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Clinical recommendations; Cystinosis; Multidisciplinary care Recomendaciones clínicas; Cistinosis; Atención multidisciplinaria Recomanacions clíniques; Cistinosi; Atenció multidisciplinària Cystinosis, a rare autosomal recessive lysosomal storage disorder, results in an abnormal accumulation of the amino acid cystine in multiple organs and tissues of the body. Renal symptoms typically develop in the first few months of life, with extra-renal manifestations becoming apparent over the next 10–20 years, which require coordinated multidisciplinary care. Here, we describe a consensus-based guidance to support the management of adolescents and adults living with cystinosis. The programme was led by a Steering Committee (SC) of six experts in the management of patients with cystinosis, who identified a list of 15 key questions reflecting the multi-organ effects of cystinosis. An Extended Faculty (EF) of eight additional specialists was invited to answer the questions via an online digital platform using a quasi-Delphi approach. The consolidated answers were summarized into recommendations. Where evidence was lacking, recommendations were developed using collective expert consensus. The EF was asked to agree/disagree with the clinical recommendations. The expert-agreed clinical recommendations provide guidance that considers both renal and extra-renal systems. The topics covered are advice on fertility and family planning, consideration of the nervous, muscular, ophthalmic, cardio-respiratory, endocrine, dermatological and gastrointestinal systems, as well as guidance on dental care, diet, lifestyle, and improving quality of life and psychological well-being. In summary, this work outlines recommendations and a checklist for clinicians with a vision for improving and standardizing the multidisciplinary care for patients with cystinosis. The programme was supported by Chiesi Farmaceutici Spa. Chiesi was not involved in the content or outcomes of the programme which were solely determined by the SC and extended faculty experts.

Poor responses to mRNA COVID-19 vaccine have been reported after 2 vaccine injections in kidney transplant recipients (KTRs) treated with belatacept. We analyzed the humoral response in belatacept-treated KTRs without a history of SARS-CoV-2 infection who received three injections of BNT162b2-mRNA COVID-19 vaccine. We also investigated vaccine immunogenicity in belatacept-treated KTRs with prior COVID-19 and characterized symptomatic COVID-19 infections after the vaccine in belatacept-treated KTRs. Among the 62 belatacept-treated KTRs (36 [58%] males), the median age (63.5 years IQR [51-72]), without COVID-19 history, only four patients (6.4%) developed anti-SARS-CoV-2 IgG with low antibody titers (median 209, IQR [20-409] AU/ml). 71% were treated with mycophenolic acid and 100% with steroids in association with belatacept. In contrast, in all the 5 KTRs with prior COVID-19 history, mRNA vaccine induced a strong antibody response with high antibody titers (median 10 769 AU/ml, IQR [6410-20 069]) after two injections. Seroprevalence after three-vaccine doses in 35 non-belatacept-treated KTRs was 37.1%. Twelve KTRs developed symptomatic COVID-19 after vaccination, including severe forms (50% of mortality). Breakthrough COVID-19 occurred in 5% of fully vaccinated patients. Administration of a third dose of BNT162b2 mRNA COVID-19 vaccine did not improve immunogenicity in KTRs treated with belatacept without prior COVID-19. Other strategies aiming to improve patient protection are needed.

Background Due to increased risk of pyelonephritis, patients with intestinal reconstruction of the lower urinary tract (IRLUT) have long been advised against kidney transplantation. The aim of this study was to compare the outcomes of transplantation between patients with IRLUT and patients with normal LUT (NLUT) using propensity score matching method. Methods The study included 23 kidney recipients with IRLUT matched to 46 kidney recipients with NLUT using known allograft survival and pyelonephritis risk factors as covariates. One‐, 5‐, and 10‐year graft survival, pyelonephritis, and surgical complications occurrence and graft function were compared. Results One‐, 5‐, and 10‐year graft survival were 96%, 91%, and 63% in the IRLUT group and 96%, 88%, and 70% in the NLUT group, respectively (p = 0.72). Patients with IRLUT had increased cumulative risk of pyelonephritis at 10 years (70% vs. 19%; log‐rank

Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4-68.5]) were converted to belatacept (median of 11.5 months [2.5-37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R- CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls [2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR

Anti-denatured HLA-Cw antibodies are highly prevalent, whereas anti-native HLA-Cw antibodies seem to lead to random flow cytometry crossmatch results. We aimed to reassess crossmatch prediction for anti-HLA-Cw using 2 types of single antigen flow beads (classical beads and beads with diminished expression of denatured HLA), and to compare the pathogenicity of preformed anti-denatured and anti-native HLA-Cw antibodies in kidney transplantation. We performed 135 crossmatches with sera reacting against donor HLA-Cw (classical beads fluorescence ≥500); only 20.6% were positive. Forty-three (31.6%) were anti-denatured HLA antibodies (beads with diminished expression of denatured HLA fluorescence

