SciELO - Scientific Electronic Library Online

 
vol.66 issue4Cefazolin sodium pentahydrate combined with vacuum sealing drainage in the treatment of open fracture complicated with soft tissue injurymiR-125a-5p inhibits cancer stem cells phenotype and epithelial to mesenchymal transition in glioblastoma author indexsubject indexarticles search
Home Pagealphabetic serial listing  

Services on Demand

Journal

Article

Indicators

Related links

Share


Revista da Associação Médica Brasileira

Print version ISSN 0104-4230On-line version ISSN 1806-9282

Rev. Assoc. Med. Bras. vol.66 no.4 São Paulo Apr. 2020  Epub June 15, 2020

https://doi.org/10.1590/1806-9282.66.4.437 

ORIGINAL ARTICLE

Reduction of functional cardiovascular reserve in the stages of chronic kidney disease

Juliana Schneider1  4 
http://orcid.org/0000-0002-4517-7753

Paula Caitano Fontela1  2  4 
http://orcid.org/0000-0003-0086-7037

Matias Nunes Frizzo1  3 
http://orcid.org/0000-0001-5578-4656

Ligia Beatriz Bento Franz1  3 
http://orcid.org/0000-0001-7826-838X

Olvânia Basso de Oliveira4 
http://orcid.org/0000-0002-9581-2882

Eliane Roseli Winkelmann1  3 
http://orcid.org/0000-0002-4922-6516

1. Departamento de Ciências da Vida, Universidade Regional do Noroeste do Estado do Rio Grande do Sul, Ijuí, RS, Brasil.

2. Programa de Pós-Graduação em Ciências Pneumológicas, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil.

3. Programa de Pós-Graduação em Atenção Integral à Saúde, Universidade Regional do Noroeste do Estado do Rio Grande do Sul, Ijuí, RS, Brasil.

4. Hospital de Caridade de Ijuí, Ijuí, RS, Brasil.


SUMMARY

OBJECTIVE

Patients with chronic kidney disease (CKD) present reduced oxygen consumption at peak exercise (VO2 peak). No studies have evaluated objective measures of the cardiovascular reserve, besides VO2 peak and VO2 at the anaerobic threshold (VO2 AT), and compared these measures among ckd patients at different stages of the disease.

METHODS

Fifty-eight patients [pre-dialysis group (PD)=26, hemodialysis group (HD)=20, and post-kidney transplant group (KT)=12] were included. The following measures of cardiovascular reserve were obtained: 1) peak heart rate (HR); 2) peak systolic blood pressure (SBP); 3) VO2 peak and % predicted; 4) VO2 AT and % of predicted VO2; 5) peak circulatory power; 6) ventilatory efficiency for the production of carbon dioxide (VE/VCO2 slope); 7) oxygen uptake efficiency slope (OUES); and 8) recovery of gas exchange.

RESULTS

The VO2 peak and VO2 AT in the PD, HD, and KT groups were reduced to 86% and 69%, 70% and 57%, and 79% and 64% of the predicted value, respectively. Patients in the HD group had lower VO2 peak (17.5±5.9 vs. 23.2±8.2 [p-value=0.036]) and VO2 AT (14.0±5.2 vs. 18.3±4.7 [p-value=0.039]) compared to patients in the KT group. OUES was significantly lower in the HD group compared to the KT group (p-value=0.034). Age in the PD, HD, and KT groups and sedentary lifestyle in the KT group were predictors of VO2 peak.

CONCLUSIONS

CKD patients presented a reduction in cardiovascular reserve regardless of the stage of the disease. However, hemodialysis patients presented a greater reduction of cardiovascular reserve when compared to post-kidney transplant patients.

Key words: Renal insufficiency, chronic; Exercise test; Kidney transplantation; Renal dialysis

RESUMO

OBJETIVO

Pacientes com doença renal crônica (DRC) apresentam redução no consumo de oxigênio no pico do exercício (VO2 pico). Nenhum estudo avaliou medidas objetivas da reserva cardiovascular, além do VO2 pico e do VO2 no limiar anaeróbio (LA), e comparou essas medidas entre pacientes com DRC nos diferentes estágios da doença.

