International Urology and Nephrology 34: 565572, 2002. 2003 Kluwer Academic Publishers. Printed in the Netherlands.

565

Possible factors contributing to similar peritoneal dialysis outcome in patients over 60 years of age and the younger ones
Alicja E. Grzegorzewska & Magdalena Leander
Chair and Department of Nephrology, Transplantology and Internal Diseases, Karol Marcinkowski University of Medical Sciences, Pozna, Poland

Abstract. The aim of studies was a comparison of dialysis adequacy, nutritional parameters, results of the peritoneal equilibration test (PET) and selected standard clinical and laboratory data in peritoneal dialysis (PD) patients with different age, but comparable PD duration and outcome. Two groups of patients were examined: group I (n = 21, 9 F, 12 M) age 67.7 4.5 yrs, PD duration 20.1 12.1 months; group II (n = 21, 9 F, 12 M) age 42.8 9.1 yrs, PD duration 20.7 12.1 months. Parameters of PD adequacy, results of PET, markers of nutrition and standard laboratory measures were determined every 3 months to the end of PD treatment. First obtained values, mean values representing the entire PD course and last values obtained before the end of PD therapy were compared in group I and II. Differences in results obtained at the beginning and at the end of PD therapy were also compared in each group. At the beginning of PD therapy the older patients showed higher total fat mass (TFM) expressed as % of total body mass (TBM), lower lean body mass (LBM), lower serum levels of iron, phosphorus and creatinine as well as lower transferrin saturation. When mean values representing the entire PD course were compared, the older patients showed higher TFM as % of TBM and serum ferritin level, whereas lower values were observed for diastolic blood pressure (DBP), LBM, serum creatinine, phosphorus and iron. At the end of PD therapy TFM as % of TBM and serum ferritin level remained higher in older patients as well as lower both DBP and LBM were maintained. Additionally, serum cholesterol level and residual renal function (RRF) became at the end of PD treatment higher in the older individuals compared to the younger ones. The difference in RRF between the two groups was caused by the decline in RRF in the younger patients with relatively stable values of RRF in the older ones. Nutritional parameters improved in the course of PD only in the younger group. In conclusion, the older patients reach similar PD outcome parameters compared to the younger ones while they show higher TFM as % of TBM, stable RRF and more satisfactory DBP. However, elderly patients show a greater progress in the deterioration of indices of both inammation and atherosclerosis and therefore are not able to improve nutritional parameters. Key words: Age, Blood pressure, Nutrition, Peritoneal dialysis Abbreviations: BMI body mass index; BSA body surface area; BUN blood urea nitrogen; CAPD continuous ambulatory peritoneal dialysis; CRP C-reactive protein; D dialysate; DBP diastolic blood pressure; DEI daily energy intake; DNB daily nitrogen balance; DPI daily protein intake; E erythrocytes; Hb hemoglobin; IBM ideal body mass; LBM lean body mass; P plasma; PD peritoneal dialysis; PET peritoneal equilibration test; PLT platelets; RFF residual renal function; TBM total body mass; TBW total body water; TFM total fat mass; WBC white blood cells Introduction Growth in the number of dialysis patients over the age of 60 years is occurring coincidentally with the overall aging of the general population and higher acceptance rate of elderly end-stage renal disease (ESRD) patients to regular dialysis treatment. In 1997, according to the United States Renal Data System, about 45% of current uremic patients and 51% of new dialysis patients were over 65 years old [1]. Peritoneal dialysis (PD), especially continuous ambulatory peritoneal dialysis (CAPD), is an acceptable

