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The aim of this study was to estimate the incidence of COVID-19 disease in the French national population of dialysis patients, their course of illness and to identify the risk factors associated with mortality. Our study included all patients on dialysis recorded in the French REIN Registry in April 2020. Clinical characteristics at last follow-up and the evolution of COVID-19 illness severity over time were recorded for diagnosed cases (either suspicious clinical symptoms, characteristic signs on the chest scan or a positive reverse transcription polymerase chain reaction) for SARS-CoV-2. A total of 1,621 infected patients were reported on the REIN registry from March 16th, 2020 to May 4th, 2020. Of these, 344 died. The prevalence of COVID-19 patients varied from less than 1% to 10% between regions. The probability of being a case was higher in males, patients with diabetes, those in need of assistance for transfer or treated at a self-care unit. Dialysis at home was associated with a lower probability of being infected as was being a smoker, a former smoker, having an active malignancy, or peripheral vascular disease. Mortality in diagnosed cases (21%) was associated with the same causes as in the general population. Higher age, hypoalbuminemia and the presence of an ischemic heart disease were statistically independently associated with a higher risk of death. Being treated at a selfcare unit was associated with a lower risk. Thus, our study showed a relatively low frequency of COVID-19 among dialysis patients contrary to what might have been assumed., Graphical abstract

BackgroundAcute kidney injury (AKI) is still characterized by a high mortality rate. While most patients with AKI are admitted in conventional medical units, current available data are still obtained from studies designed for patients admitted in intensive care units (ICU). Our study aimed to elaborate and validate an in-hospital death prognosis score for AKI admitted in conventional medical care units.MethodsWe included two prospective cohorts of consecutive patients with AKI admitted between 2001 and 2004 (elaboration cohort (EC)) and between 2010 and 2014 (validation cohort (VC)). We developed a scoring system from clinical and biological parameters recorded at admission from the EC to predict in-hospital mortality. This score was then tested for validation in the VC.ResultsThree-hundred and twenty-three and 534 patients were included in the EC and VC cohorts, respectively. The proportion of in-hospital death were 15.5% (EC) and 8.9% (VC), mainly due to sepsis. The parameters independently associated with the in-hospital death in the EC were Glasgow score, oxygen requirement, fluid overload, blood diastolic pressure, multiple myeloma and prothrombin time.The in-hospital death prognosis score AUC was 0.845 +/− 0.297 (p ConclusionsOur in-hospital death prognosis score is the first to be prospectively developed and validated for AKI admitted in a conventional medical care unit. Based on current parameters, easily collected at time of admission, this score could be a useful tool for physicians and nephrologists to determine the in-hospital death prognosis of this AKI population.

Additional file 1: Table S1. Comparison between dead and alive patients pooling patients from elaboration and validation cohorts. (DOCX 15 kb)

BACKGROUND Chronic exposure to exogenous antigens causes accumulation of proinflammatory CD57(+)CD28(-) hyperactivated CD8(+) T cells that may promote atherosclerosis. We hypothesized that persistent alloimmune responses may induce immune activation and contribute to posttransplant atherosclerosis. METHODS This hypothesis was tested in a single-center cohort of 577 kidney transplant patients. Propensity score analysis was performed to address potential confounding variables by indication. Immune exhaustion was studied in subcohort of 103 patients. RESULTS Five hundred seventy-seven consecutive renal transplant recipients were included. Seventy-seven atherosclerotic events (AE) (12.3%) occurred during a mean follow-up of 7 years. The cumulative incidence of AE increased with the number of human leukocyte antigen (HLA) mismatches (18%, 10%, and 5% in patients with 5-6, 3-4, and 0-2 mismatches, respectively; P=0.012). Human leukocyte antigen mismatch number (hazards ratio, 1.35; 95% confidence interval, 1.10-1.66, for each supplementary mismatch; P=0.005) was an independent risk factor for AE. In the propensity score match analysis, having received a well-matched kidney conferred a reduced risk of AE (hazards ratio, 0.22; 95% confidence interval, 0.05-0.95; P=0.044). We observed a significant correlation between HLA mismatch numbers and circulating CD57(+)CD28(-) CD8(+) T cells (R=0.31; P=0.017). These CD8(+) T cells were more frequent in patients with more HLA mismatches (P

T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)-induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87±31 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8(+) T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs.

Background. For many nephrologists, patients with polycystic kidney disease (PKD) have an increased risk of complications and technique failure on peritoneal dialysis (PD) due to enlarged kidneys. The literature showed that PD can be as good a therapeutic option as haemodialysis (HD) for patients with PKD. However, no study has focused on the impact of polycystic kidney size on outcomes for patients on PD. Methods. This is a retrospective monocentric study. Fifty-eight patients with PKD started dialysis between January 2000 and December 2010: 24 on PD and 34 on HD. Kidney size assessed by abdominal computed tomography scans was available for 45 patients (19 on PD and 26 on HD). PD technique survival, specific PKD complications and mechanical and infectious PD complications, as need for pre-transplant nephrectomy and kidney transplantation, were considered. Results. The two cohorts were similar in terms of age and body surface area. The median kidney size was not significantly different between PD and HD patients [19.1 cm (12.5–32.5) versus 16.5 cm (11.8–33.8), respectively, P = 0.13]. However, we identified an increased number of PD patients with larger kidneys [(>25 cm) (27.8% on PD versus 7.7% on HD (P = 0.07)]. Neither cystic (infection or haemorrhage) nor mechanical complications (hernias and leaks) were different in PD or HD. Ten patients experienced PD-related peritonitis, mainly due to non-enteric bacterial pathogens. The main reason for stopping PD and HD was transplantation. Six PD patients underwent nephrectomy in order to access the transplant programme. Among them, five were maintained on PD after surgical procedure with good adequacy dialysis criteria. Conclusions. We observed no deleterious impact of kidney size on outcomes on PD when compared with HD. A large kidney size in patients with PKD is not a contraindication to PD. Patients for whom a pre-transplant nephrectomy is mandatory can also safely opt for PD as a dialysis method.

Background. Studies exploring the impact of overweight on mortality have reported controversial results in dialysis patients; some have found overweight to increase mortality, whereas others suggest that it offers a survival advantage. We conducted a prospective study to evaluate the impact of overweight on atherosclerotic events (AE) in dialysis patients with special respect to the malnutrition/inflammation complex syndrome (MICS). Methods. Five hundred and forty-one hemodialysis patients from 11 dialysis centers in France were included. A number of baseline parameters including traditional and nontraditional cardiovascular (CV) risk factors were measured and the cohort was followed prospectively. Results. Over a mean follow-up of 39 months, 207 patients (38.3%) experienced an AE. Overweight, defined by a body mass index greater than 25 kg/m 2 , was associated with increased risk of AEs [RR: 1.68 (CI: 1.11–3.56)], and CV mortality [RR: 1.51 (CI: 1.07–2.13)]. The effect of overweight was different in patients with and without MICS. Age, diabetes, a previous history of CV disease, high serum levels of homocysteine and MICS were also associated with an increased risk of AEs. Conclusions. Similar to the general population, overweight contributes to an increased risk for AEs and CV mortality in hemodialysis patients. The presence or absence of MICS can modify the impact of overweight on development of AEs and mortality in this population.