MÉTODOS

Cinquenta e oito pacientes [grupo pré-diálise (PD)=26, grupo hemodiálise (HD)=20 e grupo pós-transplante (PT)=12] foram incluídos. As seguintes medidas da reserva cardiovascular foram obtidas: 1) frequência cardíaca (FC) pico; 2) pressão arterial sistólica (PAS) pico; 3) VO2 pico e % do predito; 4) VO2 LA e % do VO2 predito; 5) potência circulatória pico; 6) eficiência ventilatória para a produção de dióxido de carbono (VE/VCO2 slope); 7) eficiência ventilatória para o consumo de oxigênio (Oues); 8) recuperação das trocas gasosas.

RESULTADOS

O VO2 pico e o VO2 LA nos grupos PD, HD e PT foram reduzidos para 86% e 69%, 70% e 57%, e 79% e 64% do valor previsto, respectivamente. Pacientes do grupo HD obtiveram VO2 pico (17,5±5,9 vs. 23,2±8,2 [p=0,036]) e VO2 LA (14,0±5,2 vs. 18,3±4,7 [p=0,039]) mais baixo, comparado aos pacientes PT. A Oues foi significativamente menor no grupo HD comparado ao grupo PT (p=0,034). Idade nos grupos PD, HD e PT, e sedentarismo no grupo PT foram preditores do VO2 pico.

CONCLUSÃO

Pacientes com DRC apresentam redução da reserva cardiovascular independentemente do estágio da doença. No entanto, pacientes em hemodiálise apresentam uma redução mais acentuada da reserva cardiovascular quando comparados aos pacientes pós-transplante.

Palavras-Chave: Insuficiência renal crônica; Teste de esforço; Transplante de rim; Diálise renal

INTRODUCTION

The cardiopulmonary exercise test (CPET) is considered a standard reference in the evaluation of cardiopulmonary and metabolic responses to aerobic exercise in patients with cardiovascular diseases1 . Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease2 . Complex changes in the cardiovascular system of CKD patients result in structural and functional changes that may lead to reduced tolerance to exercise and quality of life, increased morbidity, and finally, premature death3 .

Exercise capacity depends on the health of the cardiovascular system in maintaining the transport of oxygen and carbon dioxide between the cellular and pulmonary systems4 . A reduction in exercise capacity limits the range of physical activities a patient can perform. Several measures of the functional cardiovascular reserve, in addition to those traditionally used, can be obtained from a CPET and have been used to evaluate patients with heart failure5 , 6 .

Several studies have already demonstrated a reduction in the functional cardiovascular reserve through a reduction of oxygen uptake at peak exercise (VO2 peak) in CKD patients7 - 10 . However, we are not aware of any previous studies that evaluated objective measures of the cardiovascular reserve, besides VO2 peak and VO2 at the anaerobic threshold (AT), and compared these measurements among CKD patients at different stages of the disease. Therefore, the objective of this study was to evaluate measures of functional cardiovascular reserve in CKD patients at different stages of the disease [pre-dialysis (PD), hemodialysis (HD), and post-kidney transplant (KT)] and to determine the predictors of VO2 peak in these groups of patients. We hypothesized that although these patients have CKD in common, measurements of functional cardiovascular reserve would be significantly different in the different stages of CKD. The knowledge of these changes and differences may guide the treatment and implementation of preventive measures for other diseases, especially cardiovascular ones, which may occur due to renal disease.

METHODS

Study design

A secondary analysis was carried out using the dataset of research performed with patients who were submitted to pre-dialysis treatment, hemodialysis, or kidney transplant under follow-up at the Nephrology Unit of the Charity Hospital of Ijuí-RS. The pieces of research were cross-sectional studies conducted between 2012 and 2014. The researcher responsible for the dataset approved its use.

