SURVIVAL OF ELDERLY PATIENTS ON PERITONEAL DIALYSIS: RETROSPECTIVE STUDY OF 292 PATIENTS, FROM 1982 TO

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1 Peritoneal Dialysis International, Vol. 22, pp Printed in Canada. All rights reserved /02 $ Copyright 2002 International Society for Peritoneal Dialysis SURVIVAL OF ELDERLY PATIENTS ON PERITONEAL DIALYSIS: RETROSPECTIVE STUDY OF 292 PATIENTS, FROM 1982 TO 1999 François Vrtovsnik, 1,3 Raphaël Porcher, 2,4 Catherine Michel, 1 Gilles Hufnagel, 1 Guillaume Queffeulou, 1 France Mentré, 2 and Françoise Mignon 1 Departments of Nephrology 1 and Biostatistics, 2 Hôpital Xavier Bichat, Assistance Publique des Hôpitaux de Paris; INSERM U 426, 3 Faculté de Médecine Xavier Bichat, Université Denis Diderot; and INSERM U444, 4 Faculté Saint Antoine, Université Paris, Paris, France Background: Dialysis is becoming increasingly frequent in patients over 75 years of age. Age is a superimposed comorbid factor commonly associated with poor prognosis in these patients. Objective: To analyze the survival of 292 patients aged over 75 years on initiation of peritoneal dialysis (PD) from September 1982 to September Design: Retrospective study. Setting: Nephrology department in a University Hospital. Results: Mean age was 81.5 years (range years); 178 patients were over 80 years and 60 patients were over 85 years. Sex ratio was 136F/156M. Ninety-day mortality rate was 12%. Excluding the first 3 months, median patient survival was 21.6 months; 226 patients died on PD and 24 were shifted to hemodialysis. Survival was inversely correlated with the Charlson combined comorbidity index (CCI), but independent of predialysis hemoglobin and serum albumin levels. Over three selected periods, , , and , an increase was found in mean age (79.7 ± 3.3, 82.6 ± 3.9, and 81.8 ± 4.4 years; p < 0.001), CCI (7.6 ± 1.59, 8.0 ± 1.52, and 8.5 ± 1.63; p = 0.01), and predialysis creatinine clearance (6.2 ± 2.3, 6.4 ± 2.4, and 9.8 ± 3.8 ml/minute; p < 0.001). Median survival was similar in the various selected periods (21.0, 21.5, and 25.4 months). The incidence of peritonitis decreased from 0.63 to 0.21 episodes per patient year. Conclusion: From 1982 to 1999, mean age and comorbidity increased on initiation of dialysis in elderly patients, with no increase in mortality. Survival in elderly patients on PD was related to the age comorbidity index. KEY WORDS: Elderly; survival; comorbidity index. Several studies have shown that, when appropriate corrections are applied for differences in case mix, patient survival on peritoneal dialysis (PD) is Correspondence to: F. Vrtovsnik, Department of Nephrology, Hôpital Xavier Bichat, 46 rue Henri-Huchard, F-75875, Paris Cedex, France. fvrtovsnik@wanadoo.fr Received 4 April 2001; accepted 12 July similar to that on hemodialysis (1 6). Little is known about the results of PD in elderly patients, despite the fact that the incidence of renal failure is growing faster in the elderly population than in any other group. Recent data from the United States Renal Data System (USRDS) show that 51% of incident dialysis patients were above 65 years of age and 23% were above 75 years (7). In Europe, these percentages were 49% and 19% (ERA-EDTA Registry, unpublished data). Overall patient survival on PD has improved during the past two decades (8,9). It is not clear whether this improvement is also present in the elderly. Because it allowed home dialysis even in elderly patients incapacitated by high comorbidity, and because it obviated the need for creating costly new hemodialysis units, in 1982 our department adopted the policy of proposing PD as the first-line renal replacement therapy (RRT) for all patients aged 75 years or older who needed dialysis treatment for end-stage renal failure. Hemodialysis was used only when the patient refused PD or when obvious contraindications were present. From 1982 to 1999, 752 patients had been enrolled in the PD program; 292 (39%) were 75 years or older at initiation of dialysis. The objective of the present retrospective study was to analyze patient survival in this cohort and possible factors that may have influenced outcome. PATIENTS AND METHODS PATIENTS Between September 1982 and September 1999, 292 patients aged over 75 years had been enrolled in the PD program. Apart from formal refusal by the patient or family, the only criteria for exclusion were dementia or a very short life expectancy (e.g., disseminated metastases). Dialysis dose prescription relied on medical evaluation of both clinical and biochemical data. Reasons for shifting from PD to hemodialy- 73

