients With End-Stage Renal Disease
E J Kouidi

Outcomes of Long-Term Exercise Training in Dialysis Patients: Comparison of Two Training Programs
E Kouidi 1, D Grekas, A Deligiannis, A Tourkantonis

Cardiac Effects of Exercise Rehabilitation in Hemodialysis Patients
A Deligiannis 1, E Kouidi, E Tassoulas, P Gigis, A Tourkantonis, A Coats