Patients were included in this study if they were at least 18 years old and had all data from the evaluation protocol in the databases, which included complete clinical evaluation, laboratory analysis, and cardiopulmonary testing.

Study population

A total of 241 patients were followed up at the Nephrology Unit of the Charity Hospital of Ijuí-RS and screened between 2012 and 2014. From this total, 72 patients were included in previous research, of which 58 had complete biochemical and exercise capacity data and, therefore, were analyzed in this study ( Fig. 1 ).

FIGURE 1 

Data collection and variables

Clinical and demographic data were recorded, including age, sex, CKD etiology, time of current treatment, weight, height, body mass index (BMI), and presence of cardiovascular risk factors [sedentary lifestyle, systemic arterial hypertension (SAH), diabetes mellitus (DM), alcoholism, and smoking]. The laboratory data of creatinine, urea, potassium, hemoglobin, and hematocrit were collected from recent hematological and biochemical tests whose values were recorded on the medical records of the patients who were registered in the databases.

The CPET or maximum incremental exercise test was performed on a treadmill (Imbrasport, Porto Alegre, Brasil), with the following ramp protocol: initial speed of 1 km.h-1 and final speed of 6 km.h-1; and initial inclination of 0% and final inclination of 10%. Exhausted gases were analyzed every 20 seconds through a gas analyzer (total metabolic analysis system, TEEM 100, Aero Sport, Ann Arbor, Michigan). Blood pressure was measured every 3 minutes with a sphygmomanometer. Heart rate (HR) was determined using the R-R interval from 12 electrocardiogram leads. The CPET variables were calculated as described by Dall’Ago et al.11 . In summary, the VO2 peak was defined as the highest value achieved during the test for 20 seconds, and peak circulatory power was calculated as the product of VO2 peak and peak systolic blood pressure (peak SBP). The recovery kinetics of oxygen uptake (T1/2VO2) was evaluated as the time required for a 50% decrease from the VO2 peak and calculated using the least-squares model, according to Dall’Ago et al.11 . The oxygen uptake efficiency slope (OUES) was calculated as the slope of the linear regression line between VO2 and the logarithm of ventilation (VE)12 . The evaluation of ventilatory efficiency was calculated using the linear regression model relating the VE and carbon dioxide production (VCO2) during the exercise. For this, data from the entire cardiopulmonary test were used, from the beginning to the peak of the exercise. The slope values of the VE/VCO2 ratio line were used for the analysis of ventilatory efficiency. The first ventilatory threshold (also known as the anaerobic threshold) was determined by reviewing the gas exchange curves and was the heart rate in which the ventilatory equivalent for oxygen increases systematically without an increase in the ventilatory equivalent for carbon dioxide1 . The prediction equation of the maximal oxygen uptake (VO2 max), proposed by Almeida et al.13 for the Brazilian population, was used. All patients continued taking their usual medication prescribed by their physicians.

Statistical analysis

Normality was measured using the Kolmogorov-Smirnov test. Depending on the distribution of the variable, continuous data were described through the mean and standard deviation or median and interquartile range and compared by ANOVA (Tukey) or Kruskal-Wallis test, as appropriate. Categorical variables were presented as a percentage and were compared by Chi-square test or Fisher’s exact test, as appropriate.

The VO2 peak (in mL.kg-1.min-1) adjusted for age and body mass index was the outcome variable of primary interest in this study and, therefore, was used as a dependent variable for regression modeling analyses. To identify important predictors of VO2 peak, a sequence of regression modeling analyzes were performed. Patient data were analyzed separately to determine the variables that were predictive of the VO2 peak within each group. Significantly different variables between groups were first analyzed in a univariate linear regression model. Then, those significantly associated in the univariate analysis (p-value<0.05) were included in a multiple linear regression model. All data were stored and analyzed in the Statistical Package for the Social Sciences (SPSS) software for windows v. 20.0. A significance level of 5% was adopted.

