Association between kidney retransplantation and survival according to age in the French national cohort of dialysis patients.

The mean age of patients returning to dialysis after a first kidney transplantation (KT) has increased in the past decades. We aimed to assess the association between second KT (2KT) and survival according to age at the time of return to dialysis. Data of 5334 patients registered in the French Renal Epidemiology and Information Network (REIN) (mean age 56.6 ± 13.6 years) who returned to dialysis after a first KT were collected. The association of 2KT with death was assessed using a propensity score-based analysis taking into account baseline and follow-up variables. In relisted patients (3272 patients, 61.3%), retransplantation was associated with better overall survival in comparison with patients who remained in dialysis (adjusted HR 0.75 [0.63-0.89], p = .0009). The survival advantage conferred by retransplantation gradually declined with increasing age (adjusted HR 0.41 [0.24-0.70] in patients <50, HR 0.94 (0.69-1.27) in patients aged 70 or older, p for interaction 0.034 for age considered as a continuous variable). 2KT is associated with better survival as opposed to remaining on dialysis after a first kidney graft failure. Nevertheless, this survival benefit is age dependent and diminishes with increasing age. The risk/benefit ratio should be comprehensively assessed in the oldest patients when relisting is considered.

Prognostic value for long-term graft survival of estimated glomerular filtration rate and proteinuria quantified at 3 months after kidney transplantation.

BACKGROUND: The estimated glomerular filtration rate (eGFR) measured at 1 year is the usual benchmark applied in kidney transplantation (KT). However, acting on earlier eGFR values could help in managing KT during the first post-operative year. We aimed to assess the prognostic value for long-term graft survival of the early (3 months) quantification of eGFR and proteinuria following KT. METHODS: The 3-, 6- and 12-month eGFR using the Modified Diet in Renal Disease equation (eGFRMDRD) was determined and proteinuria was measured in 754 patients who underwent their first KT between 2000 and 2010 (with a mean follow-up of 8.3 years) in our centre. Adjusted associations with graft survival were estimated using a multivariable Cox model. The predictive accuracy was estimated using the C-index and net reclassification index. These same analyses were measured in a multicentre validation cohort of 1936 patients. RESULTS: Both 3-month eGFRMDRD and proteinuria were independent predictors of return to dialysis (all P < 0.05) and there was a strong correlation between eGFR at 3 and 12 months (Spearman's ρ = 0.76). The predictive accuracy of the 3-month eGFR was within a similar range and did not differ significantly from the 12-month eGFR in either the derivation cohort [C-index 62.6 (range 57.2-68.1) versus 66.0 (range 60.1-71.9), P = 0.41] or the validation cohort [C-index 69.3 (range 66.4-72.1) versus 71.7 (range 68.7-74.6), P = 0.25]. CONCLUSION: The 3-month eGFR was a valuable predictor of the long-term return to dialysis whose predictive accuracy was not significantly less than that of the 12-month eGFR in multicentre cohorts totalling >2500 patients. Three-month outcomes may be useful in randomized controlled trials targeting early therapeutic interventions.

[Towards an extension of the REIN registry to patients with chronic kidney disease at stage 5 not treated with dialysis or transplantation? A pilot study]. / Vers une extension du registre REIN aux patients avec une maladie rénale chronique au stade 5 non traités par dialyse ou greffe ? Étude pilote.

