Covid-19 en transplantation rénale,leçons du registre français

The Covid-19 pandemic hits the French transplant population on March 3, 2020. Very quickly, a French registry was set up on behalf of the French Society of Transplantation allowing the collection of confirmed cases of Covid-19 occurring in kidney transplant recipients in almost all French centers. The analysis of this registry in conjunction with the data from the Agence de la Biomédecine (Cristal) has enabled us to obtain instructive results. We first showed that the incidence of severe forms among transplant patients hospitalized for Covid-19 was 46% and that their mortality was 22.8%. The risk factors for severe forms and mortality are described. Then we showed, by comparing transplant patients with immunocompetent patients matched for the main severity factors of the disease, that mortality among transplant patients was higher (17.9% vs 11.4%; P < 0.001). In multivariate analysis, a creatinine level at admission above 115 μmol/L was associated with death, whereas being transplanted was not. Finally, comparing the transplant cohort with patients on the kidney transplant waiting list during the period from February to June 2020, we found that patients on the waiting list had a higher Covid-19-related excess mortality than transplant patients, mainly in areas of low viral circulation. In conclusion, the French Registry of transplant patients with Covid-19, which was rapidly set up at the beginning of the epidemic, has already enabled us to draw several lessons about this initially unknown infection, particularly in kidney transplant patients, a population which appeared to be particularly at risk.     

Fas/Fas Ligand pathways gene polymorphisms in pediatric renal allograft rejection

BackgroundAn essential milestone in pediatric transplantation is to find noninvasive biomarkers to monitor acute rejection (AR). In this retrospective (Case-control) study, we examined the role of Fas − 670A/G and Fas Ligand (FasL) − 843C/T gene polymorphisms in allograft nephropathy in pediatric renal transplant recipients.MethodsIn 47 pediatric kidney transplant recipients and 20 healthy controls, Fas − 670A/G and FasL − 843C/T gene polymorphisms as well as serum soluble Fas Ligand level (sFasL) were measured.ResultsSerum sFasL levels were significantly higher in transplant recipients children than that in controls (548.25 ± 298.64 pg/ml vs 143.17 ± 44.55 pg/ml, p = 0.0001). There was no significant difference between patients with AR and those without AR in regards to serum sFasL levels (567.70 ± 279.87 pg/ml vs 507.85 ± 342.80 pg/ml, p = 0.56). Fas − 670A/G genotypes or alleles were not significantly different between controls and transplant recipients and among transplant recipients with and without AR. (P > 0.05 for all). FasL − 843C/T genotypes were not different between transplant recipients and controls and among transplant recipients with and without AR (P > 0.05 for all). However, Frequency of C allele in transplant patients was significantly higher than that in the control group (44.68% vs 25%, P = 0.03). FasL − 843C/T alleles were significantly different between patients with and without AR (P = 0.03). The percentages of C allele were higher in children with AR (58.82% vs 36.67%). We found that serum FasL and serum creatinine were variables that were independently associated with AR.ConclusionThis study suggests that FasL gene polymorphisms in peripheral blood might be accurate in detecting cellular AR.     

Has the COVID-19 pandemic changed the clinical picture and tumour stage at the time of presentation of patients with colorectal cancer? A retrospective cohort study

IntroductionTreatment of patients with Coronavirus Disease 2019 (COVID-19) has affected the management of patients with colorectal cancer (CRC). The aim of this study was to compare the diagnosis delay, symptoms, and stage of patients with CRC during the pandemic with a control cohort.Material and methodsPatients referred to the CRC multidisciplinary team between September 2019 and January 2020 (cohort 1, control group) were compared with those who presented between September 2020 and March 2021 (cohort 2, pandemic group).Results389 patients were included, 169 in cohort 1 and 220 in cohort 2. No differences were observed in the main characteristics of the patients. CRC screening and anaemia were the most common causes leading to the diagnosis of the tumour in cohort 1 and 2, respectively (p < 0.001). Diagnostic and therapeutic delay was longer in cohort 2 [6.4 (95% CI 5.8–6.9) vs. 4.8 (95% CI 4.3–5.3) months, p < 0.001]. More patients required non-elective treatment in the pandemic cohort (15.5% vs. 9.5%, p = 0.080). The tumour stage was more advanced in patients in cohort 2 [positive nodes in 52.3% vs. 36.7% (p = 0.002), and metastatic disease in 23.6% vs. 16.6% (p = 0.087)].ConclusionCRC patients in the pandemic cohort had a longer diagnostic and therapeutic delay and less patients were diagnosed because of CRC screening. In addition, patients with CRC during the pandemic needed non-elective treatment more frequently than patients in the control cohort, and their tumour stage tended to be more advanced.     