2 VRTOVSNIK et al. JANUARY 2002 VOL. 22, NO. 1 PDI sis were persistent or relapsing peritonitis, adequacy or ultrafiltration problems, and extraperitoneal leakage of dialysis fluid. Patients were routinely evaluated every 4 6 weeks. Peritonitis was diagnosed in the presence of at least two of the following criteria: cloudy effluent with more than 100 white blood cells/ mm 3, positive dialysate culture, and clinical symptoms of peritonitis. RECORDED DATA The following data were retrieved from individual clinical records: age, sex, underlying renal disease, mode of entry, PD regimen, connection system, duration on dialysis, comorbidity, peritonitis episodes, and cause of death. The PD regimen was classified as continuous ambulatory PD (CAPD) with or without assistance of a nurse or a family member for connection, or automated PD, which could be continuous cyclic PD, nocturnal intermittent PD (NIPD), or intermittent PD. A comorbidity score was determined according to Charlson s Comorbidity Index (CCI) (see Table 1) (10). Values of plasma creatinine, serum albumin, and hemoglobin were collected on initiation of dialysis and on follow-up when available. Primary renal diagnosis relied essentially on history and clinical grounds, as histopathological analysis of kidney biopsy was rarely performed considering the late referral of most patients. Three separate periods were defined in order to determine whether patient survival had improved with progress in PD technique since Period 1 included 88 patients who started dialysis between 1982 and A second 6-year period was subsequently defined as 1989 to September 1995, when erythropoietin and improved connection systems became available (143 patients). The third period was from 1995 until the end of inclusion in May 1999 (61 patients). At that time, all patients were treated with new connection systems. Data were collected until the end of the observation period in September 1999, giving a minimum follow-up of 4 months. Early mortality was defined as death within 90 days of inclusion. Data were analyzed only in the 253 patients who survived longer than 90 days. A survival analysis was performed in which only death was considered a final event and patients were censored for transfer to hemodialysis or to another institution, lost to follow-up, or at the end of the observation period; any deaths occurring after 2 weeks of transfer were censored. STATISTICAL METHODS Data are presented as mean ± standard deviation unless specified otherwise. 74 TABLE 1 Charlson s Weighted Index of Comorbidity Assigned weights for conditions Condition 1 Myocardial infarction Congestive heart failure Peripheral vascular disease Cerebrovascular disease Dementia Chronic pulmonary disease Connective tissue disease Ulcer disease Mild liver disease Diabetes 2 Hemiplegia Moderate or severe renal disease Diabetes with end-organ damage Any tumor Leukemia Lymphoma 3 Moderate or severe liver disease 6 Metastatic solid tumor AIDS The combined age comorbidity index is calculated as the sum of the score given for each condition and the score corresponding to the age. Each decade of age over 50 years adds 1 point in risk. Survival curves were estimated using the Kaplan Meier method and were compared by log-rank tests for discrete variables (11). Discrete variables in the univariate analysis were sex, age (split into four categories: years, years, years, > 90 years), period, PD technique, need for assistance to perform dialysis, diagnosis of diabetes, and CCI (split into three categories: < 7, 7 9, 9). A Cox proportional hazard model was used to model the predictive value of age as a continuous variable, as well as creatinine clearance, predialysis hemoglobin level, serum albumin, and CCI (12). A multivariate Cox proportional hazard model was used in which all previously cited variables were entered and backward elimination was used to remove nonsignificant variables, with a type I error of The validity of the proportional hazards assumption was tested using Grambsch and Therneau goodness of fit test (13). Interactions between variables in the final model were studied. Early death rates (death within 90 days following inclusion) were compared between periods using a chi-square test. Peritonitis rates were calculated as the number of episodes per patient year. Comparison of measures of hemoglobin and serum albumin at inclusion and at 3 months and 6 months were performed with a repeated measure analysis of variance. The differences between the three periods were tested using a chi-square test. Other differences