BACKGROUND Fractalkine (CX3CL1) and its receptor (CX3CR1) are involved in antitumor immunity. Two common single nucleotide polymorphisms of the CX3CR1 gene, V249I and T280M, have been associated with reduced fractalkine signaling characterized by decreased adhesive function, signaling, and chemotaxis of leukocytes. We hypothesized that a renal transplant recipient (RTR) carrying the homozygous I249M280 genotype could experience more cancer due to lower CX3CL1-dependent antitumorigenic effects. METHODS We studied the association between these polymorphisms and cancer incidence in two independent cohorts of RTR, including a total of 622 patients. RESULTS The median follow-up was 8.7 and 7.9 years for the first and second cohorts, respectively. Analysis of 622 patients identified 20 (3.2%) I249M280 homozygous patients, 321 (51.6%) V249T280 homozygous patients, and 281 (45.2%) heterozygous patients. I249M280 homozygotes have an independent increased risk of cancer (hazard ratio [95% confidence interval], 3.3 [1.04-10.52], P=0.043 for cohort 1 and 9.2 [1.67-50.91], P=0.011 for cohort 2) compared with other patients. Age and male gender were also risk factors for cancer occurrence. CONCLUSIONS CX3CR1 gene polymorphism is associated with a higher rate of cancer in RTRs. Such findings may be used to influence immunosuppressive strategies and optimize patient management.

The natural history and clinical significance of posttransplant Epstein-Barr virus (EBV) infection remain largely unknown. The aims of this study are to describe the incidence, risk factors and consequences of EBV infection after kidney transplantation. A total of 383 consecutive patients having received a kidney transplant between January 2002 and December 2010 were included. EBV polymerase chain reaction (PCR) was performed every 2 weeks for 3 months, and every 4 weeks for the next 9 months. A total of 155 of the 383 patients (40%) had at least one positive viremia during the first year posttransplant. The median time to viremia was day 31 posttransplant (14-329). A total of 73 (47%) had EBV viremia > 10(3) log and 23 (15%) had positive viremia for more than 6 months. EBV D+/R- patients (12/18 (67%) versus 143/365 (39%), p = 0.02) and those having received antithymocyte globulins (ATG) (54% vs. 35%; p

Some data suggest that cytomegalovirus (CMV) may be involved in atherogenesis. However, there are few data suggesting that CMV may contribute to posttransplantation atherosclerosis. We studied a cohort of 570 consecutive renal transplant recipients. The impact of CMV on atherosclerotic events was analyzed with respect to other known main cardiovascular risk factors. The mean follow-up duration (± SD) was 87 ± 31 months. A total of 357 patients were considered to be CMV exposed, and 213 were considered to be CMV naive. Cox regression analysis revealed that CMV exposure (hazard ratio [HR], 1.80 [95% confidence interval {CI}, 1.06-3.05]; P = .030) was an independent risk factor for atherosclerotic events. A total of 213 patients remained CMV negative during follow-up, 225 CMV-positive patients had no replication after transplantation, and 132 CMV-positive patients experienced CMV replication after transplantation. Atherosclerotic event rates were 8.5%, 13.3%, and 18.2%, respectively (P = .034). Cox regression analysis revealed that patients with posttransplantation CMV replication had an increased risk of atherosclerotic events (HR, 2.06 [95% CI, 1.03-4.15]; P = .042) and death (HR, 1.76 [95% CI, 1.08-2.89]; P = .024). There was also a trend toward an increased risk of atherosclerotic events in CMV-positive patients without posttransplantation replication (HR, 1.62 [95% CI, .91-3.05]; P = .098). Both pretransplantation CMV exposure and posttransplantation CMV replication contribute to the increased risk of cardiovascular disease in transplant recipients.

Background Before establishing a prospective cohort, an initial pilot study is recommended. However, there are no precise guidelines on this subject. This paper reports the findings of a French regional pilot study carried out in three nephrology departments, before realizing a major prospective Non Dialysis Chronic Renal Insufficiency study (ND-CRIS). Methods We carried out an internal pilot study. The objectives of this pilot study were to validate the feasibility (regulatory approval, providing patients with information, availability of variables, refusal rate of eligible patients) and quality criteria (missing data, rate of patients lost to follow-up, characteristics of the patients included and non-included eligible patients, quality control of the data gathered) and estimate the human resources necessary (number of clinical research associates required). Results The authorizations obtained (CCTIRS – CNIL) and the contracts signed with hospitals have fulfilled the regulatory requirements. After validating the information on the study provided to patients, 1849 of them were included in three centres (university hospital, intercommunal hospital, town hospital) between April 2012 and September 2015. The low refusal rate (51 patients) and the characteristics of non-included patients have confirmed the benefit for patients of participating in the study and provide evidence of the feasibility and representativeness of the population studied. The lack of missing data on the variables studied, the quality of the data analyzed and the low number of patients lost to follow-up are evidence of the quality of the study. By taking into account the time spent by CRAs to enter data and to travel, as well as the annual patient numbers in each hospital, we estimate that five CRAs will be required in total. Conclusion With no specific guidelines on how to realize a pilot study before implementing a major prospective cohort, we considered it pertinent to report our experience of P-ND-CRIS. This experience confirms that i) feasibility, ii) quality of data and iii) evaluating the resources required must be validated before carrying out a large prospective cohort study such as ND-CRIS. Electronic supplementary material The online version of this article (doi:10.1186/s12882-017-0463-3) contains supplementary material, which is available to authorized users.

The role of Cytomegalovirus (CMV) in carcinogenesis is controversial. We studied whether CMV may contribute to cancer occurrence in renal transplant recipients. We studied a prospective cohort of 455 consecutive patients who received a kidney transplant between January 1995 and December 2006. All cancers and types of cancers were assessed. Lymphocyte phenotype and cytokines production were analysed according to CMV status in a subset population of this cohort. Mean follow-up was 84 ± 29 months. One hundred and nineteen cancers (26.2%) occurred during the study follow-up. There was a higher cumulated incidence of cancers in CMV-exposed patients (30.4% vs. 20%; P = 0.018). Mean time to cancer occurrence was shorter in CMV-exposed patients than in CMV-naive patients (4.7 ± 2.6 vs. 6.7 ± 2.8; P = 0.001). Cox regression analysis revealed that both pretransplant CMV exposure (HR, 1.83; 95% CI, 1.17-2.88; P = 0.009) and post-transplant CMV replication (HR, 2.17; 95% CI, 1.02-4.59; P = 0.044) were risk factors for cancer. Among CD8+ T cells, exhausted T cells assessed as CD57+CD28- were expanded in CMV-exposed patients (26 ± 20 vs. 9 ± 8%; P

Background IgA nephropathy (IgAN) is the causative disease of at most 10% of patients on dialysis and waiting for kidney transplantation. The disease can recur on the graft and it is important to know the exact impact of such recurrence on overall results of transplantation in this subgroup of young recipients. Material/methods This is a retrospective study done in two closed centers over three decades with a final number of 142 recipients (111 men; median age of 42.2 years at surgery) with biopsy-proven IgAN among 1979 transplanted patients (7.2%). The mean follow-up time was 6.6 years. Recurrence was defined clinically as proteinuria over 1 g/day ± haematuria and associated with ≥1+ IgA mesangial deposits on the graft biopsy. We used Cox regression and Kaplan-Meier survival curves to study the event. Results Patient survival was excellent: 92% at 10 y; graft survival was 53% at 10y and similar to other recipients. The clinico-pathological (full) recurrence (CPR) was observed overall in 25 cases (17.6%) leading to graft loss in 10 cases (7%). The cumulative rate at 10 y of full recurrence and graft loss due to CPR was 21% and 13% respectively. We could not demonstrate any major influence of immunosuppression (induction or maintenance) or other factors on full recurrence. In addition, 10.5% of recipients disclosed only pathological recurrence without significant clinical consequences. Conclusions Despite significant prevalence of full recurrence after grafting, the overall good results observed still validate renal transplantation in this subgroup of IgAN recipients.

