Acute Kidney Injury (AKI) is strongly associated with adverse outcome and mortality independently of the cause of renal damage [1][2][3] . The mechanisms determining the deleterious systemic effects of AKI are poorly understood and specific interventions, including optimization of renal replacement therapy, had a marginal effect on AKI-associated mortality in clinical trials [4][5][6][7][8] . The kidney contributes to up to 40% of systemic glucose production by gluconeogenesis during fasting and stress conditions, mainly synthesized from lactate in the proximal tubule [9][10][11][12] , rendering this organ a major systemic lactate disposal 13 . Whether kidney gluconeogenesis is impaired during AKI and how this might influence systemic metabolism remains unknown. Here we demonstrate that glucose production and lactate clearance are impaired during human AKI using renal arteriovenous catheterization in patients. Using single cell transcriptomics in mice and RNA sequencing in human biopsies, we show that glycolytic and gluconeogenetic pathways are modified during AKI in the proximal tubule specifically, explaining the metabolic alterations. We further demonstrate that impaired renal gluconeogenesis and lactate clearance during AKI are major determinants of systemic glucose and lactate levels in critically ill patients. Most importantly, altered glucose metabolism in AKI emerged as a major determinant of AKIassociated mortality. Thiamine supplementation restored renal glucose metabolism and substantially reduced AKI-associated mortality in intensive care patients. This study highlights an unappreciated systemic role of renal glucose and lactate metabolism in stress conditions, delineates general mechanisms explaining AKI-associated mortality and introduces a potential therapeutic intervention for a highly prevalent clinical condition with limited therapeutic options.To study the impact of AKI on renal glucose and lactate metabolism, we performed renal vein catheterization in patients undergoing cardiac surgery with cardiopulmonary bypass and experiencing (n=18) or not (n=87) post-operative AKI (Supplementary Table 1). We found a switch from net renal lactate uptake to net renal lactate release in patients experiencing AKI (-0.01±0.03 mmol/min to 0.02±0.02 mmol/min, p<0.001). Moreover, AKI patients showed a decrease in the renal net glucose release (0.06±0.07 mmol/min to 0.01±0.04 mmol/min, p=0.016) compared to the control group (Fig. 1 a,b). This suggested a simultaneous reduction of gluconeogenesis and activation of glycolysis in the kidney in response to AKI. Glycosuria was unlikely to be involved since all patients had arterial glucose levels below the glycosuria threshold (5.4 ± 0.94 mmol/L). To further characterize this process, we compared kidney allograft biopsies obtained during transplantation shortly (49±16 minutes) after

Early RRT initiation strategy was not associated with any improvement of 60-day mortality in patients with severe acute kidney injury and septic shock or ARDS. Unnecessary and potentially risky procedures might often be avoided in these fragile populations. Clinical trial registered with www.clinicaltrials.gov (NCT 01932190).

Disseminated toxoplasmosis is infrequent after kidney transplant transmission but life‐threatening because of a lack of diagnostic suspicion as well as specific chemoprophylaxis recommendations. Solid organ transplantation has resulted in few cases of disseminated toxoplasmosis presenting with associated hemophagocytic syndrome. Herein, we report, within the context of a donor/receiver mismatch, a case of a toxoplasmosis associated with hemophagocytic syndrome in a kidney transplant recipient. Molecular and serological investigations confirmed Toxoplasma gondii transmission through the kidney graft.

Both intraoperative peak inspiratory pressure and FiO are independent factors significantly associated with development of a postoperative pulmonary complication in emergency laparotomy patients. Further studies are required to identify causality and to demonstrate if their manipulation could lead to better clinical outcomes.