3 PDI JANUARY 2002 VOL. 22, NO. 1 SURVIVAL OF THE ELDERLY ON PERITONEAL DIALYSIS were evaluated using the chi-square test, Fisher s exact test, the Wilcoxon rank-sum test, or the Kruskall Wallis test, as appropriate. All p values were two-sided, with a significance level of 5%. All analyses were performed using SAS 6.12 (SAS Institute, Cary, North Carolina, USA) and S-Plus 4.5 (MathSoft Inc., Seattle, Washington, USA) software packages. RESULTS PATIENT CHARACTERISTICS The gender ratio was 136F/156M. Mean age was 81.6 ± 4.0 years and median age was 81.2 years; 178 patients were over 80 years of age and 60 patients were over 85 years of age. Age distribution is shown in Figure 1. Progressive aging of the population at initiation of dialysis was demonstrated when the three periods were compared (Table 2). Primary renal diagnosis was available in 212 patients and is depicted in Table 3. Peritoneal dialysis was the first dialysis therapy in 95.6% of cases; dialysis had to be initiated because of terminal chronic renal failure in 92.8%; 7 patients had to initiate dialysis because of heart failure, and 14 started PD in the setting of acute renal failure. No significant difference in the mode of entry was found among the three study periods. Charlson s score of comorbidity could be calculated in 68/88 patients in period 1, 118/143 patients in period 2, and in 59/61 patients in period 3. The CCI was very high, with a mean index of 8.0 ± Moreover, CCI was significantly higher in patients initiating dialysis in period 3 compared to periods 1 and 2 (CCI 7.6 ± 1.6 in period 1, 8.0 ± 1.5 in period 2, and 8.5 ± 1.6 in period 3; p = 0.01; Figure 2). Charlson s comorbidity index was significantly higher in the 21 patients initiating PD because of acute renal failure or heart failure compared to those with chronic uremia (CCI 8.8 ± 1.95 vs 8.0 ± 1.74, p = 0.045). The proportion of patients with the lowest CCI (< 7) decreased from 26.5% in period 1 to 11.9% in period 3 (p = 0.035). Conversely, the proportion of patients with CCI above 9 increased from 10.3% in period 1 to 30.5% in period 3, although this increase did not reach statistical significance. No statistical difference in the percentage of identified comorbid conditions, including diabetes, was found among the three periods. Cardiovascular comorbidity, excluding hypertension, was present in 72.5% of patients. Data on recombinant erythropoietin (rhuepo) treatment were available in 120 patients in period 2 and in all patients in period 3. During period 2, 27 patients (22.5%) were treated with rhuepo; this score increased to 74% of patients during period 3. Treatment with rhuepo was associated with improved predialysis hemoglobin levels in period 3 compared Figure 1 Distribution of elderly patients per age group over the three periods of observation. Data are presented for 292 patients initiating dialysis. TABLE 2 Baseline Characteristics of 292 Patients Initiating Peritoneal Dialysis Age at initiation of dialysis (years) 79.7± ±3.9 a 81.8±4.4 b Hemoglobin (g/dl) 9.0± ± ±1.6 b Serum albumin (g/l) 34.0± ± ±4.6 b Creatinine clearance (ml/min) 6.2± ± ±3.8 b Mean predialysis values of hemoglobin, serum albumin, and creatinine clearance. Creatinine clearance was calculated by the Cockcroft Gault formula. a p < 0.05, period 2 versus period 1. b p < 0.001, period 3 versus periods 1 and 2. to periods 1 and 2 (Table 2). Moreover, mean hemoglobin level increased on PD during periods 2 and 3. The 0-, 3-, and 6-month hemoglobin values were 9.0 ± 1.6, 9.4 ± 1.3, and 9.5 ± 1.2 g/dl in period 1 [p = not significant (NS)]; 9.1 ± 1.4, 9.9 ± 1.3, and 10.1 ± 1.4 g/dl in period 2 (p < 0.001); and 9.9 ± 1.6, 10.6 ± 1.6, and 11.3 ± 1.0 g/dl in period 3 (p < 0.001). Predialysis serum albumin was higher in period 3 compared to periods 1 and 2 (Table 2). A decrease in serum albumin over time, from 35.4 ± 5.4 g/l on initiation of dialysis to 32.5 ± 6.2 g/l at the end of follow-up, was noticed (p < 0.001), but there was no difference between the periods. Evaluation of predialysis residual renal function by Cockcroft Gault estimation of creatinine clearance showed a signifi- 75

4 VRTOVSNIK et al. JANUARY 2002 VOL. 22, NO. 1 PDI TABLE 3 Primary Renal Diagnosis Renal diagnosis n (%) Renal vascular disease 53 (25) Glomerulonephritis 32 (15) Diabetic nephropathy 36 (17) Chronic interstitial nephritis 38 (18) Polycystic kidney disease 5 (2) Uropathy 7 (3) Myeloma 7 (3) Other 34 (16) Diabetes was present in 60 patients, but data consistent with the diagnosis of diabetic nephropathy were found in only 36 patients. In 34 patients, renal diagnosis remained undetermined or another renal diagnosis was advocated. Figure 2 Charlson s combined age comorbidity index was calculated in elderly patients with more than 90 days survival on peritoneal dialysis from each study period. Boxplot analysis of results is presented. Period 1 = ; period 2 = ; period 3 = *p < 0.05 versus period 1. cantly higher value during the last period compared to periods 1 and 2 (Table 