Kidney allograft rejection is a major issue because it causes graft failure and because immunosuppressive treatments used for its prevention increase the risk of infections and cancers. In systemic ...lupus patients, hydroxychloroquine is used to prevent immune flares with decreased doses of immunosuppressants. Hydroxychloroquine can be safely used in kidney transplant recipients when indicated for autoimmune disease, but its effect on allograft rejection is unknown. We hypothesized that it may prevent kidney allograft rejection. We conducted a nationwide retrospective propensity-matched study on kidney transplantations of patients treated with hydroxychloroquine in France between 2008 and 2018. We analyzed the incidence of allograft rejection or failure within the first year after transplantation. The rates of rejection or allograft failure were not different between the 188 patients treated with hydroxychloroquine at the time of transplantation and their propensity matched controls. Hydroxychloroquine treatment in association with standard immunosuppressive treatment does not prevent rejection in kidney allograft recipients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
ABSTRACT
Background
This national multicentre retrospective cohort study aimed to assess the long-term outcomes of dual kidney transplantation (DKT) and compare them with those obtained from single ...kidney transplantation (SKT).
Methods
Our first analysis concerned all first transplants performed between May 2002 and December 2014, from marginal donors, defined as brain death donors older than 65 years, with an estimated glomerular filtration rate (eGFR) lower than 90 mL/min/1.73 m2. The second analysis was restricted to transplants adequately allocated according to the French DKT program based on donor eGFR: DKT for eGFR between 30 and 60, SKT for eGFR between 60 and 90 mL/min/1.73 m2. Recipients younger than 65 years or with a panel-reactive antibody percentage ≥25% were excluded.
Results
The first analysis included 461 DKT and 1131 SKT. DKT donors were significantly older (77.6 versus 74 years), had a more frequent history of hypertension and a lower eGFR (55.1 versus 63.6 mL/min/1.73 m2). While primary nonfunction and delayed graft function did not differ between SKT and DKT, 1-year eGFR was lower in SKT recipients (39 versus 49 mL/min/1.73 m2, P < 0.001). Graft survival was significantly better in DKT, even after adjustment for recipient and donor risk factors. Nevertheless, patient survival did not differ between these groups. The second analysis included 293 DKT and 687 SKT adequately allocated with donor eGFR and displayed similar results but with a smaller benefit in terms of graft survival.
Conclusions
In a context of organ shortage, DKT is a good option for optimizing the use of kidneys from very expanded criteria donors.
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/m 2 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.
This study aimed to evaluate how 5 preservation solutions for static cold storage affected kidney transplant outcomes. It included all first single kidney transplants during 2010‐2014 from donations ...after brain death in the French national transplant registry, excluding preemptive transplants and transplants of kidneys preserved with a hypothermic perfusion machine. The effects of each preservation solution on delayed graft function (DGF) and 1‐year transplant failure were evaluated with hierarchical multivariable logistic regression models. The study finally included 7640 transplanted kidneys: 3473 (45.5%) preserved with Institut Georges Lopez‐1 solution (IGL‐1), 773 (10.1%) with University of Wisconsin solution, 731 (9.6%) with Solution de Conservation des Organes et Tissus (SCOT, organ and tissue preservation solution), 2215 (29.0%) with Celsior, and 448 (5.9%) with histidine–tryptophan–ketoglutarate. Primary nonfunction rates did not differ by solution. After adjustment for donor, recipient, and transplant characteristics, the DGF risk was significantly lower with IGL‐1 than with all other solutions (odds ratio OR 0.55, 95% confidence interval CI 0.48‐0.64). Conversely, SCOT was associated with a DGF risk significantly higher than the other solutions (OR 2.69, 95% CI 2.21‐3.27) and triple that of IGL‐1 (OR 3.37, 95% CI 2.72‐4.16). One year after transplantation, the transplant failure rate did not differ significantly by preservation solution. The difference between the groups for 1‐year mean creatinine clearance was not clinically relevant.
This study compares outcomes in a French multicenter cohort of donation after brain death kidney transplants according to the 5 preservation solutions used for static cold storage, showing that preservation solution type was associated with differential risk of delayed graft function but not 1‐year graft survival.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Cardiac arrest (CA) causes renal ischemia in one-third of brain-dead kidney donors before procurement. We hypothesized that the graft function depends on the time interval between CA and organ ...procurement.
We conducted a retrospective population-based study on a prospectively curated database. We included 1469 kidney transplantations from donors with a history of resuscitated CA in 2015-2017 in France. CA was the cause of death (primary CA) or an intercurrent event (secondary CA). The main outcome was the percentage of delayed graft function, defined by the use of renal replacement therapy within the first week posttransplantation.
Delayed graft function occurred in 31.7% of kidney transplantations and was associated with donor function, vasopressors, cardiovascular history, donor and recipient age, body mass index, cold ischemia time, and time to procurement after primary cardiac arrest. Short cold ischemia time, perfusion device use, and the absence of cardiovascular comorbidities were protected by multivariate analysis, whereas time <3 d from primary CA to procurement was associated with delayed graft function (odds ratio 1.38).
This is the first description of time to procurement after a primary CA as a risk factor for delayed graft function. Delaying procurement after CA should be evaluated in interventional studies.
