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Objectives: The utility of thrombolysis and/or thrombectomy in patients with mild stroke and large vessel occlusion (LVO) remains inconclusive. This retrospective study compared short-term and long-term outcomes in patients treated with best medical therapy (BMT group) versus with intravenous thrombolytics and/or endovascular thrombectomy (intervention group)., Methods: Patients with acute ischemic stroke (AIS), LVO, and National Institutes of Health Stroke Score (NIHSS) ≤5 were included. Data collected includes demographics; hospital length of stay (LOS); modified Rankin scale (mRS) at admission, discharge, and follow-up; hemorrhagic conversion; and disposition. Bivariate analyses were conducted to compare outcomes between groups., Results: Of the 29 patients, 15 were treated with BMT and 14 underwent intervention. Median hospital LOS was slightly longer in the intervention group (6.5 [IQR=4 to 12] vs. 5 [IQR=3 to 5] d, P=0.070). Everyone in the BMT group had a favorable outcome (mRS 0 to 2) at discharge and follow-up, unlike the intervention group's rate at discharge (100% vs. 71.4%, P=0.042), This gap was closed at follow-up between BMT group (median=33 d, IQR=28 to 48) and intervention group (median=44.5 days, IQR=30 to 48) (100% vs. 85.7%, P=0.224). Hemorrhagic conversion rates were similar between groups. More patients in the BMT group were discharged home (80% vs. 42.9%, P=0.079)., Conclusions: Patients with AIS, low NIHSS, and LVO, who received thrombolytics and/or thrombectomy had longer hospital LOS, higher mRS at discharge and follow-up, and were less likely to be discharged home, though these trends were not statistically significant. Our study is limited by a small sample size and these findings should be further explored in larger studies., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Increasing attention has recently been paid to discrepancies between office and ambulatory blood pressure (BP) control in patients with chronic kidney disease (CKD), but information on mechanisms underlying circadian BP variations in CKD remains scarce. We described circadian BP patterns and their predictors in patients with CKD stages 1 to 5 referred for kidney function testing in a French tertiary hospital: 1122 ambulatory BP measurements from 635 participants. Factors associated with daytime and nighttime systolic BP (SBP) as well as with nocturnal SBP dipping (ratio of average nighttime to daytime SBP) were analyzed with linear mixed regression models. Participants (mean age 55 ± 16 years; 36% female, mean GFR 51 ± 22 mL/min/1.73m 2 ) had a mean daytime and nighttime SBP of 130 ± 17 and 118 ± 18 mm Hg, respectively. The prevalence of impaired dipping (nighttime over daytime SBP ratio ≥ 0.9) increased from 32% in CKD stage 1 to 68% in CKD stages 4-5. After multivariable adjustment, measured GFR, diabetes, and sub-Saharan African origin were more strongly associated with nighttime than with daytime SBP, which led to significant associations with altered nocturnal BP dipping. For a 1 SD decrease in measured GFR, nighttime BP was 2.87 mmHg (95%CI, 1.44-4.30) higher and nocturnal SBP dipping ratio was 1.55% higher (95%CI, 0.85-2.26%). In conclusion, the prevalence of impaired nocturnal BP dipping increases substantially across the spectrum of CKD. Along with sub-Saharan African origin and diabetes, lower measured GFR was a robust and specific predictor of higher nighttime BP and blunted nocturnal BP decline., (© 2024. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Lithium induces nephrogenic diabetes insipidus (NDI) and microcystic chronic kidney disease (CKD). As previous clinical studies suggest that NDI is dose-dependent and CKD is time-dependent, we investigated the effect of low exposition to lithium in a long-term experimental rat model. Rats were fed with a normal diet (control group), with the addition of lithium (Li + group), or with lithium and amiloride (Li + /Ami group) for 6 months, allowing obtaining low plasma lithium concentrations (0.25 ± 0.06 and 0.43 ± 0.16 mmol/L, respectively). Exposition to low concentrations of plasma lithium levels prevented NDI but not microcystic dilations of kidney tubules, which were identified as collecting ducts (CDs) on immunofluorescent staining. Both hypertrophy, characterized by an increase in the ratio of nuclei per tubular area, and microcystic dilations were observed. The ratio between principal cells and intercalated cells was higher in microcystic than in hypertrophied tubules. There was no correlation between AQP2 messenger RNA levels and cellular remodeling of the CD. Additional amiloride treatment in the Li + /Ami group did not allow consistent morphometric and cellular composition changes compared to the Li + group. Low exposition to lithium prevented overt NDI but not microcystic dilations of the CD, with differential cellular composition in hypertrophied and microcystic CDs, suggesting different underlying cellular mechanisms., (© 2024 The Authors. Archiv der Pharmazie published by Wiley‐VCH GmbH on behalf of Deutsche Pharmazeutische Gesellschaft.)

