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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 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.

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.

International audience; 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.

Supplemental digital content is available in the text., 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.

Several studies have investigated geographical variations in access to renal transplant waiting lists, but none has assessed the impact on these variations of factors at both the patient and geographic levels. The objective of our study was to identify medical and non-medical factors at both these levels associated with these geographical variations in waiting-list placement in France. We included all incident patients aged 18-80 years in 11 French regions who started dialysis between January 1, 2006, and December 31, 2008. Both a multilevel Cox model with shared frailty and a competing risks model were used for the analyses. At the patient level, old age, comorbidities, diabetic nephropathy, non-autonomous first dialysis, and female gender were the major determinants of a lower probability of being waitlisted. At the regional level, the only factor associated with this probability was an increase in the number of patients on the waiting list from 2005 to 2009. This finding supports a slight but significant impact of a regional organ shortage on waitlisting practices. Our findings demonstrate that patients' age has a major impact on waitlisting practices, even for patients with no comorbidity or disability, whose survival would likely be improved by transplantation compared with dialysis.

International audience; 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, malig-nancy), 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.

The objective was to take into consideration patient concerns for an original qualitative approach to the elaboration of three therapeutic education programs (TEP) designed for chronic renal failure patients, transplantation recipients, and dialysis patients. Four discussion groups involved patients with non-terminal chronic renal failure (one group), transplantation recipients (one group), and dialysis patients (two groups). Topics discussed were patients' knowledge of the TEP and their disease and treatment, patients' expectations concerning the educative content and the organisation of the TEP. For all levels of chronic renal failure, patient expectations focused on nutrition, treatments, and the social and occupational supportive network. Patients with non-terminal renal failure also expressed their expectations concerning the comprehension of laboratory tests and the course of their renal disease. Transplantation recipients wanted to strengthen their knowledge about graft evolution and immunosuppression. Dialysis patients expressed their concerns about disease announcement and the decision for dialysis. While certain topics were common, patients were preoccupied by different problems depending on their degree of renal insufficiency. Nephrolor thus integrated these different levels of concern into the elaboration of E'Dire programs designed for non-terminal renal failure patients and EDUGREFFE for transplant recipients. The third program designed for dialysis patients is currently in the development phase.

Background There are discrepancies regarding the impact of preemptive 2nd kidney transplantation (PSKT) on graft survival. The present study aimed to determine whether the association between PSKT and outcome varies over time and whether this association is era dependent. Methods A total of 266 patients underwent SKT (244 non-PSKT, 22 PSKT) in our center from 1985 to 2015. Association between PSKT and graft survival (allograft failure from any cause including death) was assessed with the use of Cox models. Results During a median follow-up of 6.7 years, 116 events were recorded: 72 returns to dialysis and 44 deaths before return to dialysis. Survival curves diverged up to 5 years (5-year survivals: PSKT, 94.1 ± 5.7%; non-PSKT, 76.8 ± 2.9%) but they converged thereafter (12-year survivals: PSKT, 50.9 ± 15.2%; non-PSKT, 55.5 ± 3.9%). After adjustment for age and living-donor status, PSKT tended to be associated with better graft survival (hazard ratio [HR], 0.18; 95% confidence interval [CI], 0.02–1.27; P = .08) within the first 5 years of SKT but tended to be associated with worse outcome thereafter (HR, 2.36; 95% CI, 0.97–5.72; P = .06; P for interaction with time = .04). In addition, a significant interaction was identified between PSKT and SKT year ( P for interaction = .04). In the multivariable model, the estimated HR for PSKT was 2.54 (95% CI, 0.88–7.35; P = .08) in 1990 as opposed to 0.16 (95% CI, 0.02–1.17; P = .07) in 2012. Conclusions The effect of PSKT on graft survival varies over time and according to year of the procedure. Although the benefit observed within the first 5 years of SKT appears to fade over time, overall graft survival seemingly improved in more recent years.

Adherence to immunosuppressive treatments is a major concern in transplanted patients.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.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.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.

International audience; 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.

Background. Short-term intensified dosing using enteric-coated mycophenolate sodium (EC-MPS) reduces rejection after kidney transplantation without compromising safety and may facilitate steroid avoidance. Methods. In a 6-month, multicentre open-label trial, 222 de novo kidney transplant recipients at low-immunological risk were randomized to steroid avoidance or maintenance steroids with interleukin (IL)-2 receptor antibody (IL-2RA) induction, EC-MPS (2160 mg/day to Week 6, 1440 mg/day thereafter) and cyclosporine. Results. The primary end point; treatment failure at Month 6 [biopsy-proven acute rejection (BPAR), graft loss, death or loss to follow-up], occurred in 17.9% (20/ 112) of steroid-avoidance patients and 14.5% (16/110) of controls (difference 3.4%, 95% confidence interval -6.3 to 13.1, P = 0.47 for superiority testing). BPAR occurred in 11.6 and 7.3% of patients in the steroid-avoidance and control arms, respectively (P = 0.27). Creatinine clearance was similar at Month 6 (steroid-avoidance 56 ± 18 mL/ min/1.73m 2 , controls 60 ± 22 mL/min/1.73m 2 , P = 0.34). Cytomegalovirus infection, as reported by investigators, occurred in 12.5% of steroid-avoidance patients and 22.7% of controls (P = 0.045). Conclusions. A regimen of early intensified EC-MPS dosing with calcineurin inhibitor and IL-2RA induction permits oral steroid avoidance in adult kidney transplant patients at low-immunological risk without compromising efficacy at 6 months' follow-up.