International audience; Background Atypical hemolytic uremic syndrome (HUS) is associated with high recurrence rates after kidney transplant, with devastating outcomes. In late 2011, experts in France recommended the use of highly individualized complement blockade-based prophylaxis with eculizumab to prevent post-transplant atypical HUS recurrence throughout the country.Methods To evaluate this strategy's effect on kidney transplant prognosis, we conducted a retrospective multicenter study from a large French nationwide registry, enrolling all adult patients with atypical HUS who had undergone complement analysis and a kidney transplant since January 1, 2007. To assess how atypical HUS epidemiology in France in the eculizumab era evolved, we undertook a population-based cohort study that included all adult patients with atypical HUS (n=397) between 2007 and 2016.Results The first study included 126 kidney transplants performed in 116 patients, 58.7% and 34.1% of which were considered to be at a high and moderate risk of atypical HUS recurrence, respectively. Eculizumab prophylaxis was used in 52 kidney transplants, including 39 at high risk of recurrence. Atypical HUS recurred after 43 (34.1%) of the transplants; in four cases, patients had received eculizumab prophylaxis and in 39 cases they did not. Use of prophylactic eculizumab was independently associated with a significantly reduced risk of recurrence and with significantly longer graft survival. In the second, population-based cohort study, the proportion of transplant recipients among patients with ESKD and atypical HUS sharply increased between 2012 and 2016, from 46.2% to 72.3%, and showed a close correlation with increasing eculizumab use among the transplant recipients.Conclusions Results from this observational study are consistent with benefit from eculizumab prophylaxis based on pretransplant risk stratification and support the need for a rigorous randomized trial.

Belatacept could be the treatment of choice in renal-transplant recipients with renal dysfunction attributed to calcineurin inhibitor (CNI) nephrotoxicity. Few studies have described its use in patients with donor-specific antibody (DSA).We retrospectively evaluated conversion from CNIs to belatacept in 29 human leukocyte antigen-immunized renal-transplant recipients. Data about acute rejection, DSA, and renal function were collected. These patients were compared with 42 nonimmunized patients treated with belatacept.Patients were converted from CNIs to belatacept a median of 444 days (interquartile range, 85-1200) after transplantation and were followed up after belatacept conversion, for a median of 308 days (interquartile range, 125-511). At conversion, 16 patients had DSA. Nineteen DSA were observed in these 16 patients, of which 11/19 were1000 mean fluorescence intensity (MFI), 7/19 were between 1000 and 3000 MFI, and one was3000 MFI. At last follow-up, preexisting DSA had decreased or stabilized. Seven patients still had DSA with a mean MFI of 1298 ± 930 at the last follow-up. No patient developed a de novo DSA in the DSA-positive group. In the nonimmunized group, one patient developed de novo DSA (A24-MFI 970; biopsy for cause did not show biopsy-proven acute rejection or microinflammation score). After belatacept conversion, one antibody-mediated rejection was diagnosed. The mean estimated glomerular filtration rate improved from 31.7 ± 14.2 mL/min/1.73 m to 40.7 ± 12.3 mL/min/1.73 m (P0.0001) at 12 months after conversion. We did not find any significant difference between groups in terms of renal function, proteinuria, or biopsy-proven acute rejection.We report on a safe conversion to belatacept in human leukocyte antigen-immunized patients with low DSA levels.

EBV-positive mucocutaneous ulcer (EBV-MCU) is a rare EBV-positive B-cell lymphoproliferative disorder occurring in immunocompromised patients such as patients with solid organ or hematopoietic stem cells transplantation. EBV-MCU often consists of an isolated and circumscribed cutaneous or mucosal ulcerative lesion with a self-limited growth potential and a high regression rate upon immunosuppressive treatment withdrawal or rituximab therapy. Nevertheless, the pathophysiology of this latent infection leading to clonal lymphoproliferation is not well established. We report here two cases of EBV-MCU in kidney transplant recipients with a dissociated immune response to EBV with the absence of EBV-related antibodies and a positive T-cell response to EBV suggesting a potential specific oncogenic mechanism in this lymphoproliferative disorder.

Introduction During the coronavirus disease 2019 (Covid-19) pandemic, several physicians have questioned pursuing belatacept in kidney-transplant patients in order to reduce the risk of nosocomial transmission during the monthly infusion. The effect of the conversion from belatacept to another immunosuppressive regimen is underreported. The aim of the present retrospective study was to assess the effect on kidney function and the clinical outcome of the conversion from belatacept to another regimen. Methods We have identified 44 maintenance kidney transplantation patients from five French kidney transplantation centers who were converted from belatacept to another regimen either because of a complication (n = 28) or another reason (patients’ request or belatacept shortage, n = 13). The follow-up after the conversion from belatacept was 27.5 ± 25.3 months. Results Overall, mean estimated glomerular filtration rate (eGFR) decreased from 44.2 ± 16 ml/min per 1.73 m2 at conversion from belatacept to 35.7 ± 18.4 ml/min per 1.73 m2 at last follow-up (P = 0.0002). eGFR significantly decreased in patients who had been given belatacept at transplantation as well as in those who had been converted to belatacept earlier. The decrease was less significant in patients who had stopped belatacept without having experienced any complications. Finally, eGFR decreased more severely in patients who were converted to calcineurin inhibitors (CNIs), compared to those who received mammalian target of rapamycin inhibitor (mTORi). Few patients also developed diabetes and hypertension. Conclusions Thus, transplantation physicians should avoid stopping belatacept when not clinically required., Graphical abstract

