Pérez-Sáez et al. BMC Nephrology (2019) 20:233 https://doi.org/10.1186/s12882-019-1412-0 RESEARCH ARTICLE Open Access Early outcomes of kidney transplantation from elderly donors after circulatory death (GEODAS study) María José Pérez-Sáez1, Omar Lafuente Covarrubias2, Domingo Hernández3, Francesc Moreso4, Edoardo Melilli5, Javier Juega6, Erika de Sousa7, Paula López-Sánchez2, María Luisa Rodríguez-Ferrero8, Naroa Maruri-Kareaga9, María Dolores Navarro10, Rosalía Valero11, María Auxiliadora Mazuecos12, Francisco Llamas13, Paloma Martín-Moreno14, Antón Fernández-García15, Jordi Espí16, Carlos Jiménez17, Ana Ramos18, Eva Gavela19, Julio Pascual1*†, Jose M. Portolés2*† and on behalf of the GEODAS Group Abstract Background: Spain has dramatically increased the number of controlled circulatory death donors (cDCD). The initial selection criteria for considering cDCD for kidney transplantation (KT) have been expanded progressively, with practically no limits in donor age during the last years. We aimed to analyze the early clinical outcomes using expanded (> 65 years) cDCD in comparison with standard ones. Methods: Observational multicenter study including 19 transplant centers in Spain. We performed a systematic inclusion in a central database of every KT from expanded cDCD at each participant unit from January-2012 to January-2017. Surgical procedures and immunosuppressive protocols were based on local practices. Data was analyzed in the central office using logistic and Cox regression or competitive-risk models for multivariate analysis. Median time of follow-up was 18.1 months. Results: 561 KT were performed with kidneys from cDCD, 135 from donors older than 65 years. As expected, recipients from older cDCD were also older (65.8 (SD 8.8) vs 53.7 (SD 11.4) years; p < 0.001) and with higher comorbidity. At 1 year, no differences were found amongst older and younger cDCD KT recipients in terms of serum creatinine (1.6 (SD 0.7) vs 1.5 (SD 0.8) mg/dl; p = 0.29). Non-death censored graft survival was inferior, but death-censored graft survival was not different (95.5 vs 98.2% respectively; p = 0.481). They also presented a trend towards higher delayed graft function (55.4 vs 46.7%; p = 0.09) but a similar rate of primary non-function (3.7 vs 3.1%; p = 0.71), and acute rejection (3.0 vs 6.3%; p = 0.135). In the multivariate analysis, in short follow-up, donor age was not related with worse survival or poor kidney function (eGFR < 30 ml/min). (Continued on next page) * Correspondence: julpascual@gmail.com; josem.portoles@salud.madrid.org † Julio Pascual and Jose M. Portolés are Senior co-authorship. 1 Nephrology Department and Kidney Transplantation Program, Hospital del Mar, Parc de Salut Mar, Universitat Autónoma Barcelona and Universitat Pompeu Fabra, Nephropaties Research Group Institute Mar for Medical Research, Passeig Maritim 25-29, 08003 Barcelona, Spain 2 Nephrology & Transplant Department, University Hospital Puerta de Hierro, Universidad Autónoma Madrid, Public Research Net RedInRen ISCIII 016/009, C/Manuel de Falla s/n, 28222 Majadahonda, Madrid, Spain Full list of author information is available at the end of the article © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Pérez-Sáez et al. BMC Nephrology (2019) 20:233 Page 2 of 8 (Continued from previous page) Conclusions: The use of kidneys from expanded cDCD is increasing for older and comorbid patients. Short-term graft outcomes are similar for expanded and standard cDCD, so they constitute a good-enough source of kidneys to improve the options of KT wait-listed patients. Keywords: Kidney transplantation, Elderly donors, Donors after circulatory death, Clinical outcomes, Delayed graft function Background the early results obtained with KT from elderly cDCD do- Kidney transplantation (KT) from donors after cardiac nors, both in terms of early clinical outcomes – primary death (DCD) might imply poorer graft outcomes, as non function (PNF) and delayed graft function (DGF) – as circulatory death constitutes an injury to the organs that well as 1st year patient and graft survival, in order to may result in lower graft survival [1]. To minimize that, reassure with the strategy of using these kidneys for aged DCD are only considered for KT if they fit strict criteria, recipients or change the policy if needed. including younger donor age than donors after brain death (DBD). In the US, around 50% of expanded Methods criteria donor (ECD)-DCD kidneys are discarded, com- Observational and multi-center registry, including 19 pared