Risk Factors for Adverse Outcomes in Kidney Transplants From Donors After Circulatory Death With Normothermic Regional Perfusion: A Systematic Analysis.

BACKGROUND: This study examined 1071 adult primary kidney transplants from the French-controlled donation after the circulatory determination of death (cDCD) program, which uses normothermic regional perfusion (NRP), and involves short cold ischemia times (CIT) and constrained asystole times differing by donor age. METHODS: Logistic regression identified risk factors for primary nonfunction (PNF), delayed graft function (DGF), and graft failure. RESULTS: Risk factors for PNF included donor hypertension, admission for ischemic vascular stroke, and HLA DR mismatches. Risk factors for DGF included functional warm ischemia time >40 min, dialysis >2 y, recipient body mass index of 30 kg/m2 or higher, recipient diabetes, and CIT >10 h. Risk factors for 1-y graft failure included donor hypertension, donor lung recovery, ostial calcification, recipient cardiovascular comorbidities, and HLA DR mismatches. A high donor estimated glomerular filtration rate protected against DGF and graft failure at 1-y. After adjustment restricted to recipient and graft factors and donor age, the risks of PNF, DGF, and graft failure increased with donor age up to 65 y and then remained stable. CONCLUSIONS: The study suggests that cDCD kidney transplants are highly successful, but also that its outcomes are influenced by lung recovery, poor HLA DR matching, and warm ischemia times differing with donor age. Our study identified several risk factors for kidney transplantation failure after cDCD with systematic use of NRP and some of them seem as modifiable variables associated with cDCD transplant outcome.

Optimal donation of kidney transplants after controlled circulatory death.

Controlled donation after circulatory death (cDCD) is used for "extended criteria" donors with poorer kidney transplant outcomes. The French cDCD program started in 2015 and is characterized by normothermic regional perfusion, hypothermic machine perfusion, and short cold ischemia time. We compared the outcomes of kidney transplantation from cDCD and brain-dead (DBD) donors, matching cDCD and DBD kidney transplants by propensity scoring for donor and recipient characteristics. The matching process retained 442 of 499 cDCD and 809 of 6185 DBD transplantations. The DGF rate was 20% in cDCD recipients compared with 28% in DBD recipients (adjusted relative risk [aRR], 1.43; 95% confidence interval [CI] 1.12-1.82). When DBD transplants were ranked by cold ischemia time and machine perfusion use and compared with cDCD transplants, the aRR of DGF was higher for DBD transplants without machine perfusion, regardless of the cold ischemia time (aRR with cold ischemia time <18 h, 1.57; 95% CI 1.20-2.03, vs aRR with cold ischemia time ≥18 h, 1.79; 95% CI 1.31-2.44). The 1-year graft survival rate was similar in both groups. Early outcome was better for kidney transplants from cDCD than from matched DBD transplants with this French protocol.

Kidney Transplant From Uncontrolled Donation After Circulatory Death: Contribution of Normothermic Regional Perfusion.

BACKGROUND: The French uncontrolled donors after circulatory death (DCD) protocol restricts donor age to <55 years, no-flow time to <30 minutes, and functional warm ischemia time to <150 minutes. In situ kidney perfusion can be performed at either 4°C (in situ cooling [ISC]) or 33-36°C (normothermic regional perfusion [NRP]). Hypothermic machine perfusion is systematically used. Only nonimmunized first transplant recipients were eligible. To improve the management of uncontrolled DCD, we tried to identify factors predictive of outcome. METHODS: We identified all kidney transplants from uncontrolled DCD between 2007 and 2014 from the French Transplant Registry. Risk factors for primary nonfunction (PNF; n = 37) and poor renal function (estimated glomerular filtration rate < 30 mL/min or graft loss at 1 y, n = 66) were analyzed by using a multivariate logistic model. RESULTS: This study analyzed 499 kidney transplantations, 50% of which were performed with NRP. Mean functional warm ischemia time was 135 minutes. Mean cold ischemia time was 14 hours. The principal PNF risk factor was young donor age (odds ratio [OR] = 0.95; P = 0.002). A sensitivity analysis showed a higher risk of PNF with ISC than with NRP (OR = 4.5; P = 0.015). Risk factors for poor renal function were donor body mass index (OR = 1.2; P < 0.001) and ISC versus NRP. Univariate analysis of uncontrolled DCD-specific risk factors showed no-flow time, functional warm time, and cold ischemia time did not affect the risk of PNF or poor renal function. CONCLUSIONS: Uncontrolled DCD kidneys are an additional source of valuable transplants. NRP appears to decrease graft failure by restoring oxygenated blood as the first step of preconditioning.

Kidney allograft fibrosis after transplantation from uncontrolled circulatory death donors.