Recent advances in stem cell research have led to the creation of organoids, miniature replicas of human organs, offering innovative avenues for studying diseases. Kidney organoids, with their ability to replicate complex renal structures, provide a novel platform for investigating kidney diseases and assessing drug efficacy, albeit hindered by labor-intensive generation and batch variations, highlighting the need for tailored cryopreservation methods to enable widespread utilization. Here, we evaluated cryopreservation strategies for kidney organoids by contrasting slow-freezing and vitrification methods. 118 kidney organoids were categorized into five conditions. Control organoids followed standard culture, while two slow-freezing groups used 10% DMSO (SF1) or commercial freezing media (SF2). Vitrification involved V1 (20% DMSO, 20% Ethylene Glycol with sucrose) and V2 (15% DMSO, 15% Ethylene Glycol). Assessment of viability, functionality, and structural integrity post-thawing revealed notable differences. Vitrification, particularly V1, exhibited superior viability (91% for V1, 26% for V2, 79% for SF1, and 83% for SF2 compared to 99.4% in controls). 3D imaging highlighted distinct nephron segments among groups, emphasizing V1's efficacy in preserving both podocytes and tubules in kidney organoids. Cisplatin-induced injury revealed a significant reduction in regenerative capacities in organoids cryopreserved by flow-freezing methods, while the V1 method did not show statistical significance compared to the unfrozen controls. This study underscores vitrification, especially with high concentrations of cryoprotectants, as an effective approach for maintaining kidney organoid viability and structure during cryopreservation, offering practical approaches for kidney organoid research., (© 2024. The Author(s).)

Background: The use of diuretics in patients on haemodialysis (HD) is thought to maintain diuresis. However, this assumption and the optimal dose are based on little scientific evidence, and associations with clinical outcomes are unclear., Methods: We reported international variations in diuretic use and loop diuretic dose across 27 759 HD patients with dialysis vintage <1 year in the Dialysis Outcomes and Practice Patterns Study phases 2-5 (2002-2015), a prospective cohort study. Doses of torsemide (4:1) and bumetanide (80:1) were converted to oral furosemide-equivalent doses. Adjusted Cox, logistic and linear regressions were used to investigate the association of diuretic use and dose with outcomes., Results: Diuretic utilization varied widely by country at vintage <3 months, ranging from >80% in Germany and Sweden to <35% in the USA, at a median dose ranging from 400-500 mg/day in Germany and Sweden to <100 mg/day in Japan and the USA. Neither diuretic use nor higher doses were associated with a lower risk of all-cause mortality, a higher risk of hospitalization for fracture or elevated parathyroid hormone levels, but the prescription of higher doses (>200 mg/day) was associated with a higher risk of all-cause hospitalization., Conclusions: Substantial international differences exist in diuretic prescriptions, with use and doses much higher in some European countries than the USA. The prescription and higher doses of loop diuretics was not associated with improved outcomes., Competing Interests: D.W., A.K. and B.B. are employees of Arbor Research Collaborative for Health, which administers the DOPPS. R.P.-F. has received consulting fees from Bayer, Boehringer Ingelheim, AstraZeneca, GSK, Akebia, Fibrogen and Fresenius Medical Care and honoraria from Bayer, Boehringer Ingelheim, AstraZeneca, GSK, Akebia, Fibrogen and Fresenius Medical Care and has participated on a data and safety monitoring board for Bayer, Boehringer Ingelheim, AstraZeneca, GSK, Akebia and Fresenius Medical Care. N.T. has received an Société Francophone de Néphrologie Dialyse et Transplantation research grant and Agence Nationale de la Recherche Young Researcher grant, both to their institution; is on the Data Safety Monitoring Committee of the Programme Hospitalier de Recherche Clinique; and is a board member of the French Society of Nephrology, French Society of Physiology and European Society of Clinical Investigation. E.S. reports a grant or contract from Bayer; consulting fees from AstraZeneca; payment or honoraria from the National Kidney Foundation for American Journal of Kidney Diseases editorial board participation; and is on the German Society of Nephrology executive board. S.H.J. has no conflicts of interest to declare. A.V. received payment or honoraria from Baxter and Braun. K.N. received support for the present manuscript from Kyowa Kirin, Kissei, Torii, Bayer, Astellas and Asahi Kasei. P.A.U.T. is member of the CKJ editorial board and has received consulting fees from AstraZeneca, Amgen, Astellas and Leo Pharma; payment or honoraria from Baxter, Astellas and Vifor Pharma and support for attending meetings and/or travel from Hemotech, GSK, and AstraZeneca., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Objectives: Optimal blood pressure (BP) control is key to prevent cardiovascular complications in patients with chronic kidney disease (CKD). We described the prevalence and factors associated with masked hypertension in CKD., Methods: We analyzed 1113 ambulatory 24-h BP monitoring (ABPM) records of 632 patients referred for kidney function evaluation. Masked hypertension was defined as office BP less than 140/90 mmHg but daytime BP at least 135/85 mmHg or nighttime BP at least 120/70 mmHg. Factors associated with masked hypertension were assessed with mixed logistic regression models., Results: At inclusion, 424 patients (67%) had controlled office BP, of whom 56% had masked hypertension. In multivariable analysis conducted in all visits with controlled office BP ( n  = 782), masked hypertension was positively associated with male sex [adjusted OR (95% confidence interval) 1.91 (1.16-3.27)], sub-Saharan African origin [2.51 (1.32-4.63)], BMI [1.11 (1.01-1.17) per 1 kg/m 2 ], and albuminuria [1.29 [1.12 - 1.47] per 1 log unit), and was negatively associated with plasma potassium (0.42 [0.29 - 0.71] per 1 mmol/L) and 24-h urinary potassium excretion (0.91 [0.82 - 0.99] per 10 mmol/24 h) as well as the use of renin-angiotensin-aldosterone (RAAS) blockers (0.56 [0.31 - 0.97]) and diuretics (0.41 [0.27 - 0.72])., Conclusion: Our findings support the routine use of ABPM in CKD, as more than half of the patients with controlled office BP had masked hypertension. Weight control, higher potassium intake (with caution in advanced CKD), correction of hypokalemia, and larger use of diuretics and RAAS blockers could be potential levers for better out-of-office BP control., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

High-throughput drug screening is crucial for advancing healthcare through drug discovery. However, a significant limitation arises from available in vitro models using conventional 2D cell culture, which lack the proper phenotypes and architectures observed in three-dimensional (3D) tissues. Recent advancements in stem cell biology have facilitated the generation of organoids-3D tissue constructs that mimic human organs in vitro . Kidney organoids, derived from human pluripotent stem cells, represent a significant breakthrough in disease representation. They encompass major kidney cell types organized within distinct nephron segments, surrounded by stroma and endothelial cells. This tissue allows for the assessment of structural alterations such as nephron loss, a characteristic of chronic kidney disease. Despite these advantages, the complexity of 3D structures has hindered the use of organoids for large-scale drug screening, and the drug screening pipelines utilizing these complex in vitro models remain to be established for high-throughput screening. In this study, we address the technical limitations of kidney organoids through fully automated 3D imaging, aided by a machine-learning approach for automatic profiling of nephron segment-specific epithelial morphometry. Kidney organoids were exposed to the nephrotoxic agent cisplatin to model severe acute kidney injury. An U.S. Food and Drug Administration (FDA)-approved drug library was tested for therapeutic and nephrotoxicity screening. The fully automated pipeline of 3D image acquisition and analysis identified nephrotoxic or therapeutic drugs during cisplatin chemotherapy. The nephrotoxic potential of these drugs aligned with previous in vivo and human reports. Additionally, Imatinib, a tyrosine kinase inhibitor used in hematological malignancies, was identified as a potential preventive therapy for cisplatin-induced kidney injury. Our proof-of-concept report demonstrates that the automated screening process, using 3D morphometric assays with kidney organoids, enables high-throughput screening for nephrotoxicity and therapeutic assessment in 3D tissue constructs., (© 2024 IOP Publishing Ltd.)

The use of animal models in therapeutic development has long been the standard practice. However, ethical concerns and the inherent species differences have prompted a reevaluation of the experimental approach in human disease studies. The urgent need for alternative model systems that better mimic human pathophysiology has led to the emergence of organoids, innovative in vitro models, to simulate human organs in vitro. These organoids have gained widespread acceptance in disease models and drug development research. In this mini review, we explore the recent strides made in kidney organoid differentiation and highlight the synergistic potential of incorporating organ-on-chip systems. The emergent use of microfluidic devices reveals the importance of fluid flow in the maturation of kidney organoids and helps decipher pathomechanisms in kidney diseases. Recent research has uncovered their potential applications across a wide spectrum of kidney research areas, including hemodynamic forces at stake in kidney health and disease, immune cell infiltration, or drug delivery and toxicity. This convergence of cutting-edge technologies not only holds promise for expediting therapeutic development but also reflects an acknowledgment of the need to embrace innovative and more human-centric research models., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Kidney organoids are three-dimensional structures generated from pluripotent stem cells (PSCs) that are capable of recapitulating the major structures of mammalian kidneys. As this technology is expected to be a promising tool for studying renal biology, drug discovery, and regenerative medicine, the functional capacity of kidney organoids has emerged as a critical question in the field. Kidney organoids produced using several protocols harbor key structures of native kidneys. Here, we review the current state, recent advances, and future challenges in the functional characterization of kidney organoids, strategies to accelerate and enhance kidney organoid functions, and access to PSC resources to advance organoid research. The strategies to construct physiologically relevant kidney organoids include the use of organ-on-a-chip technologies that integrate fluid circulation and improve organoid maturation. These approaches result in increased expression of the major tubular transporters and elements of mechanosensory signaling pathways suggestive of improved functionality. Nevertheless, continuous efforts remain crucial to create kidney tissue that more faithfully replicates physiological conditions for future applications in kidney regeneration medicine and their ethical use in patient care. NEW & NOTEWORTHY Kidney organoids are three-dimensional structures derived from stem cells, mimicking the major components of mammalian kidneys. Although they show great promise, their functional capacity has become a critical question. This review explores the advancements and challenges in evaluating and enhancing kidney organoid function, including the use of organ-on-chip technologies, multiomics data, and in vivo transplantation. Integrating these approaches to further enhance their physiological relevance will continue to advance disease modeling and regenerative medicine applications.

The kidneys, by equilibrating the outputs to the inputs, are essential for maintaining the constant volume, pH, and electrolyte composition of the internal milieu. Inability to do so, either because of internal kidney dysfunction (primary alteration) or because of some external factors (secondary alteration), leads to pathologies of varying severity, leading to modification of these parameters and affecting the functions of other organs. Alterations of the functions of the collecting duct (CD), the most distal part of the nephron, have been extensively studied and have led to a better diagnosis, better management of the related diseases, and the development of therapeutic tools. Thus, dysfunctions of principal cell-specific transporters such as ENaC or AQP2 or its receptors (mineralocorticoid or vasopressin receptors) caused by mutations or by compounds present in the environment (lithium, antibiotics, etc.) have been demonstrated in a variety of syndromes (Liddle, pseudohypoaldosteronism type-1, diabetes insipidus, etc.) affecting salt, potassium, and water balance. In parallel, studies on specific transporters (H + -ATPase, anion exchanger 1) in intercalated cells have revealed the mechanisms of related tubulopathies like distal renal distal tubular acidosis or Sjögren syndrome. In this review, we will recapitulate the mechanisms of most of the primary and secondary alteration of the ion transport system of the CD to provide a better understanding of these diseases and highlight how a targeted perturbation may affect many different pathways due to the strong crosstalk and entanglements between the different actors (transporters, cell types)., (© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine.)

Background: Lithium therapy during bipolar disorder is associated with an increased risk of chronic kidney disease (CKD) that is slowly progressive and undetectable at early stages. We aimed at identifying kidney image texture features as possible imaging biomarkers of decreased measured glomerular filtration rate (mGFR) using radiomics of T2-weighted magnetic resonance imaging (MRI)., Methods: One hundred and eight patients treated with lithium were evaluated including mGFR and kidney MRI, with T2-weighted sequence single-shot fast spin-echo. Computed radiomic analysis was performed after kidney segmentation. Significant features were selected to build a radiomic signature using multivariable Cox analysis to detect an mGFR <60 ml/min/1.73 m². The texture index was validated using a training and a validation cohort., Results: Texture analysis index was able to detect an mGFR decrease, with an AUC of 0.85 in the training cohort and 0.71 in the validation cohort. Patients with a texture index below the median were older (59 [42-66] vs. 46 [34-54] years, p = .001), with longer treatment duration (10 [3-22] vs. 6 [2-10] years, p = .02) and a lower mGFR (66 [46-84] vs. 83 [71-94] ml/min/1.73m², p < .001). Texture analysis index was independently and negatively associated with age (β = -.004 ± 0.001, p < .001), serum vasopressin (-0.005 ± 0.002, p = .02) and lithium treatment duration (-0.01 ± 0.003, p = .001), with a significant interaction between lithium treatment duration and mGFR (p = .02)., Conclusions: A renal texture index was developed among patients treated with lithium associated with a decreased mGFR. This index might be relevant in the diagnosis of lithium-induced renal toxicity., (© 2022 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Introduction: Lithium treatment can induce nephrogenic diabetes insipidus (NDI), but no consensus intervention is offered to date. We evaluated in these patients patterns of urine concentration and the correlates of 24-hour urine output., Methods: Prospective, single-center, observational study of 217 consecutive lithium-treated individuals, with 24-hour urine collection, desmopressin (1-deamino-arginine vasopressin [DDAVP]) concentrating test, fasting plasma vasopressin measurement (copeptin measurement in n = 119), and measured glomerular filtration rate (mGFR). Maximal urine osmolality (MaxUosm) was the highest level during the DDAVP test., Results: Of the individuals, 21% displayed polyuria (>3 l/d), but 55% displayed elevated fasting vasopressin level (>5 pg/ml). Uosm was significantly lower and urinary output and free water clearance were significantly higher in individuals treated for >10 years. MaxUosm was >600 mOsm/KgH 2 O in 128 patients (59%), among which vasopressin was increased in 51%, associated with higher lithium dose (950 [750-1200] vs. 800 [500-1000] mg/d, P  < 0.001). All patients with lithium daily dose ≥1400 mg/d had high vasopressin levels. In multivariable analysis, 24-hour urine output was associated with higher lithium daily dose (β 0.49 ± 0.17, P  = 0.005), female sex (β -359 ± 123, P  = 0.004), daily osmolar intake (β 2.21 ± 0.24, P  < 0.001), MaxUosm (β -2.89 ± 0.35, P  < 0.001), and plasma vasopressin level (β 10.17 ± 4.76, P  = 0.03)., Conclusion: Higher lithium daily dose was associated with higher vasopressin levels and higher urine output, independently of other factors. Daily osmolar intake was also associated with higher 24-hour urine output. These results suggest that controlled salt and protein intake and lithium dose might reduce polyuria in these patients., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Several clinical settings require an accurate estimation of the physiologically expected extracellular fluid volume (ECFV). We aimed to analyze the performances of existing ECFV-estimating equations and to develop a new equation., Methods: The performances of 11 ECFV-estimating equations were analyzed in 228 healthy kidney donor candidates (Bichat Hospital, Paris, France) who underwent ECFV measurement using the distribution volume of 51 Cr-labeled EDTA ( 51 Cr-EDTA). An equation was developed using a penalized linear modeling approach (elastic net regression) and externally (Tenon Hospital, Paris, France, N =  142) validated., Results: Participants from Bichat (mean age 45.2 ± 12.0 years, 43.0% men) and Tenon (47.8 ± 10.3 years, 29.6% men) hospitals had a mean measured ECFV of 15.4 ± 2.8 l and 15.1 ± 2.1 l, respectively. Available ECFV-estimating formulae have highly variable precision and accuracy. The new equation incorporating body weight, height, sex, and age had better precision and accuracy than all other equations in the external validation cohort, with a median bias of -0.20 (95% CI: -0.35 to -0.05) l versus -2.63 (-2.87 to -2.42) l to -0.57 (- 0.83 to -0.40) l and 0.21 (0.12 to 0.43) l to 2.89 (2.65 to 3.11) l, for underestimating and overestimating equations, respectively, an interquartile range for the bias of 0.88 (0.70 to 1.08) l versus 0.91 (0.71 to 1.20) l to 1.93 (1.67 to 2.25) l, and an accuracy within 10% of 90.9% (83.8 to 94.4) versus 88.0% (81.0 to 92.3) to 8.5% (4.2 to 13.4). These results were consistent across subgroups defined by sex, body mass index (BMI), body surface area (BSA), age, and ethnicity., Conclusion: We developed and validated a new equation to estimate the individual reference value of ECFV, which is easily usable in clinical practice. Further validation in cohorts including individuals of extreme age and corpulence remains needed., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Objectives: Early kidney damage during lithium treatment in bipolar disorder is still hypothetical. We aimed at identifying the determinants of a decreased measured glomerular filtration rate (mGFR) and the accuracy of kidney MRI imaging in its detection. Methods: In this cross-sectional cohort study, 217 consecutive lithium-treated patients underwent mGFR and kidney MRI with half-Fourier turbo spin-echo and Single-shot with long echo time sequences. Results: Median age was 51 [27-62] years, and median lithium treatment duration was 5 [2-14] years. 52% of patients had a stage 2 CKD. In multivariable analysis, the determinants of a lower mGFR were a longer lithium treatment duration (β -0.8 [-1; -0.6] ml/min/1.73 m 2 GFR decrease for each year of treatment), a higher age (β -0.4 [-0.6; -0.3] ml/min/1.73 m 2 for each year of age, p < 0.001), albuminuria (β -3.97 [-6.6; -1.3], p = 0.003), hypertension (β -6.85 [-12.6; -1.1], p = 0.02) and hypothyroidism (β -7.1 [-11.7; -2.5], p = 0.003). Serum lithium concentration was not associated with mGFR. Renal MRI displayed renal microcyst(s) in 51% of patients, detected as early as 1 year after lithium treatment initiation. mGFR and lithium treatment duration were strongly correlated in patients with microcyst(s) (r = -0.64, p < 0.001), but not in patients with no microcysts (r = -0.24, p = 0.09). The presence of microcysts was associated with the detection of an mGFR <45 ml/min/1.73 m 2 (AUC 0.893, p < 0.001, sensitivity 80%, specificity 81% for a cut-off value of five microcysts). Conclusion: Lithium treatment duration and hypothyroidism strongly impacted mGFR independently of age, especially in patients with microcysts. MRI might help detect early lithium-induced kidney damage and inform preventive strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tabibzadeh, Faucon, Vidal-Petiot, Serrano, Males, Fernandez, Khalil, Rouzet, Tardivon, Mazer, Dubertret, Delavest, Marlinge, Etain, Bellivier, Vrtovsnik and Flamant.)

Background: Augmented renal creatinine clearance (ARC) (≥130 ml min-1 1.73 m-2) is frequent in intensive care unit (ICU) patients and may impact patient outcome., Objectives: To compare glomerular filtration rate (GFR) measured with iohexol plasma clearance and creatinine clearance in critically ill patients with augmented renal clearance., Design: Single-centre, retrospective study., Setting: French University Hospital ICU from November 2016 to May 2019., Patients: Adult patients with augmented renal clearance who had a measurement of iohexol plasma clearance., Main Outcome Measure: Agreement between 6 h creatinine clearance (6 h CrCl) and iohexol plasma clearance (GFRio)., Results: Twenty-nine patients were included. The median 6 h creatinine clearance was 195 [interquartile range (IQR) 162 to 251] ml min-1 1.73 m-2 and iohexol clearance was 133 [117 to 153] ml min-1 1.73 m-2. Sixteen patients (55%) had hyperfiltration (clearance >130 ml min-1 1.73 m-2) measured with iohexol clearance. Mean bias between iohexol and creatinine clearance was -80 [limits of agreement (LoA) -216 to 56 ml min-1 1.73 m-2]. For Cockcroft and Gault Modification of Diet in Renal Disease equation (MDRD), Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) formulae, mean biases were, respectively -27 (LoA -99 to 45), -14 (LoA -86 to 59) and 15 (LoA -33 to 64) ml min-1 1.73 m-2., Conclusion: In the present study, we found that in patients with augmented renal creatinine clearance, half of the patients do not have hyperfiltration using iohexol clearance measurements. We observed an important bias between 6 h CrCl and GFRio with large LoA. In critically patients with ARC, 6 h CrCl does not reliably estimate GFR and 6 h CrCl nearly systematically overestimates renal function. Comparison of creatinine-based GFR estimations and GFRio show acceptable bias but wide LoA., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Kidney involvement is a common complication during SARS-CoV-2 infection. Its association with poor outcomes, especially in critically ill patients, raises issues whether kidney involvement reflects multi-organ damage or if it is a specific feature of the infection. Based on observational studies, autopsy series, and on current understanding of the route of entry of the virus, this review will highlight the different types of kidney involvement during COVID-19 and put them in the perspective of the different pathophysiological hypotheses. Virus entry route through ACE2 ligation and TMPRSS2 coligation allows identifying potential viral targets in the kidney, including tubules, endothelial cells, and glomerulus. While reports have described damages of all these structures and virus kidney tropism has been identified in renal extracts in autopsy series, no direct viral infection has been found in the latter structures thus far on kidney biopsies. Notwithstanding the technical challenge of disclosing viral invasion within tissues and cells, viral direct cytopathogenic effect generally does not appear as the cause of the observed renal damage. Inflammation and altered hemodynamics, described as "viral sepsis," might rather be responsible for organ dysfunction, including kidneys. We shall place these various mechanisms into an integrated vision where the synergy between direct viral pathogenicity and systemic inflammation enhances renal damage. As SARS-CoV-2 inexorably continues its rampant spread, understanding the sequence of events in the kidneys might thus help inform improved therapeutic strategies, including antiviral drugs and immunomodulators., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Le Stang, Desenclos, Flamant, Chousterman and Tabibzadeh.)

Background: Optimal parathyroid hormone (PTH) control during non-dialysis chronic kidney disease (ND-CKD) might decrease the subsequent risk of parathyroid hyperplasia and uncontrolled secondary hyperparathyroidism (SHPT) on dialysis. However, the evidence for recommending PTH targets and therapeutic strategies is weak for ND-CKD. We evaluated the patient characteristics, treatment patterns and PTH control over the first year of haemodialysis (HD) by PTH prior to HD initiation., Methods: We studied 5683 incident HD patients from 21 countries in Dialysis Outcomes and Practice Patterns Study Phases 4-6 (2009-18). We stratified by PTH measured immediately prior to HD initiation and reported the monthly prescription prevalence of active vitamin D and calcimimetics over the first year of HD and risk of PTH >600 pg/mL after 9-12 months on HD., Results: The 16% of patients with PTH >600 pg/mL prior to HD initiation were more likely to be prescribed active vitamin D and calcimimetics during the first year of HD. The prevalence of PTH >600 pg/mL 9-12 months after start of HD was greater for patients who initiated HD with PTH >600 (29%) versus 150-300 (7%) pg/mL (adjusted risk difference: 19%; 95% confidence interval : 15%, 23%). The patients with sustained PTH >600 pg/mL after 9-12 months on HD were younger, more likely to be black, and had higher serum phosphorus and estimated glomerular filtration rates at HD initiation., Conclusions: Increased PTH before HD start predicted a higher PTH level 9-12 months later, despite greater use of active vitamin D and calcimimetics. More targeted PTH control during ND-CKD may influence outcomes during HD, raising the need for PTH target guidelines in these patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Multiple-choice question (MCQ) tests are commonly used to evaluate medical students, but they do not assess self-confidence nor penalize lucky guess or harmful behaviors. Based on a scoring method according to the appropriateness of confidence in answers, the study aimed at assessing knowledge self-monitoring and efficiency, and the determinants of self-confidence., Methods: A cross-sectional study of 842 s- and third-year medical students who were asked to state their level of confidence (A: very confident, B: moderately confident and C: not confident) during 12 tests (106,806 events). A bonus was applied if the level of confidence matched with the correctness of the answer, and a penalty was applied in the case of inappropriate confidence., Results: Level A was selected more appropriately by the top 20% students whereas level C was selected more appropriately by the lower 20% students. Efficiency of higher-performing students was higher when correct (among correct answers, rate of A statement), but worse when incorrect compared to the bottom 20% students (among incorrect answers, rate of C statement). B and C statements were independently associated with female and male gender, respectively (OR for male vs female = 0.89 [0.82-0.96], p = 0.004, for level B and 1.15 [1.01-1.32], p = 0.047, for level C)., Conclusion: While both addressing the gender confidence gap, knowledge self-monitoring might improve awareness of students' knowledge whereas efficiency might evaluate appropriate behavior in clinical practice. These results suggest differential feedback during training in higher versus lower-performing students, and potentially harmful behavior in decision-making during clinical practice in higher-performing students.

Background: Chronic kidney disease is associated with a high cardiovascular risk. Compared with glomerular filtration rate-matched CKD patients (CKDps), we previously reported a 2.7-fold greater risk of global mortality among kidney transplant recipients (KTRs). We then examined aortic stiffness [evaluated by carotid-femoral pulse wave velocity (CF-PWV)] and cardiovascular risk in KTRs compared with CKDps with comparable measured glomerular filtration rate (mGFR)., Methods: We analysed CF-PWV in two cohorts: TransplanTest (KTRs) and NephroTest (CKDps). Propensity scores were calculated including six variables: mGFR, age, sex, mean blood pressure (MBP), body mass index (BMI) and heart rate. After propensity score matching, we included 137 KTRs and 226 CKDps. Descriptive data were completed by logistic regression for CF-PWV values higher than the median (>10.6 m/s)., Results: At 12 months post-transplant, KTRs had significantly lower CF-PWV than CKDps (10.1 versus 11.0 m/s, P = 0.008) despite no difference at 3 months post-transplant (10.5 versus 11.0 m/s, P = 0.242). A lower occurrence of high arterial stiffness was noted among KTRs compared with CKDps (38.0% versus 57.1%, P < 0.001). It was especially associated with lower mGFR, older age, higher BMI, higher MBP, diabetes and higher serum parathyroid hormone levels. After adjustment, the odds ratio for the risk of high arterial stiffness in KTRs was 0.40 (95% confidence interval 0.23-0.68, P < 0.001)., Conclusions: Aortic stiffness was significantly less marked in KTRs 1 year post-transplant than in CKDps matched for GFR and other variables. This observation is compatible with the view that the pathogenesis of post-transplant cardiovascular disease differs, at least in part, from that of CKD per se ., (© The Author(s) 2020. Published by Oxford University Press on behalf of ERA-EDTA.)

Lithium salts are the main treatment of bipolar disorder, which is characterized by potentially life-threatening maniac and/or depressive episodes. They have proven efficient in the prevention and treatment of acute episodes as well as in the prevention of suicidal risk. However, this efficacy is counterbalanced by a narrow therapeutic range that can lead to potentially harmful overdose, and by adverse long-term events. Nevertheless, they remain first-line treatment, notwithstanding therapeutic alternatives. In this review, we will describe toxic effects of long-term treatment at therapeutic levels of lithium salts. Regarding renal effects, early-impaired urine concentrating ability might lead to polyuria and polydipsia, and even to hypernatremia if free access to water is compromised. Long-term lithium treatment might also lead to chronic kidney disease, characterized by tubulo-interstitial multicystic nephropathy. End-stage renal disease requiring renal replacement therapy is a rare complication. Major extra-renal toxic effects are hypercalcemia and hypothyroidism. Treatment cessation due to these adverse events should be a multidisciplinary and case-by-case decision based on the benefit/risk ratio. Since these toxic effects are mild and display slow progression, treatment cessation is uncommon. However, regular medical and biological check-up is needed in order to prevent these disorders, and patients might be referred to nephrologists and/or endocrinologists once the disorders are established., (Copyright © 2019 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier Masson SAS. All rights reserved.)

Rationale & Objective: Chronic kidney disease (CKD) characterized by decreased glomerular filtration rate (GFR) is often accompanied by various degrees of impaired tubular function in the cortex and medulla. Assessment of tubular function may therefore be useful in establishing the severity of kidney disease and identifying those at greater risk for CKD progression. We explored reductions in urinary concentrating ability, a well-known feature of CKD, as a risk factor for GFR decline and end-stage renal disease (ESRD)., Study Design: Prospective longitudinal cohort study., Setting & Participants: 2,084 adult patients with CKD stages 1 to 4 from the French NephroTest Cohort Study., Predictor: Fasting urinary osmolality measured using delta cryoscopy., Outcomes: ESRD, mortality before ESRD, and measured GFR (mGFR) assessed using 51 Cr-EDTA renal clearance., Analytical Approach: Cause-specific hazards models were fit to estimate crude and adjusted associations of urinary osmolality with ESRD and death before ESRD. Linear mixed models with random intercepts were fit to evaluate the association of urinary osmolality with slope of decline in mGFR., Results: At baseline, mean age was 58.7±15.2 (SD) years with a median mGFR of 40.2 (IQR, 29.1-54.5) mL/min/1.73m 2 and a median fasting urinary osmolality of 502.7±151.7mOsm/kg H 2 O. Baseline fasting urinary osmolality was strongly associated with mGFR (R=0.54; P < 0.001). 380 ESRD events and 225 deaths before ESRD occurred during a median follow-up of 5.9 (IQR, 3.8-8.2) years. Patients with lower baseline fasting urinary osmolality had higher adjusted risk for ESRD but not for mortality (HRs of 1.97 [95% CI, 1.26-3.08] and 0.99 [95% CI, 0.68-1.44], respectively, for the lowest vs highest tertile). Based on a mixed linear model adjusted for baseline mGFR and clinical characteristics, patients in the lowest tertile of baseline urinary osmolality had a steeper decline in kidney function (-4.9% ± 0.9% per year; P < 0.001) compared with patients in the highest tertile., Limitations: Fasting was self-reported., Conclusions: Fasting urinary osmolality may be a useful tool, in addition to GFR and albuminuria, for assessing nonglomerular damage in patients with CKD who are at higher risk for CKD progression., (Copyright © 2019 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.)

Green tea is widely used as a ''healthy'' beverage due to its high level of antioxidant polyphenol compounds. However tea is also known to contain significant amount of oxalate. The objective was to determine, in a cross-sectional observational study among a population of 273 hypercalciuric stone-formers referred to our center for metabolic evaluation, whether daily green tea drinkers ( n = 41) experienced increased stone risk factors (especially for oxalate) compared to non-drinkers. Stone risk factors and stone composition were analyzed according to green tea status and sex. In 24-h urine collection, the comparison between green tea drinkers and non-drinkers showed no difference for stone risk factors such as urine oxalate, calcium, urate, citrate, and pH. In females, the prevalence of calcium oxalate dihydrate (COD) and calcium phosphate stones, assessed by infrared analysis (IRS) was similar between green tea drinkers and non-drinkers, whereas prevalence of calcium oxalate monohydrate (COM) stones was strikingly decreased in green tea drinkers (0% vs. 42%, p = 0.04), with data in accordance with a decreased oxalate supersaturation index. In males, stone composition and supersaturation indexes were similar between the two groups. Our data show no evidence for increased stone risk factors or oxalate-dependent stones in daily green tea drinkers.