RESULTS

Characteristics of the patient population

Fifty-eight patients were included in this study. The characteristics of these patients are shown in Table 1 . The CKD patients of the three groups had similar (a) sociodemographic and clinical characteristics: age (p-value=0.202), sex (p-value=0.526), BMI (p-value=0.790), time of CKD (p-value=0.084); and (b) prevalence of comorbidities such as: hypertension (p-value=0.340), DM (p-value=0.768), smoking (p-value=0.237), and alcoholism (p-value=0.146).

TABLE 1 CHARACTERISTICS OF THE STUDY POPULATION IN THE DIFFERENT STAGES OF CHRONIC KIDNEY DISEASE 

Variables PD (n = 26) HD (n = 20) KT (n = 12) p-value
Age, years 61.2 ± 16.3 56.2 ± 11.3 53.3 ± 8.6 0.202
Males, n (%) 17 (65.4) 14 (70.0) 10 (83.3) 0.526
BMI, kg.m-2 27.8 ± 4.3 26.8 ± 4.3 27.4 ± 5.3 0.790
Treatment timea, months 12.0 [5.5 – 36.0] 36.0 [14.5 – 50.2] 31.0 [20.5 – 207.5] 0.084
Comorbidities, n (%)
SAH 23 (88.5) 15 (75.0) 11 (91.7) 0.340
DM 13 (50.0) 8 (40.0) 6 (50.0) 0.768
Sedentary lifestyleb 21 (80.8) 17 (85.0)§ 5 (41.7)‡ 0.015*
Smoking 4 (15.4) 1 (5.0) 0 (0.0) 0.237
Alcoholism 8 (30.8) 7 (35.0) 0 (0.0) 0.146
Biochemical parameters
Creatinine, mg.dL-1 3.2 ± 1.5† 9.3 ± 2.5§ 1.5 ± 0.3‡ <0.001*
Urea, mg.dL-1 106.6 ± 43.3† 160.1 ± 46.4§ 55.3 ± 15.0‡ <0.001*
Potassium, mEq.L-1 8.8 ± 11.7† 5.2 ± 0.8 4.4 ± 0.4‡ 0.004*
Hemoglobin, g.dL-1 12.3 ± 2.1† 9.7 ± 1.6§ 13.8 ± 1.5 <0.001*
Hematocrit, % 37.6 ± 6.0† 29.8 ± 5.0§ 41.7 ± 4.6 <0.001*
Anemiac, n (%) 13 (50.0)† 20 (100.0)§ 4 (33.3) <0.001*

PD: pre-dialysis group; HD: hemodialysis group; KT: post-kidney transplant group; BMI: body mass index; CKD: chronic kidney disease; SAH: systemic arterial hypertension; DM: diabetes mellitus. a: Treatment time, months: this variable refers to the time of conventional treatment through the use of medication in the PD group, the time of hemodialysis treatment in the HD group, and the time since kidney transplant for the KT group. b: The patient was considered sedentary if he/she reported not performing any physical activity at least 3 times a week for at least 30 minutes. c: Anemia was defined according to World Health Organization criteria (hemoglobin <13 g.dL-1 in men and <12 g.dL-1 in women). Values for categorical variables are presented as frequency (percentage); values for continuous variables are presented as mean ± standard deviation or median [interquartile range]; the p-value was calculated by the Tukey test or Kruskall-Wallis test for continuous variables and Chi-square test or Fisher's exact test for categorical variables. * p-value ≤0.05. † p-value = 0.05 when compared to the PD and HD groups (Mann-Whitney test or Fisher’s exact test). ‡ p-value = 0.05 when compared to the PD and KT groups (Mann-Whitney test or Fisher’s exact test). § p-value = 0.05 when compared to the HD and KT groups (Mann-Whitney test or Fisher’s exact test).

