Are peritoneal dialysis patients with and without residual renal function equivalent for survival study? Insight from a retrospective review of the cause of death

Cheuk-Chun Szeto, Teresa Yuk-Hwa Wong, Kai-Ming Chow, Chi-Bon Leung and Philip Kam-Tao Li

Department of Medicine, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China



   Abstract
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Background. It remains unknown whether results of survival studies in anuric patients can be extrapolated to those who still have significant urine output. It is possible that after a prolonged period on dialysis, anuric patients are qualitatively different from patients with residual renal function.

Methods. We performed a retrospective review to study the cause of death of 296 peritoneal dialysis patients of our centre over a 7 year period, and compared the mortality and distribution of cause of death between patients with and without residual renal function.

Results. One hundred and forty-two cases (48.0%) died of vascular diseases, 82 cases (27.7%) died of infections and 72 cases (24.3%) died of other causes. Anuric patients had a higher overall mortality rate than non-anuric patients (14.9 vs 9.9%, P=0.0005), and the difference was almost completely attributed to the difference in mortality from vascular diseases (8.0 vs 4.1%, P<0.0001). Vascular disease was a more common cause of death in anuric patients than those with residual renal function (55.3 vs 40.8%, P=0.011). The difference was largely explained by the higher prevalence of sudden cardiac death in anuric patients (39 in 149 vs 19 in 147 cases). Patients without pre-existing cardiovascular disease more commonly died of vascular disease after they became anuric (47.4 vs 34.0%, P=0.017). The difference could not be explained by the longer duration of dialysis in anuric patients because there was no significant change in the distribution of cause of death with time on dialysis (chi-square test, P=0.341).

Conclusions. Our observation suggests that peritoneal dialysis patients with and without residual renal function are qualitatively different. Studies on peritoneal dialysis adequacy and survival in anuric patients should only be extrapolated to the general dialysis population with caution.

Keywords: dialysis adequacy; renal failure; survival



   Introduction
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Peritoneal dialysis adequacy has a profound impact on the mortality and morbidity of patients treated with continuous ambulatory peritoneal dialysis (CAPD) [15]. Although Chinese dialysis patients have a better overall survival [6,7], dialysis adequacy remains an independent predictor of mortality and morbidity in this ethnic group [8].

Most of the studies on peritoneal dialysis adequacy focused on the total clearance of small molecules in patients with significant residual renal function [15]. Bhaskaran et al. [9] and our group [10] reported that peritoneal clearance had an independent effect on survival in anuric patients. However, it remains unknown whether the result in anuric patients can be extrapolated to those who still have significant urine output [11]. Although the mortality rate remained relatively constant with time on dialysis [5,8,10], most of these studies only had a median follow-up of 2 years. It could be argued that after a prolonged period on dialysis, anuric patients are qualitatively different from patients with residual renal function. In the light of this possibility, we performed a retrospective review to study the cause of death in detail in all peritoneal dialysis patients of our centre over a 7 year period, and compared the distribution of cause of death between patients with and without residual renal function.



   Subjects and methods
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
Case selection
All patients who received peritoneal dialysis in our unit and died between January 1995 and December 2001 were reviewed. Data completeness was assured by our computerized Renal Registry, which was established by the end of 1994. Deaths within 12 months after conversion from peritoneal dialysis to haemodialysis or transplantation were also reviewed because recent studies showed that there was an excess early mortality of CAPD patients after conversion [12,13]. Most of the patients in this review were participants in two of our previous prospective studies on peritoneal dialysis adequacy [8,10].

Clinical records of the patients were reviewed. Baseline data including age, sex, underlying renal disease, body height, weight, requirement of helper for dialysis exchanges, hepatitis B status, presence of diabetes mellitus, and pre-existing cardiovascular disease at the initiation of dialysis were obtained. As described in our previous studies [8,10], pre-existing cardiovascular disease was defined as angina, class III to IV congestive heart failure, a history of previous myocardial infarction, cerebrovascular accident, or amputation for vascular disease at the initiation of dialysis.

The cause of death of each patient was determined by reviewing the medical records, autopsy reports and coroner's files. For convenience of analysis, the cause of death was classified into three categories: vascular, infection and miscellaneous. Vascular deaths included cases of sudden cardiac death, coronary heart disease, cerebrovascular disease and peripheral vascular disease. Sudden cardiac death was defined as death as a result of cardiac disease (as evident by typical symptoms, abnormal electrocardiogram and/or cardiac enzyme levels, or autopsy findings) that occurred with less than 24 h between symptom onset and death [14]. Infection included deaths due to peritonitis and non-peritonitis infections.

