Peritoneal dialysis patient survival: a comparison between a Swedish and a Korean centre

Sung Hee Chung1,2, Olof Heimbürger2, Bengt Lindholm2 and Hi Bahl Lee1

1 Hyonam Kidney Laboratory, Soon Chun Hyang University, Seoul, Korea and 2 Divisions of Baxter Novum and Renal Medicine, Department of Clinical Science, Karolinska University Hospital Huddinge, Stockholm, Sweden

Correspondence and offprint requests to: Hi Bahl Lee, MD, PhD, Professor of Medicine/Nephrology, Hyonam Kidney Laboratory, Soon Chun Hyang University, 657 Hannam-dong, Yongsan-ku, Seoul 140-743, Korea. Email: hblee{at}hkl.ac.kr



   Abstract
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Background. Dialysis patient mortality remains high, and this high mortality may be due to many factors. In peritoneal dialysis (PD) patients, old age, co-morbid diseases, malnutrition, low residual renal function (RRF) and a high peritoneal transport rate have been shown to influence survival, but the relative importance of these factors may differ between different patient populations. Besides, centre practice patterns may differ between centres and may influence patient survival. In addition, the literature suggests that dialysis patient survival may be better in Asian than in Caucasian patients.

Methods. The influence of centre and patient characteristics on patient survival was investigated in 132 Korean and 106 Swedish incident PD patients, who underwent initial biochemical measurements and assessment of adequacy of dialysis, nutritional status, RRF and peritoneal transport characteristics.

Results. At the start of PD, Korean patients had a higher prevalence of diabetes, peritoneal Kt/Vurea, peritoneal creatinine clearance and peritoneal fluid removal, and lower body mass index, RRF and dialysate to plasma creatinine concentration ratio (D/P Cr) compared with Swedish patients. Significantly more patients from Korea were placed on temporary haemodialysis before PD (100 out of 132) when compared with Swedish patients (21 out of 106). During the follow-up, there was a significantly higher rate of transfer to other units in Korea and a significantly higher rate of kidney transplantation in Sweden. On Kaplan–Meier analysis, overall patient survival did not differ and relative risk for death was also not different between the two centres even after adjustment for age, diabetes, cardiovascular disease, RRF and D/P Cr. On Cox proportional hazards multivariate analysis, age, diabetes, RRF and D/P Cr were found to be independent predictors of mortality in the combined cohort of patients. While age, diabetes and D/P Cr were independent predictors of mortality in Korean patients, age and RRF independently predicted mortality in Swedish patients.

Conclusion. Although there were significant differences in centre and patient characteristics, we were unable to confirm a survival advantage for Korean over Swedish PD patients. The results of this study suggest that the reported difference in survival between Asian and Caucasian dialysis patients may have been due, in part, to differences in centre and patient characteristics rather than to race as such. The genetic influence on patient characteristics remains, however, to be elucidated.

Keywords: nutrition; patient survival; peritoneal dialysis; peritoneal transport rate; race; residual renal function; risk factor for mortality; technique survival



   Introduction
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Peritoneal dialysis (PD) patients have equal or better survival probability than haemodialysis (HD) patients in the first 2–3 years on dialysis, but the mortality of dialysis patients as a whole remains high. The reasons for high mortality may be multifactorial. Old age, co-morbid diseases, malnutrition, low residual renal function (RRF) and an increased peritoneal transport rate have been shown to be associated with high mortality in PD patients.

On the other hand, several reports in the literature suggest that racial difference may influence patient survival in dialysis populations [1–4]. A study from the USA [2] found that Caucasian-American dialysis patients had a higher mortality risk than Asian-American patients, even after adjusting for demographics, diabetes, co-morbidity and nutritional factors. Similarly, data from the Canadian Dialysis Registry [3] showed that the risk of death in Caucasian patients was significantly increased when compared with Asian and African-American patients after adjusting for co-morbidity. Finally, several reports from East Asian countries [5–7] consistently demonstrated a higher patient survival rate in East Asians on PD than in Caucasian patients in Western countries.

