1 Department of Nephrology, Academic Medical Centre, University of Amsterdam, 2 NECOSAD Foundation, Amsterdam and 3 Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
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Abstract |
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Methods. Two hundred and fifty consecutive new patients were included in this prospective multi-centre study. Data were collected 3 months after start of dialysis. Multivariate linear regression analysis was used to explain the variability of parameters of nutritional state and blood pressure.
Results. Mean age was 57 years, co-morbid conditions were present in 51%, diabetes mellitus in 18%, and cardiovascular disease in 28%. Decreased protein intake was related to diminished residual renal function. Our patients did not have more co-morbidity than Dutch patients participating in a European study some years earlier. Comparison with other studies was complicated by the use of different definitions of co-morbidity and of selected patient populations.
Conclusions. Despite the fact that Dutch dialysis patients have become older and the incidence of diabetic nephropathy has increased, no conclusions could be drawn on a concomitant increase in co-morbidity. This patient group may serve as a reference population to study future changes in patient case-mix within the Netherlands. Furthermore, the use of common international definitions of co-morbidity is needed to be able to make comparisons of survival data.
Keywords: clinical status; co-morbidity; end-stage renal disease; haemodialysis; mortality; peritoneal dialysis
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Introduction |
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The ageing and increased sickness are in part illustrated by the following figures. In the United States, the mean age of new dialysis patients has increased from 55 years in 1984 to 59 years in 1992, while the incidence of diabetes mellitus as primary renal disease rose from 27 to 36% and that of hypertension from 25 to 30% [3,4]. In Europe, the mean age of adult patients starting renal replacement therapy increased from 46 years in 1977 to 57 years in 1992, whereas the incidence of ESRD due to diabetes mellitus grew from 4 to 17% and that due to renal vascular disease from 7 to 14% [5]. A similar trend occurred in the Netherlands [5,6], although the incidence of ESRD caused by diabetes was somewhat lower than in the rest of Europe: 12% in 1992 [6].
Data on the non-renal co-morbidity of the US patients starting dialysis are collected by the United States Renal Data System. Also other investigators evaluated the incidence and sometimes the growth in the number of co-morbid conditions in the US [7,8] and Canada [9,10]. Less is known on the presence of co-morbid conditions in Europe. Neither the registry of the European Renal AssociationEuropean Dialysis and Transplant Association (ERAEDTA) nor the Dutch renal replacement registry (RENINE) routinely collect these data. Yet, especially co-morbidity will influence the outcome of renal replacement therapy. Therefore, Khan et al. recently stated that unadjusted comparisons between survival data from different centres or countries are at best meaningless and at worse misleading because of the potential imbalances in age, co-morbidity etc., in different patients [11]. The same holds for the comparison of survival data over time. The aim of this study was therefore to obtain more data on the clinical condition of patients starting dialysis in the Netherlands and to put these into a European perspective.
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Subjects and methods |
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Data collection
Primary renal disease and co-morbidity.
Renal disease was classified according to the codes of the ERAEDTA Registry. Co-morbid conditions present at the start of dialysis were scored. Cardiovascular disease was recorded when one of the following conditions had been present: angina pectoris, myocardial infarction, Class III to IV congestive heart failure, or peripheral vascular disease. Systemic disease was considered to be present in patients with diabetic nephropathy, hypertensive nephrosclerosis, lupus nephritis, amyloidosis, and scleroderma. The co-morbidity risk for patient survival was expressed as Davies risk score [12], whereas the combined risk of co-morbidity and age was estimated as Khan risk score [13].
Blood pressure, functional status and wellbeing.
In haemodialysis (HD), blood pressure was measured before and after dialysis over a period of two weeks. The systolic and the diastolic pressures were averaged. In peritoneal dialysis (PD), blood pressure was measured at a routine visit in the outpatient clinic. Mean arterial blood pressure was calculated as diastolic blood pressure+1/3 (systolic blood pressurediastolic blood pressure).
Functional status and wellbeing were determined by the Karnofsky index, scored by a physician or a nurse, and by the 36-Item Short Form Health Survey Questionnaire (SF-36) [14,15], which was completed by the patients. The scales of the SF-36 were combined into a physical component summary score (PCS-score). Higher scores in these instruments indicate a better functional status and wellbeing.
Laboratory investigations.
Blood tests included plasma urea, plasma creatinine, haemoglobin, serum albumin, calcium and phosphate. In HD, the blood samples were taken prior to a dialysis session.
Nutritional status.