to 30–40% of ECD-DBD [2]. However, a signifi- transplant centers in Spain. Data from all cDCD (Maas- cant number of discarded ECD-DCD kidneys may be tricht type III) KT performed from January 2012 to acceptable for KT [2]. In fact, as age of patients listed January 2017 were collected and prospectively recorded for KT is continuously rising [3, 4], DCD age criteria has by nephrologists at each center database following the also increased in recent years in many countries, espe- same structure. For this analysis, a data manager central cially in Europe [5–11], where policies are more open to office merged anonymous databases in a single one. In- expand donor pool criteria, in contrast to the US, where formed consent for kidney transplantation and local the potential poorer outcomes could lead to a higher electronic data management was obtained according to discarded organ rate. each center’s Institutional Review Board policy, and a In Spain, improvements in organ procurement and central research Ethics Committee of H.U. Puerta de assessment tools have allowed us to expand donor Hierro approved the project. A pre-defined analysis after acceptance criteria [12]. Particularly, age limits have the first 500 cDCD KT was performed in order to evalu- been expanding, so that age itself is not usually a signifi- ate the early results obtained with kidneys from donors cant limiting factor. In contrast, more than half of avail- over 65 years, and to establish strategy changes if able kidneys from donors ≥65 years old are discarded in needed. This age cut-point was chosen based on the the US [13], despite their argued benefits in terms of upper limit recommended by the 1st version of Spanish patient survival, both after brain death [14–16] and after National Transplant Organization cDCD strategy guides circulatory death [17], comparing to remain on dialysis. in 2012 [19]. In Spain, old donors usually allocate into However, the increase in donor age is associated with re- old recipients, but there are not any pre-established duced graft function as well as limited recipient and common strategy between centers, being the finally deci- graft survival [18]. Moreover, it has been recently postu- sion made by each center. Sample size was estimated for lated that the use of aged DCD could be detrimental in a 15% difference in DGF incidence rate between groups. elderly recipients [10, 11]. Graft extraction was performed with or without ante- In 2012, Spain developed a strategy to encourage the mortem vascular cannulation, depending on the center. use of controlled DCD (cDCD) for transplantation, a The immunosuppressive regimen included induction with modality less used in our environment because of the rabbit anti-thymocyte globulin (Thymoglobulin®, Sanofi, high rate of brain-death donation [19]. That resulted in France) or basiliximab (Simulect®, Novartis, Swizerland), a dramatic increase in cDCD transplantation, from 1.4% and maintenance with steroids as well as the combination of the total donors in 2012 to 18% in 2016 [20]. The tacrolimus-mycophenolate or tacrolimus-everolimus, same year, GEODAS working group was created with tailored to patient immunological risk and according to the purposes of: 1) collecting data regarding KT from center’s local practice. cDCD; and 2) sharing protocols, outcomes analysis and Local standardized serum creatinine (colorimetric) and experiences [21]. glomerular filtration rate (GRF) estimated by Modified- As donor age in this modality has also experienced a sub- Diet Renal Disease-4 (MDRD-4) formula were recorded stantial change during the last years, we aimed to analyze at month 1, 3, 6 and every 6 months thereafter. Clinical Pérez-Sáez et al. BMC Nephrology (2019) 20:233 Page 3 of 8 events such as acute rejection, graft loss or patient death p < 0.001), more frequently females, diabetics (51.4% vs were recorded as they occurred. Delayed graft function 26.1%, p < 0.001) and with higher percentage of previous (DGF) was defined as the need of dialysis during the 1st cardiovascular events (20.7% vs 7.8%, p < 0.001). Donor week after KT. cause of death was more frequently a stroke. They were also better HLA matched and received less frequently thy- Statistics moglobulin as induction therapy (Table 1). Data are shown as mean and standard deviation or per- Regarding early clinical events, the group that received centages and event rates depending on variable nature. a KT from an older cDCD experienced a trend towards Continuous variables were compared using t-Student