2). were transferred to hemodialysis within 90 days of initiating PD. Three patients recovered renal function and stopped dialysis; 13 patients had moved to another institution before completion of the study and were censored. No patient was proposed for kidney transplantation. A marked decrease in the incidence of peritonitis and an increase in the percentage of patients who remained free of peritonitis were noted during the observation period (Figure 3). The number of peritonitis episodes was 89/1691 patient months in period 1, 96/2521 patient months in period 2, and 16/898 patient months in period 3, corresponding to a mean incidence of peritonitis of 0.63, 0.44, and 0.21 peritonitis episodes per year, respectively (p < ). The proportion of patients who had a single episode of peritonitis was 18%, with no significant difference between the periods. The percentage of patients with multiple episodes of peritonitis strongly decreased over the study period: from 35% in period 1, to 20% in period 2, to 1 patient in period 3; p < 0.001). Mean incidence of peritonitis was not significantly different in patients who did not require assistance to perform PD (0.72 episodes/patient year, p = NS). Gram-positive cocci were identified in 58% of peritonitis episodes, with no significant difference between the three periods. Escherichia coli was the causative micro-organism of 13 episodes in 11 patients; Enterobacter, Pseudomonas, and water-associated gram-negative rods were cultured in 15 cases in 14 patients. Eight peritonitis episodes were caused by yeasts. Culture-negative peritonitis was diagnosed in 7 cases (3.6%). The overall mortality rate due to peri- CHARACTERISTICS OF DIALYSIS Home PD was performed in 209/247 patients (84.6%), including 204 patients on CAPD and 38 patients who underwent hospital-based NIPD. Most patients (94.9%) required assistance to perform PD exchanges. Death was the cause of cessation of PD in 77.7%; 25 (8.6%) were still on PD at the end of the observation period. Twenty-one patients (8.2%) were shifted to hemodialysis (8/81 patients in period 1, 11/122 patients in period 2, and 2/49 patients in period 3) because of catheter dysfunction or laparotomy in 12 patients and because of peritonitis in 9 patients, with no difference between the periods. Four patients 76 Figure 3 Incidence of peritonitis during periods 1, 2, and 3 in elderly patients with more than 90 days survival on peritoneal dialysis (A). Proportion of patients who remained free of peritonitis over the three study periods (B). Data were lacking in 19% of patients in period 1, 16.8% of patients in period 2, and in 2 patients in period 3. Period 1 = , period 2 = , period 3 =

5 PDI JANUARY 2002 VOL. 22, NO. 1 SURVIVAL OF THE ELDERLY ON PERITONEAL DIALYSIS tonitis was 5.2% in the 96 patients with at least 1 documented episode of peritonitis. ANALYSIS OF SURVIVAL The early-mortality rate in the 292 patients was 12.1% (35 patients). It was 5.8% in period 1, 13.5% in period 2, and 18.3% in period 3 (p = 0.057). Although the differences were not significant, over the whole study, the early-mortality rate was higher in the oldest age group: 10.5% in patients years, 11.4% in patients years, 15.4% in patients years, and 25% in patients over 90 years. Mean CCI was not different between patients who remained on PD for more than 90 days and those who died early. Among the population of patients who survived more than 90 days, 61 patients were still alive at the end of the observation period. The causes of death in the remaining 192 patients did not differ between the periods (Table 4). Cardio- and cerebrovascular deaths were identified in 26% and 11%. Dementia, progressive deterioration of general status, and cessation of dialysis were identified in 22% of patients ( waning syndrome, Table 4). Two cases of suicide were recorded. Cancer was diagnosed in 34 patients, but it was the recorded cause of death in only 6 patients; 5 patients with cancer were still alive at the end of the study. Median survival was 21.6 months for the 253 patients who survived more than 90 days (Figure 4). Patients initiating PD in the setting of acute renal failure or heart failure had a nonsignificantly lower survival (17.2 ± 12.0 months vs 23.5 ± 16.7 months, p = NS). No significant relationship was found between duration of survival and hemoglobin or serum albumin levels at initiation of dialysis or Figure 4 Kaplan Meier survival curves. Data were analyzed in elderly patients with more than 90 days survival on peritoneal dialysis. Analysis of survival in the overall population of patients is shown. calculated residual predialysis creatinine clearance. Similarly, diagnosis of diabetes, gender, period of initiation of