Male Microchimerism at High Levels in Peripheral Blood Mononuclear Cells from Women with End Stage Renal Disease before Kidney Transplantation

Patients with end stage renal diseases (ESRD) are generally tested for donor chimerism after kidney transplantation for tolerance mechanism purposes. But, to our knowledge, no data are available on natural and/or iatrogenic microchimerism (Mc), deriving from pregnancy and/or blood transfusion, acquired prior to transplantation. In this context, we tested the prevalence of male Mc using a real time PCR assay for DYS14, a Y-chromosome specific sequence, in peripheral blood mononuclear cells (PBMC) from 55 women with ESRD, prior to their first kidney transplantation, and compared them with results from 82 healthy women. Male Mc was also quantified in 5 native kidney biopsies obtained two to four years prior to blood testing and in PBMC from 8 women collected after female kidney transplantation, several years after the initial blood testing. Women with ESRD showed statistically higher frequencies (62%) and quantities (98 genome equivalent cells per million of host cells, gEq/M) of male Mc in their PBMC than healthy women (16% and 0.3 gEq/M, p<0.00001 and p = 0.0005 respectively). Male Mc was increased in women with ESRD whether they had or not a history of male pregnancy and/or of blood transfusion. Three out of five renal biopsies obtained a few years prior to the blood test also contained Mc, but no correlation could be established between earlier Mc in a kidney and later presence in PBMC. Finally, several years after female kidney transplantation, male Mc was totally cleared from PBMC in all women tested but one. This intriguing and striking initial result of natural and iatrogenic male Mc persistence in peripheral blood from women with ESRD raises several hypotheses for the possible role of these cells in renal diseases. Further studies are needed to elucidate mechanisms of recruitment and persistence of Mc in women with ESRD

Male microchimerism in peripheral blood of women awaiting kidney transplantation correlates positively with HLA allo-immunization (102.19)

Abstract Microchimerism is the persistence of a small population of donor or fœtal cells, in graft recipients or in mothers. It appears after transfusion, pregnancy, transplantation and has been implicated in graft rejection, tolerance and auto-immunity. Anti-HLA Ab can appear under identical circumstances. Why and how such Ab persist for decades is only partially understood. We questioned if male microchimerism in the peripheral blood of women could be one of the mechanisms allowing the maintenance of anti-HLA Ab production. We evaluated 46 women, waiting for a first kidney graft, for the presence or absence of anti-HLA Ab using an ELISA. A Panel Reactive Ab was determined using Luminex® technology. Y chromosomal DNA was identified by nested PCR using specific primers of the SRY region. All patients were pregnant and/or transfused. In the Ab+ group (n=24), all women were sensitized and in the Ab− group (n=22), all women were unsensitized. Thirty-nine percent of all women (18/46) carried a male microchimerism: 54% in the Ab+ group (13/24) vs. 22% in the Ab− group (5/22) with pχ2= 0.029. We found a significant frequency of male microchimerism in the peripheral blood of women with kidney disease, which positively correlated with the presence of anti-HLA Ab.</jats:p

Factors associated with Health-Related Quality of Life in Kidney Transplant Recipients in France

Abstract Background Health-Related Quality of Life (HRQoL) assessment after kidney transplantation has become an important tool in evaluating outcomes. This study aims to identify the associated factors with HRQoL among a representative sample size of Kidney Transplant Recipients (KTR) at the time of their inclusion in the study. Methods Data of this cross-sectional design is retrieved from a longitudinal study conducted in five French kidney transplant centers in 2011, and included KTR aged 18 years with a functioning graft for at least 1 year. Measures include demographic, psycho-social and clinical characteristics. To evaluate HRQoL, the Short Form-36 Health Survey (SF-36) and a HRQoL instrument for KTR (ReTransQol) were administered. Multivariate linear regression models were performed. Results A total of 1424 patients were included, with 61.4% males, and a mean age of 55.7 years (±13.1). Demographic and clinical characteristics were associated with low HRQoL scores for both questionnaires. New variables were found in our study: perceived poor social support and being treated by antidepressants were associated with low scores of Quality of Life (QoL), while internet access was associated with high QoL scores. Conclusion The originality of our study’s findings was that psycho-social variables, particularly KTR treated by antidepressants and having felt unmet needs for any social support, have a negative effect on their QoL. It may be useful to organize a psychological support specifically adapted for patients after kidney transplantation

Renal Function and NODM in De Novo Renal Transplant Recipients Treated with Standard and Reduced Levels of Tacrolimus in Combination with EC-MPS

