Physical Function and Clinical Outcomes in Hemodialysis Patients: China Dialysis Outcomes and Practice Patterns Study

Abstract

Background

Hemodialysis (HD) patients usually have impaired physical function compared with the general population. Self-reported physical function is a simple method to implement in daily dialysis care. This study aimed to examine the association of self-reported physical function with clinical outcomes of HD patients.

Methods

The Dialysis Outcomes and Practice Patterns Study (DOPPS) is a prospective cohort study. Data on 1,427 HD patients in China DOPPS5 were analyzed. Self-reported physical function was characterized by 2 items of “moderate activities limited level” and “climbing stairs limited level.” Demographic data, comorbidities, hospitalization, and death records were collected from patients' records. Associations between physical function and outcomes were analyzed using COX regression models.

Results

Compared to “limited a lot” in moderate activities, “limited a little” and “not limited at all” groups were associated with lower all-cause mortality after adjusted for covariates (HR: 0.652, 95% CI: 0.435–0.977, and HR: 0.472, 95% CI: 0.241–0.927, respectively). And, not limited in moderate activities was associated with lower risk of hospitalization than the “limited a lot” group after adjusted for covariates (HR: 0.747, 95% CI: 0.570–0.978). Meanwhile, compared to “limited a lot” in climbing stairs, “limited a little” and “not limited at all” groups were associated with lower all-cause mortality (HR: 0.574, 95% CI: 0.380–0.865 and HR: 0.472, 95% CI: 0.293–0.762, respectively) but not hospitalization after fully adjusted.

Conclusion

Higher limited levels in self-reported physical function were associated with higher risk of all-cause mortality and hospitalization in HD patients.

Introduction

Physical function is a widespread measurement tool that most likely represents a composite result of many different physiological and psychosocial factors. Compared with the general population, a reduction of physical function could be observed in patients with early stage of CKD [1, 2], and this condition gets worse and more pronounced in hemodialysis (HD) patients [3, 4]. Numerous CKD patients suffer from fatigability, muscle wasting, muscle weakness, and sarcopenia [5]. Evidence from studies of the general population and CKD patients demonstrated that impaired physical function was strongly associated with increased all-cause mortality and other outcomes [6, 7, 8, 9]. The clinical practice guidelines for cardiovascular disease in dialysis patients published by the Kidney Disease Outcomes Quality Initiative (K/DOQI) suggested that nephrology and dialysis staff should measure patients' physical function and encourage them to increase physical activity [10]. However, staff in many nephrology departments and dialysis centers did not routinely assess patients' physical function, explain the importance of exercise, or provide measures for preventing the deterioration of physical function [11]. A 2003 survey indicated that only 38% of their nephrologists reported frequently assessing patients' physical activity condition and counseling sedentary patients to increase activity [12].

There are a number of methods available to assess physical activity levels, such as gait speed, the intermittent shuttle walk test, the 6-min walk test, peak oxygen uptake, and questionnaires [13, 14, 15]. Although many tests have been validated in the general population, some of them were not suitable for dialysis patients. There are many issues that need to be considered in the assessment of the physical function of dialysis patients. For example, dialysis patients are more likely to have sarcopenia than others, and they usually have weakness and fluid overload problems [16, 17]. Other considerations include time available for testing since they spend a lot of time lying down or sitting for dialysis treatment every week, suitable location (dialysis center vs. laboratory), and staff expertise [11]. These factors may limit the reliability, reproducibility, and prognostic utility of various assessment methods of physical function.

However, self-reported measures, such as Short-Form 12 (SF-12) [18, 19], may offer a more operative, convenient, and cost-effective way to assess dialysis patients' physical function. SF-12 is a self-reported questionnaire, which is frequently used to assess health-related quality of life [20]. SF-12 is shorter than SF-36. The physical component summary (PCS) score and mental component summary (MCS) score can be calculated by using SF-12. In our previous study, we found that a lower PCS score was associated with higher all-cause mortality (unpublished data). In SF-12, there are 2 items that represent physical function, namely, the moderated activities limited level and climbing stairs limited level. They are important basic movements that can be easily assessed as part of physical function evaluation.

Therefore, we hypothesized that higher limited levels of self-reported physical function (moderated activities and climbing stairs limited level) were associated with a higher risk of mortality and hospitalization among HD patients. We conducted a large prospective cohort study using data from China Dialysis Outcomes and Practices Patterns Study (DOPPS) to investigate whether these 2 simple items of self-reported physical function were associated with mortality and first hospitalization.