Nutritional status was assessed by the body mass index (BMI), percentage of lean body mass (% LBM), serum albumin, and an estimation of dietary protein intake. Percentage of LBM was determined by measurement of skinfold thickness at four sites (biceps, triceps, subscapular, and iliac) by trained nurses. In HD patients these assessments took place after a dialysis session. The dietary protein intake was estimated as protein equivalent of nitrogen appearance (PNA) (in HD, PNA (g/24 h)=9.35xurea generation rate (mg/min)+0.294xurea distribution volume (l) [16]; in PD, PNA (g/24 h)=19+0.2134xurea appearance (mmol/24 h) [17]) normalized to actual body weight (nPNA). The urea distribution volume (V) was determined by the formulae of Watson et al. for total body water [18]. Anthropometric parameters and serum albumin were combined to a malnutrition index, corrected for age, sex, height, and frame size, as described by Harty et al. [19], but without the use of the subjective global assessment. A score of 11 or higher was defined as severe malnutrition.
Renal function and therapy.
In HD, urine was collected during the interdialytic interval and in PD during 24 h. From this collection daily urine volume, renal Kt/Vurea, renal creatinine clearance, and residual GFR (rGFR) were calculated. The latter was defined as the mean of the urea and creatinine clearances. Haemodialysis Kt/Vurea was estimated using a second-generation Daugirdas formula [20]. Peritoneal Kt/Vurea and creatinine clearance were calculated from a 24-h dialysate collection. Data on medication were collected from the medical records.
Literature search.
A Medline search was performed to retrieve references of studies providing information on co-morbidity in dialysis patients and published in the English language over the period of January 1985 to June 1998. Dialysis, survival or mortality, comorb*, and adult were used as search terms. From the retrieved references we selected studies that fulfilled the following criteria: (i) information present on co-morbid conditions at the start of renal replacement therapy of ESRD patients receiving dialysis, other than data on primary renal diseases; (ii) no restriction made to a subgroup of the adult dialysis population; the only selection permitted was one on treatment modality; and (iii) European patient population.
Analytical methods
Demographic and clinical characteristics were used to explain the variability of parameters of nutritional state and blood pressure in multivariate linear regression. A two-sided P value less than 0.05 was considered statistically significant.
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Results |
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Blood tests, nutritional status, renal function and therapy characteristics
Table 3 shows the results of the blood tests, and data on the nutritional status and residual renal function. As expected, most patients were anaemic and the mean serum albumin level was in the low normal range. Multivariate analysis showed that dietary protein intake was lower in older patients and in patients with a lower rGFR. Age and rGFR explained 20% of the variance, 15% of which was accounted for by the rGFR. We could not establish a relationship between rGFR and other parameters of nutritional state such as BMI, albumin or per cent LBM.
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Literature search
The Medline search for studies on the co-morbidity in dialysis patients resulted in the retrieval of 101 documents. Seven publications out of these fulfilled the additional selection criteria [13,2126]. One publication, which also matched the criteria but which was not found in the Medline search, was added [27]. The results are summarized in Table 4.
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Discussion |
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Time trends in co-morbidity in the Netherlands
Comparison of the age and primary renal disease of our patients with the RENINE data (mean age 1992, 56.6 years; DM 19931995, 14.2%) suggests that our sample was representative for new Dutch dialysis patients in the years 1993 to 1995 [5,6]. Only two other studies reported information on the co-morbid conditions of new Dutch dialysis patients [13,26]. Struijk et al. [26] reported a similar prevalence of systemic disease in a group of patients who started PD in the late eighties as we did in our patient population. The Dutch Nijmegen/Veldhoven (NV) subgroup in the international study of Khan et al. [13] comprised 267 patients starting renal replacement therapy on average six years earlier than our group. This NV subgroup was representative of the new Dutch dialysis patients in the late eighties with respect to age [5]. At first sight, those patients seemed more sick than ours. For a valid comparison with our patient group we then excluded from the NV subgroup all patients who died in the first 90 days of RRT. As a result, the mean age in that subgroup decreased to 52 years and the risk was reduced to low in 37%; medium in 34% and high in 29% of the patients. This still suggests more co-morbidity in the NV subgroup than in our patient population. However, as we did not have information on the distribution of the co-morbid conditions among the NV patients surviving the first 3 months of renal replacement therapy, our findings do not permit a conclusion with regard to a development in co-morbidity since 1985.
