The Incidence of Antibody-Mediated Rejection Is Age-Related, Plateaus Late After Kidney Transplantation, and Contributes Little to Graft Loss in the Older Recipients.

It is not known whether antibody-mediated rejection (ABMR) is age-related, whether it plateaus late after transplantation, and to what extent it contributes to graft loss in older recipients. Patients transplanted between 2010 and 2015 (n = 1,054) in a single center had regular follow-up until January 2023. Recipients were divided into age groups at transplantation: 18-39 years ("young"), 40-55 years ("middle age"), and >55 years ("elderly"). Ten years after transplantation the cumulative % of recipients with ABMR was 17% in young, 15% in middle age, and 12% in elderly recipients (p < 0.001). The cumulative incidence of ABMR increased over time and plateaued 8-10 years after transplantation. In the elderly, with a median follow-up of 7.5 years, on average 30% of the recipients with ABMR died with a functional graft and ABMR contributed only 4% to overall graft loss in this group. These results were cross-validated in a cohort of recipients with >15 years follow-up. Multivariate cox-regression analysis showed that increasing recipient age was independently associated with decreasing risk for ABMR. In conclusion, the cumulative risk for ABMR is age-dependent, plateaus late after transplantation, and contributes little to overall graft loss in older recipients.

Increasing Kidney-Exchange Options Within the Existing Living Donor Pool With CIAT: A Pilot Implementation Study.

Computerized integration of alternative transplantation programs (CIAT) is a kidney-exchange program that allows AB0- and/or HLA-incompatible allocation to difficult-to-match patients, thereby increasing their chances. Altruistic donors make this available for waiting list patients as well. Strict criteria were defined for selected highly-immunized (sHI) and long waiting (LW) candidates. For LW patients AB0i allocation was allowed. sHI patients were given priority and AB0i and/or CDC cross-match negative HLAi allocations were allowed. A local pilot was established between 2017 and 2022. CIAT results were assessed against all other transplant programs available. In the period studied there were 131 incompatible couples; CIAT transplanted the highest number of couples (35%), compared to the other programs. There were 55 sHI patients; CIAT transplanted as many sHI patients as the Acceptable Mismatch program (18%); Other programs contributed less. There were 69 LW patients; 53% received deceased donor transplantations, 20% were transplanted via CIAT. In total, 72 CIAT transplants were performed: 66 compatible, 5 AB0i and 1 both AB0i and HLAi. CIAT increased opportunities for difficult-to-match patients, not by increasing pool size, but through prioritization and allowing AB0i and "low risk" HLAi allocation. CIAT is a powerful addition to the limited number of programs available for difficult-to-match patients.

Tacrolimus Monotherapy is Safe in Immunologically Low-Risk Kidney Transplant Recipients: A Randomized-Controlled Pilot Study.

In this randomized-controlled pilot study, the feasibility and safety of tacrolimus monotherapy in immunologically low-risk kidney transplant recipients was evaluated [NTR4824, www.trialregister.nl]. Low immunological risk was defined as maximal 3 HLA mismatches and the absence of panel reactive antibodies. Six months after transplantation, recipients were randomized if eGFR >30 ml/min, proteinuria <50 mg protein/mmol creatinine, no biopsy-proven rejection after 3 months, and no lymphocyte depleting therapy given. Recipients were randomized to tacrolimus/mycophenolate mofetil (TAC/MMF) or to taper and discontinue MMF at month 9 (TACmono). 79 of the 121 recipients were randomized to either TACmono (n = 38) or TAC/MMF (n = 41). Mean recipient age was 59 years and 59% received a living donor transplant. The median follow-up was 62 months. After randomization, 3 TACmono and 4 TAC/MMF recipients experienced a biopsy-proven rejection. At 5 years follow-up, patient survival was 84% in TACmono versus 76% in TAC/MMF with death-censored graft survival of 97% for both groups and no differences in eGFR and proteinuria. Eleven TACmono recipients had an infectious episode versus 22 TAC/MMF recipients (p < 0.03). Donor-specific anti-HLA antibodies were not detected during follow-up in both groups. Tacrolimus monotherapy in selected immunologically low-risk kidney transplant recipients appears safe and reduces the number of infections.