Methods

Study Design and Subjects

DOPPS is an international prospective cohort study of in-center adult HD patients including >20 countries in the world, which has been described in previous published papers [21, 22]. China was included in DOPPS4 (2009–2012). China DOPPS4 is an observational, cross-sectional study that collects data from a random sample of patients from a representative and random sample of HD units. Then, in DOPPS5 (2012–2015), we finished a 3-year cohort study, including collection of longitudinal data. China DOPPS was carried out in the 3 large cities in the metropolitan areas of China (Beijing, Shanghai, and Guangzhou). We randomly selected 15 dialysis facilities in each city from a stratified list of all HD facilities treating >25 HD patients and included an average of 30 patients at each facility. The inclusion criteria for participants were age ≥18 years and treated with regular HD for >3 months. Finally, there were 1,427 patients who participated in China DOPPS5.

Of the 1,427 patients, 134 patients were excluded from the present analysis as they did not answer the questions of self-reported physical function in the patient questionnaire survey. Baseline demographic and clinical data were collected at the start of participation in DOPPS5.

Items to Assess Physical Function

In China DOPPS5, there were 2 items about physical function as part of SF-12v2 in the patient questionnaire survey. The 2 items were “does your health now limit you in moderate activities, such as moving a table, pushing a vacuum cleaner, bowling, or playing golf? If so, how much?” and “does your health now limit you in climbing several flights of stairs? If so, how much?” Both the items had 3 response options: 1, “yes, limited a lot”; 2, “yes, limited a little”; and 3, “no, not limited at all.” This questionnaire was completed by a fixed investigator in each HD unit to keep the consistent standard.

Outcomes

The primary end-point event was all-cause mortality. The secondary end-point event was the first hospitalization with any causes during the follow-up period. The hospitalization event was defined as an inpatient hospitalization with an overnight stay, which was registered in the DOPPS survey. Observation or outpatient records were not included in this analysis.

Statistics Analysis

Continuous variables were represented as mean ± SD or median (25th and 75th) according to the results of the normality test. Categorical variables were expressed as percentage. We stratified data according to the moderate activity limited level and climbing stairs limited level, respectively. Differences in mean or median among groups were evaluated by using ANOVA or the nonparametric test. And, categorical data were compared by using the χ² test.

Survival curves were produced by using the Kaplan-Meier method and estimated by using the log-rank test. Associations between the moderate activity limited level, climbing stairs limited level, and all-cause mortality were analyzed using COX regression models. All COX models accounted for facility clustering effects by using the robust sandwich covariance estimate. Survival time for COX models of all-cause mortality was the time from study entry to the end of study or to death. And, failure time for COX models of hospitalization was the time from study entry to the end of study or to the first hospitalization. We made 1 unadjusted model and 3 adjusted models for each end-point. The adjusted covariates included in model 1 were age, gender, and vintage; model 2: model 1 variables plus BMI, hemoglobin (Hgb), albumin (Alb), single-pooled Kt/V, urine output, and vascular access type; and model 3: model 2 variables plus comorbidities (diabetes, coronary artery diseases, congestive heart failure, other cardiovascular diseases, cerebrovascular disease, hypertension, peripheral vascular disease, hepatitis B and C, lung disease, and cancer).

We performed the MI procedure to impute missing data, and continuous and categorical variables were imputed by fully conditional specification regression and logistic regression, respectively. After 20 steps of imputation, 20 data sets were combined for the final analysis of the Cox regression model and generalized linear mixed model. Percentages of missing for most variables were <10%, except for single-pooled Kt/V (36.2%). A p value <0.05 was found to be statistically significant. All statistical analyses were performed with SAS, version 9.4 (SAS Institute, Cary, NC, USA).

Results

Demographic Data and Clinical Characteristics

There were 1,233 patients who had baseline self-reported moderated activities limited levels. Overall, 466 patients (37.8%) responded that their moderate activities limited levels were “yes, limited a lot,” 497 (40.3%) said “yes, limited a little,” and 270 (21.9%) said “no, not limited at all.” Patients with a lower self-reported moderate activities level tended to be older and women. They also had a higher possibility of longer dialysis vintage, higher proportion of urine output <200 mL/day and catheter use, and lower serum Alb and Hgb, with more comorbidities, such as diabetes, coronary artery diseases, congestive heart failure, other cardiovascular diseases, cerebrovascular disease, peripheral vascular disease, and lung disease (Table 1). The baseline characteristics of all patients, nonresponders, and sample patients are shown in online suppl. Table 1; for all online suppl. materials, see www.karger.com/doi/10.1159/000513897.