higher rate of DGF, though the difference was not statis- statistics or Wilcoxon’s test if variables were not nor- tically significant (55.4% vs 46.7%, p = 0.09). Neither we mally distributed. Categorical variables were compared found any difference in PNF or acute rejection rates with two-tailed Chi-square statistics. Significance was (Table 2). When analyzing other potential risk factors considered when p < 0.05. Patient and graft survival was for PNF and DGF through logistic regression models, estimated by Kaplan-Meier curves (log-rank test). Three CIT longer than 17 h was found to be a risk factor for statistical models for survival were used to increase the PNF (OR 3.25 [1.02–10.33; p = 0.046]), while dialysis vin- robustness of the analysis: logistic regression, Cox re- tage longer than 24 months prior to KT conditioned gression and competing risk regression analyses. DGF (OR 3.44 [2.39–4.94; p < 0.001, Table 3). Logistic regression was used to estimate Odds Ratio In terms of graft function, recipients from older do- (OR) for 1st year cumulative mortality. Uni and multi- nors showed lower eGFR at 1 year, but not statistically variate Cox regression models were carried out to different serum creatinine (1.60 vs 1.51 mg/dl; p = 0.29, estimate hazard ratio (HR) for survival. Backward step Table 2). In the multivariate analysis, the risk for poor multivariable regression was performed with principal renal function (1st year eGFR < 30 ml/min) associated variable (old vs. young donor), considering as possible with DGF (4.12 [2.07–8.22]; p < 0.001) but not with confounders from donor those included in KDPI donor age (Table 3). (ethnicity, cause of death, serum creatinine > 1.5 mg/dl, On the other hand, cumulative mortality during 1st diabetes mellitus, hypertension, etc.). We also included year was higher for recipients of older cDCD grafts other potential confounders as recipient age, sex and (1.9% vs 6.9%; p = 0.004, Table 2). Logistic regression comorbidity, cold ischemia time (CIT), human leukocyte model adjusted by recipient age and comorbidities antigen (HLA) mismatches, prior dialysis modality, prior showed that recipient age was the only risk factor re- KT, time on dialysis prior to transplant as well as other lated to patient death, conferring a 11% excess risk for usual risk variables such as serum creatinine or induc- mortality per each recipient’s year (OR 1.11 [1.04–1.19]; tion treatment. Variables with p value< 0.1 in the univar- p = 0.002, Table 3). iate analysis were included in the multivariable Survival analyses (estimated by KM method) showed a backward modeling process, besides other variables that lower 1st-year-graft survival among those kidneys from were clinically relevant for the outcome. We also used cDCD donors> 65 years (87.6% vs 96.2%; p = 0.02). How- competitive-risk models for graft and patient survival, ever, death-censored graft survival was similar in both considering graft loss, death and loss to follow-up as groups (95.5% vs 98.25; p = 0.481) (Fig. 1). We per- competitive events. Results are shown as sub-Hazard formed Cox regression and competing risk multivariate Ratio (sHR). analyses in order to analyze donor age impact on graft On the other hand, we tested multivariate models for survival. Adjusted-models did not show that donor age the impact of donor age group on early clinical outcomes: itself and isolated was associated with graft survival but primary-non-function (PNF, defined as grafts that never eGFR< 30 ml/min at 1-year increased the risk eight -fold functioned), DGF, poor kidney function at 12 months (sHR 8.34 [2.82–24.65; p < 0.001, Table 4). (defined as eGFR < 30 mL/min). Patients with PNF were On the other hand, 1st-year patient survival was also excluded for further analyses of other outcomes. poorer (91.8% vs 97.9%; p = 0.01). Nine patients from the Analysis was performed using Stata v14 (StataCorp group of older donors died with functioning graft during the 2015, Stata Statistical Software, College Station, TX). first year after transplantation (mostly in the first 6 months after transplantation) due to cardiovascular events (n = 4), Results sudden death of uncertain origin (n = 1), cancer (n = 1), 561 KT recipients from cDCD were included in the study. sepsis (n = 1), pulmonary embolism (n = 1), and unknown Of them, 135 received a KT from a cDCD donor > 65 cause (n = 1). Again, the multivariate analysis revealed that years. Compared to patients that received a KT from a only recipient age was as risk factor for patient