Biochemical data differed significantly between the PD, HD, and KT groups ( Table 1 ). Creatinine and urea levels were higher in patients in the HD group when compared to patients in the PD group (p-value<0.001; p-value=0.005) and KT group (p-value<0.001; p-value<0.001), respectively. Additionally, creatinine and urea levels were higher in patients in the PD group when compared to patients in the KT group (p-value=0.050; p-value=0.012), respectively. Potassium was significantly higher in the PD group when compared to the HD (p-value=0.050) and KT (p-value=0.042) groups. Hemoglobin and hematocrit levels were lower, and consequently the percentage of patients with anemia was higher in the HD group when compared to the PD (p-value=0.001; p-value=0.001) and KT groups (p-value<0.001; p-value<0.001).

Functional cardiovascular reserve

Metabolic data of the CPET for the three groups are presented in Fig. 2 . When compared to patients in the KT group, patients in the HD group had lower VO2 peak (17.5±5.9 vs. 23.2±8.2 [p-value=0.036]), corresponding to 70.5% vs. 79.5% of the predicted VO2 peak, and VO2 AT (14.0±5.2 vs. 18.3±4.7 [p-value=0.039]), corresponding to 56.7% vs. 63.7% of the predicted VO2 peak. Patients in the PD group presented lower peak circulatory power values when compared to those in the HD group (p-value=0.002). The OUES was significantly lower in the HD group when compared to the KT group (p-value=0.034).

FIGURE 2 

Independent predictors of VO2 peak

The increase in age was negatively associated with VO2 peak in patients in the PD group (b=-0.13; p-value=0.034), HD group (b=-0.33; p-value=0.002), and KT group (b=-0.66, p-value=0.011). A sedentary lifestyle was negatively and significantly associated with VO2 peak in patients in the KT group (b=-11.63, p-value= 0.007), but not in the PD (b=-1.85, p-value=0.487) and HD (b=-2.67, p-value=0.483) groups. The analysis of the multiple linear regression model for the KT group was performed. In the post-kidney transplant patient population, the constant VO2 peak was 54.59 mL.kg-1.min-1 (adjusted R2=0.76; p-value<0.001). Higher age (b=-0.51 [95% CI=-0.85 – -0.18], p-value=0.007) and sedentary lifestyle (b=-9.28 [95% CI= -14.83 – -3.72], p-value=0.004) were significant predictors of lower VO2 peak.

DISCUSSION

To our knowledge, this is the first study to evaluate measures of functional cardiovascular reserve in CKD patients and their association with the stages of kidney disease. Studies involving objective measures of the functional cardiovascular reserve are common for patients with heart disease5 , 6 , but for CKD patients, such studies are rare. In this study, we detected that VO2 peak and VO2 AT in pre-dialysis, hemodialysis, and post-kidney transplant patients were reduced to 86% and 69%, 70% and 57%, and 79% and 64% of the predicted value, respectively. A previous study has shown that reduced VO2 peak and VO2 AT values were associated with an increased risk of premature death in CKD patients14 . The present study further demonstrated that these parameters were significantly reduced in patients in the HD group compared to patients in the KT group. Other findings were that a) patients in the PD group had lower values of circulatory power when compared to those in the HD group, and b) OUES was significantly lower in the HD group when compared to the KT group.

OUES and circulatory power are variables which are evaluated less frequently than other traditional indices. Reduced OUES values5 , 15 and circulatory power16 , 17 predict a worse prognosis in heart disease. Despite the great potential of these variables for clinical evaluation16 - 18 , we did not find its use in the population of CKD patients, so our data are pioneering and can serve as a comparison for future studies. When comparing our OUES data with those from another population that also had a chronic limiting disease, such as patients with heart failure (1.96 ml.min- 1 )5 , our patients performed worse regardless of the stage of CKD; only the KT group had slightly similar values.

VO2 peak, VO2 AT, and OUES were significantly better in post-kidney transplant patients, confirming their better exercise capacity when compared to patients in the HD group. These findings corroborate the literature that shows that kidney transplant is the only treatment that offers better survival compared to other renal replacement therapies. A successful kidney transplant reduces the risk of cardiovascular mortality when compared to maintaining dialysis therapy14 , 19 , 20 . A recent study has demonstrated an improvement in the survival of patients with reduced functional cardiovascular reserve after kidney transplant14 .