Background. Increased arterial stiffness (AS) is a major determinant of cardiovascular complications in end-stage renal disease (ESRD) patients. Little is known about AS evolution after kidney transplantation. The aim of the study was to characterize the evolution of AS after kidney transplantation in a population of ESRD patients, in comparison to those remaining in dialysis. Methods. Eighty-eight patients (age between 35 and 65) were recruited from the waiting list for kidney transplantation of the University Hospital of Nancy. Two vascular evaluations were performed at a 1-year interval. During this interval, 39 patients were transplanted and 49 remained in dialysis. Results. At inclusion, median pulse-wave velocity (PWV) was similar in transplanted patients and transplantationpending patients, respectively, 9.2 (7.9–11.9) and 9.8 (7.7–12.1) m/s. No difference between the two groups was found at the 1-year interval. Median of time after transplantation was 6.3 (3.8–10.1) months. Median of blood pressure (MBP) decreased only in the transplanted patients [99 (93–112) versus 96 (90–101) mmHg, P < 0.01] Multivariate analysis showed that PWV changes depend on changes in MBP and baseline PWV. Conclusion. Although no difference in the 1-year PWV evolution was found, the low MBP value in transplanted patients allow to expect a better long-term evolution of AS and a better cardiovascular prognosis after kidney transplantation than in transplantation-pending patients.

Renal transplantation in patients with autosomal dominant polycystic kidney disease (ADPKD) is a medical and surgical challenge. Detailed longitudinal epidemiological studies on large populations are lacking and it is mandatory to care better for these patients. The success of such a project requires the development of a validated epidemiological database. Herein, we present the results of the largest longitudinal study to date on renal transplant in patients with ADPKD. The 15-year outcomes following renal transplantation of 534 ADPKD patients were compared with 4779 non-ADPKD patients. This comprehensive, longitudinal, multicenter French study was performed using the validated database, DIVAT (Donnees Informatisees et VAlidees en Transplantaion). We demonstrate that renal transplantation in ADPKD is associated with better graft survival, more thromboembolic complications, more metabolic complications, and increased incidence of hypertension, whereas the prevalence of infections is not increased. This study provides important new insights that could lead to a better care for renal transplant patients with ADPKD.

Large analyses have demonstrated that pre-emptive kidney transplantation (PKT) leads to significant improvements in patient and graft survival when compared with transplantation performed after a period of dialysis. We analysed 1585 patients who received a first renal transplantation from a deceased donor between 2000 and 2004 in four French transplantation centres. The objective was to compare the characteristics of the deceased donor transplantations with or without previous dialysis and to evaluate the impact of PKT and length of dialysis on patient and graft outcomes. Mean age of recipients was 48.1 ± 13.4 years, 62% were men, and 118 (7.4%) of them received a pre-emptive transplantation. For the nonpre-emptive patients, mean time on pretransplant dialysis was 3.4 ± 3.2 years. Pretransplant factors independently related to pre-emptive transplantation were year of transplantation, centre and recipients characteristics: gender, diabetes history, blood group and donor age. Patients with pretransplant dialysis were three times more likely to have delayed graft function than pre-emptive transplant patients, and were 10 times more likely to receive post-transplant dialysis. Five-year patient survival was 92.9%. Five-year graft survival was 89.0%. Neither pre-emptive transplantation nor time on dialysis was significantly associated with patient and/or graft survival.

Resume Introduction La transplantation renale a partir d’un donneur vivant est une methode de choix pour pallier le deficit d’organes. La nephrectomie laparoscopique grâce a ses avantages en termes de morbidite s’est developpee dans ce sens. La securite du geste peut etre amelioree par une assistance robotique. Methode Nous rapportons les 35 premiers prelevements assistes par robot utilises par notre centre. Resultats Apres des explorations anatomiques et fonctionnelles precises, tous les donneurs ont choisi l’option du prelevement par cœliochirurgie assistee par robot. La duree moyenne d’hospitalisation a ete de 5,5 jours. La creatininemie moyenne a un, deux, trois et quatre ans a ete respectivement de 107, 104, 91 et 71 μmol/l. Concernant les receveurs, aucune dialyse n’a ete necessaire apres la greffe. Aucune complication vasculaire n’a ete observee. Les complications urologiques ont ete : six lymphoceles, une stenose ureterale et une necrose ureterale. Dix patients (29 %) ont presente 16 rejets prouves par biopsie. Apres un suivi moyen de 3,8 ± 1 ans, la survie des donneurs et des receveurs est de 100 % a quatre ans et 34 greffons sont fonctionnels avec une creatininemie moyenne de 107, 124, 125 μmol/l respectivement a un, deux, trois et quatre ans. Conclusions Au vu de la tres faible morbidite et des bons resultats a long terme concernant donneurs et receveurs, la laparoscopie robot-assistee semble etre une technique sure et efficace. En offrant des conditions optimales au chirurgien preleveur, elle pourrait contribuer a l’augmentation du nombre de greffes realisees avec donneur vivant en France.

Resume La transplantation renale apporte un benefice important en termes de survie, de morbidite associee et de qualite de vie percue par le patient. Grâce a l’amelioration des resultats, en France, plus de 20 000 personnes vivent avec un greffon fonctionnel. Toutefois, comparee a la sante de la population generale, il reste encore de nombreux progres a obtenir. La prise en charge medicale optimale fait intervenir de nombreux praticiens, au premier rang desquels le medecin generaliste. Les actions sont multiples et necessitent un suivi excluant toute inertie medicale. Les recommandations recemment publiees par la Haute Autorite de Sante permettent de baliser efficacement le terrain.

Summary Renal allograft biopsies ( n = 34) of two different populations of patients according to the immunological risk (high versus low-risk) have been compared retrospectively. The presence of polymorphonuclear leukocytes in peritubular capillaries was more frequent in the high-risk group. The C4d staining was positive in 10% of the low-risk patients and in 50% of the high-risk patients ( P = 0.03). There were more early graft loss, renal infarctions, interstitial hemorrhage, severe glomerulitis, neutrophilic glomerulitis and Banff III grade rejection in the positive C4d group. In conclusion, half of the immunized patients had a humoral rejection, patients with a C4d positive rejection had more early graft loss and more severe histological lesions.