Effect of residual renal function
We examined the effect of residual renal function and duration of dialysis on the cause of death. The presence of residual renal function at the time of death was inferred from the last dialysis adequacy assessment, which included a 24 h urinary collection and was performed at least yearly as described in our previous study [8]. Anuria was defined as no appreciable urine output [10].

We further quantified the relative risks (RR) of death from various causes between anuric and non-anuric patients. Since patients might change from non-anuric to anuric with time on dialysis, the basic population of peritoneal dialysis patients in our unit for each calendar year from 1995 to 2001 was retrieved from our computerized Renal Registry (see above). For each calendar year, all patients were categorized into anuric and non-anuric according to the result of their first dialysis adequacy assessment of the year. The total populations of anuric and non-anuric peritoneal dialysis patients throughout the study period were then calculated from the arithmetic sum of each calendar year.

Statistical analysis
Statistical analysis was performed by SYSTAT 7.0 for Windows software (SPSS Inc., Chicago, IL, USA). All data were expressed as means±SD unless otherwise specified. Data were compared by chi-square test, Fisher's exact test or Student's t-test as appropriate. The RR of death, and their 95% confidence interval (CI), from vascular diseases, infection and miscellaneous causes for anuric patients, with reference to non-anuric patients, were determined. A P-value of <0.05 was considered significant. All probabilities were two-tailed.



   Results
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
During the 7 years of the period reviewed, there were 2510 patient-years treated with peritoneal dialysis in our unit. We identified 309 patients who received peritoneal dialysis and died. Thirteen patients were excluded because they died after at least 12 months after conversion to haemodialysis or transplantation. We reviewed the remaining 296 patients. The crude mortality rate was 11.8% per patient-year. The median survival after dialysis was 35.7 months (range 1 day to 161 months). Their baseline demographic data are summarized in Table 1Go. The cause of death in the whole study population is summarized in Table 2Go. As expected, there was a higher proportion of vascular deaths in patients with pre-existing cardiovascular disease than those without (61.5 vs 40.6%, P=0.003) (Figure 1Go). There was no significant difference in the distribution of cause of death between diabetic and non-diabetic patients (Figure 1Go).


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Table 1.  Baseline characteristics of the patients being reviewed

 

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Table 2.  Summary of causes of death

 


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Fig. 1.  Cause of death in patients (A) with and without pre-existing cardiovascular disease; and (B) with and without diabetes mellitus. CVD, pre-existing cardiovascular disease; DM, diabetes mellitus.

 
Effect of residual renal function
The distribution of cause of death in patients with and without residual renal function are summarized in Table 3Go. Vascular disease was a more common cause of death in anuric patients than those with residual renal function (55.3 vs 40.8%, P=0.011). The difference was largely explained by the higher prevalence of sudden cardiac death in anuric patients (39 in 149 cases vs 19 in 147 cases, see Table 3Go). As expected, anuric patients were dialysed longer (59.7±30.3 vs 23.3±22.4 months, P<0.001) (Table 4Go). The difference in distribution of cause of death was not explained by the difference in dialysis adequacy or nutritional status (Table 4Go).


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Table 3.  Cause of death and residual renal function

 

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Table 4.  Dialysis adequacy and nutritional status in patients with and without residual renal function

 
We further quantified the RR of death from various causes between anuric and non-anuric patients, as summarized in Table 5Go. During the study period, there were 1030 patient-years treated in our unit being anuric, and 1480 patient-years treated in our unit non-anuric. Anuric patients had a higher overall mortality rate than non-anuric patients (14.9 vs 9.9%, P=0.0005), and the difference was almost completely attributed to the difference in mortality from vascular diseases (8.0 vs 4.1%, P<0.0001). The mortality rate from infections and miscellaneous causes did not differ significantly between anuric and non-anuric patients.


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Table 5.  Relative mortality risk for anuric in comparison to non-anuric patients

 
When patients with and without pre-existing cardiovascular disease were analysed separately, patients without pre-existing cardiovascular disease more commonly died of vascular disease after they became anuric (47.4 vs 34.0%, P=0.017) (Figure 2Go). For patients with pre-existing cardiovascular disease, there was no significant difference in the distribution of cause of death between those with and without residual renal function (Figure 2Go). When diabetic and non-diabetic patients were analysed separately, there was no significant difference in the distribution of cause of death in either group.



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Fig. 2.  Comparison of the cause of death in patients with and without residual renal function: (A) patients without pre-existing cardiovascular disease; and (B) patients with pre-existing cardiovascular disease.

