Nephrology 16 (2011) 715–719
Original Article
Life expectancy of Chinese patients with chronic kidney disease without dialysis nep_1504
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CHEUK-CHUN SZETO, BONNIE CHING-HA KWAN, KAI-MING CHOW, WING-FAI PANG, VICKIE WAI-KI KWONG, 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
KEY WORDS: renal failure, survival, uraemia.
ABSTRACT: Aim:
Correspondence: Dr Cheuk-Chun Szeto, Department of Medicine & Therapeutics, Prince of Wales Hospital, Chinese University of Hong Kong, Shatin, N.T., Hong Kong, China. Email:
[email protected] Accepted for publication 29 June 2011. Accepted manuscript online 20 July 2011. doi:10.1111/j.1440-1797.2011.01504.x Conflict of interest statement: The results presented in this paper have not been published previously in whole or part, except in abstract format. All authors declare no conflict of interest.
SUMMARY AT A GLANCE This paper describes the survival of people with advanced chronic kidney disease managed without dialysis. It uses an anticipated start date for dialysis based on an eGFR of 7 mL/min per 1.73 m2 and separates people based on whether they were offered dialysis and subsequently declined (declining group) or never offered due to comorbidities (conservative group). The timing and cause of death from first assessment is described, providing better information for people treated without dialysis.
Long term dialysis is life-saving for patients with end stage renal disease (ESRD). However, in ESRD patients with multiple comorbid conditions, dialysis may actually be futile, and conservative management is advisable. We studied the life expectancy of Chinese ESRD patients treated conservatively. Methods: We reviewed 63 consecutive ESRD patients who were treated conservatively in our centre. Duration of survival was calculated from the date of initial assessment for dialysis, as well as the expected date of needing dialysis based on previous trend of renal function decline. Results: At the end of the observation period, 55 patients died. Twelve patients died before the expected date of needing dialysis because of unrelated reasons, while 36 deaths were directly attributed to uraemia. The median overall survival after initial assessment for dialysis was 41.3 months (95% confidence interval (CI), 33.2 to 49.4 months). The median overall survival was 6.58 months (inter-quartile range, 0.92 to 9.33 months) from the theoretical date of needing dialysis. The survival from the theoretical date of needing dialysis did not correlate with patient age, sex, diabetic status, or baseline renal function. Conclusions: In Chinese ESRD patients treated conservatively, the median survival is around 6 months after the theoretical date of needing dialysis. Our result provides an important piece of information for the decision of dialysis and patient counselling.
Long term dialysis is a life-saving treatment for patients with end stage renal disease (ESRD). In a minority of ESRD patients, however, the clinical conditions and level of selfsufficiency make it doubtful whether dialysis may actually be futile, worsening their quality of life, or simply prolonging the dying process.1 In fact, there is a substantial risk of death or functional decline within a relatively short time for elderly © 2011 The Authors Nephrology © 2011 Asian Pacific Society of Nephrology
patients with advanced chronic kidney diseases,2 favouring a conservative approach to the management of these patients. Given the evolving epidemiological scenario of ESRD, there is a growing need to rely on solid data to decide whether to recommend conservative therapy rather than long term dialysis.3 Unfortunately, there is little published evidence on the clinical outcome and life expectancy of
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patients with advanced chronic kidney disease (CKD) treated conservatively.1,4,5 In a recent study, Wong et al.6 reported a median overall survival of 1.95 years, and a one-year overall survival of 65% in 73 patients with advanced CKD treated conservatively. Although dialysis is generally associated with longer survival in patients aged over 75 years, those with multiple comorbidities, ischaemic heart disease in particular, do not survive longer than those treated conservatively.7,8 In a review of 63 advanced CKD patients treated conservatively, Smith et al.9 reported that in high-risk, highly dependent patients with renal failure, the decision to dialyze or not has little impact on survival, and dialysis in such patients risks unnecessary suffering before the unavoidable death. However, most of the published series focused on western population, which has a different body composition and dietary pattern as compared to Chinese patients. In this study, we examined the life expectancy of Chinese ESRD patients treated conservatively.
METHODS Case selection We identified 298 consecutive patients with progressive renal insufficiency referred to the out-patient nephrology clinic of Prince of Wales Hospital, Hong Kong, from 1 July 1997 to 30 June 2001 for assessment of renal replacement therapy. This cohort has been described in our previous report on the use of reciprocal serum creatinine plot for the monitoring of renal function deterioration.10 In Hong Kong, the standard policy was dialysis would be offered, with minimal cost to the patient, to all patients who were judged by their responsible nephrologist to be physically fit for dialysis and considered to be able to benefit from dialysis.11,12 Of these 298 patients, 235 subsequently received long-term dialysis or preemptive kidney transplantation. We reviewed the remaining 63 patients who were treated conservatively. In 38 of them, renal replacement therapy was considered not appropriate, mostly because of multiple coexisting medical illnesses; they were designated as the Conservative Group. The other 25 patients were considered suitable candidates for dialysis but the offer was declined by the patient despite repeated explanation; they were designated as the Declining Group.