To date, it is important to know more about the population of CKD stage 5 patients in order to better understand the practices of access to renal replacement therapy (RRT) or conservative treatment and to anticipate future needs. In April 2015, at the instigation of the Scientific Committee of REIN, a working group was formed to reflect on the opportunity and feasibility of a data collection on these patients. Between September 2017 and March 2018, 21 participating centers included 390 patients over a period of at least one month. The data collected included the patient's living conditions, level of study, mode of referral, clinical data and the therapeutic project. The median age at baseline was 71.4years (IQR: 58.4-80.4), 39.9% were diabetic. The median eGFR was 12mL/min/1.73m2 (IQR: 9-14). At inclusion, 77% of the patients were already followed in nephrology, 11% had been referred by a general practitioner. For the majority of patients included (81%), there was a RRT project. In 10% of cases, there was a project of conservative care, in 5% of cases the project was not yet decided and in 7% the project had not been yet discussed. At the latest news (median time 4.0months), 35% of patients were dialyzed, 9 (2%) have been pre-emptively transplanted, 25 (6%) died, 210 (54%) were still with a CKD stage 5. Our pilot study has shown the feasibility and interest of setting up such a data collection. Such a registry will provide important public health information regarding the demographic of nephrologists and advanced practices nurses. At the local level, this information will help the department to organize themselves to set-up pre-RRT information, implementation of care pathway nurses and multidisciplinary meetings for difficult cases. However, our pilot study shows that to ensure the completeness of the collection, the tracking upstream or downstream of nephrology consultations for eligible patients is essential and therefore requires dedicated human time on site.

Which is the best predictor of de novo donor-specific antibodies in a cohort of non-sensitized first kidney transplantation: Antigenic, allelic, epitope, or physiochemical HLA mismatches?

BACKGROUND: Assessment of human leukocyte antigen (HLA) matching by using high-resolution allele typing and knowledge of HLA molecule structure may lead to better prediction of de novo donor-specific antibody (dnDSA) development. METHODS: We conducted a single-center cohort study among 150 non-sensitized first kidney transplant recipients to compare the association between antigenic (Ag), allelic (Al), eplet (Ep), amino acid (AAMS) HLA matching and electrostatic (EMS) and hydrophobic (HMS) mismatch scores, and the development of dnDSA. RESULTS: After a mean follow-up time of 49.3 ± 17.7 months, 18 patients (12%) developed dnDSA. The number of HLA mismatches (MM) was significantly associated with the development of dnDSA. The optimal threshold, determined by Harrell's C-index, varied according to the method (5 MM for Ag, P = 0.006; 6 for Al, P = 0.009; 22 for Ep, P = 0.005; 42 for AAMS, P = 0.0007; 45 for EMS, P = 0.009 and 44 for HMS, P = 0.026). C-indices were similar for all matching approaches, suggesting a similar prediction of dnDSA development. CONCLUSION: In this cohort of low immunological risk transplant patients, the use of Al or Ep matching did not improve the prediction of dnDSA development in comparison with the traditional approach.

Comparison of graft and patient survival according to the transplantation centre policy for 1-year screening biopsy among stable kidney recipients: a propensity score-based study.

BACKGROUND: The clinical utility of screening biopsies (SBs) at 1 year post-transplantation is still debated, especially for stable kidney graft recipients. Given the heterogeneity in practices between transplantation centres, the objective of this study was to compare graft and patient survival of stable patients according to whether they were followed up in a transplantation centre with or without a policy for having an SB at 1 year post-transplantation. MATERIALS: From a French multicentre cohort, we studied 1573 kidney recipients who were alive with stable graft function at 1 year post-transplantation, with no acute rejection in their first year post-transplantation. RESULTS: Using propensity score-based analyses, we did not observe any significant difference in the relative risk for graft failure between patients from centres with a 1-year SB policy and those from other centres [hazard ratio = 1.15, 95% confidence interval (CI) 0.86-1.53]. The corresponding adjusted survival probability at 8 years post-transplantation was 69% (95% CI 61-74%) for patients from centres with a 1-year SB policy versus 74% (95% CI 67-79%) for those from other centres. CONCLUSION: A 1-year SB policy for stable patients may not lead to therapeutical benefits for improved graft and patient survival. Further studies examining the benefits versus the risks of a 1-year SB policy are warranted to demonstrate the long-term utility of this intervention.

The age-calibrated measured glomerular filtration rate improves living kidney donation selection process.

