Characteristics and prognostic outcome factors in elderly peritoneal dialysis patients:a prospective observational study

Background: This study aimed to analyze the characteristics, outcomes and prognosis factors of survival in elderly peritoneal dialysis patients, so as to better understand the status of elderly peritoneal dialysis patients and improve their quality of life. Methods: This study was a prospective, observational study that included peritoneal dialysis (PD)patients.Categorizing by age, elderly group aged ≥ 65, younger group aged < 65. Clinical characteristics, survival and transferring to hemodialysis were compared between two groups.Meanwhile, risk factors for death in elderly PD patients were explored. Results: A total of 202 PD patients were enrolled, including 61 in elderly group and 141 in younger group. Among elderly individuals,serum albumin and normalized protein catabolic rate(nPCR) decreased, the incidence of previous cardiovascular, cerebrovascular diseases and Charlson Comorbidity Index(CCI) were higher.The major primary disease in elderly patients was diabetic nephropathy, signi�cant differences were found between elderly and younger group(P < 0.01). The mortality in elderly group was substantially higher, 27 patients (44.3%) died in elderly group and 21 patients(14.3%) died in younger group .The 1-year,2-year,3-year,4-year survival rate were 81.97%, 70.49%, 60.66%, 55.74% respectively. Cardiovascular disease was the main cause of death in elderly PD patients. Higher BMI, CCI, and previous ischemic heart disease were risk factors for long-term survival of elderly PD patients. Compared with the younger group, elderly patients were less likely to transfer to hemodialysis: 2 cases (3.3%) in elderly group and 23 cases (16.3%) in younger group. Peritonitis was the primary reason for converting to hemodialysis(HD) in both two groups. Conclusions: Poor nutrition, more complications and diabetic nephropathy were characteristics of elderly PD patients. High BMI, CCI and previous ischemic heart disease were independent predictors of death in elderly PD patients. Cardiovascular disease was the main cause of death in elderly PD patients(cid:0)while the chief reason of transferring to hemodialysis


Background
Chronic kidney disease is a global public health problem and becoming increasingly common.A survey in China found that patients with chronic kidney disease stage 3(CKD3) were about 1.2million in 2012, and the average age was 63.6 years [1].With the development of CKD to the end stage, peritoneal dialysis has become one of the main renal replacement therapies and a better choice of elderly patients with end stage renal disease because of its small in uence on hemodynamics, protection of residual renal function, low cost and simple operation [2].
Elderly PD patients have unique clinical characteristics, and incline to have multiple comorbidities, including diabetes, hypertension, cardiovascular and cerebrovascular diseases [3].Many factors can in uence the clinical outcomes of elderly PD patients such as comorbidities, complications, age and nutritional de ciency [4,5].However, previous studies were mainly retrospective studies, and the in uencing factors of death varied in different countries.Some studies had shown that death was the main reason for patients to withdraw from peritoneal dialysis,moreover, age and peritonitis are the risk factors for patients to withdraw from peritoneal dialysis [6,7].However, there are few reports about the causes of withdrawal from PD in China, especially transferring to hemodialysis.
In this study,we intended to analyze the characteristics, prognosis (death, transferring to hemodialysis) of elderly PD patients by comparing with younger group, and assess the in uencing factors of mortality in elderly patients.

Patients and groups
The study was approved by the ethics committee of the Cangzhou Central Hospital in Cangzhou City, Hebei Province, China.Written informed consent was attained from each patient.202patients who received continuous ambulatory peritoneal dialysis from January 2016 to January 2017 in the Department of Nephrology of Cangzhou Central Hospital were enrolled in this prospective observational study.They did the exchange themselves only after successful training by primary nurses.Conventional PD solutions (Dianeal 1.5%,2.5%,or 4.25% dextrose; Baxter Healthcare, Guangzhou, China), Y-sets, and twin-bag systems were used.According to age, PD patients were divided into elderly group (age ≥ 65) and younger group(age < 65).Elderly was de ned as ≥65 years old at PD initiation.Patients should met the following criteria: age > 18 years old, rst peritoneal dialysis treatment and dialysis time more than 3 months, complete data.The exclusion criteria included incomplete data, loss of follow-up, those who did not cooperate with follow-up, transferred to other dialysis centers, Additionally, we did not include patients who was diagnosed as acute renal failure, multiple organ failure.End of follow-up was de ned as the day of the outcome (death or transfer to hemodialysis) or end of follow-up (January 2020).