However, centre and patient characteristics may differ between study populations, and these differences may affect patient survival. It is important to evaluate systematically the difference in all predictors of death before the difference in survival is attributed to racial difference. We therefore compared the centre and patient characteristics between incident PD patients from one Korean and one Swedish centre and examined whether these differences influence patient survival in patients of different racial background.



   Patients and methods
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Patients
A total of 238 incident PD patients from Soon Chun Hyang University Hospital, Korea (132 patients) and Karolinska University Hospital Huddinge, Sweden (106 patients) were included in the present retrospective study. The Korean patients started PD between June 24, 1994 and June 19, 2000, whereas the Swedish patients started PD between January 10, 1992 and October 13, 1998. All patients underwent assessment of nutrition, adequacy of dialysis, RRF and peritoneal transport characteristics at a mean of 8 days (range 2–30 days) after beginning PD. One hundred and thirty-six patients were male (57%), 117 patients (49%) had diabetes (type I or type II) and 50 patients (21%) had cardiovascular disease (CVD). CVD was defined as a past history of or current myocardial infarction, angina, peripheral vascular disease or cerebrovascular disease. Their mean age was 54.7±13.4 years (range 23–84).

Comparisons of centre and patient characteristics at the start of PD between the two centres are shown in Tables 1 and 2, respectively.


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Table 1. Comparison of centre practice patterns between two centers

 

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Table 2. Comparison of patient characteristics at the start of PD

 
The end-points of the study were patient death, transplantation, transfer to HD or other units, or the end of the study period. The study period lasted for a mean of 20.5±14.2 months. The patients were censored at the time of renal transplantation, transfer to HD or to other units, or at the end of the study period. The study ended on July 31, 2000 for Korean and June 30, 1999 for Swedish patients.

Nutritional assessment
The nutritional status of patients was assessed by subjective global assessment (SGA; Korean patients only), biochemical measurements, body mass index, calculation of normalized protein equivalent of total nitrogen appearance (nPNA) and urea kinetic studies.

SGA. We used a seven-point Likart-type scale of four items: weight loss, anorexia, subcutaneous fat and muscle mass. Each item was given scores to produce a global assessment. Scores of 1–2 represented severe malnutrition; 3–5, moderate to mild malnutrition; and 6–7, normal nutrition.

Body mass index. The body mass index was calculated as weight (in kg)/[height in m)]2.

Estimated protein intake. Dietary protein intake was estimated from the protein equivalent of total nitrogen appearance (PNA) using the equation PNA = 15.1 + 6.95 urea nitrogen appearance (UNA) (g/24 h) + protein loss (g/24 h). UNA and protein losses were determined from the measured urea and protein excretion in dialysate and urine. PNA was normalized to desirable body weight (nPNA) obtained from the Metropolitan height and weight table [8].

Adequacy of dialysis
Weekly total Kt/Vurea and weekly total creatinine clearance (CCr) were calculated from a 24 h collection of dialysate and urine. The distribution volume of urea (V), which is generally assumed to be equal to total body water, was calculated from the Watson equation.

Peritoneal, renal and total fluid removal in ml/day were also obtained as an adequacy index.

Residual renal function
RRF was estimated by calculating the mean of renal clearances of urea and creatinine from a 24 h urine collection.

Peritoneal equilibration test (PET)
The PET was performed with a standard 4 h dwell period using a 4.25% (Korean patients) or 2.27% (Swedish patients) glucose concentration for a 2 l volume exchange.

Biochemical analyses
A fasting venous blood sample was taken before the morning exchange. Blood chemistries were analysed by standard techniques. Concentrations of creatinine in dialysate and blood samples were measured by the Jaffe method and were corrected for glucose interference. Serum albumin was determined by the bromcresol purple method in the Swedish patients and by the bromcresol green method in the Korean patients. The serum albumin was corrected by the formula suggested by Joseph et al. [9] since the bromcresol purple method is reported to yield a lower value of serum albumin concentration when compared with the bromcresol green method [9].