Although VO2 peak, VO2 AT, and OUES were better in the post-kidney transplant patients, all the other measures of the functional cardiovascular reserve were not significantly different from the patients in the PD and HD groups. This evidences that the improvement in exercise capacity is not complete, and that it depends on other factors such as the adoption of a healthy lifestyle with regular practice of exercise. For the KT patients, a sedentary lifestyle was a significant independent predictor of lower VO2 peak. Physical training has been shown to improve VO2 peak in patients undergoing long-term hemodialysis21 .

Comparable reduced VO2 peak values (18.8 mL.kg-1.min-1)10 ; (18.5 mL.kg-1.min-1)21 ; (18.6 mL.kg-1.min-1)7 were documented in previous studies in CKD patients undergoing hemodialysis, but other measures of the cardiovascular reserve were not available for comparison7 , 22 . A comparison with data from Sietsema et al.7 , 22 reveals that our patients’ hemoglobin levels were lower (11.2 and 11.8 g.dL-1), although the dialysis time was similar (41.5 and 32.0 months). Our patients were older and had a higher BMI, which may result in a lower VO2 peak; however, the VO2 peak was comparable across studies.

The hemoglobin levels of patients in our study were lower (11.8 g.dL-1) when compared to the study of Ting et al.10 , despite dialysis time (32.0 months), age (53.3 years), and BMI (27.2 kg.m-2) being similar. This study evaluated other objective measures of cardiovascular reserve such as VO2 peak (73.4% of predicted), VO2 AT (11.2 mL.kg-1.min-1), VO2 AT (43.9% of predicted VO2), VE/VCO2 slope (29.3), and HR peak (132.8 bpm), which were also relatively similar to those found in our study; however, our HD patients presented worse performance, except in VO2 AT.

Patients in the studied HD group presented a higher prevalence of anemia and significantly lower hemoglobin and hematocrit levels when compared to patients in the PD and KT groups. It is known that the presence of anemia in CKD is determined by different factors such as relative erythropoietin (EPO) deficiency, iron deficiency, inflammation, hyperparathyroidism, blood loss, decreased half-life of red blood cells, and deficiency of folic acid and vitamin B1223 .

Creatinine and urea are markers traditionally used to characterize the impairment of glomerular function. In our study, the values of these two markers for all three groups support the values of erythrocyte parameters since the greater the renal damage, the lower the EPO production, and consequently, the lower the erythrocyte production leading to an anemic state24 . Thus, even using recombinant human erythropoietin, hemodialysis patients present a greater degree of anemia, and a greater degree of functional impairment. Pre-dialytic patients still have higher hemoglobin concentrations due to better renal integrity. Patients after renal transplantation, due to the production of the grafted organ, are able to produce a greater amount of EPO and, therefore, have higher hemoglobin levels.

Hemoglobin and iron are involved in the processes of releasing oxygen to tissues, so they may affect exercise capacity. A recent study in patients with heart failure observed a significant reduction in exercise capacity in parallel to reduced hemoglobin levels, and in patients with anemia and iron deficiency, exercise capacity was significantly lower than in patients with isolated anemia or iron deficiency25 . We observed a significant difference in hemoglobin levels between the PD, HD, and KT groups, and in the VO2 peak and VO2 AT between the HD and KT groups. However, in a subgroup analysis, we did not observe a significant difference in VO2 peak between patients with and without anemia (p-value=0.390); additionally, there was no correlation between hemoglobin levels and VO2 peak (r=0.189; p-value=0.250) and VO2 AT (r=0.174, p-value=0.290). This evidences that in this population, regardless of the CKD stage, anemia did not significantly affect the measures of cardiovascular reserve and was not a predictor of VO2 peak.