Polyclonal antithymocyte globulins (ATG) induce persistent changes in T-lymphocyte subsets characterized by low CD4 T. The mechanisms remain partly unknown. Prostaglandin E(2) (PGE(2)) is involved in lymphocyte homeostasis. Whether PGE(2) may be involved in persistent CD4 T-cell lymphopenia after ATG is unknown. We examined the association between this polymorphism and CD4 T-cell count in 159 renal transplant recipients (RTR) who received ATG. Analysis of these patients identified 6 CC (3.8%), 32 GC (22.6%), and 117 GG (73.6%) genotypes. Patients with the GG genotype had significantly higher serum PGE(2) concentrations, leading us to compare C carriers with GG patients. Carriers of the C allele had lower CD4 T cell count 1 year (235 ± 96 vs 323 ± 227/mm(3); p = 0.022) and 2 years posttransplant (325 ± 79 vs 422 ± 231/mm(3); p = 0.024). In multivariate analysis, the C allele (p = 0.029) conferred an increased risk of posttransplant CD4 T-cell lymphocytopenia. Pretransplant T-cell receptor excision circle levels were lower in C carriers. COX-2 gene promoter polymorphism at position -765 (G → C) is associated with persistent CD4 T-cell lymphopenia after ATG in RTR. This effect is likely to be mediated by the actions of PGE(2) on thymus function and viability.

Post-transplant diabetes mellitus (PTDM) is a well-known complication in renal transplant recipients (RTRs). While a number of risk factors for PTDM have been identified, the potential impact of pre-transplant dialysis modality on subsequent development of PTDM has not yet been explored. We performed a multicenter retrospective study on 2010 consecutive RTRs who did not have a history of diabetes prior to renal transplantation. PTDM was defined as a need for anti-diabetic therapy in an RTR without a history of diabetes prior to transplantation. Analysis of the risk factors for development of PTDM was performed with respect to pre-transplant dialysis modality. A total of 137 (6.8%) patients developed PTDM; 7% in the hemodialysis group and 6.5% in the peritoneal dialysis (PD) group (p = 0.85). In the multivariate analysis, age (p

International audience; BACKGROUND: To define the role of mammalian target of rapamycin inhibitors in kidney transplantation, we compared efficacy and safety of two immunosuppressive regimens-a calcineurin inhibitor-free regimen with depletive induction versus a calcineurin inhibitor-based regimen. METHODS: De novo renal allograft recipients were randomized before transplantation to receive sirolimus (SRL; n=71, group A) or tacrolimus (n=70, group B). All patients received mycophenolate mofetil and corticosteroids. In group A, patients received rabbit antithymocyte globulin induction. In group B, antithymocyte globulin therapy could be given in case of delayed graft function. The estimated glomerular filtration rate (GFR) (Nankivell's formula) at month 12 was the primary endpoint. RESULTS: GFR showed no significant difference at month 12, with 56.1 in group A versus 58.4 mL/min/1.73 m in group B. In functioning grafts, renal function was significantly better in the SRL group, with higher GFR values at months 1, 2, 3, 6, and 9 (P

International audience; Prolonged CD4 T cell lymphopenia after administration of polyclonal anti-thymocyte globulins increases the rate of posttransplantation morbidity, but whether impaired immune reconstitution affects survival is unknown. We studied the effect of CD4 T cell lymphopenia on survival in 302 consecutive prevalent renal transplant recipients and the role of thymic function in CD4 T cell reconstitution and posttransplantation outcomes in 100 consecutive incident renal transplant recipients. We followed the prevalent cohort for a mean duration of 92 months. Of these 302 patients, 81 (27%) had persistent CD4 T cell counts 1 year (24.1 versus 7.6%; P < 0.001). Furthermore, in Cox regression analysis, CD4 T cell lymphopenia associated with a nearly five-fold risk for death (adjusted hazard ratio [HR] 4.63; 95% confidence interval [CI] 1.91 to 10.65; P = 0.001). In the incident cohort, we estimated thymic function by T cell receptor excision circles (TRECs) per 150,000 CD3+ cells, which predicted efficient CD4 T cell reconstitution. Higher pretransplantation TREC values associated with lower risks for cancer (adjusted HR 0.39; 95% CI 0.15 to 0.97; P = 0.046) and infection (HR 0.29; 95% CI 0.11 to 0.78; P = 0.013). In summary, prolonged polyclonal anti-thymocyte globulin-induced CD4 T cell lymphopenia is an independent risk factor for death. Determination of pretransplantation thymic function may identify patients at higher risk for CD4 T cell lymphopenia and posttransplantation morbidity, including cancer and infections.

International audience; Renal transplantation is considered to be a cost-effective therapy, but hospital medical costs are not accurately known. The aim of this work was to evaluate the costs of hospital stay for renal transplantation. This retrospective study included all patients who underwent renal transplantation between January 1, 2004, and December 31, 2005, in our University hospital. The incurred costs were determined using our center's analytical accounting (AA). The mean local cost was then compared with the median national cost of hospitalization for renal transplantation, based on a sample of participating centers contributing to the National Cost Scale (NCS) per homogenous diagnosis-related group (DRG). These mean costs were weighed against the financing obtained by national rates of the case-mix based payment system (termed T2A). Data were collected from 77 patients. Their mean length of stay was 19.4 days. AA determined the cost of management to be euro14,100 per patient. National economic approaches were significantly higher: euro16,389 for NCS and euro17,369 for national rates. Thus, the specific DRG rate (case mix index) of renal transplantation covers the expenses incurred by our center. These results are rather interesting; however, it is unlike those obtained for the management of other diseases such as acute myeloid leukemia, where T2A underestimates the actual cost by 2-4 times. Last, the hospital budget and T2A must be considered as a whole. The fact that DRGs with favorable and unfavorable pricing balance out should be taken into account.

International audience; Perforin (P), Granzyme B (GB) and Fas-Ligand (FAS-L) are cytotoxic molecules involved in acute rejection (AR) after renal transplantation. A noninvasive diagnostic test to monitor AR and other complications could improve clinical management. We investigated the predictive and diagnostic interest of target mRNA measurements, with a quantitative PCR assay, in AR, as well as in other clinical complications recurrent in kidney transplantation. One hundred and sixty-two urine specimens from 37 allograft recipients were investigated. Clinical settings were AR, urinary tract infection (UTI), cytomegalovirus infection (CMVi) or disease (CMVd), chronic allograft nephropathy (CAN), delayed graft function (DGF) and stable graft course (controls). In the case of AR, mRNA levels of all three molecules were significantly higher than in recipients not showing any clinically evident signs of complication. Indeed, it was observed that expression levels of P, GB and Fas-L mRNA also increase in other clinical situations such as UTI, CMV and DGF. Finally, kinetic studies in three patients with AR revealed that increased P, GB and Fas-L mRNA levels could precede or were concomitant with increased serum creatinin levels. P, GB and Fas-L gene expression in urine specimens were upregulated in AR episodes but also in UTI, CMV infection and DGF. Therefore, this technique would appear to be of limited clinical value as a noninvasive method of diagnosing AR.

International audience; Stable renal transplant recipients (RTR) display high rates of atherosclerotic events (AE). Innate immunity and especially vascular inflammation play a role in the pathogenesis of atherosclerosis. It is illustrated both by an increased occurrence of postrenal transplant cardiovascular events in patients with elevated levels of C-reactive protein and by a correlation between posttransplant AE and Toll-like receptor-4 Asp299Gly polymorphism. Here, we analyze the influence NOD2/CARD15 gene polymorphism since NOD2 can modulate macrophage pro-inflammatory activity and macrophage is present in early atherosclerotic lesions. The incidence of single nucleotide polymorphism (SNP) in the three major polymorphic region of NOD2 gene (SNP8, SNP12 and SNP13) was assessed in 182 RTR and the correlation between such polymorphism and the development of AE was analyzed. No correlation was observed between NOD2 gene polymorphism and the occurrence of AE after renal transplantation. NOD2 gene polymorphism thus does not appear to influence cardiovascular complications in RTR.