Mannose-binding lectin-2 and ficolin-2 gene polymorphisms and clinical risk factors for acute rejection in kidney transplantation

IntroductionThere is growing evidence that the lectin pathway is significantly associated with acute rejection. Rare studies associated both gene polymorphisms of MBL2 and FCN2 with acute rejection after kidney transplantation. The aim of the present study was to investigate the role of the lectin gene profile and clinical risk factors such as PRA level on acute rejection in kidney transplant recipients.MethodsWe prospectively analyzed 157 kidney transplant recipients with and without acute rejection. A total of 6 well-known functional single-nucleotide polymorphisms in the MBL2 gene and 5 in the FCN2 gene of the recipients were determined by gene sequencing. MBL2 and FCN2 genotypic variants were analyzed for association with the incidence of acute rejection within the first year after kidney transplantation.ResultsAfter adjusting for variables of P < 0.2, we found the differences in the incidence of acute rejection were only according to panel-reactive antibodies (odds ratios (OR) = 6.468, 95% confidence intervals (CI) = 2.017–20.740, P = 0.002) and the HH genotypes of MBL2 promoter ? 550 (OR = 2.448, 95%CI = 1.026–5.839, P = 0.044).ConclusionPanel-reactive antibodies and the HH genotypes of MBL2 promoter ? 550 have significant impacts on the risk of developing acute rejection after kidney transplantation.     

Influence of immune activation on the risk of allograft rejection in human immunodeficiency virus-infected kidney transplant recipients

BackgroundHIV infection is associated with high rates of acute rejection following kidney transplantation. The underlying mechanisms for such predisposition are incompletely understood. Pathological immune activation is a hallmark of chronic HIV infection that persists despite effective antiretroviral therapy. We hypothesized that the baseline levels of T cell activation in HIV⁺ candidates would correlate with their risk of acute rejection following kidney transplantation.MethodsSingle-center retrospective cohort analysis of HIV⁺ adult kidney transplants performed between October 2006 and September 2013. The frequency of CD3⁺ HLA-DR⁺ cells measured by flow cytometry served as a surrogate marker of immune activation. Patients were categorized into tertiles of activation, and the rates of biopsy-proven acute rejection were compared across groups.Results(1) Compared to matched HIV⁻ controls, the baseline number of CD3⁺ HLA-DR⁺ cells was higher in HIV⁺ kidney transplant candidates. (2) Abnormally high levels of activation did not decrease with transplant-associated immunosuppression. (3) Patients categorized within the lower and middle CD3⁺ HLA-DR⁺ tertiles had higher probability of rejection during the first 3 years post-transplant compared to those in the higher activation tertile (36.9% vs. 0%; log-rank P = 0.04).ConclusionsPathological immune activation in HIV⁺ transplant candidates does not explain their increased susceptibility to allograft rejection. Paradoxically, those with the highest levels of immune activation seem to be less prone to rejection.     

Profil épidémiologique et clinique,et survie à 90 jours des patients incidents en hémodialyse chronique au cours de la pandémie à SARS-CoV2 au Cameroun : expérience de l’hôpital général de Douala