The relative importance of donor age in deceased and living donor kidney transplantation.

In deceased donor kidney transplantation donor age is known to influence graft survival. The influence of living donor age on graft survival is questioned. We compared the influence of living and deceased donor age on the outcome of renal transplantation. All 1821 transplants performed in our center between 1990 and 2009 were included in the analysis. Observation was until April 2012. A total of 941 patients received a deceased donor kidney and 880 a living donor kidney. In multivariate Cox analysis, recipient age, maximum and current panel reactive antibodies, transplant year, HLA-mismatches, donor age, donor gender, donor type, delayed graft function, and calcineurin inhibitor (CNI) and prednisone as initial immunosuppression were found to have a significant influence on death-censored graft failure. The influence of both living and deceased donor age followed a J-shaped curve, above 30 years the risk increased with increasing age. Donor type and donor age had an independent influence. The graft failure risk of deceased donor transplantation is almost twice that of living donor transplantation so that a 60-year-old living donor kidney has the same graft failure risk as a 20-year-old deceased donor kidney.

Causes of Kidney Graft Failure in a Cohort of Recipients With a Very Long-Time Follow-Up After Transplantation.

Background: Biopsy-proven causes of graft loss many years after kidney transplantation are scarcely documented. Methods: Patients transplanted between 1995 and 2005 (n = 737) in a single center were followed on a regular basis until 2021. The recipients were divided according to age at transplantation into 3 groups; 18-39 years (young), 40-55 years (middle age), and older than 55 years (elderly). For cause biopsies of renal transplants were clustered into the categories, rejection, IFTA, return original disease, and diagnosis of de novo kidney disease. Results: Rejection was the main cause of graft failure censored for death at every time period after transplantation. The incidence of T cell-mediated rejection (TCMR) became rare 6 years after transplantation while the cumulative incidence of antibody-mediated rejection (ABMR) increased over time (1.1% per year). ABMR was not diagnosed anymore beyond 15 years of follow-up in recipients without pre-transplant donor-specific antibodies (DSA). An episode of TCMR was associated with an increased incidence of ABMR diagnosis in the short-term but did not increase the overall incidence of AMBR not in the long-term. Death as a cause of graft failure was an important competitive risk factor long after transplantation and resulted in a significantly lower frequency of rejection-related graft loss in the elderly group (11 vs. 23% in the young group at 15 year follow-up). Conclusion: Rejection is a major cause of graft loss but recipient's age, time after transplantation, and the presence of DSA before transplantation determine the relative contribution to overall graft loss and the type of rejection involved.

Creating Options for Difficult-to-match Kidney Transplant Candidates.

BACKGROUND: Most transplantation centers recognize a small patient population that unsuccessfully participates in all available, both living and deceased donor, transplantation programs for many years: the difficult-to-match patients. This population consists of highly immunized and/or ABO blood group O or B patients. METHODS: To improve their chances, Computerized Integration of Alternative Transplantation programs (CIAT) were developed to integrate kidney paired donation, altruistic/unspecified donation, and ABO and HLA desensitization. To compare CIAT with reality, a simulation was performed, including all patients, donors, and pairs who participated in our programs in 2015-2016. Criteria for inclusion as difficult-to-match, selected-highly immunized (sHI) patient were as follows: virtual panel reactive antibody >85% and participating for 2 years in Eurotransplant Acceptable Mismatch program. sHI patients were given priority, and ABO blood group incompatible (ABOi) and/or HLA incompatible (HLAi) matching with donor-specific antigen-mean fluorescence intensity (MFI) <8000 were allowed. For long-waiting blood group O or B patients, ABOi matches were allowed. RESULTS: In reality, 90 alternative program transplantations were carried out: 73 compatible, 16 ABOi, and 1 both ABOi and HLAi combination. Simulation with CIAT resulted in 95 hypothetical transplantations: 83 compatible (including 1 sHI) and 5 ABOi combinations. Eight sHI patients were matched: 1 compatible, 6 HLAi with donor-specific antigen-MFI <8000 (1 also ABOi), and 1 ABOi match. Six/eight combinations for sHI patients were complement-dependent cytotoxicity cross-match negative. CONCLUSIONS: CIAT led to 8 times more matches for difficult-to-match sHI patients. This offers them better chances because of a more favorable MFI profile against the new donor. Besides, more ABO compatible matches were found for ABOi couples, while total number of transplantations was not hampered. Prioritizing difficult-to-match patients improves their chances without affecting the chances of regular patients.

