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Abstract
Objectives Physical inactivity is a major adjustable lifestyle risk factor in renal patients; nevertheless, research on the association of physical activity (PA) with chronic kidney disease (CKD) is unclear.
Design Cross-sectional.
Setting We evaluated the secondary care related to the nephrology specialists.
Participants We evaluated PA in 3374 Iranian patients with CKD aged ≥18 years. Exclusion criteria were current or prior kidney transplantation, dementia, institutionalisation, expected to start renal replacement therapy or leave the area within study duration, participation in a clinical trial or inability to undergo the informed consent process.
Primary and secondary outcome The renal function parameters were measured and compared with PA, assessed by the Baecke questionnaire. Estimated glomerular filtration rate, haematuria and/or albuminuria were used to estimate decreased kidney function and the incidence of CKD. To estimate the relationship between PA and CKD, we used the multinomial adjusted regression models.
Results In the first model, findings indicate that the patients with the lowest PA score had significantly higher odds of CKD (OR 1.44, 95% CI 1.16 to 1.78; p=0.01), adjustment for age and sex attenuated this relationship (OR 1.25, 95% CI 1.56 to 1.78, p=0.04). Furthermore, adjusting for low-density lipoprotein, high-density lipoprotein, triglyceride, fasting blood glucose, body mass index, waist circumference, waist/hip ratio, coexisting diseases and smoking made this relationship insignificant (OR 1.23, 95% CI 0.97 to 1.55; p=0.076). After adjusting for potential confounders, we found that patients with lower PA have higher odds of CKD stage 2 (OR 1.62, 95% CI 1.13 to 2.32; p=0.008), no association with other CKD stages.
Conclusion These data suggest that physical inactivity contributes to the risk of early CKD, so encouraging patients with CKD to maintain higher PA levels could be used as a simple and useful tool to decrease the risk of disease progression and its related burden.
- CLINICAL PHYSIOLOGY
- Risk management
- Nephrology
- Chronic renal failure
- Dialysis
Data availability statement
Data are available on reasonable request.
This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
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STRENGTHS AND LIMITATIONS OF THIS STUDY
The large sample size and various variables were among the strength factors of the study.
Using a questionnaire, which is subjected to a number of biases, is among the limitations of this study.
Unmeasured confounders and subaccurate socioeconomic data are among the limitations of this study.
A cross-sectional design of the study that precludes us from interpreting the causality are among the limitations of this study.
Since this study was conducted among Iranian chronic kidney disease (CKD) and non-CKD participants, further studies are needed on this topic to validate our findings and yield accurate results.
Introduction
Chronic kidney disease (CKD) is recognised as an enormous public health burden associated with poor quality of life, high costs for healthcare systems and premature mortality.1 The global prevalence of this disease is rapidly increasing, especially in low-income and middle-income countries.2 Among various known factors, genetics, environmental factors and lifestyle play important roles in the development of the disease.3 4 Due to the existence of several risk factors in the incidence of CKD, it is necessary to identify modifiable factors related to lifestyle and target them to prevent the progression of this disease.
Epidemiological studies identify physical inactivity as an influential lifestyle factor in preventing non-communicable diseases,5 including some types of cancer, coronary heart disease and type 2 diabetes.6 Physical inactivity also has been hypothesised as a modifiable risk factor for CKD; however, the results of studies conducted on the relationship between physical activity (PA) and risk of developing CKD are inconsistent and contradictory. Some findings have shown that inactivity is associated with decreased glomerular filtration rate (GFR) and increased incidence of end-stage renal disease (ESRD).7–9 Also, in the US National Survey of Health and Nutrition, lack of PA was associated with a significant increase in the risk of ESRD and death.10 However, the findings of a population-based study among Australian adults did not show a significant relationship between leisure time, PA and the incidence of CKD.11 The results of a recent study among American adults aged 25–65 years also failed to prove any significant relationship between PA and the estimated glomerular filtration rate (eGFR).12
It is also noteworthy that studies that have so far examined the association between PA and kidney disease have been mainly conducted among western populations, while there is limited information in Asian countries, especially in the Middle East. For example, studies conducted in Saudi Arabia13 and Turkey14 did not even report any results pursuant to the association of PA with CKD. Similarly, studies in Iran have rarely considered PA in relation to CKD. Therefore, we used a population-based cross-sectional study to examine the association of PA with CKD in the Iranian general population. The results will be used to inform health agencies on the importance of lifestyle factors in the context of CKD and could be used as a basis for future research and interventions in high-risk populations.