The benefit of prescribing angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-II receptor antagonists (ARB) to kidney transplant recipients remains controversial. We investigated determinants and prescribing patterns of ACEi/ARB during the first year following kidney transplantation. All recipients of a first kidney transplant performed at the university hospital of Nancy (France) between January 1997 and June 2004 were included. Determinants of ACEi/ARB prescription were identified by Cox models among various recipient characteristics (at transplantation and during follow-up), donor characteristics and transplant parameters. Of 491 patients, 28.9% started using ACEi/ARB during the year after transplantation, and 26.9% were taking them at one yr. Recipient determinants of ACEi/ARB use were male sex (HR: 1.82, p = 0.003), pre-transplant hypertension (HR: 2.27, p = 0.0002) and ACEi/ARB administration (HR: 1.85, p = 0.002), post-transplant proteinuria (HR: 1.62, p

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.

International audience; Although cold ischemia time has been widely studied in renal transplantation area, there is no consensus on its precise relationship with the transplantation outcomes. To study this, we sampled data from 3839 adult recipients of a first heart-beating deceased donor kidney transplanted between 2000 and 2011 within the French observational multicentric prospective DIVAT cohort. A Cox model was used to assess the relationship between cold ischemia time and death-censored graft survival or patient survival by using piecewise log-linear function. There was a significant proportional increase in the risk of graft failure for each additional hour of cold ischemia time (hazard ratio, 1.013). As an example, a patient who received a kidney with a cold ischemia time of 30 h presented a risk of graft failure near 40% higher than a patient with a cold ischemia time of 6 h. Moreover, we found that the risk of death also proportionally increased for each additional hour of cold ischemia time (hazard ratio, 1.018). Thus, every additional hour of cold ischemia time must be taken into account in order to increase graft and patient survival. These findings are of practical clinical interest, as cold ischemia time is among one of the main modifiable pre-transplantation risk factors that can be minimized by improved management of the peri-transplantation period.

Post-transplant lymphoproliferative disease (PTLD) is a rare but severe complication of renal transplantation. Reduction of immunosuppression is essential for controlling PTLD but may induce graft loss. Retransplantation after PTLD is considered dangerous, because immunosuppressive treatment resumption may trigger hematological relapse. We retrospectively report six patients (five adults, one child) who underwent a second renal transplantation after successfully treated PTLD. Epstein-Barr virus (EBV) serology was positive before the first transplantation in all patients except the child. Post-transplant lymphoproliferative disease was detected 6.6 months (range 4.5–9.4) after transplantation. Lymphoproliferation was always monomorphic, B-cell, and EBV-related. Post-transplant lymphoproliferative disease was confined to the renal allograft (n = 4), multilocular (n = 1) or cerebral (n = 1). Immunosuppression tapering (6/6) and transplantectomy (5/6) led to hematological remission in all patients. Retransplantation was performed 77 months (range 50–128) after PTLD diagnosis. Immunosuppression included steroids (n = 6), ATG (n = 2), anti-CD25 (n = 2), cyclosporine (n = 4), tacrolimus (n = 2), mycophenolate mofetil (n = 4) and azathioprine (n = 1). After a median follow up of 30 months (range 24–47) patient survival was 100%, with no recurrence of PTLD. In conclusion, renal retransplantation can be considered in patients with monomorphic PTLD history, without major risk of hematological recurrence.

Background: Most studies looking at how the outcome of end-stage renal disease (ESRD) is affected by the timing and quality of the care received before initiation of renal replacement therapy (RRT) are inconclusive. Methods: Five hundred and two adult French patients (age, 62.8 ± 16 years) receiving their first RRT were enrolled in a 2-year, community-based, prospective study. Subjects were assigned to 1 of 5 groups depending on the time between their first serum creatinine reading above 2 mg/dL (177 μmol/L): chronic renal failure (CRF) and nephrology referral (NR) and RRT. Multivariate logistic regression was used to analyze 90-day survival data, and data concerning long-term survival and inclusion on the waiting list for renal transplantation were analyzed using Cox proportional hazards regression. Results:Overall survival rates were 88% at 90 days, 77.2% at 1 year, 65.2% at 2 years, and 54.2% at 3 years. The nephrology referral pattern was associated with age and systolic blood pressure, and independently predicted early death. Compared with group 1 (NR > 12 months), odds ratios (confidence interval 95%) were 2.7 (1.2 to 6.3) for group 2 (NR ≤ 12 months or >4 months), 2.8 (1.0 to 8.0) for group 3 (NR ≤ 4 months or >1 month), 4.9 (2.2 to 11.0) for group 4 (NR ≤ 1 month; CRF > 1 month), and 5.2 (2.2 to 12.3) for group 5 (NR ≤ 1 month; CRF ≤ 1 month). Independent predictors of death in 90-day survivors were age, cardiac disease with previous episodes of heart failure, vascular disease, low diastolic blood pressure, and group 3 referral pattern. Not being entered on the waiting list for renal transplantation was predicted by age, diabetes, vascular disease, and nonelective first dialysis. Conclusion:Late nephrology referral is strongly associated with early death. Emergency first dialysis is an independent risk factor for not being placed on the waiting list for transplantation. Among 90-day survivors, referral pattern has little influence on mortality, which is mainly determined by cardiovascular complications at initiation of RRT.