Living Donor Kidney Transplantation Should Be Promoted Among "Elderly" Patients.

Age criteria for kidney transplantation have been liberalized over the years resulting in more waitlisted elderly patients. What are the prospects of elderly patients on the waiting list? METHODS: Between 2000 and 2013, 2622 patients had been waitlisted. Waiting time was defined as the period between dialysis onset and being delisted. Patients were categorized according to age upon listing: <25; 25-44; 45-54; 55-64; and >64 years. Furthermore, the influence of ABO blood type and panel reactive antibodies on outflow patterns was studied. RESULTS: At the end of observation (November 2017), 1957 (75%) patients had been transplanted, 333 (13%) had been delisted without a transplantation, 271 (10%) had died, and 61 (2%) were still waiting. When comparing the age categories, outflow patterns were completely different. The percentage of patients transplanted decreased with increasing age, while the percentage of patients that had been delisted or had died increased with increasing age, especially in the population without living donor. Within 6 years, 93% of the population <25 years had received a (primarily living) donor kidney. In the populations >55 years, 39% received a living donor kidney, while >50% of patients without a living donor had been delisted/died. Multivariable analysis showed that the influence of age, ABO blood type, and panel reactive antibodies on outflow patterns was significant, but the magnitude of the influence of the latter 2 was only modest compared with that of age. CONCLUSIONS: "Elderly" (not only >64 y but even 55-64 y) received a living donor kidney transplantation less often. Moreover, they cannot bear the waiting time for a deceased donor kidney, resulting in delisting without a transplant in more than half the population of patients without a living donor. Promoting living donor kidney transplantation is the only modification that improves transplantation and decreases delisting/death on the waiting list in this population.

High pretransplant parathyroid hormone levels increase the risk for graft failure after renal transplantation.

BACKGROUND: Calcium (Ca), phosphate (P), and parathyroid hormone (PTH) are important variables influencing the risk for cardiovascular disease in dialysis patients. We studied the influence of long-standing Ca-P disregulation on renal transplant survival. METHODS: Pretransplant PTH, Ca, P, total protein (TP), albumin, and alkaline phosphatase (AP) values were gathered in all 407 patients that received a renal transplant in our center between January 1, 2000 and July 1, 2004. Other variables expected to influence the risks were included. RESULTS. In the Cox proportional hazards analysis the risk for graft failure censored for death was significantly influenced by pretransplant PTH concentration (P = 0.008) and donor type (P < 0.001). The influence of PTH on the risk for patient death was not significant. The risk for acute rejection was studied but PTH level did not have a significant influence on this risk (P = 0.055). The risk for delayed graft function was not influenced by PTH level. CONCLUSION: Serum PTH levels have an independent influence on the risk for graft failure censored for death. Efforts to improve calcium-phosphate-PTH homeostasis in patients on the waiting list for renal transplantation should be encouraged also to improve graft survival.

A High Comorbidity Score Should Not be a Contraindication for Kidney Transplantation.