Statistical analysis
Student's t-test or Kruskal–Wallis test was used to compare the difference in clinical characteristics between different subgroups. {chi}2 test or Fisher's exact test was used to compare the nominal variables between different subgroups. Actuarial survival rates were determined by the Kaplan–Meier method. A log-rank test was used to compare the patient and technique survival between subgroups. The Cox proportional hazards model was used to identify the factors predicting patient mortality. The Cox model for multivariate analysis was constructed by those factors significant at univariate analysis. Data are presented as mean±SD. A difference was considered significant when the P-value was <0.05.



   Results
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Centre characteristics at the start of PD
As shown in Table 1, Korean patients were more often placed on temporary HD prior to PD than Swedish patients (76 vs 20%). There was no difference in the prevalence of automated PD (APD) and icodextrin use, median continuous ambulatory PD (CAPD) volume or CAPD exchange number between the two centres. PD utilization rate was higher in the Korean centre (36 vs 20%).

Patient characteristics at the start of PD
Patient characteristics in Korean and Swedish PD centres are shown in Table 2. At the start of PD, Korean PD patients had a higher prevalence of diabetes, higher peritoneal Kt/Vurea, peritoneal CCr and peritoneal fluid removal, but lower body mass index, dialysate to plasma creatinine concentration ratio (D/P Cr), RRF, renal Kt/Vurea, total Kt/Vurea, renal CCr, total CCr and renal fluid removal compared with Swedish PD patients. There was no difference in age, gender, prevalence of CVD, corrected serum albumin, nPNA or total fluid removal.

Final status of study patients
The final status of Korean and Swedish patients is shown in Table 3. At the end of follow-up, 24 Korean (18.2%) and 22 Swedish (20.8%) PD patients had died and 39 Korean (29.6%) and 31 (29.2%) Swedish patients had transferred to HD. Two Korean (1.5%) and 25 Swedish (23.6%) patients underwent kidney transplantation. Thirteen Korean (9.8%) and no Swedish patients were transferred to other units.


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Table 3. Final status of study patients

 
The causes of death were infection (38%), CVD (29%), other (4%) and unknown (29%) for the Korean patients, and CVD (41%), infection (23%), other (13%) and unknown (23%) for the Swedish patients. The causes of technique failure were peritonitis (72%), other infection (8%), loss of ultrafiltration (13%) and other (7%) for the Korean patients, and peritonitis (52%), other infection (10%), inadequate PD (29%), loss of ultrafiltration (3%) and other (6%) for the Swedish patients.

Comparison of National Registry data from Korea and Sweden
In order to examine if the two centres represent the national dialysis practice in the respective countries, the National Registry data [10,11] were compared, as shown in Table 4. Significantly more patients received kidney transplantation in Sweden, whereas more patients were on dialysis (both HD and PD) in Korea. The incidence and prevalence of diabetes were significantly higher among Korean patients, while the prevalence of CVD and CVD death was higher in Sweden. There was no difference in prevalence and incidence of end-stage renal disease (ESRD) between the two countries.


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Table 4. Comparison of national registry data, 2002

 
Patient and technique survival
Patient survival rates are shown in Figures 1 and 2. On Kaplan–Meier analysis, overall patient survival was not significantly different between Korean and Swedish PD patients (P = 0.68). The 1-, 2- and 3-year survival rate were 91.1, 86.4 and 72.6% for Korean, and 94.9, 83.0 and 63.5% for Swedish patients (Figure 1). Adjusted relative risk of death was also not different between the two centres (Table 5).



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Fig. 1. Probability of patient survival. Overall patient survival was not different between Korean and Swedish PD patients (P = 0.68). The number in parentheses indicates the number of patients at risk.

 


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Fig. 2. Probability of survival between diabetic and non-diabetic patients. Patient survival was significantly lower in diabetic compared with non-diabetic patients (P = 0.01). However, survival was not different between Korean diabetic and Swedish diabetic patients (P = 0.73).

