Détermination du débit de filtration glomérulaire au cours de la drépanocytose au Sénégal: Schwartz, Cockcroft et Gault, MDRD, CKD-EPI ou JSCCS ?

La détermination du Débit de Filtration Glomérulaire (DFG) est importante chez les drépanocytaires du fait qu’ils constituent un groupe de patients chez lesquels des atteintes rénales sont fréquemment décrites notamment l’hyperfiltration glomérulaire. Dès lors, à une époque où les calculateurs en ligne proposent simultanément différentes formules de détermination du DFG, il serait important d’évaluer au sein d’une population noire africaine drépanocytaire l’équivalence entre ces formules qui ont été développées et validées sur des populations caucasiennes et afro-américaines à DFG normal ou diminué. Ainsi cette étude avait pour but d’évaluer l’interchangeabilité des différentes formules de détermination du DFG en les appliquant à des drépanocytaires. Des enfants et adultes sénégalais drépanocytaires homozygotes ont été alors recrutés et leur DFG calculé. La fréquence de l’hyperfiltration glomérulaire et celle de l’insuffisance rénale ont été calculées à partir des résultats obtenus avec les formules de Schwartz et du CKD-EPI. La concordance des différentes formules a été évaluée avec la méthode Bland-Altman. Au total 56 adultes et 62 enfants ont été inclus dans l’étude. L’insuffisance rénale a été notée chez 1,78% des adultes et 9,68% des enfants ; l’hyperfiltration glomérulaire chez 66,10% des adultes et 25,8% des enfants. Par rapport aux formules de référence (CKD-EPI, Schwartz), tous les biais relevés étaient significativement différents de zéro à l’exception de celui de Cockcroftet Gault qui était statistiquement nul. Les limites de concordance étaient toutes inacceptablement larges par rapport aux limites attendues à l’exception de celles du CKD-EPI sans ajustement sur la race. Ainsi, la formule de Schwartz n’était pas interchangeable avec celle du JSCCS chez les enfants, tout comme celle du CKD-EPI ne l’était pas non plus avec celles du JSCCS, de Cockcroft, du MDRD ou du CKD-EPI sans ajustement sur la race chez les adultes drépanocytaires.   English title: Determination of glomerular filtration rate in sickle cell disease in Senegal: Schwartz, Cockcroft and Gault, MDRD, CKD-EPI or JSCCS? Determination of Glomerular Filtration Rate (GFR) is important in patients living with sickle cell disease (SCD) because they constitute a group of patients where kidney dysfunction is frequently described, in particular glomerular hyperfiltration. Therefore, at a time when online calculators simultaneously propose different formulas to estimate GFR, it would be important to evaluate in a black African population living with SCD the equivalence between these formulas which have been developed and validated on Caucasian and African American populations with normal or decreased GFR. Thus, the aim of this study was to evaluate interchangeability of different GFR formulas in a group of patients living with SCD. Homozygous Senegalese sickle cell children and adults were then recruited and their GFR computed using Schwartz and JSCCS in children, Cockcroft and Gault, CKD-EPI with and without adjustment for ethnicity, MDRD and JSCCS formulas in adults. The frequency of glomerular hyperfiltration and renal failure was computed based on the results generated using Schwartz and CKD-EPI formulas. The agreement between formulas was assessed with BlandAltman method. A total of 56 adults and 62 children were included in this study. Renal failure was observed in 1.78% of adults and 9.68% of children; glomerular hyperfiltration in 66.10% of adults and 25.8% of children. Compared with reference formulas (CKD-EPI, Schwartz), all biases found were significantly different from zero except for Cockcroft and Gault formula bias, which was statistically zero. The limits of agreement were all unacceptably wide compared with the expected limits with the exception of CKD-EPI without adjustment for ethnicity. Thus, Schwartz formula would not be interchangeable with JSCCS formula in children, nor was the CKD-EPI formula interchangeable with the JSCCS, Cockcroft and Gault, MDRD or CKD-EPI without adjustment for ethnicity formulas in adults living with sickle cell anemia

Intermittent preventive treatment of malaria in infants: how does it work and where will it work?

We discuss the potential public health impact of IPTi by estimating the cases of malaria, anaemia and hospital admissions likely to be averted in different transmission settings; and we review the mechanism of action, choice of drugs regimens, and the effect on immunity of IPTi. IPTi using an efficacious drug is likely to substantially reduce cases of clinical malaria in moderate to high transmission settings. However, geographical heterogeneity in malaria transmission could hamper rolling out IPTi as a national policy

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field