Abstract
Background/aims: A few patients stay on peritoneal dialysis (PD) for 5 years or longer from initiation of therapy. We investigated patient survival and factors affecting mortality in PD patients. Methods: This was a retrospective study including 354 PD patients. The demographic, clinical, and biochemical data were collected from the medical records. Two hundred patients were excluded. Evaluation was carried out on data from 154 patients, including 83 surviving 5 years or more and 71 who were taken as surviving less than 5 years. Results: Mean age, number of comorbid diseases, prevalence of diabetes mellitus (DM), rate of mandatory preference of PD, making their PD exchanges with help from anyone were lower in surviving patients, and education level was higher in surviving patients. Advanced age, high rate of mandatory preference of PD, high rate of baseline high, and high-average peritoneal transporters were associated with an increased risk of death. Conclusion: Long-term survival is possible for PD patients, particularly nondiabetics, those having higher education level, those with a self-preference of PD, and those making PD exchanges without any help.
INTRODUCTION
A few patients stay on peritoneal dialysis (PD) for 5 years or longer from initiation of therapy. All nephrologists are well aware that the 5-year survival on any form of dialysis averages only 34%. The overall 5-year mortality for dialysis patients has improved by only a modest amount.Citation1
The clinical outcomes of PD patients are affected by many factors, including age, the presence of comorbid disease, nutritional status, and membrane transport property.Citation2–6 There are some studies about mortality in PD patients in our country.Citation7,8 This is the first publication about comparison and analysis of patients’ survival in a retrospective cohort that survived on PD between 5 years or more and less than 5 years from in west Turkey. We investigated patient survival and factors affecting mortality in Turkish PD patients.
MATERIALS AND METHODS
The records of 354 patients for whom PD therapy was started due to end-stage renal disease (ESRD) in our PD unit between June 2001 and September 2011 were evaluated retrospectively. Totally 200 patients who met the following criteria were excluded: patients who recovered renal function and no longer required dialysis, patients below 18 years of age, patients with data missing (those who came from another city for the first PD control to us but inaccessible anyway after this time), patients following other PD units, patients with less than 90 days following initiation of PD, patients transferred to hemodialysis (HD), and patients who underwent renal transplantation before 5 years. Data of the remaining 154 patients were collected in paper charts and evaluated, including data of 83 patients surviving 5 years or more and 71 patients who were taken as surviving less than 5 years.
Age, gender, body mass index (BMI), educational levels of the patients, and socio-demographic characteristics such as presence of anybody helping to administer the PD (by themselves, their children, other persons like health-care workers, etc.), and the preferred way of PD (i.e., patient preference, his/her own decision or other compulsory choice, etc.) were investigated in-depth from patient records. PD preference means the preference of PD treatment by patients themselves or mandatorily because of many causes (vascular problems, cardiac problems, accessibility of the center, etc.). Follow-up time of PD therapy, whether there was a history of HD before PD therapy, and duration of HD, if present, were recorded.
We classified educational status of patients as “lower” (illiterate, primary school) or “higher” (junior high school, high school, and university and higher). Comorbidities such as cardiovascular disease (CVD), cerebrovascular events, lung disease, liver disease, and malignancy were recorded.
Systolic and diastolic blood pressure measurements, daily urine volumes, and daily mean ultrafiltration amounts of all patients were recorded at the beginning and during the last visit of PD therapy. Serum urea, creatinine, calcium, phosphorus, albumin, intact parathyroid hormone (iPTH), hemoglobin, and ferritin values were recorded at the beginning of treatment and during the last monitoring. The beginning of treatment for continuous ambulatory peritoneal dialysis (CAPD) is defined as the time after patients have been catheterized and educated, when patients start using the standard 2 L four times CAPD regimen. The beginning of treatment for APD is defined as the time that patients started PD at the necessary exchange volume. This time is approximately 2–3 weeks after PD catheter insertion. We used a standard solution containing 132 meq/L of sodium along with 3.5 meq/L calcium, 1.5 meq/L magnesium, 35 meq/L lactate, and 102 meq/L of chloride. Glucose concentrations were ordered according to volume status.
Total (peritoneal plus residual renal) weekly peritoneal urea clearance (Kt/V) and creatinine clearance (CCr) measurement and a peritoneal equilibration test (PET) were performed approximately 4 weeks after dialysis commencement. To calculate the initial clearance (Kt/V), the volume of distribution (V) was measured with the Watson formulaCitation6 using the actual body weight. BMI is defined as the individual’s body weight divided by the square of his/her height.