Recommendations on the glomerular filtration rate (GFR) threshold compatible with living kidney donation are not agreed upon. The recent KDIGO guidelines suggested a reset of the conventional cutoff value of 80 to 90 mL/min/1.73 m2. While GFR physiologically declines with age, it is unclear whether and how age should be taken into account for selecting acceptable pre-donation GFR. In this multicenter retrospective study encompassing 2007 kidney donors in France, we evaluated the impact of age using two threshold measured GFR (mGFR)s (80 and 90 mL/min/1.73 m2). Three groups of donors were defined according to baseline mGFR: below 80, 80-89.9 and 90 mL/min/1.73 m2 or more. Thirty-two percent of donors were selected despite an mGFR below 90 mL/min/1.73 m2. Donors with the lowest mGFR were significantly older (60 ± 9 vs. 47 ± 11 years) and this applied to both male and female donors. The lifetime-standardized renal reserve, defined as the pre-donation mGFR value divided by the expected number of remaining years of life, was similar irrespective of baseline mGFR groups. Similar results were obtained when eGFR was used instead of mGFR. Finally, in a subgroup of 132 donors with repeated mGFR five years after donation, the magnitude of mGFR decrease was similar in all groups (-34.3%, -33.9%, and -34.9% respectively). Thus, the decision to accept individuals with mGFR lower than 90 mL/min/1.73 m2 for kidney donation is highly dependent on the age of the candidate. Hence, threshold values lower than 90 mL/min/1.73 m2 are reasonable for older donors. Age-calibrated mGFR may improve efficiency of the selection process.

Sirolimus for Secondary Prevention of Skin Cancer in Kidney Transplant Recipients: 5-Year Results.

Purpose Transplant recipients who develop cutaneous squamous cell carcinomas are at high risk for multiple subsequent skin cancers. Sirolimus has been shown to reduce the occurrence of secondary skin cancers, but no study included a follow-up exceeding 2 years. We extended at 5 years the TUMORAPA randomized trial of sirolimus-based immunosuppressive regimen versus calcineurin inhibitor-based immunosuppression. Methods Kidney transplant recipients receiving calcineurin inhibitors who had at least one cutaneous squamous cell carcinoma were randomly assigned to receive sirolimus as a substitute for calcineurin inhibitors (n = 64) or to maintain their initial treatment (n = 56). The primary end point was survival free of squamous cell carcinoma at 5 years. Secondary end points included the occurrence of other skin cancers, renal function, patient and graft survival, and treatment tolerance. Results Survival free of cutaneous squamous cell carcinoma was significantly longer in the sirolimus group than in the calcineurin inhibitor group ( P = .007). In the sirolimus group, the number of patients with new skin cancers was significantly lower compared with the calcineurin inhibitor group: 22% versus 59% for squamous cell carcinomas ( P < .001), 34% versus 66% for other skin cancers ( P < .001), and 20% versus 37.5% for basal cell carcinomas ( P < .05). Kidney graft function, patients, and graft survival were similar in both groups. In the sirolimus group, the mean number of serious adverse effects per patient decreased from 1.16 during the first 2 years, to 0.83 between years 2 and 5. Conclusion In kidney transplant recipients with previous cutaneous squamous cell carcinomas, the antitumoral effect of conversion from calcineurin inhibitors to sirolimus was maintained at 5 years, and sirolimus tolerance was satisfactory.

Poor Patient and Graft Outcome After Induction Treatment by Antithymocyte Globulin in Recipients of a Kidney Graft After Nonrenal Organ Transplantation.

BACKGROUND: End-stage renal failure occurs in a substantial number of patients having received a nonrenal transplantation (NRT), for whom a kidney transplantation is needed. The medical strategy regarding the use of immunosuppression (IS) for a kidney graft in patients after an NRT is not well established. The prekidney grafts long-term IS advocates for a mild induction, such as using anti-IL-2R antibodies, whereas addition of new incompatibilities and anti-HLA preimmunization may suggest using stronger IS such as induction by polyclonal antithymocyte globulins (ATG). METHODS: We performed Cox multivariate and propensity score analysis of our validated transplant database to study the impact of the type of induction therapy on kidney graft survival of recipients of a kidney graft after NRT. RESULTS: We report here that kidney transplantation after NRT treated with an ATG induction has a poorer outcome (kidney and recipient survival) than that with an anti-IL-2R induction. After accounting for potential baseline differences with a multivariate Cox model, or by adjusting on a propensity score, we found that despite patients having received ATG cumulate more risk factors, ATG appears independently involved. As animal-derived biotherapeutics induce antiglycan antibodies and particularly anti-N-glycolylneuraminic acid (Neu5Gc) IgGs which may activate endothelial cells in patients and grafts, we also investigated the magnitude and the nature of the anti-Neu5Gc elicited by the induction and showed that induction was associated with a shift in anti-Neu5Gc IgG repertoire. Possible reasons and mechanisms of a deleterious ATG usage in these patients are discussed. CONCLUSIONS: Our study suggests that ATG induction after a kidney transplantation in recipients already under maintenance IS for a NRT should be used cautiously.

