Regional Differences in Waiting Times for Kidney Transplantation in Germany

Abstract

Background

In order to achieve short ischemia times between organ donation and transplantation, regional organ allocation has been assigned priority in the development of allocation rules for kidney transplantation. It is unclear whether this leads to differences in regional waiting times in Germany.

Methods

A retrospective cohort study over a 24-month observation period was conducted, including all patients who received a kidney-only graft allocated via the standard Eurotransplant Kidney Allocation System (ETKAS) (n = 1487) or the Eurotransplant Senior Program (ESP) (n = 566). Multiple linear regression analyses were performed to investigate differences in waiting times across the regions (ETKAS) or subregions (ESP) as defined by the German Organ Procurement Organization (DSO). Associations between the number of regionally procured kidneys (n = 1444) and regional waiting times were investigated.

Results

In ETKAS, the median waiting time was 8.9 years (interquartile range [IQR] 6.7–10.6); in ESP, it was 3.9 (2.4 –5.3) years. Compared with the reference region with the shortest waiting time, waiting times in other regions were 0.6 to 1.7 years longer in ETKAS and 1.3 to 4.4 years longer in ESP. The ratio of the number of patients on the waiting list for a particular region to the number of organs donated in that region was associated with the waiting time in ETKAS (R2 = 0.70). In ESP, this association was markedly less pronounced (R2 = 0.45).

Conclusion

In Germany, waiting times depend strongly on the region where a patient is listed for kidney transplantation, especially in ESP. These findings call the current allocation algorithms into question and imply a need for suitable modification.

The processes that lead to the identification and transplantation of suitable recipients after potential organ donors have been reported are highly complex. In Germany, the German Organ Procurement Organization (DSO, Deutsche Stiftung Organtransplantation) coordinates all steps involved in an organ donation procedure. The DSO is also responsible for the related preparatory measures and the subsequent transport of the donor organs to the transplant centers. In a transplant center, patients requiring a donor organ are prepared for transplantation and listed in “active status” as “transplantable” on a common waiting list at the independent mediator Eurotransplant (ET) with headquarter in Leiden, the Netherlands (box). The rules by which Eurotransplant allocates donor organs to patients on the waiting list are set by the participating countries. In Germany, donor organs are allocated according to the German Medical Association’s guidelines (Richtlinien) on transplantation medicine.

BOX. Listing for kidney transplantation in Germany.

Patients with irreversible end-stage kidney disease must be reported to a transplant center by their treating physicians. The center’s interdisciplinary transplant boards must then immediatedly (section 10(2) German Transplantation Act [TPG]) decide on the acceptance of a patient on the waiting list for a kidney transplant. This decision is made in interdisciplinary transplantation conferences. The criteria for admission are detailed in the guidelines for organ transplantation as required by section 16 of the German Transplantation Act. In Germany, patients aged younger than 65 years are as per the rules included in the standard allocation program Eurotransplant Kidney Allocation System (ETKAS). At age 65, those affected must decide whether to move from ETKAS to the Eurotransplant Senior Programm (ESP) where waiting times are much shorter. It is common that patients with end-stage kidney disease are not presented to transplant centers in order to be put on the waiting list until months to years after becoming dialysis dependent or they spend long periods of time in inactive status on waiting lists due to severe comorbidities. Regardless of listing, all patients continuously accumulate waiting time points from the first day of renal replacement therapy. However, organs can only be offered to those who are in active status on the waiting list.

The German Transplantation Act (TPG, deutsches Transplantationsgesetz) stipulates that organs are to be allocated to suitable patients according to guidelines that reflect the state of the art in medical science, in particular according to the likelihood of success as well as urgency (section 12 (3) TPG) (1). In order to meet these requirements, the allocation follows algorithms which vary according to the organ to be transplanted. Kidneys from deceased donors are allocated via the standard Eurotransplant Kidney Allocation System (ETKAS), for recipients 65 years and older via the Eurotransplant Senior Program (ESP), and via special allocation programs.

In ETKAS, points are awarded for various criteria. For each available organ, these points are recalculated based on the individual criteria, ultimately resulting in a total score for each patient on the waiting list. The organ is then offered to the patient with the highest score, provided the blood group is compatible. Besides the points for tissue compatibility between donor and recipient (a maximum of 400 points), the probability of a well-matched organ becoming available (mismatch probability, a maximum of 100 points) and the waiting time since start of renal replacement therapy (33 points per year of waiting time) are taken into account. In addition, a national bonus (100 points) and a regional bonus (further 200 points) are awarded if the donor organ originates from Germany and from the same region as the recipient, respectively (2, 3). To better coordinate organ donation, DSO has divided Germany into seven regions and 15 subregions.