BACKGROUND: Currently, potential kidney transplant patients more often suffer from comorbidities. The Charlson Comorbidity Index (CCI) was developed in 1987 and is the most used comorbidity score. We questioned to what extent number and severity of comorbidities interfere with graft and patient survival. Besides, we wondered whether the CCI was best to study the influence of comorbidity in kidney transplant patients. METHODS: In our center, 1728 transplants were performed between 2000 and 2013. There were 0.8% cases with missing values. Nine pretransplant comorbidity covariates were defined: cardiovascular disease, cerebrovascular accident, peripheral vascular disease, diabetes mellitus, liver disease, lung disease, malignancy, other organ transplantation, and human immunodeficiency virus positivity. The CCI used was unadjusted for recipient age. The Rotterdam Comorbidity in Kidney Transplantation score was developed, and its influence was compared to the CCI. Kaplan-Meier analysis and multivariable Cox proportional hazards analysis, corrected for variables with a known significant influence, were performed. RESULTS: We noted 325 graft failures and 215 deaths. The only comorbidity covariate that significantly influenced graft failure censored for death was peripheral vascular disease. Patient death was significantly influenced by cardiovascular disease, other organ transplantation, and the total comorbidity scores. Model fit was best with the Rotterdam Comorbidity in Kidney Transplantation score compared to separate comorbidity covariates and the CCI. In the population with the highest comorbidity score, 50% survived more than 10 years. CONCLUSIONS: Despite the negative influence of comorbidity, patient survival after transplantation is remarkably good. This means that even patients with extensive comorbidity should be considered for transplantation.

Alternative Living Kidney Donation Programs Boost Genetically Unrelated Donation.

Donor-recipient ABO and/or HLA incompatibility used to lead to donor decline. Development of alternative transplantation programs enabled transplantation of incompatible couples. How did that influence couple characteristics? Between 2000 and 2014, 1232 living donor transplantations have been performed. In conventional and ABO-incompatible transplantation the willing donor becomes an actual donor for the intended recipient. In kidney-exchange and domino-donation the donor donates indirectly to the intended recipient. The relationship between the donor and intended recipient was studied. There were 935 conventional and 297 alternative program transplantations. There were 66 ABO-incompatible, 68 domino-paired, 62 kidney-exchange, and 104 altruistic donor transplantations. Waiting list recipients (n = 101) were excluded as they did not bring a living donor. 1131 couples remained of whom 196 participated in alternative programs. Genetically unrelated donors (486) were primarily partners. Genetically related donors (645) were siblings, parents, children, and others. Compared to genetically related couples, almost three times as many genetically unrelated couples were incompatible and participated in alternative programs (P < 0.001). 62% of couples were genetically related in the conventional donation program versus 32% in alternative programs (P < 0.001). Patient and graft survival were not significantly different between recipient programs. Alternative donation programs increase the number of transplantations by enabling genetically unrelated donors to donate.

Understanding the influence of ethnicity and socioeconomic factors on graft and patient survival after kidney transplantation.

BACKGROUND: Studies on the influence of socioeconomic factors and ethnicity on the results of kidney transplantation have led to various outcomes. In this study, we analyzed the influence of a combination of these factors on graft and patient survival in a population of kidney transplant recipients. METHODS: This retrospective study included all 1,338 patients who received a kidney transplant between 2000 and 2011 (825 living, 513 deceased donor transplantations). Both clinical and socioeconomic variables were studied. Clinical variables were recipient age, gender, ethnicity, original disease, maximum and current panel reactive antibodies, ABO blood type, retransplants, pretreatment, time on dialysis, comorbidity, transplant year, total number of HLA mismatches, donor type (living or deceased), age and gender, and calcineurin inhibitor treatment. Each recipient's postal code was linked to a postal code area information database to extract information on housing value, income, percentage non-Europeans in the area, and urbanization level. RESULTS: In multivariable analysis, graft survival censored for death was significantly influenced by recipient age, maximum panel reactive antibodies, HLA mismatches, donor type, donor age, and calcineurin inhibitor treatment. Patient survival was significantly influenced by recipient age, comorbidity, transplant year, and donor type. Socioeconomic factors and ethnicity did not have a significant influence on graft and patient survival. CONCLUSIONS: Though ethnicity and socioeconomic factors do not influence survival after kidney transplantation, the favorable influence of living donor type is of paramount importance. As non-Europeans and patients with unfavorable socioeconomic variables less often receive a living donor kidney transplant, their survival may be unfavorable after all.