Aims Eculizumab is an anti-C5 monoclonal antibody approved for rare diseases including atypical haemolytic-uraemic syndrome. The maintenance phase dosing regimen is identical for all adult patients: 1200 mg every 2 weeks. Recent studies reported an overexposure in many patients when considering a target trough concentration range of 50-100 mg/L. The aim of the present work was to validate the feasibility of therapeutic drug monitoring of eculizumab in atypical haemolytic-uraemic syndrome patients. Methods We performed a 2-step prospective multicentre study. In the first phase, we developed a pharmacokinetic population model using data from 40 patients and identified patients for whom a 1-week lengthening of interval between infusions would lead to a trough concentration above 100 mg/L. In the second phase, selected patients were allocated a 1-week extension and eculizumab trough concentrations were monitored. Results The model confirmed the previously reported influence of bodyweight on elimination clearance and predicted that 36 (90%) patients would be eligible for interval extension. In the second phase of the study, a 1-week lengthening of interval between infusions was performed in 15 patients whose trough concentration at the next visit was predicted with a Bayesian model to be above 100 mg/L. After interval extension, 10 patients (67%) presented measured trough concentrations over 100 mg/L. No biological or clinical recurrence of disease was observed, even in the 5 patients with concentrations below 100 mg/L in whom the initial dosing regimen was resumed. Conclusion Safe eculizumab interval adjustment is feasible with a PK monitoring.

Higher rates of severe COVID-19 have been reported in kidney transplant recipients (KTRs) compared to nontransplant patients. We aimed to determine if poorer outcomes were specifically related to chronic immunosuppression or underlying comorbidities. We used a 1:1 propensity score-matching method to compare survival and severe disease-free survival (defined as death and/or need for intensive care unit [ICU]) incidence in hospitalized KTRs and nontransplant control patients between February 26 and May 22, 2020. Patients were matched for risk factors of severe COVID-19: age, sex, body mass index, diabetes mellitus, preexisting cardiopathy, chronic lung disease, and basal renal function. We included 100 KTRs (median age [interquartile range (IQR)]) 64.7 years (55.3-73.1) in three French transplant centers. After a median follow-up of 13 days (7-30), transfer to ICU was required for 34 patients (34%) and death occurred in 26 patients (26%). Overall, 43 patients (43%) developed a severe disease during a median follow-up of 8.5 days (2-14). Propensity score matching to a large French cohort of 2017 patients hospitalized in 24 centers, revealed that survival was similar between KTRs and matched nontransplant patients with respective 30-day survival of 62.9% and 71% (p = .38) and severe disease-free 30-day survival of 50.6% and 47.5% (p = .91). These findings suggest that severity of COVID-19 in KTRs is related to their associated comorbidities and not to chronic immunosuppression.

Background Oral anticoagulation therapy is frequently prescribed to kidney transplant recipients (KTRs) for prevention and treatment of thrombotic events. Over the past 10 y, direct oral anticoagulants (DOACs) have shown similar efficacy with a safety profile equal or superior to that of vitamin K antagonist anticoagulants (VKAs) in the general population. However, little data are available on kidney transplantation. Methods We investigated the efficacy (thrombotic events) and safety (hemorrhagic and other adverse events and graft outcomes) of DOACs in a cohort of KTRs with a renal function >30 mL/min. We then compared these patients to a control group treated by VKA. Results Fifty-two KTRs treated by DOACs between 2013 and 2018 at Necker Hospital were included. Patients were with a mean age of 62 ± 13 y old and a mean glomerular filtration rate of 59 ± 20 mL/min/1.73m. The major indication was atrial fibrillation (n = 31 [60%]). Apixaban was the most commonly used agent (n = 36 [69%]). No thrombotic complications were reported under DOAC until last follow-up (14.1 ± 13 mo). In comparison to 50 controls under VKA during the same period, the bleeding rate under DOAC was significantly lower (11.5 versus 22.9 per 100 patient-y, P = 0.037) with a hazard ratio of 0.39 (95% confidence interval, 0.19-0.85, P = 0.041). No significant changes in kidney function, rejection rate, or hemoglobin level were reported. Conclusions DOACs appear to be effective and safe anticoagulants in KTRs with stable renal function.

Monogenic forms of Steroid-Resistant Nephrotic Syndrome (SRNS) have been widely characterized, but genetic screening paradigms preferentially address congenital, infantile onset, and familial cases. Our aim was to characterize the distribution of disease-causing gene mutations in adults with sporadic SRNS or focal segmental glomerulosclerosis (FSGS). We selected adult patients with non-syndromic, biopsy-proven FSGS or SRNS in the absence of known family history. Strict clinical criteria included lack of response to glucocorticoids and cyclosporine, and no recurrence after kidney transplantation. Mutations in SRNS genes were detected using a targeted gene panel. Sixteen of 135 tested participants (11.8%) carried pathogenic mutations in monogenic SRNS genes, and 14 others (10.4%) carried two APOL1 high-risk alleles. Autosomal recessive disease was diagnosed in 5 participants, autosomal dominant disease in 9, and X-linked disease in 2. Four participants carried a de novo heterozygous mutation. Among the 16 participants with identified mutations in monogenic SNRS genes, 7 (43.7%) had type IV collagen mutations. Mutations in monogenic SNRS genes were identified primarily in participants with proteinuria onset before 25 years of age, while the age at disease onset was variable in those with APOL1 high-risk genotype. Mean age at diagnosis was lower and renal survival was worse in participants with identified mutations in SNRS genes than in those without mutations. We found a significant rate of pathogenic mutations in adults with SRNS, with Type IV collagen mutations being the most frequent. These findings may have immediate impact on clinical practice.

