Abstract
Despite improvements in dialysis therapy, the mortality rate of patients with end stage renal disease (ESRD) has remained high. A relatively high proportion of uremic patients dies within one year after the initiation of dialysis treatment. The aim of this study was to evaluate predictors for this early mortality in patients with ESRD. A total of 66 uremic patients were included in the study. Patients were divided in those who survived <1 year (n = 17) and those who survived ≥1 year (n = 49). We compared the prevalence of diabetes and hypertension and of vascular diseases as well as the prevalence of heart insufficiency (EF<30%) and left ventricular hypertrophy (LVH). Additionally, we estimated the laboratory parameters serum creatinine, creatinine clearance, BUN, cholesterol, triglycerides, fibrinogen, serum protein, serum albumin and hemoglobin, and evaluated the indications for the initiation of dialysis therapy in both patient groups. The patients with survival <1 year were significantly older (64 ± 12 vs. 54 ± 14 years, p<0.01) and showed a lower BMI (22 ± 3 vs. 25 ± 3, p<0.01) than those who survived >1 year. The prevalence of diabetes (70% vs. 31%, p<0.05), cardiac insufficiency (70% vs. 16%, p<0.025), cardiovascular disease (65% vs. 28%, p<0.05) and peripheral vascular diseases (70% vs. 28%, p<0.05) was significantly higher in the patients with early mortality. The prevalence of hypertension was similar in both groups, however, the prevalence of LVH was significantly higher in the patients who survived <1 year (88% vs. 37%, p<0.05). Laboratory parameters were not significantly different in the two groups of patients, with the exception of serum albumin, which was significantly lower in the patients with early mortality (3.5 ± 0.6 vs. 3.9 ± 0.4 g/l, p<0.02). Hyperhydration was the most common indication for the start of dialysis in patients with early mortality (59% vs. 13%, p<0.025). Cardiac insufficiency was the most common cause of death in these subjects (n = 10, 59%). Six individuals (12%) died within four weeks after initiating dialysis therapy. Thus, there are several predictors for early mortality in end-stage renal disease patients, including high age, low BMI, the presence of diabetes, coronary heart disease, heart insufficiency and LVH, as well as low serum albumin levels. A relatively high percentage of patients die shortly after the start of dialysis therapy. Heart insufficiency is the most common cause of early death in these patients.
INTRODUCTION
Several factors such as nutritional status and adequate dose of dialysis influence the survival rate of patients on chronic hemodialysis Citation[[1]], Citation[[2]]. Despite improvements in dialysis technology and overall improvements in healthcare, the mortality rate of patients with end-stage renal disease (ESRD) remained high at approximately 20% Citation[[3]]. Moreover, a relatively large proportion of uremic patients die early after the start of renal replacement therapy, and many of them suffer from coronary heart disease and heart insufficiency Citation[[4]], Citation[[5]]. Some of these patients die immediately or within four weeks after the start of dialysis therapy, and some of them are not registered as “chronic” dialysis patients in the national registries. Published data concerning the reasons for the especially early mortality of uremic patients are scarce.
The aim of our study was to evaluate the predictors for this early mortality in patients with ESRD. We investigated the characteristic features of patients on chronic dialysis who died within one year in comparison to dialysis patients who survived longer. Additionally, we compared the predialysis management of both patient groups.
PATIENTS AND METHODS
The study was carried out in 66 patients (45 male, 21 female) who had started maintenance hemodialysis therapy (n = 60) or CAPD (n = 6) in 1997 and 1998 at our dialysis center. Patients who died immediately or within four weeks after initiating dialysis treatment (n = 6) were also included. The end points of the study were death of the patients or expiry of the observation period of at least 12 months of dialysis therapy. Those who received a kidney graft during the observation period (n = 2) were excluded from the study. We divided the patients into two groups–-those with and without early mortality (survival<12 months)–-and compared their primary renal diseases. The clinical characteristics of both patient groups are summarized in . Diagnosis of diabetic nephropathy was based on the onset of persistent proteinuria (>0.5 g protein/24 h-urine) with normal urine sediment and normal kidney sonography. The diagnosis of vascular nephropathy was based on the demonstration of normal urine sediment without proteinuria and reduced kidney size in ultrasound investigation. The diagnosis of glomerulonephritis and interstitial nephritis was established by renal biopsy.