Demographic and clinical data collection
The demographic data including gender, age, body mass index(BMI), etiological diagnosis (diabetic nephropathy, hypertensive renal damage, primary glomerular disease), peritonitis, bacterial culture results (gram-positive or gram-negative bacilli) were collected.We also recorded outcomes of patients: continue PD, death, transferring to hemodialysis, kidney transplantation and time of death, reasons of death, causes of transferring to hemodialysis.The chalson index of comorbidity (CCI) was used to measure comorbidity [8].The following variables were recorded: white blood cells (WBC), red blood cells (RBC),hemoglobin (HGB), platelets (PLT), albumin, alanine aminotransferase (ALT), aspertate aminotransferase (AST), total bilirubin, direct bilirubin, serum creatinine, urea nitrogen, serum calcium, potassium, sodium, ferritin, total Kt/ V value, residual Kt/ V, weekly creatinine clearance rate(WCcr), residual creatinine clearance rate, nPCR, dialysis time; whether the patients used angiotensin-converting enzyme inhibitors/angiotensin receptor blocker (ACEI / ARB) drugs, ever had cerebrovascular disease, ISD, heart failure or not.All blood samples were measured with commercial kits and an autoanalyzer.The albumin level was measured by using the bromocresol green method.Total Kt/V was calculated as the sum of residual renal Kt/V and peritoneal Kt/V using the urea clearances from 24-h urine and dialysate e uent collections by standard methods [9].Protein catabolic rate normalized to body weight (nPCR) was measured by Manbu E-Heath Technology(Beijing),using 24-h urine and dialysate e uent collections [10].

Statistical analysis
Data analyses were performed by SPSS23.0 and R 3.6.1 version.
Results were expressed as mean ± standard deviation (SD) , median and inte rquartile ranges, numbers and percentages (%), as appropriate.
Kolmogorov-Smirnov test was used to examine the normality of all numeric continuous variables.Independent sample t-tests were used if with a normal d istribution.Nonparametric tests (Mann-Whitney U test) were used to examine variables without a normal distribution , when comparing between groups.
Categorical data were compared between elderly and younger groups by chi-square test.When there was only less than 5 observations in an group-outcome combination, Fisher's test was used.The Kaplan-meier survival curve was performed to investigate the difference of survival and transferring to hemodialysis between the elderly and the younger group.Multivariate Cox regression analysis was used to screen risk factors of mortality in elderly patients.Using the backward method , the entry probability was set as 0.05, and the removal probability was set as 0.10.R 3.6.1 version was constructed to draw nomogram map for building model to predict survival.All tests were two-sided, and P values <0.05 were considered statistically signi cant.

General characteristics of elderly patients
We enrolled 202 PD patients, including 61 in elderly group and 141 in younger group, with a median follow-up time of 44 months (Figure 1).Compared with the younger group, elderly patients were more likely to have lower albumin and nPCR, more comorbidity, especially with cardiovascular and cerebrovascular diseases.Diabetic nephropathy was common in elderly group , the difference was statistically signi cant (P < 0.01).Table 1 showed baseline characteristics of patients grouped by age(see below).

Outcomes of elderly patients
To the end of the study, 121 (59.9%) patients continued to receive PD, 48 (23.8%) died, 25 (12.4%) were transferred to hemodialysis, 8 (3.9%) received a kidney transplantation.Among elderly group, 27 (44.3%)died, 2 (3.3%) were transferred to hemodialysis, and 1 (1.6%) received a kidney transplantation.Due to small number of kidney transplantation patients in elderly group, the following was not further discussed.Table 2 showed the outcomes of all peritoneal dialysis patients.
(Figure 2 Kaplan-Meier survival curve between elderly and younger patients )The survival time of elderly group was signi cantly lower than that of younger group.The 1-year, 2-year, 3-year and 4-year survival rate were 81.97%, 70.49%, 60.66% and 55.74% respectively.The main cause of death in elderly PD patients was cardiovascular disease, while in younger group was infection.Table 3 Transferring to HD in elderly patients 2 3.3% elderly PD patients, 23(16.3%)younger group transferred to HD. Elderly patients with PD were less likely to convert to HD. Peritonitis was the chief reason for both elderly and younger PD patients to transfer to HD (Table 4).

Prognostic mortality factors in elderly PD patients
For elderly PD patients, univariate analysis Cox regression analysis indicated that BMI, CCI, previous ISD, peritonitis, dialysis time were the risk factors for the long-term survival of the elderly PD patients.BMI, CCI and ISD remained independent signi cant predictors of long-term survival of elderly PD patients by multivariate Cox regression analysis (Table 5 and Figure 3).The impact of peritonitis,dialysis time disappeared in multivariate analysis.The survival model of elderly PD was establish ed by R 3.6.1 version(Figure4).CCI was related to peritonitis (r = 0.471, P < 0.001) and dialysis time (r = 0.260, P = 0.043), these may be a confounding factor.