dialysis, or PD mode did not influence survival. Patients not requiring assistance to perform PD exchanges had a better median survival compared to the others, 42.7 versus 21.5 months, but this difference was not significant. Patients were stratified into three groups according to their CCI: below 7 (19.2% of the population), 7 9 (61.2%), and above 9 (19.6%). This index was a strong predictor of survival (Figure 5). Median survival ranged from 39.5 months in patients with CCI < 7, to 21.0 months (7 9) and 17.0 months (> 9); p < Compared to the group with the lowest scores (< 7), the corresponding hazard ratios were 2.02 ( ) and 2.8 ( ) in patients with 7 < CCI < 9 and TABLE 4 Cause-Specific Peritoneal Dialysis (PD) Mortality by Calendar Period in Patients Surviving Longer Than 90 Days on PD n (%) n (%) n (%) n (%) Patients starting PD 88 (30.1) 143 (49.0) 61 (20.9) 292 Survival on PD < 90 days 6 (6.8) 21 (14.7) 12 (19.7) 39 (13.4) Survival on PD > 90 days 82 (93.2) 122 (85.3) 49 (80.3) 253 (86.6) Alive on PD at end of study or censored 11 (12.5) 23 (16.1) 27 (44.3) 61 (20.9) Cause of death Vascular a 22 (31.0) 40 (40.4) 9 (41.0) 71 (37.0) Waning syndrome 8 (11.3) 27 (27.3) 7 (31.8) 42 (21.9) Peritonitis 4 (5.6) 4 (4.0) 2 (9.1) 10 (5.2) Cancer 3 (4.2) 3 (13.6) 6 (3.1) Digestive 4 (5.6) 1 (1.0) 5 (2.6) Infection (excluding peritonitis) 2 (2.8) 6 (6.1) 1 (4.6) 9 (4.7) Unknown 18 (39.5) 21 (21.2) 49 (25.5) a Cardiovascular and cerebrovascular death are identified as vascular. 77

6 VRTOVSNIK et al. JANUARY 2002 VOL. 22, NO. 1 PDI CCI > 9, respectively. Estimated rates of survival at 1, 2, and 5 years are presented Table 5. Analysis of technique survival gave similar results, with median survivals of 36.4, 20.2, and 17.0 months in patients with CCI < 7, 7 < CCI < 9, and CCI > 9; p < Median survival was 21.6 months in patients aged years, 22.2 months for years, 18.4 months for years, and 25 months for those more than 90 years of age (NS; Figure 6). However, age and CCI as continuous variables were statistically significant factors of survival in the Cox model (p < 0.03 and p < 0.001, respectively). To allow distinction in the respective roles of age and of other comorbidity factors in survival, a modified Charlson index was calculated that excluded age; this index did not increase significantly from period 1 to period 3 (4.1 ± 1.6, 4.3 ± 1.5, and 4.8 ± 1.7 in periods 1, 2, and 3, respectively; p = 0.07). However, the backward variable elimination procedure for the multivariable Cox model identified age over 85 years, modified agerestricted Charlson index above 3, and modified agerestricted Charlson index above 5 (dummy variables) Figure 5 Kaplan Meier survival curves. Data were analyzed in elderly patients with more than 90 days survival on peritoneal dialysis. Patients were stratified according to Charlson s score of comorbidity (CCI) into three groups (CCI < 7, 7 < CCI < 9, and CCI > 9), and analysis of survival was performed. p < in CCI 7 9 versus CCI < 7. p < in CCI > 9 versus CCI < 7. as independent prognostic factors: the corresponding associated adjusted hazard ratios (and 95% Wald confidence intervals) were, respectively, 1.66 ( , p = 0.009), 1.89 ( , p = 0.014), and 2.86 ( , p = ). Indeed, median survival ranged from 41.2 months in patients with a modified age-restricted index below 3, to 20.0 months among those with a value above 5 (p < 0.005). Median survival was not significantly different between the periods (21.0 months in period 1, 21.5 in period 2, and 25.4 in period 3), despite an increase in mean age and CCI. Adding the period to the Cox model did not improve the model. However, including a period effect in the original model gave an adjusted hazard ratio of 0.68 (95% CI , p = 0.10) for period 3. Moreover, the likelihood ratio test comparing the model with an effect of period 3 with the model selected by the backward elimination procedure led to a p value of 0.09, indicating a trend to longer survival for patients in the third period, when adjusted for age and comorbidity. The high rate of censoring for patients from period 3 (53.1%) with a corresponding small number of events (23) was likely to worsen the estimate of the standard error of the regression param- Figure 6 Kaplan Meier survival curves. Data were analyzed in elderly patients with more than 90 days survival on peritoneal dialysis. Analysis of survival among age groups did not show statistical significance. 78 TABLE 5 Estimates of Survival on Peritoneal Dialysis (PD) in Relation to the Combined Comorbidity Index (CCI) for Patients Surviving at Least 90 Days on PD 1-Year survival 2-Year survival 5-Year survival n % 95% CI % 95% CI % 95% CI Overall study CCI < CCI CCI > CI = confidence interval.