Metabolic syndrome (MS) and obesity participate in the pathogenesis of kidney disease. We explored the impact of MS and post-transplant weight gain on graft survival. Two hundred ninety-two renal transplant recipients (RTRs) were included in the study. Various parameters (e.g. anthropometric, biological) were measured at the time of transplantation as well as 1 year post-transplant. The proportion of patients with overweight or obesity significantly increased during the first year post-transplant (p = 0.04). Mean weight gain was 2.7 +/- 5.8 kg. Thirty patients (10.3%) lost their graft during follow-up. In multivariate analysis, patients with an increase in body mass index (BMI) of more than 5% at 1 year post-transplant had an increased risk of graft loss with (HR: 2.82 [95% CI: 1.11-7.44], p = 0.015) or without death censoring (HR: 2.31 [95% CI: 1.06-5.04], p = 0.035). Low creatinine clearance (HR: 4.72 [95% CI: 1.63-13.69], p = 0.004), high urinary protein excretion (HR: 3.21 [95% CI: 1.27-8.18], p = 0.014) and delayed graft function (DGF) (HR: 2.621 [95% CI: 1.07-6.39], p = 0.036) were also independent risk factors for graft loss. MS did not independently predict graft loss, partly due to significant interactions with low-grade inflammation. We conclude that post-transplant weight gain significantly reduces graft survival.

Flow cytometry crossmatch (FCXM) is a more sensitive technique than classical complement-dependent cytotoxicity (CDC) for the detection of donor-directed antibody before renal transplantation. Nevertheless, the role of FCXM in predicting long-term survival of kidney grafts is still unclear. The purpose of our study was to evaluate the impact of a positive T-cell FCXM (T-FCXM) on long-term kidney allografts outcome. Of the 184 consecutive kidney transplantations performed in our center between 1 January1991 and 15 November 1996 a FCXM, performed concurrently to the pre-transplant CDCXM, was available for 170 patients. The CDCXM was negative in all recipients. Among these recipients, 12 (7.1%) had a positive T-FCXM. These patients were not different from patients with a negative T-FCXM for donor and recipient age, sex, frequency of second transplantation, number of human leukocyte antigen matches or mismatches. Frequency of immunized patients was higher in kidney recipients with a positive FCXM (58.3% vs. 24.7%; p = 0.02, chi-square test). Survival analysis revealed that kidney graft outcome was better in negative T-FCXM recipients (p = 0.03), while patient survival was not statistically different. Our results suggest that a positive pre-transplant T-FCXM despite a negative CDCXM is associated with an impaired long-term graft survival in renal allotransplantation.

Predicting coronary heart disease in renal transplant recipients: A prospective study. Background. Current cardiovascular risk calculators, widely used in the general population, have not yet been validated in renal transplant recipients. We conducted a prospective study to determine the incidence and risk factors for ischemic heart dis- ease in renal transplant recipients and to assess the relevance of the Framingham Heart Study risk calculator in this population. Methods. Three hundred and forty four consecutive renal transplant recipients free of vascular disease were enrolled. Coronary events were registered and analyzed with respect to traditional and nontraditional cardiovascular risk factors. The risk of coronary events was assessed through the Framingham Heart Study formula and the relevance of this equation was then analyzed. Results. The patients were followed for a mean duration of 72 ± 14 months. Twenty seven coronary events occurred in 27 patients (7.8%). In addition to risk factors included in the Framingham Heart Study score, C-reactive protein (CRP) level (P = 0.009), and hyperhomocysteinemia (P = 0.01) were found to be independent risk factors for ischemic heart disease events in renal transplant recipients. The Framingham Heart Study model did not predict absolute ischemic heart disease risk in the transplant population as a whole. Conclusion. Nontraditional cardiovascular risk factors greatly contribute to increased incidence of ischemic heart dis- ease events in renal transplant recipients. They should therefore be considered in preventive care of these patients which relies on reduction of overall absolute risk. Although the Framingham Heart Study score has an excellent predictive value in low-risk renal transplant recipients, it tends to underestimate the real cardiovascular risk in high-risk patients. Stable renal transplant recipients have disproportion- ately high rates of arteriosclerotic disease (1). An in- creased prevalence of traditional cardiovascular risk factors cannot fully explain this increased incidence of cardiovascular events in this population (2) and recent re

Background Antithymocyte globulin (ATG) preparations are frequently used as induction treatment in renal transplantation, but little is known about the clinical equivalence of these different agents. We performed a retrospective, single-center study to compare the long-term clinical effects of ATG Fresenius (ATGF) and Thymoglobulin (SangStat, Fremont, CA) in renal transplant recipients. Patients and methods A total of 194 consecutive renal transplant recipients were included who had undergone transplantation in our center between June 1993 and April 2001 and had received ATGF or Thymoglobulin as induction treatment. Results A total of 129 patients received ATGF and 65 patients received Thymoglobulin. Thirty patients (23%) in the ATGF group demonstrated cytomegalovirus (CMV) disease, whereas 24 patients (37%) in the Thymoglobulin group demonstrated CMV (P =0.02). Five patients (3.9%) in the ATGF group and eight patients (12.3%) in the Thymoglobulin group developed posttransplant malignancy (P =0.01). Five patients (3.9%) in the ATGF group and nine patients (13.8%) in the Thymoglobulin group died during follow-up (P =0.005). Cox regression analysis revealed that Thymoglobulin was an independent predictor of CMV disease (relative risk [RR] 2.16, confidence interval [CI] 95% [1.04-4.48]), malignancy (RR 2.16, CI 95% [1.04-4.48]), and death (RR 4.14, CI 95% [1.36-12.6]). Conclusion In renal transplant recipients, induction therapy with Thymoglobulin seems to be associated with a significantly greater incidence of CMV disease, malignancy, and death compared with ATGF.

Objectifs La maladie renale chronique (MRC) represente un lourd fardeau de sante publique. Il n’existe pas en France d’outil epidemiologique perenne dans la MRC avant dialyse. Un tel outil est utile pour connaitre l’epidemiologie de la MRC et realiser des etudes ad hoc. C’est pourquoi nous avons mis en œuvre une cohorte de patients MRC avant dialyse pris en charge dans neuf centres de nephrologie de la region Bourgogne-Franche-Comte (ND-CRIS : « non dialysis chronic renal insufficiency study »). L’objectif de ND-CRIS est de decrire periodiquement les caracteristiques des patients, leur traitement, leur evolution clinique et l’evolution de leur prise en charge. Apres une phase pilote interne de trois ans menee dans trois centres (Besancon, Mâcon, Belfort-Montbeliard) qui a inclus 1849 patients de 71,6 ans ± 12,9 ans avec un DFG (debit de filtration glomerulaire) moyen de 34 mL/mn/1,73m 2 ± 12,5, dont 1371 suivis pendant au moins 18 mois, les neuf centres ont ete ouverts depuis juillet 2015. Nous presenterons ici les premiers resultats des patients inclus jusqu’a fin juin 2016 dans les neuf centres. Methodes La cohorte est prospective ouverte et sans horizon temporel. Ont ete inclus les patients prevalents et incidents âges de plus de 18 ans avec un DFG 2 , non dialyses, non greffes, informes et n’ayant pas exprime un refus, pris en charge par les nephrologues des centres. Les variables ont ete recueillies par des assistant de recherche clinique (ARC) a l’aide d’un case report form (« CRF ») electronique dedie. Le suivi des patients a permis d’evaluer l’evolution du DFG et des comorbidites. La cohorte a recu les accords CCTIRS et CNIL. Resultats Seront presentees des donnees descriptives : (1) nombre de patients inclus jusqu’a fin juin 2016 dans les neuf centres et leurs caracteristiques (sex-ratio, moyenne d’âge, DFG moyen, repartition selon les stades de DFG, comorbidites) y compris l’exposition a des traitements d’interet (medicaments de nephroprotection – IEC et/ou ARA2, erythropoietines, supplementation martiale, chelateurs du potassium et du phosphore, traitements anticoagulants) ; (2) caracteristiques (id supra), evenements d’interet (deces, greffe, passage en dialyse, arret de suivi et departs pour un autre centre) et nombre de perdus de vue des patients ayant un suivi d’au moins 18 mois ; (3) les resultats de l’audit qualite realise sur 1303 variables dans les trois centres pilotes. Discussion Sera discutee la representativite de la cohorte, la confirmation de sa faisabilite, la qualite des donnees, le taux et la definition des perdus de vue, les caracteristiques des patients inclus et suivis pendant au moins 18 mois et leur exposition a des traitements medicamenteux d’interet. Conclusion ND-CRIS comble un manque d’outil epidemiologique en France dans l’insuffisance renale. Le caractere ouvert et incident et le nombre de patients inclus dans ND-CRIS devraient permettre de repondre a des questions auxquelles des cohortes prevalentes de plus petite taille ne peuvent repondre. Outre l’obtention de donnees contenues dans le CRF, cette cohorte permettra de realiser des etudes ad hoc. notamment en pharmacoepidemiologie et ulterieurement de servir de plateforme de recherche et d’outil de monitoring de sante publique.

