Cardiovascular disease is a major cause of morbidity, disability, and mortality in kidney transplant patients. Cumulative reports indicate that the excessive risk of cardiovascular events is not ...entirely explained by the increased prevalence of traditional cardiovascular risk factors. Atherosclerosis is a chronic inflammatory disease, and it has been postulated that posttransplant immune disturbances may explain the gap between the predicted and observed risks of cardiovascular events. Although concordant data suggest that innate immunity contributes to the posttransplant accelerated atherosclerosis, only few arguments plead for a role of adaptive immunity. We report and discuss here consistent data demonstrating that CD8+ T cell activation is a frequent posttransplant immune feature that may have pro-atherogenic effects. Expansion of exhausted/activated CD8+ T cells in kidney transplant recipients is stimulated by several factors including cytomegalovirus infections, lymphodepletive therapy (e.g., antithymocyte globulins), chronic allogeneic stimulation, and a past history of renal insufficiency. This is observed in the setting of decreased thymic activity, a process also found in elderly individuals and reflecting accelerated immune senescence.
Depuis presque 30 ans, l’utilisation de la photo-chimiothérapie (PEC) a montré son efficacité dans le contrôle de la maladie du greffon contre l’hôte et dans le traitement du rejet d’allogreffe ...cardiaque et pulmonaire. L’utilisation de la PEC en transplantation rénale pourrait apporter un bénéfice thérapeutique sans majoration du risque infectieux ou oncologique, tant en prévention que dans le traitement du rejet. Il existe peu de données sur les mécanismes d’action de la PEC, les principales hypothèses reposant sur les résultats observés dans la maladie du greffon contre l’hôte ou en transplantation cardiaque et pulmonaire. La PEC induirait des modifications de l’immunité innée et adaptative dont la restauration d’un équilibre de la balance Th1/Th2 et une expansion des sous-populations LT/B régulatrices ainsi qu’une modification de l’environnement cytokinique avec enrichissement en IL-10. En France, des études cliniques et mécanistiques sont en cours pour affiner la place de la PEC dans les stratégies d’immunomodulation en transplantation rénale.
Acute 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.
We 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.
Three-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 < 0.001) after validation in the VC.
Our 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.
Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially ...in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA.
Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome.
Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of > 4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity.
Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.
Background
Non-tunneled hemodialysis catheters are currently used for critically ill patients with acute kidney injury requiring extracorporeal renal replacement therapy. Strategies to prevent ...catheter dysfunction and infection with catheter locks remain controversial.
Methods
In a multicenter, randomized, controlled, double-blind trial, we compared two strategies for catheter locking of non-tunneled hemodialysis catheters, namely trisodium citrate at 4% (intervention group) versus unfractionated heparin (control group), in patients aged 18 years or older admitted to the intensive care unit and in whom a first non-tunneled hemodialysis catheter was to be inserted by the jugular or femoral vein. The primary endpoint was length of event-free survival of the first non-tunneled hemodialysis catheter. Secondary endpoints were: rate of fibrinolysis, incidence of catheter dysfunction and incidence of catheter-related bloodstream infection (CRBSI), all per 1000 catheter-days; number of hemorrhagic events requiring transfusion, length of stay in intensive care and in hospital; 28-day mortality.
Results
Overall, 396 randomized patients completed the trial: 199 in the citrate group and 197 in the heparin group. There was no significant difference in baseline characteristics between groups. The duration of event-free survival of the first non-tunneled hemodialysis catheter was not significantly different between groups: 7 days (IQR 3–10) in the citrate group and 5 days (IQR 3–11) in the heparin group (
p
= 0.51). Rates of catheter thrombosis, CRBSI, and adverse events were not statistically different between groups.
Conclusions
In critically ill patients, there was no significant difference in the duration of event-free survival of the first non-tunneled hemodialysis catheter between trisodium citrate 4% and heparin as a locking solution. Catheter thrombosis, catheter-related infection, and adverse events were not statistically different between the two groups.
Trial registration
Registered with Clinicaltrials.gov under the number NCT01962116. Registered 14 October 2013.
L’immunosénescence participe au développement des maladies liées à l’âge (infections, maladies cardiovasculaires et cancers). Les patients insuffisants rénaux chroniques terminaux présentent une ...mortalité prématurée par rapport à la population générale, secondaire à une plus grande susceptibilité à la survenue d’infections, d’événements cardiovasculaires et de cancers, pathologies habituellement rencontrées chez les personnes âgées et associées à l’immunosénescence. L’insuffisance rénale chronique engendre un vieillissement prématuré du compartiment lymphocytaire T, notamment concernant la fonction thymique qui joue un rôle clé dans la survenue précoce de pathologies du vieillissement chez ces patients insuffisants rénaux chroniques. Le niveau d’immunosénescence influence également le devenir en transplantation rénale, notamment les risques de survenue de rejet aigu et d’infections. Une réversion partielle de l’immunosénescence pré-transplantation est observée pour certains patients transplantés rénaux. En conclusion, afin de limiter la morbi-mortalité des patients insuffisants rénaux chroniques dont l’incidence augmente tous les ans, la meilleure connaissance de l’immunosénescence induite par l’urémie ouvre la voie à des études cliniques et des pistes thérapeutiques innovantes. Les approches thérapeutiques de réversion et de prévention de l’immunosénescence feront partie de la prise en charge des patients insuffisants rénaux chroniques dans l’avenir.
Immune senescence is associated with age-related diseases (i.e. infectious disease, cardiovascular diseases and cancers). Chronic kidney disease patients die prematurely when compared with general population, because of a higher occurrence of infections, cardiovascular events and cancer. These diseases are commonly observed in the elderly population and frequently associated with immune senescence. Indeed, chronic kidney disease causes a premature aging of the T lymphocyte compartment, widely related to a decrease in thymic function, a phenomenon that plays a key role in the onset of age-related diseases in chronic kidney disease patients. The degree of immune senescence also influences patients’ outcome after renal transplantation, particularly the risk of acute rejection and infections. Partial reversion of pre-transplant immune senescence is observed for some renal transplant patients. In conclusion, to reduce the increasing incidence of morbidity and mortality of chronic kidney disease patients, a better knowledge of uremia-induced immune senescence would help to pave the way to build clinical studies and promote innovative therapeutic approaches. We believe that therapeutic reversion and immune senescence prevention approaches will be part of the management of chronic kidney disease patients in the future.
We reported the case of a female in chronic dialysis since 3 years who developed a normocytic a regenerative anemia with no evident etiology. A bone marrow smear revealed a copper deficiency, a rare ...cause of anemia in general and dialyzed populations. Copper supplementation improved anemia with a decrease in transfusions rate and erythropoietin dosage. This case suggests that a copper deficiency has to be considered when a myelodysplastic syndrome is associated with neurologic symptoms and granulocytes precursors vacuolization identified in bone marrow smear. A blood titration of trace elements should be considered in front of a refractory anemia with no evident etiology.
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