Clinical management After referral for the dialysis assessment, all patients were followed at least 8 weekly by a nephrologist and a renal nursing specialist. Clinical management was decided by individual nephrologists not affected by the study. Renal function test, including serum creatinine, urea and albumin levels, was assessed at every clinic visit. Estimated glomerular filtration rate (GFR) was calculated by a standard equation.13 As described in our previous report,10 we predict the date of starting dialysis by the reciprocal serum creatinine plot, based on all available results of serum creatinine. In general, patients were started on dialysis when the estimated GFR was below 7 mL/min per 1.73 m2.
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Table 1 Demographic and baseline clinical data Conservative group No. patients Sex (M : F) Age (years) Body weight (kg) Body height (cm) Renal diagnosis, no. patient (%) Glomerulonephritis Diabetic nephropathy Hypertensive nephrosclerosis Obstructive uropathy Others/unknown Major comorbidity, no. patients (%) Diabetes Cardiovascular disease Cerebrovascular disease Peripheral vascular disease Charlson’s comorbidity index Baseline renal function Serum creatinine (mmol/L) Estimated GFR (mL/min per 1.73 m2)
38 17:21 71.7 1 4.4 59.3 1 9.7 158.5 1 7.3 1 32 1 1 3
(2.6%) (84.2%) (2.6%) (2.6%) (7.9%)
Declining group 25 15:10 58.8 1 13.6 58.3 1 11.2 161.1 1 7.9 3 9 2 4 7
(12.0%) (36.0%) (8.0%) (16.0%) (28.0%)
32 (84.2%) 24 (63.2%) 6 (15.8%) 4 (10.5%) 7.47 1 0.92
9 (36.0%) 5 (20.0%) 0 1 (4.0%) 4.48 1 1.16
300.5 1 111.9 18.3 1 6.0
356.9 1 165.2 17.6 1 7.3
GFR, glomerular filtration rate.
Data collection The clinical records of all patients were reviewed. All clinical and biochemical data were collected prospectively in the pre-dialysis program of our centre after informed consent, and the present study represents a retrospective analysis of these data. Survival status was censored on 31 December 2008. Duration of survival was computed by two methods as the time from the initial referral for dialysis: (i) overall survival; and (ii) uraemia-free survival, for which all deaths not related to complications of chronic renal failure were considered as censoring events. In addition, the overall survival as from the time when the estimated GFR fell below 7 mL/min per 1.73 m2 (i.e. the theoretical date of starting dialysis) was also analyzed.
Statistical analysis Statistical analysis was performed by SPSS for Windows software version 15.0 (SPSS Inc., Chicago, IL, USA). All data were expressed as mean 1 standard deviation (SD) unless otherwise specified. Data were compared by c2 test, Fisher’s exact test, or Student’s t-test as appropriate. Kaplan–Meier analysis and the log rank test were used to compare the actuarial and technique survival between patient groups. A P-value of less than 0.05 was considered significant. All probabilities were two-tailed.
RESULTS Baseline demographic and clinic data of the 63 patients are summarized in Table 1. The conservative group were older, had a higher prevalence of pre-existing diabetes, cardiovascular disease, and Charlson’s comorbidity index than the © 2011 The Authors Nephrology © 2011 Asian Pacific Society of Nephrology
CKD survival without dialysis
declining group (details not shown). The body size and kidney function upon referral, however, were similar.
(A) 1. 0
Survival after initial assessment
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Overall survival
At the end of the study period, 55 patients died, six lost to follow up, and two survived without the need of dialysis. The causes of death were uraemia (36 cases), cardiovascular disease (nine cases), stroke (one case), infection (six cases), and other specific causes (three cases). The median overall survival after initial assessment for dialysis was 41.3 months (95% confidence interval (CI), 33.2 to 49.4 months), while the median uraemia-free survival was 53.0 months (95% CI, 41.3 to 64.7 months). There was no significant difference in the overall survival or uraemia-free survival between the groups (Fig. 1). With Cox regression analysis, baseline GFR was the only independent predictor of overall survival (adjusted hazard ratio 0.858, 95% CI 0.811 to 0.907, P < 0.0001) as well as uraemia-free survival (adjusted hazard ratio 0.822, 95% CI 0.766 to 0.883, P < 0.0001). Neither overall survival nor uraemia-free survival was related to patient age, sex, or diabetic status.