566 form of renal replacement therapy in elderly uremic patients [2, 3, 4, 5]. Peritonitis rates, incidence of dialysate leakage and bleeding are usually reported as not different in elderly and younger patients [2, 4]. Most authors have observed that exit-site and tunnel infections are similarly or less frequent in elderly than in younger PD patients [4, 6]. Occurrence of hernia or differences in PD technique survival between older and younger patients are not uniformly presented in the scientic literature [4, 7]. On the other hand, the elderly PD patients with multiple comorbid diseases have worse outcome than majority of the younger patients [8, 9]. The aim of our study was to assess whether dialysis adequacy, nutritional parameters, results of the peritoneal equilibration test (PET) or selected standard clinical and laboratory data are similar in older (over 60 years) and younger (below 60 years) patients who reach the same PD duration and outcome. Causes of ESRD in group I included: chronic glomerulonephritis (5 patients), chronic pyelonephritis (7 patients), diabetic nephropathy (4 patients), hypertensive nephrosclerosis (2 patients), polycystic kidney disease (2 patients), unknown disease (1 patient). In group II, underlying renal disease was chronic glomerulonephritis (10 patients), chronic pyelonephritis (3 patients), diabetic nephropathy (4 patients), hypertensive nephrosclerosis (3 patients), Henoch-Schnlein syndrome (1 patient). Comorbidity grade was evaluated at the beginning of PD using the method of Davies et al. (11). Results of estimation of PD adequacy, residual renal function (RRF), PET, dietary intake, markers of nutrition, and routine clinical and laboratory data were collected every three months to the end of PD treatment. The methodology for measurements of the data mentioned above has been partially described in earlier papers [12, 13]. In brief, adequacy parameters included Kt/V, total creatinine clearance (l/week/1.73 m2 of body surface area BSA), protein nitrogen appearance (PNA) and nursing assessment score described by Keshaviah et al. [14]. BSA was calculated based on height, weight, sex, and age of the patient [15]. Values of PNA were normalized to both ideal body mass (IBM) and TBM. Standard PET was performed according to Twardowski et al. [16]. Total daily energy intakes (DEI) and daily protein intakes (DPI) were normalized to IBM, calculated using the formulas of Potton [17]. Anthropometric indices of nutritional status included total body mass (TBM), lean body mass (LBM), total fat mass (TFM) and body mass index (BMI). TFM was calculated from total body density, using body weight and the sum of the four skin fold measurements [18]. LBM was calculated as TBW/0.73, where TBW = total body water [14]. TBW was estimated using the Watson nomogram [19]. Blood samples were taken after overnight fast at the end of the overnight exchange, and then clinical assessments were performed. Dialysate was collected for a 24-hour period preceding the early morning exchange on the day of the assessment. Urine collections lasted 2448 hours and were nished before taking blood samples. Total nitrogen concentration was measured in dialysate and urine by the modied method of Kjeldahl [20]. Daily nitrogen balance (DNB) was calculated as the difference between nitrogen intake and nitrogen loss. The xed amount of 1.824 g was taken into consideration to account for nitrogen from protein (1.504 g) and amino acids (0.32 g) lost daily

Patients and methods Between 14 October 1992 and 2 October 2000, 117 uremic patients were treated with ambulatory peritoneal dialysis in our PD unit. At the beginning of PD, 90 patients were younger then 60 years, whereas 27 patients (23.1% of all patients) had more than 60 years of age. Among all 117 patients, two groups were retrospectively selected. Group I consisted of 21 PD patients who were older than 60 years (67.7 4.5 years, range 60.477.2 years) at the start of PD; group II included 21 PD patients younger than 60 years (42.0 9.1 years, range 24.757.4 years), chosen as comparison subjects for each of these patients of group I. Patients of group II were matched those of group I for gender (9 females and 12 males in each group), PD duration (20.1 12.1 months and 20.7 12.1 months in group I and II, respectively) and outcome (in each group ve patients died, four were transferred to hemodialysis, ten continue on PD treatment). In two older patients, in whom renal function improved, CAPD treatment was discontinued [10]. Two younger patients who underwent kidney transplantation after similar PD duration were matched with these patients. Six patients in the age exceeding 60 years at the onset of PD were not included in the study because there were no patients younger than 60 years who could be matched with these patients (4 cases), or they were previously treated with hemodialysis (2 cases).