ImportanceGiven the high risk of thrombosis and anticoagulation-related bleeding in patients with hypoxemic COVID-19 pneumonia, identifying the lowest effective dose of anticoagulation therapy for these patients is imperative.ObjectivesTo determine whether therapeutic anticoagulation (TA) or high-dose prophylactic anticoagulation (HD-PA) decreases mortality and/or disease duration compared with standard-dose prophylactic anticoagulation (SD-PA), and whether TA outperforms HD-PA; and to compare the net clinical outcomes among the 3 strategies.Design, Settings, and ParticipantsThe ANTICOVID randomized clinical open-label trial included patients with hypoxemic COVID-19 pneumonia requiring supplemental oxygen and having no initial thrombosis on chest computer tomography with pulmonary angiogram at 23 health centers in France from April 14 to December 13, 2021. Of 339 patients randomized, 334 were included in the primary analysis—114 patients in the SD-PA group, 110 in the HD-PA, and 110 in the TA. At randomization, 90% of the patients were in the intensive care unit. Data analyses were performed from April 13, 2022, to January 3, 2023.InterventionsPatients were randomly assigned (1:1:1) to receive either SD-PA, HD-PA, or TA with low-molecular-weight or unfractionated heparin for 14 days.Main Outcomes and MeasuresA hierarchical criterion of all-cause mortality followed by time to clinical improvement at day 28. Main secondary outcome was net clinical outcome at day 28 (composite of thrombosis, major bleeding, and all-cause death).ResultsAmong the study population of 334 individuals (mean [SD] age, 58.3 [13.0] years; 226 [67.7%] men and 108 [32.3%] women), use of HD-PA and SD-PA had similar probabilities of favorable outcome (47.3% [95% CI, 39.9% to 54.8%] vs 52.7% [95% CI, 45.2% to 60.1%]; P = .48), as did TA compared with SD-PA (50.9% [95% CI, 43.4% to 58.3%] vs 49.1% [95% CI, 41.7% to 56.6%]; P = .82) and TA compared with HD-PA (53.5% [95% CI 45.8% to 60.9%] vs 46.5% [95% CI, 39.1% to 54.2%]; P = .37). Net clinical outcome was met in 29.8% of patients receiving SD-PA (20.2% thrombosis, 2.6% bleeding, 14.0% death), 16.4% receiving HD-PA (5.5% thrombosis, 3.6% bleeding, 11.8% death), and 20.0% receiving TA (5.5% thrombosis, 3.6% bleeding, 12.7% death). Moreover, HD-PA and TA use significantly reduced thrombosis compared with SD-PA (absolute difference, −14.7 [95% CI −6.2 to −23.2] and −14.7 [95% CI −6.2 to −23.2], respectively). Use of HD-PA significantly reduced net clinical outcome compared with SD-PA (absolute difference, −13.5; 95% CI −2.6 to −24.3).Conclusions and RelevanceThis randomized clinical trial found that compared with SD-PA, neither HD-PA nor TA use improved the primary hierarchical outcome of all-cause mortality or time to clinical improvement in patients with hypoxemic COVID-19 pneumonia; however, HD-PA resulted in significantly better net clinical outcome by decreasing the risk of de novo thrombosis.Trial RegistrationClinicalTrials.gov Identifier: NCT04808882

No abstract

Background Malignant hypertension is macrovascular and microvascular endothelial injury responsible for multiple organ damage. Considering the anatomical and functional homologies between the posterior pole of the eye and the kidney, ophthalmological explorations may inform clinicians on the mechanisms underpinning concurrent kidney injury in this condition. More specifically, we investigated whether the wall-to-lumen ratio (WLR) of retinal arterioles measured by adaptive optics ophthalmoscopy could be correlated to WLR of kidney arterioles as determined by pathology. We sought to estimate the incidence of retinal arteriole occlusion a supposedly uncommon complication of malignant hypertension Methods All patients hospitalized in our renal Intensive Care Unit for malignant hypertension between 2016 and 2019 were referred to ophthalmological examinations Results Twenty-seven patients were included. Median retinal WLR was 0.39 [0.31-0.47] and was correlated with initial systolic (r=0.56, p=0.003) and mean blood pressure (r=0.46, p=0.02) upon admission. The retinal WLR was not correlated to renal pathological findings, as assessed by juxtaglomerular WLR (r=0.38, p=0.2), ratio of glomerulosclerosis (r=-0.39, p=0.2) or tubulo-interstitial fibrosis (r=-0.45, p=0.08). Retinal WLR was not associated with neurological or cardiovascular end-organ damage. Branch retinal artery occlusion were detected in 18.5% of patients and exudative retinal detachment in 29.6% of patients, without any significant correlation with canonical signs of retinal hypertension including optic disc swelling Conclusions In the setting of malignant hypertension, we failed to demonstrate a significant relationship between WLR and other meaningful end-organ injuries. However, branch retinal artery occlusion and exudative retinal detachment may have been hitherto underestimated

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.