The use of belatacept is not yet approved for maintenance in kidney transplant patients. This retrospective multicenter European study aimed to assess the efficacy and safety of conversion to belatacept in a large cohort of patients in a real-life setting and to identify the predictive factors for improved kidney function after the switch.Two hundred nineteen maintenance kidney transplant patients from 5 European kidney transplant centers were converted to belatacept at 21.2 months (0.1-337.1 months) posttransplantation, mainly because of impaired kidney function. Thirty-two patients were converted to belatacept within the first 3 months posttransplantation. The mean duration of follow-up was 21.9 ± 20.2 months.The actuarial rate of patients still on belatacept-based therapy was 77.6%. Mean estimated glomerular filtration rate increased from 32 ± 16.4 at baseline to 38 ± 20 mL/min per 1.73 m (P0.0001) at last follow-up. Conversion to belatacept before 3 months posttransplantation was the main predictive factor for a significant increase in estimated glomerular filtration rate (of 5 and 10 mL/min per 1.73 m at 3 and 12 months after the switch, respectively). Eighteen patients (8.2%) presented with an acute rejection episode after conversion; 3 developed a donor-specific antibody. Overall efficacy and safety were good, including for the 35 patients that had a donor-specific antibody at conversion.The conversion to belatacept was effective, especially when performed early after transplantation.

Background After observing a case of plasma exchange-mediated hepatitis E virus (HEV) infection in a kidney transplant recipient, we investigated the relationship between plasma exchange and HEV infection after kidney transplantation. Methods A cohort of 263 patients who underwent kidney transplantation from January 1, 2011, through December 31, 2012, was screened for HEV markers, including anti-HEV IgG and IgM antibodies and HEV ribonucleic acid (RNA), on 3 consecutive blood samples: 1 before, 1 with a mean (standard deviation) of 9.5 (9) months, and 1 with a mean (standard deviation) of 18.2 (6.6) months after transplantation, respectively. Transfusional investigation was performed in patients with detectable HEV RNA. We explored the relationships between plasma exchange, posttransplantation transaminase elevation and HEV markers acquisition. Results Overall, 24 (9.1%) patients had acquired HEV markers on the first posttransplantation sample, including 2 patients with detectable HEV RNA, and 7 (2.3%) patients had long-term persistent HEV markers on the second posttransplantation sample, including 3 patients with detectable HEV RNA without detectable anti-HEV antibodies. Plasma exchange was an independent risk factor for the acquisition of posttransplantation and long-term persistent HEV markers. Pathogen-reduced plasma-borne transmission of HEV was demonstrated. Plasma exchange and long-term persistent HEV markers were risk factors of posttransplantation transaminase elevation. Conclusions Plasma exchange, including with pathogen-reduced plasma, is a risk factor for posttransplantation HEV infection and transaminase elevation. Screening for HEV RNA should be carried out in kidney transplant recipients treated with plasma exchange.

Atypical hemolytic uremic syndrome (aHUS) is an orphan disease with a high rate of recurrence after kidney transplantation. However, reports of successful prevention of posttransplant aHUS recurrence with eculizumab emerged a few years ago. To further delineate its optimal use, we describe the largest series of kidney transplant recipients treated with prophylactic eculizumab.Twelve renal transplant recipients with aHUS-related end-stage renal disease received eculizumab: 10 from day 0 and 2 at the time of recurrence (days 6 and 25). Clinical and histological features, complement assessment, and free eculizumab measurements were analyzed. The median follow-up was 24.6 months.Five patients had failed at least 1 previous renal transplant from aHUS. A genetic mutation was identified in 9 patients, anti-H antibodies were found in 2. No patient demonstrated biological recurrence of thrombotic microangiopathy under treatment. Three antibody-mediated rejections (AMRs) occurred without detectable C5 residual activity. AMR was associated with subclinical thrombotic microangiopathy in 2 patients. One patient lost his graft after several complications, including AMR. One patient experienced posttransplant C3 glomerulonephritis. The last median serum creatinine was 128.2 ± 40.8 μmol/L.These data confirm that eculizumab is highly effective in preventing posttransplantation aHUS recurrence, yet may not fully block AMR pathogenesis.

Introduction and background The complement system which belongs to the innate immune system acts both as a first line of defence against various pathogens and as a guardian of host homeostasis. The role of complement has been recently highlighted in several aspects of kidney transplantation: ischaemia-reperfusion, antibody-mediated rejection and native kidney disease recurrence. Sources of data Experimental data, availability of complement-blocking molecules (mainly the anti-C5 monoclonal antibody, eculizumab) and several trials in human kidney transplant recipients has led to some areas of agreement and some disappointment. Areas of agreement and controversies So far, eculizumab has shown great efficacy in treatment and prevention of atypical haemolytic and uraemic syndrome, some efficacy in the prevention of antibody-mediated and so far no efficacy in the prevention of delayed graft function. Growing points Among the numerous potentially available drugs potentially interfering with complement, recent focus has been made on C1 blockers in the setting of antibody-mediated rejection with promising results. Areas timely for developing research Complement is now recognized as a major player in transplant immunology, several targets are going to be tested to define precisely which ones may be potentially useful in clinical practice.