567 through the gastrointestinal tract and the skin [21, 22]. This xed amount of nitrogen was subtracted from values of nitrogen intake. Results are expressed by mean standard deviation. The rst obtained values (those shown before three months of PD therapy), mean values representing the entire PD course in each patient and last values obtained before the end of PD therapy were compared in groups (the Mann-Whitney test). Differences in results obtained at the beginning and at the end of PD therapy were also compared in each group (the Wilcoxon test). The corrected chi-squared test was applied for comparison of percentile differences in the peritoneal permeability between groups. Signicance was dened at p < 0.05.
Table 1. The results showing signicant differences (p < 0.05) in patients of groups I and II Group I Group II

The results of the beginning of peritoneal dialysis TFM as % TBM 33.1 7.4 29.0 13.9 LBM, kg 66.9 7.4 71.0 13.9 Serum iron, g/dl 87.4 34.8 104.8 26.1 Transferrin saturation, % 26.8 10.0 34.5 12.0 Serum creatinine, mg/dl 7.53 2.34 9.03 2.23 Serum phosphorus, mg/dl 4.34 0.90 5.49 1.70 Blood pH 7.40 0.04 7.36 0.05 22.6 2.6 20.7 2.9 HCO , mmol/l 3 Weakness, scores 2.80 0.74 2.62 0.65 The mean results representing the entire course of peritoneal dialysis TFM as % TBM 32.3 5.7 27.0 8.1 LBM, kg 66.7 5.7 73.1 8.1 Serum iron, g/dl 87.6 23.5 95.7 15.1 Serum creatinine, mg/dl 8.37 2.82 10.62 2.82 Serum creatinine/height 0.050 0.017 0.063 0.016 ratio Serum phosphorus, mg/dl 4.54 0.81 5.44 1.20 Blood pH 7.40 0.03 7.37 0.04 Serum ferritin, ng/ml 1017 668 449 412 DBP, scores 2.80 0.30 2.47 0.49 The results of the end of peritoneal dialysis in patients of groups I and II TFM as % TBM 32.2 5.5 28.0 10.7 LBM, kg 67.8 5.5 72.0 10.7 Blood pH 7.41 0.03 7.38 0.05 Serum ferritin, ng/ml 842 524 522 359 Serum total cholesterol, 250 55 210 41 mg/dl DBP, scores 2.88 0.30 2.40 0.70 35.8 51.8 13.1 21.3 RRF, l/wk/1.73 m2 BSA BSA body surface area DBP diastolic blood pressure LBM lean body mass RRF residual renal function TBM total body mass TFM total fat mass

Results At the beginning of PD therapy the older patients showed higher TFM calculated as percent TBM, lower LBM, lower serum iron level and transferrin saturation. Lower serum creatinine and phosphorus concentrations as well as higher blood pH and bicarbonate level were observed in the older group under comparable PD adequacy parameters. Clinical scoring for feeling of weakness revealed worse results in the younger group (Table 1). Dietary intake was similar at the beginning of PD treatment in the two groups, however, DPI showed a tendency (p > 0.05) to be lower (0.84 0.39 g/kg IBM) in the older patients than in the younger ones (1.03 0.50 g/kg IBM). Comorbidity grade was 2.48 1.59 and 1.67 1.32 for group I and II, respectively. When mean values representing the entire PD course were analyzed in both groups, the older patients showed similar nutritional differences to those observed at the PD beginning as the younger patients. Additionally, the older group had over two times higher mean serum ferritin levels, but scoring assessment of diastolic blood pressure (DBP) showed worse values in the younger group (Table 1). At the end of PD therapy, TFM as percent of TBM, serum ferritin level and blood pH remained higher, whereas LBM was maintained lower in the older group compared to the respective parameters in the younger group (Table 1). Additionally, serum level of total cholesterol at the end of PD treatment was signicantly higher in the older individuals compared to the younger ones (Table 1), although differences in DEI and daily intake of cholesterol were not signi-

cant between groups. On the other hand, DBP scores remained better and RRF was higher in the older group (Table 1). The difference in RRF between groups at the end of PD treatment was caused by the decrease in RRF in the younger patients, whereas RRF was relatively stable in the older group (Figure 1). A decrease in RRF and daily urine volume (0.84 0.72 L vs 0.50 0.70 L, p < 0.05) in the younger subjects was accompanied by a fall in urine loss of total protein (1.33 1.84 g/day vs 0.76 1.44 g/day, p < 0.05)

568

Figure 1. Residual renal function (RRF) at the beginning and at the end of peritoneal dialysis (PD) course.