survival, in- younger donor, patients that received a KT from cDCD > creasing the risk around 10% per each recipient’s year of 65 years were older (65.8 (8.8) years vs 53.7 (11.4) years, age, both with Cox and competing risk analyses (Table 4). Pérez-Sáez et al. BMC Nephrology (2019) 20:233 Page 4 of 8 Table 1 Baseline characteristics among kidney transplant recipients from donors > 65 years and ≤ 65 years Donor ≤65 years Donor > 65 years p-value (n = 426) (n = 135) Recipient characteristics Age (years, mean (SD)) 53.7 (11.4) 65.8 (8.8) < 0.001 Age > 65 years (%) 14.6 61.3 < 0.001 Female Gender (%) 30.1 35.6 0.23 Black Race (%) 1.4 0.7 0.5 Diabetes mellitus (%) 26.1 51.4 < 0.001 Previous cardiovascular eventa (%) 7.8 20.7 < 0.001 Cause of end-stage renal disease (%) Hypertensive nephropathy 12.4 11.9 Diabetic nephropathy 11.3 22.2 Glomerulonephritis 19.0 12.6 Interstitial 11.0 11.9 0.03 Polycystic 15.3 11.1 Others 6.7 5.9 Unknown 19.7 23.7 Previous renal replacement therapy (%) Hemodialysis 73.1 83.0 Peritoneal Dialysis 21.0 14.8 0.05 Preemptive kidney transplant 5.9 2.2 Dialysis vintage (years, median [IQR]) 1.1 [2.0–3.6] 1.3 [2.6–4.0] 0.08 Patients with previous kidney transplant (%) 8.4 7.4 0.7 Donor characteristics Age (years, mean (SD)) 52.7 (9.1) 72.0 (4.9) < 0.001 Female Gender (%) 26.3 45.9 < 0.001 Expanded criteria donors (%) 29.3 100 < 0.001 Stroke as Cause of death (%) 49.2 67.8 < 0.001 Transplant characteristics Number of HLA mismatches (median (IQR)) 4 [3–5] 4 [3–5] 0.003 Cold ischemia time (hours, median (IQR)) 11 [7–18] 9.5 [7–16.5] 0.326 Warm ischemia time (min, median (IQR)) 23.5 [15–36.5] 26 [16–35] 0.901 Induction treatment (Thymoglobulin, %) 70.7 57 0.003 Maintenance (Tacrolimus+MPA + steroids, %) 82.9 80.7 0.57 Time of follow-up (years, median [IQR]) 1.6 [0.9–2.6] 1.1 [0.7–1.8] < 0.001 SD standard deviation, MPA mycophenolic acid, IQR interquartile range a Acute myocardial infarction, stroke or peripheral vascular disease (amputation) Table 2 Patient and transplant outcomes among kidney transplant recipients from donors > 65 years and ≤ 65 years Donor ≤65 years Donor > 65 years p-value (n = 426) (n = 135) Early patient mortality (at first year, %) 1.9 6.9 0.004 Primary non-function (%) 3.1 3.7 0.71 Delayed graft function (%) 46.7 55.4 0.09 Acute rejection (%) 6.3 3.0 0.135 Creatinine at 12 month (mg/dl, mean (SD)) 1.51 (0.8) 1.60 (0.7) 0.29 eGFR at 12 month (ml/min, mean (SD)) 57.9 (24.7) 49.2 (20.0) < 0.001 eGFR estimated glomerular filtration rate calculated by MDRD-4 Pérez-Sáez et al. BMC Nephrology (2019) 20:233 Page 5 of 8 Table 3 Risk factors for relevant patient and allograft early from an elderly donor, but it seems to be related to re- outcomes estimated with multivariate logistic regression analysis cipient age. Donor age itself and isolated did not have OR 95% CI p-value any impact on patient neither graft survival at short Primary non-function term, although it was associated with poorer graft func- Donor age > 65 years (vs ≤65 years) 2.50 [0.77–8.09] 0.128 tion in terms of eGFR. As ECD-DCD donors may constitute more than 40% Cold ischemia time > 17 h (vs shorter) 3.25 [1.02–10.33] 0.046 of the total DCD donor pool in some centers [11], ef- Delayed graft function forts are targeted now to analyze outcomes using kid- Donor age > 65 years (vs ≤65 years) 1.33 [0.87–2.03] 0.19 neys that come from those suboptimal donors. Some Dialysis vintage > 24 months (vs shorter) 3.44 [2.39–4.94] < 0.001 reports have analyzed outcomes using ECD-DCD donors eGFR< 30 ml/min at month 12 in the US [1, 22, 23], Europe [7–11] and Japan [24]. Donor age > 65 years (vs ≤65 years) 1.15 [0.60–2.20] 0.427 Overall, results from ECD-DCD donors are poorer than those obtained with standard-DCD donors, though not Delayed graft function (vs immediate) 4.12 [2.07–8.22] < 0.001 inferior to ECD-DBD donors [1, 7, 9, 22, 24]. However, Early patient mortality (first year) these studies included KT recipients from classical ECD Donor age > 65 year (vs ≤65 years) 1.37 [0.46–4.10] 0.578 defined by Organ Procurement Transplant Network Recipient age (per year) 1.11 [1.04–1.19] 0.002 (OPTN, donors older than 60 years-old, or between 50 OR odds ratio, CI confidence interval, eGFR estimated glomerular filtration rate and 60 years-old with two of the following risk factors: cardiovascular death, serum creatinine > 1.5 mg/dl or Finally, we aimed to investigate which old donors hypertension) but few studies have analyzed the results might carry a higher risk for the recipients, considering with very