Quality of Life and Health Status among those receiving Renal Replacement Therapy in Trinidad and Tobago. West Indies.

Background A cross sectional study was conducted over a 1-year period in order to evaluate quality of life and health state for patients receiving renal replacement therapy in a resource constrained Caribbean island of Trinidad and Tobago. Methods Five hundred and thirty patients were enlisted in the study. For those who had received renal transplants (n=100) and for those on peritoneal dialysis (n=80), all were included. Among the 1000-odd patients who were receiving haemodialysis 350 were studied using convenience sampling. To be included, one had to be on renal replacement therapy for 3 months or more and at least 18 years of age. The Kidney Disease Quality of Life (KDQOL-36) and the EuroQol (EQ-5D-3L) instruments were administered after demographic data were collected. Transplant recipients were further evaluated with the Kidney Transplant Questionnaire (KTQ). Inferential analysis of data included 95% condence intervals, hypothesis testing, multiple regression and analysis of variance. SPSS24, STATA14 and MINITAB18 were used. Results Of the 530 patients, 52.5% were male and 37.5% were in the 56-65 years age group. Hypertension (68.9%) and type 2 diabetes mellitus (50.5%) were reported as the main causes of kidney disease. The KDQOL-36 domain scores and signicantly associated variables included modality of renal replacement (p=0.000), age (p=0.001), Charlson’s Comorbidity Index (p=0.001), income (p=0.000) and employment status (p=0.000). Transplant patients performed the best in the KDQOL-36. The mean visual analogue scale and index scores from the EQ-5D-3L were highest among renal transplant recipients (p=0.000). Conclusion Renal transplant recipients enjoy the best quality of life and health state among patients on renal replacement therapy in Trinidad and Tobago.

to all patients once they are deemed suitable for this therapy. The attending nephrologist determines referrals to the renal transplantation unit and criteria must be ful lled to be considered for transplantation.
The aim of this study is to investigate differences in health related quality of life for patients receiving different types of renal replacement therapy to better allocate resources in the future. Findings will also aid physicians in guiding choices of therapy tailored to individual circumstances and educate patients in their decision making when considering modality of renal replacement therapy.

Study description
Patients receiving renal replacement therapy in Trinidad and Tobago start dialysis or receive a renal

Inclusion and exclusion criteria
Inclusion criteria had been patients receiving a transplant or on dialysis for 3 months or more and at least 18 years of age. Studies had shown that this period is essential for adaptation to activities of daily living and return to regular functioning. 6,[9][10] Exclusion criteria had been those on renal replacement therapy for less than 3 months and persons less than 18 years of age. Furthermore, persons hospitalized within 4 weeks from administration of the questionnaires were excluded from this study in keeping with the recommendation of the developers of the KDQOL (Kidney Disease Quality of Life) instrument used to obtain data to assess quality of life.

Sample size
Since there is no formula determining sample sizes for non-random sampling the formula for the size of simple random samples was used to determine the number of participants that would be needed for the study.
In this formula N = 1383 was the approximate number of patients on renal replacement therapy in Trinidad and Tobago at the time of the study, , is the standard normal distribution two-tailed 5% value and d = 0.05 is the margin of error. The estimated minimum sample size was 384 patients. These included at least 262 haemodialysis patients from private centres and 61 from public centres, 35 transplant recipients and 26 patients on peritoneal dialysis using approximate number of patients on each therapy. This study had a sample size of 530, constituting the following: 100 transplant patients, 80 peritoneal dialysis patients, 264 private haemodialysis patients and 86 public haemodialysis patient.
All peritoneal dialysis and renal transplant patients meeting inclusion criteria were investigated. Convenience sampling was used to select haemodialysis participants form both public and private institutions. Strati ed random sampling was done among 16 private facilities for haemodialysis. Geographical locations using distributions within health facilities were used to obtain ratios for strati ed random sampling. These were the North Central, North West, and South West regional health facilities.
The 16 private haemodialysis centres were located within these regional health authorities. These private facilities were distributed in a 1:1:2 ratio respectively. Thirteen haemodialysis centres that included all the public centres and 8 private centres were studied.