Antiphospholipid antibodies as a risk factor for atherosclerotic events in renal transplant recipients. Background Epidemiologic studies reported that antiphospholipid antibodies (APAs) were independent predictors of atherosclerotic events. We recently reported a high prevalence of APAs in renal transplant recipients. Nevertheless, the role of APAs on atherosclerotic events has not been prospectively studied in this high-risk population. Methods Participants in the study were 324 consecutive renal transplant recipients. Patients were enrolled between January 1996 and May 1998 and followed up until June 2002. Results The patients were followed for a mean duration of 62 ± 26months. Eighty seven (26.8%) patients exhibited APAs. We found a slight, but significant, correlation between total plasma homocysteine (tHcy) concentration and anticardiolipin (ACA) titers ( r = 0.26; P = 0.036). Fifty six athersclerotic events (17.2%) occurred in 54 patients. Atherosclerotic events occurred more frequently in patients with APAs (33% vs. 9%; P = 0.0003) and ACAs levels were higher in patients who experienced atherosclerotic events (23.7 ± 13.1IU vs. 13.9 ± 9.4 IU; P = 0.003). APAs were associated with an increased risk of atherosclerotic events (RR, 2.82; 95% CI, 1.17 to 5.31). Cox regression analysis also revealed that age above the median (RR, 5.21; 95% CI, 1.67 to 17.13), a previous history of cardiovascular disease (RR, 3.54; 95% CI, 1.57 to 10.43), hyperhomocysteinemia (RR, 4.01; 95% CI, 1.22 to 14.61), and current smoking (RR, 2.17; 95% CI, 1.01 to 6.72) were risk factors for atherosclerotic events. Conclusion The presence of APAs is an independent cardiovascular risk factor in renal transplant recipients. Prevention trials are necessary to assess the efficacy and safety of anticoagulation therapy in transplant patients with APAs.

C-reactive protein and cardiovascular disease in peritoneal dialysis patients.BackgroundElevated plasma concentrations of C-reactive protein (CRP) is a risk factor for cardiovascular disease (CVD) in the general population and in hemodialysis patients. The prognostic value of CRP is less well known in peritoneal dialysis (PD) patients. We examined the association between CRP and cardiovascular event (CVE) in a large population of PD patients.MethodsTwo hundred and forty patients starting PD were enrolled in this prospective study. The role of CRP was analyzed with respect to other known cardiovascular risk factors.ResultsThe patients were followed for a mean duration of 41 ± 21 months; the median value of CRP was 7 mg/L. Eighty-nine cardiovascular events (CVE; 37.1%) occurred in 84 patients and the CRP levels were higher in patients who experienced CVE (27 ± 14 vs. 6 ± 8 mg/L; P < 0.0001). In the Cox model, patients in the three lower quartiles of the CRP levels had a decreased risk of CVE compared with those in the highest quartile. Cox regression analysis also revealed that age, a previous history of cardiovascular disease, hyperhomocysteinemia and hypoalbuminemia were risk factors for CVE. CRP levels were higher in patients who died during the study period (25 ± 12 vs. 5 ± 8 mg/L; P = 0.003). In the Cox model, patients with CRP levels above the median had an increased risk of death compared with those in the lowest quartile.ConclusionsChronic inflammation, as reflected by elevated CRP levels, is frequent in patients starting PD and independently contributes to an increased incidence of CVE in this population.

Introduction La maladie renale chronique (MRC) est un enjeu majeur de sante publique. Les cohortes sont des outils epidemiologiques d’interet pour rechercher les liens entre les facteurs biologiques, comportementaux et environnementaux et les effets sanitaires. Un tel outil apparait alors essentiel pour connaitre les trajectoires d’evolution des patients avant mise en place d’un traitement de suppleance et l’exploration plus large des determinants sous-jacents a ces differents profils d’evolution. Patients et methodes Nous presentons ici une etude de cohorte prospective ouverte sans horizon temporel determine, specialisee dans la MRC pre-suppleance nommee Non-dialysis – chronic renal insufficiency study (ND-CRIS). Ont ete inclus les patients prevalents et incidents de plus de 18 ans avec un debit de filtration glomerulaire estime Resultats Cette etude a debute par une phase pilote d’une duree de 3 ans (2012–2015) menee dans 3 centres de la region Bourgogne Franche Comte (Besancon, Mâcon, Belfort-Montbeliard) ayant permis l’inclusion de 1849 patients avec un taux de refus de participation bas (51 non participants). Depuis 2015, 6 centres supplementaires de la meme region ont ete ouverts avec a la fin decembre 2016, 3452 patients inclus. Le suivi moyen est de 17,4 mois pour les 2443 patients ayant au moins une consultation de suivi. Discussion La cohorte ND-CRIS comble un manque d’outil epidemiologique en France dans la MRC. En effet, les cohortes actuelles sont a inclusion fermee presentant comme limites la perte de representativite dans le temps et l’impossibilite de surveiller des tendances temporelles sur le long terme. Conclusion Le caractere ouvert et incident et le nombre de patients inclus devraient permettre de repondre a des questions auxquelles des cohortes prevalentes de plus petite taille ne peuvent repondre. Cette cohorte peut egalement servir de plateforme de recherche et d’outil de monitoring de sante publique.

Introduction Dans l’insuffisance renale, la connaissance de la typologie des patients et de leur parcours de soins est un enjeu pour les professionnels de sante et pour les tutelles afin d’adapter les moyens alloues a leur prise en charge. L’etude Non-dialysis – chronic renal insufficiency study (ND-CRIS) est une cohorte prospective ouverte sans horizon temporel, realisee en region Bourgogne–Franche Comte etudiant des patients atteints de MRC de stade 3 et plus mais non dialyses. Patients et methodes Les patients adultes sont recrutes depuis 2012, a l’occasion d’une consultation aupres d’un nephrologue. Leurs donnees cliniques et biologiques sont recueillies par un attache de recherche clinique a partir du dossier medical de la structure dans laquelle ils sont suivis par leur nephrologue habituel. Fin 2016, pres de 3500 patients sont inclus permettant d’etablir une premiere photographie de la MRC dans cette region. Resultats Au total, 3452 patients ont ete inclus : 2061 hommes, 1391 femmes soit un ratio H/F de 1,48. Âge moyen : 72 ans (19–99) identique pour les 2 sexes. Nephropathies vasculaires 32,4 % mixte (diabete-hypertension) 16 % diabete seul 8,6 % glomerulopathies 9 %, nephropathies tubulo-interstitielles 6,4 % pkrd 4,1 % autres 5,6 % inconnu ou non disponible 17,7 %. Stades de la MRC : 3A : 22 %, 3B : 39,3 %, 4 : 31,5 %, 5 : 6,9 %. Hypertension (HTA) : traitee chez 3109 patients, consideree equilibree pour 33,7 % d’entre eux seulement. Discussion Le patient type suivi pour une MRC de stade 3 ou plus en Bourgogne–Franche Comte appartient majoritairement au 3e ou au 4e âge. Il s’agit plutot d’un homme sauf dans la tranche des plus de 90 ans du fait de la survie plus longue du sexe feminin identique a la population generale. Il est souvent traite pour une HTA insuffisamment equilibree dans 2/3 des cas malgre le recours a une association d’anti-hypertenseurs chez 75 % des patients. Conclusion La cohorte ND-CRIS, prospective et ouverte est un outil performant qui, au-dela de cette photographie a l’inclusion des patients atteints de MRC permettra dans les annees qui viennent d’evaluer leur evolution clinique et biologique tout au cours de leur parcours de soin. Elle mesurera egalement les interventions du nephrologue sur leur devenir.