elderly donors, i.e., older than 65 years-old [10]. early clinical outcomes. By adding classical donor car- Normally, studies have not been focused on patient diovascular risk factors (serum creatinine > 1.5 mg/dl, survival using expanded DCD donors, though we can diabetes mellitus and cardiovascular as the cause of find a reported one-year-patient survival ranged from 85 death), we found that older donors with one or two of to 91% among recipients who received kidneys from those previous risk factors associated with significant ECD-DCD donors [7, 10, 23]. Two studies also com- higher DGF rate (Table 5). Similar analyses for PNF, pared the mortality between those who underwent KT poor kidney function (1st year eGFR < 30 ml/min) and from an ECD-DCD donor and those who remained 1st year mortality were not significant (data not shown). waitlisted on dialysis. They found that among older recipients (> 65 years), there was no benefit in terms of Discussion survival using kidneys from old DCD donors (> 65 years) In this study, we present early clinical outcomes using [10, 11], and younger recipients might have the potential KT from cDCD older than 65 years. We found higher benefit of the expansion in DCD donor criteria accept- 1st year mortality among KT patients receiving a kidney ance [11]. In a recent observational study in patients A B C Patient survival Graft survival Death censored graft survival 1.00 1.00 1.00 0.90 0.90 0.90 0.80 0.80 0.80 0.70 0.70 0.70 0.60 0.60 0.60 0 .5 1 1.5 2 0 .5 1 1.5 2 0 .5 1 1.5 2 Follow-up (years) Follow-up (years) Follow-up (years) Number at risk Number at risk Number at risk Donors<=65y 426 378 298 233 155 Donors<=65y 426 378 298 233 155 Donors<=65y 426 378 298 233 155 Donor>65y 135 111 76 42 20 Donor>65y 135 111 76 42 20 Donor>65y 135 111 76 42 20 Donor <= 65y Donor <= 65y Donor <= 65y Donor > 65y Donor > 65y Donor > 65y Fig. 1 Kaplan-Meier survival curves between kidney transplant recipients from donors > 65 years and ≤ 65 years. a Patient survival; b Graft survival; c Death-censored graft survival Pérez-Sáez et al. BMC Nephrology (2019) 20:233 Page 6 of 8 Table 4 Risk factors for relevant patient and allograft early outcomes estimated with Cox regression analysis (HR) and competing risk analysis (sHR) Risk factor HR 95% CI p-value sHR 95% CI p-value Patient survival Model 1 (raw) Donor age > 65y (vs ≤ 65 years) 2.94 [1.22–7.11] 0.016 3.17 [1.38–7.27] 0.015 Model 2 (adjusted by recipient age) Donor age > 65y (vs ≤ 65 years) 1.17 [0.44–3.08] 0.751 1.26 [0.48–3.34] 0.636 Recipient age 1.10 [1.04–1.16] 0.001 1.1 [1.05–1.16] < 0.001 Model 3 (adjusted by recipient age + previous CV event) Donor age > 65y (vs ≤ 65 years) 1.06 [0.40–2.82] 0.900 1.06 [0.36–3.12] 0.910 Recipient age 1.10 [1.04–1.16] 0.001 1.09 [1.04–1.15] < 0.001 Previous CV event 2.02 [0.76–5.36] 0.158 2.00 [0.73–5.47] 0.178 Death-censored graft survival Model 1 (raw) Donor age > 65y (vs ≤ 65 years) 1.30 [0.47–3.60] 0.620 1.28 [0.47–3.47] 0.631 Model 2 (adjusted by recipient age) Donor age > 65y (vs ≤ 65 years) 1.17 [0.44–3.08] 0.751 1.00 [0.30–3.38] 0.997 Recipient age 1.10 [1.04–1.16] 0.001 1.02 [0.97–1.07] 0.425 Model 3 (adjusted by eGFR< 30 ml/min at first month) Donor age > 65y (vs ≤ 65 years) 0.66 0.15–3.01 0.595 0.58 [0.12–2.74] 0.487 eGFR< 30 ml/min at first month 8.70 2.99–25.25 < 0.001 8.34 2.82–24.65 < 0.001 HR hazard ratio, sHR sub-hazard ratio, CI confidence interval, eGFR estimated glomerular filtration rate, CV cardiovascular older than 65 years old receiving an old kidney from differences in 1st year death-censored-graft survival re- DCD donors over 65, Peter-Sengers et al. showed a 15% gardless donor age, highlighting that differences observed higher mortality than we found among our recipients. in non-censored graft survival are related to a higher rate Although we have included recipients younger than 65 of patient mortality during the 1st year within recipients years old, our cohort included recipients of a special who received a kidney from an older donor. high-risk profile, with a mean age near 66 years, high Disparities have been found in other outcomes such prevalence of diabetes (> 50%) and previous cardiovas- as DGF or PNF. While the US Registry found no differ- cular events (> 20%). When we analyzed the risk fac- ences in terms of among ECD-DCD donors and non- tors implicated in early patient survival, we confirmed ECD-DCD donors, the UK cohort found a higher rate that only patient age was involved in patient prognosis of both PNF and DGF between older donors