No abstract

Acute kidney injury (AKI) is one of the most important complications in COVID-19 patients and is considered a negative prognostic factor with respect to patient survival. The occurrence of direct infection of the kidney by SARS-CoV-2, and its contribution to the renal deterioration process, remains a controversial issue. By studying 32 renal biopsies from COVID-19 patients we confirmed that the major pathological feature of COVID-19 is acute tubular injury (ATI).Using smFISH, we showed that the SARS-CoV-2 infects living renal cells and that infection, which parallels renal ACE2 expression levels, is associated to increase death. Mechanistically, a transcriptomic analysis uncovered specific molecular signatures in SARS-CoV-2 infected kidneys as compared to healthy kidneys and non-COVID-19 ATI kidneys. On the other hand, we demonstrated that SARS-CoV-2 and Hantavirus, two RNA viruses, activated different genetic networks despite they triggered the same pathological lesions. Finally, we identified XAF1 as a critical target of SARS-CoV-2 infection. In conclusion, this study demonstrates that SARS-CoV2 can directly infect living renal cells and identified specific druggable molecular targets that can potentially aid in the design of novel therapeutic strategies to preserve renal function in severely affected COVID-19 patients.

Background Renal arcuate vein thrombosis (RAVT) is a rare and recently recognized cause of acute kidney injury (AKI) in young adults. However, the precise incidence and underlying pathophysiologic mechanisms leading to AKI in these patients remain elusive. Methods This study included all patients who underwent a kidney biopsy over a 40-month period sent to the pathology department of Necker-Enfants Malades Hospital, with evidence of RAVT. We performed coagulation tests, genetic testing for thrombophilia, complete urine toxicologic screening and kidney metagenomic sequencing to identify an underlying cause of thrombosis. Results We report five pediatric cases of RAVT discovered on kidney biopsy performed in the setting of unexplained AKI. Investigations did not reveal an underlying cause of thrombosis but only a significant NSAIDs use was reported in 4/5 patients supporting a potential link between NSAIDs use and RAVT. By performing metagenomic sequencing on kidney biopsy samples, we detected SARS-CoV-2 RNA in the kidney of one patient. These results suggest that systemic SARS-CoV-2 infection may also be a key contributing factor of renal thrombosis, particularly by inducing potential endothelial disruption. Conclusions In conclusion, RAVT-induced AKI appears to be a multiple-Hit-mediated disease in which NSAIDs consumption and viral infection such as SARS-COV-2 may be crucial contributing factors. These findings may have significant public health implications given the prevalence of NSAIDs use in the general population. Increased awareness and additional study of future cases may lead to a better understanding of this rare cause of AKI in children and young adults.

L’insuffisance rénale chronique est une définition biologique caractérisée par la diminution du débit de filtration glomérulaire. Quelle qu’en soit la cause initiale, son origine est toujours une réduction néphronique, une diminution du nombre d’unités fonctionnelles du rein, appelées néphrons. Après une agression rénale initiale, les néphrons sains restants vont assurer la filtration permettant le maintien d’une fonction rénale normale. Mais, progressivement, ces néphrons vont s’altérer et vont être remplacés par du tissu fibreux. Cette altération du parenchyme va entraîner un ensemble de symptômes biologiques et histologiques réunis sous le terme de maladie rénale chronique : augmentation de la créatininémie, protéinurie, glomérulosclérose et fibrose interstitielle.