 

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Table 5. Predictors of mortality on Cox multivariate analysis [RR (95% CI)]

 
Patient survival was significantly lower in the diabetic compared with the non-diabetic patients (P = 0.01) but diabetic patient survival was not different between Korean and Swedish centres (P = 0.73) (Figure 2).

Technique survival rate was not different between the two centres (P = 0.65). The 1-, 2- and 3-year technique survival rate were 86.0, 73.6 and 60.5% for the Korean, and 89.8, 65.9 and 51.9% for the Swedish patients.

Patient characteristics in surviving and the deceased patients
Patients who died during the follow-up period were older, had a higher prevalence of diabetes or CVD and lower corrected serum albumin concentration, RRF, renal CCr, total CCr and total fluid removal compared with those who survived (Table 6).


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Table 6. Comparison of patient characteristics between surviving and deceased patients

 
Predictors of mortality
Predictors of mortality are shown in Table 5. On Cox proportional hazards analysis, age, diabetes, RRF and D/P Cr were found to be independent predictors of mortality in the combined cohort of patients. Age, diabetes and D/P Cr were independent predictors of mortality in Korean patients, whereas age and RRF independently predicted mortality in Swedish patients. Race and CVD did not predict mortality.



   Discussion
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 
Several reports [1–4] suggested that East Asian patients on dialysis have survival advantages over their Caucasian counterparts. In a longitudinal cohort study, Wang et al. [12] reported that patient survival was significantly better in Asians than in Caucasians, the 2-year patient survival rate being 91% for Asians and 78% for Caucasians. However, in the present study, overall patient survival was not different between Korean and Swedish PD patients, with a 2-year patient survival rate of 86.4% for the Korean and 83.0% for the Swedish patients. Furthermore, the relative risk for mortality was not different between patients from the two centres even after adjustment for age, presence of diabetes or CVD, RRF and D/P Cr. The average life expectancy of the general population in Korea and Sweden (73 vs 77 years, respectively, for males and 80 vs 82 years, respectively, for females) is also not different.

PD patient survival is influenced by many factors. Better preservation of RRF has been reported to be associated with better clinical outcome. In the present study, we found that RRF had an impact on mortality in the Swedish patients, but not in the Korean patients. This may be explained by the fact that, in Korean patients, the low RRF at the start of PD was due mostly to temporary HD for 6–8 weeks prior to PD in most (100 out of 132) of the patients but not due to delayed start of dialysis itself.

Since the ADEMEX study [13], the role of peritoneal solute clearance in patient survival has been questioned. In anuric patients from Hong Kong [6], however, higher peritoneal clearance of small solutes was associated with better patient survival. Although renal clearance and peritoneal clearance may not be equivalent, peritoneal solute clearance may, therefore, make a contribution to patient survival. Indeed, in the present study, despite low RRF, Korean patients achieved an average total Kt/Vurea of 2.17 and equal survival probability compared with Swedish patients.

On the other hand, inadequate fluid removal has been shown to be a potential risk factor for mortality in PD patients [14]. Indeed, in the present study, patients who died during the follow-up had lower total fluid removal than those who remained on PD. There was no difference in total fluid removal or patient survival rate between Korean and Swedish patients. The findings that Korean patients had lower renal but higher peritoneal fluid removal and achieved equal total fluid removal suggest that high peritoneal fluid removal may compensate for low renal fluid removal and improve patient survival. This observation is in agreement with data from Europe [15] showing that in anuric APD patients, low peritoneal fluid removal was associated with poor patient survival.

In the present study, a high peritoneal transport rate was an independent predictor of mortality in Korean patients but not in Swedish patients. Although the reasons for this discrepancy are not clear, it is possible that already high D/P Cr in Swedish patients at the start of PD may have reduced the impact of a high peritoneal transport rate on survival, or higher RRF in the Swedish patients at the start of PD may have compensated for the higher D/P Cr. Indeed, D/P Cr lost its predictive power for mortality in Swedish patients when the multivariate analysis included RRF. Although PET tests were carried out using a 4.25% solution in Korean patients and a 2.27% solution in Swedish patients, D/P Cr should not be significantly different between the two techniques [16,17]. Heimbürger et al. [18], however, observed significant differences in D/P Cr using different solutions.