Resume Plus de 50 ans apres le succes des deux premieres transplantations renales realisees a Boston et a l’hopital Necker a Paris, la transplantation renale est devenue le traitement de choix de l’insuffisance renale chronique terminale, car elle ameliore non seulement la qualite de vie des patients, mais aussi leur quantite de vie. En France, plus de 3700 transplantations renales sont realisees chaque annee, et plus de 40 000 patients vivent avec un greffon fonctionnel. Ce traitement de l’insuffisance renale chronique terminale requiert une evaluation precise du futur receveur puis une prise en charge specialisee multidisciplinaire capable de prevenir, depister et traiter l’ensemble des pathologies associees et des complications de l’immunosuppression. L’ambition de cet article n’est pas de decrire de maniere exhaustive tous les aspects de la transplantation renale, mais a partir de l’experience d’une equipe, des donnees de la litterature recente et des recommandations nationales et internationales, d’essayer de fournir une vision synthetique et chronologique du suivi precoce apres la transplantation.

Little is known about the long-term progression of adult nephropathic cystinosis patients. Our objective was to study central nervous system complications in cystinosis patients in the era of early cysteamine treatment, using advanced neuroimaging techniques. Neurological examination and multimodal brain 3 Tesla MRI were performed in 21 adult cystinosis patients, including 18 infantile cystinosis patients, 20 controls matched for age and renal function, and 12 healthy controls. Differences in gray matter volume and rest cerebral blood flow (CBF) using arterial spin labeling sequence were investigated using whole-brain voxel-based approach. Median age was 33.8 years (18.7-65.8). Seven patients (38.9%) presented with at least one central nervous system clinical abnormality: two (11.1%) with seizures, three (16.7%) with memory defects, five (27.8%) with cognitive defect, and one (5.5%) with stroke-like episode. These patients had a worse compliance to treatment (compliance score 2 vs 1, P = .03) and received a lower median cysteamine dose (0.9 g/day vs 2.1 g/day, P = .02). Among patients with infantile cystinosis, 13 (72.2%) showed cortical atrophy, which was absent in controls, but it was not correlated with symptoms. Cystinosis patients showed a significant gray matter decrease in the middle frontal gyrus compared with healthy controls and a significant negative correlation between the cystine blood level and rest CBF was observed in the right superior frontal gyrus, a region associated with executive function. Compliance to cysteamine treatment is a major concern in these adult patients and could have an impact on the development of neurological and cognitive complications.

Background During routine post-kidney transplant care, most European transplant physicians screen patients for asymptomatic bacteriuria. The usefulness of this strategy is debated. To make screening cost-effective, asymptomatic bacteriuria should be prevalent enough to justify the expense, and antibiotics should improve patient outcomes significantly if asymptomatic bacteriuria is detected. Regrettably, the prevalence of asymptomatic bacteriuria among kidney transplant recipients is not well defined. Methods To determine the prevalence of asymptomatic bacteriuria among kidney transplant recipients, we did a cross-sectional study among kidney transplant recipients undergoing routine surveillance in three outpatient transplant clinics in Belgium and France. We excluded patients who were in the first two months post-transplantation and/or had a urinary catheter. Asymptomatic participants who had a urine culture with one organism isolated at .105 CFU/mL were asked to provide a confirmatory urine specimen. Asymptomatic bacteriuria was defined per Infectious Diseases Society of America guidelines. Results We screened 500 consecutive kidney transplant recipients. Overall, the prevalence of asymptomatic bacteriuria was 3.4% (17/500 patients). It was similarly low among kidney transplant recipients who were between 2 and 12 months after transplantation (1.3%, 1/76 patients) and those who were farther after transplantation (3.8%, 16/424 patients: P = 0.49). Asymptomatic bacteriuria was significantly associated with female gender (risk ratio 3.7, 95% CI 1.3-10.3, p = 0.007) and older age (mean age: 61 ± 12 years [bacteriuric participants], versus 53 ± 15 years [non-bacteriuric participants], p = 0.03). One participant's colistin-resistant Escherichia coli isolate carried the globally disseminated mcr-1 gene. Conclusions Among kidney transplant recipients who are beyond the second month post-transplant, the prevalence of asymptomatic bacteriuria is low. Further studies are needed to ascertain the cost-effectiveness of a screen-and-treat strategy for asymptomatic bacteriuria in this population., SCOPUS: ar.j, info:eu-repo/semantics/published

Background Diarrhoea is one of the most frequent complications after kidney transplantation (KT). Non-infectious diarrhoea has been associated with reduced graft survival in kidney transplant recipients. However, the risk factors for renal allograft loss following diarrhoea remain largely unknown. Methods Between January 2010 and August 2011, 195 consecutive KT recipients who underwent standardized microbiological workups for diarrhoea at a single centre were enrolled in this retrospective study. Results An enteric pathogen was readily identified in 91 patients (47%), while extensive microbiological investigations failed to find any pathogen in the other 104. Norovirus was the leading cause of diarrhoea in these patients, accounting for 30% of the total diarrhoea episodes. The baseline characteristics were remarkably similar between non-infectious and infectious diarrhoea patients, with the exception that the non-infectious group had significantly lower graft function before diarrhoea (P = 0.039). Infectious diarrhoea was associated with a longer duration of symptoms (P = 0.001) and higher rates of acute kidney injury (P = 0.029) and hospitalization (P Conclusion Our study shows that pre-existing conditions (re-transplantation, chronic graft dysfunction and late occurrence) determine the primary functional long-term consequences of post-transplant diarrhoea.