The rationale behind the regional bonus is a preferential allocation of an organ to recipients living in close proximity to the donor to reduce the out-of-the-body time (also referred to as the cold ischemia time) to a minimum, as this has an beneficial effect on long-term organ function (4).

In ESP, organs of donors aged 65 years and older are allocated to recipients in the same age group. Previously, it was assumed that the ischemic tolerance of organs of older patients, referred to as Expanded Criteria Donors (ECD), is shorter compared to that of younger donors. Even though more recent studies have not confirmed this assumption (5), in ESP subregional allocation is still the primary criterion for organ allocation, besides taking waiting time and blood group compatibility into account (2, 3). This means that, ideally, the organ should be allocated to a recipient living close to the donor. Considering this, ESP allocates organs primarily within the 15 subregions.

In Germany, the donor rate relative to the population shows regional variation. At the same time, the number of waitlisted patients varies between regions and subregions (6). Thus, it is reasonable to assume that the ratio of the number of patients on the waiting list to the number of regionally procured organs also differs between the various regions or subregions and that in Germany regional waiting times for kidney transplantation are impacted by this. The aim of our study was to test the hypothesis of differences in regional waiting times, since, with respect to the allocation of organs, patients can expect an equal opportunity of receiving an organ, regardless of where they are listed for transplantation.

Methods

Transplanted patients

Eurotransplant provided data on the patients who underwent kidney transplantation (n = 2917) in Germany during the observation period of 24 months (1 February 2019 to 31 January 2021). Only patients who received an organ in ETKAS (n = 1 487, including recipients of kidneys with matched human leukocyte antigen [HLA] loci A, B and DR (so-called “full house“ kidneys) or in ESP (n = 566) according to the rules were included in the analysis to avoid distortion of waiting times as a result of prioritized allocation. Patients were excluded in case of the following: transplantation after rescue allocation, high-urgency status or pediatric bonus, participation in the acceptable mismatch program, and after multi-organ transplantation (n = 819). Patients with incomplete data on waiting times were also excluded (n = 45).

Waiting list patients and organ donors

DSO provided data on waiting list patients and organ donors. For the analyses in ETKAS, all waiting list patients younger than 65 years listed in active status and all organ donors aged between 16 and 64 years were investigated and, for the analyses in ESP, all waiting list patients aged 65 or older listed in active status and all organ donors aged 65 or older were investigated. The number of donated organs refers here only to those organs that were actually transplanted. Given the ongoing fluctuations on the waiting lists, the average number of waiting list patients per year was estimated to be one-third of the patients listed in active status on the waiting list on 31 December 2018, 31 December 2019 and 31 December 2020. The annual number of donated organs was calculated by taking half the number of donated organs between 1 February 2019 and 31 January 2021.

Statistical analysis

Continuous data were expressed as median (interquartile range, IQR), categorical data as absolute and relative frequencies. Multiple linear regression analyses on the impact of regions (ETKAS) or subregions (ESP) on waiting time (first day of renal replacement therapy until transplantation) were performed with the variables known to be relevant: age at transplantation, sex, blood type, sum of HLA mismatches between donor and recipient (only ETKAS), virtual panel reactivity (vPRA), and the ratio of time listed in active status to total time since enrollment on the waiting list (ratio A/T). (7). Regression coefficient beta and 95% confidence intervals (95% CI) were reported in order to assess effect size. The relationship between the number of waiting list patients, the number of donated and transplanted kidneys per region (ETKAS) or subregion (ESP), and the waiting time was presented using linear regression analysis with the corrected coefficient of determination R2 (proportion of variance of the dependent variable that can be explained by the independent variables). Due to the relatively short observation period of 24 months, sensitivity analyses were performed to check the robustness of the results obtained by evaluating the 12-month periods 1 February 2019 to 31 January 2020 and 1 February 2020 to 31 January 2021 separately. All analyses were performed using SPSS version 26 (SPSS Inc. Chicago, Illinois, USA).

Ethics committee approval

The Ethics Committee of the University of Regensburg did not express any concerns about the study (22–2948–104).