Questionnaires
The and is valid and reliable in many populations. [24][25][26][27][28] The domain components include a physical and mental subset, burden of illness, symptoms and effect of disease on life.
The EuroQol (EQ-5D-3L) self-reported health instrument was also included. The EQ-5D-3L classi cation system has ve domains: mobility, self-care, ability to perform usual activities, pain/discomfort and anxiety/depression. Each dimension is scored from 1 to 3 with 1 representing ' no problems', 2 representing 'moderate problems', and 3 representing 'extreme problems'. The EQ-5D-3L self reported health instrument also includes a visual analogue scale on which a respondent provides their selfassessed health rating on a 0 (worst health imaginable) to 100 (best health imaginable) scale. The EQ-5D-3L value set for Trinidad and Tobago was used to determine utility values for patients on all modalities of renal replacement therapy. 29 Trinidad and Tobago EQ-5D-3L population norms from a forthcoming study were used to compare EQ-5D-3L results for the patients on renal replacement therapy. Data collection and informed consent Preparation for eldwork included piloting and editing the questionnaire, creating a eld manual to guide the data collection process and a coding dictionary to facilitate data to be used for data coding (qualitative data) prior to data entry. Prospective data collectors were trained in the use of the eld manual. Data was regularly tested for high inter-collector reliability (Cohen's kappa) and high agreement with a gold standard. All persons in this study provided informed consent in writing. Participants were thoroughly counselled on the undertakings of the research. Questionnaires were administered in an interview-based format and con dentiality was maintained.

Ethical approval
All permissions were obtained for public and private institutions. The ethics committees from the corresponding regional health facilities: North Central, North West, South West, Eastern and Tobago gave their approvals. The University of the West Indies ethics committee granted approval for this research.

Data Entry and Analysis
The statistics software Statistical Package for the Social Sciences (SPSS) version 24 and Microsoft EXCEL was used for data entry and editing prior to data analysis. Preliminary computations included calculating a CCI for each patient. This index categorizes patients according to their probability of surviving different diseases during the 10-year period subsequent to the date on which the index was computed. 23 The lower the index the greater the probability of survival. Figure 1 shows the probability associated with each index value.
Subsequently SPSS version 24, MINITAB version 18 and STATA version 14 were used for both descriptive and inferential data analysis. Descriptive methods included frequency and percentage distribution tables, and summary statistics. Inferential methods included 95% con dence intervals, hypothesis testing at the 5% level of signi cance, multiple regression analysis and analysis of variance.
Reliability of the KDQOL questionnaire and the KTQ in this population was tested with Cronbach's alpha.
The validity of these questionnaires were analysed with Pearson's correlation. (2 tailed)

Results
Baseline characteristics A total of 530 (97.1%) of the 546 patients selected participated in the study and their characteristics are shown in Table 1. The 16 patients who declined were on haemodialysis. Figure 2 shows the age groups of the patients. Underweight patients were predominantly on peritoneal dialysis and the prevalence of obesity was greater among haemodialysis patients ( Figure 3). Patients on renal replacement therapy reported hypertension and type 2 diabetes mellitus as the main causes of chronic kidney disease ( Figure 4). In 84% of persons, the diagnosis of chronic kidney disease was made when patients required renal replacement therapy.
Thirty three percent of patients on haemodialysis had an arteriovenous stula or graft (AVF/G) as their primary access type. Almost half of the patients with permanent catheters were managed for catheter related blood stream infections. Infective endocarditis was reported in 15% of those patients. With respect to comorbidities, all patients with a CCI ≥ 6 were on haemodialysis. No transplant or peritoneal dialysis patients had a CCI ≥ 6. These patients constituted 15% of the total number of patients on haemodialysis.

KDQOL-36 scores and variables studied
The KDQOL total and domain scores were calculated as percentages.  Table 4 shows that patients on haemodialysis with an AVF/G reported higher mean KDQOL scores than those with haemodialysis catheters (p=0.000).    EQ-5D-3L results The mean VAS and mean index values seen in Table 6 were best among the transplant group followed by peritoneal dialysis then haemodialysis (p=0.000). Table 7 shows that transplant patients perform better than haemodialysis patients based on both the EQ-VAS and index values. Additional le 1, supplementary table 1 shows the EQ-5D-3L health states that were observed for the 3 groups in this study. Four EQ-5D-3L states were observed among transplant patients. Ninety ve percent of the transplant recipients were in the full health state (11111). None of the transplant recipients reported level three on any of the EQ-5D dimensions. In comparison to population norms for age and gender in Trinidad and Tobago, the health state pro le for transplant patients was better than the normal population. Table 6 shows the EQ-VAS and index values for the three groups. On both measures, the transplant group has the highest values and the haemodialysis group had the lowest values.  Table 7 shows the results of ordinary least squares regression model for EQ-VAS and EQ-5D index values with controls for age and gender. Transplant is used as the reference category with dummy variables for peritoneal dialysis and haemodialysis. The coe cients for peritoneal dialysis and haemodialysis in these models are -8.63,-25.74 and -0.08, -0.20 for EQ-VAS and EQ-5D respectively.

