All analysis variables were tabulated with summary statistics, and graphical representations were used as appropriate. Statistical tests were used to highlight interesting aspects of the data, such as differences between the groups in the analyzed endpoints. The tests were conducted with a two-sided alternative and the p-values will be reported. Statistical significance is declared for p-values below 5%. If appropriate, 95% confidence intervals for point estimates based on suitable distributions were additionally provided. No correction of the significance level for multiple comparisons was performed.
All data analyses were performed using the statistical package R 2.0.1 (The R Foundation for Statistical Computing), for Windows XP. Statistical support was provided by Corrado Bernasconi, M.D. Ph.D.
Based on the definition of the ESP and the 2 Control groups (see 2.1 and 2.2) Eurotransplant provided data on a total of 3456 patients transplanted between 4 January 1999 and 4 January 2004. 7 patients from non-heart beating donors and 18 ESP patients for whom either the donor or the recipient was less than 65 years of age at time of transplant were excluded from all analyses, leaving a total number of 3431 patients for the analysis. Due to the definition of the two Control groups there is an overlap of 109 patients between Control 1 and 2(Table 5; see also 3.2.).
N
%
Total number of patients 3431 100.00
ESP
1406 40.98
Control 1 446 13.00
Control 2 1687 49.17 Overlap between Control 1 and 2 109 3.18
(excluded patients: see below)
(ETKAS, donor ≥ 65 y)
(ETKAS, recipient ≥ 60 and
Figure 7 shows the number of patients in each of the groups by year of transplantation. The number of patients transplanted in the ESP increased from 227 in 1999 to 382 in 2003.
The analysis for all evaluations concerning rejections was performed with the “updated patient population” only. In the data collection tool "no information” concerning rejection events and "no rejection" were not distinguished. Since detailed rejection data are available only for the "updated patient group", it was decided to restrict the analysis to this population.
The time of documented follow up was comparable in all groups indicating that there is no systematic error in the data capture (data not shown).
No imputation of missing data was done. This implies that some of the analyses could in effect be performed only on a subset of the entire analysis population.
As far as the analysis of rejection is concerned, it should be mentioned that the outcome “no rejection” could not be distinguished form the absence of rejection information. For analysis purposes, both cases were considered as no rejection, but the analysis population was restricted to the 2877 patients for which rejection information was collected.
With regard to SCr values it was agreed to exclude outliers (value < 10 or > 1000 μmol/l). Waiting times < 4 weeks and > 15 years were excluded from the waiting time analysis. However, values incorrectly expressed in mg/dl were kept if the value with supposedly correct unit fell between the 100-300 μmol/l limits.
Acute rejection episodes reported with a normal biopsy as well as cases with no biopsy and cases that were not treated were not considered acute rejections in the analysis.
The time on the waiting list for transplantation is defined as the time between first dialysis and transplantation.
• month 6 +/- 14 days • month 12 +/- 1 months
Immediate graft function: No dialysis required within the first 7 days post transplant
When entering serum creatinine values the following time windows applied:
• week 2 +/- 2 days • month 1 +/- 3 days • month 3 und 6 +/- 14 days • year 1-5 +/- 1 month
Date last seen
Date of patient’s most recent visit to the transplant centre and
Clinical condition
Clinical condition as judged by the treating physician (poor, good, excellent)
Readmissions to hospital (number) number of readmissions to hospital (= same location as transplant centre) for any reason during the observation period. Completion of this field seemed to cause some difficulties and inconsistencies might impact on analysis.
Demographic and background data are summarized for the ESP and the 2 Control groups.
The subdivision into categories of certain variables is only used in the presentation of summary statistics to but not in the statistical models except for the grouping of the reason for end-stage renal disease (ESRD), cause of graft loss and death, and the preservation solution.
Continuous variables were compared by means of the Wilcoxon rank-sum test. Categorical variables, including proportions were analyzed with the chi-square test or in selected cases with Fisher’s exact test. Survival times were analyzed using the Kaplan-Meier method. A plot of the estimated probabilities of survival was created and log-rank tests of the difference between groups in survival probabilities were carried out.
Cox regression analysis was used to additionally evaluate the impact of baseline and treatment characteristics (including HLA matches and selected IS regimens) on:
Patient survival
Graft survival
Time to AR
Cox regression models were also used to evaluate early graft function and the occurrence of AR as predictors for patient and graft survival.