Results

Differences in waiting time between the regions in ETKAS and ESP

Within the period of 24 months, 1487 patients in the ETKAS standard allocation scheme underwent kidney transplantation in Germany. During the period concerned, the median waiting time for a deceased-donor organ was 8.9 years (IQR 6.7–10.6). Significant differences in waiting time were found among the seven DSO regions. While in the Central region, patients had to wait 8.0 years (IQR 6.0–9.5) for transplantation, the median waiting time in the Northern region was 9.7 years (IQR 6.9– 11.1) (figure 1). In the multiple regression analysis, regional waiting time differences persisted even after adjustment for the allocation-relevant criteria number of HLA mismatches between donor and recipient (HLA-MM), blood group and virtual panel reactivity (vPRA) as well as the known factors age, sex and ratio of time listed in active status to total time since enrollment on the waiting list (A/T ratio) (7) (table 1). Sensitivity analyses of the 12-month periods from 1 February 2019 to 31 January 2020 and from 1 February 2020 to 31 January 2021, respectively, showed comparable results (eTable 1, eTable 2).

Figure 1.

Eurotransplant Kidney Allocation System (ETKAS): Association between waiting time, number of patients on the waiting list, and number of organs donated in the various regions of the German Organ Procurement Organization (DSO).

The figures in red represent the number of waiting list patients per region/number of kidneys donated in that region.

Table 1. Multiple linear regression analysis: Factors influencing waiting time in ETKAS.

	B [95% CI]	p-value
Age at KTX	–0.01 [–0.02; 0]	0.13
Sex
Female	Reference category
Male	0.09 [–0.14; 0.32]	0.45
Blood group
A	Reference category
AB	–2.66 [–3.13; –2.18]	<0.001
B	0.90 [0.55; 1.25]	<0.001
0	1.86 [1.61; 2.11]	<0.001
Number of HLA MMs
0	Reference category
1–2	4.05 [3.73; 4.37]	<0.001
3–4	5.18 [4.88; 5.47]	<0.001
5–6	7.32 [6.63; 8.01]	<0.001
vPRA at KTX	0.01 [0; 0.01]	<0.001
A/T ratio	–1.81 [–2.28; –1.34]	<0.001
DSO region
Baden-Wuerttemberg	1.45 [0.99; 1.91]	<0.001
Bavaria	1.09 [0.64; 1.55]	<0.001
Central	Reference category
North	1.73 [1.30; 2.16]	<0.001
North East	1.45 [0.96; 1.95]	<0.001
North Rhine-Westphalia	0.59 [0.17; 1.01]	0.006
East	0.73 [0.23; 1.23]	0.004

Dependent variable: First day of renal replacement therapy to KTX (years);

corrected R² 0.55, p<0,001 One-way analysis of variance (ANOVA);

Explanation of the regression coefficient B by means of an example:

A B value of 1.73 in the region North means that—independent of the other factors—the waiting time in the region North is on average 1.73 years longer than in the reference region Central.

A/T ratio, ratio of number of days listed in active status to number of all days since admission to the waiting list; B, regression coefficient Beta; DSO, German Organ Procurement Organization (Deutsche Stiftung Organtransplantation); ETKAS, Eurotransplant Kidney Allocation System; HLA, human leukocyte antigen; HLA MM, sum of HLA mismatches between donors and recipients with regard to HLA A, B and DR; CI, confidence interval; KTX, kidney transplantation; vPRA, virtual panel reactivity

eTable 1. ETKAS: Sensitivity analysis of the periods 1 February 2019 to 31 January 2020 (2019) and 1 February 2020 to 31 January 2021 (2020).

DSO region	Period	Median waiting time (years)	Donor kidneys (n)	Waiting list patients(n)*	Waiting list patients/donor kidneys
Baden-Wurttemberg	2019	9.79	136	856	6.29
	2020	8.45	117	891	7.61
Bavaria	2019	9.09	183	954	5.21
	2020	9.10	172	936	5.44
Central	2019	8.20	145	524	3.61
	2020	7.36	161	520	3.23
North	2019	9.69	168	1412	8.40
	2020	9.54	163	1364	8.37
North East	2019	9.73	102	809	7.93
	2020	8.87	98	770	7.85
North Rhine–Westphalia	2019	8.36	224	1442	6.44
	2020	8.49	206	1433	6.95
East	2019	8.48	115	556	4.83
	2020	8.33	135	549	4.06

*Waiting list patients 2019: (31/12/2018 + 31/12/2019)/2 and 2020: (31/12/2019 + 31/12/2020)/2, respectively

ETKAS, Eurotransplant Kidney Allocation System; DSO, German Organ Procurement Organization (Deutsche Stiftung Organtransplantation)

eTable 2a. Multiple linear regression analysis: Factors waiting time ETKAS 01/02/2019 to 31/01/2020 (sensitivity analysis).