Short Leukocyte Telomere Length Precedes Clinical Expression of Atherosclerosis: The Blood-and-Muscle Model.

RATIONALE: Short telomere length (TL) in leukocytes is associated with atherosclerotic cardiovascular disease (ASCVD). It is unknown whether this relationship stems from having inherently short leukocyte TL (LTL) at birth or a faster LTL attrition thereafter. LTL represents TL in the highly proliferative hematopoietic system, whereas TL in skeletal muscle represents a minimally replicative tissue. OBJECTIVE: We measured LTL and muscle TL (MTL) in the same individuals with a view to obtain comparative metrics for lifelong LTL attrition and learn about the temporal association of LTL with ASCVD. METHODS AND RESULTS: Our Discovery Cohort comprised 259 individuals aged 63±14 years (mean±SD), undergoing surgery with (n=131) or without (n=128) clinical manifestation of ASCVD. In all subjects, MTL adjusted for muscle biopsy site (MTLA) was longer than LTL and the LTL-MTLA gap similarly widened with age in ASCVD patients and controls. Age- and sex-adjusted LTL (P=0.005), but not MTLA (P=0.90), was shorter in patients with ASCVD than controls. The TL gap between leukocytes and muscle (LTL-MTLA) was wider (P=0.0003), and the TL ratio between leukocytes and muscle (LTL/MTLA) was smaller (P=0.0001) in ASCVD than in controls. Findings were replicated in a cohort comprising 143 individuals. CONCLUSIONS: This first study to apply the blood-and-muscle TL model shows more pronounced LTL attrition in ASCVD patients than controls. The difference in LTL attrition was not associated with age during adulthood suggesting that increased attrition in early life is more likely to be a major explanation of the shorter LTL in ASCVD patients. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02176941.

Preemptive second kidney transplantation is associated with better graft survival compared with non-preemptive second transplantation: a multicenter French 2000-2014 cohort study.

The impact of preemptive second kidney transplantation (2KT) on graft and patient survival is poorly established. The association between preemptive 2KT (p2KT, N = 93) and outcomes was estimated in a multicenter French cohort of 2KT (N = 1314) recipients using propensity score methods. During the follow-up, there were 274 returns to dialysis and 134 deaths. p2KT was associated with lower death-censored graft loss (HR = 0.39 [0.18-0.88], P = 0.024) and graft failure from any cause including death (HR = 0.42 [0.22-0.80], P = 0.008). Similar associations were observed for death with a functioning graft, although not reaching statistical significance (HR = 0.47 [0.17-1.26], P = 0.13). There was a significant interaction between donor type and p2KT (P for interaction = 0.016). Indeed, p2KT was not significantly associated with the risk of graft failure from any cause including death in living donor 2KT (P = 0.39), whereas the association was substantial in the deceased donor subset (HR = 0.30 [0.14-0.64], P = 0.002). Of note, the adjusted graft survival of p2KT with deceased donor paralleled that of 2KT with living donor, either preemptive or not (93.8% vs. 88.6% at 4 years and 76.1% vs. 70.5% at 8 years, P = 0.13). This large French multicenter study analyzed using propensity scores suggests that p2KT is associated with better graft prognosis.

Horizontal mixture model for competing risks: a method used in waitlisted renal transplant candidates.