Information is lacking concerning concomitant administration of enteric-coated mycophenolate sodium with tacrolimus (EC-MPS+Tac) in renal transplant recipients (RTxR). In this 6-month, prospective, open-label, multicenter study, de novo RTxR were randomized (1 : 1) to low-dose (LD) or standard-dose (SD) Tac with basiliximab, EC-MPS 720 mg bid, and steroids. Primary objective was to compare renal function at 6-month posttransplantation. Secondary objectives were to compare the incidences of biopsy-proven acute rejection (BPAR), graft loss and death, and new-onset diabetes mellitus (NODM). 292 patients (LD n=151, SD n=141) were included. Mean Tac levels were at the low end of the target range in standard-exposure patients (SD, n=141) and exceeded target range in low-exposure patients (LD = 151) throughout the study. There was no significant difference in mean glomerular filtration rate (GFR) between treatments (ITT-population: 63.6 versus 61.0 mL/min). Incidence of BPAR was similar (10.6% versus 9.9%). NODM was significantly less frequent in LD Tac (17% versus 31%; P=0.02); other adverse effects (AEs) were comparable. EC-MPS+Tac (LD/SD) was efficacious and well tolerated with well-preserved renal function. No renal function benefits were demonstrated, possibly related to poor adherence to reduced Tac exposure

Comparison of longitudinal quality of life outcomes in preemptive and dialyzed patients on waiting list for kidney transplantation

International audiencePURPOSE:The waiting list period for kidney transplantation can be lengthy and associated with a deteriorated health-related quality of life (HRQoL). It might also be experienced differently depending on the experience of renal replacement therapy (preemptive or dialyzed patients), and the type of dialysis. The main objective of this study is to measure and compare HRQoL changes in preemptive, hemodialysis (HD), and peritoneal dialysis (PD) patients during the waiting list period for kidney transplantation.METHODS:A sample of adult patients on kidney transplant waiting list from three French University Hospital centers was recruited. HRQoL was measured using the SF-36 and a specific questionnaire (ReTransQol), which were collected every 6 months before transplantation in preemptive, HD, and PD patients. Mixed-effects models taking into account time and possible confounding factors were used to compare HRQoL changes between the three groups.RESULTS:Preemptive (n = 230), HD (n = 177), and PD patients (n = 39) were enrolled. The renal replacement therapy modalities, time (time on waiting list and age at registration), and gender were associated with HRQoL changes. The HD and PD patients had a significantly lower perceived HRQoL on Role Physical, Social Functioning, and Role Emotional dimensions than the preemptive patients, with lower scores for PD compared to HD patients. The HRQoL scores of all patients were lower compared to the French general population for all dimensions.CONCLUSIONS:A better understanding of pre-transplantation patients' experience can help improving patient care with adapted educational programs and psychological support depending on the type of renal replacement therapy

Néphropathies secondaires à un déficit en cobalamine C : première étude histopathologique comparative

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Effects of cyclosporine A pretreatment of deceased organ donors on kidney graft function (Cis-A-rein): study protocol for a randomized controlled trial

Abstract Background Renal transplantation represents the treatment of choice of end-stage kidney disease. Delayed graft function (DGF) remains the most frequent complication after this procedure, reaching more than 30%. Its prevention is essential as it impedes early- and long-term prognosis of transplantation. Numerous pharmacological interventions aiming to prevent ischemia-reperfusion injuries failed to reduce the rate of DGF. We hypothesize that cyclosporine as an early preconditioning procedure in donors would be associated with decreased DGF. Methods The Cis-A-rein study is an investigator-initiated, prospective, multicenter, double-blind, randomized, controlled study performed to assess the effects of a donor preconditioning with cyclosporine A on kidney grafts function in transplanted patients. After randomization, a brain dead donor will receive 2.5 mg kg−1 of cyclosporine A or the same volume of 5% glucose solution. The primary objective is to compare the rate of DGF, defined as the need for at least one dialysis session within the 7 days following transplantation, between both groups. The secondary objectives include rate of slow graft function, mild and severe DGF, urine output and serum creatinine during the first week after transplantation, rate of primary graft dysfunction, renal function and mortality at 1 year. The sample size (n = 648) was determined to obtain 80% power to detect a 10% difference for rate of DGF at day 7 between the two groups (30% of the patients in the placebo group and 20% of the patients in the intervention group). Discussion Delayed graft function is a major issue after renal transplantation, impeding long-term prognosis. Cyclosporine A pretreatment in deceased donors could improve the outcome of patients after renal transplantation. Trial registration ClinicalTrials.gov, ID: NCT02907554 Registered on 20 September 2016.