	B [95% CI]	p-value
Age at KTX	–0.02 [–0.03; 0]	0.012
Sex
Female	Reference category
Male	0.17 [– 0.13; 0.47]	0.264
Blood group
A	Reference category
AB	–2.75 [–3.37; –2.13]	<0.001
B	0.61 [0.18; 1.05]	0.006
O	1.83 [1.51; 2.14]	<0.001
Number of HLA MMs
0	Reference category
1–2	3.88 [3.45; 4.31]	<0.001
3–4	5.17 [4.78; 5.56]	<0.001
5–6	5.88 [4.99; 6.77]	<0.001
vPRA at KTX	0.01 [0; 0.01]	0.013
A/T ratio	–2.00 [–2.59; –1.41]	<0.001
DSO region
Baden Wurttemberg	1.27 [0.67; 1.86]	<0.001
Bavaria	0.78 [0.21; 1.34]	0.007
Central	Reference category
North	1.54 [1.00; 2.09]	<0.001
North East	1.34 [0.71; 1.98]	<0.001
North Rhine–Westphalia	0.15 [–0.38; 0.68]	0.580
East	0.37 [–0.26; 1.01]	0.249

Dependent variable: 1. First day of dialysis to KTX (years);

corrected R² = 0.55, p<0.001 One-way analysis of variance (ANOVA);

A/T ratio: ratio of number of days listed in active status to number of all days since admission to the waiting list; regression coefficient Beta; DSO, German Organ Procurement Organization (Deutsche Stiftung Organtransplantation); ETKAS, Eurotransplant Kidney Allocation System; HLA, human leukocyte antigen; HLA MM, sum of HLA mismatches between donors and recipients with regard to HLA A, B and DR;

CI, confidence interval; KTX, kidney transplantation; vPRA, virtual panel reactivity

In ESP, 566 patients underwent kidney transplantation during the same period. The median waiting time in Germany was 3.7 years (IQR 2.4–5.3). There were also significant differences in waiting times with respect to in which of the 15 subregions the transplantation was performed. The shortest median waiting time was 1.5 years (IQR 0.9–1.8) in the Homburg/Saar subregion, whereas affected patients in the Erlangen subregion had to wait a median of 5.0 years (IQR 3.6–7.6) for a kidney to become available (figure 2). The multiple regression analysis confirmed the differences in waiting times between the subregions. Compared to the Homburg subregion, the waiting times in all other subregions was prolonged by up to 4.4 years (95% CI: [3.1; 5.8]) on average (table 2). In the sensitivity analysis, the waiting times in the subregions were comparable in the two 12-month periods (etable 3); likewise, the differences in the regression analyses were confirmed (eTable 4, eTable 5).

FIGURE 2.

Eurotransplant Senior Program (ESP): Association between waiting time, number of patients on the waiting list and number of organs donated and transplanted in the various subregions of the German Organ Procurement Organization (DSO).

The upper figures in red represent the number of waiting list patients per subregion/number of kidneys donated in that region. The lower figures in red represent the percentage of kidneys donated in a subregion that were then also transplanted in that subregion.

Table 2. Multiple linear regression analysis: Factors influencing waiting times in ESP.

	B [95% CI]	p-value
Age at KTX	–0.07 [–0.12; –0.03]	0.002
Sex
Female	Reference category
Male	–0.06 [–0.44; 0.32]	0.75
Blood group
A	Reference category
AB	–0.21 [–1.10; 0.69]	0.65
B	0.67 [0.03; 1.31]	0.04
0	1.12 [0.75; 1.50]	<0.001
vPRA at KTX	0.02 [0.01; 0.03]	0.002
A/T ratio	0.16 [–0.43; 0.74]	0.60
DSO subregion
Freiburg	4.41 [3.07; 5.76]	<0.001
Stuttgart	2.61 [1.55; 3.67]	<0.001
Munich	3.80 [2.71; 4.88]	<0.001
Erlangen	3.97 [2.67; 5.27]	<0.001
Homburg/Saar	Reference category
Mainz	1.36 [0.07; 2.66]	0.04
Marburg	1.33 [0.05; 2.62]	0.04
Cologne/Bonn	1.77 [0.63; 2.91]	0.002
Düsseldorf	2.27 [1.22; 3.33]	<0.001
Münster	3.26 [2.04; 4.47]	<0.001
Hannover	3.61 [2.47; 4.74]	<0.001
Hamburg	2.50 [1.41; 3.59]	<0.001
Rostock	2.61 [0.91; 4.32]	0.003
Berlin	3.47 [2.39; 4.56]	<0.001
Leipzig	2.48 [1.43; 3.53]	<0.001

