scholarly journals Gender differences in the susceptibility of hospital-acquired acute kidney injury: more questions than answers

2020 ◽  
Vol 52 (10) ◽  
pp. 1911-1914 ◽  
Author(s):  
Helmut Schiffl
Keyword(s):  
Acute Kidney Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Menopausal Status ◽  
Kidney Injury ◽  
Basic Research ◽  
Epidemiological Studies ◽  
Experimental Models ◽  
Increased Risk ◽  
Hospital Acquired

Abstract Hospital-acquired acute kidney injury (HA-AKI) is a heterogeneous renal syndrome which occurs in different clinical settings. It is characterized by multiple aetiologies, various pathogeneses and unpredictable outcomes. HA-AKI, once predominantly viewed as a self-limited and reversible short-term condition, is now recognized as a harbinger for chronic kidney disease and a cause of long-term morbidity with an increased risk of cardiovascular, renal and cancer mortality. Recent clinical studies contradict the generally held belief that female sex is a risk factor for HA-AKI. They show, consistent with basic research performed with experimental models of AKI, that only male sex is associated with HA-AKI. The presence of testosterone, more likely than the absence of estrogen, plays a critical role in sex differences in the susceptibility of ischemia/reperfusion kidney injury. The conflicting data in epidemiological studies related to sex as susceptibility variable for human AKI, underscore the need for more rigorous, well designed observational studies taking into account the menopausal status and hormone therapy.

scholarly journals Higher Ambient Nitrogen Dioxide Is Associated With An Elevated Risk Of Hospital-Acquired Acute Kidney Injury

2021 ◽  
Author(s):  
Pinghong He ◽  
Ruixuan Chen ◽  
Liping Zhou ◽  
Yanqin Li ◽  
Licong Su ◽  
...  
Keyword(s):  
Air Pollution ◽  
Acute Kidney Injury ◽  
Nitrogen Dioxide ◽  
Multivariable Analysis ◽  
Kidney Injury ◽  
Onset Date ◽  
Ambient Level ◽  
Increased Risk ◽  
Pm2.5 And Pm10 ◽  
Hospital Acquired

Abstract Background Previous studies have suggested that long-term exposure to air pollution increased the risk of chronic kidney disease and its progression. However, the effect of air pollution on the risk of acute kidney injury (AKI) has not been studied. We aim to evaluate the transient effect of air pollution on the risk of hospital-acquired AKI (HA-AKI). Methods We selected from the Epidemiology of AKI in Chinese Hospitalized patients (EACH2 study) AKI cases of which the onset date could be unambiguously determined. We obtained city-specific daily averages of the ambient level of particulate matter (PM2.5 and PM10), carbon monoxide (CO), nitrogen dioxide (NO2), sulfur dioxide (SO2) and ozone (O3), from the Ministry of Environmental Protection of China. We used the time-stratified case crossover approach to examine the association between the ambient level of air pollutants and the risk of HA-AKI in the selected cases. Results A total of 11,293 AKI cases that met the inclusion and exclusion criteria were selected. In univariable analysis, the ambient levels of NO2 and SO2, were significantly associated with the risk of HA-AKI. In the multivariable analysis that incorporated all six pollutants in the same model, NO2 was the sole pollutant whose level remained to be associated with the risk of AKI (p < 0.001). The relationship between level of NO2 and the risk of HA-AKI appeared to be linear, with an estimated odds ratio of 1.063 (95% CI: 1.026, 1.101) for each increment of one median absolute deviance in the exposure. The association was consistent across the subgroups stratified by age, gender, baseline estimated glomerular filtration rate, AKI severity, need for intensive care, and season. Conclusions Higher ambient level of NO2 was associated with an increased risk of HA-AKI in hospitalized adults in China.

scholarly journals Inflammaging and Complement System: A Link Between Acute Kidney Injury and Chronic Graft Damage

2020 ◽  
Vol 11 ◽  
Author(s):  
Rossana Franzin ◽  
Alessandra Stasi ◽  
Marco Fiorentino ◽  
Giovanni Stallone ◽  
Vincenzo Cantaluppi ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Complement System ◽  
Kidney Diseases ◽  
Critical Role ◽  
Graft Function ◽  
Kidney Injury ◽  
Increased Risk ◽  
Wide Range ◽  
Renal Aging