but com- without any influence of donor age or donor comor- paring to donors younger than 40 years [7]. However, bidity. These findings highlight the importance of a an update of the UK Registry showed similar rates of carefully selection of the recipient, in order to avoid PNF and similar 5-year graft survival between ECD- early patient mortality. DCD and brain-dead ECD KT [8]. The study from the In terms of graft survival, kidney grafts from ECD- Netherlands found a high-rate of both PNF (12.7%) and DCD donors have shown inferior survival than those DGF (74.1%) in recipients > 65y who received organs from standard DCD donors [1, 24], though similar to from donors > 65 y [10]. Our PNF rate was similar ECD-DBD ones [7, 22]. One-year-graft survival has been between the groups and below 4% and the only factor reported from 74 to 90% [7, 9, 23, 24], similar to ours, that increased the risk was a prolonged cold ischemia despite our donors were almost 5 years older than those time, consistently with other authors’ findings [7]. In from the study by Peter-Sengers et al. which reported our study, the incidence of DGF was high in both the oldest ones so far [10]. In fact, we found no groups, with a clear tendency of higher rate among re- cipients from older donors. The multivariate analysis Table 5 Risk factors for relevant renal allograft outcomes showed that donor age itself was not associated with estimated with logistic regression analysis higher rate of DGF, but if we considered high-risk OR 95% CI p-value donor profile (older plus other comorbidities) the risk Delayed graft function is increased by three-fold. Poorer kidney function has also been shown in kidneys Donor age > 65 years + 0 risk factor 1.32 0.79–2.22 0.30 from ECD-DCD donors [7, 9]. In fact, two-thirds of old Donor age > 65 years + 1 risk factor 1.79 1.05–3.05 0.03 recipients from DCD donors over 65 y presented with Donor age > 65 years + 2 risk factors 3.84 1.91–7.72 < 0.001 eGFR< 30 ml/min at 1st year [10]. We did not find any Donor risk factors are defined as creatinine > 1.5 mg/dl, cardiovascular death statistical difference in terms of serum creatinine at 1st and hypertension. Similar analyses for Primary non function, estimated glomerular filtration rate < 30 ml/min at 12 months and early patient mortality year after transplantation although kidney function was were not significant poorer in recipients from elderly cDCD. Pérez-Sáez et al. BMC Nephrology (2019) 20:233 Page 7 of 8 Our study is limited by the sample size and the relative collection and drafted the paper. PLS contributed to the study design and short-term follow-up. However, we aimed to analyze 1st the statistical analysis. JMP contributed to conceptualization of the idea, study design, statistical analysis and drafted the paper. JP contributed to year results using elderly cDCD in our media, to know conceptualization of the idea, study design and drafted the paper. JMP and results and implement the proper strategy changes if JP supervised the study. The rest of the authors (DH, FM, EM, JJ, EdS, MLRF, needed. In fact, this is the first study that analyzes out- NMK, MDN, RV, MAM, FL, PMM, AFG, JE, CJ, AR, EG) contributed to data collection and the final revision of the manuscript. All authors read and comes in an important number of elderly cDCD (mean approved the final manuscript. age 72 years) allocated to a high-risk recipient cohort. We found a higher mortality compared to recipients Funding who received organs from younger donors. However, in This project was co-founded by Public Research Net REDINREN ISCIII 16/009/ 009, Renal Foundation FRIAT & Research Institute Segovia Arana-HU Puerta the multivariate model the recipient age accounted for de Hierro. OLC, PLS and JMP belong to the latter institution (HU Puerta de all the risk and the weight of the donor age over the Hierro). Funding was used for human resources: data manager and death risk disappeared. Three different multivariate stat- statistician support. istical models showed these results, which reflects their Availability of data and materials consistency. On the other hand, short-term graft survival The database and the analysis are safeguarded in the central servers of a was similar and donor age itself did not have any impact public health institution (Hospital Puerta de Hierro). Any access to the original database should be properly requested to the corresponding author in patient or graft outcomes. and approved by Ethics Scientific Committee. Conclusions Ethics approval and consent