Introduction De fortes doses de vitamine D3 (cholecalciferol, CL) ont ete preconisees pour reduire le risque de diabete de type 2, d’evenements cardiovasculaires majeurs (MACE) et de cancer, qui sont des complications frequentes chez les patients transplantes renaux (PTR). Patients/Materiels et methodes L’etude VITALE est un essai prospectif, multicentrique (30 departements Francais), en double aveugle, controle (NCT01431430). Les PTR adultes ayant des concentrations seriques de 25(OH)-vitamine D (25OHD) Observation/Resultats Entre janvier 2012 et decembre 2013, 536 PTR (âge moyen [ecart type] 50,8 [13,7] ans, 335 hommes) ont ete inclus. Les caracteristiques cliniques et biologiques de depart ne differaient pas entre les groupes DE (n = 269) et DF (n = 267). Dans les groupes DE et DF, la 25OHD etait de 20,2 (8,1) versus 19,2 (7,0) ng/mL a j0 et de 43,1 (12,8) versus 25,1 (7,4) ng/mL apres 24 mois, respectivement (p Discussion Nous rapportons les resultats du premier essai interventionnel visant a evaluer les effets extra-osseux du traitement par vitamine D3 apres transplantation renale. Le nombre de patients inclus correspond a notre objectif initial. Conclusion Par rapport aux ANC, de fortes doses de CL n’induisent pas d’effets indesirables notables mais ne reduisent pas l’incidence des complications non squelettiques apres transplantation renale.

There is an increasing number of anti-HLA sensitized and highly sensitized renal transplant candidates on waiting lists, and the presence of donor-specific alloantibodies (DSAs) at the time of transplantation leads to acute and chronic antibody-mediated rejection (AMR). Acceptable short-term outcomes have been described, notably because of desensitization protocols, but mid- and long-term data are still required.Our high immunologic risk program included 95 patients with high peak or day 0 DSA levels (mean fluorescence intensity [MFI]3000) with a complement-dependent cytotoxicity-negative crossmatch, who received a posttransplant desensitization protocol starting at day 0 with high-dose intravenous immunoglobulin, plasma exchanges, and eventually rituximab. Their characteristics were compared with a control group including 39 patients with a lower immunologic risk (MFI between 500 and 3000 at day 0) who received the same posttransplant desensitization.The median MFI of the immunodominant class I or II DSA in the peak or day 0 serum was 9421 (interquartile range, 4959-12 610). An AMR occurred during the first posttransplant year in 31 patients (32.6%), and at one year, the rate of chronic AMR was 39.5%. The 1-, 3-, 5- and 7-year death-censored allograft survival rates were 98%, 91%, 86%, and 78%, respectively, with concomitant recipient survival rates of 97%, 93%, 85%, and 79%, respectively.These results suggest that DSA-sensitized patients with high MFI levels can receive transplantation across the HLA-barrier, with the use of an intensified posttransplant immunosuppressive therapy starting at day 0 combined with close clinical, immunologic, and histologic monitoring.

Acute clinical antibody-mediated rejection is currently defined by (1), an acute renal failure occurring during the first months following transplantation, (2), at least a microcirculation inflammation (glomerulitis and peritubular capillaritis) on kidney biopsy and (3), the presence in peripheral blood of donor specific antibodies, mostly anti-human leukocyte antigen (HLA) antibodies. The prognosis of this rejection is scored using the severity of vascular lesions and the positivity of C4d on peritubular capillaries. Recently, a subclinical variety of antibody-mediated rejection was recognized as an entity because, as the clinical rejection, it leads to chronic antibody-mediated rejection, currently the most frequent cause of graft loss. The description of these various aspects of antibody-mediated rejection allowed a better understanding of its pathophyiology that may lead in a near future to a more specific treatment.

Anti-HLA donor-specific antibodies (DSAs) cause acute and chronic antibody-mediated rejection (AMR). However, the clinical relevance of anti-HLA-C antibodies remains unclear. We evaluated the clinical relevance of the presence of anti-HLA-C DSA at day 0 in renal transplant recipients. In this retrospective, case-controlled study, 608 patients who underwent kidney transplantation between August 2008 and March 2012 were screened for the presence of isolated anti-HLA-C DSA at day 0. A total of 22 renal transplant recipients were selected and followed for a period of 1 year. AMR was classified according to the Banff classification. The 22 patients were compared with 88 immunized patients. Acute AMR was diagnosed in six patients (27.3%). The median level of DSA at day 0 was 1179 (530-17,941). The mean fluorescence intensity in the anti-C group was 4966 (978-17,941) in the AMR group and 981 (530-8012) in the group of patients without AMR. Acute AMR was diagnosed less frequently in the 88 immunized individuals (9.1%) than in the DSA anti-C group (p = 0.033). The level of DSA at day 0 was predictive for AMR (p = 0.017). Patients with a high level of pretransplant anti-HLA-C DSAs are likely to develop acute AMR during the first year after transplantation.

