Impact of pre-transplant dialysis modality on the outcome and health-related quality of life of patients after simultaneous pancreas-kidney transplantation

Medical data from patients with insulin-dependent diabetes mellitus (type 1 or 2) and ESRD who received SPKT at the University Hospital of Leipzig between 2000 and 2016 were retrospectively analyzed. Our data source comprised a prospectively collected electronic database. Approval for this analysis was granted by the local ethics committee [AZ: Nr: 111–16-14,032,016]. Patients undergoing pre-emptive transplantation, re-transplants, living donor kidney transplantation, those aged younger than 18 years, and those with missing data were excluded from the study.

Special emphasis was placed on the outcome of dialysis modality before transplantation (HD versus PD), recipient and donor characteristics, intra- and postoperative variables and complications such as patient, graft as well as HRQoL outcomes before (during dialysis) and after transplantation. Characteristics included age, gender, body mass index (BMI, weight in kg/height in m²), duration of insulin-dependent diabetes mellitus, duration of dialysis, and time on the waiting list. Cardiovascular disease included information about peripheral arterial obstructive disease and coronary heart disease (coronary artery bypass graft or stent). Peri- and post-transplant data included information on cold ischemia time of the kidney/pancreas, immunosuppressive therapy as well as patient and organ graft function.

Furthermore, complications occurring during the first 3 months after transplantation were analyzed. Surgical complications were defined as the need for relaparotomy within the first 3 months after transplantation. Intra-abdominal infections were defined as the development of infected fluid collection that required an intervention and/or antibiotic drug therapy. Gastrointestinal bleedings were defined as bleedings requiring relaparotomy or endoscopy, or patients suffering from sudden anemia combined with either melena or hematemesis. Other bleedings comprising intra-abdominal hemorrhages, were diagnosed by CT scan or relaparotomy performed due to acute anemia.

For measuring the HRQoL in this study, the most commonly-used and internationally-validated Medical Outcomes Study 36-Item Short Form Health Survey (SF-36) questionnaire was used. Patients were asked to evaluate their HRQoL before transplantation (undergoing dialysis), such as 1 year after transplantation. Therefore, SF-36 forms were completed at different time points after transplantation, but not earlier than 1 year after transplantation.

HRQoL was evaluated in a second assessment through written HRQoL questionnaires (SF-36) sent to all patients with an invitation to complete a quality-of-life survey retrospectively. The SF-36 survey was sent by mail to patients’ home addresses. Additionally, patients were interviewed via telephone or during a clinical visit, as indicated. Return envelopes were included free of charge. A period of 2 weeks was envisaged for returning questionnaires. All patients who had not returned the questionnaire after 2 weeks were contacted a second time via mail or telephone within another 14 days. Altogether, patients had 4 weeks to submit their responses. Prior to the study, informed consent of all patients and the local ethics committee [AZ: Nr: 111–16-14,032,016] was obtained. Because the HRQoL assessment was performed separately, it was not possible to correlate HRQoL scores with all clinical data. The average time span between transplantation and completion of the questionnaires was 8.6 ± 2.9 years.

The SF-36 has 36 questions (without specific one for renal failure or diabetes) that assess the ability to perform vigorous activities and activities for daily living and participate in social, family and occupational activities. Eight scales/dimensions describe domains of physical functions (PF, ten items), role limitations due to physical problems (PR, four items), bodily pain (BP, two items), a general perception of health (GH, five items), energy and vitality (VIT, four items), social functions (SF, two items), role limitations due to emotional problems (RE, three items), and mental health (MH, five items). The subscales can be combined into two summation scales measuring the overall physical and mental HRQoL: a physical component summary (PCS = PF + PR + BP + GH) and a mental component summary (MCS = VIT + SF + RE + MH). Subscale scores were transformed to a 0–100 scale, with 0 representing the least to 100 representing the greatest well-being.

The pancreas and kidney grafts were procured according to the guidelines provided by Eurotransplant (ET) [14]. As described earlier, the pancreas was explanted in a no-touch technique [15]. An illiac y-graft was used for reconstruction of the superior mesenteric and the lienal artery. The pancreas was transplanted transabdominally using a standard technique with an intraperitoneal location in the right iliac fossa [16]. Exocrine drainage was carried out with a side-to-side duodenojejunostomy [3, 17]. Kidneys were transplanted transabdominally into the left iliacal fossa. The ureter was implanted into the bladder according to the Lich-Gregoir technique using a double J intra-ureteral splint [16].

Immunosuppressive therapy comprised an induction therapy with the interleukin-2 receptor antagonist basiliximab or antithymocyte globulin, followed by a triple maintenance immunosuppression consisting of calcineurin inhibitors (tacrolimus or cyclosporine), and/or antimetabolites (mycofenolate mofetil or sirolimus) and tapered steroids (prednisolone).