Methods
Study design and subjects
This study reports baseline data from a cross-sectional population-based study conducted in Iran, in cooperation with Isfahan University of Medical Sciences. In brief, subjects were recruited from those visiting the healthcare centres within Isfahan city. The details of methodology were presented elsewhere.15 All participants were chosen at random from health centres based on the calling and advertisement. Eligibility criteria were age >18 years and CKD of any stage not requiring dialysis. Exclusion criteria were current or prior kidney transplantation, dementia, institutionalisation, expected to start renal replacement therapy or leave the area within study duration, participation in a clinical trial or inability to undergo the informed consent process. The screening phase of the original study ran from 2017 to 2019. In total, 3374 individuals were included.
Biochemical measurements
Venous blood and urine samples were collected in the morning after an overnight fast. Laboratory parameters included fasting blood glucose (FBG), serum levels of total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and serum triglyceride (TG), albumin, and creatinine.
eGFR was used as an indicator of kidney function and urine abnormalities were defined as the presence of albuminuria and/or haematuria, indicators for kidney damage. eGFR was assessed using Chronic Kidney Disease-Epidemiology Collaboration equation.16 Patients with albumin to creatinine ratio of less than 30, 30–299 and equal or higher than 300 mg/g, were classified as normal to mildly increased normal (A1), moderately increased albuminuria (A2) and severely increased albuminuria (A3), respectively.
Pursuant to the established NKF-KDOQI (National Kidney Foundation’s Kidney Disease Outcomes Quality Initiative) criteria, CKD was defined as the presence of decreased kidney function (eGFR<60 mL/min/1.73 m2), or presence of albuminuria (albumin equivalent to or >30 mg/g creatinine in a random urine sample), and/or haematuria (RBC (Red Blood Cell) >2 per high power field was considered as positive).17 18
Physical activity
We used the Persian version of the Baecke Habitual Physical Activity Questionnaire, a reliable and valid instrument that can be used to measure the level of habitual functional activities in Persian-speaking subjects.19–21 This tool consists of 16 questions within three main domains (occupational, sport and recreational) and examines PA level in the previous 12 months.22 Activities are scored from 1 to 5 and the total scores vary from 3 to 15. The most and the least activities for each index are indicated by 5 and 1 scores, respectively.
Other variables
Blood pressure was measured in the sitting position (Omron BF511 (Omron, Kyoto, Japan)); two measurements were obtained and the average of the measurements was used. Body weight ((Zyklusmed ZYK-MS01, China), to the nearest 0.1 kg, height (Seca, USA), waist circumference (midpoint between the lower costal margin and iliac crest) and hip circumference (the widest part of your buttocks), all to the nearest 0.5 cm, were measured by trained personnel. Current smoking status and history of cardiovascular and cerebrovascular events were obtained by an interview-administered protocol.
Statistical analysis
Participant characteristics were summarised by tertiles of PA. Data were described using frequency and proportion (n, %) and compared using χ2 or Fisher’s exact tests. For continuous variables, median with the first and third quartile of the distribution quantitative data was used. Kruskal-Wallis test was used to compare the differences of the continuous variables between tertiles of PA.