Transplantation results of completely HLA-mismatched living and completely HLA-matched deceased-donor kidneys are comparable.

BACKGROUND: Human leukocyte antigen (HLA) mismatches are known to influence graft survival in deceased-donor kidney transplantation. We studied the effect of HLA mismatches in a population of recipients of deceased-donor or living-donor kidney transplantations. METHODS: All 1998 transplantations performed in our center between 1990 and 2011 were included in this retrospective cohort study. Four different multivariable Cox proportional hazard analyses were performed with HLA mismatches as continuous variable, as categorical variable (total number of HLA mismatches), as binary variable (zero vs. nonzero HLA mismatches), and HLA-A, -B, and -DR mismatches included separately. RESULTS: Nine hundred ninety-one patients received a deceased-donor kidney and 1007 received a living-donor kidney. In multivariable Cox analysis, HLA mismatches, recipient age, current panel-reactive antibodies, transplant year, donor age, calcineurin inhibitor treatment, and donor type were found to have a significant and independent influence on the risk of graft failure, censored for death. Variables representing the total number of HLA-A, -B, and -DR mismatches had a significant and comparable influence in all analyses. CONCLUSIONS: The influence of HLA mismatches on death-censored graft survival holds true for both deceased- and living-donor kidney transplantation. However, the relative risk of death-censored graft failure of a 2-2-2 mismatched living-donor kidney is comparable with that of a 0-0-0 mismatched deceased-donor kidney.

15-year follow-up of a multicenter, randomized, calcineurin inhibitor withdrawal study in kidney transplantation.

BACKGROUND: Calcineurin inhibitors (CNIs) are essential immunosuppressive drugs after renal transplantation. Because of nephrotoxicity, withdrawal has been a challenge since their introduction. METHODS: A randomized multicenter trial included 212 kidney patients transplanted between 1997 and 1999. All patients were initially treated with mycophenolate mofetil (MMF), cyclosporine A (CsA), and prednisone (pred). At 6 months after transplantation, 63 patients were randomized for MMF/pred, 76 for MMF/CsA, and 73 for MMF/CsA/pred. Within 18 months after randomization 23 patients experienced a rejection episode: MMF/pred (27.0%), MMF/CsA (6.8%) and MMF/CsA/pred (1.4%) (P<0.001). RESULTS: During 15 years of follow-up, 73 patients died with a functioning graft, and 43 patients lost their graft. Ninety-six were alive with a functioning graft. Intention-to-treat analysis did not show a significant difference in patient and graft survival. In multivariate analysis, death-censored graft survival was significantly associated with serum creatinine at 6 months after transplantation and maximum PRA but not with the randomization group. CNI withdrawal did not result in a reduced incidence of or death by malignancy or cardiovascular disease. Death-censored graft survival was significantly worse in those patients randomized for CNI withdrawal that had to be reverted to CNI. Independent of randomization group, compared with no rejection, death-censored graft survival was significantly worse in 23 patients with acute rejection after randomization. CONCLUSION: Fifteen years after conversion to a CNI free regimen, there was no benefit regarding graft and patient survival or regarding prevalence of or death by comorbidities. However, rejection shortly after CNI withdrawal was associated with decreased graft survival.

Genetic variants of FOXP3 influence graft survival in kidney transplant patients.

