Performance of creatinine-based equations to estimate glomerular filtration rate in White and Black populations in Europe, Brazil and Africa.

peer reviewed("[en] BACKGROUND: A new Chronic Kidney Disease Epidemiology Collaboration equation without the race variable has been recently proposed (CKD-EPIAS). This equation has neither been validated outside USA nor compared with the new European Kidney Function Consortium (EKFC) and Lund-Malmö Revised (LMREV) equations, developed in European cohorts. METHODS: Standardized creatinine and measured glomerular filtration rate (GFR) from the European EKFC cohorts (n = 13 856 including 6031 individuals in the external validation cohort), from France (n = 4429, including 964 Black Europeans), from Brazil (n = 100) and from Africa (n = 508) were used to test the performances of the equations. A matched analysis between White Europeans and Black Africans or Black Europeans was performed. RESULTS: In White Europeans (n = 9496), both the EKFC and LMREV equations outperformed CKD-EPIAS (bias of -0.6 and -3.2, respectively versus 5.0 mL/min/1.73 m², and accuracy within 30% of 86.9 and 87.4, respectively, versus 80.9%). In Black Europeans and Black Africans, the best performance was observed with the EKFC equation using a specific Q-value (= concentration of serum creatinine in healthy males and females). These results were confirmed in matched analyses, which showed that serum creatinine concentrations were different in White Europeans, Black Europeans and Black Africans for the same measured GFR, age, sex and body mass index. Creatinine differences were more relevant in males. CONCLUSION: In a European and African cohort, the performances of CKD-EPIAS remain suboptimal. The EKFC equation, using usual or dedicated population-specific Q-values, presents the best performance in the whole age range in the European and African populations included in this study.","[en] ",""

Memory CD8 T cells and graft outcome in transplantation

En transplantation rénale, malgré une amélioration de la prise en charge des rejets aigus, les patients restent exposés au risque de dysfonction chronique secondaire à la néphrotoxicité des immunosuppresseurs ainsi qu’à des phénomènes de rejet chronique cellulaire et/ou humoral. Identifier précocement les patients à haut risque de perte de greffon et plus particulièrement ceux présentant un sur risque immunologique demeure un défi. Les T CD8+ sont des acteurs majeurs de l’alloréactivité et une augmentation des T CD8+ mémoires de type TEMRA (CD45RA+CCR7-) est associée à un risque deux fois plus élevé de dysfonction chronique. Nous avons étudié l’impact de la répartition des sous populations lymphocytaires T CD8+ circulantes à un an post transplantation sur le devenir du greffon. Nous montrons qu’indépendamment des facteurs de risque cliniques et biologiques classiques inclus dans le score KTFS (Kidney Tranplant Failure Score), un pourcentage de T CD8+ TEMRA >32,7% ou de T CD8+ EM (CD45RA-CCR7-) 4,17), un taux de T CD8+ EM 32.7% or EM CD8 (CD45RA-CCR7-) 4.17), a low percentage of EM CD8 (<36%) is associated with a 2.5-fold higher risk of graft loss. Finally, while EM and TEMRA CD8 share the same cytotoxic capacities after donor-specific stimulation, we show that TEMRA CD8 can be activated independently of their TCR through the Fc receptor CD16. These results demonstrate the importance of monitoring memory CD8 T cells in transplantation and highlight the need to design innovative therapeutic strategies targeting CD8

Blood biomarkers of kidney transplant rejection, an endless search?

International audienceThe tailoring of immunosuppressive treatment is recognized as a promising strategy to improve long-term kidney graft outcome. To guide the standard care of transplant recipients, physicians need objective biomarkers that can identify an ongoing pathology with the graft or low intensity signals that will be later evolved to accelerated transplant rejection. The early identification of 'high-risk /low-risk' patients enables the adjustment of standard of caring, including managing the frequency of clinical visits and the immunosuppression dosing. Given their ease of availability and the compatibility with a large technical array, blood-based biomarkers have been widely scrutinized for use as potential predictive and diagnostic biomarkers. Areas covered: Here, the authors report on non-invasive biomarkers, such as modification of immune cell subsets and mRNA and miRNA profiles, identified in the blood of kidney transplant recipients collected before or after transplantation. Expert commentary: Combined with functional tests, the identification of biomarkers will improve our understanding of pathological processes and will contribute to a global improvement in clinical management

ANCA-negative pauci-immune crescentic glomerulonephritis associated with Fabry disease: lesson for the clinical nephrologist

International audienceNo abstract availabl

Minimal change disease relapse following SARS-CoV-2 mRNA vaccine

International audienceNo abstract availabl

Renal cortical volume: High correlation with pre- and post-operative renal function in living kidney donors

International audienc

GZMB+ B cells, a key factor of cell immunity in human?

International audienc

EARLY EXPANSION OF TEMRA CD8 WITH INNATE-LIKE FUNCTION IDENTIFIES KIDNEY TRANSPLANT RECIPIENTS AT HIGH-RISK OF GRAFT FAILURE

