Health-related quality of life (HQOL) following kidney transplantation is a topic that is gaining importance. It has been shown that patients with a functioning kidney graft present a significantly higher HQOL compared to patients on dialysis (1–4). Other studies focused on HQOL in renal transplant recipients under different immunosuppressive protocols (5, 6). However, assessment of HQOL was limited to the first or second year after kidney transplantation. Because graft survival rates have improved dramatically within the last decades, HQOL of long-term transplant recipients might be of high interest. Furthermore, the question arose whether factors influencing HQOL in long-term transplant recipient can be identified. Studies focusing on long-term HQOL in kidney transplanted patients using validated questionnaires are very limited (7). We have studied HQOL in recipients presenting stable function of kidney grafts for more than 15 years who are continuously under care in our outpatient clinic. For assessment of HQOL, validated tools such as the SF-36 Health Survey (8) and the Kidney Transplant Questionnaire (KTQ) (9) were utilized.
PATIENTS AND METHODS
For this retrospective study, adult recipients with a functioning kidney graft more than 15 years after transplantation were objected. Patients receiving a kidney graft between January 1, 1970 and December 31, 1989 were considered. To allow for a close follow-up, only recipients who were seen in our outpatient clinic within the last 12 months were included. Multi-organ recipients and recipients under 18 years of age at the time of evaluation were excluded. Actual kidney function, blood pressure, antihypertensive and immunosuppressive medication were analyzed using most recent data from the outpatient clinic. The study was reviewed by the local ethic committee and was performed in accordance with the Declaration of Helsinki.
Assessment of Quality of Life
Quality of life was assessed at the same time point in all kidney graft recipients. The Standard German Version of the 36-Item Health Survey (SF-36), a validated quality-of-life survey (10), and the Kidney Transplant Questionnaire-25 (KTQ-25), a disease-specific questionnaire for patients with a renal transplant (9), were sent to each individual recipient in January 2005.
The SF-36 survey contains 36 questions for HQOL assessment grouped into eight different health concepts: physical functioning (PF), role physical (RP), physical pain (BP), general health (GH), vitality (VT), social functioning (SF), role emotional (RE), and mental health (MH). The number of questions directed to each health concept ranges from 2 (for SF and BP) to 10 (for PF). A mean score is produced for each health concept, ranging from 0 to 100 with higher scores indicating a better outcome. Results of our study population is compared with mean score values of the general healthy population from the SF-36 validation study (11).
The KTQ-25 questionnaire contains 25 items grouped into five dimensions: physical symptoms (six patient-specific items), fatigue (five items), uncertainty/fear (four items), appearance (four items), and emotions (six items). Scale scores for each item can range from 1 to 7. Higher scores indicate fewer problems and a superior quality of life. KTQ-25 results of study patients are presented in comparison to pretransplant patients from the validation study performed by Laupacis et al. (9). Additionally, recipients were invited to define their socioeconomic situation.
The follow-up of transplant recipients until June 2005 was studied based on data collected in our transplant outpatient clinic. Therefore, the Amis/Windows Version 1.0 software package was utilized. Mean follow-up of recipients was 19.5 years and ranged from 15.1 to 32.2 years. For statistical analyses SPSS software package (SPSS Inc., Chicago, IL) was used. Differences in the mean score value of SF-36 and KTQ-25 among subgroups were analyzed by two-tailed, unpaired t test as indicated.
From January 1, 1970 to December 31, 1989 a total of 1,801 kidneys were transplanted at our center (Fig. 1). Considering inclusion and exclusion criteria, a total of 171 kidney graft recipients qualified for this study. Of those, 139 recipients returned both completed questionnaires (response rate: 81.3%). Details of the study population are given in Table 1. Mean age of recipients was 55 years and ranged from 24 to 82 years. The majority of recipients were married (66%) or lived in a close relationship (6%), whereas 28% of recipients lived alone (Table 1). All recipients were off dialysis and actual mean creatinine was 156 μmol/L (range: 55 to 680 μmol/L).
Current immunosuppressive therapy consisted of a double regimen based on calcineurin inhibitors (CNI) and steroids in 84 recipients (60%); of those, eight patients received tacrolimus and 76 received cyclosporine. A CNI-based triple immunosuppressive regimen was used in 21 recipients (15%), including 20 patients on cyclosporine and one patient on tacrolimus; seven of those patients received mycophenolate mofetil and 14 received azathioprine. The remaining 34 recipients (25%) were on CNI-free immunosuppression using steroids and azathioprine (n=27), steroids and mycophenolate mofetil (n=6), or steroids and sirolimus (n=1).
Currently, 29% of recipients are employed and 7% are seeking employment. Fifty-eight percent of recipients are retired. There was no difference in mean age among subgroups (Table 2).
Results from SF-36 questionnaires are given in Table 3. In the categories RP, SF, RE and MH, results of our study population were comparable to the general population. In the remaining four categories, mean score values were lower in comparison to the healthy population. In a subgroup analysis, there were highly significant better scores detectable among recipients who were employed at the time of quality of life assessment in seven out of eight health concepts (Table 3). Furthermore, recipients living in a close relationship such as married couples or cohabitants revealed higher score values in all categories compared to recipients living alone. A statistical significance was reached in the categories of SF and MH. Recipients who were on CNI-free immunosuppression had a statistically significant better quality of life in the category of RE compared to patients treated with a CNI-based regimen. When recipients were divided into two groups regarding their blood pressure, there was a significantly better outcome for recipients with a systolic blood pressure below 130 mmHg for the aspects PF, BP, GH, and SF. The level of diastolic blood pressure or the number of antihypertensive drugs did not account for any significant difference (data not shown). Other factors analyzed such as age or sex of recipients, kidney graft function, and age of donors had no influence on SF-36 aspects (data not shown).