Baseline data are presented as mean values with the standard deviation (SD), minimum or maximum range such as the proportion percentage (%). Baseline data were compared with appropriate statistical significance test including the Student’s t–test, χ2, analysis of variance (ANOVA), Kruskal-Wallis and Wilcoxon–Mann–Whitney tests. Analysis of covariance (ANCOVA) was used to adjust the difference between the two groups after SPKT, with hemodialysis as one predictor and baseline measurements of HRQoL domains (before SPKT) as the other. Survival rates were calculated using the Kaplan-Meier analysis and the log-rank test was applied to test statistical significance. Graft survival was calculated as the time from initial transplant to graft failure (re-start of dialysis), censoring for death with a functioning graft and grafts still functioning at time of analysis. Patient survival is defined as time from transplant to patient death, censoring for patients still alive at time of analysis. If a recipient was alive or lost to follow-up at time of last contact, then survival time was censored at time of last contact. Multivariate Cox proportional hazards analysis was applied to assess independent predictors of patient death and pancreas graft failure, including clinically-relevant variables and/or those presenting P ≤ 0.15 in univariate analysis: recipient gender, BMI and age, dialysis modality (HD versus PD), time on dialysis, years of diabetes mellitus, concomitant cardiovascular disease and surgical complications. SPSS software (SPSS Inc., Chicago, Illinois, USA, version 21.0) was used for statistical analysis and graphs. A P value < 0.05 was considered as statistically significant.

The overall study population included 83 patients receiving SPKT in our department between 2000 and 2016. At the time of transplantation, 64 patients obtained HD and nineteen patients used PD. Continuous ambulatory peritoneal dialysis was used by fourteen patients (74%) and automatic peritoneal dialysis was used by five patients (26%) among the PD group. Recipient, donor and graft characteristics according to the different dialysis types prior to transplantation are summarized in Table 1. The two groups were similar for the majority of their pre-transplant characteristics, while the number of female recipients was higher in the PD group (P = 0.017), and a history of depression was more frequent in the HD group (P = 0.049). HLA mismatches, post-transplant immunosuppressive regimes and lengths of hospital stay did not show significant differences between the two groups (data not shown).

Infectious complications remain a significant cause of morbidity and mortality after SPKT [3, 4, 6, 18]. A much-debated question is whether pre-transplant PD increases the risk for intra-abdominal infections after transplantation due to the risk of catheter-associated peritonitis. Binaut et al. showed a higher rate of parietal sepsis in PD patients after kidney transplantation alone (KTA) compared with patients who received HD prior to transplantation [19]. Martins et al. reported a significantly higher rate of pancreas loss due to infection among PD patients after SPKT (HD: 3.4% versus PD: 12.8%; P = 0.042), whereas ten out of 39 (25.6%) PD patients had peritonitis in their past [20]. By contrast, other studies have reported no difference in surgical outcome between HD and PD patients after SPKT [21‐24]. Our analysis could not reveal significant differences in intra-abdominal infection rates after SPKT between the two groups, and there was no correlation between the incidence of pre-transplant peritonitis and post-transplant intra-abdominal infection. Besides dialysis modality, the incidence of intra-abdominal infection after SPKT may be related to other factors, namely surgical technique (especially pancreas-anastomosis), the length of hospital stays and the intensity of immunosuppression.

In the literature, there are reports of an increased graft loss in PD patients compared with HD patients post-transplant. After KTA, an increased graft loss in PD patients is reported, mainly due to renal vascular thrombosis [25, 26]. In a study investigating outcomes after SPKT, Martins et al. reported a significantly higher rate of thrombosis-driven relaparotomy in PD patients compared with HD patients. Moreover, they recognized a near significant higher rate of renal graft loss due to thrombosis in PD patients compared with HD patients [20]. In our study, no correlations were found between pre-transplant dialysis modality and patient or graft survival. Only the rate of pancreas graft failure due to thrombosis was non-significantly higher in the PD group (HD: 4.7% versus PD: 15.8%, P = 0.10). However, these data must be interpreted with caution, because other variables such as patient comorbidities (cardiovascular diseases, BMI), along with recipient age and time on dialysis might be additional factors that influence the outcome and survival.

There are some notable limitations of this study that should be mentioned, related to the data source and study design. The main limitations of the study are its retrospective nature, the heterogenous group size and the fact that all data collection was undertaken at one time, which make it difficult to evaluate the causality of the findings and associations. As such, there may be some amount of variation from year to year with changes in the outcome and level of HRQoL. Second, not only disease or dialysis modality determine one’s view of life quality, but also many non-disease factors (work, education, and other sociodemographic factors) play important additive role in the perception of HRQoL. The option for PD or HD normally depends on the patient’s condition (comorbid situations, vascular and peritoneal conditions), autonomy and convenience, as well as the health care system (dialysis center factors).