Table 1.

Baseline characteristics of HD patients according to the moderate activities limited level

Variable	Moderate activities limited level			p value
	yes, limited a lot (n = 466)	yes, limited a little (n = 497)	no, not limited at all (n = 270)
Demographics
Age, years	67 (55, 77)	58 (48, 67)	53 (43, 62)	<0.0001*
Male, %	45.2	57.7	66.3	<0.0001*
Vintage, years	3.1 (0.9, 6.4)	2.3 (0.8, 5.0)	2.7 (1.0, 5.4)	0.0095*
BMI	21.6 (19.1, 24.1)	21.4 (19.4, 23.8)	21.5 (19.4, 23.6)	0.9798
Urine output >200 mL/day, %	26.6	34.4	37.6	0.0037*
Primary kidney diseases, %
Glomerulonephritis	33.9	43.4	57.4
Diabetic nephropathy	33.9	22.4	13.7	−
Hypertensive nephropathy	18.7	16.5	12.5
Others	13.5	17.7	16.5
Laboratory tests
Hgb, g/dL	10.4 (8.9, 11.6)	10.5 (9.3, 11.7)	10.9 (9.6, 11.7)	0.0153*
Alb, g/dL	3.8 (3.5, 4.1)	4.0 (3.8, 4.2)	4.1 (3.9, 4.3)	<0.0001*
White blood cells, 109/L	5.9 (4.9, 7.2)	6.0 (5.0, 7.2)	6.0 (4.7, 7.2)	0.8801
Dialysis prescription
spKt/V	1.3 (1.2, 1.5)	1.4 (1.2, 1.5)	1.3 (1.1, 1.5)	0.2035
Dialysis <3 times/week, %	19.8	21.2	25.2	0.2218
Fistula use, %	78.2	90.1	94.3	<0.0001*
Comorbidities, %
Diabetes	36.2	25.2	15.8	<0.0001*
Coronary artery disease	37.5	22.4	9.0	<0.0001*
Congestive heart failure	31.5	19.4	14.5	<0.0001*
Other cardiovascular disease	27.5	17.9	12.3	<0.0001*
Cerebrovascular disease	22.6	11.7	4.5	<0.0001*
Hypertension	84.4	88.4	85.8	0.1961
Peripheral vascular disease	14.0	5.9	3.7	<0.0001*
Hepatitis	12.2	14.1	13.0	0.6871
Lung disease	8.0	3.6	1.9	0.0003*
Cancer (nonskin)	4.8	3.5	2.6	0.3058

HD, hemodialysis; Hgb, hemoglobin; Alb, albumin; spKt/V, single-pooled Kt/V.

^*p < 0.05.

Meanwhile, data on the self-reported climbing stairs limited level were available for 1,254 patients. In total, 339 patients (27.0%) responded that their climbing stairs limited levels were “yes, limited a lot,” 471 (37.6%) said “yes, limited a little,” and 440 (35.1%) reported “no, not limited at all.” Similar to the results of the moderate activities limited level, patients who reported lower ability of climbing stairs tended to be older and women. They also had a higher possibility of higher proportion of urine output <200 mL/day and catheter use and lower serum Alb and Hgb, with more comorbidities, such as diabetes, coronary artery diseases, congestive heart failure, other cardiovascular diseases, cerebrovascular disease, peripheral vascular disease, and lung disease (online suppl. Table 2).

Associations between Moderated Activities Limited Level and Outcomes

Among 1,233 patients who reported moderated activities limited levels, 166 (13.5%) died and 552 (44.8%) had hospitalization records during the follow-up period. According to the results of Kaplan-Meier analysis, patients with higher limited levels of moderate activities had significantly higher risk of all-cause mortality and hospitalization (log-rank test, p < 0.0001, Fig. 1a, b). In the fully adjusted COX model, “no, not limited at all” and “yes, limited a little” in moderate activities were associated with decreased risk of all-cause mortality compared with the “yes, limited a lot” group (HR: 0.472, 95% CI: 0.241–0.927, and HR: 0.652, 95% CI: 0.435–0.977, respectively) (Table 2; Fig. 2a). After adjusting for all the covariates, “not limited” in moderate activities was negatively associated with hospitalization (HR: 0.747, 95% CI: 0.570–0.978) compared with the “limited a lot” group, but the “a little limited” group did not show a significantly negative relationship with hospitalization (HR: 0.954, 95% CI: 0. 753–1.207) (Table 3; Fig. 2b).