Dependent variable: First day of renal replacement therapy to KTX (in years);

Corrected R² = 0.21, p<0.001 One-way analysis of variance (ANOVA);

Explanation of the regression coefficient B by means of an example:

A B value of 4.41 in the Freiburg subregion means that—regardless of other factors—the waiting time for an organ is in the Central region on average 4.41 years longer than in the reference region Homburg.

A/T ratio, ratio of number of days listed in active status to number of all days since admission to the waiting list; B, regression coefficient Beta; DSO, German Organ Procurement Organization (Deutsche Stiftung Organtransplantation); ESP, Eurotransplant Senior Program; CI, confidence interval; KTX, kidney transplantation; ESP, Eurotransplant Senior Program; CI, confidence interval; KTX, kidney transplantation; vPRA, virtual panel reactivity

eTable 3. ESP: Sensitivity analysis of the periods 1 February 2019 to 31 January 2020 (2019) and 1 February 2020 to 31 January 2021 (2020).

ESP subregion	Period	Median waiting time (years)	Donor kidneys (n)	Waiting list patients (n)*	Waiting list patients/ donor kidneys
Freiburg	2019	5.84	14	61	4.36
	2020	4.68	17	60	3.53
Stuttgart	2019	3.39	42	91	2.17
	2020	2.66	31	98	3.16
Munich	2019	4.99	30	192	6.40
	2020	4.41	31	192	6.19
Erlangen	2019	4.81	24	90	3.75
	2020	5.34	10	89	8.90
Homburg	2019	1.12	22	23	1.05
	2020	1.59	25	28	1.12
Mainz	2019	2.21	22	35	1.59
	2020	2.39	26	41	1.58
Marburg	2019	2.98	15	26	1.73
	2020	2.15	10	17	1.70
Cologne/Bonn	2019	3.18	25	78	3.12
	2020	3.37	25	92	3.68
Düsseldorf	2019	3.47	47	154	3.28
	2020	3.73	30	152	5.07
Münster	2019	3.78	9	58	6.44
	2020	4.75	17	53	3.12
Hannover	2019	4.46	24	237	9.88
	2020	4.77	15	228	15.20
Hamburg	2019	3.24	28	115	4.11
	2020	3.77	38	122	3.21
Rostock	2019	3.81	12	20	1.67
	2020	3.61	23	23	1.00
Berlin	2019	4.47	34	247	7.26
	2020	4.56	17	236	13.88
Leipzig	2019	3.68	59	133	2.25
	2020	3.36	40	132	3.30

*Waiting list patients 2019: (31/12/2018 + 31/12/2019)/2 and 2020: (31/12/2019 + 31/12/2020)/2

ESP. Eurotransplant Senior Program

eTable 4. Multiple linear regression analysis: Factors waiting time ESP 01/02/2019 to 31/01/2020 (sensitivity analysis).

	B [95% CI]	p-value
Age at KTX	–0.07 [–0.14; –0.01]	0.033
Sex
Female	Reference category
Male	0.03 [–0.48; 0.54]	0.905
Blood group
A	Reference category
AB	–0.49 [–1.68; 0.70]	0.421
B	0.89 [0.09; 1.70]	0.030
O	1.42 [0.90; 1.94]	<0.001
vPRA at KTX	0.01 [0; 0.03]	0.084
A/T ratio	0.15 [–0.62; 0.92]	0.707
DSO subregion
Freiburg	4.86 [2.87; 6.85]	<0.001
Stuttgart	2.55 [1.17; 3.93]	<0.001
Munich	3.42 [1.99; 4.85]	<0.001
Erlangen	4.10 [2.37; 5.84]	<0.001
Homburg/Saar	Reference category
Mainz	1.16 [–0.56; 2.88]	0.185
Marburg	1.55 [–0.23; 3.32]	0.087
Cologne/Bonn	1.32 [–0.20; 2.85]	0.089
Düsseldorf	2.17 [0.79; 3.55]	0.002
Münster	2.88 [1.30; 4.46]	<0.001
Hannover	3.47 [1.97; 4.97]	<0.001
Hamburg	2.31 [0.89; 3.74]	0.002
Rostock	2.73 [0.42; 5.04]	0.021
Berlin	3.20 [1.78; 4.62]	<0.001
Leipzig	2.47 [1.12; 3.81]	<0.001