Lola Jacquemont and Gaëlle Tilly are co-authorsInternational audienceAs CD8 TEMRA cells are associated with higher risk of long-term graft dysfunction, in this study, we evaluate if the monitoring of CD8-related biomarkers could improve the prognostic capacities of a clinical-based scoring system (Kidney Transplant Failure Score; KTFS). We also characterize the functionality of TEMRA and especially their reactivity upon donor-specific stimulation. 286 kidney-transplant recipients prospectively enrolled were followed for more than 8-years. 51 return in dialysis. We demonstrate that the frequency of early memory CD8 cells (EM) and TEMRA measured at 1-year post-transplantation is correlated with the risk to return in dialysis during time. For patients at high-risk of long-term graft dysfunction (according to KTFS), the use of one-year TEMRA frequency allows the discrimination of patients that will lose their graft from those that will not. Donor-specific reactivities from TEMRA and EM were similar with an early expression of CD25+CD69+CD107a+ and the high secretion of pro-inflammatory and cytotoxic molecules. Importantly, we identify an innate-like signature of TEMRA, with more than 5-fold higher expression of FCGR3A (CD16) by TEMRA as compared to NAIVE and EM. Cross-linking of CD16 triggers the secretion of TNFa and IFNg by TEMRA and their cytotoxic function and was further enhanced by the provision of IL-15. Finally, we demonstrate TEMRA and not EM display in vitro Antibody Dependent Cell Cytotoxicity conferring to TEMRA features of both adaptive and innate-like immunity and showing that anti-HLA antibodies, a major risk factor for long-term allograft outcome, could activate TEMRA in a TCR-independent manner leading to the inflammatory response

EARLY EXPANSION OF TEMRA CD8 WITH INNATE-LIKE FUNCTION IDENTIFIES KIDNEY TRANSPLANT RECIPIENTS AT HIGH-RISK OF GRAFT FAILURE

Lola Jacquemont and Gaëlle Tilly are co-authorsInternational audienceAs CD8 TEMRA cells are associated with higher risk of long-term graft dysfunction, in this study, we evaluate if the monitoring of CD8-related biomarkers could improve the prognostic capacities of a clinical-based scoring system (Kidney Transplant Failure Score; KTFS). We also characterize the functionality of TEMRA and especially their reactivity upon donor-specific stimulation. 286 kidney-transplant recipients prospectively enrolled were followed for more than 8-years. 51 return in dialysis. We demonstrate that the frequency of early memory CD8 cells (EM) and TEMRA measured at 1-year post-transplantation is correlated with the risk to return in dialysis during time. For patients at high-risk of long-term graft dysfunction (according to KTFS), the use of one-year TEMRA frequency allows the discrimination of patients that will lose their graft from those that will not. Donor-specific reactivities from TEMRA and EM were similar with an early expression of CD25+CD69+CD107a+ and the high secretion of pro-inflammatory and cytotoxic molecules. Importantly, we identify an innate-like signature of TEMRA, with more than 5-fold higher expression of FCGR3A (CD16) by TEMRA as compared to NAIVE and EM. Cross-linking of CD16 triggers the secretion of TNFa and IFNg by TEMRA and their cytotoxic function and was further enhanced by the provision of IL-15. Finally, we demonstrate TEMRA and not EM display in vitro Antibody Dependent Cell Cytotoxicity conferring to TEMRA features of both adaptive and innate-like immunity and showing that anti-HLA antibodies, a major risk factor for long-term allograft outcome, could activate TEMRA in a TCR-independent manner leading to the inflammatory response

Terminally Differentiated Effector Memory CD8+ T Cells Identify Kidney Transplant Recipients at High Risk of Graft Failure

International audienceSignificance Statement Identifying biomarkers for predicting kidney transplant failure requires better understanding of the immune response to chronic allogeneic stimulation. The authors demonstrated that 1 year after kidney transplantation, the composition of CD8 + memory T cell subsets in blood—specifically the ratio of terminally differentiated effector memory (TEMRA) and effector memory CD8 + T cells—is associated with risk for subsequent graft failure and adds predictive value to a previously reported eight-variable clinical risk score. They also found that TEMRA CD8 + T cells display a novel T cell receptor–independent mechanism of activation that is mediated through CD16 engagement and results in inflammation and antibody-dependent cellular cytotoxicity. These findings suggest a pivotal role for TEMRA CD8 + T cells in chronic humoral and cellular rejection leading to kidney transplant failure. Future clinical benefits may include the use of CD8 + memory T cell monitoring to improve risk prediction for graft failure and development of therapeutic strategies targeting TEMRA CD8 + T cells. Background Identifying biomarkers to predict kidney transplant failure and to define new therapeutic targets requires more comprehensive understanding of the immune response to chronic allogeneic stimulation. Methods We investigated the frequency and function of CD8 + T cell subsets—including effector memory (EM) and terminally differentiated EM (TEMRA) CD8 + T cells—in blood samples from 284 kidney transplant recipients recruited 1 year post-transplant and followed for a median of 8.3 years. We also analyzed CD8 + T cell reactivity to donor-specific PBMCs in 24 patients who had received living-donor kidney transplants. Results Increased frequency of circulating TEMRA CD8 + T cells at 1 year post-transplant associated with increased risk of graft failure during follow-up. This association remained after adjustment for a previously reported composite of eight clinical variables, the Kidney Transplant Failure Score. In contrast, increased frequency of EM CD8 + T cells associated with reduced risk of graft failure. A distinct TEMRA CD8 + T cell subpopulation was identified that was characterized by expression of Fc γ RIIIA (CD16) and by high levels of proinflammatory cytokine secretion and cytotoxic activity. Although donor-specific stimulation induced a similar rapid, early response in EM and TEMRA CD8 + T cells, CD16 engagement resulted in selective activation of TEMRA CD8 + T cells, which mediated antibody-dependent cytotoxicity. Conclusions At 1 year post-transplant, the composition of memory CD8 + T cell subsets in blood improved prediction of 8-year kidney transplant failure compared with a clinical-variables score alone. A subpopulation of TEMRA CD8 + T cells displays a novel dual mechanism of activation mediated by engagement of the T-cell receptor or of CD16. These findings suggest that TEMRA CD8 + T cells play a pivotal role in humoral and cellular rejection and reveal the potential value of memory CD8 + T cell monitoring for predicting risk of kidney transplant failure