BackgroundThe effect of COVID-19 pandemic on end stage renal disease patient who should initiated dialysis are limited in Sub-Saharan Africa is unknown. We sought to describe the epidemiologic and clinical profile of newly admitted patient in chronic haemodialysis during the COVID-19 pandemic in Cameroon and evaluate their survival between 90 days of dialysis initiation.Material and methodWe conducted a cohort study of 6 months from April to October 2020. End stage renal disease patients newly admitted in the haemodialysis facility of the General Hospital of Douala were included. Patients with confirmed or suspected COVID-19 were identified. Socio-demographic, clinical and biological data at dialysis initiation as well as mortality between the 90 days of dialysis initiation were registered.ResultsA total of 57 incident patients were recorded from April to October 2020 with a monthly mean of 9.5 patients. The mean age was 46.95 ± 13.12 years. Twenty-four COVID-19 were identified with a frequency of 49% among emergency admission. Pulmonary œdema (79.2% vs. 42.4%; P = 0.006) and uremic encephalopathy (83.4% vs. 53.6%; P = 0.022) were more common in COVID-19. The overall survival at 90 days was 48% with a tendency to poor survival among COVID-19 and patients with low socioeconomic level. In Cox regression, low socioeconomic level increase the risk of instant death by 3.08.ConclusionSARS-CoV2 seem to increase nephrology emergency and poor survival in haemodialysis at 90 days.     

Influencia del confinamiento por COVID-19 en los resultados ponderales durante el primer año tras la gastrectomía vertical

IntroductionCOVID-19 pandemic has lead to lockdown of population in many countries. In Spain, the state of alarm was established from March 15 to June 20, 2020. Usually this fact decreased people's mobility and physical activity, in addition to producing or exacerbating psychological disorders. Our aim was to determine the influence that this condition had over the short-term ponderal results of patients undergoing laparoscopic vertical gastrectomy from May 2019 to May 2020.MethodsCase-control study for comparing the percentage of excess weight lost (%EWL) and the percentage of total weight lost (%TWL) of patients that underwent a VG during the last year, so they were affected by lockdown in April and part of March 2020 (group 1), to the %EWL and %TWL of a control group (group 2), obtained from our previous series.ResultsThe mean %EWL in group 1 is 47,37 ± 18,59 and in group 2 is 51,13 ± 17,59, being p = 0,438. Meanwhile, the mean %TWL in group 1 is 21,14 ± 8,17 and in group 2 is 24,67 ± 8,01, with p = 0,115.ConclusionsPopulation lockdown by COVID-19 did not get worse short-term results of vertical gastrectomy. More studies with a larger number of patients are necessary to draw firm conclusions.     

Evolution of secondary hyperparathyroidism in patients following return to hemodialysis after kidney transplant failure

IntroductionSevere uncontrolled secondary hyperparathyroidism and kidney transplantation history are both risk factors for fractures in hemodialyzed patients. Moreover, patients who return to dialysis after transplant failure have more severe infections/anemia and higher mortality risk than transplant-naive patients starting dialysis with native kidneys. In this context, our aim was to test the hypothesis that transplant failure patients have more secondary hyperparathyroidism than transplant-naive patients.MethodsWe retrospectively compared 29 transplant failure patients to 58 transplant-naive patients matched for age, sex, chronic kidney disease duration and diabetes condition (1 transplant failure/2 transplant-naive ratio), who started dialysis between 2010 and 2014. Clinical and biological data were collected at baseline, 6 and 12 months.FindingsAt baseline, neither serum parathyroid hormone (transplant-naive: 386 ± 286 pg/mL; transplant failure: 547 ± 652 pg/mL) nor serum 25-hydroxyvitamin D (transplant-naive: 27.8 ± 17.0 μg/L, transplant failure: 31.1 ± 14.9 μg/L) differed between groups. However, serum parathyroid hormone at 12 months and the proportion of patients with uncontrolled secondary hyperparathyroidism (parathyroid hormone > 540 pg/mL, KDIGO criteria) were significantly higher in transplant failure than in transplant-naive (parathyroid hormone: 286 ± 205 vs. 462 ± 449, P < 0.01; uncontrolled secondary hyperparathyroidism: 30% vs. 13%, P < 0.01, respectively). Within the transplant failure group, patients with uncontrolled secondary hyperparathyroidism at 12 months were younger than patients with normal or low parathyroid hormone.DiscussionThis retrospective and monocentric study suggests that transplant failure patients are more likely to develop secondary hyperparathyroidism. Thus, finding high serum parathyroid hormone in young transplant failure patients, who are expected to undergo further transplantations, should incite physicians to treat early and more aggressively this complication.     