Infections were classified as catheter infections, either exit site infections (defined as drainage, erythema, or exit-site pain) or tunnel infections (defined as swelling or pain/tenderness with or without erythema over the catheter tunnel) for PD. Pneumonia was defined by radiologic evidence of pneumonia in the clinical setting of pneumonia. Peritonitis was defined by the presence of cloudy effluent with 100 white cells/l, with 50% of these being polymorphonuclear cells. Bacteremia and fungemia were defined by positive blood cultures. The factors associated with mortality were investigated for all patients. The patient’s survival rate was calculated from date of PD initiation to termination of PD or to the end of the follow-up (30 September 2011).
STATISTICS
We performed statistical analyses with the Scientific Package for Social Science (version 13.0; SPSS Inc.,Chicago, IL, USA). Mann–Whitney U test and Chi-square test were used for nonparametric variables. For independent and paired-samples, the t-test was used for analyzing clinical and biochemical parameters between the beginning and the last visit values. We also analyzed the risk factors and calculated their hazard ratio (HR) for patient mortality using backward logistic regression of the Cox proportional hazards method. Differences were considered statistically significant for p-values <0.05.
RESULTS
Patients’ Basic Demographics
Three hundred fifty-four patients were included in the study. Totally 200 patients were excluded from the study because of the following reasons: 1 patient’s renal functions recovered and no longer required dialysis; 6 patients were below 18 years old; 5 patients had data missing, 15 patients followed by other PD units; 6 patients’ PD histories were less than 90 days, 103 patients transferred to HD, and 64 patients underwent renal transplantation. The remaining 154 patients’ data were evaluated, including 83 patients surviving 5 years or more and 71 patients who were taken as surviving less than 5 years.
At the initiation of the study, the mean age of the study population was 48.6 ± 16.4 years, the mean follow-up duration was 54.5 ± 35.8 months. Males constituted 41.6% of patients and the mean BMI was 23.6 ± 4.3 kg/m2. Diabetes was the most common cause of ESRD (27.2%), followed by chronic glomerulonephritis (18.2%), and primary hypertension (14.3%). Demographic data of both groups are summarized in .
Table 1. Demograhics and baseline characteristics of patients.
Surviving patients had lower rates of comorbid disease (p = 0.0001) and prevalence of diabetes mellitus (DM) (p = 0.003), higher education level (p = 0.04) compared to the other group. The rates of mandatory preference of PD (p < 0.001) and making their PD exchanges with help from anyone (p < 0.001) were also lower in patients surviving 5 years or more. Other basic demographic data were not statistically different between groups at initiation of the study (p > 0.05) ().
Patients’ Clinical Parameters
At the beginning of study, total Kt/V urea (p = 0.001), total weekly creatinine clearance (WCCr) (p = 0.001), serum creatinine level (p = 0.011), serum albumin level (p = 0.001), and residual renal function (RRF) (p = 0.017) were all statistically higher in the PD survival group than in the PD non-survival group. There was no significant difference between groups in comparison with other clinical parameters (p > 0.05). In addition, PET was different between the groups (p = 0.001) ().
Table 2. Clinical and laboratory data of two groups at the beginning of PD.
Incidence of peritonitis and catheter exit site/tunnel infection attacks were found as 16.7 ± 14.4 versus 49.4 ± 31.5 patient-months and 17.9 ± 14.8 versus 63.5 ± 29.3 patient-months, respectively. They were statistically lower in the survival group than in the non-survival group (p = 0.001, p = 0.001, respectively).
Patients’ Outcomes
In non-survival group, mean follow-up time was 20.3 ± 1.9 months. Infectious events (49.3%) were the most important cause of death (). Cause of infection was classified as peritonitis (n = 23), pneumonia (n = 5), or infection of unknown focus (n = 7). A multivariate Cox proportional hazards regression model revealed that advanced age (RR = 1.057, p = 0.021), mandatory preference of PD (RR = 0.999, p = 0.049), high rate of baseline high and high-average PET (RR = 0.181,p = 0.008), low serum albumin level (RR = 0.333, p = 0.002), high peritonitis status (RR = 0.056,p = 0.001), and last RRF (RR = 1.006, p = 0.003) were significantly associated with an increased risk of death.