We used multinominal-adjust regression models to estimate ORs and their 95% CIs for the association of PA with odds of CKD and also across its stages. Analyses were performed using three adjusted and one crude models. Model 1 was adjusted for gender and age (continuous variable), model 2 additionally adjusted for HDL, LDL, TG, FBG, body mass index (BMI), waist circumference, waist to hip ratio (continuous variable) and smoking (yes/no categorical variable). Model 3, in addition to variables in model 2, was adjusted for comorbidities and musculoskeletal diseases (yes/no categorical variable). A p<0.05 was considered as a statistically significant.
Patient and public involvement
No patient involved.
Results
The study population consisted of 3374 individuals with a mean age of 49 years. Basic characteristics of participants are presented in table 1. The distribution of patients with CKD and also stratified by different stages of CKD across tertiles of PA scores are presented in table 2. As can be seen. 18.6% of the population was diagnosed with CKD. Subjects with the lowest PA level were most likely to have CKD and CKD stage 2, as well as less likely to have CKD stage 1, compared with those with the highest PA.
Basic characteristics of participants based on CKD stage groups
The distribution of patients with chronic kidney disease (CKD) across tertiles of physical activity score
Demographic information, coexisting diseases, anthropometric measures and laboratory data of study population across tertiles of PA are shown in online supplemental table 1. In the analysis of whole population, patients in the highest tertile of PA compared with lowest tertile were more likely to be male, smoker, as well as, less likely to have cerebrovascular accidents, diabetes mellitus, hypertension, cardiovascular disease and dyslipidaemia. Moreover, they had lower age, BMI, waist circumference, hip circumference, waist to hip ratio, TG, as well as higher eGFR, weight and height. In the analysis of population diagnosed with CKD, subjects in the highest tertile of PA compared with those of the lowest tertile were less likely to have cerebrovascular accidents, hypertension and cardiovascular disease, as well as more likely to be male. Furthermore, they had lower age, as well as higher eGFR and height. In the subgroup analysis of non-CKD patients, those in the bottom tertile of PA compared with top tertile had higher age, weight, BMI, waist circumference, hip circumference, waist to hip ratio, TG, as well as lower height. Also, they were more likely to have diabetes mellitus, hypertension and dyslipidaemia. Moreover, non-CKD patients in the highest tertile of PA were more likely to be male and smoker.
Supplemental material
The OR and the corresponding 95% CIs for the association between PA and CKD—as a whole—and CKD per stage are shown in table 3. In the crude model, patients with the lowest PA compared with the highest had significantly higher odds of CKD (OR 1.44, 95% CI 1.16 to 1.78; p=0.01). Further adjustment for age and sex (model 1) attenuated the relationship (OR 1.25, 95% CI 1.007 to 1.56; p=0.04). However, controlling for HDL, LDL, TG, FBG, BMI, waist circumference, waist to hip ratio, smoking and coexisting diseases (model 2) made this relationship insignificant (OR 1.23, 95% CI 0.97 to 1.55; p=0.076). The CKD subjects in the lowest tertile of PA compared with the greatest tertile had higher risk of CKD stage 2 in the crude model (OR 2.09, 95% CI 1.49 to 2.91; p<0.001). After controlling for potential confounders (model 3), lower PA showed to be associated with higher odds of CKD stage 2 (OR 1.62, 95% CI 1.13 to 2.32; p=0.008). No significant association was observed between tertiles of PA status and stages 1, 3 and 4 of CKD.
Logistic regression of the association between physical activity (PA) and chronic kidney disease
Discussion
The present population-based cross-sectional survey is among the first to investigate the association between PA status and risk of CKD among the Iranian population seeking care from specialty clinics of Isfahan, Iran. We found that patients with lower PA are at higher risk for developing CKD; however, this was not independent of potential confounders including HDL, LDL, TG, FBG, BMI, waist circumference, waist to hip ratio, smoking and coexisting diseases. Moreover, lower PA was also independently associated with a higher risk for stage 2 of CKD. These findings highlighted the importance of PA, especially among the high-risk population for CKD.