This study is characterized by the initial exploration of measures of functional cardiovascular reserve in CKD patients and by comparing these measures between the different stages of the disease. Like any study, it has some limitations. First, although the literature indicates that measures of the functional cardiovascular reserve are prognostic markers in patients with heart failure, the cross-sectional nature and relatively small sample size of the present study did not allow us to expand the prognostic utility of both indices. Therefore, further prospective evaluations in this population are required to use these measures as prognostic markers.

CONCLUSIONS

Our study shows that patients with CKD present a reduction of functional cardiovascular reserve regardless of the stage of the disease they are in. However, hemodialysis patients presented a greater reduction of cardiovascular reserve when compared to post-kidney transplant patients. Since a sedentary lifestyle was an independent predictor of the lowest VO2 peak in post-kidney transplant patients, the importance of physical training to improve functional cardiovascular reserve is emphasized, especially in these patients.

REFERENCES

1. American Thoracic Society; American College of Chest Physicians. ATS/ ACCP Statement on cardiopulmonary exercise testing. Am J Respir Crit Care Med. 2003;167(2):211-77. [ Links ]

2. Foley RN, Parfrey PS, Sarnak MJ. Epidemiology of cardiovascular disease in chronic renal disease. J Am Soc Nephrol. 1998;9(12 Suppl):S16-23. [ Links ]

3. Beddhu S, Baird BC, Zitterkoph J, Neilson J, Greene T. Physical activity and mortality in chronic kidney disease (NHANES III). Clin J Am Soc Nephrol. 2009;4(12):1901-6. [ Links ]

4. Arena R, Sietsema KE. Cardiopulmonary exercise testing in the clinical evaluation of patients with heart and lung disease. Circulation. 2011;123(6):668-80. [ Links ]

5. Arena R, Myers J, Hsu L, Peberdy MA, Pinkstaff S, Bensimhon D, et al. The minute ventilation/carbon dioxide production slope is prognostically superior to the oxygen uptake efficiency slope. J Card Fail. 2007;13(6):462-9. [ Links ]

6. Arena R, Myers J, Guazzi M. The clinical and research applications of aerobic capacity and ventilatory efficiency in heart failure: an evidence-based review. Heart Fail Rev. 2008;13(2):245-69. [ Links ]

7. Sietsema KE, Amato A, Adler SG, Brass EP. Exercise capacity as a predictor of survival among ambulatory patients with end-stage renal disease. Kidney Int. 2004;65(2):719-24. [ Links ]

8. Johansen KL. Physical functioning and exercise capacity in patients on dialysis. Adv Renal Replace Ther. 1999;6(2):141-8. [ Links ]

9. Sezer S, Elsurer R, Ulubay G, Ozdemir FN, Haberal M. Factors associated with peak oxygen uptake in hemodialysis patients awaiting renal transplantation. Transplant Proc. 2007;39(4):879-82. [ Links ]

10. Ting SMS, Hamborg T, McGregor G, Oxborough D, Lim K, Koganti S, et al. Reduced cardiovascular reserve in chronic kidney failure: a matched cohort study. Am J Kidney Dis. 2015;66(2):274-84. [ Links ]

11. Dall’Ago P, Chiappa GR, Guths H, Stein R, Ribeiro JP. Inspiratory muscle training in patients with heart failure and inspiratory muscle weakness. A randomized trial. J Am Coll Cardiol. 2006;47(4):757-63. [ Links ]

12. Gademan MG, Swenne CA, Verwey HF, van de Vooren H, Haest JC, van Exel HJ, et al. Exercise training increases oxygen uptake efficiency slope in chronic heart failure. Eur J Cardiovasc Prev Rehabil. 2008;15(2):140-4. [ Links ]

13. Almeida AEM, Stefani CM, Nascimento JA, Almeida NM, Santos AC, Ribeiro JP, et al. Equação de predição do consumo de oxigênio em uma população brasileira. Arq Bras Cardiol. 2014;103(4):299-307. [ Links ]

