Quality of life in simultaneous pancreas–kidney transplant recipients

Abstract:  Background:  Simultaneous pancreas‐kidney transplantation (SPK Tx) allows dialysis and insulin therapy to be discontinued and improves the complications of diabetes mellitus type 1 (DM1). This study measure quality of life (QoL) in SPK transplant recipients and determine if there are differences in QoL between these patients and those with DM1 in renal replacement therapy (RRT).

Currently, simultaneous pancreas-kidney transplantation (SPK Tx) is the treatment of choice in selected patients with type 1 diabetes mellitus (DM1) and end-stage renal disease (ESRD) (1). A functioning SPK transplant allows dialysis and insulin therapy to be discontinued and stabilizes or improves the complications of DM1. Nevertheless, to a greater or lesser degree, these complications (physical and psychological alterations, secondary effects of immunosuppressive therapy and the need for lifelong medication and medical follow-up) can persist after SPK Tx. Health professionals have mainly investigated the clinical features of transplant recipients. However, in the last few years, interest in analyzing perceived health and healthrelated quality of life (QoL) has increased. This latter concept includes the features of QoL most closely associated with a particular disease, its treatment and follow-up and therefore those elements most susceptible to modification by the health system.
The general aim of this study was to measure health-related QoL in our population with SPK Tx and to determine whether there are significant differences between these patients and those with DM1 and ESRD who continue to receive renal replacement therapy (RRT) and insulin therapy. More specific aims were to evaluate whether there are significant differences between the study groups and the means of the Spanish reference population in the distinct dimensions of a QoL questionnaire and whether other variables such as Isla  age, sex, yearsÕ duration of DM1, length of dialysis, and time since SPK Tx significantly affect health-related QoL.

Patients and methods
To measure the health-related QoL of SPK Tx recipients and patients with DM1 and ESRD, we performed an observational, cross-sectional study in Hospital Clı´nic de Barcelona between 2004 and 2005. During this period, 90 SPK Tx were performed in this hospital (43.6% of all SPK Tx performed in Spain). At the start of the study, both grafts were functioning in 71 patients (78.8%). Of these, two patients were excluded because they were followed-up in another province. The sample was composed of 69 patients. A further 34 DM1 patients with ESRD under RRT on the waiting list for SPK Tx or kidney Tx were included. Inclusion criteria were maintained function in both grafts in SPK Tx recipients, and age equal to or less than 55 yr, length of RRT greater than one yr, and no severe vascular or neuropathic complications in DM1 patients with ESRD under RRT.
To evaluate QoL, the Spanish version of the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) was selected as it is one of the most widely used instruments, all articles published on its metric properties support is reliability, validity and sensitivity, and no differences have been found in its internal consistency between self-administered questionnaires and those administered through interview (2). The SF-36, was developed by Ware (3,4) and adapted and validated for Spain by Alonso et al. (5). In addition to the SF-36, the following variables were recorded: type of treatment (SPK Tx or RRT), type of RRT sex, age, DM1 duration, and length of RRT. For the data analysis, the instructions for the standardization of content and scoring of the Spanish version of the SF-36 were followed (6).

Statistical analysis
Descriptive analysis of the variables was performed by calculating frequencies for qualitative variables and means, standard deviation, median and range for quantitative variables, as well as 95% confidence intervals for means. To analyze the association between the scores obtained on the SF-36 and clinical and sociodemographic variables, the chi-squared test or FisherÕs exact test were used. To compare means, Student t-test or the Mann-Whitney U-test was used, depending on the sample size of each group and the number of different values observed in each of the variables.
Subsequently, to determine whether there were statistically significant differences in QoL dimensions between SPK transplant recipients and patients under RRT, adjusted by other variables that could influence these dimensions, a multiple linear regression model and/or two-way ANOVA with co-variables and interaction effects were constructed. Independent variables were sex, age, duration of DM1, study group, and length of dialysis. In variables significantly departing from normal distribution, transformation of the dependent variable was performed. In all the models constructed, possible multicolinearity and the potential effects of interaction were studied. Nonsignificant variables and interaction effects were removed from the model. In dimensions showing few values in their distribution, an ordinal regression (PLUM) model was constructed. The binomial test was used to compare the scores obtained on the QoL dimensions with the means of the Spanish reference population according to sex and age and according to the year in which SPK Tx was performed.