When a patient is registered on renal transplant waiting list, she/he expects a clear information on the likelihood of being transplanted. Nevertheless, this event is in competition with death and usual models for competing events are difficult to interpret for non-specialists. We used a horizontal mixture model. Data were extracted from two French dialysis and transplantation registries. The "Ile-de-France" region was used for external validation. The other patients were randomly divided for training and internal validation. Seven variables were associated with decreased long-term probability of transplantation: age over 40 years, comorbidities (diabetes, cardiovascular disease, malignancy), dialysis longer than 1 year before registration and blood groups O or B. We additionally demonstrated longer mean time-to-transplantation for recipients under the age of 50, overweight recipients, recipients with blood group O or B and with pre-transplantation anti-HLA class I or II immunization. Our model can be used to predict the long-term probability of transplantation and the time in dialysis among transplanted patients, two easily interpretable parts. Discriminative capacities were validated on both the internal and external (AUC at 5 years = 0.72, 95% CI from 0.68 to 0.76) validation samples. However, calibration issues were highlighted and illustrated the importance of complete re-estimation of the model for other countries. We illustrated the ease of interpretation of horizontal modelling, which constitutes an alternative to sub-hazard or cause-specific approaches. Nevertheless, it would be useful to test this in practice, for instance by questioning both the physicians and the patients. We believe that this model should also be used in other chronic diseases, for both etiologic and prognostic studies.

Cost-effectiveness of home telemonitoring in chronic kidney disease patients at different stages by a pragmatic randomized controlled trial (eNephro): rationale and study design.

BACKGROUND: Home telemonitoring has developed considerably over recent years in chronic diseases in order to improve communication between healthcare professionals and patients and to promote early detection of deteriorating health status. In the nephrology setting, home telemonitoring has been evaluated in home dialysis patients but data are scarce concerning chronic kidney disease (CKD) patients before and after renal replacement therapy. The eNephro study is designed to assess the cost effectiveness, clinical/biological impact, and patient perception of a home telemonitoring for CKD patients. Our purpose is to present the rationale, design and organisational aspects of this study. METHODS: eNephro is a pragmatic randomised controlled trial, comparing home telemonitoring versus usual care in three populations of CKD patients: stage 3B/4 (n = 320); stage 5D CKD on dialysis (n = 260); stage 5 T CKD treated with transplantation (n= 260). Five hospitals and three not-for-profit providers managing self-care dialysis situated in three administrative regions in France are participating. The trial began in December 2015, with a scheduled 12-month inclusion period and 12 months follow-up. Outcomes include clinical and biological data (e.g. blood pressure, haemoglobin) collected from patient records, perceived health status (e.g. health related quality of life) collected from self-administered questionnaires, and health expenditure data retrieved from the French health insurance database (SNIIRAM) using a probabilistic matching procedure. DISCUSSION: The hypothesis is that home telemonitoring enables better control of clinical and biological parameters as well as improved perceived health status. This better control should limit emergency consultations and hospitalisations leading to decreased healthcare expenditure, compensating for the financial investment due to the telemedicine system. TRIAL REGISTRATION: This study has been registered at ClinicalTrials.gov under NCT02082093 (date of registration: February 14, 2014).

Trajectories of CKD-MBD biochemical parameters over a 2-year period following diagnosis of secondary hyperparathyroidism: a pharmacoepidemiological study.