Dependent variable: First day of renal replacement therapy to KTX (in years);

corrected R² = 0.24. p<0.001 One-way analysis of variance (ANOVA);

A/T ratio, ratio of number of days listed in active status to number of all days since admission to the waiting list; B, regression coefficient Beta; DSO, German Organ Procurement Organization (Deutsche Stiftung Organtransplantation);ESP, Eurotransplant Senior Program; CI, confidence interval; KTX, kidney transplantation; vPRA, virtuelle Panelreaktivität

Association between waiting time and number of organ donors

During the observation period, anually 6542 patients between 16 and 64 years were actively listed for kidney transplantation in Germany. Over the same time period, 1063 organs were procured from donors 65 years and younger (figure 1). In the age group 65 years and older, there were 792 waiting list patients and 381 organs donated from ≥ 65-year-old donors (figure 2). The ratio of patients on the waiting list to the number of organs donated varied widely across the regions (< 65 years) and subregions (≥ 65 years) (Figure 1, Figure 2).

Number of regionally procured kidneys/year.

In light of these differences, we proceeded to investigate whether there was a relationship between the waiting list donor organ ratio and the waiting time before kidney transplantation across regions (ETKAS) and subregions (ESP). The regions showed a high correlation in this respect (R² 0.70. Figure 3a). This finding prompted the conclusion that in ETKAS, 70% of the variation in waiting time could be explained by the regional ratio of waiting list patients to donor organs. For ESP, this association was significantly less pronounced on the subregional level (R² 0.45, Figure 3b). These findings were also confirmed in the sensitivity analyses (eTabelle 1, eTabelle 3, eFigure 1, eFigure 2).

eTable 2b. Multiple linear regression analysis: Factors waiting time ETKAS 01/02/2020 to 31/01/2021 (sensitivity analysis).

	B [95% CI]	p-value
Age at KTX	0 [–0.01; 0.02]	0.804
Sex
Female	Reference category
Male	–0.12 [–0.48; 0.24]	0.521
Blood group
A	Reference category
AB	–2.53 [–3.27; –1.80]	< 0.001
B	1.35 [0.78; 1.92]	< 0.001
O	1.83 [1.43; 2.22]	< 0.001
Number of HLA MMs
0	Reference category
1–2	4.25 [3.76; 4.74]	< 0.001
3–4	5.15 [4.71; 5.60]	< 0.001
5–6	9.06 [7.98; 10.14]	< 0.001
vPRA at KTX	0.01 [0; 0.01]	0.005
A/T ratio	–1.64 [–2.39; –0.90]	< 0.001
DSO region
Baden Württemberg	1.65 [0.92; 2.37]	< 0.001
Bavaria	1.56 [0.82; 2.30]	< 0.001
Central	Reference category
North	1.87 [1.19; 2.56]	< 0.001
North East	1.49 [0.71; 2.27]	< 0.001
North Rhine-Westphalia	1.06 [–0.40; 1.72]	0.002
East	1.13 [0.34; 1.92]	0.005

Dependent variable: First day of renal replacement therapy to NTX (years);

corrected R² = 0.57, p<0.001 One-way analysis of variance (ANOVA);

B, regression coefficient Beta; HLA, human leukocyte antigen;

HLA MM, sum of HLA mismatches between donors and recipients with regard to HLA A, B and DR;

DSO, German Organ Procurement Organization (Deutsche Stiftung Organtransplantation); CI, confidence interval; KTX, kidney transplantation; ratio A/T, ratio of number of days listed in active status to number of all days since admission to the waiting list; vPRA, virtual panel reactivity

Average number of waiting list patients per region/year.

Number of regionally procured kidneys/year.