Persistent ATG-induced CD4(+) T cell lymphopenia is associated with serious clinical complications. We tested the hypothesis that ATG induces accelerated immune senescence in renal transplant recipients (RTR). Immune senescence biomarkers were analyzed at transplant and one-year later in 97 incident RTR -62 patients receiving ATG and 35 receiving anti-CD25 mAb (α-CD25). This consisted in: (i) thymic output; (ii) bone marrow renewal of CD34(+) hematopoietic progenitor cells (CD34(+) HPC) and lymphoid (l-HPC) and myeloid (m-HPC) progenitor ratio; (iii) T cell phenotype; and (iv) measurement of T cell relative telomere length (RTL) and telomerase activity (RTA). Clinical correlates were analyzed with a 3 year follow-up. Thymic output significantly decreased one-year posttransplant in ATG-treated patients. ATG was associated with a significant decrease in l-HPC/m-HPC ratio. Late stage differentiated CD57(+) /CD28(-) T cells increased in ATG-treated patients. One-year posttransplant T cell RTL and RTA were consequently lower in ATG-treated patients. ATG is associated with accelerated immune senescence. Increased frequency of late differentiated CD4(+) T cell frequency at transplantation tended to be predictive of a higher risk of subsequent opportunistic infections and of acute rejection only in ATG-treated patients but this needs confirmation. Considering pretransplant immune profile may help to select those patients who may benefit from ATG to prevent severe infections and acute rejection.

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Background: Cyclosporine A (CsA) nephrotoxicity is a non-immunologic factor of chronic allograft dysfunction (CAD) in kidney transplant recipients. Mycophenolate mofetil (MMF) may allow CsA dosage reduction or even complete withdrawal in selected populations with CsA nephrotoxicity or CAD. The aim of the present study was to evaluate the efficacy and safety of CsA withdrawal after azathioprine (AZA)-MMF conversion in a population of stable renal transplant recipients. Methods: Twenty-eight first cadaver kidney recipients were included. AZA was then discontinued, MMF was introduced and after 4 months CsA was completely withdrawn. All patients underwent inuline clearance measurement and renal biopsy at inclusion and at the end of the follow-up (40 wk). Results: CsA was completely discontinued in 20 patients. No patient lost his graft during the study period, but 1 patient experienced a reversible acute rejection episode. Inuline clearance improved significantly in the whole series. At the end of follow-up, histological worsening was observed in 50% of patients without any specific risk factor. In these patients, inuline clearance did not improve. Systolic blood pressure, the need for anti-hypertensive drugs and HDL cholesterol improved. Conclusion: In stable kidney transplant recipients, CsA withdrawal after AZA replacement by MMF switch was safe with regard to acute rejection. It improved blood pressure and the lipid profile, but, in 50% of patients was associated with histologic deterioration.

Background. The prevalence and clinical significance of antiphospholipid antibodies (APAs) have not been extensively studied in non-systemic lupus erythematosus (non-SLE) renal transplant recipients. Methods. To further define the prevalence and clinical significance of APAs in non-SLE renal transplant recipients and the appearance of dialysis-related APAs after renal transplantation, we conducted a retrospective study on 178 renal transplant recipients. Documentation of anticardiolipin antibodies (ACAs) and lupus anticoagulant in non-SLE renal transplant recipients, retrospective documentation of ACAs on pretransplant frozen plasma and standardized collection of demographic characteristics and posttransplant history of thrombosis were assessed. Results. Fifty of 178 patients (28.1%) had APAs. Transplant duration was shorter and hemodialysis duration was longer in patients with APAs. A posttransplant history of both venous and arterial thrombosis was more frequent in patients with posttransplant APAs (respectively, 18% vs. 6.2% [P

BACKGROUND Previous studies have demonstrated that hyperhomocyst(e)inaemia is present in patients with impaired renal function and is correlated with cardiovascular disease. Because conflicting data are available on the prevalence, determinants, and clinical significance of hyperhomocyst(e)inaemia in renal-transplant recipients, we conducted the largest cross-sectional study on homocysteine determinants and clinical correlates in renal transplant recipients. METHODS Plasma homocyst(e)ine concentrations and factors known to influence homocysteine metabolism were analysed in 224 renal transplant recipients. Atherosclerotic complications were evaluated with respect to plasma homocysteine concentrations. RESULTS Mean plasma homocyst(e)ine was 21.3+/-9.7 micromol/l. After adjusting for age, gender, transplant duration, and creatinine clearance, patients with and without cyclosporin A (CsA) had similar plasma homocyst(e)ine concentrations (16.9+/-5.9 micromol/l in CsA(+) patients vs 16.3+/-5.2 micromol/l in CsA(-) patients; P=0.3). We found a significant inverse relationship between plasma homocyst(e)ine and folate concentrations in both CsA(+) (r=-0.243; P

Introduction Background. The clinical and immunological relevance of a positive B-cell flow-cytometry (B-FCXM ) Pretransplant crossmatch ( XM ) detection of anticrossmatch in renal transplantation is still donor IgG antibodies to HLA class I molecules contracontroversial. indicates renal transplantation. The presence of such Methods. We retrospectively analysed 145 consecutive antibodies is associated with hyperacute graft rejection cadaveric renal transplantations performed from as well as reduced graft survival. Presently, comMay 1991 to September 1995 in our institution. All plement-dependent cytotoxicity (CDC ) test remains grafts were transplanted following a negative IgG the standard pretransplant crossmatch technique. T-cell complement-dependent cytotoxicity crossmatch However, graft rejection and overall poor graft survival ( T-CDCXM ). Concomitantly to CDCXM, B-cell and can be observed despite a negative CDCXM. T-cell FCXM were performed and results were Development of alternative methods for the detection expressed as a mean fluorescence index ( FI ). Two of recipient serum antibodies directed against donor groups were compared: 116 recipients grafted with a determinants is therefore necessary. Several teams pernegative B-FCXM vs a group of 19 patients grafted form the anti-globulin assay, increasing the sensitivity with a positive B-FCXM. of the standard CDC by the addition of a complementResults. The two groups were similar for length of fixing anti-human IgG. Flow-cytometry crossmatch cold ischaemia, donor and recipient’s age and degree ( FCXM ) is a more sensitive technique that allows the of HLA mismatching. The proportion of patients with detection of low titres of both complement-dependent pre-transplant anti-HLA class I antibodies or a retrans- and -independent anti-donor antibodies, and is thereplantation was significantly increased in the positive fore increasingly used in addition to the standard CDC B-FCXM group vs the negative B-FCXM group. test [reviewed in 1]. FCXM has been reported to be at Recipient survival at 48 months was not significantly least as sensitive as the anti-globulin assay [2]. diVerent in the two groups. However, graft survival at A positive T-FCXM has been recognized as associ12 and 48 months was significantly poorer in the ated with higher rejections episodes and lower graft positive B-FCXM than in negative B-FCXM (68% vs survival after renal retransplantation [3,4], as well as 90% at 12 months: P=0.007, and 57% vs 79% at 48 after primary renal transplantation [5‐7]. However, in months: P=0.02). Within the positive B-FCXM two recent studies, T-FCXM showed no advantage group, no diVerences were found in pre-transplant over the CDCXM [8,9]. Performing crossmatches on anti-HLA class I or II alloimmunization as well as T and B lymphocytes is justified by the diVerential retransplantation frequency between the patients who expression of HLA class I and II molecules on lympholost their graft and the patients who did not. cytes. In contrast to T lymphocytes, B lymphocytes Conclusion. Our results suggest that a pretransplant express HLA class II molecules constitutively and positive B-FCXM is associated with an impaired long- HLA class I molecules at a higher density than T cells. term graft survival in renal allotransplantation. Positive B-cell crossmatches may be due to antibodies directed against non-HLA antigens (e.g. autoantibod