Background. Induction therapy with antithymocyte globulin (ATG) reduces the incidence of acute rejection after transplantation. A study was undertaken to assess the efficacy and safety of ATG induction on tacrolimus-based and cyclosporine A (CsA)-based therapies compared with immediate tacrolimus triple therapy in kidney transplant recipients. Methods. In a 6-month, open-label, randomized, prospective study conducted in 30 European centers, 555 renal transplant patients were randomly assigned to tacrolimus triple therapy (Tac triple, n=185), ATG induction with tacrolimus (ATG-Tac, n= 186), or ATG induction with CsA microemulsion (ATG-CsA, n=184); all were combined with azathioprine, and corticosteroids. The primary endpoint was incidence and time to first acute rejection episode confirmed by biopsy. Results. Patient demographics and clinical parameters at baseline were similar. Patient and graft survival rates were similar in all groups. The incidence of clinically apparent acute rejection was significantly higher (P=0.003) for Tac triple (33.0%) compared with ATG-Tac (22.6%) and the incidence for ATG-Tac was significantly lower (P=0.004) than for ATG-CsA (37.0%). The incidences of acute rejection confirmed by biopsy (primary endpoint) were 25.4%, 15.1%, and 21.2% for Tac triple, ATG-Tac, and ATG-CsA, respectively (Tac triple vs. ATG-Tac, P=0.004). The incidences of corticosteroid-resistant acute rejection were 7.0% (Tac triple), 4.8% (ATG-Tac), and 10.9% (ATG-CsA) (ATG-Tac vs. ATG-CsA, P=0.038). In the ATG groups, the incidences of leukopenia, thrombocytopenia, serum sickness, fever, and cytomegalovirus infection were significantly higher (P

The purpose of our study was to quantify renal transplant parenchymal sonographic enhancement using pulse-inversion imaging (PII) and intermittent emission after contrast administration by means of bolus and infusion techniques, and to evaluate renal perfusion functional indices. A total of 34 patients, presenting with minor abnormalities (n = 14) and cortical perfusion changes due to parenchymal disorders (n = 12) or renal artery stenosis (n = 8) were included. Cardiac-triggered contrast-enhanced PII ultrasound (US) was performed after administration of SHU 508 A (Schering AG, Berlin, Germany), using a high mechanical index, a frame rate of one image every four cardiac cycles for bolus study, and a decreasing frame rate for infusion study. Compared to baseline values, peak enhancement ratio ranged from 5.6 to 14.7 using a bolus administration, and reached a value of 2.1 to 4.0 using infusion technique. Qualitative analysis showed heterogeneous enhancement in most allografts presenting with acute parenchymal disease (p = 0.03). In bolus studies, time to peak, wash-in and wash-out slopes increased in renal transplants with parenchymal disease and renal artery stenosis (p = 0.0001). Infusion administration exhibited no plateau in signal level, and no significant difference in enhancement ratio was found between groups of patients. Triggered PII after contrast agent administration provides morphologic and quantitative information about cortical vascularity in renal transplants.

International audience; Delayed graft function (DGF) is a common complication in kidney transplantation and is known to be correlated with short-and long-term graft outcomes. Here we explored the possibility of developing a simple tool that could predict with good confidence the occurrence of DGF and could be helpful in current clinical practice. We built a score, tentatively called DGFS, from a French multicenter and prospective cohort of 1844 adult recipients of deceased donor kidneys collected since 2007, and computerized in the Données Informatisées et VAlidées en Transplantation databank. Only five explicative variables (cold ischemia time, donor age, donor serum creatinine, recipient body mass index, and induction therapy) contributed significantly to the DGF prediction. These were associated with a good predictive capacity (area under the ROC curve at 0.73). The DGFS calculation is facilitated by an application available on smartphones, tablets, or computers at www.divat.fr/en/online-calculators/ dgfs. The DGFS should allow the simple classification of patients according to their DGF risk at the time of transplantation, and thus allow tailored-specific management or therapeutic strategies.

International audience; Data from the national French Renal Epidemiology and Information Network (REIN) registry were used to compare survival between transplant recipients under age 65 who resumed dialysis after graft failure during 2007-2009 and transplant-naïve incident dialysis patients matched for age, gender, diabetes mellitus, and year of starting dialysis. Among 911 transplant patients who returned to dialysis, 103 had died by 1 January 2011. Multivariate analysis showed that age over 48 years, coronary artery disease, peripheral artery disease, and inability to walk unassisted were significant predictors of death. In the case-control analysis, the observed mortality rates in 778 transplant failure and 778 transplant-naïve dialysis patients were 11.8 and 10.8%, respectively. Kaplan-Meier estimates of survival after transplant failure vs. the transplant-naïve controls were 95.2 vs. 94.1% at 1 year, 90.3 vs. 88.8% at 2 years, and 84.2 vs. 80.2% at 3 years (log rank P=0.197 overall). Dialysis in transplant failure vs. transplant-naïve patients was not associated with significantly increased mortality. At the start of dialysis, the serum creatinine levels and the rate of unplanned dialysis were significantly lower in transplant failure patients compared with transplant-naïve controls. Thus, in patients under 65 years of age in France, survival of dialysis patients after graft loss is similar to that of incident dialysis patients who have not undergone transplantation.

International audience; Compared to dialysis, kidney transplantation appears to be the best treatment for chronic kidney failure, even for older aged patients. Nevertheless, the individual benefit of transplanting elderly patients has to be balanced against the corresponding increase in the number of patients awaiting grafts. We analyzed the excess mortality related to kidney transplant recipients by taking into account the expected mortality of the general population (additive regression model for relative survival). We applied this method to a cohort of patients who received a first deceased-donor kidney transplant between 1998 and 2009 in France (DIVAT, n = 3641). Overall 10-year mortality was 13%. As expected, recipient age was the main risk factor associated with overall mortality. In contrast, recipient age was no longer significantly associated with the excess of mortality related to kidney transplant status by subtracting the expected mortality of the general population. Delayed graft function (DGF), pretransplantation immunization, and past history of diabetes appeared as the main risk factors of this higher mortality rate. Our results constitute a strong argument in favor of kidney transplantation, regardless of the patient's age. Preventing DGF may be more effective for decreasing the risk of death specifically attributable to the disease.