Fig. 1.

Kaplan-Meier curves for different limited levels of self-reported physical function in HD patients. Survival curves of all-cause mortality in different limited levels of moderate activities (a); survival curves of first hospitalization in different limited levels of moderate activities (b); survival curves of all-cause mortality in different limited levels of climbing stairs (c); and survival curves of the first hospitalization in different limited levels of climbing stairs (d). Log-rank test, p < 0.001. HD, hemodialysis.

Table 2.

Associations between moderate activities limited level and all-cause mortality in different COX regression models

	Unadjusted model HR (95% CI)	Adjusted model 1 HR (95% CI)	Adjusted model 2 HR (95% CI)	Adjusted model 3 HR (95% CI)
Moderate activities limited level
Yes, limited a lot	Ref.	Ref.	Ref.	Ref.
Yes, limited a little	0.408 (0.300–0.555)	0.549 (0.382–0.780)	0.615 (0.414–0.916)	0.652 (0.435–0.977)
No, not limited at all	0.229 (0.119–0.439)	0.355 (0.183–0.687)	0.414 (0.212–0.810)	0.472 (0.241–0.927)
Climbing stairs limited level
Yes, limited a lot	Ref.	Ref.	Ref.	Ref.
Yes, limited a little	0.380 (0.265–0.545)	0.480 (0.329–0.701)	0.530 (0.356–0.787)	0.574 (0.380–0.865)
No, not limited at all	0.229 (0.150–0.348)	0.361 (0.230–0.567)	0.411 (0.259–0.654)	0.472 (0.293–0.762)

Adjusted model 1: adjusted for age, gender, and vintage; adjusted model 2: model 1 + BMI, Hgb, Alb, spKt/V, urine output, and vascular access type; and adjusted model 3: model 2 + comorbidities (diabetes, coronary artery diseases, congestive heart failure, other cardiovascular diseases, cerebrovascular disease, hypertension, peripheral vascular disease, hepatitis B and C, lung disease, and cancer). Hgb, hemoglobin; Alb, albumin; spKt/V, single-pooled Kt/V.

Fig. 2.

Associations between self-reported physical function and outcomes. Associations between moderate activities limited level and all-cause mortality (a); associations between the climbing stairs limited level and all-cause mortality (b); associations between the moderate activities limited level and first hospitalization (c); and associations between the climbing stairs limited level and first hospitalization (d). Adjusted model 1: adjusted for age, gender, and vintage; adjusted model 2: model 1 + BMI, Hgb, Alb, spKt/V, urine output, and vascular access type; and adjusted model 3: model 2 + comorbidities (diabetes, coronary artery diseases, congestive heart failure, other cardiovascular diseases, cerebrovascular disease, hypertension, peripheral vascular disease, hepatitis B and C, lung disease, and cancer). Hgb, hemoglobin; Alb, albumin; spKt/V, single-pooled Kt/V.

Associations between Climbing Stairs Limited Level and Outcomes

Among 1,254 patients with results of climbing stairs limited levels, 170 (13.6%) of them died and 563 (44.9%) had hospitalization records over the follow-up period. From the survival curves, we found that higher limited levels of climbing stairs had higher risk of all-cause mortality and hospitalization (log-rank test, p < 0.0001, Fig. 1c, d). In the fully adjusted COX model, “no, not limited at all” and “yes, limited a little” in climbing stairs were significantly associated with decreased risk of all-cause mortality compared with the “yes, limited a lot” group (HR: 0.472, 95% CI: 0.293–0.762, and HR: 0.574, 95% CI: 0.380–0.865, respectively) (Table 2; Fig. 2c). However, after adjusted for characteristics and comorbidities, neither “no limited” nor “limited a little” in climbing stairs was significantly associated with decreased risk of hospitalization (HR: 0.809, 95% CI: 0.629–1.042, and HR: 0.848, 95% CI: 0.655–1.099, respectively) (Table 3; Fig. 2d).