Post-transplant erythrosis (PTE) develops in 9%-22% of all renal transplant recipients. Defined as a persistently elevated hematocrit (0.51), it occurs most commonly during the first 2 years post-transplantation in hypertensive males with excellent allograft function. Several studies have focused on a major role for angiotensin II in PTE pathogenesis, and some case reports have suggested that losartan is an effective treatment for PTE. Nevertheless, its long-term safety and efficiency have not been reported in renal transplant recipients suffering from PTE. We describe four patients successfully treated with losartan for PTE. Hematocrit remained normal for 21, 18, 15, and 15 months, respectively, after the beginning of losartan therapy. Mean erythropoietin concentration was not modified by treatment (17 +/- 3.7 mU/ml vs 17 +/- 3.8 mU/ml) and serum creatinine concentration remained stable. We conclude that losartan is a safe and effective long-term treatment for PTE.

Few data are available about the muscle status in renal transplant recipients. Moreover, the list of myotoxic drugs is growing longer and some of them are likely to be prescribed in renal transplant patients. These conditions may act as confounding factors in case reports of both cyclosporin and colchicine myopathies. Moreover no study has evaluated the frequency of myopathy in patients on both colchicine and cyclosporin. We conducted a retrospective study including all renal transplant recipients followed in our unit in whom colchicine was prescribed since January 1994. Clinical and biological data of patients on both colchicine and cyclosporin were analysed. Secondly case subjects were compared with matched controls not receiving colchicine but cyclosporin. Ten patients received colchicine in association with cyclosporin. Five patients (50%) experienced muscular symptoms and when performed, muscular histology showed vacuolar myopathy. All five patients improved after colchicine withdrawal. Cases with and without muscular symptoms did not differ in age, transplant duration, and serum creatinine level. Mean duration of colchicine therapy was 12.2 +/- 4.4 months in cases with muscular symptoms and 6.8 +/- 4.6 months in cases without muscular symptoms (P < 0.05). No control complained of either muscular pain nor weakness (P < 0.0005). Only one patient (3.3%) had elevated serum creatine phosphokinase concentration (P < 0.0005). We conclude that myopathy is very frequent in patient on both colchicine and cyclosporin. Muscular symptoms improve in all patients after colchicine withdrawal.

Background Previous small studies have reported favorable results of peritoneal dialysis (PD) in the setting of chronic refractory heart failure (CRHF). We evaluated the impact of PD in a larger cohort of patients with CHRF where end-stage renal disease was excluded. Methods All patients who received PD therapy for CRHF between January 1995 and December 2010 in two medical centers in France were included in this retrospective study. Baseline characteristics were compared with clinical parameters during the first year after initiation of PD. Mortality, safety, and sustainability of PD were also analyzed. Results The 126 patients included had a mean age of 72 ± 11 years and an estimated glomerular filtration rate of 33.5 ± 15.1 mL/min/1.73 m2. Mean time on PD was 16 ± 16.6 months. During the first year, patients with a left ventricular ejection fraction (LVEF) of 30% or less experienced improvement in cardiac function (30% ± 10% vs 20% ± 6%, p < 0.0001). We observed a significant reduction in the number of days of hospitalization for acute decompensated heart failure after PD initiation (3.3 ± 2.6 days/patient–month vs 0.3 ± 0.5 days/patient–month, p < 0.0001). One-year mortality was 42%. Conclusions In CRHF, PD significantly reduces the number of days of hospitalization for acute heart failure. Improved LVEF may have led to the comparatively good 1-year survival in this cohort.

Cytomegalovirus (CMV) infection is reported to be capable of modifying endothelial surface with subsequent increased risk of thromboembolic complications. Nevertheless, there are only sparse reports on its role in the development of bleeding diathesis. Here we report two renal transplant recipients who manifested severe coagulation disorders associated with acute CMV infection. Antiviral therapy was followed by consistent correction of coagulation abnormalities.

Renal-transplant recipients have a higher prevalence of thromboembolic events compared with the general population. This elevated risk has been attributed to immunosuppressive drugs as well as metabolic and immunologic factors. Cytomegalovirus (CMV) infection, a frequent complication of transplantation, is known to modify endothelial phenotype from anticoagulant into procoagulant. There are few reports addressing the association of venous thromboembolism with CMV infection in immunocompetent patients. Some authors have also reported cases of arterial thrombosis in transplant recipients presenting CMV infection. However, the association of venous thromboembolic events with CMV infection has not yet been discussed in these patients. We present seven cases of simultaneous acute CMV infection and venous thromboembolism in renal-transplant recipients and suggest a potential causative effect.

BACKGROUND We conducted a prospective, uncontrolled, open study to assess the relationship between homocysteine (tHcy) and oxidative stress in chronic, stable, renal transplant recipients (RTR). METHODS Included in the study were 17 chronic, stable RTR. All the patients received folic acid (5 mg/day). tHcy and total antioxidant capacity (TAOC) were measured before and at the end of the study period. RESULTS Mean tHcy concentration was 26+/-10 micromol/L. tHcy significantly decreased during the study period (26+/-10 vs. 18+/-7 micromol/L; P

Prolonged CD4 T cell lymphopenia after polyclonal antithymocyte globulins (ATG) is associated with an increased rate of cancers. Here, we examined whether pre-transplant thymic function estimated by TREC levels is predictive of cancer occurrence following ATG treatment.The impact of TREC on cancer occurrence was analyzed in 115 consecutive incident renal transplant recipients having received ATG.Mean follow-up was 7.5±2.6years. After ATG induction, patients with the lowest pre-transplant TREC values had lower post-transplant CD4(+) and CD4(+) CD45RA(+) CD45RO(-) T cell counts, and a higher frequency of T cells with a regulatory phenotype (CD127(+)CD4(+)CD25(+)Foxp3(+)). Log-transformed pre-transplant TREC values were significantly lower in patients who developed cancer after transplantation (p0.0001). The cumulative incidence of cancer was higher in patients having the lowest pre-transplant TREC values (T1 [low]: 47.4%, T2 [medium]: 12.5%, and T3 [high]: 2.7%; p0.0001). In multivariate analysis, pre-transplant TREC value was the only predictive factor of cancer (HR, 0.39; 95% CI, 0.16 to 0.97, for one log (TREC/10(6) PBMC); p=0.046).Pre-transplant thymic function is associated with an increased rate of post-transplant cancer in patients having received ATG. Omitting ATG in recipients with low pre-transplant TREC values should be considered.