7 PDI JANUARY 2002 VOL. 22, NO. 1 SURVIVAL OF THE ELDERLY ON PERITONEAL DIALYSIS eters, and thereby partially mask an improvement in survival for patients in period 3. DISCUSSION Our results demonstrate that, from 1982 to 1999, mean age and comorbidity on initiation of dialysis increased in patients aged over 75 years, and that, when the CCI was taken into account, improved survival was demonstrated on PD. The retrospective nature of this study carries limitations in interpretation of the data. However, these limitations are probably small. First, all patients older than 75 years with terminal renal failure were proposed PD as their first RRT, making a selection bias unlikely. Second, all patients but one from the first study period, and all but 9 of the 143 in period 2 died, which renders overestimation of survival unlikely. Third, in this singlecenter study, the same team of physicians took care of the patients during the entire study, although there were changes in practices over time. Therefore, discrepancies in dialysis management are unlikely to account for differences among subgroups. Fourth, the precise analysis of the specific role of dialysis dose in elderly patients survival on PD was beyond the scope of this study. Finally, this analysis provides the basis for risk stratification and prospective evaluation of the effect of dialysis dose on survival in elderly patients. EVALUATION OF COMORBIDITY AND PREDICTION OF SURVIVAL Comorbidity is an established factor of patient survival on dialysis. The importance of a more precise evaluation of this parameter has been emphasized by previous studies (14 17). Our results show that the role of increasing age in patient survival on RRT should not be overstated. Also, the ominous prognosis that diabetes mellitus carries in younger patients on RRT was not confirmed in the elderly (9). This is in accordance with the results of Chandna et al., who showed that the value of age in predicting survival was outweighed by the comorbidity score and functional status (16). The early mortality rate in our population was similar (13.5%) to that in the ERA-EDTA report for patients over 75 years starting RRT in (9.8%) (18). In the 1991 USRDS annual data report, the early mortality rate was 11% in patients aged years, but reached 18% in patients aged years and 26% in patients over 85 years of age. This increase was attributed to increased comorbidity (19). Mean early mortality was 8.7% (range 2.7% 13.1%) in five European centers. Wide disparities between the centers were at least in part related to differences in comorbidity (20). A nonsignificant increase in early mortality rate was found in the present study from periods 1 to 3. MANAGEMENT OF PD IN THE ELDERLY AND SURVIVAL The sex ratio contrasted with the expected female predominance in the general elderly population. However, these data were consistent with other published reports of increased incidence of chronic and terminal renal failure in men in all age groups (7,21,22). Indeed, the reason for the recognized predominance of males on RRT is not unique. A marked decrease in peritonitis incidence was found in the last period. New connection systems, including double-bag and Y-set systems, were introduced in 1989 and strongly reduced the risk and incidence of hand-borne peritoneal infections (23). These systems were used uniformly in the last study period. Most notably, the number of patients who presented with more than one episode of peritonitis either a relapse or involving a different pathogen has decreased since Similarly, the proportion of patients remaining free of peritonitis has steadily increased, and nearly doubled over the three study periods. As most patients benefited from trained home-nurse assistance, this decrease in peritonitis episodes most likely reflects technique progress rather than patient selection. Significant increases in predialysis values of hemoglobin, albumin, and creatinine clearance were observed from period 1 to period 3. We did not find a significant relationship between patient survival and serum albumin or creatinine clearance, which contrasts with data from other studies (24). This lack of relationship may reflect specific characteristics of our population group. It is also possible that the negative effects of low serum albumin were confounded by the very high comorbidity and the short mean follow-up, as their beneficial or detrimental values were more prominent with elapsing years after initiation of dialysis (1,25,26). Finally, these results are in agreement with other studies that failed to find a significant relationship between serum albumin and survival in multivariate analysis, and suggest that the role of hypoalbuminemia is probably small when comorbidity is taken into account (27). Earlier referral of and/or improved management of predialysis renal failure in patients in period 3 is suggested by the higher residual creatinine clearance on initiation of dialysis, as well as the higher predialysis albumin and hemoglobin levels. This could account for the relatively improved survival during this period. The validity of Cockcroft Gault determination of creatinine clearance is strongly restricted at extreme ages of life or levels of renal function, and calculated values may overestimate residual renal function (28). 79