Immune reconstitution syndrome-like entity in lung transplant recipients with invasive aspergillosis

BackgroundIncidence, characteristics, and risk-factors for invasive aspergillosis (IA)-associated immune reconstitution syndrome (IRS) in lung transplant recipients are not known.MethodsPatients comprised 68 lung transplant recipients with proven/probable IA followed for 12 months. IRS was defined based on previously proposed criteria.ResultsIn all, 7.3% (5/68) of the patients developed IRS based on aforementioned criteria, a median of 56 days after initiation of antifungal therapy. This entity was associated with heart–lung transplantation (p = 0.006), anti T-cell agent use (p = 0.003), discontinuation of calcineurin inhibitor agent (p = 0.002), and disseminated IA (p = 0.069). In a risk assessment model, IRS developed in 0% (0/55) of the patients with none of the aforementioned factors, 28.6% (2/7) with one, 33.3% (1/3) with two, and in 1/1 patient with 3 factors (X² for trend p = 0.0001). Three out of 5 patients with IRS died and 2 of 3 deaths in this group were due to chronic rejection.ConclusionsOverall 7% of the lung transplant recipients with IA appear to develop an IRS-like entity. Clinically assessable factors can identify patients at risk for post-transplant IA-associated IRS. Deaths due to chronic rejection were significantly higher in patients with IRS than those without IRS.     

Utilidad de la embolización vascular prequirúrgica de tumores renales con trombo tumoral en la vena renal izquierda

Introduction and objectivesPreoperative renal artery embolization (PRAE) for large renal masses may be performed prior to nephrectomy in order to simplify the procedure and reduce intraoperative bleeding. The objective of this work is to determine the role of PRAE on intraoperative bleeding and postoperative complications in left renal tumors with tumor thrombus limited to the left renal vein (level 0).Material and methodsRetrospective analysis to evaluate 46 patients who underwent left radical nephrectomy and thrombectomy for the treatment of renal cell carcinoma with level 0 tumor thrombus during the period 1990-2020. PRAE was limited to those cases in which surgical access to the main renal artery was presumed a priori difficult in the preoperative imaging study (n = 9; 19.6%). Intraoperative bleeding was estimated based on the perioperative transfusion rate, and postoperative complications were categorized according to the Clavien-Dindo classification. The Chi-squared test was used for comparisons. A multivariate analysis was performed to identify predictors of transfusion and complications.ResultsThere were no significant differences in the overall complication rate (11.1% vs. 32.4%, P = .19), major complication rate (0% vs.8.1%, P = .51), or transfusion rate (11.1% vs. 19%, P = .49) between both groups (PRAE vs. non-PRAE). In the multivariate analysis, PRAE did not behave as a predictor of complications (OR:0.11, 95%CI 0.01-2.86; P = .18) nor transfusion (OR:0.46, 95%CI 0.02-7.38;P = .58).ConclusionsIn our study on left renal cell carcinomas with level 0 tumor thrombus and difficult access to the main renal artery, PRAE was not associated with increased bleeding or postoperative complications, and it did not behave as an independent predictor of these variables. Therefore, it could be used as a preoperative maneuver to facilitate vascular management in selected cases.     

Simulación sanitaria durante la COVID-19: una experiencia con los residentes de Anestesiología

BackgroundThe restrictions to stop COVID-19 pandemic have had a negative impact in simulation. However, it is imperative to develop new strategies that facilitate healthcare education.ObjectiveTo describe a simulation in healthcare based on the learning of non-technical skills and performed under the restrictions of COVID-19 pandemic.MethodsQuasi-experimental study of an educational activity performed through simulation with Anaesthesiology residents in November 2020. Twelve residents participated in 2 consecutive days. A questionnaire was filled related to the performance of non-technical skills that encompasses leadership, teamwork and decision making. The complexity of the scenarios and the non-technical skills results obtained between the 2 days were analysed. Advantages and challenges were documented when a clinical simulation is performed under COVID-19 restrictions.ResultsThe global performance of the teams improved when comparing first and second day (79.5 vs. 88.6%, P < .01). Leadership was the worst section rated, however, was the one that showed the best improvement (70 vs. 87.5%, P < .01). The complexity of the simulation cases had no relation with the group performance in leadership and teamwork but affected task management results. General satisfaction was over 75%. The main challenges to develop the activity were the technology required to adapt virtuality to simulation and the time spent for the preparation of it. No cases of COVID-19 were reported within the first month after the activity.ConclusionClinical simulation can be done in the context of COVID-19 pandemic, obtaining satisfactory learning results but requiring the adaptation of institutions to the new challenges it implies.     