Table 1. Clinical Characteristics of Chronic Dialysis Patients Who Survived <One Year and One Year After Initiation of Dialysis Treatment
For each group, we estimated the renal function parameters creatinine clearance (based on 24-h creatinine clearance determination), serum-creatinine and BUN, as well as the parameters for nutritional status Citation[[6]] serum-cholesterol, triglycerides, fibrinogen, total serum protein, serum albumin and hemoglobin (Hitachi autoanalyzer) at the start of dialysis therapy. In addition, we evaluated the prevalence of diabetes, hypertension, vascular disease, cardiac insufficiency and LVH in both groups. Cardiac insufficiency was defined as ejection fraction <30%. Cardiac insufficiency and LVH were diagnosed by echocardiographic investigation (Ultrasound Scanner 3.5 MHz, Ultramark 5 and Ultramark 9). Cerebrovascular disease was defined as lumen narrowing plaques of the carotic artery in a Doppler sonographic investigation or as a stroke in history (Linear Ultrasound Scanner 7.4 MHz, Ultramark 5 and Ultramark 9). The diagnosis of cardiovascular disease was based on ischemic changes in an electrocardiogram or a myocardial infarction in history. Peripheral vascular disease was diagnosed in the presence of intermittent pain or amputation of the lower leg.
We also compared the percentage of patients on erythropoietin therapy and controls in the outpatient care unit (>one control/year) during the predialysis period, and evaluated the indications for the start of dialysis therapy in both patient groups.
The initially prescribed dialysis therapy was 240 min per session three times per week. The average dose of hemodialysis per week at the end of the study was 13.2 ± 0.4 h in the patients with early mortality and 13.4 ± 0.6 h in the group with late mortality (NS).
In patients who died within the 12 month observation period, the causes of death were established clinically or by autopsy (n = 10). The causes of death were heart insufficiency (n = 10), myocardial infarction (n = 1), sepsis (n = 2), malignant diseases (n = 2), pneumonia (n = 1) and myocarditis (n = 1).
Statistics
Results were usually expressed as means ± S.D. For statistical analysis, we used the unpaired Students t-test to compare differences between the groups and the chi-square test to compare prevalences. The level of statistical significances was chosen as p<0.05.
RESULTS
Patients with early mortality were significantly older (64 ± 12 vs. 54 ± 14 years, p<0.01) and had a lower BMI (22 ± 3 vs. 25 ± 3, p<0.01) than those with late mortality. The most common primary renal disease was diabetic nephropathy (53%) in the patient group with early mortality and glomerulonephritis (36%) in the other group, as shown in .
During the pre-dialysis period, only 47% of the patients with early mortality received erythropoietin substitution in contrast to 73% of the patients who survived longer (NS). Additionally, during the same period, the percentage of patients with controls in the outpatient care unit was significantly lower in the patient group with early mortality (23% vs. 67%, p<0.05). The most common indication for the start of dialysis therapy was hyperhydration in 59% of the patients with early mortality, in contrast to 13% of patients who survived longer (p<0.025). Dialysis therapy was started at the planned date without uremic symptoms in no subject with early mortality, but in 53% of the patients who survived for more than one year (p<0.02). The indications for the start of dialysis therapy in both groups of patients are summarized in .
Table 2. Indication for Initiating Dialysis Treatment in Patients Who Survived <One Year and ≥ One Year of End-Stage Renal Disease
The parameters for renal function at the start of renal replacement therapy were not significantly different in the two groups; mean BUN values were only marginally higher in the individuals with early mortality (116 ± 41 vs. 92 ± 21 mg/dl, NS). At the same time, patients with early mortality showed significantly lower serum concentrations of albumin (3.5 ± 0.6 vs. 3.9 ± 0.4 g/l, p<0.02) which served as a parameter for nutritional status and indicator for prognosis. All other measured laboratory parameters were not significantly different in the two patient groups, as shown in .