International audience; Background and Objectives. Contradictory results are reported concerning the influence of anemia on patient and graft survival after renal transplantation. Assuming that level of renal function and anemia are strongly correlated, posttransplantation anemia (PTA) may have a different impact depending on the stage of chronic kidney disease (CKD).Methods. This study is a retrospective multicenter analysis using the DIVAT French database. The prevalence, risk factors, and influence of 12-month PTA (World Health Organization's definition) on patient and graft survival were analyzed according to CKD stage (Modification of Diet in Renal Disease equation).Results. The prevalence of 12-month PTA in our cohort of 4217 patients was 41.1%. Multivariate analysis demonstrated that worse renal function, donor age, period of transplantation, induction therapy, and mTOR inhibitors were significant risk factors for PTA. Posttransplantation anemia was a significant risk factor for all-cause mortality in CKD stages 1 to 2T (hazard ratio, 2.39; 95% confidence interval, 1.99Y4.40) and 3T (hazard ratio, 1.52; 95% confidence interval, 1.08Y2.15) and for cardiovascular mortality only on CKD stages 1T and 2T. In renal transplant recipients with CKD stages 4 to 5T, patient and graft survival were similar in patients with versus without anemia. Graft survival was not influenced by PTA, whatever the CKD stage.Conclusions. Posttransplantation anemia is associated with decreased patient survival only in CKD stages 1T, 2T, and 3T. Posttransplantation anemia has no influence on graft survival regardless of CKD stage.

Background. The aim of this study was to compare the efficacy and safety of induction treatment with antithymocyte globulins (ATG) followed by tacrolimus therapy with immediate tacrolimus therapy in renal transplant recipients. Methods. This 12-month, open, prospective study was conducted in 15 centers in France and 1 center in Belgium; 309 patients were randomized to receive either induction therapy with ATG (n=151) followed by initiation of tacrolimus on day 9 or immediate tacrolimus-based triple therapy (n=158). In both study arms, the initial daily tacrolimus dose was 0.2 mglkg. Steroid boluses were given in the first 2 days and tapered thereafter from 20 mg/day to 5 mg/day. Azathioprine was administered at 1-2 mg/kg per day. Results. At month 12, biopsy-confirmed acute rejections were reported for 15.2% (induction) and 30.4% (noninduction) of patients (P=0.001). The incidence of steroid-sensitive acute rejections was 7.9% (induction) and 22.2% (noninduction)(P=0.001)). Steroid-resistant acute rejections were reported for 8.6% (induction) and 8.9% (noninduction) of patients. A total of nine patients died. Patient survival and graft survival at month 12 was similar in both treatment groups (97.4% vs. 96.8% and 92.1% vs. 91.1%, respectively). Statistically significant differences in the incidence of adverse events were found for cytomegalovirus (CMV) infection (induction, 32.5% vs. noninduction, 19.0%, P=0.009), leukopenia (37.3% vs. 9.5%, P

Background. The efficiency of immunosuppressive drugs prescribed after organ transplantation is mostly monitored through clinical and biological signs of organ rejection or infection. However, it may be expected that some patients develop subtle alterations of their reconstituting immune system, not immediately associated with clinical events. Identification of such anomalies could be useful to alert clinicians for possible future complications. Methods. A systematic follow-up of peripheral lymphocyte subsets, performed in a cohort of 89 kidney transplant recipients, identified severely skewed CD4/ CD8 ratios in 32 patients. For 19 patients, the expression of specific T cell receptor fragments was examined using a panel of 10 monoclonal antibodies. Abnormal control of spontaneously Epstein Barr virus-infected B cells was tested by investigating for the generation of spontaneous lymphoblastoid cell lines in 17 cases. The incidence of rejection and infectious episodes was monitored. Results. A bias in T cell receptor fragments usage was detected in 14/19 cases, involving Vβ8 in all cases. Spontaneous lymphoblastoid cell lines of Epstein Barr positive B blasts developed in 9 of 17 cases. Eleven patients had early rejection episodes and 16 presented with viral primo-infection or reactivation. The incidence of rejection and infectious episodes was higher in the group of 32 patients who developed such abnormal patterns than in the 57 who did not. Conclusion. Transient bias in the T cell receptor repertoire may be observed during immune reconstitution after kidney transplantation, perhaps related to abnormal lymphocyte functions and associated to an impaired control of rejection and/or infectious agents.

Resume Le principal element du dispositif legislatif et reglementaire concernant les prelevements sur donneurs vivants est la loi n o 2004-800 du 6 aout 2004 relative a la bioethique completee par le decret n o 2005-443 du 10 mai 2005 fixant les ressorts territoriaux et la composition des Comites d’experts. Les points importants de la revision sont : la creation de l’Agence de la biomedecine, l’elargissement du cercle des donneurs, l’expression du consentement devant le president du Tribunal de grande instance (TGI), l’extension des competences des Comites d’experts, la mise en place d’un registre de suivi des donneurs, la prise en charge financiere de tous les frais lies au don. A travers la circulaire DHOS du 1 er mars 2005 : pour les etablissements transplanteurs, l’activite de greffe avec donneur vivant est prise en charge, dans le cadre de la tarification a l’activite (T2A), par le groupe homogene de sejour (GHS) transplantation renale, le forfait greffe et le forfait MIG (missions d’interet general).

Fifty years after the first kidney grafts, the ethical problems raised by harvesting an organ from a living donor remain a difficult issue for the French nephrology community. We summarize here the ethical principles guiding biomedicine. Respect for human rights requires careful control ensuring that all potential donors receive complete neutral information and are spared from any type of pressure. The principle of not causing harm must be considered in the context of modern medicine where, under certain conditions, individual risk related to a medical intervention is considered acceptable. Living-donor transplantation can have a potentially beneficial effect for the donor and improves access to grafts for patients whose only other solution would be a cadaver graft. We also discuss nonconventional living donors: ABO or HLA incompatible spouses and at-risk donors, for example, elderly donors.