Preemptive therapy for cytomegalovirus based on real-time measurement of viral load in liver transplant recipients

BackgroundReal-time PCR has emerged as the preferred diagnostic assay for CMV. However, its utility as a preemptive therapy tool for CMV disease and related outcomes in liver transplant recipients has not been fully defined.MethodsPatients comprised 117 consecutive liver transplant recipients who underwent CMV surveillance monitoring using real-time PCR. Preemptive therapy with valganciclovir was employed upon detection of viremia. Baseline viral load was considered high based on log values (median).ResultsCMV viremia developed in 54% (63/117) of the patients, including 77% of R−/D+, 63% of R+/D+, 43% of R+/D−, and 10% of R−/D− patients. Overall, 23% (15/63) of the patients had recurrent viremia; R− serostatus (p = 0.065) but not initial viral load correlated with recurrent viremia (p = 0.80). At 12 months post-transplant, CMV disease occurred in 0.85% (1/117) of the patients (R+/D + recipient). None (0/30) of the R−/D + patients had CMV disease. Patients with CMV viremia treated preemptively did not differ significantly from those who never developed CMV viremia with regards to bacterial or fungal infections, rejection, graft loss, mortality rate, and probability of survival at 12 months (p > 0.05 for all variables). The above outcomes also did not differ for patients with high (> 1.9 logs) vs. low viral load (< 1.9 logs) (p > 0.05 for all outcomes).ConclusionsPreemptive therapy guided by real-time PCR based monitoring led to outcomes in all patients or in those with high viral loads that were comparable to outcomes in patients who never developed viremia or had low viral loads, respectively. Late-onset CMV disease at 12 months was observed in < 1% of all patients.     

20 años de experiencia en trasplante renal en bloque de donantes pediátricos en receptores adultos

BackgroundEn bloc kidney transplantation from pediatric donors into adult recipients increases the donor pool. However, this surgical procedure is not widely performed in many transplant centers. To evaluate the long-term outcomes of bloc kidney transplantation from pediatric donors into adult recipients in a single center.Material and methodsRetrospective analysis of 42 patients who received pediatric cadaveric bloc kidney transplantation in our center since 1999. Median follow-up period was 73 months (5-233) in which renal function tests were taken and complications registered.ResultsWe have performed 42 bloc kidney transplantation from pediatric donors into adult recipients in our center. The recipients’ age was 44.1 ± 11.8 years. Pediatric donors were 22.4 ± 14.7 months old and weighted 11.3 ± 3.6 kg. Cold ischemia time was 15.7 ± 4.5 hours. During a median follow-up of 73 months, 35 patients (83.3%) had graft survival with excellent function (first-year serum creatinine levels of 0.99 ± 0.25 mg/dl). There were 7 graft losses (16.7%) in the immediate postoperative period (4 cases of vascular thrombosis, one anastomosis dehiscence and 2 cortical necrosis).ConclusionsThe pediatric en bloc renal graft transplantation into adults is a safe technique with excellent medium- to long-term functional performance. The vast majority of significant complications leading to graft loss were reported in the immediate postoperative period. A good selection of donors and recipients as well as an adequate surgical technique are essential to minimize the occurrence of adverse events.     