OBJECTIVES: To define groups of patients according to the changes of biochemical parameters, that is, serum calcium, phosphate and parathyroid hormone (PTH), over a 2-year follow-up period using group-based multi-trajectory modeling (GBMM) among a cohort of dialysis patients with newly diagnosed secondary hyperparathyroidism (SHPT) (ie, PTH≥500 ng/L for the first time) and to compare their patient characteristics and treatments. DESIGN: Pharmacoepidemiological study. SETTING: In the 12 dialysis units located in the French region of Lorraine. PARTICIPANTS: A total of 269 dialysis patients with newly diagnosed SHPT were prospectively included from December 2009 to May 2012 and followed-up for 2 years. RESULTS: We identified four distinct trajectory groups: 'rapid PTH drop' experiencing a rapid and sharp decrease (over weeks) in PTH level associated with decreasing phosphate level within normal range (n=34; 12.7%), 'gradual PTH decrease' experiencing a gradual and continuous decrease (over months) in PTH level and maintaining phosphate at a middle level throughout the study (n=98; 36.4%), 'slow PTH decrease with high phosphate' experiencing a slow decrease in PTH level associated with a relatively high phosphate level (n=105; 39.0%) and 'uncontrolled SHPT' with high levels of PTH and phosphate throughout the study (n=32; 11.9%). Patients in the 'uncontrolled SHPT' group were significantly (p<0.00001) younger than patients in other groups. Kidney Disease Improving Global Outcomes (KDIGO) targets for PTH, phosphate and calcium were reached simultaneously for 14.9% of patients at baseline and 16.7% at the end of the study. Patients were given cinacalcet more frequently at months 3 and 6 in the 'rapid PTH drop' and at month 24 in the 'uncontrolled SHPT' groups. CONCLUSIONS: Over 2 years following a new SHPT diagnosis, a younger age and a higher rate of alkaline phosphatase were associated to a continuous uncontrolled SHPT. Patients with the lowest PTH at the end of the follow-up tended to receive more often cinacalcet. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT02888639, post results.

[The history of kidney transplantation]. / L'histoire de la greffe rénale.

Medical advances which have marked the history of transplantation include the work of Jean Dausset on the HLA system from 1952, brain death described in 1959 and prolonged organ preservation. This article looks back at the major turning points.

Competing risk of death and end-stage renal disease in incident chronic kidney disease (stages 3 to 5): the EPIRAN community-based study.

BACKGROUND: Although chronic kidney disease (CKD) affects a growing number of people, epidemiologic data on incident CKD in the general population are scarce. Screening strategies to increase early CKD detection have been developed. METHODS: From a community-based sample of 4,409 individuals residing in a well-defined geographical area, we determined the number of patients having a first serum creatinine value ≥1.7 mg/dL and present for at least 3 months that allowed us to calculate an annual incidence rate of CKD (stages 3 to 5). CKD (stages 3 to 5) was defined by estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We also described the primary care, outcomes and risk factors associated with outcomes using competing risks analyses for these CKD patients. RESULTS: A total of 631 incident CKD patients (stages 3 to 5) were followed-up until the occurrence of death and dialysis initiation for more than 3 years. The annual incidence rate of CKD (stages 3 to 5) was estimated at 977.7 per million inhabitants. Analyses were performed on 514 patients with available medical data. During the study, 155 patients (30.2 %) were referred to a nephrologist, 193 (37.5 %) died and 58 (11.3 %) reached end-stage renal disease and initiated dialysis. A total of 139 patients (27.6 %) had a fast decline of their renal function, 92 (18.3 %) a moderate decline and the 272 remaining patients had a physiological decline (21.1 %) or a small improvement of their renal function (33.0 %). Predictors of death found in both Cox and Fine-Gray multivariable regression models included age at diagnosis, anemia, active neoplasia and chronic heart failure, but not a low glomerular filtration rate (GFR). Age at diagnosis, anemia and a low GFR were independently associated with dialysis initiation in Cox model, but anemia was not found to be a risk factor for dialysis initiation in Fine-Gray model. CONCLUSIONS: This large cohort study provided useful epidemiological data on incident CKD (stages 3 to 5) and stressed the need to improve the hands-on implementation of clinical practice guidelines for the evaluation and the management of CKD in primary care.

Adherence to and Acceptance of Once-Daily Tacrolimus After Kidney and Liver Transplant: Results From OSIRIS, a French Observational Study.