Discussion
Overview Quality of life is a di cult and complex construct to measure that involves the interplay of numerous factors and extends into all aspects of an individual's functioning. Wilson and Cleary provide a model that starts at a cellular level and progresses to the individual interacting with society. 31 Quality of life not only encompasses genetics and the environment but also includes social, cultural, economic and psychological measurements. In assessing the success of therapy, quality of life and state of health has been used throughout the years as indicators of treatment outcome and subsequently can be employed to evaluate the cost effectiveness of therapies.
In this population, about 90% of patients on renal replacement are on dialysis and two thirds of the haemodialysis patients have permanent catheters as their primary access type. These ndings emphasize the importance of this study in a Caribbean population and the impact of the factors affecting quality of life. Robinson et al has shown differences in the patient population on renal replacement therapy across the continents. 32 In particular, it was seen that most of the patients in Japan on haemodialysis use an arteriovenous stula. 32 The majority of patients around the globe have renal transplants. 32 Biological factors

Mode of renal replacement therapy
In 1985, Evans and colleagues measured the quality of life of patients undergoing dialysis and transplantation. They found that 79.1% of transplant patients were able to function at nearly normal levels compared to between 47.5% and 59.1% of dialysis patients depending on the type of dialysis. 33 In this study it was found that patients who received renal transplants had better quality of life scores compared with dialysis patients. ( Figure 5, investigated in a future study. The ordinary least squares regression model in Table 7 shows that by placing patients on peritoneal dialysis or having a renal transplantation drastically improves quality of life for the number of years on renal replacement therapy. The decrement in quality of life is greatest in the haemodialysis group. There is a marked difference of 17 VAS points and 0.12 utility for patients on haemodialysis compared to peritoneal dialysis. A transition from peritoneal dialysis to haemodialysis would impact greatly on quality of life for suitable candidates.
Renal transplant recipients were also maintained on their therapy for longer periods than persons on other forms of therapy. Using a period of 5 years on renal replacement therapy, 8% of patients were on haemodialysis while about one third of all transplant recipients had functioning grafts. These ndings can be due to a number of reasons including comorbidities, age and type of access among this group, which will in uence mortality. Renal transplantation when compared to other forms of renal replacement therapy is associated with fewer hospitalizations and death in uencing the cost effectiveness of this modality around the world. [34][35] Renal transplantation is the most physiologically similar to one's body as a mode of renal replacement therapy. Among transplant recipients, immunologic similarity can further be assessed with haplotype match between donor and recipient. Transplantation is also the least time consuming method of all modalities. Haemodialysis patients have approximately 3 sessions of haemodialysis per week, while peritoneal dialysis patients undergo dialysis sessions at their home. It is therefore expected that renal transplantation should lead to a better quality of life.

Lifestyle diseases
During this study, it was shown that almost three quarter of patients on renal replacement therapy in Trinidad and Tobago were diabetic and/or hypertensive. When patients with other stages of chronic kidney disease are taken into consideration, these numbers may be larger for this population. Over 80% of patients were diagnosed with kidney disease when renal replacement was necessary. This nding exposes the inadequacies of screening and the necessity for better strategies for preventing and treating lifestyle diseases in our setting.
Patients on haemodialysis also had more comorbidities than patients on other types of renal replacement suggesting that haemodialysis is associated with more complications. A CCI ≥ 6 equivalent to a 10-year survival probability of 0 was found only among the haemodialysis group.

Alcohol use
It has been shown that smoking and alcohol cessation in patients with renal disease may lead to a better quality of life. Francisco et al showed that patients who never smoked cigarettes or did not consume alcohol had higher quality of life scores. 36 Patients with a higher quality of life may have fewer stressors and engage less frequently in these detrimental habits. In this study, patients who consumed 5 units or less of alcohol weekly had better quality of life scores.

AVF/G for haemodialysis
Patients with an AVF/G had better mean KDQOL-36 scores when compared to patients with permanent catheters. (Table 4) It has been shown that this access type is not only cost e cient but offers a better quality of life for patients because of fewer complications than a permanent catheter. 37,38 Patients who were on haemodialysis for a longer time possibly were able to obtain an AVF/G before others because of the length of time in the public health care system. Improved quality of life in the older dialysis patients was likely due to the presence of an AVF/G.