Further analysis of transplanted organs from donors aged 65 years and older revealed that the proportion of organs donated and then transplanted in this (and not another) subregion varied substantially between the subregions. While, for example, in the Rostock subregion only 23% of the organs donated there were also transplanted in this subregion, this proportion amounted to 89% in the Stuttgart subregion (figure 2).

Discussion

Our analyses show significant differences in median waiting times for kidney transplantation in Germany, depending on the region in which a patient was listed for transplantation. In regions with a high number of donor organs, waiting times were shorter compared to regions with less donor organs relative to the number of waiting list patients.

These findings do not come as a surprise at first glance. The ETKAS standard allocation scheme prioritizes regional allocation by awarding 200 points to all patients listed in the same region as the donated organ in order to minimize cold ischemia time between organ donation and transplantation (3). For the position on the waiting list, this regional bonus is relevant, because it accounts for about 25% of the total score at the time of transplantation (own data). Since older organs with ECD criteria are assumed to have reduced ischemic tolerance, organ allocation in ESP is—other than considering blood group and patient waiting time—based solely on maintaining short ischemia times through subregional allocation (3).

Given these findings, it was surprising that the association between the waiting list patient-donor organ ratio and median waiting time at the subregional level was markedly lower in ESP compared to ETKAS. There are several possible explanations for this. In subregions with relatively high numbers of donors, procured organs were more frequently allocated to recipients outside this subregion (figure 2). This presumably indicates that transplant centers located in this subregions have been more selective in accepting donor organs. In turn, it can be hypothesized that less stringent selection criteria had to be accepted in subregions with fewer donors. ECD organs, i.e. organs of persons with significant pre-existing and concomitant diseases, are always accepted based on individual criteria of the corresponding center. This is expressly provided for in the current guideline on kidney transplantation (3) and also a well-known factor influencing waiting time (8). In addition, rescue allocation of organs of donors aged 65 years and older has increased significantly in recent years (9). In this procedure, organs that have either already been rejected several times or need to be allocated as quickly as possible for other reasons are offered to the transplant centers located closest to the donor hospital (3, 10). Rescue allocation is not based on DSO-defined subregions. While 11% of organs from donors aged 65 years and older were allocated via the rescue allocation scheme in 2012, this figure had risen to 29% by 2021 (11). The reasons for this are unclear, but could be related to the removal and acceptance of increasingly marginal donor organs in response to the growing organ shortage. It is highly likely that center-specific acceptance criteria for ECD organ have an impact on waiting times, especially during rescue allocation. Therefore, it would be of general interest to link center-specific acceptance criteria with long-term outcomes after kidney transplantation in order to develop uniform, evidence-based regulations.

In ETKAS, the ratio of active to total time on the waiting list (A/T ratio) was a relevant factor influencing waiting time for transplantation. On the one hand, this could be an indicator of the frailty, i.e. the burden of comorbidities, as sicker patients have to be temporarily taken off the active waiting list more frequently and for longer periods of time. On the other hand, this finding also points to differences in waiting list management by the various transplant centers. In order to improve equal opportunities for patients in Germany in the long term, a more detailed analysis of this aspect would be necessary.

The data underlying our analyses are limited to a 24-month period. We cannot exclude the possibility that evaluating a longer period of time would have led to different results. However, this is unlikely given the small annual fluctuations in the number of patients listed and transplanted and in the number of organs donated (6), and given the results of our sensitivity analyses. Only data from patients whose transplantations were performed under the standard allocation programs ETKAS and ESP were considered for our analyses to avoid bias in waiting times arising from prioritized allocation, for example, high urgency transplantation or transplantation in children. This corresponded to approximately 70% of all kidney transplant recipients over the study period. Differences in the clinical focus of individual centers – multiple organ transplants, for example, are not performed at all of the 47 German transplant centers – may also have contributed to differences in regional results.

The advantages and disadvantages of regional versus national allocation have been the subject of intense debate in many countries for years. The great success of Spanish transplant medicine, for example, is attributed in part to the regional allocation that prevails in Spain (12). Hospital staff are highly motivated to identify organ donors when they know it will benefit their own patients. Ultimately, however, our findings call into question the principle of equal opportunity in organ allocation in Germany currently set out in the kidney transplantation guideline (3). Patients with end-stage kidney disease typically approach the transplant center closest to where they live in order to be put on the waiting list, assuming, of course, that they are neither favored nor disadvantaged by this selection. The differences in the waiting time shown in this article, especially in ESP, as well as the decreasing application of the standard allocation rules as a result of the rescue procedure should be taken as an opportunity to revise and further develop the currently applicable guideline for kidney transplantation. The principle laid down in section 12(3) of the German Transplantation Act (TPG) that the waiting lists of transplant centers are to be treated as a single waiting list should be taken into account, as should the requirement that donor organs be allocated according to urgency and likelihood of success. Finally, it is important to point out that equality of opportunity could also be improved if German hospitals were consistent and uniform in fulfilling their legal obligation to identify donors and realize organ donations.