Objectives We aimed to assess the clinical value of FDG-PET/CT in patients with ANCA-associated vasculitis. Materials and methods We retrospectively included 16 patients with ANCA-associated vasculitis who underwent 21 FDG-PET/CT between 2009 and 2013, in 2 university hospitals from the Paris suburb area. All FDG-PET/CTs were retrospectively analyzed and compared to clinical, biological and conventional imaging data at baseline and during the follow-up. Results ANCA-associated vasculitis was granulomatosis with polyangiitis (GPA, n = 10), microscopic polyangiitis (MPA, n = 4), and eosinophilic GPA (EGPA, n = 2). PET was performed at initial presentation in 14 cases and during the follow-up in 7 cases. At baseline, PET was positive in 100% of GPA patients (8/8) and in 50% (3/6) of patients with other ANCA-vasculitis (p = 0.05). FDG uptake tended to be higher in patients with GPA in comparison to patients with MPA/EGPA (median SUVmax: 5 versus 2.5; p = 0.08). Sinonasal, lung, cardio-vascular and kidney involvements were all accurately identified by PET, except in one MPA patient with glomerulonephritis. As expected, skin, joint, eye and peripheral nervous system impairments were not detected by PET. No occult site was detected by PET, except in 2 salivary gland FDG uptake without clinical abnormalities. Patients with GPA exhibited a higher number of positive sites on PET (2 [1.75–2.25] versus 0.5 [0–1], p = 0.006) than patients with MPA/EGPA. In pooled data including our study and the literature data of GPA patients (n=31), SUVmax was associated with Birmingham Vasculitis Activity Score (BVAS) (r=0.49; p=0.03). Conclusion FDG-PET/CT accurately identifies organ localizations in GPA, other than in nervous system, eye and skin, but do not bring additional benefit to the usual organ screening. The value of FDG-PET/CT in other ANCA-associated vasculitis need to be further addressed.

Introduction Le trafic d’organe, le tourisme de transplantation et le commerce de greffons ont fait l’objet d’un sommet a Istanbul au printemps 2008 aboutissant a la Declaration d’Istanbul dont le but etait de condamner et de faire cesser ces pratiques [1] . En collaboration avec l’Agence de la biomedecine, une enquete nationale aupres des medecins des centres de transplantation renale avait ete realisee entre 2008 et 2012. Patients/Materiels et methodes Nous avons reactualise, en 2017, les donnees medicales de cette cohorte, notamment les complications et la survie des greffons et des patients et evalue le nombre de nouveaux patients transplantes en France dans le cadre du tourisme de transplantation depuis 2012. Observation/Resultats Nous avons identifie 59 patients dont 41 hommes et 18 femmes, qui ont ete transplantes a l’etranger a partir de rein de donneurs remuneres, entre 1985 et 2017. Onze patients ont ete transplantes avant 2000, 38 entre 2000 et 2008 et 10 apres 2008. La duree mediane de suivi etait de 5,6 annees (3,7 ; 12,1). La creatinine moyenne etait a 111 ± 49,2 μmol/L a la date du dernier controle. Quatre patients ont presente des complications chirurgicales (deux stenoses de l’artere du greffon, une infection de cicatrice et un hematome). Les infections representaient la complication la plus frequente puisqu’elles ont concerne 34 patients. Parmi eux, il y eu une seroconversion VHC, sept reactivations VHC, deux reactivations VHB, une coreactivation VHC et VHB, deux tuberculoses dont une disseminee, trois pneumocystose, une aspergillose, deux infections fongiques. Seize patients ont presente un rejet dont 7 rejets humoraux et un rejet mixte. Quatorze patients (23,7 %) ont perdu leur greffon. Onze patients (18,6 %) sont decedes. Discussion/Conclusion Le tourisme de transplantation en France reste un phenomene marginal. Le nombre de patients transplantes avec un greffon provenant d’un donneur remunere est en nette regression depuis la conference d’Istanbul en 2008. Ces pratiques sont associees a une importante morbi-mortalite [2] . Neanmoins, chez les patients n’ayant pas presente de complications, la fonction du greffon demeure satisfaisante a long terme.

Introduction La transition est definie par le processus au cours duquel le patient est oriente d’une prise en charge pediatrique vers une prise en charge adulte. En transplantation renale, elle peut alterer l’observance au traitement immunosuppresseur et aggraver le pronostic de la greffe a long terme. Methodes Nous avons etudie retrospectivement une cohorte monocentrique de 74 patients transplantes renaux transferes de soins pediatriques a une prise en charge en secteur adulte entre decembre 2007 et octobre 2017 a l’hopital Necker. La transition etait definie comme la premiere consultation avec un nephrologue adulte. Une periode de suivi minimale d’un an apres la transition etait requise. Afin d’evaluer le pronostic de la transplantation renale apres la transition, le debit de filtration glomerulaire estime (DFGe) a 12 mois ainsi que la prevalence de perte de greffon et de rejet aigu ont ete determines. Les facteurs associes a la perte de greffon en periode post-transition, definie par le retour en dialyse ou la retransplantation renale, ont egalement ete analyses. Resultats obtenus ou attendus Le delai moyen de transfert vers la prise en charge adulte depuis la greffe renale etait de 9,5 ± 5,2 ans. L’âge moyen a la transition etait de 23 ± 4 ans. Le DFGe moyen etait de 71 ± 27 mL/min/1,73 m2 au moment de la transition et etait stable a 12 mois. En periode post-transition, 9 (12 %) et 12 (16 %) patients ont eu au moins un rejet aigu et perdu leur greffon, respectivement. Le delai moyen entre la transition et la perte du greffon etait de 32 mois. En analyse univariee, un âge inferieur a 20 ans au moment de la transition, un delai court entre la greffe renale et la transition ainsi qu’un DFGe abaisse a la transition etaient associes a une augmentation du risque de perte de greffon apres la transition ( Fig. 1 ). Conclusion Ces donnees suggerent que la transition n’a pas d’impact deletere sur les resultats de la transplantation renale, en particulier quand elle est effectuee tardivement. Il semble donc important de ne pas l’accelerer pour limiter le risque de perte du greffon a long terme. Des etudes incluant des effectifs plus importants sont necessaires pour confirmer ces resultats.