FOXP3(+) regulatory T cells (Treg) play a role in controlling alloreactivity. It has been shown that short (GT)n dinucleotide repeats (≤(GT)15; S) in the promoter region of the FOXP3 gene enhance the promoter activity when compared to long (GT)n repeats (≥(GT)16; L). The present study retrospectively investigated the influence of this (GT)n FOXP3 gene polymorphism on renal allograft survival. A total of 599 consecutive first-time kidney transplant patients (median follow-up time 7.7 years) were subdivided according to their FOXP3 genotype into the S-genotype group (SG) and the L-genotype group (LG). The SG was superior to the LG in both general graft survival censored for death (logrank test, p=0.013) and graft survival following acute rejection (p=0.021). Multivariate analysis defined the (GT)n FOXP3 dinucleotide repeat polymorphism as an independent factor and confirmed an advantage for the SG in renal allograft survival (HR=0.67, 95% CI 0.48-0.94, p=0.02). This gene association study identified a beneficial effect of FOXP3 genetic variants on graft survival in kidney transplant patients.

Accumulation of unfavorable clinical and socioeconomic factors precludes living donor kidney transplantation.

BACKGROUND: In the past 30 years, the number of living donor kidney transplantations has increased considerably and nowadays outnumbers the deceased donor transplantations in our center. We investigated which socioeconomic and clinical factors influence who undergoes living or deceased donor kidney transplantation. METHODS: This retrospective study included all 1338 patients who received a kidney transplant between 2000 and 2011 in the Erasmus MC Rotterdam. Clinical and socioeconomic variables were combined in our study. Clinical variables were recipient age, gender, ethnicity, original disease, retransplants, ABO blood type, panel-reactive antibody, previous treatment, and transplantation year. Each recipient's postcode was linked to a postcode area information data base, to extract demographic information on urbanization level, percentage non-Europeans in the area, income, and housing value. Chi-square, analysis of variance, and univariate and multivariate logistic regression analyses were performed. RESULTS: There were significant differences between the recipients of a living versus deceased donor kidney transplantation. In multivariate logistic regression analyses, 10 variables had a significant influence on the chance of receiving living donor kidney transplantation. Clinical and socioeconomic factors had an independent influence on this chance. Patients with ABO blood type O and B have smaller chances. Highly sensitized and elderly patients have smaller chances especially when combined with a collection of other unfavorable factors. Accumulation of unfavorable factors in non-Europeans prevents their participation in living donation programs. CONCLUSION: Both clinical and socioeconomic factors are associated with participation in living or deceased donor kidney transplantation. This study highlights the populations that would benefit from educational intervention regarding living donor transplantation.

The functional polymorphism Ala258Ser in the innate receptor gene ficolin-2 in the donor predicts improved renal transplant outcome.

BACKGROUND: Innate immunity plays a role in controlling adaptive immune responses. METHODS: We investigated the clinical relevance of single nucleotide polymorphisms in 22 genes encoding innate, secreted, and signaling pattern recognition receptors in a total of 520 donor-recipient pairs of postmortem, human leukocyte antigen-DR-compatible kidney transplantations. Associations with rejection incidence were tested in an a priori randomized training set and validation set. RESULTS: Polymorphisms in TLR-3 (rs3775296) in the recipients and in ficolin-2 (rs7851696; Ala258Ser) and C1qR1 (rs7492) in the donors showed the strongest association with severe rejection. In multivariate analysis, presence of the ficolin-2 Ala258Ser variant in the donor predicted lower incidence of severe rejection (odds ratio=0.3; 95% confidence interval, 0.1-0.9; P=0.024) and of graft loss (hazard ratio=0.5; 95% confidence interval, 0.2-1.0; P=0.046) independently of clinical risk factors. Ficolin-2 messenger RNA expression was detected in pretransplantation biopsies from 69 donor grafts. Serum and tissue ficolin-2 levels were unaffected by genotype. Ficolin-2 protein, which bound to dying cells, was detected in donor kidneys in a passenger leukocyte-like pattern. Indeed, monocytes, monocyte-derived macrophages, and peripheral blood mononuclear cells expressed ficolin-2. Donor grafts with the ficolin-2 Ala258Ser variant contained significantly elevated expression of interleukin 6, having ascribed cytoprotective effects. It has been described that Ala258Ser leads to increased binding capacity of ficolin-2 to N-acetylglucosamine. CONCLUSIONS: Presence of the ficolin-2 Ala258Ser polymorphism in the donor independently predicts improved graft outcome. Based on mechanistic data, we propose that this functional polymorphism leads to more efficient handling of injured cells by phagocytozing cells, resulting in decreased intragraft exposure to danger signals and dampened alloimmune responses.