Time trends in co-morbidity in Europe
Comparison of our data with those of other European studies was only partly possible. In a Swedish single centre study, Hylander et al. [21] demonstrated an increase in age and a rise in the number of co-morbid conditions from the sixties to the eighties. Rodriguez-Carmona et al. [25] of Spain also showed an increase in age, but an increase in co-morbidity was less obvious. All other studies reported combined data over a period lasting from 2 [23] to 17 years [22] and could therefore not be used to show a trend in time.
Differences in case-mix within Europe
Only the study reported by Khan et al. [13] allowed comparison of co-morbidity between countries and centres. As they used common definitions of co-morbid disease in new ESRD populations not selected for treatment modality, and therefore less subject to patient selection bias, these authors could show that Greek patients were younger and at a lower risk than patients from other countries [13]. Although the NV subgroup had the highest percentage of high-risk patients, the difference with other centres was not statistically significant.
Other patient and treatment characteristics
Other studies reported higher [21,28], similar [29,30], or lower [3133] blood pressures than were found in our patients. In the elderly patients we found a lower diastolic blood pressure. This finding is consistent with the age-related changes in blood pressure in the general population [34]. A survey performed by the ERAEDTA Registry showed that 83% of the dialysis patients were receiving antihypertensive medication [35]. According to European standards the use of antihypertensives in our patient population was therefore relatively low.
Studies reporting the functional status of new dialysis patients are lacking. The Karnofsky index in a Dutch group of prevalent patients who had been on dialysis for almost 4 years [36] was similar to that in ours. Another cross-sectional study was performed in patients who had already been on HD for a number of years, but who were still able to participate actively in their dialysis treatment [37]. In this selected group the Karnofsky index was higher than in our patients. So far, no European data are available on the functional status and wellbeing of dialysis patients as assessed with the physical component summary score of the SF-36. DeOreo from the United States [38] reported a slightly lower score of 35 in 1000 new and prevalent HD patients with a mean age of 58 years, suggesting that these patients were more impaired than ours. This difference may be explained by the fact that part of the US patients had already been on dialysis treatment for a longer period of time. However, most differences between our data and those from other studies remain difficult to interpret because other studies comprised cross-sectional samples of selected patients groups who were heterogeneous with respect to therapy history.
Three months after the start of dialysis rGFR was 2.9 ml/min/1.73 m2. Preliminary data from the USRDS Morbidity and Mortality study showed that rGFR was 4.9 ml/min in PD patients and 3.4 ml/min in HD patients at 60 days after the start of dialysis [39]. This suggests that US PD patients may have started dialysis relatively early. Three studies have reported mean residual creatinine clearances at the time of initiation of dialysis ranging from 4.3 to 6.9 ml/min [4042]. This corresponds to 4370 l/week, which is slightly higher than the residual creatinine clearance of 40 l/week/1.73 m2 in our group. A part of this difference may be explained by the decrease in residual renal function during the first 3 months of dialysis treatment in our patients. On the other hand, the CANUSA study in PD patients reported a mean residual renal creatinine clearance of 39 l/week/1.73 m2 at the start of dialysis [10]. As the preservation of residual renal function in PD is relatively good [42], this suggests a creatinine clearance at 3 months after the start of dialysis similar to that in our group.
With regard to nutritional state, we confirmed the findings of both Ikizler et al. and Churchill who reported a decreased protein intake with diminished glomerular filtration rate [43,44]. In our study rGFR explained a substantial percentage of variance in dietary protein intake, but relationships with other parameters of nutritional state were not found. Although Churchill showed such associations in PD patients, his analyses were univariate and the reported correlation coefficients were very low, suggesting even lower percentages of explained variance.
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Conclusions |
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Appendix |
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Acknowledgments |
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The nursing and dietetic staff of the following dialysis units, who collected most of the clinical data, are gratefully acknowledged for their assistance: Medical Centre, Alkmaar; Academic Medical Centre, Amsterdam; Diatel Noord-Holland, Amsterdam; Rijnstate Hospital, Arnhem; Medisch Spectrum Twente, Enschede; Leyenburg Hospital, 's-Gravenhage; Groot Ziekengasthuis, 's-Hertogenbosch; Stichting Thuisdialyse Noord-Nederland, Haren; Streekziekenhuis, Hilversum; Dialysis Center 't Gooi, Hilversum; University Hospital, Maastricht; St. Antonius Hospital, Nieuwegein; Stichting Thuisdialyse Midden-West Nederland, Utrecht; and St. Joseph Hospital, Veldhoven.
The authors also wish to thank Ank Feller, Barbara Nijman and Roos Wisse for their assistance in the logistics of this study.
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References |
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