Psychological support before kidney donation is advocated by all authors, but not systematically proposed by all transplantation centers. An analysis of the literature shows that there are many positive aspects to organ donation including improved self-esteem and quality of life. But many secondary psychological effects can also be observed: fear of giving, fear of receiving, laborious evaluation period, problems in the event of complications for the donor or graft failure, anxiety of the spouses of donators and recipients. Despite these problems, donators are highly motivated and very few experience regret after the donation, creating a strong(er) donor-recipient relationship after the graft.

ies suggest that in these cases erythrocytosis may be caused by defective regulation of erythroid progenitor Background. Erythrocytosis is relatively common after renal transplantation and is associated with a higher proliferation, possibly due to particular cellular interactions or the eVect of cyclosporin on erythropoiesis. risk of thromboembolism. Its aetiology is unclear and there is still debate about the most frequently suggested causes. The culture in vitro of erythroid progenitors is Key words: erythrocytosis; erythroid progenitors; regarded as a useful tool for the diVerential diagnosis erythropoietin; renal transplantation of patients with unclear erythrocytosis. We studied the growth in vitro of bone marrow erythroid progenitors from renal transplant patients with erythrocytosis and controls without erythrocytosis Subjects and methods. Thirteen renal transplant Introduction patients with erythrocytosis and 12 normocythaemic renal transplant controls were studied. The clinical Successful renal transplantation usually corrects renal characteristics of these patients were evaluated and anaemia within 8 to 10 weeks [1]. However, the serum erythropoietin ( Epo) and ferritin levels were haematocrit continues to rise in some patients even determined. Bone marrow erythroid progenitors were after complete correction of anaemia, resulting in postcultured both with and without the addition of Epo to transplant erythrocytosis (PTE ) with significant morthe medium. bidity due to thromboembolism. The published incidResults. Samples from six polycythaemic patients and ence rates for PTE are between 6.5 and 38.4% [2‐7]. seven controls did not grow spontaneously in the The cause of PTE is unclear. The haematocrit may absence of exogenous Epo. Three cases of post- increase because of a reduction in plasma volume. This transplant erythrocytosis and five controls produced is known as spurious erythrocytosis [8], and it responds CFU-E, but not BFU-E. A few CFU-E and BFU-E to increased salt and water intake. The haematocrit grew spontaneously in samples from four polycy- may also increase because of an increase in red blood thaemic patients but not in samples from the controls. cell (RBC ) mass. This is true erythrocytosis. The two Addition of 1 unit per millilitre Epo caused similar situations can be distinguished only by isotopic measincreases in the number of colonies in both polycy- urements of RBC mass and plasma volume [4]. Many thaemic patients and controls. Of the nine patients aetiological factors have been linked to true PTE, eligible for follow-up, all four with spontaneous growth including acute and chronic rejection [9], transplant of BFU-E had transient erythrocytosis and four of the artery stenosis [10], increased Epo formation by the five patients with no spontaneous growth or spontan- native kidneys [11,12], smoking and diabetes [3,13], eous growth of CFU-E only had persistent erythro- and the type and dose of immunosuppressive therapy cytosis requiring treatment with ACE inhibitors. used [6 ]. Treatment with rHuEpo prior to transplantaConclusions. Pathophysiology of post-transplant ery- tion may protect against PTE [14]. None of these throcytosis is heterogeneous. In one-third of the underlying factors is enough in itself to account compatients, there was unexpected, spontaneous and tran- pletely for the pathogenesis of PTE [7]. Culture of sient growth of BFU-E which was not predictive of erythroid progenitors in vitro is useful for the diVerenpermanent erythrocytosis. The results of stem-cell stud- tial diagnosis of patients with unclear erythrocytosis [15]. We have therefore studied the growth in vitro of

Background. Reports have suggested that hepatitis C virus (HCV)-infected kidney recipients may develop de novo glomerular lesions caused by the virus. We studied the relationships between pretransplantation anti-HCV antibodies and the occurrence of proteinuria and the link with short- and long-term patient and graft survival. Methods. A total of 322 consecutive renal recipients treated at a single center from 1989 to 1994 whose sera were routinely assayed for anti-HCV antibodies at the time of transplantation were analyzed. The risks of persistent proteinuria (>1 g/day), graft loss, or death were estimated by Kaplan-Meier analysis. The relationship between clinical variables and each outcome was examined by Cox multivariate regression analysis. Results. Before transplantation, 9.6% of the recipients were anti-HCV antibody positive. Persistent proteinuria developed in 13.6% recipients. The presence of anti-HCV antibodies was strongly associated with proteinuria (relative risk [RR]=5.36, 96% confidence interval [CI] =2.49-11.51). Proteinuria occurred more frequently in second grafts (RR=2.64, 95% CI=1.10-6.29). The number of HLA-A,B mismatches was an independent risk factor (RR=1.55, 95% CI=1.10-2.19). Recipient age (RR=0.80, 95% CI=0.63-1.02) and duration of dialysis (RR=0.86, 95% CI=0.77-0.96) were protective factors. Histology of biopsies from 26/44 recipients with proteinuria showed that de novo glomerular lesions were more frequent in HCV-positive patients, although the difference was not significant. One- and five-year graft survival rates were significantly worse in patients with proteinuria (90.7% and 41.1%) than in patients without it (95.6% and 91.8%) (P