and albumin (0.70 1.01 g/day vs 0.24 0.34 g/day, p < 0.05). Dietary histories did not reveal signicant differences in dietary intake between groups, but in the younger group nutritional parameters (TBM, LBM, BMI and DNB) improved in the course of PD (Figure 2). There were no signicant changes in peripheral blood morphology, electrolytes, glucose, urea, total protein and albumin concentrations between groups and in the PD course in group I and group II. There were no signicant changes in weekly Kt/V, total creatinine clearance and protein nitrogen appearance. Means of these kinetic indices were adequately maintained during the entire PD treatment in both groups. At the beginning of PD therapy the percentage of peritoneal low transporters from the vascular to the mesothelial side of the peritoneal membrane in the older group was 14%, low-average transporters 52%, high-average transporters 29% and high transporters 5%. The percentage of low transporters from the mesothelial to the vascular side of the membrane in this group was 19%, low-average transporters 38%, high-average transporters 33% and high transporters 10%. In the younger group, percentage of respective

transporters from the vascular to the mesothelial side of the membrane was 33%, 24%, 29% and 14%; and from the mesothelial to the vascular side 5%, 33%, 33% and 29%. Percentile patterns of the peritoneal permeability was not statistically different between groups. In the course of PD treatment in the older group a decrease in the dialysate to plasma (D/P) ratio for creatinine was observed (Figure 3).

Discussion It has been reported that malnutrition is more frequent in elderly patients, compared to younger patients, treated with PD [23, 24]. Among elderly patients, those over 75 years had worse nutritional parameters than younger individuals, even those who are 66 75 years old [24]. In our patients, even at the onset of PD, the older patients had worse protein nutrition compared to the younger subjects. The former showed lower LBM whereas TBM was not signicantly different between groups. Lower serum concentrations of creatinine and phosphorus, frequently shown in the elderly patients compared to the younger subjects [1, 25], as well as higher blood pH and bicarbonate level

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Figure 2. Selected nutritional parameters at the beginning and at the end of peritoneal dialysis (PD) course in patients of group II.

Figure 3. Results of standard peritoneal equilibration test in the course of peritoneal dialysis (PD). Values of dialysate/plasma (D/P) ratio for creatinine and dialysate/dialysis solution (D/Do) ratio for glucose are shown and compared to ranges established for low (L), low-average (LA), high-average (HA) and high (H) transporters [27].