 

Effect of duration on dialysis
Since the time on dialysis is a potential confounding factor of residual renal function, we next evaluate the effect of duration of dialysis on the distribution of cause of death. For convenience of analysis, the duration of dialysis were semi-quantitatively classified into four categories: less than 6 months, 6–24 months, 24–60 months and over 60 months. The cause of death in these four groups of patients are summarized in Table 6Go. There was no significant change in the distribution of cause of death with time on dialysis (overall chi-square test, P=0.341).


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Table 6.  Cause of death and duration of dialysis

 
When diabetic and non-diabetic patients were analysed separately, there was no significant change in the distribution of cause of death with time on dialysis in both diabetic and non-diabetic patients. Similarly, when patients with and without pre-existing cardiovascular disease were analysed separately, there was no significant change in the distribution of cause of death with time on dialysis in either group of patients.



   Discussion
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 
In this retrospective study, we found that anuric patients had a higher mortality than those with residual renal function, and vascular disease was the major cause of excess mortality in anuric patients. The difference in the distribution of cause of death was particularly prominent in patients without pre-existing cardiovascular diseases and could not be explained by the longer duration of dialysis in anuric patients. Our observation suggests that peritoneal dialysis patients with and without residual renal function are qualitatively different. Studies on peritoneal dialysis adequacy and survival in anuric patients should only be extrapolated to the general dialysis population with caution.

From our previous studies on Chinese peritoneal dialysis patients, we found that the overall mortality remained constant over time and was similar between patients with and without residual renal function [8,10]. A similar observation is made from the data of the CANUSA study [5]. At a glance, the constant mortality over time would suggest that new cases and prevalent cases, and possibly patients with and without residual renal function, are equivalent in survival studies of peritoneal dialysis. However, the result of our present study shows that anuric patients had a nearly 50% higher mortality rate than patients with residual renal function. Our observation certainly agrees with the general clinical impression of most nephrologists. In retrospect, the mortality data from prospective cohort studies might be biased because most of the reported studies had a median follow-up of 2 years [5,8,10]. A genuinely constant overall mortality of peritoneal dialysis patients over an extended period of time could not be inferred from these studies. Furthermore, it was common for observational studies on dialysis adequacy to exclude high-risk patients who were unlikely to survive for 6 months [5,8,10]. Most of these patients were predictably anuric. As a result, the mortality rate of anuric patients in published cohort studies might be underestimated.

In general, the cause of death in our dialysis population was similar to other reported series [5,15,16]. Nevertheless, we found that sudden cardiac death was a common cause of death in anuric patients. Our finding is easily explained: there is circumstantial evidence to show that the prevalence of ventricular dysfunction, vascular calcification and silent coronary ischaemia increases with time on dialysis and loss of residual renal function [17,18]. The effect is particularly prominent in patients without pre-existing cardiovascular disease because it takes time for accelerated atherosclerosis to develop in this group of patients, while patients with pre-existing cardiovascular disease probably die for that reason before they develop anuria.

What is the cause of the difference? Although better than haemodialysis, peritoneal dialysis is not very effective for removing toxins of middle or large molecular weight [19], which tend to accumulate with time and cause complications [20]. It is generally believed that the body composition of peritoneal dialysis patients changes with time [2124]. Previous studies found that creatinine metabolism [21], peritoneal solute transport [22], nutritional status [23] and quality of life [24] of dialysis patients gradually change with the time and loss of residual renal function. The result of our present study provides further evidence to support that the biological characteristics of peritoneal dialysis patients do change after the loss of residual renal function.

In the present study, we did not find a difference in the distribution of cause of death between diabetic and non-diabetic patients. However, it is important to note that previous studies from our group [8,10] and others [5] all showed that diabetic patients had a higher absolute mortality than non-diabetic patients. Although diabetic patients are expectantly prone to cardiovascular deaths, their mortality rate from infection is also higher than that of non-diabetic patients because of the immunological disturbance in diabetic patients. Furthermore, our local practice tends to exclude patients with multiple medical diseases from the dialysis programme [25]. For example, less than half of the diabetic patients in the present study had pre-existing vascular disease prior to dialysis. As a result, the mortality rate from vascular disease in our diabetic dialysis patients would be underestimated.



   Acknowledgments
 
This study was supported in part by the CUHK research accounts 6900972 and 6900570.

Conflict of interest statement. None declared.



   Notes
 
Correspondence and offprint requests to: Dr C. C. Szeto, Department of Medicine and Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. Email: ccszeto{at}cuhk.edu.hk Back



   References
 Top
 Abstract
 Introduction
 Subjects and methods
 Results
 Discussion
 References
 

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Received for publication: 21. 8.02
Accepted in revised form: 22.11.02





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