Animal models to study cognitive impairment of chronic kidney disease.

Mild cognitive impairment (MCI) is common in people with chronic kidney disease (CKD) and its prevalence increases with progressive loss of kidney function. MCI is characterized by a decline in cognitive performance greater than expected for an individual age and education level but with minimal impairment of instrumental activities of daily living. Deterioration can affect one or several cognitive domains (attention, memory, executive functions, language, and perceptual motor or social cognition). Given the increasing prevalence of kidney disease, more and more people with CKD will also develop MCI causing an enormous disease burden for these individuals, their relatives and society. However, the underlying pathomechanisms are poorly understood and current therapies mostly aim at supporting patients in their daily life. This illustrates the urgent need to elucidate the pathogenesis, and potential therapeutic targets and test novel therapies in appropriate preclinical models. Here, we will outline the necessary criteria for experimental modelling of cognitive disorders in CKD. We discuss the use of mice, rats and zebrafish as model systems and present valuable techniques through which kidney function and cognitive impairment can be assessed in this setting. Our objective is to enable researchers to overcome hurdles and accelerate preclinical research aimed at improving therapy of people with CKD and MCI.

Acute and chronic kidney dysfunction and prognosis following thrombectomy for ischemic stroke.

INTRODUCTION: Patients with Chronic Kidney Disease (CKD) have an increased risk of stroke and CKD seems associated with worse outcome after a stroke. The main objective of our study RISOTTO was to evaluate the influence of CKD and Acute Kidney Injury (AKI) on the clinical outcome and mortality of ischemic stroke patients after thrombolysis and/or thrombectomy. METHODS: This multicenter cohort study included patients in the acute phase of ischemic stroke due to a large artery occlusion managed by thrombectomy. Functional outcome at 3 months was assessed by modified Rankin Scale (mRS). RESULTS: 280 patients were included in the analysis. Fifty-nine patients (22.6%) had CKD. At 3 months, CKD was associated with similar functional prognosis (mRS 3-6: 50.0% vs. 41.7%, p=0.262) but higher mortality: 24.2% vs. 9.5%, p=0.004. In univariate analysis, patients with CKD had a higher burden of white matter hyperintensities (Fazekas 1.7±0.8 vs. 1.0±0.8, p=0.002), lower initial infarcted volume with equivalent severity, and lower recanalization success (86.4% vs. 97.0%, p=0.008) compared to non-CKD patients. Forty-seven patients (20.0%) developed AKI. AKI was associated with poorer 3-month functional outcome (mRS 3-6: 63.8% vs. 49.0%, p=0.002) and mortality: 23.4% vs. 7.7%, p=0.002. In multivariate analysis, AKI appeared as an independent risk factor for poor functional outcome (mRS 3-6: adjOR 2.79 [1.11-7.02], p=0.029) and mortality: adjOR 2.52 [1.03-6.18], p=0.043 at 3 months, while CKD was not independently associated with 3-month mortality and poor neurological outcome. CONCLUSION: AKI is independently associated with poorer functional outcome and increased mortality at 3 months. CKD was not an independent risk factor for 3-month mortality or poor functional prognosis.

Assessment of epidemiology and outcomes of adult patients with kidney-limited thrombotic microangiopathies.

Thrombotic microangiopathies (TMA) are usually associated with hematological features (RH-TMA). The epidemiology of TMA limited to kidneys (RL-TMA) is unclear Therefore, patients with TMA and native kidney biopsies were identified during 2009-2022 in 20 French hospitals and results evaluated. RL-TMA was present in 341/757 (45%) patients and associated with lower creatinine levels (median 184 vs 346 µmol/L) than RH-TMA. RL-TMA resulted from virtually all identified causes, more frequently from anti-VEGF treatment and hematological malignancies but less frequently from shigatoxin-associated hemolytic uremic syndrome (HUS), systemic sclerosis, gemcitabine and bacterial infection, and even less frequently when three or more causes/triggers were combined (RL-TMA: 5%; RH-TMA: 12%). RL-TMA was associated with significantly lower major cardiovascular events (10% vs 20%), kidney replacement therapy (23% vs 43%) and death (12% vs 20%) than RH-TMA during follow-up (median 28 months). Atypical HUS (aHUS) was found in 326 patients (RL-TMA: 43%, RH-TMA: 44%). Among the 69 patients with proven complement-mediated aHUS, eculizumab (anti-C5 therapy) was used in 43 (62%) (RL-TMA: 35%; RH-TMA: 71%). Among the 257 other patients with aHUS, including 51% with RL-TMA, eculizumab was used in 29 but with unclear effects of this treatment. Thus, RL-TMA represents a very high proportion of patients with TMA and results from virtually all known causes of TMA and includes 25% of patients with complement-mediated aHUS. Adverse outcomes of RL-TMA are lower compared to RH-TMA but remain significant. Anti-C5 therapy was rarely used in RL-TMA, even in proven complement-mediated aHUS, and its effects remain to be assessed.

Diagnostic yield of exome sequencing in early onset hypertensive nephropathy in adults.

INTRODUCTION: Hypertensive nephrosclerosis (HN) ranks as one of the most frequent causes of chronic kidney disease (CKD), but its very existence has repeatedly been called into question, especially in young adults. Its diagnostic framework is established chiefly on non-specific clinical criteria and its defining histopathological set of features are in fact shared by numerous other conditions. Genetic testing based on exome sequencing (ES) has emerged as a comprehensive tool to detect Mendelian diseases in timely fashion in nephrology with a significant number of re-established diagnoses. The aim of this study was to investigate the diagnostic yield of ES in patients with a clinical diagnosis of hypertensive nephropathy. METHOD: Since September 2018, ES has been readily available as part of the routine diagnostic work-up in our institution. The indication of ES includes hypertensive nephropathy of early onset (i.e., < 45 years old). We retrospectively collected the ES data performed in the context of hypertensive nephropathy in our institution between September 2018 and February 2021. RESULTS: A total of 128 patients were sequenced in the context of hypertensive nephropathy with early onset. The chief indications of ES were an early onset of CKD (47%), family history of kidney disease (8%), or both (18%). We detected diagnostic variants in 19 of the 128 patients (15%) encompassing a total of 13 different monogenic disorders. The diagnostic yield of ES was lower in patients of African ancestry (diagnostic yield of 7% versus 30% in non-African ancestry patients, p<0.001). CONCLUSIONS: The high diagnostic yield of ES (15%) in a population of patients thought to have HN casts further doubts on the validity of the existing diagnosis criteria, including histological criteria, supposed to characterize the condition. This was especially true in patients with no African ancestry where ES positivity reached 30%.

Kidney biopsy for the diagnosis and treatment of kidney diseases. Recommendations from the French speaking Society of Nephrology (SFNDT) and French National Authority for Health (HAS) 2022

Kidney Biopsy (KB) is a crucial diagnostic tool in the field of renal diseases and is routinely performed in nephrology departments. A previous survey conducted by the Société Francophone de Néphrologie Dialyse Transplantation (SFNDT) revealed significant disparities in clinical practices, sometimes conflicting with the existing literature and recently published recommendations. In response, the SFNDT wished to promote the development of best practice guidelines, under the auspices of the French National Authority for Health (HAS), to establish a standardized framework for performing kidney biopsies in France.

La biopsie rénale (BR) est un outil diagnostique crucial dans le domaine des maladies rénales et est pratiquée en routine dans les services de néphrologie. Une précédente enquête menée par la Société francophone de néphrologie, dialyse et transplantation (SFNDT) a révélé d'importantes disparités dans les pratiques cliniques, parfois en contradiction avec la littérature existante et les recommandations récemment publiées. En réponse, la SFNDT a souhaité promouvoir l'élaboration de recommandations de bonnes pratiques, sous l'égide de la Haute Autorité de santé (HAS), afin d'établir un cadre standardisé pour la réalisation des biopsies rénales en France.

The highlights in nephrology in 2023 / Les temps forts en néphrologie en 2023

This article aims to summarize the "Quoi de neuf en néphrologie?" session held at the 2023 SFNDT Congress in Liège and sessions focused on updates regarding IgA nephropathy (NIgA) and ANCA-associated vasculitis. The agenda for the nephrology "Quoi de neuf en néphrologie?" session this year was to review key publications from non-nephrology journals, discussing topics such as nephroprotection, treatment of glomerulopathies (IgA and APOL1), clinical trials on arterial hypertension, urinary lithiasis, and other areas of renal physiology, including glomerular filtration rate estimation.

Cet article a pour but de résumer d'une part la session « Quoi de neuf en néphrologie ? ¼ qui a eu lieu au congrès de la Société francophone de néphrologie, dialyse et transplantation (SFNDT) 2023 à Liège en Belgique, mais également les sessions portant sur les actualités de la néphropathie à IgA (NIgA) et des vascularites associées aux anticorps anticytoplasme des polynucléaires neutrophiles (ANCA). Le cahier des charges du « Quoi de neuf en néphrologie ? ¼ cette année était de reprendre les principaux articles publiés dans des revues hors néphrologie et s'est articulé sur les publications autour de la néphroprotection, du traitement des glomérulopathies (IgA et APOL1), des essais cliniques sur l'hypertension artérielle ou dans la lithiase urinaire, ou dans d'autres champs de la physiologie rénale comme l'estimation du débit de filtration glomérulaire.

Kidney Transplantation in Patients With AA Amyloidosis: Outcomes in a French Multicenter Cohort.

RATIONALE & OBJECTIVE: Outcomes of kidney transplantation for patients with renal AA amyloidosis are uncertain, with reports of poor survival and high rates of disease recurrence. However, the data are inconclusive and mostly based on studies from the early 2000s and earlier. STUDY DESIGN: Retrospective multicenter cohort study. SETTING & PARTICIPANTS: We searched the French national transplant database to identify all patients with renal AA amyloidosis who underwent kidney transplantation between 2008 and 2018. EXPOSURES: Age, cause of amyloidosis, use of biotherapies, and C-reactive protein levels. OUTCOMES: Outcomes were all-cause mortality and allograft loss. We also reported amyloidosis allograft recurrence, occurrence of acute rejection episodes, as well as infectious, cardiovascular, and neoplastic disease events. ANALYTICAL APPROACH: Kaplan-Meier estimator for mortality and cumulative incidence function method for allograft loss. Factors associated with patient and allograft survival were investigated using a Cox proportional hazards model and a cause-specific hazards model, respectively. RESULTS: 86 patients who received kidney transplants for AA amyloidosis at 26 French centers were included. The median age was 49.4 years (IQR, 39.7-61.1). The main cause of amyloidosis was familial Mediterranean fever (37 cases; 43%). 16 (18.6%) patients received biotherapy after transplantation. Patient survival rates were 94.0% (95% CI, 89.1-99.2) at 1 year and 85.5% (77.8-94.0) at 5 years after transplantation. Cumulative incidences of allograft loss were 10.5% (4.0-17.0) at 1 year and 13.0% (5.8-20.1) at 5 years after transplantation. Histologically proven AA amyloidosis recurrence occurred in 5 transplants (5.8%). An infection requiring hospitalization developed in 55.8% of cases, and there was a 27.9% incidence of acute allograft rejection. Multivariable analysis showed that C-reactive protein concentration at the time of transplantation was associated with patient survival (HR, 1.01; 95% CI, 1.00-1.02; P=0.01) and allograft survival (HR, 1.68; 95% CI, 1.10-2.57; P=0.02). LIMITATIONS: The study lacked a control group, and the effect of biotherapies on transplantation outcomes could not be explored. CONCLUSIONS: This relatively contemporary cohort of patients who received a kidney transplant for AA amyloidosis experienced favorable rates of survival and lower recurrence rates than previously reported. These data support the practice of treating these patients with kidney transplantation for end-stage kidney disease. PLAIN-LANGUAGE SUMMARY: AA amyloidosis is a severe and rare disease. Kidney involvement is frequent and leads to end-stage kidney disease. Because of the involvement of other organs, these patients are often frail, which has raised concerns about their suitability for kidney transplantation. We reviewed all patients with AA amyloidosis nephropathy who underwent kidney transplantation in France in the recent era (2008-2018) and found that the outcomes after kidney transplantation were favorable, with 85.5% of patients still alive 5 years after transplantation, a survival rate that is comparable to the outcomes of patients receiving a transplant for other forms of kidney diseases. Recurrence of amyloidosis in the transplanted kidney was infrequent (5.8%). These data support the practice of kidney transplantation for patients with AA amyloidosis who experience kidney failure.

Cognitive impairment and the blood-brain barrier in chronic kidney disease: role of the uremic toxins / Atteinte neurocognitive et barrière hémato-encéphalique au cours de la maladie rénale chronique : rôle des toxines urémiques

Patients with chronic kidney disease (CKD) have an increased risk of cognitive disorders, presenting as vascular dementia, compared with the general population. These cognitive disorders occur early during the course of the kidney disease and evolve in parallel with the decline in glomerular filtration rate. They affect 30 to 80 % of patients with stage 5 CKD. Kidney transplantation only partially improves cognitive impairment. In this narrative review, we summarize the epidemiology and recent clinical and experimental data on cognitive impairment in CKD and discuss the potential specific mechanisms. Among the factors associated with cognitive impairment, the accumulation of uremic toxins such as indoxyl sulfate appears to be a specific risk factor for cognitive decline. These toxins have an endothelial toxicity that can disrupt the cerebral endothelium. The rupture of the blood-brain barrier (BBB) is a mechanism implicated in several neurodegenerative pathologies and systemic diseases with cerebral tropism. Recent experimental findings in CKD indicate that disruption of the BBB appears to be an important mechanism behind cognitive impairment in CKD. In murine models of CKD, increased BBB permeability is linked to memory impairment and aryl hydrocarbon receptor activation following accumulation of circulating indoxyl sulfate. This disruption of the BBB could also have harmful consequences for stroke susceptibility and drug neurotoxicity in CKD patients.

Les patients atteints de maladie rénale chronique (MRC) présentent un risque accru de troubles neurocognitifs par rapport à la population générale, se présentant sous la forme d'une démence vasculaire. Ces troubles cognitifs interviennent précocement dans la maladie rénale et évoluent en parallèle au déclin du débit de filtration glomérulaire. Ils concernent 30 à 80 % des patients au stade 5 de la MRC. La transplantation rénale n'améliore que partiellement les troubles cognitifs. Dans cette revue narrative, nous résumons l'épidémiologie et les données cliniques et expérimentales récentes sur les troubles cognitifs dans la MRC, et nous en abordons les mécanismes spécifiques potentiels. Parmi les facteurs associés aux atteintes cognitives, l'accumulation des toxines urémiques, comme l'indoxyl sulfate, apparaît comme un facteur de risque spécifique de déclin cognitif. Ces toxines possèdent une toxicité endothéliale pouvant perturber l'endothélium cérébral. La rupture de la barrière hémato-encéphalique (BHE) est un mécanisme impliqué dans plusieurs pathologies neuro-dégénératives et des maladies systémiques à tropisme cérébral. Les résultats de travaux expérimentaux récents dans la MRC indiquent que la rupture de la BHE semble être un mécanisme important des troubles cognitifs au cours de la MRC. Dans les modèles murins de MRC, la perméabilité accrue de la BHE est liée à l'atteinte de la mémoire et à l'activation d'Aryl hydrocarbon Receptor suite à l'accumulation d'indoxyl sufate circulant. Cette rupture de la BHE pourrait également avoir des conséquences néfastes sur la susceptibilité aux accidents vasculaires cérébraux (AVC) et à la neurotoxicité médicamenteuse chez les patients MRC.

Drugs with a negative impact on cognitive function (Part 1): chronic kidney disease as a risk factor.

People living with chronic kidney disease (CKD) frequently suffer from mild cognitive impairment and/or other neurocognitive disorders. This review in two parts will focus on adverse drug reactions resulting in cognitive impairment as a potentially modifiable risk factor in CKD patients. Many patients with CKD have a substantial burden of comorbidities leading to polypharmacy. A recent study found that patients seen by nephrologists were the most complex to treat because of their high number of comorbidities and medications. Due to polypharmacy, these patients may experience a wide range of adverse drug reactions. Along with CKD progression, the accumulation of uremic toxins may lead to blood-brain barrier (BBB) disruption and pharmacokinetic alterations, increasing the risk of adverse reactions affecting the central nervous system (CNS). In patients on dialysis, the excretion of drugs that depend on kidney function is severely reduced such that adverse and toxic levels of a drug or its metabolites may be reached at relatively low doses, unless dosing is adjusted. This first review will discuss how CKD represents a risk factor for adverse drug reactions affecting the CNS via (i) BBB disruption associated with CKD and (ii) the impact of reduced kidney function and dialysis itself on drug pharmacokinetics.

Chronic Myelomonocytic Leukemia Patients With Lysozyme Nephropathy and Renal Infiltration Display Markers of Severe Disease.

Introduction: Chronic myelomonocytic leukemia (CMML) is a hematologic disorder that is an overlap syndrome between myelodysplastic syndromes and myeloproliferative neoplasms, and can be associated with autoimmune and inflammatory diseases. This study aimed to describe kidney involvement in patients with CMML, their treatments, and outcomes. Methods: We conducted a French and American multicenter retrospective study in 15 centers, identifying patients with CMML with acute kidney injury (AKI), chronic kidney disease (CKD), and urine abnormalities. Results: Sixteen patients (males, n = 14; median age 76.5 years [71.9-83]) developed a kidney disease 6 months [1.6-25.6] after the diagnosis of CMML. At the time of kidney disease diagnosis, median urinary protein-to-creatinine ratio was 2 g/g [1.25-3.4], and median serum creatinine was 2.26 mg/dl [1.46-2.68]. Fourteen patients (87.5%) underwent a kidney biopsy, and the 2 main pathological findings were lysozyme nephropathy (56%) and renal infiltration by the CMML (37.5%). Ten patients received a new treatment following the CMML-associated kidney injury. Among patients with monitored kidney function, and after a median follow-up of 15 months [9.9-34.9], 4 patients had CKD stage 3, 4 had CKD stage 4, 1 had an end-stage kidney disease. In our patient series, 2 patients evolved to an acute myeloid leukemia (AML), and 5 died. Compared with 116 CMML controls, patients who had a kidney involvement had a higher monocyte count (P < 0.001), had more CMML-1 (P = 0.005), were more susceptible to develop an AML (P = 0.02), and were more eligible to receive a specific hematologic treatment, with hydroxyurea, or hypomethylating agents (P < 0.001), but no survival difference was seen between the 2 groups (P = 0.6978). Conclusion: In this cohort of patients with CMML with a kidney injury, the 2 most frequent renal complications were lysozyme-induced nephropathy and renal infiltration by the CMML. Kidney involvement should be closely monitored in patients with CMML.

Weaning Maintenance Therapy in Lupus Nephritis: For Whom, When, and How?

Lupus nephritis (LN) is one of the main determinants of the severity of systemic lupus erythematosus (SLE). LN flares can lead to organ damage with chronic kidney disease (CKD) or even end-stage kidney disease (ESKD) and impair patients' survival. The "treat-to-target" strategy, which aims at obtaining and maintaining remission or low disease activity of SLE to alleviate symptoms and prevent organ damage, also refers to the control of residual activity in the kidney. But damage in SLE can also come from treatments, and toxicities related to long-term use of treatments should be prevented. This may contribute to the frequent nonadherence in patients with SLE. The de-escalation or even weaning of treatments whenever possible, or "think-to-untreat" (T2U) strategy, is to be considered in patients with LN. This possibility of treatment weaning in LN was explored in retrospective cohorts, on the basis of long-term clinical remission. It was also proposed prospectively with a kidney-biopsy-based approach, combining clinical and pathologic remission to secure treatment weaning. The WIN-Lupus trial was the first randomized controlled trial comparing the continuation to the discontinuation of maintenance immunosuppressive therapy (IST) after 2 to 3 years in patients with LN in remission. It showed a higher risk of severe SLE flares in patients who discontinued treatment, but also a possibility of weaning without flare in some patients, who need to be better identified. We propose here a narrative review of the available literature on the weaning of treatment in LN and discuss how to secure a T2U strategy.

Kidney disease and stroke: epidemiology and potential mechanisms of susceptibility.

Patients with chronic kidney disease (CKD) have an increased risk of both ischaemic and haemorrhagic stroke compared with the general population. Both acute and chronic kidney impairment are independently associated with poor outcome after the onset of a stroke, after adjustment for confounders. End-stage kidney disease (ESKD) is associated with a 7- and 9-fold increased incidence of both ischaemic and haemorrhagic strokes, respectively, poorer neurological outcome and a 3-fold higher mortality. Acute kidney injury (AKI) occurs in 12% of patients with stroke and is associated with a 4-fold increased mortality and unfavourable functional outcome. CKD patients seem to have less access to revascularisation techniques like thrombolysis and thrombectomy despite their poorer prognosis. Even if CKD patients could benefit from these specific treatments in acute ischaemic stroke, their prognosis remains poor. After thrombolysis, CKD is associated with a 40% increased risk of intracerebral haemorrhage (ICH), a 20% increase in mortality and poorer functional neurological outcomes. After thrombectomy, CKD is not associated with ICH but is still associated with increased mortality, and AKI with unfavourable outcome and mortality. The beneficial impact of gliflozins on the prevention of stroke is still uncertain. Non-traditional risk factors of stroke, like uraemic toxins, can lead to chronic cerebrovascular disease predisposing to stroke in CKD, notably through an increase in the blood-brain barrier permeability and impaired coagulation and thrombosis mechanisms. Preclinical and clinical studies are needed to specifically assess the impact of these non-traditional risk factors on stroke incidence and outcomes, aiming to optimize and identify potential therapeutic targets.

Nephrosclerosis in young patients with malignant hypertension.

BACKGROUND: Nephrosclerosis is one of the histopathological consequences of severe or malignant hypertension (MH), some of the pathophysiology of which has been extrapolated from essential polygenetic arterial hypertension. Despite our recent description of unsuspected ciliopathies with MH, causes of MH in young patients with severe renal impairment are poorly understood. METHODS: To refine and better describe the MH phenotype, we studied clinical and prognostic factors in young patients receiving a kidney biopsy following their first episode of MH. Patients were identified retrospectively and prospectively from eight centres over a 35-year period (1985-2020). Keywords were used to retrospectively enrol patients irrespective of lesions found on renal biopsy. RESULTS: A total of 114 patients were included, 77 (67%) of whom were men, average age 34 years, 35% Caucasian and 34% African origin. An isolated clinical diagnosis of severe nephrosclerosis was suggested in only 52% of cases, with 24% primary glomerulopathies. Only 7% of patients had normal renal function at diagnosis, 25% required emergency dialysis and 21% were eventually transplanted. Mortality was 1% at the last follow-up. Independent prognostic factors significantly associated with renal prognosis (6-month dialysis) and predictive of end-stage renal disease were serum creatinine on admission {odds ratio [OR] 1.56 [95% confidence interval (CI) 1.34-1.96], P < .001} and renal fibrosis >30% [OR 10.70 (95% CI 1.53-112.03), P = .03]. Astonishingly, the presence of any thrombotic microangiopathy lesion on renal biopsy was an independent, protective factor [OR 0.14 (95% CI 0.02-0.60), P = .01]. The histopathological hallmark of nephrosclerosis was found alone in only 52% of study patients, regardless of ethnicity. CONCLUSIONS: This suggests that kidney biopsy might be beneficial in young patients with MH.

Ultra-lung-protective ventilation and biotrauma in severe ARDS patients on veno-venous extracorporeal membrane oxygenation: a randomized controlled study.

BACKGROUND: Ultra-lung-protective ventilation may be useful during veno-venous extracorporeal membrane oxygenation (vv-ECMO) for severe acute respiratory distress syndrome (ARDS) to minimize ventilator-induced lung injury and to facilitate lung recovery. The objective was to compare pulmonary and systemic biotrauma evaluated by numerous biomarkers of inflammation, epithelial, endothelial injuries, and lung repair according to two ventilator strategies on vv-ECMO. METHODS: This is a prospective randomized controlled study. Patients were randomized to receive during 48 h either ultra-lung-protective ventilation combining very low tidal volume (1-2 mL/kg of predicted body weight), low respiratory rate (5-10 cycles per minute), positive expiratory transpulmonary pressure, and 16 h of prone position or lung-protective-ventilation which followed the ECMO arm of the EOLIA trial (control group). RESULTS: The primary outcome was the alveolar concentrations of interleukin-1-beta, interleukin-6, interleukin-8, surfactant protein D, and blood concentrations of serum advanced glycation end products and angiopoietin-2 48 h after randomization. Enrollment was stopped for futility after the inclusion of 39 patients. Tidal volume, respiratory rate, minute ventilation, plateau pressure, and mechanical power were significantly lower in the ultra-lung-protective group. None of the concentrations of the pre-specified biomarkers differed between the two groups 48 h after randomization. However, a trend to higher 60-day mortality was observed in the ultra-lung-protective group compared to the control group (45 vs 17%, p = 0.06). CONCLUSIONS: Despite a significant reduction in the mechanical power, ultra-lung-protective ventilation during 48 h did not reduce biotrauma in patients with vv-ECMO-supported ARDS. The impact of this ventilation strategy on clinical outcomes warrants further investigation. Trial registration Clinical trial registered with www. CLINICALTRIALS: gov ( NCT03918603 ). Registered 17 April 2019.

Impact of Dexamethasone and Inhaled Nitric Oxide on Severe Acute Kidney Injury in Critically Ill Patients with COVID-19.

Background: Acute kidney injury (AKI) is the second most frequent condition after acute respiratory distress syndrome (ARDS) in critically ill patients with severe COVID-19 and is strongly associated with mortality. The aim of this multicentric study was to assess the impact of the specific treatments of COVID-19 and ARDS on the risk of severe AKI in critically ill COVID-19 patients. Methods: In this cohort study, data from consecutive patients older than 18 years admitted to 6 ICUs for COVID-19-related ARDS requiring invasive mechanical ventilation were included. The incidence and severity of AKI, defined according to the 2012 KDIGO definition, were monitored during the entire ICU stay until day 90. Patients older than 18 years admitted to the ICU for COVID-19-related ARDS requiring invasive mechanical ventilation were included. Results: 164 patients were included in the final analysis; 97 (59.1%) displayed AKI, of which 39 (23.8%) had severe stage 3 AKI, and 21 (12.8%) required renal replacement therapy (RRT). In univariate analysis, severe AKI was associated with angiotensin-converting enzyme inhibitors (ACEI) exposure (p = 0.016), arterial hypertension (p = 0.029), APACHE-II score (p = 0.004) and mortality at D28 (p = 0.008), D60 (p < 0.001) and D90 (p < 0.001). In multivariate analysis, the factors associated with the onset of stage 3 AKI were: exposure to ACEI (OR: 4.238 (1.307−13.736), p = 0.016), APACHE II score (without age) (OR: 1.138 (1.044−1.241), p = 0.003) and iNO (OR: 5.694 (1.953−16.606), p = 0.001). Prone positioning (OR: 0.234 (0.057−0.967), p = 0.045) and dexamethasone (OR: 0.194 (0.053−0.713), p = 0.014) were associated with a decreased risk of severe AKI. Conclusions: Dexamethasone was associated with the prevention of the risk of severe AKI and RRT, and iNO was associated with severe AKI and RRT in critically ill patients with COVID-19. iNO should be used with caution in COVID-19-related ARDS.

Successful treatment with adapted high dose methotrexate in a hemodialysis patient with primary central nervous system lymphoma: 100mg/m2 seems sufficient.

High dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX. We report the case of a 64 years old woman on chronic hemodialysis with PCNSL successfully treated with HD-MTX-based chemoimmunotherapy with an adjusted dose of 100mg/m2, instead of the usual dose of 3500mg/m2, and daily hemodialysis started 24h later. The patient had no significant toxicity and was in complete remission at 1 year after the end of the treatment. We argue that ESRD is not an absolute pitfall to the use of HD-MTX for hematological malignancies. Experts should consider the use of adjusted dose at 100mg/m2 as a viable therapeutic modality in ESRD patients.

Presence of specific SARS-COV2 antibodies in hemodialysis patients and their caregivers after the first wave of COVID-19.

Hemodialysis (HD) patients are at risk for severe COVID-19 and cannot comply with social distancing. SARS-COV2 seroprevalence in French patients and caregivers after the first wave of COVID-19 is unknown. SeroCOVIDial is a prospective study conducted between June and December 2020. SARS-COV2 seroprevalence was evaluated by a rapid serological test (BIOSYNEX) in HD patients and caregivers, and the presence or not of anti-SARS-COV2 neutralizing or non-neutralizing antibodies in patients was also determined by ELISA and seroneutralization. In June 2020, 451 HD patients and 238 caregivers were included. Overall SARS-COV2 seroprevalence was 8.4% (patients) and 6.7% (caregivers), and was 87.1% (patients) and 90.0% (caregivers) in participants with a previously documented SARS-COV2 infection. Overall seroprevalence reached 13.8% (patients) and 12.6% (caregivers) following the second epidemic wave. During the follow-up, 38 (8.4%) patients died (9 of COVID-19). Among the 44 (10.6%) patients who became infected, only two were seropositive at M0. The levels of anti-SARS-COV2 antibodies decreased over time in patients and caregivers. The BIOSYNEX test showed 82.9% sensitivity and 97.7% specificity. Prevalence of anti-SARS-COV2 antibodies was low in HD patients and caregivers after the first epidemic wave but rose after the second wave. A rapid serological test showed good performances and could be useful for future monitoring of anti-SARS-COV2 antibodies.

Successful treatment with adapted high dose methotrexate in a hemodialysis patient with primary central nervous system lymphoma: 100mg/m2 seems sufficient / Tratamiento exitoso con una dosis elevada y adaptada de metotrexato en una paciente de hemodiálisis con linfoma primario del sistema nervioso central: 100 mg/m2 parece suficiente

High dose methotrexate (HD-MTX) based chemoimmunotherapy is a central part of the standard approach to treatment of primary central nervous system lymphoma (PCNSL). Renal dysfunction leads to delayed MTX complete elimination and critical MTX concentration. Despite the recommendations, hemodialysis status should not exclude HD-MTX.We report the case of a 64 years old woman on chronic hemodialysis with PCNSL successfully treated with HD-MTX-based chemoimmunotherapy with an adjusted dose of 100mg/m2, instead of the usual dose of 3500mg/m2, and daily hemodialysis started 24h later. The patient had no significant toxicity and was in complete remission at 1 year after the end of the treatment.We argue that ESRD is not an absolute pitfall to the use of HD-MTX for hematological malignancies. Experts should consider the use of adjusted dose at 100mg/m2 as a viable therapeutic modality in ESRD patients. (AU)

La quimioinmunoterapia basada en una dosis elevada de metotrexato (HD-MTX) es una parte central del enfoque terapéutico estándar del linfoma primario del sistema nervioso central (PCNSL). La insuficiencia renal causa la demora de la eliminación completa de MTX, así como la concentración crítica del mismo. A pesar de las recomendaciones, el estatus de hemodiálisis no debería excluir la HD-MTX.Reportamos el caso de una mujer de 64 años con PCNSL y tratamiento de hemodiálisis crónica que fue exitosamente tratada con quimioinmunoterapia basada en HD-MTX con una dosis ajustada de 100 mg/m2, en lugar de la dosis habitual de 3.500 mg/m2, iniciándose la hemodiálisis diaria al cabo de 24 h. La paciente no reflejó toxicidad significativa y experimentó remisión completa al cabo de un año desde la finalización del tratamiento.Nosotros argumentamos que la enfermedad renal en etapa terminal (ESRD) no constituye un escollo en absoluto para utilizar la HD-MTX para neoplasias hematológicas. Los expertos deberían considerar el uso de una dosis ajustada a 100 mg/m2 como modalidad terapéutica viable en los pacientes de ESRD. (AU)