Adiposity stores
Increased adiposity may be favourable for patients on haemodialysis providing an anti in ammatory bene t during times of cellular stress. [39][40][41][42][43] Studies have shown improved survival and a better quality of life of patients with a BMI >25 on haemodialysis. [41][42][43] Age and gender Additional le 2, supplementary gure 1 shows that younger patients reported fewer problems in the haemodialysis group in both male and female. A similar trend is seen in the normal population where younger patients report fewer problems. The changes of the aging process on organ function may account for these ndings. A study that looked at patients on haemodialysis showed improved quality of life in younger patients. 44 Older female patients on peritoneal dialysis reported fewer problems that those in the younger age groups while the extremes of age among male peritoneal dialysis patients reported more problems. Male transplant recipients in the 18 to 24 years group and 45-54 years group reported more problems. A future study for reasons for this trend should be considered.

Social factors Employment
Employment status signi cantly in uenced quality of life. The majority of the employed population on renal replacement were transplant recipients followed by patients on peritoneal dialysis ( Table 2). It is possible that patients receiving transplants were able to take advantage of employment opportunities because of more time availability. Transplant recipients followed by patients on peritoneal dialysis were able to obtain or continue their previous form of employment after commencing these modes of renal replacement therapy. In Canada, in the rst 2 years after renal replacement therapy, employment opportunities was the best in the transplant subset. 10 Table 2 also shows that in the occupation category of managers and professionals, transplant recipients formed the majority of these categories followed by patients on haemodialysis.

Economic status
Like employment, income is another factor affecting quality of life of patients receiving renal replacement therapy. This was also seen in another study by Alvares and colleagues. 8 In this population, patients earning more than $4000 Trinidad and Tobago dollars monthly (equivalent to approx. 600 US Dollars) had better mean quality of life scores.

Renal replacement therapy options
Options for renal replacement therapy include renal transplantation, peritoneal dialysis and haemodialysis. Similar to worldwide health care systems, each mode of therapy has speci c requirements and criteria before initiation, some being more rigorous than others.
Haemodialysis in our population is associated with the poorest quality of life and the most problems reported by patients using the KDQOL-36 and EQ5D-3L questionnaires respectively. The 17 VAS points difference and 0.12 utility for patients on haemodialysis compared to peritoneal dialysis suggests that a transition to peritoneal dialysis can signi cantly affect health status. This also means that the choice of renal replacement therapy ultimately in uences quality of life.
Certain modes of renal replacement therapy in our setting is associated with multiple checkpoints and prerequisites that should be satis ed, greater engagement of patients and their families and better support systems. As a result, these modalities of therapy like renal transplantation and peritoneal dialysis produce patients that are more likely to adhere to therapy and management of comorbidities. Table 9 demonstrates the requirements and factors implicated in this study for each modality of renal replacement therapy in our population.

Limitations
The quality of life and health state of patients who were diagnosed with end stage renal disease and do not wish for renal replacement therapy can be analysed as a further sub group. Renal clearances during peritoneal dialysis and haemodialysis can be investigated in further studies as this will establish the e ciency of dialysis for patients. Quality of life of the normal population and patients receiving transplants is another potential area of further study.

Policy implication
This study should guide policies to improve quality of life of persons on renal replacement therapy. Prevention of chronic kidney disease and other lifestyle diseases in this population should be priority in healthcare. A stula rst effort for all patients on haemodialysis should be the gold standard and early stula or graft protocols in all centres should be implemented.
Improved psychosocial support networks for dialysis patients and educational programmes for patients and families when deciding choice of renal replacement therapy should be introduced.
Haemodialysis centres require revision of protocols and strict adherence to guidelines to reduce catheter related bloodstream infections. Auditing at dialysis centres with strict quality control can be increased to focus on the issues patients encounter. Performing quality of life assessments for patients on renal replacement therapy in all centres can be instituted to improve care and compare treatment in an aim to prolong survival. In other settings, patient reported outcome measurements use the KDQOL among other questionnaires for internal quality improvement activities. 45 The institution of policies for patients to be commenced on peritoneal dialysis once they are eligible instead of haemodialysis would signi cantly improve the health and quality of life of these patients.  Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Most data generated or analysed during this study are included in this published article and its supplementary information les.

Figure 2
Age groups of patients on renal replacement therapy Self-reported cause of kidney disease Figure 5