Thrombotic microangiopathy (TMA) is one of the hallmark vascular lesions of antiphospholipid syndrome nephropathy (APSN). These lesions are at high risk of recurrence after kidney transplantation. The complement pathway is thought to be active in this process. We used eculizumab to treat three consecutive kidney transplant recipients with posttransplant TMA due to APSN recurrence that was resistant to plasmapheresis and explored the complement deposition and apoptotic and vascular cell markers on the sequential transplant biopsies. Treatment with eculizumab resulted in a rapid and dramatic improvement of the graft function in all three patients and in improvement of the TMA lesions within the graft. None of these patients had TMA flares after eculizumab was withdrawn. At the time of TMA diagnosis, immunofluorescence studies revealed intense C5b-9 and C4d depositions at the endothelial cell surface of the injured vessels. Moreover, C5b-9 colocalized with vessels exhibiting a high rate of apoptotic cells. Examination of sequential biopsies during eculizumab therapy showed that TMA lesions, C4d and apoptotic markers were rapidly cleared but the C5b-9 deposits persisted for several months as a footprint of the TMA. Finally, we noticed that complement inhibition did not prevent the development of the chronic vascular changes associated with APSN. Eculizumab seems to be an efficient method for treating severe forms of posttransplant TMA due to APSN recurrence. Terminal complement inhibition does not prevent the development of chronic APSN.

The clinical and bacteriological consequences of routinely performing highly sensitive bacterial screening of kidney transplant preservation solution (PS) are not known. To evaluate the clinical and microbiological impacts of this strategy, we retrospectively analyzed 200 consecutive kidney allograft recipients from March 2009 to February 2011 for whom PS samples were routinely screened. PS were inoculated into aerobic and anaerobic blood culture bottles, as well as blood agar plates. A rectal swab for extended-spectrum β-lactamase-producing Enterobacteriaceae (EBSL-PE) faecal carriage was also routinely obtained from each patient at admission and every 7 days until hospital discharge. In addition, a standard culture of drain fluid was collected on the day after kidney transplantation. Complete samples and cultures of PS were performed in 165 cases (82.5%), and 62 (37.6%) had positive blood culture results. The most frequent microbial agent isolated was coagulase-negative staphylococci (51.8%). Of these 62 positive samples, only seven (11.3%) were confirmed to contain the same organism by the standard culture method. Drain fluid and PS culture positivity with the same microorganism occurred in only two patients. Of the 62 patients with positive PS cultures, 26 (41.9%) received pre-emptive antibiotic therapy initiated within 48 h post-transplant. During the hospitalization period, patients with a positive PS culture, regardless of whether they received pre-emptive antibiotic therapy, did not exhibit any invasive infections (urinary, blood, peritoneal or wound) related to the microorganisms isolated in the PS. Patients with positive PS cultures who were treated with antibiotic therapy acquired significantly more colonizing ESBL-PE than patients who did not receive antibiotics (53.8% vs. 16.6%; P = 0.01); these patients also developed more clinical infections related to the ESBL-PE (23.1% vs. 5.2%; P < 0.01). The use of antibiotics for patients with positive PS cultures was an independent risk factor for ESBL-PE acquisition in both univariate and multivariate analyses. In conclusion, the use of more sensitive culture methods increases the rate of bacterial contamination of PS and is associated with an increased prescription of antibiotics and increased ESBL-PE carriage and related infections. Therefore, the systematic use of PS blood bottle cultures in kidney transplantation may have no benefit and might increase the rate of ESBL-PE emergence.

Treatment of end stage renal disease has an impact on patients’ physical and psychological health, including quality of life (QoL). Nowadays, it is known that reducing the dialysis period has many advantages regarding QoL and medical outcomes. Although preemptive transplantation is the preferred strategy to prevent patients undergoing dialysis, its psychological impact is unknown. Moreover, transplantation can be experienced in a completely different manner among patients who were on dialysis and those who still had a functioning kidney at the time of surgery. Longitudinal data are often collected to allow analyzing the evolution of patients’ QoL over time using questionnaires. Such data are often difficult to interpret due to the patients’ changing standards, values, or conceptualization of what the questionnaire is intended to measure (e.g. QoL). This phenomenon is referred to as response shift and is often linked to the way the patients might adapt or cope with their disease experience. Whether response shift is experienced in a different way among patients who were on dialysis and those who still had a functioning kidney at time of surgery is unknown and will be studied in the PreKit-QoL study (trial registration number: NCT02154815). Understanding the psychological impact of pre-emptive transplantation is an important issue since it can be associated with long-term patient and graft survival. Adult patients with a pre-emptive transplantation (n = 130) will be prospectively included along with a control group of patients with a pre-transplant dialysis period