In the survival group, mean follow-up time was 88.7 ± 2.9 months. The descriptive statistics of the results are given in . Statistical analysis showed a significant increase in serum albumin (p = 0.037), serum Ca (p = 0.0119), Hb levels (p = 0.001), and decrease in serum P level (p = 0.001) and RRF (p = 0.001). By 30 September 2011, 41 patients were still on PD, 7 patients had undergone renal transplantation, 14 patients had been transferred to HD, and 21 patients had died. The most common cause of death was cardiovascular events (47.6%) (). The causes of cardiovascular events were classified as coronary artery disease (n = 3), congestive heart failure (n = 5), and cardiac arrhythmia (n = 2). The Cox proportional hazards regression model revealed that self-preference of PD (RR = 0.001, p = 0.004) and initial high RRF (RR = 0.854, p = 0.013) were factors affecting mortality significantly.
Table 3. Comparison of baseline and last parameters of patients surviving 5 years or more.
Table 4. Causes of death according to groups.
Even though the most common cause of death is different in both groups, there was statistically no relationship between comparison of causes of death in both groups (p > 0.05).
DISCUSSION
In patients surviving 5 years or more, there was a lower prevalence of DM, comorbid diseases, and peritonitis. Additionally, these patients had higher education level, higher serum creatinine and albumin levels, and initial RRF. In these patients, mortality rates due to cardiovascular events were high. Influential factors on mortality were self-preference of PD and initial high RRF.
Advancing technologies, earlier referral, and better management of comorbid disease states and infections have all positively impacted the mortality rate of the dialysis population. The mortality rates of ESRD have significantly declined over the past decade. Similarly, adjusted 5-year survival on PD has improved 7.5% between the 1992–1996 and 1997–2001 periods, and is now similar for HD and PD patients at 33.5% and 33.9%, respectively.Citation9,10 There are several patient factors affecting survival on PD, most of which are non-modifiable (such as age, presence of diabetes, ESRD etiology, etc.). All the modifiable factors (such as RRF, peritoneal membrane integrity, and PD-related infections) are strongly associated with long-term survival in PD patients.Citation11
The number of elderly patients with ESRD is increasing worldwide. Previous data indicate that age and presence of comorbid conditions play a significant role in dialysis mortality.Citation12–14 Lim et al.Citation15 showed that elderly patients have higher peritonitis-related and all-cause mortality, which are likely to be the consequence of greater prevalence of comorbid diseases. However, compared with younger patients, elderly patients have superior technique survival and similar peritonitis-free survival.
In general, education has been shown to have a positive impact on different health aspects and life expectancy.Citation16 Similar reports suggest that a higher education level is associated with improved survival in patients on dialysis.Citation5,17 We showed better survival rates as the education levels of PD patients increase like Kleinpeter et al.’sCitation18 study. In our study, patients living 5 years or more were younger, have higher educational status and a lower rate of comorbid conditions. Therefore, adjustment for age, educational status, and comorbid conditions are essential when comparing mortality data.
In our country, similar to the rest of the world, the most common cause of ESRD is diabetic nephropathy. Patients with diabetes have 30% increased risk of death compared with nondiabetic patients. It is likely due to the high prevalence of CVD and metabolic complications in this population.Citation19,20 In our study, diabetes was the most common cause of ESRD. Despite the high rate of detection of DM in patients living less than 5 years, it did not affect patient survival significantly.
Patients with CKD should be incorporated into educational programs on time to allow optimal choice of a dialysis method based on patient preference as well as medical indications and contraindications.Citation21 PD requires a significant patient compliance, family support, and a clear understanding about the application technique. As the first choice of treatment modality, PD should be applied treatment under suitable conditions. Own wishes is reported to be altering the survival rates favorably.Citation22
We found in our study that the patient preference may affect the patient’s survival. In other words, patients undergoing PD mandatorily have lower survival rates. Additionally, patients living less than 5 years generally needed assistance for their PD exchanges.