570 under comparable PD adequacy parameters also indirectly reect worse LBM and protein intake in the older group [26]. However, the difference in daily protein intake did not reach statistical signicance between groups, but a tendency for lower protein intake was observed in the older patients. According to Morgado et al. [27], a lower serum phosphorus level in older patients is related to their better compliance with therapeutic strategies. Inversely to LBM, TFM calculated as percent of TBM was greater in the older subjects. Earlier data have demonstrated that patients in whom body mass decreases in the course of treatment with PD have worse prognosis and higher mortality rate [28]. Recent data indicates that obesity may be a favorable prognostic factor in PD patients, as it is associated with a reduced risk of death [29]. Therefore, the greater TFM in the examined older patients could be helpful in obtaining better PD outcome. High serum ferritin levels with relatively low serum iron concentration, shown in the older patients, may reect functional iron deciency caused by inammatory status. Serum ferritin is an acute phase reactant [30], closely related to serum C-reactive protein (CRP) concentration [31]. In our earlier study, performed in CAPD patients non-selected according to age and outcome, we found a signicant positive correlation between serum CRP level and patients age, indicating a progression of inammatory status with aging of PD population [31]. The present study suggests that even those elderly patients who achieve similar PD outcome like the younger individuals are more seriously affected by inammation than younger patients. Inammatory status, leading to generation of catabolic cytokines and anorrectic components, together with a greater loss of protein with urine (but not with dialysate), observed in the older patients, are possible factors that did not allow improvement of nutritional indices in this group. However, despite lower LBM, subjective assessment of feeling of weakness was signicantly lower in the older group. According to the study of Westlie et al. [32], the elderly dialyzed patients (>60 years) show a greater life satisfaction than the younger patients. Another abnormality that may be related to inammation is atherosclerosis [33]. CAPD patients over 65 years have higher concentrations of total cholesterol, LDL-cholesterol and triglycerides, whereas HDLcholesterol and apolipoprotein A are lower than in age, sex, race and BMI matched normal controls [34]. With similar energy and cholesterol intake in both examined groups, the older patients showed higher serum cholesterol levels at the end of PD therapy. Our earlier studies indicate that lower than recommended (1.2 g/kg IBM/day) [35] protein intake is associated with elevated serum cholesterol levels in CAPD patients with poor outcome [36]. In CAPD patients, there is a signicant positive correlation between age and serum level of LDL-cholesterol and LDLcholesterol/HDL-cholesterol ratio [31]. Exacerbation of lipid abnormalities with age, without improvement in protein intake, may be related to the poor outcome. Hypoalbuminemia, concomitant with atherogenic lipid prole, increases the risk for ischemic cardiac disease due to enhanced oxidative stress, decreased NO generation and endothelium dysfunction [37]. However, analysis of PD patients who have long-term survival (not selected according to age) suggests better outcome in patients showing an incremental tendency of serum cholesterol concentration in the course of PD [38]. Three percent of uremic patients who began peritoneal dialysis experienced a signicant and persistent increase in RRF, allowing them to either stop PD or decrease the dialysis prescription temporarily [39]. In the present study such an improvement was observed in two older patients [10]. Reports from the literature indicate that the older patients show recovery of renal function (usually partial) more frequently than the younger individuals [40, 41]. As maintenance of residual renal function offers many advantages, including better appetite [42], more satisfactory nutritional status [43], higher positive nitrogen balance [A.E. Grzegorzewska, I. Mariak, unpublished data], and lesser degree of inammatory status [31], the older patients could benet from better RRF. High blood pressure is a risk factor for cardiovascular/cerebrovascular disease, which is known to be the main cause of morbidity and mortality in patients on renal replacement therapy [8, 44, 45]. Death rates due to cardiac arrest, acute myocardial infarction and other cardiac diseases increase with age of dialysis patients [1]. More acceptable DBP could positively inuence PD outcome in the examined older group. The lowest treated DBP, ranging from below 80 to below 85 mmHg, was associated with the lowest mortality from stroke [46]. In hemodialysis patients, post-dialysis DBP 90 mmHg was associated with increased cerebrovascular mortality [45]. The Framingham Heart Study indicates that occurrence of cardiovascular incidences is inversely related to values of DBP [47].

571 The examined Polish older patients did not express signicant differences in the peritoneal permeability as compared to these over 60 years old patients from Argentina [48]. In Japanese CAPD patients, the elderly individuals had higher peritoneal permeability than the middle-age group and young group. This might be the reason of lower serum albumin level in the elderly patients [49]. Our results conrm these studies, which did not show age-related differences in the peritoneal permeability [50]. Moreover, in our study the D/P ratio for creatinine indicated the decrease of the peritoneal permeability from the vascular to the mesothelial side of the membrane in the older patients in the course of PD treatment. Numerous data in age non-selected patients indicate an increase in the peritoneal permeability over time [51, 52, 53]. Our unexpected ndings in the older patients need further observations. In conclusion, our results indicate that: 1. Compared to younger PD patients the older PD patients show greater fat mass as percent of total body mass, stable RRF and more satisfactory diastolic blood pressure, which may suggest that these parameters may contribute to the comparable PD outcome to that which is achieved by the younger PD patients. 2. Even those elderly patients, who achieve similar PD outcome like the younger ones, show an increase of both serum ferritin level (deterioration of iron utilization due to chronic inammatory response?) and total cholesterol (possibility to deterioration of atherosclerosis) and are not able to improve nutritional parameters, which may inuence results of further renal replacement therapy (usually hemodialysis) if these patients cannot continue on PD treatment. References
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Acknowledgement This study was supported by the Karol Marcinkowski, University of Medical Sciences (grant no. 502-2-0161), Pozna, Poland. The paper was presented (oral session) at the VIth International Conference on Geriatrics in Nephrology and Urology, Lisbon, 18-21.03.2001. I was able to nish this paper and present it in Lisbon thanks to my Husband Wodzimierz (died 12.04.2001) who had given me spiritual forces to work despite his critical illness.

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Address for correspondence: Prof. Alicja E. Grzegorzewska, M.D, Ph.D., Chair and Department of Nephrology, Transplantology and Internal Diseases, Al. Przybyszewskiego 49, 60-355 Pozna, Poland Phone and Fax: (48)61 8464578