to participate Our results pointed at similar patient and KT short-term Data from all KT were collected and prospectively recorded by nephrologists at each center database. A data manager central office merged anonymous outcomes regardless of donor age, which may suggest databases auditing and debugging the data. Informed consent for kidney better results than those previously reported. If these transplantation and local electronic data management was obtained findings were confirmed in long-term studies, they according to each center’s Institutional Review Board policy. A central research Ethics Committee of H.U. Puerta de Hierro approved the project might generate changes in acceptance and allocation of without the need of additional consents. these grafts for KT. In fact, when we added comorbidity factors other than donors’ age, some outcomes as DGF Consent for publication seem to be affected. Careful pre-transplant evaluation Not applicable. Data come from an anonymized database for the registry and the follow-up of kidney transplantation (not containing data from any should be performed in these extremely high-risk group individual person). in order to improve outcomes, but kidneys from old cDCD should not be discarded systematically. Competing interests The authors declare that they have no competing interests. Abbreviations cDCD: Controlled donor after circulatory dead; CIT: Cold ischemia time; Author details 1 DBD: Donor after brain death; DCD: Donor after circulatory death; Nephrology Department and Kidney Transplantation Program, Hospital del DGF: Delayed graft function; ECD: Expanded criteria donor; eGFR: Estimated Mar, Parc de Salut Mar, Universitat Autónoma Barcelona and Universitat glomerular filtration rate; GEODAS (from the words in Spanish): Grupo Pompeu Fabra, Nephropaties Research Group Institute Mar for Medical Español de Trasplante renal con programas de Donante en Asistolia tipo 3 Research, Passeig Maritim 25-29, 08003 Barcelona, Spain. 2Nephrology & (Spanish Group with cDCD KidneyTransplant Programs); HLA: Human Transplant Department, University Hospital Puerta de Hierro, Universidad leucocyte antibody; KT: Kidney transplant; MDRD: Modified-diet renal disease; Autónoma Madrid, Public Research Net RedInRen ISCIII 016/009, C/Manuel PNF: Primary non-function de Falla s/n, 28222 Majadahonda, Madrid, Spain. 3H.U. Carlos Haya, Malaga, Spain. 4H. Vall d’Hebron, Barcelona, Spain. 5H. Bellvitge, Barcelona, Spain. 6H. Acknowledgements German Trias y Pujol, Barcelona, Spain. 7H. Clinic de Barcelona, Barcelona, The GEODAS Group comprises the following authors: José M. Portolés, Omar Spain. 8HGU Gregorio Marañón, Madrid, Spain. 9H.U. Cruces, Bilbao, Spain. 10 Lafuente Covarrubias, Paula López-Sánchez, Beatriz Sánchez-Sobrino (H.U. H.U. Reina Sofia, Córdoba, Spain. 11H.U. Marqués de Valdecilla, Santander, Puerta de Hierro, Madrid); María José Pérez-Sáez, Julio Pascual Santos, Ana Spain. 12H.U. Puerta del Mar, Cádiz, Spain. 13H.U. de Albacete, Albacete, Spain. 14 Zapatero (H. del Mar, Barcelona); Domingo Hernández-Marrero (H.U. Carlos C.U de Navarra, Pamplona, Spain. 15C.H.U de A Coruña, A Coruña, Spain. 16 Haya, Málaga); Francesc Moreso (H. Vall d’Hebron, Barcelona); Edoardo Melilli, H.U. La Fe, Valencia, Spain. 17H.U. de la Paz, Madrid, Spain. 18F. Jiménez Anna Manonelles (H. Bellvitge, Hospitalet, Barcelona); Javier Juega, Ricardo Díaz, Madrid, Spain. 19H.U. Dr Peset, Valencia, Spain. Lauzurica (H. Germans Trias y Pujol, Badalona); Erika de Souza, Fritz Diekmann (H. Clinic, Barcelona); María Luisa Rodríguez-Ferrero (H.U. Gregorio Marañón Received: 8 November 2018 Accepted: 6 June 2019 (Madrid); Naroa Maruri-Kareaga, Sofia Zárraga (H. de Cruces, Bilbao); María Dolores Navarro, Alberto Rodríguez-Benot (H U. Reina Sofía, Córdoba); Rosalía Valero, Juan Carlos Ruiz (H. Marqués de Valdecilla, Santander); María Auxilia- References dora Mazuecos (H Puerta del Mar, Cádiz); Francisco Llamas (C.H.U. General de 1. Locke J, Segev D, Warren D, Dominici F, Simpkins C, Montgomery R. Albacete); Paloma Martín-Moreno (Clínica Universitaria de Navarra); Ángel Outcomes of kidneys from donors after cardiac death: implications for Alonso, Antón Fernández-García (C.H.U., A Coruña); Jordi Espí, Isabel Beneyto allocation and preservation. Am J Transplant. 2007;7:1797–807. (H.U. La Fe, Valencia); Carlos Jiménez, María López-Oliva (H.U. La Paz, Madrid); 2. Singh SK, Kim SJ. Epidemiology of kidney discard from expanded criteria Ana Ramos (Fundación Jiménez Díaz, Madrid): Eva Gavela, Asunción Sancho- donors undergoing donation after circulatory death. Clin J Am Soc Nephrol. Calabuig (H Dr Peset; Valencia). 