Log rank test, P = 0.7
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Conservative group
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12
24
36
48
60
72
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Follow up (months)
(B) 1.0
Log rank test, P = 0.5
Survival from the date of needing dialysis
DISCUSSION In this observational study, we examined the survival of Chinese ESRD patients treated conservatively. Our result is comparable to other published literature on the survival of ESRD patients without dialysis.1,4,5 It is, however, important to note that the reported survival is highly heterogeneous in published literature because the time of recruitment (which is often that of the initial nephrologist assessment) is highly variable, often depends on local clinical practice. In order to have a ‘standardized’ time zero for the assessment of life expectancy, we estimated the date of needing dialysis and computed the survival from that time point. Nonetheless, previous study actually showed that the date of needing dialysis may not be reliably predicted by the trend of previous renal function decline.10 © 2011 The Authors Nephrology © 2011 Asian Pacific Society of Nephrology
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Uraemia-free survival
The clinical outcome in relation to the theoretical date of needing dialysis is summarized in Figure 2. Briefly, 12 patients died before the date of needing dialysis because of unrelated reasons, while seven patients died of disease unrelated to uraemia after the date of needing dialysis. For the 36 patients who died of clinical uraemia, six died before the theoretical date of needing dialysis, while 30 died after that date. The median survival was 6.58 months (inter-quartile range, 0.92 to 9.33 months) after the theoretical date of needing dialysis. The survival from the expected date of needing dialysis did not correlate with patient age, sex, diabetic status, or baseline renal function (details not shown).
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0.2 Conservative group
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Follow up (months) Fig. 1 Kaplan–Meier plot of (A) overall survival; and (B) uraemia-free survival.
In the present study, the overall survival from the time of needing dialysis was slightly over 6 months, which seems substantially shorter than several previous studies,6,14–17 which reported a median survival of 12 to 24 months. However, it is important to realize that most European and American nephrologists would start a patient on dialysis when the estimated GFR falls between 10 and 15 mL/min per 1.73 m2. In contrast, we generally start our patients on dialysis at the estimated GFR of 7 mL/min per 1.73 m2,
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63 patients Loss to follow up (four cases) Died of uraemia (six cases) Died of other causes (12 cases)
Theoretical date of needing dialysis (41 patients) Loss to follow up (two cases) Died of uraemia (30 cases) Died of other causes (seven cases)
Survive without dialysis (two patients)
agement during the initial assessment but subsequently changed mind and received dialysis eventually, resulting in some selection bias of our cases. Second, the sample size of the present study was small, and we could not perform elaborated survival analysis to explore other clinical predictors of survival, or to have sufficient statistical power for the comparison of survival between patients who declined dialysis and those who were advised to have conservative management because of extensive comorbid conditions. In addition, it is sometimes difficult to determine the exact cause of death by a retrospective study, and almost always impossible to declare that the death of a particular patient was entirely unrelated to renal failure. Because of the retrospective nature of our study, we did not assess the quality of life of our patients. It is our general clinical impression that most of the patients treated conservatively had reasonable quality of life before they finally succumbed. In an observational study of 11 ESRD patients, De Biase et al.23 noted that a conservative strategy is feasible for frail uraemic patients, achieving acceptable clinical results and a quality of life comparable with patients on haemodialysis. In summary, we found that the median survival was over 3 years after initial assessment for dialysis, or around 6 months after the expected date of needing dialysis. Our result provides an important piece of information for the decision of dialysis and patient counselling.
Fig. 2 Summary of the clinical outcome.
ACKNOWLEDGEMENT which possibly explains the difference in observed survival after the time of ‘needing’ dialysis. It could be argued that our patients were put on dialysis late. However, recent evidence indicates that an early initiation of dialysis does not result in a better outcome.18,19 We found that baseline renal function was an independent predictor of survival from the initial assessment, but not from the expected time of needing dialysis. This observation suggests that the survival benefit for patients who were referred early to a nephrologist but ended up on conservative management was probably the result of lead-time bias. In comparison, the survival benefit of dialysis patients who were referred early to nephrologists is well established.20,21 Contrary to common belief and our previous report,22 death unrelated to uraemia (especially cardiovascular disease) before dialysis was actually needed was not common in our cohort. This somewhat surprising observation is probably because patients with multiple cardiovascular risk factors and a high probability of death before dialysis is needed would not be referred for nephrologist assessment. Unfortunately, we do not have any data on the number of ESRD patients in our centre who were treated conservatively without seeing a nephrologist. There are several inadequacies of the present study. First, we excluded the patients who opted for conservative man-
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This study was supported in part by the CUHK research account 6901031 and the Richard Yu Chinese University of Hong Kong (CUHK) Peritoneal Dialysis (PD) Research Fund.
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