Disease-specific HQOL of the study population was compared to transplant candidates pretransplantation from the validation study performed by Laupacis et al. (Table 4). The mean score values among the study population were superior regarding physical symptoms, fatigue, uncertainty/fear, and emotions. In contrast, a better score value was achieved in patients pretransplantation in the dimension of appearance compared to our population.
In addition, subgroup analyses were performed for all five dimensions. Older recipients had statistically significant higher scores for the dimension of fatigue compared to younger recipients. As it was the case for the SF-36 analysis, recipients who were in employment at the time of evaluation presented statistically significant better results in five of six dimensions (physical symptoms, fatigue, uncertainty/fear, and emotions) than retired or unemployed patients. Married or cohabiting recipients revealed superior mean score values in all of the six dimensions of the KTQ-25 questionnaire when compared to recipients living alone. However, a statistical significance was reached only in the dimension of emotion. A blood pressure below 130 mmHg had a highly significant impact on the dimension of physical symptoms. Score values for the remaining five dimensions were slightly but not statistically significant higher for recipients presenting a blood pressure below 130 mmHg. No differences in all of the five KTQ-25 dimensions were detectable for other factors such as sex of recipients, diastolic blood pressure (<80 or ≥80 mmHg), number of antihypertensive drugs (<2 or ≥2 drugs), immunosuppressive regimen (CNI free or CNI based), kidney function (< or ≥ mean creatinine) and donor age (< or ≥ mean donor age).
In this single-center study, we focused on HQOL in recipients presenting stable graft function more than 15 years after kidney transplantation. However, one has to consider that this is a highly selected population out of a large number of recipients who were transplanted in the period from 1970 to 1989. Given the fact that recipients visiting the outpatient clinic within the last 12 months were enrolled in this study exclusively, a close follow-up for these transplant recipients was guaranteed. Multiple factors that might influence HQOL were analyzed. As tools for assessment of HQOL, two validated questionnaires—the SF-36 and the KTQ-25—were utilized. The KTQ-25, a disease-specific questionnaire, was designed to assess HQOL in stable transplant recipients (9). In this study, the self-administered KTQ-25 questionnaire was used, which has shown to be as valid and reliable as the interview version (12). The SF-36 is a well-established and validated generic instrument to assess quality of life (11). More than 80% of recipients responded to both questionnaires, which can be seen as a result of the close interaction between each patient and the transplant outpatient clinic.
In general, HQOL was satisfactory for both instruments among the study population. Surprisingly, long-term renal transplant recipients revealed score values in certain SF-36 categories—such as role physical, social functioning, role emotional, and mental health—which were comparable to the general healthy population. However, long-term immunosuppressive therapy and comorbidity among our recipients may have contributed to noticeable lower scores for the categories physical functioning, physical pain, vitality, and general health compared to the healthy population. For the KTQ questionnaire, our study population reached score values within four of five dimensions that were superior compared to patients awaiting renal transplantation (9) and comparable to renal transplant recipients within the first year after transplantation (13).
Certain studies have evaluated the influence of different immunosuppressive regimens on HQOL after kidney transplantation (6, 14). In the randomized study performed by Oberbauer and coworkers, the SF-36 and the KTQ-25 questionnaires were used to assess HQOL in renal transplant recipients after cyclosporine withdrawal compared to patients under continuing cyclosporine medication. Statistically significant better results were detectable among patients following cyclosporine withdrawal regarding the KTQ-categories fatigue and appearance as well as the SF-36 vitality dimension (6). Although these studies focused on the early period after kidney transplantation, we have investigated the influence of CNI-free versus CNI-based immunosuppressive protocols on HQOL in our patient population. CNI avoidance was associated with a better HQOL regarding the SF-36 categories physical functioning, role physical, physical pain, and role emotional. However, a statistically significant difference was only observed for role emotional. Interestingly, no difference was detectable among patients on CNI or without CNI for all of the KTQ dimensions. A further stratification of our study population comparing single immunosuppressive agents was not performed due to the high variance of the administered immunosuppressive regimens.
The professional situation had the most important impact on HQOL of our long-term transplant recipients. Employed patients revealed a superior HQOL throughout all dimensions of both questionnaires compared to job seeking and retired recipients. One has to keep in mind that the age was not different among these subgroups. However, it is likely that employed recipients were in better physical condition compared to their retired or unemployed counterparts at the time of HQOL assessment. Nevertheless, our data provide evidence that successful vocational rehabilitation following renal transplantation is not only of high importance from a socioeconomic viewpoint, but was associated with improved HQOL.
Another factor that might influence HQOL is the recipient’s social situation. Indeed, recipients who were married or cohabiting experienced a trend toward a better life quality in all of the SF-36 categories compared to recipients living alone. Highly significant better results were achieved in the categories social functioning and mental health. Score values for all KTQ dimensions were also higher for married or cohabiting recipients. A significant difference was found for the emotional dimension.
Of the other factors analyzed in this study, the most important was the presence of hypertension, defined as a systolic blood pressure >130 mmHg, which was negatively correlated with HQOL. Hypertension most likely influenced the SF-36 categories physical functioning, physical pain, general health, and social functioning. For the disease-specific KTQ-questionnaire, the presence of hypertension was associated with a lower outcome regarding physical symptoms.
In summary, we present that renal transplantation is associated with satisfactory HQOL more than 15 years after transplantation. Our data provide evidence that a close patient care might not only result in prolonged graft survival but also in improved life quality. Social and job-related rehabilitation should gain more importance in the long run. Thus, this could further increase HQOL in long-term transplant recipients.
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