2016;11(2):317–23. 3. Catalan Renal Registry. Statistical report 2014. Barcelona, Spain: Catalan Authors’ contributions Transplant Organization, Health Department, 2016. Available at: http:// MJPS contributed to data collection, conceptualization of the idea, study trasplantaments.gencat.cat/web/.content/minisite/trasplantament/registres_ design, statistical analysis and drafted the paper. OLC contributed to data activitat/registre_de_malalts_renals/arxius/Informe-estadistic-RMRC-2017.pdf Pérez-Sáez et al. BMC Nephrology (2019) 20:233 Page 8 of 8 4. 2016 USRDS Annual Data Report. Volume 2 - ESRD in the United States. Chapter 1: Incidence, Prevalence, Patient Characteristics, and Treatment Modalities. Available at: https://www.usrds.org/2016/download/v2_c01_IncPrev_16.pdf 5. Balance de Actividad en Donación y Trasplante 2015. Available at: http:// www.ont.es/Documents/Balance_Actividad_2015.pdf 6. Eurotransplant International Foundation. Annual Report 2015. Available at: https://www.eurotransplant.org/cms/mediaobject.php?file=AR_ET_20153.pdf 7. Summers DM, Johnson RJ, Hudson A, et al. Effect of donor age and cold storage time on outcome in recipients of kidneys donated after circulatory death in the UK: a cohort study. Lancet. 2013;381:727–34. 8. Summers DM, Watson CJE, Pettigrew GJ, et al. Kidney donation after circulatory death (DCD): state of the art. Kidney Int. 2015;88:241–9. 9. Nagaraja P, Roberts GW, Stephens M, et al. Impact of expanded criteria variables on outcomes ok kidney transplantation from donors after cardiac death. Transplantation. 2015;99:299–31. 10. Peters-Sengers H, Berger SP, Heemskerk MB, et al. Stretching the limits of renal transplantation in elderly recipients of grafts from elderly deceased donors. J Am Soc Nephrol. 2017;28(2):621–31. 11. Mirshekar-Syahkal B, Summers D, Bradbury LL, et al. Local expansion of donation after circulatory death kidney transplant activity improves waitlisted outcomes and addresses inequities of access to transplantation. Am J Transplant. 2017;17(2):390–400. 12. Chang GJ, Mahanty HD, Ascher NL, Roberts JP. Expanding the donor pool: can the Spanish model work in the United States? Am J Transplant. 2003; 3(10):1259–63. 13. Hart A, Smith JM, Skeans MA, et al. Kidney. Am J Transplant. 2016;16(Suppl 2):11–46. 14. Jay C, Washburn K, Dean P, et al. Survival benefit in older patients associated with earlier transplant with high KDPI kidneys. Transplantation. 2017;101(4):867–72. 15. Lloveras J, Arcos E, Comas J, Crespo M, Pascual J. A paired survival analysis comparing hemodialysis and kidney transplantation from deceased elderly donors older than 65 years. Transplantation. 2015;99:991–6. 16. Pérez-Sáez MJ, Arcos E, Comas J, et al. Survival benefit from kidney transplantation using kidneys from deceased donors aged ≥ 75 years: a time-dependent analysis. Am J Transplant. 2016;16(9):2724–33. 17. Luo X, Missie A, Chow E, Segev D. Survival benefit of kidney transplantation with expanded criteria kidney from donors after circulatory death. Am J Transplant. 2015;15(S3):1–1 Abstract no. 291. 18. Pérez-Sáez MJ, Montero N, Redondo-Pachón D, et al. Strategies for an expanded use of kidneys from elderly donors. Transplantation. 2017;101(4): 727–45. 19. Donación en Asistolia en España: Situación actual y Recomendaciones. Documento de Consenso 2012. Available at: http://www.ont.es/infesp/ DocumentosDeConsenso/DONACIÓN%20EN%20ASISTOLIA%20EN%20 ESPAÑA.%20SITUACIÓN%20ACTUAL%20Y%20RECOMENDACIONES.pdf. 20. Informe ONT 2016 .Available at: http://www.ont.es/infesp/Memorias/ Memoria%20Trasplante%20Renal.pdf 21. Portolés Pérez J, Lafuente O, Sánchez Sobrino B, et al. Kidney transplantation with organs from donors after circulatory death type 3: a prospective multicentric Spanish study (GEODAS 3). Transplant Proc. 2015; 47:27–9. 22. Doshi MD, Hunsicker LG. Short- and long-term outcomes with the use of kidneys and livers donated after cardiac death. Am J Transplant. 2007;7:122–9. 23. Singh SK, Kim SJ. Does expanded criteria donor status modify the outcomes of kidney transplantation from donors after cardiac death? Am J Transplant. 2013;13(2):329–36. 24. Teraoka S, Nomoto K, Kikuchi K, et al. Outcomes of kidney transplants from non-heart-beating deceased donors as reported to the Japan organ transplant network from April 1995-December 2003: a multi-center report. Clin Transpl. 2004:91–102. 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