Results
Sixty-nine SPK transplant recipients (41 men with a mean age of 41.78 + 6.5 yr, and 28 women with a mean age of 38.5 + 7 yr) and 34 patients receiving RRT (24 men with a mean age of 41.6 + 8.5 yr, and 10 women with a mean age of 45.9 + 5.8 yr) met the inclusion criteria. All patients completed the questionnaire (self-administered in 99 and performed through telephone interview in four). No significant differences were found between the two groups in age and sex. In contrast, significant differences were found in DM1 duration and length of RRT ( Perception of current health status compared with health one yr previously was better in SPK transplant recipients than in patients under RRT. QoL was higher in SPK transplant recipients than in patients receiving RRT, with significant differences in all dimensions. In both groups, QoL was lower in women than in men (Table 1).
Multivariate analysis revealed that SPK Tx was significantly associated with improved QoL in all dimensions of the SF-36. In both groups, sex, age and DM1 duration were significantly related to QoL. Female sex was negatively associated with the dimensions of mental health, bodily pain, vitality, role limitation-emotional, and physical functioning. Age was positively associated with mental health and a no significant negative association was found with general health (p = 0.053). Duration of DM1 was negatively associated with the dimensions of mental health and bodily pain ( Table 2). Significant differences were observed according to the year in which SPK Tx was performed. In almost all domains of the SF-36, the highest scores corresponded to the most recently transplanted patients.
Comparison of the results with the means of the reference population showed significant differences according to study group and sex. Men with SPK transplants had significantly lower scores than the reference population in the dimensions for general health, role limitations-physical and role limitations-emotional but significantly higher scores for vitality. Women with SPK transplants had significantly lower scores than the reference population in the dimension for general health. Men under RRT had significantly lower scores than the reference population for physical functioning, bodily pain, general health, and vitality, while women under RRT scored significantly lower than the reference population in all dimensions of the SF-36 (Table 3).
Comparison of the means obtained in SPK transplant recipients with those for the reference population according to the year of transplantation revealed that patients who received a transplant in the last year of the study, i.e., those most recently transplanted, had higher scores than the reference population for role limitations-physical, vitality, and role limitations-emotional.  (Table 4).

