scholarly journals “I don’t get no respect”: the role of chloride in acute kidney injury

2019 ◽  
Vol 316 (3) ◽  
pp. F587-F605 ◽  
Author(s):  
Joshua L. Rein ◽  
Steven G. Coca
Keyword(s):  
Acute Kidney Injury ◽  
Chloride Concentration ◽  
Kidney Injury ◽  
Chloride Content ◽  
Tubuloglomerular Feedback ◽  
Renal Physiology ◽  
Major Public Health Problem ◽  
Serum Chloride ◽  
Increased Risk

Acute kidney injury (AKI) is a major public health problem that complicates 10–40% of hospital admissions. Importantly, AKI is independently associated with increased risk of progression to chronic kidney disease, end-stage renal disease, cardiovascular events, and increased risk of in-hospital and long-term mortality. The chloride content of intravenous fluid has garnered much attention over the last decade, as well as its association with excess use and adverse outcomes, including AKI. Numerous studies show that changes in serum chloride concentration, independent of serum sodium and bicarbonate, are associated with increased risk of AKI, morbidity, and mortality. This comprehensive review details the complex renal physiology regarding the role of chloride in regulating renal blood flow, glomerular filtration rate, tubuloglomerular feedback, and tubular injury, as well as the findings of clinical research related to the chloride content of intravenous fluids, changes in serum chloride concentration, and AKI. Chloride is underappreciated in both physiology and pathophysiology. Although the exact mechanism is debated, avoidance of excessive chloride administration is a reasonable treatment option for all patients and especially in those at risk for AKI. Therefore, high-risk patients and those with “incipient” AKI should receive balanced solutions rather than normal saline to minimize the risk of AKI.

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.

scholarly journals Fluctuations in Serum Chloride and Acute Kidney Injury among Critically Ill Patients: A Retrospective Association Study

2019 ◽  
Vol 8 (4) ◽  
pp. 447 ◽  
Author(s):  
Tak Kyu Oh ◽  
In-Ae Song ◽  
Young-Tae Jeon ◽  
You Hwan Jo
Keyword(s):  
Acute Kidney Injury ◽  
Confidence Interval ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Odds Ratio ◽  
Kidney Injury ◽  
Icu Admission ◽  
Serum Chloride ◽  
Increased Risk ◽  
The Difference

Exposure to dyschloremia among critically ill patients is associated with an increased risk of acute kidney injury (AKI). We aimed to investigate how fluctuations in serum chloride (Cl−) are associated with the development of AKI in critically ill patients. We retrospectively analyzed medical records of adult patients admitted to the intensive care unit (ICU) between January 2012 and December 2017. Positive and negative fluctuations in Cl− were defined as the difference between the baseline Cl- and maximum Cl- levels and the difference between the baseline Cl− and minimum Cl− levels measured within 72 h after ICU admission, respectively. In total, 19,707 patients were included. The odds of developing AKI increased 1.06-fold for every 1 mmol L−1 increase in the positive fluctuations in Cl− (odds ratio: 1.06; 95% confidence interval: 1.04 to 1.08; p < 0.001) and 1.04-fold for every 1 mmol L−1 increase in the negative fluctuations in Cl− (odds ratio: 1.04; 95% confidence interval: 1.02 to 1.06; p < 0.001). Increases in both the positive and negative fluctuations in Cl- after ICU admission were associated with an increased risk of AKI. Furthermore, these associations differed based on the functional status of the kidneys at ICU admission or postoperative ICU admission.

scholarly journals Regulation of mRNA translation in renal physiology and disease

2009 ◽  
Vol 297 (5) ◽  
pp. F1153-F1165 ◽  
Author(s):  
Balakuntalam S. Kasinath ◽  
Denis Feliers ◽  
Kavithalakshmi Sataranatarajan ◽  
Goutam Ghosh Choudhury ◽  
Myung Ja Lee ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Protein Synthesis ◽  
Messenger Rna ◽  
Kidney Injury ◽  
Mrna Translation ◽  
Renal Physiology ◽  
Physiological Adaptation ◽  
Three Stages ◽  
A Site

Translation, a process of generating a peptide from the codons present in messenger RNA, can be a site of independent regulation of protein synthesis; it has not been well studied in the kidney. Translation occurs in three stages (initiation, elongation, and termination), each with its own set of regulatory factors. Mechanisms controlling translation include small inhibitory RNAs such as microRNAs, binding proteins, and signaling reactions. Role of translation in renal injury in diabetes, endoplasmic reticulum stress, acute kidney injury, and, in physiological adaptation to loss of nephrons is reviewed here. Contribution of mRNA translation to physiology and disease is not well understood. Because it is involved in such diverse areas as development and cancer, it should prove a fertile field for investigation in renal science.