In dialysis patients, the serum creatinine level is proportional to skeletal muscle mass and dietary protein intake. The serum creatinine level is a valid and clinically useful marker of protein-energy nutritional status in maintenance dialysis patients. The serum creatinine level which reflects the nutritional status is inversely related to mortality rates in patients undergoing PD.Citation23 In our study, patients with higher creatinine levels at the beginning of treatment had higher survival rates similar to the results of studies from Turkey carried out by Sipahioglu et al.Citation8 and Sarı et al.Citation24
PD patients may be severely hypoalbuminemic at the initiation of dialysis and may potentially remain at higher risk of malnutrition due to the constant protein loss in the effluent, which is significantly higher among high peritoneal transporters and during episodes of peritonitis.Citation25
Some previous studies showed that low serum albumin is an independent predictor for mortality risk in PD patients. Serum albumin levels were found to affect patients’ survival in our study. In dialysis patients, 1 g/dL decrease in serum albumin was associated with 38% increased mortality risk in PD patients. This mortality risk has been partially explained by the inflammatory pathway and thought to be a consequence of malnutrition.Citation26
RRF not only provides small-solute clearance but also plays an important role in maintaining fluid balance, phosphorus control, and removal of middle-molecular uremic toxins. It shows a strong inverse relationship with valvular calcification and cardiac hypertrophy in dialysis patients.Citation27 In addition, preservation of RRF is as important as preservation of the long-term viability of the peritoneal membrane. RRF is an important determinant of survival on dialysis. Each 1 mL/min of RRF [measured as the glomerular filtration rate (GFR)] is associated with a nearly 50% reduction in the rate of mortality.Citation28 Our study showed that in the survival group, initial RRF was higher, an effective factor on mortality rates. Initial high RRF combined with the RRF preservation may help to improve the survival of PD patients.
PD patients have different peritoneal membrane transport properties. These properties significantly affect both patients and technique survival. High transport status is a well-known risk factor for mortality in PD patients.Citation29 A meta-analysis of 20 observational studies also demonstrated that a higher peritoneal membrane solute transport rate was associated with a higher mortality risk and a trend toward higher technical failure.Citation30
In this study, we found that there was a significant difference in peritoneal membrane transport properties between two groups. The patients surviving 5 years or more had higher low-average transporters.
Peritonitis continues to be a major complication of PD. Peritonitis is not only the leading cause of technique failure but it also contributes to the mortality.Citation31,32 Fried et al.Citation33 studied the influence of peritonitis on mortality in 516 patients in a single PD unit, demonstrating lower survival rates in patients with more than one episode of peritonitis every 25 months. Sipahioglu et al.Citation8 published their experience with 423 patients, also from one single center, demonstrating an increased risk of death in patients with a higher incidence of peritonitis. The median survival of individuals with more than 1.25 episodes of peritonitis per patient year was reported to be 30 months shorter when compared to those with fewer episodes.Citation33 Our study demonstrated that, in non-survival group, peritonitis incidence was 16.7 ± 14.4 patient-months. Peritonitis status was associated with an increased risk of death.
The mortality rate of dialysis patients is eightfold higher than in age and gender-matched controls and in the United States, fewer than a third are alive after 5 years of maintenance dialysis therapy.Citation34 This high mortality is largely a result of high prevalence of CVD. Infection is the second most common cause of death.Citation35 The majority of studies in long-term PD patients do not provide detailed information about how these patients die.
The best data describing the cause of death come from the Italian studies, in which sudden or cardiovascular deaths account for 45–47%, cachexia and malignancy for 23–25%, sepsis for 12–13%, and miscellaneous causes comprising the rest.Citation36,37 Tse et al.Citation38 demonstrated that long-term survival is possible for both dialysis modalities (PD and HD), particularly for young, nondiabetic patients. They also showed that cardiovascular-related problems remain the leading cause of death. In our study, the most common cause of death was cardiovascular events in patients surviving 5 years or more. Besides this, the most common cause of death in patients surviving less than 5 years was infection events. The possible explanation for this may be characteristics of our study population in this group, that is, advanced age, higher mandatory preference rate of PD, lower education and serum albumin levels, and PD exchange rates by themselves.
CONCLUSION
Patients surviving 5 years or more have lower prevalence of DM, comorbid disease, and lower peritonitis rate; high education, serum creatinine, albumin, and initial RRF levels. CVD-dependent mortality rate was high in this group. Self-preference of PD, and initial high RRF values were effective factors on mortality.
In patients surviving less than 5 years, obligatory preference of PD, low serum albumin level, high rate of peritonitis, abundance of ones with high and high-average PET transporters, and decreased RRF values were predictors of poor patient survival. Infection-event-related mortality was high in this group.
Physicians should make every effort to achieve low peritonitis rate, ensure adequate nutrition, and preserve RRF in PD patients to improve the survival of long-term PD patients.
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
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