The aberrant activation of complement system in several kidney diseases suggests that this pillar of innate immunity has a critical role in the pathophysiology of renal damage of different etiologies. A growing body of experimental evidence indicates that complement activation contributes to the pathogenesis of acute kidney injury (AKI) such as delayed graft function (DGF) in transplant patients. AKI is characterized by the rapid loss of the kidney’s excretory function and is a complex syndrome currently lacking a specific medical treatment to arrest or attenuate progression in chronic kidney disease (CKD). Recent evidence suggests that independently from the initial trigger (i.e., sepsis or ischemia/reperfusions injury), an episode of AKI is strongly associated with an increased risk of subsequent CKD. The AKI-to-CKD transition may involve a wide range of mechanisms including scar-forming myofibroblasts generated from different sources, microvascular rarefaction, mitochondrial dysfunction, or cell cycle arrest by the involvement of epigenetic, gene, and protein alterations leading to common final signaling pathways [i.e., transforming growth factor beta (TGF-β), p16ink4a, Wnt/β-catenin pathway] involved in renal aging. Research in recent years has revealed that several stressors or complications such as rejection after renal transplantation can lead to accelerated renal aging with detrimental effects with the establishment of chronic proinflammatory cellular phenotypes within the kidney. Despite a greater understanding of these mechanisms, the role of complement system in the context of the AKI-to-CKD transition and renal inflammaging is still poorly explored. The purpose of this review is to summarize recent findings describing the role of complement in AKI-to-CKD transition. We will also address how and when complement inhibitors might be used to prevent AKI and CKD progression, therefore improving graft function.

Serum Uric Acid and Risk for Acute Kidney Injury Following Contrast

Angiology ◽  
2016 ◽  
Vol 68 (2) ◽  
pp. 132-144 ◽  
Author(s):  
Mehmet Kanbay ◽  
Yalcin Solak ◽  
Baris Afsar ◽  
Ionut Nistor ◽  
Gamze Aslan ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Clinical Trials ◽  
Uric Acid ◽  
Cohort Studies ◽  
Meta Analysis ◽  
Kidney Injury ◽  
Significant Heterogeneity ◽  
Increased Risk ◽  
Hospital Acquired ◽  
Significant Protective Effect

Contrast-induced acute kidney injury (CI-AKI) is a common cause of hospital-acquired acute kidney injury (AKI). We evaluated the evidence that uric acid (UA) plays a pathogenic role in CI-AKI. Ten studies were eligible for inclusion for meta-analysis. Hyperuricemia predicted risk for cases with AKI in prospective cohort studies. Higher levels of serum UA (SUA), as defined by the authors, were associated with a 2-fold increased risk to develop AKI (pooled odds ratio 2.03; 95% confidence interval [CI] 1.48-2.78). Significant heterogeneity was found in cohort studies ( P = .001, I2 = 85.7%). In 2 clinical trials, lowering of SUA with saline hydration was significantly associated with reduced risk for AKI compared with saline hydration alone or saline hydration with N-acetyl cysteine. An analysis of 2 randomized controlled trials found that allopurinol with saline hydration had a significant protective effect on renal function (assessed by serum creatinine values) compared with hydration alone (mean difference: −0.52 mg/dL; 95% CI: −0.81 to −0.22). Hyperuricemia independently predicts CI-AKI. Two clinical trials suggest lowering SUA may prevent CI-AKI. The mechanism by which UA induces CI-AKI is likely related to acute uricosuria.

scholarly journals Mouse model of ischemic acute kidney injury: technical notes and tricks

2012 ◽  
Vol 303 (11) ◽  
pp. F1487-F1494 ◽  
Author(s):  
Qingqing Wei ◽  
Zheng Dong
Keyword(s):  
Acute Kidney Injury ◽  
Mouse Model ◽  
Drug Testing ◽  
Ischemia Reperfusion ◽  
Small Animal ◽  
Kidney Injury ◽  
Experimental Models ◽  
Renal Ischemia

Renal ischemia-reperfusion leads to acute kidney injury (AKI), a major kidney disease associated with an increasing prevalence and high mortality rates. A variety of experimental models, both in vitro and in vivo, have been used to study the pathogenic mechanisms of ischemic AKI and to test renoprotective strategies. Among them, the mouse model of renal clamping is popular, mainly due to the availability of transgenic models and the relatively small animal size for drug testing. However, the mouse model is generally less stable, resulting in notable variations in results. Here, we describe a detailed protocol of the mouse model of bilateral renal ischemia-reperfusion. We share the lessons and experiences gained from our laboratory in the past decade. We further discuss the technical issues that account for the variability of this model and offer relevant solutions, which may help other investigators to establish a well-controlled, reliable animal model of ischemic AKI.

scholarly journals Neutrophil gelatinase-associated lipocalin (NGAL) as biomarker of acute kidney injury: a review of the laboratory characteristics and clinical evidences

2012 ◽  
Vol 50 (9) ◽  
Author(s):  
Aldo Clerico ◽  
Claudio Galli ◽  
Antonio Fortunato ◽  
Claudio Ronco
Keyword(s):  
Acute Kidney Injury ◽  
Serum Creatinine ◽  
Randomized Clinical Trials ◽  
Critical Role ◽  
Kidney Injury ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Standard Clinical Practice ◽  
Clinical Scenarios ◽  
Increased Risk ◽  
Neutrophil Gelatinase

AbstractAcute kidney injury (AKI) is a common and serious condition, currently diagnosed by functional biomarkers, such as serum creatinine measurements. Unfortunately, creatinine increase is a delayed and unreliable indicator of AKI. The lack of early biomarkers of structural kidney injury has hampered our ability to translate promising experimental therapies to human AKI. The recent discovery, translation and validation of neutrophil gelatinase-associated lipocalin (NGAL), possibly the most promising novel AKI biomarker, is reviewed here. NGAL may be measured by several methods both in plasma and urine for the early diagnosis of AKI and for the prediction of clinical outcomes, such as dialysis requirement and mortality, in several common clinical scenarios, including in the intensive care unit, cardiac surgery and renal damage due the exposition to toxic agent and drugs, and renal transplantation. Furthermore, the predictive properties of NGAL, may play a critical role in expediting the drug development process. A systematic review of literature data indicates that further studies are necessary to establish accurate reference population values according to age, gender and ethnicity, as well as reliable and specific decisional values concerning the more common clinical settings related to AKI. Furthermore, proper randomized clinical trials on renal and systemic outcomes comparing the use of NGAL vs. standard clinical practice are still lacking and accurate cost-benefit and/or cost-utility analyses for NGAL as biomarker of AKI are also needed. However, it is important to note that NGAL, in the absence of diagnostic increases in serum creatinine, is able to detect some patients affected by subclinical AKI who have an increased risk of adverse outcomes. These results also suggest that the concept and definition of AKI might need to be reassessed.

HIF-1α is transcriptionally regulated by NF-κB in acute kidney injury

2021 ◽  
Author(s):  
Zuo-Lin Li ◽  
Jia-Ling Ji ◽  
Yi Wen ◽  
Jingyuan Cao ◽  
Naresh Kharbuja ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Hypoxia Inducible Factor ◽  
Kidney Injury ◽  
Hypoxic Condition ◽  
Nuclear Factor Κb ◽  
Transcriptional Level ◽  
Oxygen Homeostasis

Oxygen homeostasis disturbances play a critical role in the pathogenesis of acute kidney injury (AKI). The transcription factor hypoxia-inducible factor-1 (HIF-1) is a master regulator of adaptive responses to hypoxia. Aside from post-translational hydroxylation, mechanism of HIF-1 regulation in AKI remains largely unclear. In this study, the mechanism of HIF-α regulation in AKI was investigated. We found that tubular HIF-1α expression significantly increased at the transcriptional level in ischemia/reperfusion (I/R)-, unilateral ureteral obstruction (UUO)-, and sepsis-induced AKI models, which was closely associated with macrophage-dependent inflammation. Meanwhile, nuclear factor-κB (NF-κB), which plays a central role in inflammation response, was involved in the increasing expression of HIF-1α in AKI, as evidenced by pharmacological modulation (NF-κB inhibitor BAY11-7082). Mechanistically, NF-κB directly bound to the HIF-1α promoter and enhanced its transcription, which occurred not only in hypoxic condition, but also in normoxic condition. Moreover, the induced HIF-1α by inflammation protected against the tubular injury in AKI. Thus, our findings not only provide novel insight into HIF-1 regulation in AKI but also offer to understand the pathophysiology of kidney diseases.

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

2021 ◽  
Vol 22 (18) ◽  
pp. 9840
Author(s):  
Charles Verney ◽  
David Legouis ◽  
Sandrine Placier ◽  
Tiffany Migeon ◽  
Philippe Bonnin ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Ischemia Reperfusion Injury ◽  
Kidney Diseases ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Experimental Models ◽  
Renal Ischemia ◽  
New Device ◽  
Rapid Induction ◽  
Clamping Device

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

scholarly journals RGMb protects against acute kidney injury by inhibiting tubular cell necroptosis via an MLKL-dependent mechanism

2018 ◽  
Vol 115 (7) ◽  
pp. E1475-E1484 ◽  
Author(s):  
Wenjing Liu ◽  
Binbin Chen ◽  
Yang Wang ◽  
Chenling Meng ◽  
Huihui Huang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Apical Membrane ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Kidney Injury ◽  
Tubular Cell ◽  
Wild Type ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Proximal Tubular

Tubular cell necrosis is a key histological feature of acute kidney injury (AKI). Necroptosis is a type of programed necrosis, which is executed by mixed lineage kinase domain-like protein (MLKL) upon its binding to the plasma membrane. Emerging evidence indicates that necroptosis plays a critical role in the development of AKI. However, it is unclear whether renal tubular cells undergo necroptosis in vivo and how the necroptotic pathway is regulated during AKI. Repulsive guidance molecule (RGM)-b is a member of the RGM family. Our previous study demonstrated that RGMb is highly expressed in kidney tubular epithelial cells, but its biological role in the kidney has not been well characterized. In the present study, we found that RGMb reduced membrane-associated MLKL levels and inhibited necroptosis in cultured cells. During ischemia/reperfusion injury (IRI) or oxalate nephropathy, MLKL was induced to express on the apical membrane of proximal tubular (PT) cells. Specific knockout of Rgmb in tubular cells (Rgmb cKO) increased MLKL expression at the apical membrane of PT cells and induced more tubular cell death and more severe renal dysfunction compared with wild-type mice. Treatment with the necroptosis inhibitor Necrostatin-1 or GSK′963 reduced MLKL expression on the apical membrane of PT cells and ameliorated renal function impairment after IRI in both wild-type and Rgmb cKO mice. Taken together, our results suggest that proximal tubular cell necroptosis plays an important role in AKI, and that RGMb protects against AKI by inhibiting MLKL membrane association and necroptosis in proximal tubular cells.

scholarly journals A Clinical Case: the Risk Factors of Acute Kidney Injury in a Cardiological Patient

2021 ◽  
Vol 17 (1) ◽  
pp. 140-145
Author(s):  
E. A. Son ◽  
M. R. Kondratyuk ◽  
E. V. Fominykh ◽  
V. V. Fomin
Keyword(s):  
Acute Kidney Injury ◽  
Renal Artery ◽  
Clinical Case ◽  
Kidney Injury ◽  
Epidemiological Studies ◽  
Risk Of Death ◽  
Increased Risk ◽  
Artery Disease ◽  
Clinical Conditions ◽  
Renal Artery Disease

Recent epidemiological studies have demonstrated that the development of a potentially reversible moderate acute kidney injury is associated with worsening clinical outcomes and an increased risk of death. This is especially true for patients with plural comorbidities who require procedures with IV radiopaque agents. This paper presents a clinical case of an elderly patient who requires coronary angiography, and who has common clinical conditions such as hypertension, multifocal atherosclerosis with the development of renal artery disease and the presence of a history of acute cerebrovascular accident and myocardial infarction, and chronic heart failure as well. Particular attention is given to assessing the risk of developing contrast-induced acute kidney injury in patients with cardiovascular disease, as well as discussing current views on the possibility of prescribing drugs that affect the reninangiotensin system in cardiac patients with concomitant renal artery disease.

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