Table 3. Laboratory Parameters at the Beginning of Dialysis Treatment in the Patients Who Died <One Year and ≥ One Year of End-Stage Renal Disease
Comparing the risk factors for life, the prevalence of diabetes (70% vs. 31%, p<0.05) and heart insufficiency (70% vs. 16%, p<0.025) as well as LVH (88% vs. 37%, p<0.05) were significantly higher in the patients with early mortality. These patients also had a higher prevalence of cardiovascular diseases (65% vs. 28%, p<0.05) and peripheral vascular diseases (70% vs. 28%, p<0.05) in comparison to the group with better survival. All risk factors for life are summarized in .
Table 4. Risk Factors for Life in the Dialysis Patients Who Survived <One Year and ≥ One Year After Initiation of Dialysis Treatment
DISCUSSION
The mortality rate of patients with ESRD is still high at approximately 20% Citation[[3]], and is due to several causes such as inadequate dialysis, malnutrition, patient non-compliance and other comorbid conditions Citation[[7]], Citation[[8]], Citation[[9]], Citation[[10]], Citation[[11]], Citation[[12]]. In addition, well known predictors of mortality in uremic patients are age and diabetic status Citation[[13]]. Cardiovascular disease is a major cause of morbidity and mortality among patients with chronic renal disease. Mortality secondary to cardiovascular disease is approximately 15 times higher in dialysis patients than in the general population Citation[[14]]. A relatively high percentage of uremic patients die within the first year and some of them die immediately or shortly after the initiation of dialysis treatment. In our study, 17 patients (26%) died within 12 months after the start of renal replacement therapy, six of them died within four weeks. Several characteristic features were observed in our patients with early mortality (survival<1 year) in comparison to those who survived longer. Patients with early mortality were significantly older, had a lower BMI and a higher prevalence of concomitant diabetes as vascular risk factor. Moreover, there was a significantly higher prevalence of coronary heart disease, peripheral vascular disease and heart insufficiency (EF<30%) as well as LVH in the patients with early mortality. In addition, the mean serum albumin level as predictor for mortality was significantly lower in these patients. All other laboratory parameters were not significantly different between the two groups of patients.
The poor prognosis of patients with heart insufficiency is well known, especially in patients with ESRD the mortality is very high Citation[[14]], Citation[[15]], Citation[[16]]. In our study, heart insufficiency was the most common cause of death (59%) in patients with early mortality. Despite continuous research, the range of effective drug therapies is still limited. In patients on hemodialysis, the intermittent weight gain and fluid loss during dialysis therapy leads to large volume changes in the heart. Especially in uremic patients with LVH, an overhydrated state may cause pulmonary congestion, and, conversely, a rapid volume loss during dialysis with ultrafiltration may result in severe hypotension Citation[[15]], Citation[[17]].
Several studies have shown that comorbid conditions at the initiation of dialysis treatment are important predictors of mortality for both hemodialysis and peritoneal dialysis Citation[[18]]. It is also well known that diabetic patients who require dialysis treatment show a lower survival rate than nondiabetic dialysis patients of the same age. However, in an earlier study, it was demonstrated that in type 2 diabetic patients with ESRD, mortality is also high in the predialysis period Citation[[19]].
Some authors reported that earlier dialysis therapy may be a way of improving the life expectancy of this population Citation[[20]]. In our present study, only a small percentage of patients with early mortality were controlled at our outpatient care unit during the pre-dialysis period, and the most common indication for the start of dialysis therapy was hyperhydration and fluid lung respectively (59%). Dialysis therapy was initiated at the planned date in 53% of our patients with longer survival but in none of the individuals with early mortality.
The calculated 1-year survival rate for all patients requiring renal replacement therapy (n = 68) was 75%. In many dialysis centers, uremic patients who die immediately after the start of dialysis therapy are not classified as “chronic” dialysis patients. Excluding those individuals who died within four weeks (n = 6/12%), the 1-year survival of our chronic dialysis patients was 84%, which is in agreement with the data in the literature Citation[[1]], Citation[[3]].
In conclusion, the predictors for early mortality in end-stage renal disease patients include age, BMI, presence of diabetes, coronary heart disease, heart insufficiency, left ventricular hypertrophy and low serum albumin concentration. Approximately 10% of the uremic patients die within four weeks after the start of dialysis therapy. Cardiac insufficiency is the major cause of early mortality in patients with end stage renal disease. Effective predialysis nephrologic care and earlier dialytic therapy may be a choice for improving the prognosis of these patients.
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