Chronic inflammation plays a pivotal role in atherosclerosis. We hypothesized that combining overweight and a greater genetic capacity to produce IL-6 predicted byIL-6gene promoter polymorphism at position -174 (G→C) may allow to identify individuals exhibiting higher IL-6 and C-reactive protein (CRP) concentrations with a higher risk of atherosclerotic events (AE). The occurrence of AE was analyzed with respect to body mass index,IL-6gene promoter polymorphism at position -174 (G→C), and other relevant risk factors, retrospectively, in 217 renal transplant recipients and, prospectively, in 132. Circulating IL-6 concentrations were closely related to BMI (r=0.55,P=.0005). In overweight patients, serum IL-6 concentration was found to be significantly lower in C carriers than in GG patients (4.2 [1.0–5.1] versus 7.3 pg/mL [4.4–100];P=.025). The incidence of AE was higher in overweight GG patients (29.5% versus 10.1%;P=.0003). In multivariate analysis, overweight-GG had an increased risk to develop AE (HR 2.96 [95% CI 1.09–8.04],P=.034in the retrospective cohort, and HR 2.99 [95% CI 0.92–9.33],P=.069in the prospective cohort). All these data are consistent with a role for both genetic and environmental determinants of inflammation (white adipose tissue mass) in the development of AE in renal transplanted patients.

Introduction L’exposition chronique a des antigenes est a l’origine de l’accumulation de lymphocytes T CD8 + CD28-CD57+ pro-inflammatoires qui peuvent contribuer a l’atherosclerose. Nous avons fait l’hypothese que la stimulation allogenique prolongee pouvait etre responsable d’une activation immunitaire et contribuer a l’atherosclerose acceleree post-transplantation. Patients et methodes L’hypothese a ete testee dans une cohorte monocentrique de 577 transplantes renaux. Une analyse en score de propension a ete realisee pour tenir compte des facteurs confondants lies a l’allocation d’un rein ayant plus ou moins de compatibilites HLA. L’activation immune a ete etudiee dans une sous-cohorte de 103 patients. Resultats Un total de 577 transplantes renaux consecutifs ont ete inclus dans l’etude. Parmi, 77 evenements atheromateux (EA) (12,3 %) sont survenus pendant la periode de suivi (7 ans). L’incidence cumulee d’EA s’elevait avec le nombre de mismatches HLA (5 %, 10 % et 18 % pour les patients ayant respectivement 0 a 2, 3 a 4 et 5 a 6 mismatches ;p = 0,012). Le nombre de mismatches HLA etait un facteur de risque independant d’EA (HR 1,35 [IC 95 % 1,10–1,66], pour chaque mismatch supplementaire ; p = 0,005). Apres appariement sur le score de propension, avoir recu un rein plus compatible (2 mismatches ou moins) reduisait significativement le risque d’EA (HR 0,22 [IC 95 % 0,05–0,95], p = 0,044). Il existait une correlation entre le nombre de mismatches HLA et le taux de lymphocytes T CD8 + CD28-CD57+ (r = 0,31 ; p = 0,017). Ces lymphocytes actives etaient plus frequent chez les patients avec plus de mismatches HLA (6,2 ± 2,6, 18,6 ± 14,7 et 26,6 ± 19,3 % chez les patients avec respectivement 0 a 2, 3 a 4 et 5 a 6 mismatches HLA ; p = 0,003). Discussion et conclusion Nos resultats suggerent que la stimulation allogenique chronique participe a l’atherosclerose acceleree apres transplantation renale.

Introduction Une antibiotherapie administree par voie intra-peritoneale est recommandee dans la prise en charge des infections peritoneales (IP) en dialyse peritoneale (DP). Neanmoins, l’utilisation de la voie systemique (per os, IV) reste a ce jour debattue dans la litterature. Patients et methodes Il s’agit d’une etude retrospective incluant tous les episodes d’IP entre janvier 2005 et decembre 2010 chez des patients incidents, au sein de 2 centres francais, l’un utilisant systematiquement la voie intra-peritoneale (« centre IP ») et l’autre la voie systemique (per os prioritairement) (« centre Syst ») en traitement d’entretien. Nous avons compare le taux d’echecs de traitement defini comme suit : retrait du catheter de DP associe ou non a une IP refractaire, deces dans les 14 jours suivant l’IP ou la survenue d’une IP recidivante. Resultats Au total 106 patients ont developpe 114 IP (57 IP pour 43 patients dans le « centre Syst » et 87 IP pour 63 patients dans le « centre IP »). Nous avons observe le meme taux d’echecs de traitement dans chaque centre (n = 17/57 (29,8 %) versus n = 26/87 (29,9 %), p = 0,99). Huit patients (47 %) dans le « centre IP » et 12 (46 %) dans le « centre Syst » etaient toujours en DP dans les suites de l’IP a 403 ± 160 et 330 ± 219 jours respectivement (p = 0,68). Une IP a Staphylocoque coagulase negatif ou « autres pathogenes » (pyocianique, corynebacterium et/ou clostridium) etaient les 2 seuls facteurs independants retrouves d’echec de traitement (OR = 9,6 [0,9–7,88], p = 0,04 et OR = 13,8 [1,09–173,7], p = 0,04, respectivement). Discussion et conclusion Dans le traitement des IP, une antibiotherapie d’entretien administree par voie systemique semble aussi efficace que la voie intra-peritoneale.

Post-transplant diabetes mellitus (PTDM) is a well-known complication in renal transplant recipients (RTRs). While a number of risk factors for PTDM have been identified, the potential impact of pre-transplant dialysis modality on subsequent development of PTDM has not yet been explored. We performed a multicenter retrospective study on 2010 consecutive RTRs who did not have a history of diabetes prior to renal transplantation. PTDM was defined as a need for anti-diabetic therapy in an RTR without a history of diabetes prior to transplantation. Analysis of the risk factors for development of PTDM was performed with respect to pre-transplant dialysis modality. A total of 137 (6.8%) patients developed PTDM; 7% in the hemodialysis group and 6.5% in the peritoneal dialysis (PD) group (p = 0.85). In the multivariate analysis, age (p 0.001), body mass index (BMI) (p 0.001), use of tacrolimus (p = 0.002), and rejection episodes (p 0.001) were identified as independent risk factors for development of PTDM. Patients in the PD group were younger (p = 0.004), had lower BMI (p = 0.07), and were less likely to have a history of hepatitis C (p = 0.007) and autosomal dominant polycystic kidney disease (p = 0.07). Adjustment for these variables did not modify the results. The results of this study suggest that pre-transplant dialysis modality does not have an impact on the subsequent development of PTDM in RTRs.

Objectives Intra-operative cisplatin-based intra-peritoneal chemotherapy (IPC) may alter renal function in patients with advanced ovarian cancer. The aim of this study was to describe postoperative alteration of renal function after cisplatin-based IPC and to identify risk factors for moderate to severe acute renal failure. Study design This prospective observational study was carried out on 77 consecutive patients who underwent cisplatin-based IPC procedures, with ( n = 23) or without ( n = 54) intra-peritoneal epinephrine, for advanced ovarian cancer. Postoperative renal function was assessed using serial serum creatinine measurements and was based on serum creatinine changes from pre-operative values, according to the risk, injury, failure, loss, end-stage kidney disease (RIFLE) classification. Patients were divided into two groups according to postoperative renal function: patients with renal injury or failure (IF group) or patients with no renal alteration or renal risk (NR group). Clinical variables were compared between the IF and NR groups using univariate and multivariate analysis. Results Postoperative acute change in renal function was observed in 34 (44.2%) patients (unimodal distribution), among whom 23 patients (29.8%) constituted the IF group. In univariate analysis, the absence of epinephrine in the IPC bath, a higher duration of severe hypotension, a lower postoperative blood protein level, and a lower volume of intra-operative diuresis were significantly associated with the occurrence of renal injury or failure. In multivariate analysis, the absence of epinephrine was the only factor associated with the occurrence of moderate to severe acute renal failure (odds ratio [95% confidence interval] = 4.49 [1.36–14.80]). Conclusions Transient acute renal dysfunction after cisplatin-based IPC associated with cytoreductive surgery is frequent and intra-peritoneal epinephrine plays a protective role.