BACKGROUND: Adherence to immunosuppressive treatments is a major concern in transplanted patients. METHODS: This 6-month French observational, longitudinal, prospective study aimed to assess patient adherence to and acceptance of once-daily tacrolimus (Advagraf) initiation in kidney and liver transplant recipients. Data from 1106 patients initiating once-daily tacrolimus during posttransplant follow-up were analyzed. Adherence and acceptance were assessed using self-administered questionnaires at inclusion and at 3 and 6 months. RESULTS: Mean age was 52.4 ± 13.2 years, 61.5% were men. For 94.9% of patients, once-daily tacrolimus was prescribed after switching from twice-daily tacrolimus. At inclusion, 20.9% of patients reported good treatment adherence, 72.0% minor nonadherence, and 7.1% were nonadherent. Mean general acceptance score (range, 0-100) was 77.7 (±24.7). At 3 months, adherence was improved in 21.1%, unchanged in 69.2%, and worsened in 9.7% of patients. Mean general acceptance score was 75.4 (±26.5). General acceptance score was improved in 28.0%, unchanged in 39.4%, and worsened in 32.7% of patients. At 6 months, similar changes in adherence and acceptance were observed. Higher general acceptance score at month 3 was significantly associated with better adherence at month 6. CONCLUSIONS: Conversion to once-daily tacrolimus led to an improved rate of adherence at month 3 in more than 20% of patients and a worsened rate of adherence in less than 10% of patients.

Mortality Prediction after the First Year of Kidney Transplantation: An Observational Study on Two European Cohorts.

After the first year post transplantation, prognostic mortality scores in kidney transplant recipients can be useful for personalizing medical management. We developed a new prognostic score based on 5 parameters and computable at 1-year post transplantation. The outcome was the time between the first anniversary of the transplantation and the patient's death with a functioning graft. Afterwards, we appraised the prognostic capacities of this score by estimating time-dependent Receiver Operating Characteristic (ROC) curves from two prospective and multicentric European cohorts: the DIVAT (Données Informatisées et VAlidées en Transplantation) cohort composed of patients transplanted between 2000 and 2012 in 6 French centers; and the STCS (Swiss Transplant Cohort Study) cohort composed of patients transplanted between 2008 and 2012 in 6 Swiss centers. We also compared the results with those of two existing scoring systems: one from Spain (Hernandez et al.) and one from the United States (the Recipient Risk Score, RRS, Baskin-Bey et al.). From the DIVAT validation cohort and for a prognostic time at 10 years, the new prognostic score (AUC = 0.78, 95%CI = [0.69, 0.85]) seemed to present significantly higher prognostic capacities than the scoring system proposed by Hernandez et al. (p = 0.04) and tended to perform better than the initial RRS (p = 0.10). By using the Swiss cohort, the RRS and the the new prognostic score had comparable prognostic capacities at 4 years (AUC = 0.77 and 0.76 respectively, p = 0.31). In addition to the current available scores related to the risk to return in dialysis, we recommend to further study the use of the score we propose or the RRS for a more efficient personalized follow-up of kidney transplant recipients.

Long term outcomes of transplantation using kidneys from expanded criteria donors: prospective, population based cohort study.

OBJECTIVES: To assess the long term outcomes of transplantation using expanded criteria donors (ECD; donors aged ≥ 60 years or aged 50-59 years with vascular comorbidities) and assess the main determinants of its prognosis. DESIGN: Prospective, population based cohort study. SETTING: Four French referral centres. PARTICIPANTS: Consecutive patients who underwent kidney transplantation between January 2004 and January 2011, and were followed up to May 2014. A validation cohort included patients from another four referral centres in France who underwent kidney transplantation between January 2002 and December 2011. MAIN OUTCOME MEASURES: Long term kidney allograft survival, based on systematic assessment of donor, recipient, and transplant clinical characteristics; preimplantation biopsy; and circulating levels of donor specific anti-HLA (human leucocyte antigen) antibody (DSA) at baseline. RESULTS: The study included 6891 patients (2763 in the principal cohort, 4128 in the validation cohort). Of 2763 transplantations performed, 916 (33.2%) used ECD kidneys. Overall, patients receiving ECD transplants had lower allograft survival after seven years than patients receiving transplants from standard criteria donors (SCD; 80% v 88%, P<0.001). Patients receiving ECD transplants who presented with circulating DSA at the time of transplantation had worse allograft survival after seven years than patients receiving ECD kidneys without circulating DSA at transplantation (44% v 85%, P < 0.001). After adjusting for donor, recipient, and transplant characteristics, as well as preimplantation biopsy findings and baseline immunological parameters, the main independent determinants of long term allograft loss were identified as allocation of ECDs (hazard ratio 1.84 (95% confidence interval 1.5 to 2.3); P < 0.001), presence of circulating DSA on the day of transplantation (3.00 (2.3 to 3.9); P < 0.001), and longer cold ischaemia time (> 12 h; 1.53 (1.1 to 2.1); P = 0.011). Recipients of ECD kidneys with circulating DSA showed a 5.6-fold increased risk of graft loss compared with all other transplant therapies (P < 0.001). ECD allograft survival at seven years significantly improved with screening and transplantation in the absence of circulating DSA (P < 0.001) and with shorter (<12 h) cold ischaemia time (P=0.030), respectively. This strategy achieved ECD graft survival comparable to that of patients receiving an SCD transplant overall, translating to a 544.6 allograft life years saved during the nine years of study inclusion time. CONCLUSIONS: Circulating DSA and cold ischaemia time are the main independent determinants of outcome from ECD transplantation. Allocation policies to avoid DSA and reduction of cold ischaemia time to increase efficacy could promote wider implement of ECD transplantation in the context of organ shortage and improve its prognosis.