8 VRTOVSNIK et al. JANUARY 2002 VOL. 22, NO. 1 PDI However, mean patient weight was not different between periods (data not shown), so higher calculated clearance may be taken as an indicator of better residual renal function and of earlier referral in the last period. The deleterious consequences of late versus early referral to the nephrologist have been reviewed (29). In addition to improved predialysis management of renal insufficiency attributed to early referral, early start of dialysis has itself been advocated to slow down the decrease in residual renal function and to ameliorate survival (30). In contrast, late referral to the nephrology team has been associated with higher mortality within the first 3 12 months on dialysis and with reduced median survival (16, 31,32). TRENDS IN SURVIVAL OF ELDERLY PD PATIENTS Recently, data from the Canadian PD registry showed a reduction in overall PD mortality rate since 1982, from 230 per 1000 patient years in , to 162 per 1000 patient years in , which was attributed to technique improvements and better patient management (8). De Vecchi et al. compared mortality in young (40 60 years) and old (> 70 years) nondiabetic PD patients: mean survival was 33 months (young) and 27 months (old), and causes of death were not different (22). A mean therapy duration of 20 months was reported by Gorban Brennan et al. in 18 patients aged over 80 years who were on PD from (33). Two-year survival was 59% in the 213 patients aged over 75 years in the French multicenter study by Benevent et al. (34). Median survival in the 48 patients aged over 75 years starting dialysis from 1992 to 1995 in the study by Chandna et al. was 19 months (16). Our data indicate that median patient survival has remained in the 2-year range since the beginning of the observation period, despite a mean aging by 2 years and an increase in the comorbidity index. Moreover, statistical analysis points toward longer survival in the third period, when adjusting for age and comorbidity. In conclusion, the growing incidence of terminal renal failure in the elderly requires a precise evaluation of survival and identification of prognostic factors in this age group. Our results show that Charlson s CCI is a valuable prognostic factor in this population and that elderly patients have benefited from better management of chronic renal failure and improvements in PD technique in the past two decades. ACKNOWLEDGMENTS This work was supported by a grant from the Association pour l utilisation du rein artificiel, Paris. The authors thank Prof. Raymond T. Krediet and Dr. Friedo Dekker for helpful discussion of the manuscript, and 80 Kitty Jager for providing data from the ERA-EDTA registry. Special thanks to Céline Joly and Kawthar Khelal for their precious help in the preparation of the manuscript. REFERENCES 1. Maiorca R, Brunori G, Zubani R, Cancarini C, Manili L, Camerini C, et al. Predictive value of dialysis adequacy and nutritional indices for mortality and morbidity in CAPD and HD patients. A longitudinal study. Nephrol Dial Transplant 1995; 10: Schaubel DE, Morrison HI, Fenton SSA. Comparing mortality rates on CAPD/CCPD and hemodialysis. The Canadian experience: fact or fiction? Perit Dial Int 1998; 18: Fenton SSA, Schaubel DE, Desmeules M, Morrison HI, Mao Y, Copleston P, et al. Hemodialysis versus peritoneal dialysis: a comparison of adjusted mortality rates. Am J Kidney Dis 1997; 30: Vonesh EF, Moran J. Mortality in end-stage renal disease: a reassessment of differences between patients treated with hemodialysis and peritoneal dialysis. J Am Soc Nephrol 1999; 10: Murphy SW, Foley RN, Barrett BJ, Kent GM, Morgan J, Barré P, et al. Comparative mortality of hemodialysis and peritoneal dialysis in Canada. Kidney Int 2000; 57: Jager KJ, Merkus MP, Boeschoten EW, Dekker FW, Tijssen JGP, Krediet RT. What happens to patients starting dialysis in The Netherlands? Neth J Med (in press). 7. United States Renal Data System. Incidence and prevalence of ESRD. In: USRDS 1999 annual data report. Bethesda, MD: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 1999: Schaubel DE, Fenton SSA. Trends in mortality on peritoneal dialysis: Canada, J Am Soc Nephrol 2000; 11: Elinder C-G, Jones E, Briggs JD, Mehls O, Mendel S, Piccoli G, et al. Improved survival in renal replacement therapy in Europe between 1975 and An ERA- EDTA registry study. Nephrol Dial Transplant 1999; 14: Charlson ME, Pompei P, Ales KL, MacKenzie CR. A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. J Chronic Dis 1987; 40: Kaplan E, Meier P. Non-parametric estimation from incomplete observations. J Am Stat Assoc 1958; 35: Cox D. Regression models and life tables. J R Stat Soc 1972; B34: Grambsch PM, Therneau TM. Proportional hazards tests and diagnostics based on weighted residuals. Biometrika 1994; 81: Wright LF. Survival in patients with end-stage renal disease. Am J Kidney Dis 1991; 17: Khan IH, Catto GRD, Edward N, Fleming LW, Henderson IS, MacLeod AM. Influence of coexisting disease on survival on renal-replacement therapy.