14. Ting SM, Iqbal H, Kanji H, Hamborg T, Aldridge N, Krishnan N, et al. Functional cardiovascular reserve predicts survival pre-kidney and post-kidney transplantation. J Am Soc Nephrol. 2014;25(1):187-95. [ Links ]

15. Davies LC, Wensel R, Georgiadou P, Cicoira M, Coats AJ, Piepoli MF, et al. Enhanced prognostic value from cardiopulmonary exercise testing in chronic heart failure by non-linear analysis: oxygen uptake efficiency slope. Eur Heart J. 2006;27(6):684-90. [ Links ]

16. Jaussaud J, Blanc P, Derval N, Bordachar P, Courregelongue M, Roudaut R, et al. Ventilatory response and peak circulatory power: new functional markers of response after cardiac resynchronization therapy. Arch Cardiovasc Dis. 2010;103(3):184-91. [ Links ]

17. Madan N, Beachler L, Konstantinopoulos P, Worley S, Sun Z, Latson LA. Peak circulatory power as an indicator of clinical status in children after Fontan procedure. Pediatr Cardiol. 2010;31(8):1203-8. [ Links ]

18. Giardini A, Specchia S, Berton E, Sangiorgi D, Coutsoumbas G, Gargiulo G, et al. Strong and independent prognostic value of peak circulatory power in adults with congenital heart disease. Am Heart J. 2007;154(3):441-7. [ Links ]

19. Meier-Kriesche HU, Schold JD, Srinivas TR, Reed A, Kaplan B. Kidney transplantation halts cardiovascular disease progression in patients with end-stage renal disease. Am J Transplant. 2004;4(10):1662-8. [ Links ]

20. Sadaghdar H, Chelluri L, Bowles SA, Shapiro R. Outcome of renal transplant recipients in the ICU. Chest. 1995;107(5):1402-5. [ Links ]

21. Kouidi EJ, Grekas DM, Deligiannis AP. Effects of exercise training on noninvasive cardiac measures in patients undergoing long-term hemodialysis: a randomized controlled trial. Am J Kidney Dis. 2009;54(3):511-21. [ Links ]

22. Sietsema KE, Hiatt WR, Esler A, Adler S, Amato A, Brass EP. Clinical and demographic predictors of exercise capacity in end-stage renal disease. Am J Kidney Dis. 2002;39(1):76-85. [ Links ]

23. Abensur H. Iron deficiency in chronic kidney disease. Rev Bras Hematol Hemoter. 2010;32(Supl.2):84-8. [ Links ]

24. Tirmenstajn-Jankovic B, Dimkovic N, Perunicic-Pekovic G, Radojicic Z, Bastac D, Zikic S, et al. Anemia is independently associated with NT-proBNP levels in asymptomatic predialysis patients with chronic kidney disease. Hippokratia. 2013;17(4):307-12. [ Links ]

25. Ebner N, Jankowska EA, Ponikowski P, Lainscak M, Elsner S, Sliziuk V, et al. The impact of iron deficiency and anaemia on exercise capacity and outcomes in patients with chronic heart failure. Results from the studies investigating co-morbidities aggravating heart failure. Int J Cardiol. 2016;205:6-12. [ Links ]

This work is associated with the Universidade Regional do Noroeste do Estado do Rio Grande do Sul.

Received: August 08, 2019; Accepted: August 31, 2019

CORRESPONDING AUTHOR: Eliane Roseli Winkelmann Rua do Comércio, 2000, Ijuí, RS, Brasil - 98700-000 Tel: +55 3332 2000 E-mail: elianew@unijui.edu.br

Authors’ contributions

Schneider J designed the study, analyzed the data, and wrote the manuscript. Fontela PC reviewed the analysis of the data and the manuscript and provided intellectual content of critical importance to the work described. Frizzo MN, Franz LBB, and Oliveira OB reviewed the manuscript. Winkelmann ER designed the study, reviewed the analysis of the data, and wrote the manuscript. All authors approved the final version of the manuscript.

Creative Commons License  This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.