Although kidney transplantation (KT) is considered the best treatment for end-stage renal disease (ESRD), there are concerns about its benefit in the obese population because of the increased ...incidence of post-transplant adverse events. We compared patients who underwent KT versus patients awaiting KT on dialysis.
We estimated the life expectancy (RMST, restricted mean survival time) for a 10-year follow-up by matching on time-dependent propensity scores. The primary outcome was time-to-death.
In patients with BMI ≥ 30 kg/m² (N = 2155 patients per arm), the RMST was 8.23 years 95%CI: 8.05-8.40 in the KT group versus 8.00 years 95%CI: 7.82-8.18 in the awaiting KT group: a difference of 2.71 months 95%CI: -0.19; 5.63. In patients with BMI ≥ 35 kg/m² (N = 212 patients per arm), we reported no significant difference (8.56 years 95%CI: 7.96-9.08 versus 8.66 years 95%CI: 8.10-9.17). Hence, we deduced that KT in patients with BMI between 30 and 35 kg/m2 was beneficial in terms of life expectancy.
Regarding the organ shortage, KT may be questionable for those with a BMI ≥ 35 kg/m². These results do not mean that BMI ≥ 35 kg/m² should be a barrier to KT, but it should be accounted in allocation systems to better assign grafts and maximize the overall life expectancy of ESRD patients.
In recent decades, the allocation policies of many countries have moved from center‐based to patient‐based approaches. The new French kidney allocation system (KAS) of donations after brain death for ...adult recipients, implemented in 2015, was principally designed to introduce a unified allocation score (UAS) to be applied locally for one kidney and nationally for the other and to replace regional borders by a new geographical model. The new KAS balances dialysis duration and waiting time to compensate for listing delays and provides more effective longevity matching between donors and recipients with better HLA and age matching. We report these changes, with their rationale and main results. Results show improved HLA matching for young recipients and more rapid access to transplant for older recipients. Young recipients also had better access to transplantation. Transplant access decreased for recipients aged 60–69 and required tuning of KAS parameters. In conclusion, our results strongly indicate that national or adequately broad geographic allocation areas, combined with multiplicative interactions between allocation criteria, permit multivariate optimization of organ allocation and thus improve national kidney sharing and balance HLA matching and age matching, at the price of longer cold ischemic times and more logistical constraints than with local allocation.
This study of the French Kidney Allocation Scheme strongly advocates for allocation areas of sufficient size, combined with multiplicative interactions among allocation criteria, to optimally balance competing considerations.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Despite national guidelines, medical practices and kidney transplant waiting list registration policies may differ from one dialysis/transplant unit to another. Benefit risk assessment variations, ...especially for elderly patients, have also been described. The aim of this study was to identify sources of variation in early kidney transplant waiting list registration in France. Among 16 842 incident patients during the period 2016–2017, 4386 were registered on the kidney transplant waiting list at the start of, or during the first year after starting, dialysis (26%). We developed various log‐linear mixed effect regression models on three levels: patients, dialysis networks, and transplant centers. Variability was expressed as variance from the random intercepts (± standard error). Although patient characteristics have an important impact on the likelihood of registration, the overall magnitude of variability in registration was low and shared by dialysis networks and transplant centers. Between‐transplant center variability (0.23 ± 0.08) was 1.8 higher than between‐dialysis network variability (0.13 ± 0.004). Older age was associated with a lower probability of registration and greater variability between networks (0.04, 0.20, & 0.93 in the 18–64, 65–74, and 75–84 age groups). Targeted interventions should focus on elderly patients and/or certain regions with greater variability in waiting list access.
Especially in elderly patients, patient case‐mix, dialysis networks, and transplant centers practices in France explain variability in kidney transplant waitlist registration at the time of or within one year of dialysis initiation.
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BFBNIB, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
End stage kidney disease increase the risk of COVID-19 related death but how the kidney replacement strategy should be adapted during the pandemic is unknown. Chronic hemodialysis makes social ...distancing difficult to achieve. Alternatively, kidney transplantation could increase the severity of COVID-19 due to therapeutic immunosuppression and contribute to saturation of intensive care units. For these reasons, kidney transplantation was suspended in France during the first epidemic wave. Here, we retrospectively evaluated this strategy by comparing the overall and COVID-19 related mortality in kidney transplant recipients and candidates over the last three years. Cross-interrogation of two national registries for the period 1 March and 1 June 2020, identified 275 deaths among the 42812 kidney transplant recipients and 144 deaths among the 16210 candidates. This represents an excess of deaths for both populations, as compared with the same period the two previous years (mean of two previous years: 253 in recipients and 112 in candidates). This difference was integrally explained by COVID-19, which accounted for 44% (122) and 42% (60) of the deaths in recipients and candidates, respectively. Taking into account the size of the two populations and the geographical heterogeneity of virus circulation, we found that the excess of risk of death due to COVID-19 was similar for recipients and candidates in high viral risk area but four-fold higher for candidates in the low viral risk area. Thus, in case of a second epidemic wave, kidney transplantation should be suspended in high viral risk areas but maintained outside those areas, both to reduce the excess of deaths of candidates and avoid wasting precious resources.
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