Discussion

We analyzed the associations between self-reported physical function and all-cause mortality and hospitalization in China DOPPS5, a large perspective cohort study of HD patients. The 2 items “moderate activities limited level” and “climbing stairs limited level” derived from the SF-12v2 reflected patient's physical function levels. We found that greater limitations in moderate activities were positively associated with all-cause mortality and hospitalization after adjusting for covariates. Meanwhile, higher limited levels of climbing stairs were significantly associated with increased risk of all-cause mortality in the fully adjusted COX model, whereas they were not significantly related to higher risk of hospitalization after adjusted for all covariates.

Our results suggested that self-reported physical function may be a useful prognostic indicator when used alongside clinical risk factors for identifying patients who are at risk for adverse outcomes. Our results were consistent with previous studies, which found that poor physical function was associated with mortality and other events. Different methods have been used in studies to evaluate participants' physical function. Sietsema et al. [23] explored that peak exercise oxygen uptake which reflected physical exercise capacity was a highly significant predictor of survival among 175 HD patients. In large cohort studies of HD patients, the PCS score based on SF-12 or SF-36 was significantly associated with increased mortality [24, 25]. Jassal et al. [26] reported that physical dependence characterized by the ability to perform activities of daily living and instrumental activities of daily living had strong dose-response associations with all-cause mortality in HD patients from 12 countries in DOPPS. Gait speed is a common test for physical performance, and Studenski et al. [27] pooled results of 9 cohorts and found that gait speed was associated with survival in older adults. Meanwhile, there were also several studies about the 6-min walking test and muscle power and strength measurements in patients with CKD [13, 28, 29, 30].

To our knowledge, this is the first study that used 2 items in SF-12 to measure self-reported physical function and explore the relationship between physical function and clinical outcomes in a large cohort of HD patients. We hope that these findings could be helpful to giving some ideas for nephrologists and dialysis staff to improve patient care. First, self-reported physical function with just 2-item questions is a simple method to assess patients' physical function and could be routinely implemented in outpatient care. Second, measuring physical function in this way does not require the use of specific instruments and venues, which is a time-saving and economical method. Finally, nephrologists are usually the primary provider of exercise counseling for dialysis patients [12, 31]. Different studies have investigated that physical exercise significantly improves physical function and muscle strength [32, 33]. The process of assessing physical function will deepen patients' awareness about improving physical function, thus becoming a motivator for doing exercise.

Our results showed that better self-reported physical function was not associated with the first hospitalization risk. There were some possible reasons. First, this hospitalization record just included the records of staying in the inpatient ward, not the records of the emergency room and observation room. Therefore, in the analysis of hospitalization risk, emergency treatment was ignored. Second, Chinese HD patients can see their nephrologists about 3 times a week. In this process, doctors diagnose and treat patients on time, avoiding many hospitalization incidents.

This study has several limitations. First, the self-reported physical function was based on the results of questionnaires. It may be more subjective and less accurate than other objective methods. Therefore, this may be a relatively simple method, but at the same time, it also loses some precision or range of measurement. Second, we excluded some patients who did not answer the questions about physical function. Although this may cause bias in the statistical results, the nonresponse rate was low, and we have fully adjusted for covariates to minimize the impact of this problem.

In conclusion, self-reported physical function was associated with all-cause mortality and hospitalization in Chinese HD patients. Assessment of self-reported physical function by 2 items such as “moderate activities limited level” and/or “climbing stairs limited level” could be a simple and operative method in daily dialysis practice to improve patients' quality of life and outcomes.

Statement of Ethics

The study was approved by the Ethics Committee of Peking University People's Hospital (ethical approval number: 2018PHB028-01). And, all patients signed the written informed consent.

Conflict of Interest Statement

The authors declare that they have no relevant financial interest.

Funding Sources

This article was supported by the National Natural Science foundation of China; the grant recipient is Li Zuo (grant number 81870524).

Author Contributions

Conception and design of research: Qingyu Niu, Xinju Zhao, Li Zuo, and Fan Fan Hou. Data analysis: Qingyu Niu and Xinju Zhao. Interpretation of the results of experiments: Qingyu Niu, Xinju Zhao, and Li Zuo. Preparation of figures: Qingyu Niu. Manuscript drafting: Qingyu Niu. Editing and revision of the manuscript: Liangying Gan, Fan Fan Hou, Xinling Liang, Zhaohui Ni, Xiaonong Chen, Yuqing Chen, and Li Zuo. Approval of the final version of the manuscript: Li Zuo and Fan Fan Hou.