Excellent long-term outcome of renal transplantation in cystinosis patients.

BACKGROUND: Cystinosis is a rare lysosomal disorder leading to end stage renal disease in more than 90 % of patients before 20 years of age. Data about safety and efficiency of renal transplantation in patients with cystinosis is scarce. We evaluated long-term outcomes of renal transplantation in adult patients with cystinosis. METHODS: Data of renal transplantation (n = 31) in 30 adult patients with cystinosis in 5 French university transplant centers between 1980 and 2013 were retrospectively analyzed. A control cohort of 93 patients was matched for age, graft date, living/deceased donor status and transplant center. RESULTS: Median age at transplantation was 20.4 years (7-36.5). At transplantation, all patients with cystinosis had corneal cystine deposits, 3 had diabetes and 7 had hypothyroidism. Graft survival was better in patients with cystinosis than in control patients (p = 0.013). Multivariate analysis confirmed that cystinosis was an independent protective factor for graft survival (Hazard Ratio (HR) 0.11; CI95 [0.02-0.61]). Specific complications of cystinosis occurred during follow up: diabetes mellitus (n = 4), hypothyroidism (n = 1), liver involvement (n = 1), neurologic involvement (n = 2). Proportion of post-transplant diabetes mellitus (PTDM) was not statistically different in cystinosis group compared to control group: 4 (13.0 %) compared to 5 (5.0 %), respectively (p = 0.25), with no differences regarding calcineurin inhibitors and steroids treatments during follow-up. CONCLUSIONS: Renal transplantation appears to be safe with excellent long-term outcomes in patients with cystinosis. These patients may receive standard immunosuppressive regimens with steroids and calcineurin inhibitors.

Anticoagulation in Chronic Hemodialysis: Progress Toward an Optimal Approach.

Appropriate anticoagulation for hemodialysis (HD) requires a subtle balance between under- and over-heparinization to prevent extracorporeal circuit (ECC) clotting and bleeding, respectively. We discuss five key issues relating to anticoagulation therapy for chronic HD in adults following a review of relevant literature published since 2002: (i) options for standardization of anticoagulation in HD settings. The major nephrology societies have issued low evidence level recommendations on this subject. Interventional studies have generally investigated novel low-molecular weight heparins and provided data on safety of dosing regimens that cannot readily be extrapolated to clinical practice; (ii) identification of clinical and biological parameters to aid individualization of anticoagulation treatment. We find that use of clinical and biological monitoring of anticoagulation during HD sessions is currently not clearly defined in routine clinical practice; (iii) role of ECC elements (dialysis membrane and blood lines), dialysis modalities, and blood flow in clotting development; (iv) options to reduce or suppress systemic heparinization during HD sessions. Alternative strategies have been investigated, especially when the routine mode of anticoagulation was not suitable in patients at high risk of bleeding or was contraindicated; (v) optimization of anticoagulation therapy for the individual patient. We conclude by proposing a standardized approach to deliver anticoagulation treatment for HD based on an individualized prescription prepared according to the patient's profile and needs.