The pathognomonic presence of IgA in the glomerular mesangium of patients with IgA nephropathy (IgAN) suggests an abnormal control of IgA metabolism in this disease that could be modified in transplanted IgAN patients. Alterations of IgA production have been demonstrated in both bone marrow samples and mucosae-associated tissues from IgAN patients, but the analysis of IgA production by peripheral B lymphocytes in culture has yielded conflicting results, some investigators showing an enhanced secretion of IgA and others reporting similar data as with control samples. Little is known about the endogenous activation state of B cells in IgAN, which can be approached by analyzing peripheral Ig-producing cells, a number of which are recirculating between lymphoid organs. In the present study, two methods were applied to appreciate the numbers of spontaneously activated peripheral B cells. The ELISPOT method provided information about short-term secretion of Igs. Intracytoplasmic immunofluorescence for IgA allowed to identify IgA-containing cells, either as short-rimmed immunocytes or as brightly stained immunoblasts with an enlarged cytoplasm. These cells were enumerated in IgAN patients (n = 31), transplanted IgAN patients (n = 27), control patients with other biopsy-proven renal diseases (nontransplanted, n = 48; transplanted, n = 38), and in healthy individuals (n = 18). The number of IgA spot-forming cells obtained in the control groups (1,251 +/- 95 cells/10(6) lymphocytes [mean +/- SE]) was consistent with those in similar previously reported studies, but differed significantly (P = 0.01) from those observed in nontransplanted IgAN patients, who had a surprisingly lower number of such cells (699 +/- 97 cells/10(6) lymphocytes); the number of IgA spot-forming cells in the transplanted IgAN patients (1,355 +/- 182 cells/10(6) lymphocytes) did not differ from that in the control groups. The same pattern was seen for IgA-containing immunoblasts. There was no difference in IgG (overall, 214 +/- 13 cells/10(6) lymphocytes) and IgM (overall, 61 +/- 10 cells/10(6) lymphocytes) spot-forming cell numbers between the five groups of individuals tested, suggesting that the anomaly noted in IgAN patients was not related to technical problems and that this could be a new feature of this renal disease. The normal levels of spontaneously activated peripheral IgA-producing cells found in transplanted IgAN patients suggest that immunosuppressive treatments could interfere with the anomalies of IgA metabolism in this disease.

Six patients with toxoplasmosis complicating renal transplantation are described, and 25 other reported cases are reviewed. The mean age of the 31 patients was 35.16 years. Most of the recipients (25 of 29) showed signs of toxoplasmosis within 3 months post-transplantation, with fever, neurological disturbances, and pneumonia as the main clinical features. Diagnosis was established at autopsy in 15 cases, by serology in 13 cases, and by direct examination, culture, or polymerase chain reaction of biological samples in 5 cases. Seventeen patients also had concomitant infections. The donor was the likely source of transmission to 10 recipients; reactivation was suspected in two cases. The source of transmission could not be determined for the remaining 19 patients. The mortality rate was 64.5%. Ten of the 11 patients given specific treatment survived, indicating that early diagnosis and therapy are essential.

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.

A case of an Epstein-Barr virus (EBV)-associated B lymphoproliferative disorder presented as a renal transplant obstruction is reported. The diagnosis was made from histology, immunohistochemistry, and EBV expression studies. Cytogenetic analysis showed the tumor to be of donor origin and revealed chromosomal translocation 46, XY, inv (1)(p35; q41), involving the EBV insertion site 1(1p35) and transforming growth factor beta 2(1q41) loci.

International audience; Early posttransplant steroid withdrawal may increase the risk of acute rejection and the occurrence of subclinical acute rejection (SCAR). We assessed the feasibility and safety of early steroid withdrawal in low-risk patients receiving cyclosporine A (CsA) and the impact of optimization of mycophenolic acid exposure on steroid withdrawal success. De novo, low-immunological risk kidney recipients received an anti-interleukin-2-receptor-α antibody induction, a short course of 7 days of corticosteroids, and CsA with 2-hr postdose concentration monitoring. They were randomized to adjusted dose (AD) of mycophenolate mofetil (MMF) using therapeutic drug monitoring (TDM) or a fixed-dose (FD) regimen. MMF 3 g was initiated posttransplant and then adjusted starting at week 2 to a 0 to 12 hr area under the concentration time curve of 40 mg · h/L versus 2 g daily, respectively. The primary endpoint was a composite of the proportion of patients experiencing biopsy-proven acute rejection (BPAR) and those with SCAR identified on the 3-month protocol biopsy. Among 247 analyzed patients, only 22 in the AD group and 17 in the FD group experienced BPAR or SCAR (P=0.46). The rate of SCAR was low: 4% (AD) and 2.5% (FD). No between-group difference in the incidence of BPAR was observed. TDM yielded MMF doses ranging from 1 to 4 g/d and significantly reduced interpatient variability at weeks 26 and 52 in the AD group. In low-immunological risk kidney recipients, MMF combined with CsA allows early corticosteroid discontinuation with good tolerability. In this group of patients, TDM of MMF does not improve clinical outcome.

Determining early surrogate markers of long-term graft outcome is important for optimal medical management. In order to identify such markers, we used clinical information from a cross-validated French database (Donnees Informatisees et VAlidees en Transplantation) of 2169 kidney transplant recipients to construct a composite score 1 year after transplantation. This Kidney Transplant Failure Score took into account a series of eight accepted pre- and post-transplant risk factors of graft loss, and was subsequently evaluated for its ability to predict graft failure at 8 years. This algorithm outperformed the traditional surrogates of serum creatinine and the estimated graft filtration rate, with an area under the receiver–operator characteristic curve of 0.78. Validation on an independent database of 317 graft recipients had the same predictive capacity. Our algorithm was also able to stratify patients into two groups according to their risk: a high-risk group of 81 patients with 25% graft failure and a low-risk group of 236 patients with an 8% failure rate. Thus, although this clinical composite score predicts long-term graft survival, it needs validation in different patient groups throughout the world.