Impacto del COVID-19 en pacientes con estenosis aórtica severa: análisis basado en inteligencia artificial

IntroductionUntreated, severe, symptomatic aortic stenosis is associated with an ominous diagnosis without intervention. This study aims to determine the impact of the COVID-19 pandemic on the mortality of patients with severe stenosis during the first wave and compare it with the same period last year.MethodsAll patients who went to the hospitals in an Spanish region during the first wave, and in the same period of previous year, were analyzed using artificial intelligence-based software, evaluating the mortality of patients with severe aortic stenosis with and without COVID-19 during the pandemic and the pre-COVID era. Mortality of the 3 groups was compared. Regarding cardiac surgeries was a tendency to decrease (P = .07) in patients without COVID-19 between the pandemic and the previous period was observed. A significant decrease of surgeries between patients with COVID-19 and without COVID-19 was shown.ResultsData showed 13.82% less admitted patients during the first wave. A total of 1,112 of them had aortic stenosis and 5.48% were COVID-19 positive. Mortality was higher (P = .01), in COVID-19 negative during the pandemic (4.37%) versus those in the pre-COVID-19 era (2.57%); it was also in the COVID-19 positive group (11.47%), versus COVID-19 negative (4.37%) during the first wave (P = .01).ConclusionsThe study revealed a decrease in patients who went to the hospital and an excess of mortality in patients with severe aortic stenosis without infection during the first wave, compared to the same period last year; and also, in COVID-19 positive patients versus COVID-19 negative.     

Immunoglobulin isotype switching of antibodies to vimentin is associated with development of transplant glomerulopathy following human renal transplantation

BackgroundImmune responses to tissue-restricted self-antigens are thought to play a role in chronic rejection after solid organ transplantation. De novo development of antibodies (Abs) to vimentin have been reported to be associated with interstitial fibrosis/tubular atrophy after kidney transplant, and it has been suggested that immunoglobulin isotype switching of Abs to vimentin may occur during this process. We aimed to determine the correlation between immunoglobulin isotype switching of Abs to vimentin and development of transplant glomerulopathy (TG) after kidney transplant, and to determine whether citrullinated modification of vimentin is required for de novo anti-vimentin development.MethodsSera were collected from 24 patients with TG (diagnosed on biopsy), 24 matched stable kidney transplant recipients (KTxRs) and 22 normal healthy subjects who did not undergo transplant. Serum vimentin Abs concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Immunoglobulin isotypes of anti-vimentin were determined using isotype-specific Abs conjugated with horseradish peroxidase. Samples were considered positive to vimentin Abs if the values were above mean + 2 × standard deviations of the levels in the healthy control subjects. Specificities of anti-vimentin for mutated citrullinated vimentin and anti-mutated citrullinated vimentin were measured by ELISA.ResultsIn this retrospective analysis of 24 KTxRs with TG, 16/24 (67%) patients with biopsy-proven TG developed Abs to vimentin (645 ± 427 ng/ml). In contrast, only 4/24 (17%) stable KTxRs had detectable Abs to vimentin (275 ± 293 ng/ml; p = 0.001). Of the patients with TG, 15/24 (63%) developed Abs to vimentin of IgG isotype (572 ± 276 ng/ml), whereas only 6/24 (25%) stable KTxRs (310 ± 288 ng/ml) had anti-vimentin of IgG isotype (p = 0.002). However, no significant difference was noted in the concentration of IgM isotype anti-vimentin between KTxRs with TG (9/24 [38%], 407 ± 401 ng/ml) and stable KTxRs (5/24 [21%], 348 ± 439 ng/ml; p = 0.631). The serum concentration of Abs specific for the mutated form of citrullinated vimentin was not significantly different between KTxRs with TG and stable KTxRs.ConclusionsPatients with biopsy-proven TG demonstrated significantly increased levels of anti-vimentin Abs of the IgG isotype compared with stable KTxRs. Anti-vimentin in stable KTxRs was primarily of IgM isotype. Therefore, the observed isotype switching of anti-vimentin from IgM to IgG isotype strongly suggests ongoing immune responses to vimentin in KTxRs diagnosed with TG. Furthermore, as opposed to patients with rheumatoid arthritis (who develop immune responses primarily to citrullinated vimentin), KTxRs diagnosed with TG developed immune responses to non-citrullinated vimentin, suggesting that modification of vimentin protein via citrullination is not required for the de novo anti-vimentin response seen in patients with TG.