Eight years of outcomes of the Dutch Living Donor Kidney Exchange Program.

In January 2004, the Dutch transplant centers agreed on a protocol for a national Living Donor Kidney Exchange Program for ABO blood type incompatible and positive cross match donor-recipient pairs. Here, we report the results of that program. All transplants performed within the Living Donor Kidney Exchange Program between January 2004 and December 2011 were analysed. We collected demographic data of recipients and donors. Univariate and multivariate Cox proportional hazard analyses were performed, including recipient age, donor age, and reason for participation in the exchange program. We studied overall uncensored survival and graft survival censored for death in both ABO blood type incompatible and positive cross match groups. We enrolled 472 donor-recipient combinations, consisting of 269 ABO blood type incompatible pairs and 203 positive cross match pairs. In the end, we performed 187 kidney transplants (40% of those enrolled) with 83 ABO blood type incompatible and 104 positive cross match pairs. Most of the transplanted recipients (119/187, 64%) had an age difference of less than 5 years with their original incompatible donors. The age differences with their actual donors varied widely, but the number of recipients with a donor > 5 years older was comparable to the number of recipients with a donor > 5 years younger. In the multivariate Cox analysis, age as a continuous variable was found to have a significant influence on graft failure. Nevertheless, the 5-year uncensored survival (85%) and the graft survival censored for death (89%) were excellent and comparable to the results of direct living donation. No differences were found between the ABO incompatible and the positive cross match groups. The Dutch Living Donor Kidney Exchange Program has a high transplant rate of 40%, with excellent 5 year graft survival.

Ethnically diverse populations and their participation in living kidney donation programs.

BACKGROUND: The number of living donor kidney transplantations increases steeply in Europeans, whereas the non-Europeans are dependent on deceased donor transplantations. We wondered whether a low attendance or a high decline of potential non-European donors could explain this difference. METHODS: This retrospective study includes all 1059 potential living kidney donors who attended our pretransplant clinic between 2000 and 2007. Potential donors were divided according to eight countries of origin: African, Dutch Antillean, European, Indonesian, Moroccan, Surinamese, Turkish, and various countries. In addition to direct living donation, alternative living donation programs are operational in our center: kidney exchange, domino paired, ABO incompatible, and anonymous donation. RESULTS: European donors predominated in both the potential (79%) and the actual donor populations (85%). Actual donors comprised 39% of non-European and 59% of the European potential donors (P<0.001). Participation in alternative donation programs is significantly less among non-European donors in comparison with European donors (3.6% vs. 12.6%, P<0.001). In all non-European populations, genetically related donors predominated, whereas genetically related and unrelated donors were equally represented in the European potential donor population (P<0.001). Partners were under-represented in all non-European populations (P<0.001). The attitude and behavior of non-Europeans with the longest duration of stay in the Netherlands were closest to that of the Europeans. The population with the shortest stay differed the most. This could possibly be attributed to integration. CONCLUSION: There are less non-European donors than expected based on the population composition. Living donor characteristics are different between Europeans and non-Europeans. The reasons for the difference deserve investigation.