Previous literature proposed that compared with the general population, patients with CKD are less physically active.10 Furthermore, among the subjects diagnosed with CKD, lower PA was shown to be associated with greater risk of CKD progression, mortality and cardiovascular events.23–25 Moreover, it has been suggested that higher levels of PA were associated with metabolic health indicators of predialysis subjects including lower serum TG concentration, lower fat mass and greater insulin sensitivity that may translate to reduced progression of CKD.26 However, the findings of previous studies in terms of the association between PA and the risk of CKD are mostly conflicting. Some studies proposed that a lower PA associated with higher CKD risk,27–32 however, others did not show such an association.11 33–36 One of the main reasons of the present controversial findings among the studies may be contributed to the differences in questionnaires applied for evaluating PA. Some studies applied a simple questionnaire including one or two items,28–30 33 34 while others implemented comprehensive ones.11 27 36 Moreover, the inconsistency might be owing to the variations in different issues including genetic, ethnicity, participants; health status, age, sex and the criteria for the definition of CKD.
We found that patients with lower PA have higher rate for CKD; however, this association was mediated by potential confounders including HDL, LDL, TG, FBG, BMI, waist circumference, waist to hip ratio, smoking and coexisting diseases. This finding implies that there is not a single risk factor for CKD, instead this is a multifactorial disease as previously shown. The role of hyperlipidaemia,37 general and central obesity,38 and smoking39 in the development of CKD were shown in the literature. Moreover, the underlying diseases including diabetes40 and cardiovascular diseases41 were also proposed to be the predictors of CKD risk. These finding justified the association between PA and CKD risk in the current study which was not independent of mentioned confounders.
This study has some strength. The large sample size of Iranian population who lived within Isfahan, Iran was used for this cross-sectional study. Furthermore, various variables including demographic information, coexisting disease, anthropometric measures and laboratory data were adjusted, which in the previous studies had not been considered. However, there are some limitations to this study. The statistical study of the association may have been hampered by the small number of individuals in stage four or none in stage five CKD. Because the participants were chosen from general patients attending healthcare centres in Isfahan city, there were few or no volunteers in these advanced stages of CKD. This was a cross-sectional study that precludes us to interpret the causality. We used a questionnaire approach to evaluate the PA of participants. Although this is a more suitable approach for large study population since it is not time-consuming and inexpensive, this method is a subjective approach that is prone to miscalculate. Moreover, questionnaires are prone to recall bias, since they depend on the memory of participants.42 Unmeasured confounders and residual confounding may affect the risk of CKD that were overlooked in this study. We did not gather accurate data on socioeconomic status of participants that might have biased the association between PA and CKD risk. The incidence of CKD was defined using a single point measurement of eGFR and/or proteinuria and/or haematuria. This method of diagnosis had a sensitivity of 100% while had a low specificity, tending the results to the null. Finally, this study provided data regarding the association between PA and CKD among the selected population who lived in Isfahan province; therefore, caution is needed when generalising our findings to other populations.
Conclusion
In conclusion, we demonstrated that higher PA among the Iranian population was associated with a lower risk for developing CKD. Further prospective cohort studies are needed on this topic to validate our findings and draw a causal link between PA and CKD.
Data availability statement
Data are available on reasonable request.
Ethics statements
Patient consent for publication
Ethics approval
This study involves human participants and this study was carried out in accordance with the Declaration of Helsinki and with the approval of the local Ethics Committee of Isfahan University of Medical Sciences (IR.MUI.REC.1396.1.086). Participants gave informed consent to participate in the study before taking part.
References
Supplementary materials
Supplementary Data
This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.
Footnotes
Contributors Conception of the study: MB, MS, MMo, SV, Sh. Se and Sh. Sh. Design of the study: FM. Analysis and interpretation of data: MB, MMa. Drafting the article: FM, MMa and MB. Revising the article: SSe, MMo, SSh, SV and MS. Providing intellectual content of critical importance to the work described: FM, MB, SSe, MMa, MMo, SSh, SV and MS. Final approval of the version to be published: FM, MB, SSe, MMa, MMo, SSh, SV and MS.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.