BACKGROUND: Existing data suggest that increased interstitial fibrosis may occur abnormally in renal transplants from donations after uncontrolled circulatory death (uDCD). METHODS: To evaluate the factors that are associated with the progression of fibrosis and its functional impact on renal grafts, we compared 76 uDCD recipients with 86 recipients of kidney donations after brain death at 1-year after transplantation. Groups were matched for donor age, rank of transplantation, and absence of human leukocyte antigen sensitization. Histology was performed on sequential biopsies in uDCD recipients. Associations between variables were analyzed using linear mixed models and univariate analyses. RESULTS: In the uDCD group, increased fibrosis was detected 3 months after transplantation compared to before implantation. After 1 year, interstitial fibrosis and tubular atrophy score was significantly greater (1.5±0.7 vs. 1.0±0.9; P=0.003) and estimated glomerular filtration rate (49.5±17.4 vs. 60.6±19.1 mL/min/1.73 m2; P=0.0003) was significantly lower in the uDCD group than in the donations after brain death group. No flow duration and donor age were significantly associated with accelerated fibrosis. Interstitial fibrosis and tubular atrophy score, interstitial inflammation score, and estimated glomerular filtration rate were significantly worse in uDCD patients with no flow longer than 10 min. CONCLUSION: Donations after uncontrolled circulatory death grafts show more fibrosis after transplantation. No flow duration is associated with accelerated fibrosis and should be considered during uDCD graft allocation.

Biopsy-confirmed de novo renal cell carcinoma (RCC) in renal grafts: a single-centre management experience in a 2396 recipient cohort.

OBJECTIVE: To study the natural history of renal cell carcinoma (RCC) development in renal grafts and their management. PATIENTS AND METHODS: We report a single-centre series of de novo RCC in allografts from a cohort of 2396 consecutive renal transplant recipients. RESULTS: In all, 17 RCCs were detected in 12 patients, representing 0.5% of kidney recipients. The mean patient age was 55 years and the time to RCC diagnosis since transplantation was 13 years. The mean diameter of the RCC was 23 mm. Biopsies were taken in all cases. Concordance between biopsy and surgical specimens was 100% for nuclear grade and pathological type. Four graft removals were performed and six patients underwent nephron-sparing surgery (NSS). Two cryoablations were performed. Overall, nine papillary RCC, five clear cell carcinomas, and one chromophobe cell carcinoma were removed surgically. The mean follow-up was 43 months. One local recurrence was reported in a patient treated by NSS. CONCLUSIONS: Our findings support evidence that radiological screening of kidney recipients allows the detection of small tumours for which a conservative management by NSS or non-surgically destructive techniques can be proposed with mid-term oncological safety. Systematic tumour biopsy may help in the management and treatment decision. Several questions remain unanswered such as the importance of mammalian target of rapamycin inhibitors in the chemoprevention of the recurrence and the genetic cell origin of RCC in renal grafts.

Preliminary results of transplantation with kidneys donated after cardiocirculatory determination of death: a French single-centre experience.

BACKGROUND: Donation after circulatory determination of death (DCDD), formerly non-heart-beating donation and donation after cardiac death, has been re-introduced into clinical practice in France since June 2006 as a potential solution to organ shortage, but this kidney transplantation programme is not popular yet, mainly because of logistical concerns and uncertainty about the long-term warm ischaemia impact on transplanted kidneys. METHODS: Our institution started the DCDD programme in January 2007, following the national 'BioMedicine Agency' protocol. We only considered uncontrolled donors with an initial no-flow period (i.e. delay between collapse and external cardiac massage start) <30 min. A 5-min stand-off period was observed before declaring the death and performing in situ cold perfusion, and since January 2010, normothermic subdiaphragmatic extracorporeal membrane oxygenation. All kidneys were machine-perfused using the hypothermic pulsatile preservation system before transplantation. Morphologic assessment and perfusion indexes were used to assess the suitability for transplantation. RESULTS: From January 2007 to December 2010, our team performed 58 kidney transplantations from uncontrolled Maastricht Category I and II donors. Mean recipient age was 47 ± 9 years. Male/female ratio was 45/13. Mean waiting time on transplantation registry was 30 months (4-180). Mean cold ischaemia time was 13 h 40 min (7-18) and pulsatile perfusion time 8 h (1-16). We had three cases (5%) of primary non-function (PNF) and 95% of delayed graft function. There was no increase in biopsy-proven acute rejection incidence (12.7%). Patient and graft survivals were 98 and 91.4%, respectively, at 1 year and 98 and 88%, respectively, at last follow-up. Estimated glomerular filtration rate ( Modification of Diet in Renal Disease formula) was 48 ± 16 mL/min/1.73 m(2) at 1 year and 48 ± 15 mL/min/1.73 m(2) at the last follow-up. CONCLUSIONS: DCDD kidneys are a valuable additional source of organs for transplantation. Our results show encouraging outcomes, which give rise to further interest in this donor pool. Respecting the national protocol is crucial to prevent PNF and deleterious warm ischaemia effect on transplanted kidney.

Pulsatile perfusion preservation for expanded-criteria donors kidneys: Impact on delayed graft function rate.

