Prospective, multicenter, controlled study of quality of life, psychological adjustment process and medical outcomes of patients receiving a preemptive kidney transplant compared to a similar population of recipients after a dialysis period of less than three years – The PreKit-QoL study protocol

Chronic kidney disease can lead to end stage renal disease (ESRD), which requires use of substitution techniques such as hemodialysis, peritoneal dialysis or kidney transplantation. Treatment of ESRD is cumbersome in terms of implementation, impact on the physical and psychological health of patients, quality of life (QoL) and it generates substantial health expenditures. It is well-known that kidney transplantation in eligible ESRD patients is the treatment of choice compared to long-term dialysis [1] since it is associated with longer survival [2]. Furthermore, the cost of transplantation is lower as compared to dialysis. Some studies have also described higher QoL for kidney transplant recipients compared to patients undergoing dialysis [3, 4] as well as more positive perceptions of illness when changing from dialysis to transplantation [5]. Hence, limiting the dialysis period before transplantation has several advantages in terms of medical outcomes, QoL and costs. In respect with the same arguments, one can expect that preemptive transplantation, i.e. the patient is placed on the transplant waiting list and transplanted prior to progression to ESRD, would be the preferred strategy. Nevertheless, the literature does not provide a clear answer regarding the benefit of preemptive transplant and even less is known about its psychological impact and its possible burden for patients: for instance, patients may not be aware of the benefit of transplantation compared to dialysis but in contrast may suffer from the consequences of transplantation. Although it is recommended to enlighten patients of all possible consequences and complications after the transplantation, patients are sometimes anyway startled since for instance they suffer after the surgery, or are uncomfortable with the load of the immunosuppressive therapy. Furthermore, in transplantation centers, it has been observed that patients receiving a preemptive transplant may consider or perceive transplantation as an event that has deteriorated their well-being [6].That may explain the high variability of preemptive transplant practice worldwide [7]. This lack of data regarding the psychological impact of preemptive transplantation constitutes a true issue since these subjective outcomes can be associated with the long-term patient and graft survival [8]. This issue is important regarding the collective impact of early registration on waiting list: preemptive transplantations are associated with an increase in the duration on waiting lists, which remains an important risk factor of graft failure. In fact, no data allows concluding on post-transplant QoL in particular because transplantation can be experienced in a completely different manner among patients who were on dialysis and those who still had a functioning kidney at the time of surgery.

Studies assessing the psychological impact and QoL of Patients with Preemptive Transplantation (PPT) compared with Patients with Dialysis before Transplantation (PDT) are lacking and it cannot be assumed that preemptive transplantations systematically improve patients’ QoL. Indeed, if few disease limitations and symptoms were experienced before transplantation, the aftermath of the graft may seem disproportionate, especially in case of post transplantation complications (infection, acute rejection, etc.). Moreover, these patients in ESRD who are not on dialysis have to simultaneously be psychologically prepared for dialysis and transplantation, without knowing which of the two treatments they will have to face first. Some patients may prepare for dialysis and then be referred for a transplant instead, for which they are not ready. In contrast, other patients might await transplantation and perceive dialysis as a failure. In this setting, a better understanding of how patients anticipate, live and face pre and post-transplantation and its consequences can contribute to enhance and better orientate educational programs to improve patient care.

The importance of studying longitudinal evolution of perceived QoL of patients with chronic disease and in identifying its possible associated factors is now well admitted [9‐11]. Such QoL data are often collected through questionnaires including different items called Patient-Reported Outcomes (PRO). Despite the fact that PRO are nowadays considered simple, valid and reliable measures of QoL, it is however clear that the cognitive processes involved in completing them are quite complex [12] and that longitudinal PRO data might sometimes be very difficult to interpret. Indeed, some studies have evidenced a stable or even a higher level of perceived Qol in patients with severe chronic conditions, despite a poor physical health state, as compared to the general population [13‐15]. By contrast, others have shown opposite results for stable patients, regarding their health status across occasions, reporting changes in QoL. This phenomenon, which might be regarded as a paradox, is sometimes referred to as response shift (RS) [16, 17]. In case of RS, there is a change in the meaning of what the PRO (QoL, anxiety, pain, etc.) is intended to measure over time or in the patient’s expectations and life priorities according to the disease evolution. It is often linked to the way the patients might adapt or cope with their disease experience. RS can result from three different processes [16, 17]: 1) changes in the patient’s internal standards of measurements called recalibration (i.e. the level of QoL or anxiety measured by the questionnaire can be interpreted differently before and after transplantation), 2) changes in the patient’s values and in the relative importance given to the questions or dimensions of QoL that are appraised before and after transplantation, called reprioritization, and 3) changes in the patient’s definition of what is being measured over time called reconceptualization. Hence, it might be problematic or even impossible to distinguish, without appropriate methods, true QoL changes from confounding RS effects. Indeed, patients may give different answers to the PRO over time, not only because their health has changed, but also because their perception on what health or QoL means to them has changed. The accurate assessment of the effect of transplantation for instance can then be obfuscated by RS and lead to biased results, poor power to detect effects of interest and therefore, erroneous conclusions [18‐21]. Indeed, RS can seriously alter the psychometric properties of PRO such as reliability, validity and ability to detect true changes (responsiveness) [22]. On the other hand, one can also highlight the therapeutic importance that the phenomenon of RS constitutes in itself by allowing a better understanding of how patients adjust to their illness. RS may well also be one of the goals of therapy in helping patients to cope with their illness and to live with it. Therefore, RS can be viewed either as a nuisance (measurement bias) or as an indication of a possible therapeutic benefit coming from some form of psychological adaptation or adjustment. In fact, it is very likely that the post-transplant QoL experienced by patients for whom first replacement therapy was transplantation might be lower than for patients who have undergone dialysis, even for a short period of time [1, 23]. The rigorous comparison of change in the QoL of preemptive kidney transplant patients and patients who were on dialysis requires taking into account the very likely occurrence of the RS phenomenon, not only in terms of detection, but also in terms of statistical adjustment in the analysis of changes in PRO data.

Our hypothesis is that preemptive kidney transplant recipients have a lower quality of life and present more difficulties regarding psychological adaptation after transplantation compared to patients who were under dialysis before surgery for less than 3 years. The designed project aims at providing a better assessment and understanding of the psychological impacts and of patients’ psychological adaptation, taking into consideration the response shift, as well as patient and graft outcomes following preemptive transplantation. This could help optimizing the management of these patients, particularly regarding therapeutic education programs and adapted implementation of psychological support.