9 PDI JANUARY 2002 VOL. 22, NO. 1 SURVIVAL OF THE ELDERLY ON PERITONEAL DIALYSIS Lancet 1993; 341: Chandna SM, Schulz J, Lawrence C, Greenwood RN, Farrington K. Is there a rationale for rationing chronic dialysis? A hospital based cohort study of factors affecting survival and morbidity. BMJ 1999; 318: Longenecker JC, Coresh J, Klag MJ, Levey AS, Martin AA, Fink NE, et al. Validation of comorbid conditions on the end stage renal disease medical evidence report: the CHOICE Study. J Am Soc Nephrol 2000; 11: Tsakiris D, Jones EHP, Briggs JD, Elinder C-G, Mehls O, Mendel S, et al. Deaths within 90 days from starting renal replacement therapy in the ERA-EDTA registry between 1990 and Nephrol Dial Transplant 1999; 14: USRDS 1991 annual data report. Survival probabilities and causes of death. Am J Kidney Dis 1991; 18(Suppl 2):S Khan IH, Campbell MK, Cantarovich D, Catto GRD, Delcroix C, Edward N, et al. Comparing outcomes in renal replacement therapy: how should we correct for case mix? Am J Kidney Dis 1996; 31: Jones CA, McQuillan GM, Kusek JW, Eberhardt MS, Herman WH, Coresh J, et al. Serum creatinine levels in the US population: third National Health and Nutrition Examination survey. Am J Kidney Dis 1998; 32: De Vecchi AF, Maccario M, Braga M, Scalamogna A, Castelnovo C, Ponticelli C. Peritoneal dialysis in nondiabetic patients older than 70 years: comparison with patients aged 40 to 60 years. Am J Kidney Dis 1998; 31: Port FK, Held PJ, Nolph KD, Turenne MN, Wolfe RA. Risk of peritonitis and technique failure by CAPD connection technique: a national study. Kidney Int 1992; 42: Blake PG, Flowerdew G, Blake RM, Oreopoulos DG. Serum albumin in patients on continuous ambulatory peritoneal dialysis predictors and correlations with outcomes. J Am Soc Nephrol 1993; 3: Foley RN, Parfrey PS, Harnett JD, Kent GM, O Dea R, Murray DC, et al. Mode of dialysis therapy and mortality in end-stage renal disease. J Am Soc Nephrol 1998; 9: Genestier S, Hedelin G, Schaffer P, Faller B. Prognostic factors in CAPD patients: a retrospective study of a 10-year period. Nephrol Dial Transplant 1995; 10: Jager KJ, Merkus MP, Dekker FW, Boeschoten EW, Tijssen JGP, Stevens P, et al. Mortality and technique failure in patients starting chronic peritoneal dialysis: results of the Netherlands Cooperative Study on the Adequacy of Dialysis. Kidney Int 1999; 55: Goldberg TH, Finkelstein MS. Difficulties in estimating glomerular filtration rate in the elderly. Arch Int Med 1987; 147: Obrador GT, Pereira BJG. Early referral to the nephrologist and timely initiation of renal replacement therapy: a paradigm shift in the management of patients with chronic renal failure. Am J Kidney Dis 1998; 31: Bonomini V, Feletti C, Scolari MP, Stefoni S. Benefits of early initiation of dialysis. Kidney Int 1985; 28(Suppl 17):S Innes A, Rowe PA, Burden RP, Morgan AG. Early deaths on renal replacement therapy: the need for early nephrological referral. Nephrol Dial Transplant 1992; 7: Khan IN, Catto GR, Edward N, MacLeod AM. Death during the first 90 days of dialysis: a case control study. Nephrol Dial Transplant 1995; 25: Gorban Brennan N, Kliger AS, Finkelstein FO. CAPD therapy for patients over 80 years of age. Perit Dial Int 1993; 13: Benevent D, Issad B, Lavaud S, Dubot P, Aguilera D, Milongo R, et al. Dialyse péritonéale chez les patients de plus de 75 ans; étude multicentrique française sur 213 cas. Bulletin de Dialyse Péritonéale 1995; 5: