Kidney Increase Natriuresis but Not Glomerular Filtration Under Veno-venous ECMO, a Retrospective Study.

PURPOSE: Acute kidney injury is a frequent complication of acute respiratory distress syndrome (ARDS). We aim to study the evolution of kidney function in patients presenting severe ARDS and requiring veno-venous extracorporeal membrane oxygenation (VV ECMO). METHODS: We conducted a multicenter retrospective study, including adult patients requiring VV ECMO for ARDS. The primary outcome was the evolution of the serum creatinine level after VV ECMO initiation. Secondary outcomes were change in urine output, and urine biochemical parameters after VV ECMO initiation. RESULTS: One hundred and two patients were included. VV ECMO was initiated after a median of 6 days of mechanical ventilation, mainly for ARDS caused by COVID-19 (73%). Serum creatinine level did not significantly differ after VV ECMO initiation (P = .20). VV ECMO was associated with a significant increase in daily urine output (+6.6 mL/kg/day, [3.8;9.3] P < .001), even after adjustment for potential confounding factors; with an increase in natriuresis. The increase in urine output under VV ECMO was associated with a reduced risk of receiving kidney replacement therapy (OR 0.4 [0.2;0.8], P = .026). CONCLUSIONS: VV ECMO initiation in severe ARDS is associated with an increase in daily urine output and natriuresis, without change in glomerular filtration rate.

Anaesthesia-Induced Transcriptomic Changes in the Context of Renal Ischemia Uncovered by the Use of a Novel Clamping Device.

Ischemia is a common cause of acute kidney injury worldwide, frequently occurring in patients undergoing cardiac surgery or admitted to the intensive care unit (ICU). Thus, ischemia-reperfusion injury (IRI) remains one of the main experimental models for the study of kidney diseases. However, the classical technique, based on non-traumatic surgical clamps, suffers from several limitations. It does not allow the induction of multiple episodes of acute kidney injury (AKI) in the same animal, which would be relevant from a human perspective. It also requires a deep and long sedation, raising the question of potential anaesthesia-related biases. We designed a vascular occluding device that can be activated remotely in conscious mice. We first assessed the intensity and the reproducibility of the acute kidney injury induced by this new device. We finally investigated the role played by the anaesthesia in the IRI models at the histological, functional and transcriptomic levels. We showed that this technique allows the rapid induction of renal ischemia in a repeatable and reproducible manner, breaking several classical limitations. In addition, we used its unique specificities to highlight the renal protective effect conferred by the anaesthesia, related to the mitigation of the IRI transcriptomic program.

Inappropriate Heart Rate Response to Hypotension in Critically Ill COVID-19-Associated Acute Kidney Injury.

Angiotensin-converting enzyme 2 (ACE2) receptor of severe acute respiratory syndrome coronavirus 2 is involved in baroreflex control mechanisms. We hypothesize that severe coronavirus infectious disease 2019 (COVID-19) patients may show an alteration in baroreflex-mediated heart rate changes in response to arterial hypotension. A pilot study was conducted to assess the response to hypotension in relation to continuous venovenous hemodiafiltration (CVVHDF) in critically ill patients with PCR-confirmed COVID-19 (from February to April 2020) and in critically ill non-COVID-19 patients with sepsis (from February 2018 to February 2020). The endpoint was a change in the heart rate in response to CVVHDF-induced hypotension. The association between COVID-19 status and heart rate change was estimated using linear regression. The study population included 6 COVID-19 patients (67% men; age 58 (53-64) years) and 12 critically ill non-COVID-19 patients (58% men; age 67 (51-71) years). Baseline characteristics, laboratory findings, hemodynamic parameters, and management before CVVHDF-induced hypotension were similar between the two groups, with the exception of a higher positive end-expiratory pressure and doses of propofol and midazolam administered in COVID-19 patients. Changes in the heart rate were significantly lower in COVID-19 patients as compared to critically ill non-COVID-19 patients (-7 (-9; -2) vs. 2 (2;5) bpm, p = 0.003), while the decrease in mean arterial blood pressure was similar between groups. The COVID-19 status was independently associated with a lower change in the heart rate (-11 (-20; -2) bpm; p = 0.03). Our findings suggest an inappropriate heart rate response to hypotension in severe COVID-19 patients compared to critically ill non-COVID-19 patients.

Retinal Arteriolar Occlusions and Exudative Retinal Detachments in Malignant Hypertension: More Than Meets the Eye.

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 tubulointerstitial fibrosis (r = -0.45, P = 0.08). Retinal WLR was not associated with neurological or cardiovascular end-organ damage. Branch retinal artery occlusion was detected in 18.5% of patients and exudative retinal detachment (ERD) 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 ERD may have been hitherto underestimated.

Author Correction: Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Altered proximal tubular cell glucose metabolism during acute kidney injury is associated with mortality.

Acute kidney injury (AKI) is strongly associated with mortality, independently of its cause. The kidney contributes to up to 40% of systemic glucose production by gluconeogenesis during fasting and under stress conditions. Whether kidney gluconeogenesis is impaired during AKI and how this might influence systemic metabolism remain unknown. Here we show that glucose production and lactate clearance are impaired during human and experimental AKI by using renal arteriovenous catheterization in patients, lactate tolerance testing in mice and glucose isotope labelling in rats. Single-cell transcriptomics reveal that gluconeogenesis is impaired in proximal tubule cells during AKI. In a retrospective cohort of critically ill patients, we demonstrate that altered glucose metabolism during AKI is a major determinant of systemic glucose and lactate levels and is strongly associated with mortality. Thiamine supplementation increases lactate clearance without modifying renal function in mice with AKI, enhances glucose production by renal tubular cells ex vivo and is associated with reduced mortality and improvement of the metabolic pattern in a retrospective cohort of critically ill patients with AKI. This study highlights an unappreciated systemic role of renal glucose and lactate metabolism under stress conditions, delineates general mechanisms of AKI-associated mortality and introduces a potential intervention targeting metabolism for a highly prevalent clinical condition with limited therapeutic options.

Disseminated toxoplasmosis associated with hemophagocytic syndrome after kidney transplantation: A case report and review.

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.

Timing of Renal Support and Outcome of Septic Shock and Acute Respiratory Distress Syndrome. A Post Hoc Analysis of the AKIKI Randomized Clinical Trial.

RATIONALE: The optimal strategy for initiation of renal replacement therapy (RRT) in patients with severe acute kidney injury in the context of septic shock and acute respiratory distress syndrome (ARDS) is unknown. OBJECTIVES: To examine the effect of an early compared with a delayed RRT initiation strategy on 60-day mortality according to baseline sepsis status, ARDS status, and severity. METHODS: Post hoc analysis of the AKIKI (Artificial Kidney Initiation in Kidney Injury) trial. MEASUREMENTS AND MAIN RESULTS: Subgroups were defined according to baseline characteristics: sepsis status (Sepsis-3 definition), ARDS status (Berlin definition), Simplified Acute Physiology Score 3 (SAPS 3), and Sepsis-related Organ Failure Assessment (SOFA). Of 619 patients, 348 (56%) had septic shock and 207 (33%) had ARDS. We found no significant influence of the baseline sepsis status (P = 0.28), baseline ARDS status (P = 0.94), and baseline severity scores (P = 0.77 and P = 0.46 for SAPS 3 and SOFA, respectively) on the comparison of 60-day mortality according to RRT initiation strategy. A delayed RRT initiation strategy allowed 45% of patients with septic shock and 46% of patients with ARDS to escape RRT. Urine output was higher in the delayed group. Renal function recovery occurred earlier with the delayed RRT strategy in patients with septic shock or ARDS (P < 0.001 and P = 0.003, respectively). Time to successful extubation in patients with ARDS was not affected by RRT strategy (P = 0.43). CONCLUSIONS: 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).

[Renal replacement therapy for acute kidney injury in the intensive care unit]. / Épuration extrarénale et insuffisance rénale aiguë en soins intensifs.

Renal replacement therapy for acute kidney injury has been used for more than 60 years. Except when life-threatening metabolic complications such as severe hyperkalaemia are present, renal replacement therapy initiation criteria are the subject of intense debate. Significant progress has been made with the publication of the AKIKI multicenter trial, which showed that a delayed renal replacement therapy initiation strategy (in the absence of life-threatening metabolic complications) was not associated with a difference in mortality compared to an early renal replacement therapy initiation strategy. In addition, this delayed strategy obviated the need for renal replacement therapy in almost 50% of cases was associated with a more rapid renal function recovery and with a lower incidence of catheter-bloodstream related infections. Research on renal replacement therapy modalities (continuous vs. intermittent renal replacement therapy, citrate vs. heparin anticoagulation, jugular vs. femoral catheterization) did not show any obvious superiority of one modality over another. Thus, the choice depends mainly on local considerations (patient recruitment, availability of modalities, staff experience). The criteria for renal replacement therapy discontinuation are still unclear due to difficulties in assessing renal function recovery. Urine output remains the main criteria in the decision to wean from renal replacement therapy. Pending the confirmation of AKIKI trial by similar studies in progress, it seems reasonable to choose a delayed renal replacement therapy initiation strategy under watchful surveillance in case of severe acute kidney injury in the absence of life-threatening metabolic complications.