Use of Intravenous Albumin: A Guideline From the International Collaboration for Transfusion Medicine Guidelines.

BACKGROUND: Albumin is used commonly across a wide range of clinical settings to improve hemodynamics, to facilitate fluid removal, and to manage complications of cirrhosis. The International Collaboration for Transfusion Medicine Guidelines developed guidelines for the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, undergoing kidney replacement therapy, or experiencing complications of cirrhosis. STUDY DESIGN AND METHODS: Cochairs oversaw the guideline development process and the panel included researchers, clinicians, methodologists, and a patient representative. The evidence informing this guideline arises from a systematic review of randomized clinical trials and systematic reviews, in which multiple databases were searched (inception through November 23, 2022). The panel reviewed the data and formulated the guideline recommendations using Grading of Recommendations Assessment, Development, and Evaluation methodology. The guidelines were revised after public consultation. RESULTS: The panel made 14 recommendations on albumin use in adult critical care (three recommendations), pediatric critical care (one recommendation), neonatal critical care (two recommendations), cardiovascular surgery (two recommendations), kidney replacement therapy (one recommendation), and complications of cirrhosis (five recommendations). Of the 14 recommendations, two recommendations had moderate certainty of evidence, five recommendations had low certainty of evidence, and seven recommendations had very low certainty of evidence. Two of the 14 recommendations suggested conditional use of albumin for patients with cirrhosis undergoing large-volume paracentesis or with spontaneous bacterial peritonitis. Twelve of 14 recommendations did not suggest albumin use in a wide variety of clinical situations where albumin commonly is transfused. INTERPRETATION: Currently, few evidence-based indications support the routine use of albumin in clinical practice to improve patient outcomes. These guidelines provide clinicians with actionable recommendations on the use of albumin.

Impaired Renal Function and Major Cardiovascular Events in Young Adults.

BACKGROUND: Cardiovascular (CV) disease in young adults (aged 18-39 years) is on the rise. Whether subclinical reductions in kidney function (ie, estimated glomerular filtration rate [eGFR] above the current threshold for chronic kidney disease but below age-expected values) are associated with elevated CV risk is unknown. OBJECTIVES: The goal of this study was to examine age-specific associations of subclinical eGFR reductions in young adults with major adverse cardiovascular events (MACEs) and MACE plus heart failure (MACE+). METHODS: A retrospective cohort study of 8.7 million individuals (3.6 million aged 18-39 years) was constructed using linked provincial health care data sets from Ontario, Canada (January 2008-March 2021). Cox models were used to examine the association of categorized eGFR (50-120 mL/min/1.73 m2) with MACE (first of CV mortality, acute coronary syndrome, and ischemic stroke) and MACE+, stratified according to age (18-39, 40-49, and 50-65 years). RESULTS: In the study cohort (mean age 41.3 years; mean eGFR 104.2 mL/min/1.73 m2; median follow-up 9.2 years), a stepwise increase in the relative risk of MACE and MACE+ was observed as early as eGFR <80 mL/min/1.73 m2 in young adults (eg, for MACE, at eGFR 70-79 mL/min/1.73 m2, ages 18-30 years: 2.37 events per 1,000 person years [HR: 1.31; 95% CI: 1.27-1.40]; ages 40-49 years: 6.26 events per 1,000 person years [HR: 1.09; 95% CI: 1.06-1.12]; ages 50-65 years: 14.9 events per 1,000 person years [HR: 1.07; 95% CI: 1.05-1.08]). Results persisted for each MACE component and in additional analyses (stratifying according to past CV disease, accounting for albuminuria at index, and using repeated eGFR measures). CONCLUSIONS: In young adults, eGFR below age-expected values were associated with an elevated risk for MACE and MACE+, warranting age-appropriate risk stratification, proactive monitoring, and timely intervention.

Kidney outcomes after methanol and ethylene glycol poisoning: a systematic review and meta-analysis.

INTRODUCTION: Ingestions with methanol, ethylene glycol, diethylene glycol, propylene glycol, and isopropanol are rare yet exceedingly dangerous conditions that may require emergent management with kidney replacement therapy. Little is known regarding short- and long-term kidney outcomes post-ingestion. OBJECTIVES: To comprehensively synthesize existing evidence regarding short- and long-term kidney and other outcomes of adult patients following these poisonings. METHODS: We developed a search strategy in MEDLINE via OVID and then translated it into other databases including EMBASE (via OVID), PubMed, CENTRAL (via OVID). The databases were searched from their dates of inception to 29 July 2021. A grey literature search was conducted in the International Traditional Medicine Clinical Trial Registry and ClinicalTrials.gov. All interventional and observational studies and case series with ≥ five participants that reported on the outcomes of toxic alcohol (methanol, ethylene glycol, diethylene glycol, propylene glycol and isopropanol) poisonings in adult patients ≥18 years old were included. Studies that reported mortality, kidney outcomes and/or complications attributed to toxic alcohol poisoning were eligible. RESULTS: The search strategy identified 1,221 citations. Sixty-seven studies (13 retrospective observational studies, one prospective observational study, 53 case series) met inclusion criteria (total N = 2,327 participants). No randomized controlled trials were identified per our prespecified criteria. Generally, included studies had small sample sizes (median of 27 participants) and were of low quality. Methanol and/or ethylene glycol poisoning made up 94.1% of included studies, whereas one study reported on isopropanol and none reported on propylene glycol. Results of the 13 observational studies of methanol and/or ethylene glycol poisoning were pooled for meta-analyses. The pooled in-hospital mortality estimates amongst patients with methanol and ethylene glycol poisoning were 24 and 11%, respectively. A more recent year of publication, female sex and mean age were associated with lower in-hospital mortality amongst individuals with ethylene glycol poisoning. Although hemodialysis was the most frequently employed kidney replacement therapy, the indications for initiation of this therapy were not reported in the majority of studies. At hospital discharge, kidney recovery occurred in 64.7-96.3% of patients with ethylene glycol poisoning. In studies of methanol and/or ethylene glycol poisoning, 2-3.7% of individuals required ongoing dialysis. Only one study reported post-discharge mortality. Furthermore, long-term toxic alcohol-mediated sequelae, such as visual and neurologic outcomes, were scarcely reported. DISCUSSION: Ingestions of methanol and ethylene glycol were associated with a significant short-term risk of mortality. Although a wealth of literature in the form of case reports and case series exists, high-quality evidence regarding kidney outcomes after these poisonings is lacking. We identified a paucity of standardized reporting in clinical presentations, therapeutics and outcomes amongst adults with toxic alcohol poisoning. Amongst the included studies, there was substantial heterogeneity encompassing study type, outcomes, duration of follow-up and treatment modalities. These sources of heterogeneity restricted our ability to perform comprehensive meta-analyses of all outcomes of interest. An additional limitation is the lack of studies pertaining to propylene glycol and the paucity of data on isopropanol. CONCLUSIONS: The indications for hemodialysis, long-term kidney recovery and long-term mortality risk vary widely in these poisonings and are inconsistently reported in the literature. This highlights the need for further research with standardized reporting of baseline kidney function, indications for initiation of kidney replacement therapy and short-term and long-term kidney outcomes. REGISTRATION: This systematic review protocol is registered at PROSPERO, CRD42018101955.

Clinicopathological differences between Bartonella and other bacterial endocarditis-related glomerulonephritis - our experience and a pooled analysis.

Background: Although Staphylococcus aureus is the leading cause of acute infective endocarditis (IE) in adults, Bartonella spp. has concomitantly emerged as the leading cause of "blood culture-negative IE" (BCNE). Pre-disposing factors, clinical presentation and kidney biopsy findings in Bartonella IE-associated glomerulonephritis (GN) show subtle differences and some unique features relative to other bacterial infection-related GNs. We highlight these features along with key diagnostic clues and management approach in Bartonella IE-associated GN. Methods: We conducted a pooled analysis of 89 cases of Bartonella IE-associated GN (54 published case reports and case series; 18 published conference abstracts identified using an English literature search of several commonly used literature search modalities); and four unpublished cases from our institution. Results: Bartonella henselae and Bartonella quintana are the most commonly implicated species causing IE in humans. Subacute presentation, affecting damaged native and/or prosthetic heart valves, high titer anti-neutrophil cytoplasmic antibodies (ANCA), mainly proteinase-3 (PR-3) specificity, fastidious nature and lack of positive blood cultures of these Gram-negative bacilli, a higher frequency of focal glomerular crescents compared to other bacterial infection-related GNs are some of the salient features of Bartonella IE-associated GN. C3-dominant, but frequent C1q and IgM immunofluorescence staining is seen on biopsy. A "full-house" immunofluorescence staining pattern is also described but can be seen in IE -associated GN due to other bacteria as well. Non-specific generalized symptoms, cytopenia, heart failure and other organ damage due to embolic phenomena are the highlights on clinical presentation needing a multi-disciplinary approach for management. Awareness of the updated modified Duke criteria for IE, a high index of suspicion for underlying infection despite negative microbiologic cultures, history of exposure to animals, particularly infected cats, and use of send-out serologic tests for Bartonella spp. early in the course of management can help in early diagnosis and initiation of appropriate treatment. Conclusion: Diagnosis of IE-associated GN can be challenging particularly with BCNE. The number of Bartonella IE-associated GN cases in a single institution tends to be less than IE due to gram positive cocci, however Bartonella is currently the leading cause of BCNE. We provide a much-needed discussion on this topic.

Meta-analytic Techniques to Assess the Association Between N-acetylcysteine and Acute Kidney Injury After Contrast Administration: A Systematic Review and Meta-analysis.

Importance: The most suitable analytic method to systematically analyze numerous trials with contradictory results is unclear. Multiple trials assessing the use of N-acetylcysteine (NAC) for prevention of contrast-induced acute kidney injury (CI-AKI) have had contradictory results with recent trials confirming a lack of benefit. Objective: To systematically review the literature on NAC for the prevention of CI-AKI, and to explore the heterogeneity, publication bias, and small-study effect to determine the most suitable analytic method in a setting where the literature is contradictory. Data Sources: Medline, Embase, and Cochrane Central Register of Controlled Trials databases were used to find randomized clinical trials (RCTs) comparing NAC with any other prophylactic agent or placebo in adults. Study Selection: The search included studies published in English from database inception to January 2020. Two independent reviewers screened the studies, extracted data, and performed the risk of bias assessment. Data Extraction and Synthesis: A meta-analysis was conducted about the effect of NAC on CI-AKI, the need for dialysis, and mortality. Fixed and random effects analyses were also performed. Funnel plots and the trim and fill method were used for assessment of publication bias. Metaregression was performed to explore the heterogeneity and subgroup analysis to examine the association between NAC and CI-AKI when studies were categorized according to sample size and number of events. Results: A total of 101 trials were included in this meta-analysis. The median sample size was 112 (range, 20 to 4993). Twenty-nine trials had a sample size of 200 or more, and only 3 trials had a sample size of 500 or more. Forty-five trials reported the need for kidney replacement therapy, and 41 trials reported mortality as an outcome. NAC seemed to show a benefit, with a pooled OR of 0.72 (95% CI, 0.63-0.82) using random effects model and a pooled OR of 0.82 (95% CI 0.76-0.90) using a fixed effects model. However, there was significant heterogeneity (I2 = 37.6; P < .001) and significant publication bias, which was reduced only when restricting to large RCTs (N ≥ 500). The clinical outcomes (ie, the need for kidney replacement therapy and mortality) revealed little heterogeneity and no publication bias, and each provided a robust neutral summary result. Conclusions and Relevance: In this meta-analysis, NAC was associated with a benefit in the prevention of CI-AKI. However, because of substantial publication bias and other biases, standard meta-analytic techniques resulted in significant heterogeneity and a spurious, or factitious, association, even when using a random effects model. When the analysis was restricted to RCTs with a large sample size to account for publication bias or restricted to trials with clinical outcomes, this issue was reduced and resulted in more robust and neutral effect sizes.

Intravenous albumin for the prevention of hemodynamic instability during sustained low-efficiency dialysis: a randomized controlled feasibility trial (The SAFER-SLED Study).

BACKGROUND: Hemodynamic instability is a frequent complication of sustained low-efficiency dialysis (SLED) treatments in the ICU. Intravenous hyperoncotic albumin may prevent hypotension and facilitate ultrafiltration. In this feasibility trial, we sought to determine if a future trial, powered to evaluate clinically relevant outcomes, is feasible. METHODS: This single-center, blinded, placebo-controlled, randomized feasibility trial included patients with acute kidney injury who started SLED in the ICU. Patients were randomized to receive 25% albumin versus 0.9% saline (control) as 100 mL boluses at the start and midway through SLED, for up to 10 sessions. The recruitment rate and other feasibility outcomes were determined. Secondary exploratory outcomes included ultrafiltration volumes and metrics of hemodynamic instability. RESULTS: Sixty patients (271 SLED sessions) were recruited over 10 months. Age and severity of illness were similar between study groups. Most had septic shock and required vasopressor support at baseline. Protocol adherence occurred for 244 sessions (90%); no patients were lost to follow-up; no study-related adverse events were observed; open label albumin use was 9% and 15% in the albumin and saline arms, respectively. Ultrafiltration volumes were not significantly different. Compared to the saline group, the albumin group experienced less hemodynamic instability across all definitions assessed including a smaller absolute decrease in systolic blood pressure (mean difference 10.0 mmHg, 95% confidence interval 5.2-14.8); however, there were significant baseline differences in the groups with respect to vasopressor use prior to SLED sessions (80% vs 61% for albumin and saline groups, respectively). CONCLUSIONS: The efficacy of using hyperoncotic albumin to prevent hemodynamic instability in critically ill patients receiving SLED remains unclear. A larger trial to evaluate its impact in this setting, including evaluating clinically relevant outcomes, is feasible. Trial registration ClinicalTrials.gov (NCT03665311); First Posted: Sept 11th, 2018. https://clinicaltrials.gov/ct2/show/NCT03665311?term=NCT03665311&draw=2&rank=1.

B cell activating factor (BAFF) from neutrophils and dendritic cells is required for protective B cell responses against Salmonella typhimurium infection.

Mice lacking B cells are more susceptible to S. typhimurium infection. How B cells contribute to protective immunity against Salmonella and what signals drive their activation are still unclear. Neutrophils (Nphs), monocytes (MOs), and dendritic cells (DCs) are involved in early immune responses to control the initial replication of S. typhimurium. These cells can produce B cell activating factor (BAFF) required for mature B cell survival and may help regulate B cell responses during Salmonella infection. Using BAFF reporter mice (BAFF-RFP+/-), we discovered that an i.p. infection with a virulent strain of S. typhimurium increased BAFF expression in splenic conventional DCs (cDC) and inflammatory Ly6Chi MOs/DCs four days post-infection. S. typhimurium infection induced the release of BAFF from Nphs, a decrease of BAFF-RFP expression and expansion of BAFF-RFP+ Nphs in the spleen and peritoneal cavity. After S. typhimurium infection, serum BAFF levels and immature and mature B cell subsets and plasma cells increased substantially. Conditional knockout (cKO) mice lacking BAFF in either Nphs or cDCs compared to control Bafffl/fl mice had reduced up-regulation of systemic BAFF levels and reduced expansion of mature and germinal center B cell subsets after infection. Importantly, the cKO mice lacking BAFF from either Nphs or cDCs had impaired induction of Salmonella-specific IgM Abs, and were more susceptible to S. typhimurium infection. Thus, Nphs and cDCs are major cellular sources of BAFF driving B cell responses, required for mounting optimal protective immunity against lethal Salmonella infection.

MicroRNA in Human Acute Kidney Injury: A Systematic Review Protocol.

BACKGROUND: Acute kidney injury (AKI) is a common complication of hospitalization with high morbidity and mortality for which no effective treatments exist and for which current diagnostic tools have limitations for earlier identification. MicroRNAs (miRNAs) are small non-coding RNAs that have been implicated in the pathogenesis of AKI, and some miRNAs have shown promise as therapeutic tools in animal models of AKI. However, less is known about the role of miRNAs in human AKI. OBJECTIVE: To evaluate the role of miRNAs in human subjects with AKI. DESIGN: Systematic review and meta-analysis. MEASUREMENTS: Quantification of miRNA levels from human blood, urine, or kidney biopsy samples, and measures of renal function as defined in the study protocol. METHODS: A comprehensive search strategy for Ovid MEDLINE All, Embase, Web of Science, and CENTRAL will be developed to identify investigational studies that evaluated the relationship between miRNA levels and human AKI. Primary outcomes will include measurements of kidney function and miRNA levels. Study screening, review and data extraction will be performed independently by 2 reviewers. Study quality and certainty of evidence will be assessed with validated tools. A narrative synthesis will be included and the possibility for meta-analysis will be assessed according to characteristics of clinical and statistical heterogeneity between studies. LIMITATIONS: These include (1) lack of randomized trials of miRNAs for the prevention or treatment of human AKI, (2) quality of included studies, and (3) sources of clinical and statistical heterogeneity that may affect strength and reproducibility of results. CONCLUSION: Previous studies of miRNAs in different animal models of AKI have generated strong interest on their use for the prevention and treatment of human AKI. This systematic review will characterize the most promising miRNAs for human research and will identify methodological constraints from miRNA research in human AKI to help inform the design of future studies. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020201253.

CONTEXTE: L'insuffisance rénale aiguë (IRA) est une complication fréquente des hospitalisations avec morbidité et mortalité élevées. Il n'existe aucun traitement efficace contre l'IRA et les outils diagnostiques actuels qui permettent son dépistage précoce comportent des limites. Les microARN (miARN) sont de petits ARN non codants ayant été impliqués dans la pathogenèse de l'IRA; certains d'entre eux se sont révélés prometteurs comme outils thérapeutiques dans les modèles animaux de l'IRA. Le rôle des miARN dans l'IRA chez l'humain est cependant moins connu. OBJECTIF: Évaluer le rôle des miARN chez les sujets humains atteints d'IRA. TYPE D'ÉTUDE: Examen systématique et méta-analyze. MESURES: La quantification des taux de miARN chez l'humain à partir d'échantillons de sang, d'urine ou de biopsie rénale, et mesure de la fonction rénale telle que définie dans le protocole de l'étude. MÉTHODOLOGIE: Une stratégie de recherche exhaustive des bases de données Ovid MEDLINE All, Embase, Web of Science et CENTRAL sera élaborée afin de répertorier les études expérimentales ayant évalué la relation entre les taux de miARN et l'IRA chez l'humain. Les principaux critères d'évaluation comprendront la mesure de la fonction rénale et des taux de miARN. Deux examinateurs procéderont de façon indépendante à la sélection des études, à leur examen et à l'extraction des données. La qualité des études et la robustesse des données seront évaluées à l'aide d'outils validés. Une synthèse descriptive sera incluse et la possibilité d'une méta-analyze sera évaluée en fonction des caractéristiques de l'hétérogénéité clinique et statistique entre les études. LIMITES: Les limites de l'étude concernent notamment (i) le manque d'essais randomisés examinant les miARN pour la prévention ou le traitement de l'IRA humaine; (ii) la qualité des études incluses; et (iii) les sources d'hétérogénéité clinique et statistique susceptibles d'affecter la robustesse et la reproductibilité des résultats. CONCLUSION: Des études antérieures sur les miARN dans différents modèles animaux de l'IRA ont suscité un vif intérêt pour leur utilization dans la prévention et le traitement de l'IRA chez l'humain. Cet examen systématique caractérisera les miARN les plus prometteurs pour la recherche sur l'IRA humaine et définira les contraintes méthodologiques de telles études, ce qui aidera à orienter la conception des études futures.

A living donor kidney transplant recipient with mycobacterium senegalense bacteremia: A case report.

Mycobacterium senegalense is primarily known in sub-Saharan Africa to cause bovine farcy, a chronic granulomatous inflammation of the skin and lymphatics in cows. Reports of M. senegalense are rare among humans. We report a unique case of M. senegalense bloodstream infection in a living donor kidney transplant recipient with multiple possible sources of infection.

Cannabis and Cigarette Use Before and After Living Kidney Donation.

BACKGROUND: It is unclear whether kidney donation leads to lifestyle changes in terms of cannabis and cigarette use. OBJECTIVE: To describe cigarette and cannabis use before and after kidney donation and to determine their associations with lifestyle and clinical factors. DESIGN: Retrospective cohort study. SETTING: The Living Kidney Donor program in the Champlain Local Health Integration Network at The Ottawa Hospital in Ottawa, Canada. PATIENTS: The study included 178 living kidney donors who donated between January 2009 and December 2018. MEASUREMENTS: Donors were screened for cannabis and cigarette use by telephone interview. Their clinical characteristics and changes in kidney function before and after donation were recorded. METHODS: Cannabis and cigarette use before and after kidney donation were compared using chi-square test. Risk factors associated with their use was examined by univariate and multivariate logistic regression. Wilcoxon rank sum test was used to examine the association of cannabis and Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI) estimated glomerular filtration rate (eGFR) at donation and at last follow-up. T-test was used to examine the association of cigarette smoking and CKD-EPI eGFR at donation and at last follow-up. RESULTS: Among 305 donors, 262 met inclusion criteria and 178 participated (mean of 4.7 ± 2.9 years from kidney donation). Cannabis and cigarette use were reported by 5% (9 of 178) and 13% (23 of 178) at donation. After donation, 8% (14 of 178) and 5% (9 of 178) started cannabis and cigarettes, respectively; 74% (17 of 23) of smokers remained smokers after donation and 88% (53 of 60) who quit smoking before donation did not restart after donation. In multivariate analysis, non-married/common-in-law status was associated with cannabis use (odds ratio, 2.73; 95% confidence interval, 1.05-7.11; P = .04). There was no difference in eGFR pre- or post-donation among cannabis or cigarette users. LIMITATIONS: The single-center study design limits generalizability. Social desirability bias may have affected survey responses and cigarette smoking was not quantified. CONCLUSIONS: Cannabis and cigarette use was uncommon in the studied population and was not associated with remaining kidney function. Cannabis use increased post-donation. Most smokers remained smokers after donation and most donors who quit smoking before donation did not restart after donation. This warrants education and support for potential donors who smoke, to quit smoking prior to donation to reduce risks of cardiovascular and end-stage kidney disease. TRIAL REGISTRATION: Not applicable as this is not a clinical trial.

CONTEXTE: On ignore si la perspective de faire don d'un rein conduit les donneurs potentiels à changer leurs habitudes de vie en matière de tabagisme et de consommation de cannabis. OBJECTIFS: Examiner la prévalence du tabagisme et de la consommation de cannabis avant et après le don d'un rein, puis déterminer leur association avec le mode de vie et les facteurs cliniques. TYPE D'ÉTUDE: Étude de cohorte rétrospective. CADRE: Le program de don de rein vivant du Réseau local d'intégration des services de santé de Champlain de l'hôpital d'Ottawa (Canada). SUJETS: L'étude a inclus 178 individus ayant fait don d'un rein entre janvier 2009 et décembre 2018. MESURES: Les donneurs ont été questionnés par téléphone sur leur consommation de cigarettes et de cannabis. Les caractéristiques cliniques et les changements dans la fonction rénale ont été enregistrés pré- et post-don. MÉTHODOLOGIE: Le test du Chi2 a été employé pour comparer la consommation de cigarettes et de cannabis pré- et post-don, tandis que les facteurs de risque associés à leur utilization ont été examinés par régression logistique univariée et multivariée. L'association entre la consommation de cannabis/le tabagisme et le CKD-EPI eGFR (débit de filtration glomérulaire estimé [DFGe] par l'équation de la Chronic Kidney Disease Epidemiology [CKD-EPI] Collaboration) a été examinée au moment du don et lors du dernier suivi par le test Wilcoxon (cannabis) ou le test t (tabagisme), selon le cas. RÉSULTATS: Des 305 donneurs admissibles, 262 répondaient aux critères d'inclusion et 178 ont participé à l'étude (moyenne: 4,7 ± 2,9 ans depuis le don). Au moment du don, 5 % (9/178) des donneurs consommaient du cannabis et 13 % (23/178) fumaient la cigarette. Après le don, 8 % (14/178) des donneurs ont commencé à consommer du cannabis et 5 % (9/178) à fumer la cigarette. La majorité des donneurs qui fumaient avant le don ont continué après le don (74 % [17/23]). La grande majorité des donneurs qui avaient cessé de fumer avant le don n'ont pas repris après (88 % [53/60]). Dans l'analyze multivariée, le fait de ne pas être marié ou conjoint de fait a été associé à la consommation de cannabis (rapport de cotes: 2,73; IC à 95 %: 1,05-7,11; p=0,04). Aucune différence n'a été observée dans les taux de filtration glomérulaire estimé pré- et post-don chez les fumeurs et les consommateurs de cannabis. LIMITES: L'étude est monocentrique, ce qui limite la généralisabilité des résultats. Un biais de désirabilité sociale pourrait avoir influé sur les réponses à l'enquête. Le tabagisme n'a pas été quantifié. CONCLUSION: Le tabagisme et la consommation de cannabis étaient peu courants dans la population étudiée; ces habitudes de vie n'ont pas été associées à la fonction rénale résiduelle. La consommation de cannabis a augmenté après le don. La plupart des fumeurs le sont demeurés après le don et la majorité des donneurs qui avaient cessé de fumer avant le don n'ont pas repris après. Ces résultats justifient de sensibiliser les donneurs potentiels à l'importance de cesser de fumer avant le don, et de les appuyer dans cette démarche, afin de réduire les risques de maladies cardiovasculaires et d'insuffisance rénale terminale.

A Systematic Review of the Effect of N-Acetylcysteine on Serum Creatinine and Cystatin C Measurements.

INTRODUCTION: N-acetylcysteine (NAC) is an antioxidant that can regenerate glutathione and is primarily used for acetaminophen overdose. NAC has been tested and used for preventing iatrogenic acute kidney injury or slowing the progression of chronic kidney disease, with mixed results. There are conflicting reports that NAC may artificially lower measured serum creatinine without improving kidney function, potentially by assay interference. Given these mixed results, we conducted a systematic review of the literature to determine whether there is an effect of NAC on kidney function as measured with serum creatinine and cystatin C. METHODS: A literature search was conducted to identify all study types reporting a change in serum creatinine after NAC administration. The primary outcome was change in serum creatinine after NAC administration. The secondary outcome was a change in cystatin C after NAC administration. Subgroup analyses were conducted to assess effect of creatinine assay (Jaffe vs. non-Jaffe and intravenous vs. oral). RESULTS: Six studies with a total of 199 participants were eligible for the systematic review and meta-analysis. There was a small but significant decrease in serum creatinine after NAC administration overall (weighted mean difference [WMD], -2.80 µmol/L [95% confidence interval {CI} -5.6 to 0.0]; P = 0.05). This was greater with non-Jaffe methods (WMD, -3.24 µmol/L [95% CI -6.29 to -0.28]; P = 0.04) than Jaffe (WMD, -0.51 µmol/L [95% CI -7.56 to 6.53]; P = 0.89) and in particular with intravenous (WMD, -31.10 µmol/L [95% CI -58.37 to -3.83]; P = 0.03) compared with oral NAC (WMD, -2.5 µmol/L [95% CI -5.32 to 0.32]; P = 0.08). There was no change in cystatin C after NAC administration. DISCUSSION: NAC causes a decrease in serum creatinine but not in cystatin C, suggesting analytic interference rather than an effect on kidney function. Supporting this, the effect was greater with non-Jaffe methods of creatinine estimation. Future studies of NAC should use the Jaffe method of creatinine estimation when kidney outcomes are being reported. Even in clinical settings, the use of an enzymatic assay when high doses of intravenous NAC are being used may result in underdiagnosis or delayed diagnosis of acute kidney injury.

BAFF Produced by Neutrophils and Dendritic Cells Is Regulated Differently and Has Distinct Roles in Antibody Responses and Protective Immunity against West Nile Virus.

B cell activating factor (BAFF) is essential for B cells to develop and respond to Ags. Dysregulation of BAFF contributes to the development of some autoimmune diseases and malignancies. Little is known about when, where, and how BAFF is produced in vivo and about which BAFF-producing cells contribute to B cell responses. To better understand BAFF functions, we created BAFF reporter (BAFF-RFP) mice and Baff floxed (Bafffl/fl ) mice. Splenic and bone marrow neutrophils (Nphs) from BAFF-RFP mice expressed the highest constitutive levels of BAFF; other myeloid subsets, including conventional dendritic cells (cDCs) and monocyte (MO) subsets, expressed lower levels. Treatment of BAFF-RFP mice with polyinosinic:polycytidylic acid increased BAFF expression in splenic Ly6Chi inflammatory MOs, CD11bhi activated NK subset, and in bone marrow myeloid precursors. Postinfection with West Nile virus (WNV), BAFF increased in CD8- cDCs and Nphs, and BAFF+ CD11bhi NK cells expanded in draining lymph nodes. The cell- and tissue-specific increases in BAFF expression were dependent on type I IFN signaling. MAVS also was required or contributed to BAFF expression in dendritic cell and MO subsets, respectively. Mice with deletion of Baff in either cDCs or Nphs had reduced Ab responses after NP-Ficoll immunization; thus, BAFF produced by both cDCs and Nphs contributes to T cell-independent Ab responses. Conversely, mice with a cDC Baff deficiency had increased mortality after WNV infection and decreased WNV-specific IgG and neutralizing Ab responses. BAFF produced by Nphs and cDCs is regulated differently and has key roles in Ab responses and protective immunity.

Targeting Antigens to CD180 but Not CD40 Programs Immature and Mature B Cell Subsets to Become Efficient APCs.

Targeting Ags to the CD180 receptor activates both B cells and dendritic cells (DCs) to become potent APCs. After inoculating mice with Ag conjugated to an anti-CD180 Ab, B cell receptors were rapidly internalized. Remarkably, all B cell subsets, including even transitional 1 B cells, were programed to process, present Ag, and stimulate Ag-specific CD4+ T cells. Within 24-48 hours, Ag-specific B cells were detectable at T-B borders in the spleen; there, they proliferated in a T cell-dependent manner and induced the maturation of T follicular helper (TFH) cells. Remarkably, immature B cells were sufficient for the maturation of TFH cells after CD180 targeting: TFH cells were induced in BAFFR-/- mice (with only transitional 1 B cells) and not in µMT mice (lacking all B cells) following CD180 targeting. Unlike CD180 targeting, CD40 targeting only induced DCs but not B cells to become APCs and thus failed to efficiently induce TFH cell maturation, resulting in slower and lower-affinity IgG Ab responses. CD180 targeting induces a unique program in Ag-specific B cells and to our knowledge, is a novel strategy to induce Ag presentation in both DCs and B cells, especially immature B cells and thus has the potential to produce a broad range of Ab specificities. This study highlights the ability of immature B cells to present Ag to and induce the maturation of cognate TFH cells, providing insights toward vaccination of mature B cell-deficient individuals and implications in treating autoimmune disorders.

New Insights Into Mechanisms of Acute Kidney Injury in Heart Disease.

Acute kidney injury is a frequent occurrence in patients with heart disease, and is associated with higher risk of adverse outcomes, including mortality. In the setting of decompensated heart failure, acute kidney injury can occur from hemodynamic and neurohormonal activation, venous congestion, and nephrotoxic medications. Certain medications, such as loop diuretics, renin angiotensin system blockers, and mineralocorticoid antagonists can seemingly cause acute kidney injury. However, this increase in creatinine level is not always associated with adverse outcomes and should be carefully differentiated so as to allow deliberate continuation of these cardio- and nephroprotective agents. In other settings such as cardiac surgery, acute kidney injury can occur from factors related to the cardiopulmonary bypass, renal hypoperfusion, or other perioperative factors. Last, patients with heart disease commonly undergo imaging procedures that require contrast administration. Contrast can indeed cause acute kidney injury, but these interventional procedures also can result in kidney injury from atheroembolic phenomena. This is well documented by the recent data reporting a higher risk of acute kidney injury from femoral compared with radial access. The advent of biomarkers of kidney injury present an opportunity for early detection, accurate differential diagnosis, as well as potentially designing innovative biomarker-enriched adaptive clinical trials.

Common errors in temporary hemodialysis catheter insertion.

Non-tunneled hemodialysis catheter (NTHC) insertion is an essential skill for nephrology practice and remains a requirement of training. However, improper insertion technique can increase the risk of potentially fatal infectious and mechanical complications. Evidence-based strategies can reduce the rates of such complications and should be integrated into practice and training. Ultrasound (US) guidance should routinely be used for NTHC insertion at the femoral and internal jugular sites (with avoidance of the subclavian site). Nephrologists should receive proper training in the use of US for line insertion. With respect to other aspects of the procedure, proper insertion technique readily prevents guidewire-induced arrhythmias. In addition, adherence to infection-control guidelines results in a sustainable reduction in bloodstream infections. All these aspects of NTHC insertion may be best taught and evaluated through a program that includes simulation-based mastery learning (SBML) training. As a separate issue, nephrologists (and intensivists) should be aware that a dysfunctional catheter should be replaced at a new site rather than being changed over a guidewire. This review of common errors related to NTHC insertion seeks to highlight evidence-based approaches to practice and training.

Sickle cell disease: a case report of renal amyloidosis.

BACKGROUND: The development of proteinuria and reduced glomerular filtration rate is associated with higher mortality among patients with sickle cell disease (SCD). AA amyloidosis, also associated with increased mortality, in SCD is rare. We present a case of a woman with homozygous sickle cell disease with nephrotic syndrome and antibodies to double stranded DNA without clinical features of systemic lupus erythematosus. Kidney biopsy reveals AA amyloidosis and is the first report of concomitant AA amyloidosis with antibodies to double stranded DNA in SCD. CASE PRESENTATION: A 40-year-old Central African woman with homozygous sickle cell disease and history of vaso-occlusive pain crises undergoes kidney biopsy for nephrotic-range proteinuria. Kidney biopsy reveals AA type amyloidosis, which is a rare manifestation of SCD in the kidney. Her anemia worsens with an ACE inhibitor, initiated to reduce proteinuria and limit GFR decline, so it was discontinued. Hydroxyurea, shown to decrease the frequency of vaso-occlusive crises and lower proteinuria, was subsequently initiated but then discontinued due to worsening anemia. Unfortunately, her glomerular filtration rate worsens. CONCLUSIONS: AA amyloidosis and antibodies to double stranded DNA can occur in sickle cell disease. ACE inhibition and hydroxyurea decrease proteinuria so they may limit progression of chronic kidney disease. Hydroxyurea also decreases frequency of vaso-occlusive pain crises so it might be helpful in limiting progression of renal AA amyloidosis. However, further studies are needed to determine optimal treatment strategies for AA amyloidosis in sickle cell disease.

Albuminuria, Reduced Kidney Function, and the Risk of ST - and non-ST-segment-elevation myocardial infarction.

Background Chronic kidney disease is a recognized independent risk factor for cardiovascular disease, but whether the risks of ST-segment-elevation myocardial infarction ( STEMI ) and non-ST-segment-elevation myocardial infarction ( NSTEMI ) differ in the chronic kidney disease population is unknown. Methods and Results Using administrative data from Ontario, Canada, we examined patients ≥66 years of age with an outpatient estimated glomerular filtration rate ( eGFR ) and albuminuria measure for incident myocardial infarction from 2002 to 2015. Adjusted Fine and Gray subdistribution hazard models accounting for the competing risk of death were used. In 248 438 patients with 1.2 million person-years of follow-up, STEMI , NSTEMI , and death occurred in 1436 (0.58%), 4431 (1.78%), and 30 015 (12.08%) patients, respectively. The highest level of albumin-to-creatinine ratio (>30 mg/mmol) was associated with a 2-fold higher adjusted risk of both STEMI and NSTEMI among patients with eGFR ≥60 mL/(min·1.73 m2) compared to albumin-to-creatinine ratio <3 mg/mmol. The lowest level of eGFR (<30 mL/[min·1.73 m2]) was not associated with higher STEMI risk but with a 4-fold higher risk of NSTEMI compared to those with eGFR ≥60 mL/(min·1.73 m2). The lowest eGFR (<30 mL/[min·1.73 m2]) and highest albumin-to-creatinine ratio (>30 mg/mmol) were associated with a greater than 4-fold higher risk of both STEMI and NSTEMI (subdistribution hazard models [95% confidence interval] 4.53 [3.30-6.21] and 4.42 [3.67-5.32], respectively) compared to albumin-to-creatinine ratio <3 mg/mmol and eGFR ≥60 mL/(min·1.73 m2). Conclusions Elevations in albuminuria are associated with a higher risk of both NSTEMI and STEMI , regardless of kidney function, whereas reduced kidney function alone is associated with a higher NSTEMI risk.

Implementation and evaluation of structured nephrology morbidity and mortality conferences: a quality education report.

BACKGROUND: Morbidity and Mortality Conferences (M&MCs) have for generations been part of the education of physicians, yet their effectiveness remains questionable. The Ottawa M&M Model (OM3) was developed to provide a structured approach to M&MCs in order to maximize the quality improvement impact of such rounds. STUDY DESIGN: We conducted a retrospective assessment of the impact of implementing nephrology-specific M&MCs using the OM3. SETTING AND PARTICIPANTS: All physicians, residents and fellows from the division of nephrology at a large academic medical center were invited to participate. QUALITY IMPROVEMENT PLAN: Structured M&MCs were implemented to identify preventable errors and generate actions to improve quality of care and patient safety. OUTCOMES: Number and nature of cases reviewed, number and nature of recommendations generated through identification of preventable health system and/or cognitive factors. MEASUREMENTS: Morbidity and/or mortality in each case were identified. A determination of the underlying factors and preventability of these events was made. A qualitative review of resulting recommendations was performed. RESULTS: Over the course of sixteen 1-h long conferences, 52 cases were presented. For all cases presented, discussion, action items and information dissemination followed the OM3. As a result of the M&MCs, 29 recommendations (emanating from 27 cases) lead to improve care delivery. LIMITATIONS: Limitations of this study include its retrospective nature and single-center design. CONCLUSIONS: The implementation of regularly scheduled M&MCs at an academic nephrology program, using a structured model, identified preventable health-systems issues and cognitive errors. Approximately one-half of the cases reviewed generated actions for health care delivery improvement.

Splenic macrophages are required for protective innate immunity against West Nile virus.

Although the spleen is a major site for West Nile virus (WNV) replication and spread, relatively little is known about which innate cells in the spleen replicate WNV, control viral dissemination, and/or prime innate and adaptive immune responses. Here we tested if splenic macrophages (MΦs) were necessary for control of WNV infection. We selectively depleted splenic MΦs, but not draining lymph node MΦs, by injecting mice intravenously with clodronate liposomes several days prior to infecting them with WNV. Mice missing splenic MΦs succumbed to WNV infection after an increased and accelerated spread of virus to the spleen and the brain. WNV-specific Ab and CTL responses were normal in splenic MΦ-depleted mice; however, numbers of NK cells and CD4 and CD8 T cells were significantly increased in the brains of infected mice. Splenic MΦ deficiency led to increased WNV in other splenic innate immune cells including CD11b- DCs, newly formed MΦs and monocytes. Unlike other splenic myeloid subsets, splenic MΦs express high levels of mRNAs encoding the complement protein C1q, the apoptotic cell clearance protein Mertk, the IL-18 cytokine and the FcγR1 receptor. Splenic MΦ-deficient mice may be highly susceptible to WNV infection in part to a deficiency in C1q, Mertk, IL-18 or Caspase 12 expression.

Protection of mice deficient in mature B cells from West Nile virus infection by passive and active immunization.

B cell activating factor receptor (BAFFR)-/- mice have a profound reduction in mature B cells, but unlike µMT mice, they have normal numbers of newly formed, immature B cells. Using a West Nile virus (WNV) challenge model that requires antibodies (Abs) for protection, we found that unlike wild-type (WT) mice, BAFFR-/- mice were highly susceptible to WNV and succumbed to infection within 8 to 12 days after subcutaneous virus challenge. Although mature B cells were required to protect against lethal infection, infected BAFFR-/- mice had reduced WNV E-specific IgG responses and neutralizing Abs. Passive transfer of immune sera from previously infected WT mice rescued BAFFR-/- and fully B cell-deficient µMT mice, but unlike µMT mice that died around 30 days post-infection, BAFFR-/- mice survived, developed WNV-specific IgG Abs and overcame a second WNV challenge. Remarkably, protective immunity could be induced in mature B cell-deficient mice. Administration of a WNV E-anti-CD180 conjugate vaccine 30 days prior to WNV infection induced Ab responses that protected against lethal infection in BAFFR-/- mice but not in µMT mice. Thus, the immature B cells present in BAFFR-/- and not µMT mice contribute to protective antiviral immunity. A CD180-based vaccine may promote immunity in immunocompromised individuals.