Discussion
With the aging of the population, spiraling rates of end stage renal failure have increased and the elderly needing for PD is gradually increasing [11].In order to improve the prognosis and quality of life in elderly patients with PD, it is especially important to explore the survival status of elderly patients and actively prevent and control the risk factors.
We analyzed the general condition of the elderly patients, the reasons for withdrawal from PD therapy, and the risk factors for survival of patients, to provide guidance for improving prognosis and prolonging the survival time of patients on PD with ESRD.
Compared with the younger group, elderly group of PD patients tended to have hypoalbuminemia and low nPCR, both of which are important indicators to evaluate the nutrition of patients [12], this result was consistent with the Kholshali et al study [13].Wang XX et al also reported that serum albumin remained lower in elderly patients [14].In the course of PD treatment, a large number of nutrients are lost in dialysis solution, and the absorption capacity of gastrointestinal function is decreased in elderly patients, leading to malnutrition.Peritoneal dialysis does not need to establish vascular access, has little impact on hemodynamics, so elderly patients with diabetes tend to choose PD.Arteriosclerosis and the incidence of cardiovascular ,cerebrovascular events is often occurred in diabetic nephropathy [15,16].Age is also a risk factor of vascular calci cation [17].Some studies have shown that elderly PD patients are inclined to develop peritonitis [18], but there was no difference in the incidence of peritonitis between elderly and younger group in this study, which was consistent with a Canada study.It was reported that elderly PD patients who were 70 years old or more had no relationship with peritonitis [19], considering that elderly patients had better family,social support and were treated with advanced antibiotics.
In this study, the mortality of elderly patients with PD was signi cantly higher than that of younger patients.Age is a risk factor for survival of PD patients [4,20].The 1,2,3,4 year survival rates of elderly PD patients were as follows: 81.97% , 70.49% , 60.66% , 55.74% .A study in China found that the 1 -, 3 -, and 5-year mortality of elderly patients with PD respectively were 79%, 56% and 30% [21], which was generally consistent with our results.Cardiovascular disease was the leading cause of death, 53.4% of elderly PD patients existed with cardiovascular complications in a retrospective study [21].The USRDS data showed that cardiovascular events were the main cause of death in dialysis patients [22], which was related with the metabolic abnormalities and the increased incidence of diabetic nephropathy in elderly PD patients.
In this study,we provided evidence that high BMI, high CCI and ISD were independent risk factors for predicting death in elderly PD patients.Patients with high BMI were inclined to have high risk of dialysis [23], and obesity could increase cardiovascular and cerebrovascular events, thus increasing the risk of death [24].However, the relationship between BMI and survival in elderly patients with PD is controversial.Some studies found that obese PD patients lived longer than those with lower BMI [25,26] considering that patients with lower BMI will increase protein consumption and in ammation, and high BMI can increase hemodynamic stability and the isolation of fat tissue from toxins [27].Another study found that baseline BMI was not related to the prognosis of peritoneal dialysis [28], so more studies are needed to explore the relationship between BMI and death in elderly PD patients.As mentioned, CCI was an important index to evaluate the complications.Sandrine genestier et al showed that CCI was positively correlated with the mortality of elderly patients [29].A retrospective analysis of 292 patients found that 2year survival rate of elderly patients with CCI score > 9 was 38%, and that of patients with CCI < 7 reached 69% [30].Elderly PD patients often suffer with ISD, and the risk of recurrence with cardiovascular and cerebrovascular events increases [31],so elderly PD patients are at high risk of death.
In this study, peritonitis was main cause of transferring to hemodialysis in both elderly and younger patients.Minli et al. [32] and Sakaci et al. [33] also found that the main cause of turning to hemodialysis was peritonitis.Elderly patients turning to hemodialysis was fewer than that of younger patients.Elderly patients had a higher risk of peritonitis-related and all-cause mortality.In a recent study from Brazil, the only factor associated with death during peritoneal infection was age [34],so elderly patients had no chance to transfer to HD.This study elucidated the characteristics of elderly PD patients, the prognosis of elderly PD patients and the risk factors for predicting death, which help nephrologists better understand the characteristics of elderly PD patients and improve the prognosis of patients.However, this study has some limitations.First of all, this study was a single center, relatively small sample study, which could not represent the situation of elderly PD patients in China, additional multiple studies are needed in larger populations to con rm the conclusion of our study.In addition, we did not analyze economic and social situation of each patient.

Conclusions
In conclusion,compared with younger group, elderly PD patients had poor nutritional status, more complications, majority of diabetic nephropathy and high mortality.High BMI, high CCI and previous ISD events were the independent risk factors to predict mortality of elderly PD patients.Cardiovascular disease was main cause of death in elderly group.Peritonitis was major reason for transferring to HD inPD patients.

Declarations Ethics approval and consent to participate
The study was approved by the ethics committee of the Cangzhou Central Hospital in Cangzhou City, Hebei Province, China.Written informed consent was attained from each patient.

Not applicable
Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available due to local regulations on the management of medical records but are available from the corresponding author on reasonable request.

Not applicable
Authors' Contributions SF and MX: project development, data collection, and management, data analysis, manuscript writing and revising; XH: data collection, data analysis; XH: manuscript editing and revising; All authors have read and approved the manuscript.
clearance rate Residual Ccr residual renal creatinine clearance rate Total Kt/v total weekly urea clearance Residual kt/v residual renal weekly urea clearance DM diabetes mellitus HRD hypertensive renal damage ISD ischemic heart disease HF heart failure DN Diabetic Nephropathy CG chronic glomerulonephritis ACEI Angiotensin-Converting Enzyme Inhibitors

Figure 1 Flow chart of the participants in this study Figure 2
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Figure 3 Cause
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