The incidence and prevalence of diabetes in the Korean dialysis population have steadily increased over the past decade and, in this study, diabetes was more common in Korean than in Swedish patients. Although there were more diabetics in the Korean centre, there was no difference in overall prevalence of CVD between Korean and Swedish patients. In this study, a quantitative measure for the severity of CVD was not available to explain the higher CVD mortality among Swedish patients. In 2002, national average CVD mortality in PD patients was 38.9% in Korea and 48% in Sweden [10,11].

Interestingly, there was also no difference in technique survival between the Korean and Swedish patients in the present study. This is in contrast to a review which found that technique survival is substantially better in Asian than in Western countries [4].

There are several obvious limitations in this study. Since only one centre each with a limited number of patients and a short duration of follow-up from the two countries was included, it may be difficult to extrapolate the results to all Korean and Swedish PD patients or to Asian and Caucasian patients. Although the two centres may not represent the practice patterns in the respective countries in all aspects, they do not deviate substantially from the respective National Registry data. Registry data from both countries [10,11] showed that the prevalence of diabetes at the start of dialysis was 40.7 and 35%, and the cardiac cause of death in PD patients was 38.9% (2003) and 48% (1998–2001) for Korean and Swedish patients, respectively.

There were several important differences in the PD practice between the two centres. While most of the Korean patients were treated with HD for 6–8 weeks before PD was started to allow time for wound healing after subcutaneous implantation of the PD catheter, most of the Swedish patients were on conservative therapy before PD. As a result, the RRF was significantly lower in Korean than in Swedish patients at the start of PD. The Korean patients, however, received a significantly higher dose of PD to achieve ‘adequate’ total solute removal and equal total fluid removal to Swedish patients.

Another major difference was that the transplantation rate was much higher in Swedish patients than in Korean patients. In general, a healthier and younger patient is more likely to receive a renal transplant, and, by censoring transplanted patients, the remaining patients should therefore have an increased proportion of less healthy patients remaining at risk. This would negatively impact the overall survival in Swedish patients. On the other hand, those who were transplanted would have stayed on PD for a shorter duration and their survival would appear better when censored at transplant. Total duration of PD was not different between Korean and Swedish patients.

There were several important differences in patient characteristics between the two centres. There were significantly more diabetics and a lower prevalence of high D/P Cr among Korean than Swedish patients.

In summary, there were significant differences in centre and patient characteristics between the two centres and yet no significant difference was observed in overall PD patient survival or relative risk of death after adjusting for independent predictors of death. Higher prevalence of diabetes, lower RRF, lower renal and total Kt/Vurea and creatinine clearance and lower renal fluid removal in Korean patients than in Swedish patients may be disadvantageous for Korean patients. On the other hand, possibly fewer or less severe CVD, relatively lower D/P creatinine, higher peritoneal Kt/Vurea and creatinine clearance, and higher peritoneal fluid removal may have been advantageous to Korean patients. The prevalence of transplantation may have affected PD patient survival in both ways. There were no significant differences in age, gender, prevalence of CVD, corrected serum albumin or nPNA between the two centres at the start of PD. The advantages may have compensated for disadvantages in Korean patients to achieve equal survival to Swedish patients. In future studies comparing patient survival between centres in different countries and/or races, all those centre and patient factors known to influence survival should be systematically studied and compared.

We conclude that the reported difference in patient survival rate between Asians and Caucasians may have been due, in part, to a difference in centre and patient characteristics rather than to race itself. The genetic influence on patient characteristics remains, however, to be elucidated.

Conflict of interest statement. None declared.