International audience; BACKGROUND: Impact of kidney transplantation on survival of French end-stage renal disease (ESRD) patients is unknown. METHODS: A total of 1495 adults living in the Lorraine region and starting renal replacement therapy from 1997 to 2003 were included. A propensity score (PS) of registration on the renal transplant waiting list was estimated. Patient survival was studied using a time-dependent Cox multivariate regression and a Cox model stratified by PS tertiles. Survival of older patients (> or =60 years) was detailed. RESULTS: Survival was associated with age, medical factors and transplantation. The hazard ratio (HR) of death for patients on dialysis compared to transplant recipients was 4.6 (95% CI: 2.9-7.2). The survival analysis stratified by PS was similar to the multivariate Cox model. The survival benefit of transplantation over dialysis persisted among elderly patients [HR: 4.6 (95% CI: 2.2-9.7)]. CONCLUSIONS: In a French community-based network, after taking into account comorbidities, transplantation was associated with longer survival even among elderly patients. Age per se should not therefore be considered as a contraindication to renal transplantation. However, elderly patients should be evaluated carefully before registration on the list. Medical guidelines should put forward a standard set of criteria for access to renal transplantation.

BACKGROUND: This large, randomized, multicenter trial evaluated if basiliximab induction and delayed tacrolimus can preserve renal function in older kidney transplant patients. METHODS: Patients aged 60 years and older received delayed tacrolimus with basiliximab and mycophenolate mofetil with early steroid discontinuation (Tac-d, n=132) or standard tacrolimus with mycophenolate mofetil and steroids until day 91 (Tac-s, n=122). Tacrolimus trough levels were 5 to 10 ng/mL after day 43 in both groups. Renal function at month 6 was measured by calculated creatinine clearance (Cockcroft-Gault formula). RESULTS: In both groups, mean recipient age was 66 years, mean donor age was 63 years with 73% of donors aged 60 years and older. Steroid discontinuation was slower than protocol specified. In the Tac-d group, 56.1% were steroid free at day 14 and 81.8% at month 6. In the Tac-s group, 37.7% were steroid free at month 4 and 63.9% at month 6. Mean (+/-SD) calculated creatinine clearance was 45.7+/-16.1 mL/min (Tac-d) and 45.0+/-18.2 mL/min (Tac-s) (P=ns), mean glomerular filtration rate (modified diet in renal disease formula) was 44.9+/-16.2 mL/min and 41.6+/-16.8 mL/min, respectively. Incidences of biopsy-proven acute rejection were 18.9% (Tac-d) and 18.0% (Tac-s). Delayed graft function was 30.3% (Tac-d) and 23.8% (Tac-s). Estimated patient survival rates (Kaplan-Meier) in the Tac-d and Tac-s groups were 96.1% vs. 99.2% and estimated graft survival rates were 90% vs. 87.6%, respectively. Safety results were similar with both regimens. CONCLUSION: Delayed tacrolimus with basiliximab induction did not provide an advantage in preserving renal function or reducing delayed graft function in older kidney transplant patients.

Nondepleting anti-CD25 monoclonal antibodies (daclizumab) and depleting polyclonal antithymocyte globulin (Thymoglobulin) both prevent acute rejection, but these therapies have not been directly compared in a high-risk, HLA-sensitized renal transplant population. We randomly assigned 227 patients, who were about to receive a kidney graft from a deceased donor, to either Thymoglobulin or daclizumab if they met one of the following risk factors: current panel reactive antibodies (PRA) >30%; peak PRA >50%; loss of a first kidney graft from rejection within 2 yr of transplantation; or two or three previous grafts. Maintenance immunosuppression comprised tacrolimus, mycophenolate mofetil, and steroids. Compared with the daclizumab group, patients treated with Thymoglobulin had a lower incidence of both biopsy-proven acute rejection (15.0% versus 27.2%; P = 0.016) and steroid-resistant rejection (2.7% versus 14.9%; P = 0.002) at one year. One-year graft and patient survival rates were similar between the two groups. In a comparison of rejectors and nonrejectors, overall graft survival was significantly higher in the rejection-free group (87.2% versus 75.0%; P = 0.037). In conclusion, among high-immunological-risk renal transplant recipients, Thymoglobulin is superior to daclizumab for the prevention of biopsy-proven acute rejection, but there is no significant benefit to one-year graft or patient survival.

Background.Focal and segmental glomerulosclerosis (FSGS) is one of the most frequent and severe primary glomerulonephritis that recurs in transplanted kidneys. Although cyclosporine seems to have no effect on the frequency of FSGS recurrence, there is evidence that cyclosporine reduces proteinuria a

Background and objectives: This study examined the efficacy of C.E.R.A., a continuous erythropoietin receptor activator, for correcting anemia in patients who had chronic kidney disease (CKD) and were not on dialysis. Design, setting, participants, & measurements: In this open-label, randomized, parallel-group, Phase III study, 324 adult patients with CKD not on dialysis nor receiving treatment with erythropoiesis-stimulating agents (ESAs) were randomly assigned (1:1) to receive subcutaneous C.E.R.A. once every 2 wk or darbepoetin alfa once weekly during an 18-wk correction period and a 10-wk evaluation period. Thereafter, patients receiving C.E.R.A. were randomly assigned to C.E.R.A. once every 2 wk or once monthly, and patients receiving darbepoetin alfa could receive darbepoetin alfa once weekly or once every 2 wk for a 24-wk extension period. Dosage was adjusted to achieve a hemoglobin (Hb) response and to maintain Hb ±1 g/dl of the response level and 11 to 13 g/dl. Primary end points were Hb response rate during correction and evaluation and change in Hb concentration between baseline and evaluation. Results: Hb response rates were 97.5% for C.E.R.A. and 96.3% for darbepoetin alfa. Adjusted mean changes in Hb from baseline to evaluation were 2.15 g/dl (C.E.R.A.) and 2.00 g/dl (darbepoetin alfa). Analysis showed that C.E.R.A. once every 2 wk was as effective as darbepoetin alfa once weekly for correcting anemia. Hb levels remained stable in all groups during the extension period. C.E.R.A. and darbepoetin alfa were well tolerated. Conclusions: Subcutaneous C.E.R.A. once every 2 wk corrects anemia in ESA–naive patients who are not on dialysis.