PURPOSE: Expanded criteria donors (ECD) kidneys are a potential solution to organ shortage, but exhibit more delayed graft function (DGF). We conducted a prospective controlled study aiming to evaluate the impact of pulsatile perfusion preservation (PPP) on DGF rate. METHODS: Inclusion criteria were: 1) ECD definition (any brain-dead donor aged > 60 years or aged 50-60 years with at least 2 of the following: history of hypertension, terminal serum creatinin level = 1.5 mg/dL, death resulting from a cerebrovascular accident; 2) Donor prolonged circulatory arrest (> 20 mn); 3) previsible cold ischemia time longer than 24 hours. In each pair of kidneys, one organ was preserved with PPP and the other organ was preserved in static cold storage. RESULTS: From February 2007 to September 2009, a total of 22 donors (44 recipients) were included. Recipients were comparable in the two groups with respect to demographic and immunological data. The rate of DGF was significantly lower (9% vs. 31.8%, p = 0.021) in the PPP group. At 1, 3, and 12 months, renal function was comparable in the two groups. CONCLUSIONS: Pulsatile perfusion preservation significantly reduced DGF rate in ECD kidney transplantation.

What is the relevance of systematic aorto-femoral Doppler ultrasound in the preoperative assessment of patients awaiting first kidney transplantation: a monocentric prospective study.

BACKGROUND: The purpose of our study was to study the relevance of a systematic aorto-femoral colour Doppler ultrasound (DUS) in the evaluation of first renal transplant receivers. METHODS: We prospectively studied 100 consecutive first renal transplant (RT) receivers. All patients had a preoperative physical examination with a careful vascular system evaluation including assessment of risk factors and colour DUS of aortic, iliac and femoral arteries. Renal transplantation was planned in the right iliac fossa with end-to-lateral vascular anastomoses. Clinical parameters, DUS results, operative and post-operative parameters at 3 months were compared according to the vascular assessment. RESULTS: Among the 84 patients presenting with a normal preoperative physical arterial examination, 12 patients (14.3%) had an abnormal DUS, revealing atherosclerotic arteries, but no case of arterial stenosis. Among the 16 patients with abnormal physical arterial examination, 10 patients (62.5%) had abnormal DUS, including 4 cases of iliac stenosis. In 3 of the 16 patients (18.8%), DUS revealed right iliac artery stenosis requiring a modification in the surgical procedure. No additional vascular procedure was reported in the case of normal preoperative vascular examination. No technical problems during arterial anastomosis and no post-transplantation arterial complications were reported. In multivariate analysis, abnormal physical examination was the most significant risk factor of atherosclerotic infiltration in DUS. CONCLUSION: The abnormality of arterial physical examination is the best clinical predictor of abnormal DUS in preoperative assessment of renal transplant receivers. However, the low sensitivity and positive predictive value of the physical examination do not support the conclusion that DUS can be avoided in patients with normal arterial physical examination. Nevertheless, in the case of arterial physical abnormality, 'for case' DUS is critical and helps in the surgical strategy in approximately 20% of cases.

Kidney retrieval after sudden out of hospital refractory cardiac arrest: a cohort of uncontrolled non heart beating donors.

INTRODUCTION: To counter the shortage of kidney grafts in France, a non heart beating donor (NHBD) program has recently been implemented. The aim of this study was to describe this pilot program for kidney retrieval from "uncontrolled" NHBD meaning those for whom attempts of resuscitation after a witnessed out-of-hospital cardiac arrest (CA) have failed (Maastricht 1 and 2), in a centre previously trained for retrieval from brain dead donors. METHODS: A prospective, monocentric, descriptive study concerning NHBD referred to our institution from February 2007 to June 2008. The protocol includes medical transport of refractory CA under mechanical ventilation and external cardiac massage, kidney protection by insertion of an intraaortic double-balloon catheter (DBC) with perfusion of a hypothermic solution, kidney retrieval and kidney preservation in a hypothermic pulsatile perfusion machine. RESULTS: 122 potential NHBD were referred to our institution after a mean resuscitation attempt of 35 minutes (20-95). Regarding the contraindications, 63 were finally accepted and 56 had the DBC inserted. Organ retrieval was performed in 27 patients (43%) and 31 kidneys out of the 54 procured (57%) have been transplanted. Kidney transplantation exclusion was related to family refusal (n = 15), past medical history, time constraints, viral serology, high vascular ex vivo resistance of the graft and macroscopic abnormalities. The 31 kidneys exhibited an expected high delayed graft function rate (92%). Despite these initial results transplanted kidney had good creatinine clearance at six months (66 +/- 24 ml/min) with a 89% graft survival rate at six months. CONCLUSIONS: This study shows the feasibility and efficacy of an organ procurement program targeting NHBD allowing a 10% increase in the kidney transplantation rate over 17 months. With a six months follow-up period, the results of transplanted kidney function were excellent.