Discussion
In the present study, QoL was higher in SPK transplant recipients than in patients receiving RRT in all dimensions of the SF-36 and this result held constant when adjustment was made for other variables such as type of treatment (SPK Tx or RRT), sex, age, DM1 duration, and length of RRT. These results coincide with those studies that have shown the effectiveness of SPK Tx in improving QoL (7)(8)(9) and with other studies that have shown the association between RRT and increased stress, anxiety, impaired self image, and reduced QoL (10)(11)(12). Women expressed a greater degree of physical and emotional limitation and therefore lower QoL than men, independent of treatment. Some studies have found no significant sex-related differences and have even found higher QoL in women, mainly in mental health (13). However, in most studies, female sex has been associated with poorer perceived health and QoL, both in healthy individuals and in those with disease (2,14).
Age has frequently been associated with worse QoL (2,15,16). However, in the present study, greater age was associated with better QoL, possibly because the patients studied were not elderly. The negative effects of age on QoL could be due not only to the effect of disease but also to that of the functional deterioration found in the elderly. In addition, as suggested by other authors (17), the SF-36 may be able to discriminate between the effect of disease and treatment and that of age on QoL.
The association between age and better QoL has been observed in studies of patients under RRT and in kidney transplant recipients (13,17) and is in agreement with other studies demonstrating that having a chronic disease and being young is associated with psychological disorders and impaired QoL (18). These findings could be explained by the difficulty of young people in coping with chronic health problems while attempting to forge a life. Comparison of the results obtained with the means of the reference population revealed that both SPK transplant recipients and patients under RRT had worse QoL, although male SPK transplant recipients had higher scores than the reference population for vitality. In a recent qualitative study, some SPK transplant recipients reported that after transplantation they had recovered their ''health,'' as well as their enjoyment of life, social relationships and, in some cases, sexual and reproductive function and occupational activity (12). However, the present study would indicate that, despite the perception of ''cure'' and the improvement achieved, SPK transplant recipients show a variety of symptoms and require treatment and medical follow-up, all of which reduce their QoL, mainly the dimension of general health. Other authors have reported that the improvement in QoL after Tx does not reach QoL levels in the general population (19).
In all dimensions, women with SPK transplants obtained lower scores and therefore showed worse QoL than men with SPK transplants. However, women showed fewer significant differences with respect to the reference population, which could be due to the smaller number of women than men in this study, reducing statistical power. The highest QoL scores were observed in the most recently transplanted patients. A result that is in agreement with those of other studies reporting decreased QoL in transplant recipients over time (13,20). Decreased QoL in these patients over time could be explained by the increase in survival, leading to greater comorbidity (21), and by psychological problems, which are less frequently examined in clinical practice. Qualitative studies have shown that SPK Tx and kidney Tx recipients viewed the transplant as a gift of life and described themselves as being ''reborn'' (22,23). However, after SPK Tx, the complications of DM1, surgery and treatment persist, as do psychological disorders in some patients. The transplant entails not merely the physical but also the imaginary and symbolic implantation of another personÕs organs. In some patients, all of these factors can lead to anxiety and identity disorders. Some studies report that transplant recipients experience a state of euphoria in the first yr after the procedure due to improvements in physical, social, sexual function and employment (24,25) and that HR-QoL scores tend to reach a peak and then decline (13,20,25). Pe´rez-San-Gregorio et al. (25) reported that transplant recipients pass through three phases: a first phase in which they require treatment and intense medical follow-up and experience difficulties in social and occupational integration, fear of graft rejection, and possible alterations in family dynamics as a result of transplantation, a second phase of adaptation, and a third phase of mental and physical exhaustion in which psychological disturbances increase. This latter phase begins some time after the first two yr of transplantation. However, time since SPK Tx ranged from two to six yr, demonstrating that the improvement in QoL after SPK Tx is maintained after the first yr.
The possible limitations of this study are due to the relatively small number of patients studied. However, it is important to note that the sample of SPK transplant recipients studied represents 97.1% of those undergoing this surgery in the study period who maintained two functioning grafts, that the number of patients under RRT represents a high percentage, given the strict inclusion criteria applied, and that significant differences were detected. QoL was higher in SPK transplant recipients than in patients receiving RRT in all dimensions of the SF-36 and this result held constant when adjustment was made for other variables such as type of treatment (SPK Tx or RRT), age, sex, DM1 duration, and length of RRT. Finally, the SF-36 does not include some health factors, such as sleep disorders and cognitive, family or sexual functions.
Despite these limitations, multivariate analysis revealed that SPK Tx is positive predictive factor of QoL. SPK Tx improves QoL, which continued to be higher in SPK transplant recipients than in patients receiving RRT and insulin during the study period, although it was lower than that in the reference population. We believe that this type of study is justified by the importance of determining the improvement in QoL after SPK Tx.
Although several studies have reported clinical improvement in patients after SPK Tx, changes in patientsÕ lives cannot be determined by clinical and biological improvements alone, but require a multidisciplinary approach that includes clinical and psychological factors (26)(27)(28)(29)(30)(31)(32)(33)(34). Several studies have observed that emotional and psychological factors are the most important predictive factors in perceived QoL after transplantation (13,31) and that these factors can be modified by psychological support (32). Although the number of publications on this topic has increased, the effects on clinical practice have been scarce (33,34). Future studies should combine QoL analysis with qualitative methodology, which provides more exhaustive information, serial QoL evaluations to determine temporal variations, and the perspective of gender to elucidate the sex differences observed in QoL.