   References
 Top
 Abstract
 Introduction
 Patients and methods
 Results
 Discussion
 References
 

  1. Korbet SM, Shih D, Cline KN, Vonesh EF. Racial differences in survival in an urban peritoneal dialysis program. Am J Kidney Dis 1999; 34: 713–720[ISI][Medline]
  2. Wong JS, Port FK, Hulbert-Shearon TE et al. Survival advantage in Asian American end-stage renal disease patients. Kidney Int 1999; 55: 2515–2523[CrossRef][ISI][Medline]
  3. Pei YP, Greenwood CM, Chery AL, Wu GG. Racial differences in survival of patients on dialysis. Kidney Int 2000; 58: 1293–1299[CrossRef][ISI][Medline]
  4. Blake PG. Peritoneal dialysis in Asia: an external perspective. Perit Dial Int 2002; 22: 258–264[ISI][Medline]
  5. Shinzato T, Nakai S, Akiba T et al. Report of the annual statistical survey of the Japanese Society for Dialysis Therapy in 1996. Kidney Int 1999; 55: 700–712[CrossRef][ISI][Medline]
  6. Szeto CC, Wong TY, Chow KM et al. Impact of dialysis adequacy on the mortality and morbidity of anuric Chinese patients receiving continuous ambulatory peritoneal dialysis. J Am Soc Nephrol 2001; 12: 355–360[Abstract/Free Full Text]
  7. Lo WK, Ho YW, Li CS et al. Effect of Kt/V on survival and clinical outcome in CAPD patients in a randomized prospective study. Kidney Int 2003; 64: 649–656[CrossRef][ISI][Medline]
  8. Metropolitan Life Insurance Company. Metropolitan height and weight tables. Stat Bull 1983; 64
  9. Joseph R, Tria L, Mossey RT et al. Comparison of methods for measuring albumin in peritoneal dialysis and hemodialysis patients. Am J Kidney Dis 1996; 27: 566–572[ISI][Medline]
  10. The Korean Society of Nephrology Registry Committee. Renal replacement therapy in Korea. Kor J Nephrol 2004; 23 [Suppl 2]: S381–S404.
  11. Schön S, Ekberg H, Wikström B, Oden A, Ahlmen J. Renal replacement therapy in Sweden. Scand J Urol Nephrol 2004; 38: 332–339[CrossRef][ISI][Medline]
  12. Wang T, Tziviskou E, Chu M et al. Differences in survival on peritoneal dialysis between oriental Asians and Caucasians: one center's experience. Int Urol Nephrol 2003; 35: 267–274[CrossRef][Medline]
  13. Paniagua R, Amato D, Vonesh E et al. Effects of increased peritoneal clearances on mortality rates in peritoneal dialysis: ADEMEX, a prospective, randomized, controlled trial. J Am Soc Nephrol 2002; 13: 1307–1320[Abstract/Free Full Text]
  14. Ates K, Nergizoglu G, Keven K et al. Effect of fluid and sodium removal on mortality in peritoneal dialysis patients. Kidney Int 2001; 60: 767–776[CrossRef][ISI][Medline]
  15. Brown EA, Davies SJ, Rutherford P et al. Survival of functionally anuric patients on automated peritoneal dialysis: the European APD Outcome Study. J Am Soc Nephrol 2003; 14: 2948–2957[Abstract/Free Full Text]
  16. Pride ET, Gustafson J, Graham A et al. Comparison of a 2.5% and a 4.25% dextrose peritoneal equilibration test. Perit Dial Int 2002; 22: 365–370[ISI][Medline]
  17. Smit W, van Dijk P, Langedijk MJ et al. Peritoneal function and assessment of reference values using a 3.86% glucose solution. Perit Dial Int 2003; 23: 440–449[ISI][Medline]
  18. Heimbürger O, Waniewski J, Werynski A, Park MS, Lindholm B. Dialysate to plasma solute concentration (D/P) versus peritoneal transport parameters in CAPD. Nephrol Dial Transplant 1994; 9: 47–59[Abstract]
Received for publication: 27. 7.04
Accepted in revised form: 11. 2.05