Median waiting times (time from initiation of renal replacement therapy to kidney transplantation) with interquartile range.

Median waiting times (time from initiation of renal replacement therapy to kidney transplantation) with interquartile range.

Average number of waiting list patients per region/year.

Figure 3.

Association between waiting list–donor organ ratio with median waiting time (time from initiation of renal replacement therapy to kidney transplantation) in Eurotransplant Kidney Allocation System (ETKAS) (a) and in Eurotransplant Senior Program (ESP) (b).

((a) Averaged value for Germany (red dot) and association in the seven DSO regions (gray dots). (b) Averaged value for Germany (red dot) and association in the seven ESP subregions (gray dots).

In ETKAS, 70% of regional differences in waiting time were explained by the ratio of waiting list patients to number of donor organs in the various regions (R² = 0.70). In ESP, this association was markedly less pronounced (R² = 0.45).

DSO, German Organ Procurement Organization (Deutsche Stiftung Organtransplantation);

RRT, renal replacement therapy; RTX, kidney transplantation; R², coefficient of determination

eFigure 1.

Sensitivity analysis Eurotransplant Kidney Allocation System (ETKAS): Association of waiting list-donor organ ratio with median waiting time in the seven regions of the German Organ Procurement Organization (DSO) in the period from 1 February 2019 to 31 January 2020 (a) and 1 February 2020 to 31 January 2021 (b).

RRT, renal replacement therapy; RTX, kidney transplantation; R², coefficient of determination

eFigure 2.

Sensitivity analysis Eurotransplant Senior Program (ESP):

Association of the waiting list–door organ ratio with the median waiting time in the 15 ESP subregions in the periods from 1 February 2019 to 31 January 2020 (a) and 1 February 2020 to 31 January 2021 (b).

RRT, renal replacement therapy; RTX, kidney transplantation; R², coefficient of determination

eTable 5. Multiple linear regression analysis: Factors waiting time ESP 01/02/2019 to 31/01/2020 (sensitivity analysis).

	B [95% CI]	p-value
Age at KTX	–0.08 [–0.15; –0.1]	0.030
Sex
Female	Reference category
Male	–0.17 [–0.78; 0.44]	0.587
Blood group
A	Reference category
AB	0.15 [–1.30; 1.60]	0.839
B	0.37 [–0.79; 1.54]	0.532
O	0.77 [0.19; 1.35]	0.009
vPRA at KTX	0.02 [0.01; 0.04]	0.005
A/T ratio	0.09 [–0.89; 1.06]	0.860
DSO subregion
Freiburg	4.29 [2.27; 6.31]	<0.001
Stuttgart	2.70 [0.99; 4.40]	0.002
Munich	4.30 [2.53; 6.08]	<0.001
Erlangen	4.02 [1.96; 6.09]	<0.001
Homburg/Saar	Reference category
Mainz	1.59 [–0.49; 3.68]	0.134
Marburg	1.01 [–0.98; 3.00]	0.318
Cologne/Bonn	2.41 [0.59; 4.22]	0.010
Düsseldorf	2.44 [0.74; 4.14]	0.005
Münster	3.85 [1.86; 5.84]	<0.001
Hannover	3.84 [2.05; 5.64]	<0.001
Hamburg	2.72 [0.98; 4.46]	0.002
Rostock	2.53 [–0.11; 5.17]	0.060
Berlin	3.83 [2.07; 5.58]	<0.001
Leipzig	2.42 [0.68; 4.16]	0.007

Dependent variable: First day of dialysis to KTX (in years);

corrected R² = 0.16. p<0.001 One-way analysis of variance (ANOVA);

B, regression coefficient Beta; DSO, German Organ Procurement Organization (Deutsche Stiftung Organtransplantation); ESP, Eurotransplant Senior Program; CI, confidence interval; KTX, kidney transplantation;

A/T ratio, ratio of number of days listed in active status to number of all days since admission to the waiting list; vPRA, virtual panel reactivity