scholarly journals Toll-Like Receptors in Acute Kidney Injury

2021 ◽  
Vol 22 (2) ◽  
pp. 816
Author(s):  
Cristina Vázquez-Carballo ◽  
Melania Guerrero-Hue ◽  
Cristina García-Caballero ◽  
Sandra Rayego-Mateos ◽  
Lucas Opazo-Ríos ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Acute Kidney Injury ◽  
Kidney Disease ◽  
Pathological Condition ◽  
Kidney Injury ◽  
Preclinical Studies ◽  
Toll Like Receptors ◽  
Middle Income ◽  
Increased Risk

Acute kidney injury (AKI) is an important health problem, affecting 13.3 million individuals/year. It is associated with increased mortality, mainly in low- and middle-income countries, where renal replacement therapy is limited. Moreover, survivors show adverse long-term outcomes, including increased risk of developing recurrent AKI bouts, cardiovascular events, and chronic kidney disease. However, there are no specific treatments to decrease the adverse consequences of AKI. Epidemiological and preclinical studies show the pathological role of inflammation in AKI, not only at the acute phase but also in the progression to chronic kidney disease. Toll-like receptors (TLRs) are key regulators of the inflammatory response and have been associated to many cellular processes activated during AKI. For that reason, a number of anti-inflammatory agents targeting TLRs have been analyzed in preclinical studies to decrease renal damage during AKI. In this review, we updated recent knowledge about the role of TLRs, mainly TLR4, in the initiation and development of AKI as well as novel compounds targeting these molecules to diminish kidney injury associated to this pathological condition.

scholarly journals Associations of Fluid Amount, Type, and Balance and Acute Kidney Injury in Patients Undergoing Major Surgery

2018 ◽  
Vol 46 (1) ◽  
pp. 79-87 ◽  
Author(s):  
L. Weinberg ◽  
M. H. G. Li ◽  
L. Churilov ◽  
A. Armellini ◽  
M. Gibney ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Fluid Balance ◽  
Kidney Injury ◽  
Chloride Content ◽  
Fluid Administration ◽  
Major Surgery ◽  
Confounding Effect ◽  
Increased Risk ◽  
Duration Of Surgery ◽  
Independent Association

Fluid administration has been reported to be associated with an increased risk of acute kidney injury (AKI). We assessed whether, after correction for fluid balance, amount and chloride content of fluids administered have an independent association with AKI. We performed an observational study in patients after major surgery assessing the independent association of AKI with volume, chloride content and fluid balance, after adjustment for Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM) score, age, elective versus emergency surgery, and duration of surgery. We studied 542 consecutive patients undergoing major surgery. Of these, 476 patients had renal function tested as part of routine clinical care and 53 patients (11.1%) developed postoperative AKI. After adjustments, a 100 ml greater mean daily fluid balance was artificially associated with a 5% decrease in the instantaneous hazard of AKI: adjusted Hazard Ratio (aHR) 0.951, 95% confidence intervals (CI) 0.935 to 0.967, P <0.001. However, after adjustment for the proportion of chloride-restrictive fluids, mean daily fluid amounts and balances, POSSUM morbidity, age, duration and emergency status of surgery, and the confounding effect of fluid balance, every 5% increase in the proportion of chloride-liberal fluid administered was associated with an 8% increase in the instantaneous hazard of AKI (aHR 1.079, 95% CI 1.032 to 1.128, P=0.001), and a 100 ml increase in mean daily fluid amount given was associated with a 6% increase in the instantaneous hazard of AKI (aHR 1.061, 95% CI 1.047 to 1.075, P <0.001). After adjusting for key risk factors and for the confounding effect of fluid balance, greater fluid administration and greater administration of chloride-rich fluid were associated with greater risk of AKI.

scholarly journals Complement activation fragments are increased in critically ill pediatric patients with severe acute kidney injury

Kidney360 ◽  
2021 ◽  
pp. 10.34067/KID.0004542021
Author(s):  
Erin K Stenson ◽  
Zhiying You ◽  
Ron Reeder ◽  
Jesse Norris ◽  
Halden F. Scott ◽  
...  
Keyword(s):  
At Risk ◽  
Acute Kidney Injury ◽  
Critically Ill ◽  
Complement Activation ◽  
Kidney Injury ◽  
Critically Ill Children ◽  
High Morbidity ◽  
Increased Risk ◽  
Severity Scores

Background:Critically ill children with acute kidney injury (AKI) suffer from high morbidity and mortality rates, and lack treatment options. Emerging evidence implicates the role of complement activation in AKI pathogenesis, which could potentially be treated with complement inhibitors. The purpose of this study is to evaluate the association between complement activation fragments and severity of AKI in critically ill children. Methods:A biorepository of critically ill children from a prior multi-site study was leveraged to identify children with stage 3 AKI and matched to patients without AKI based on PELOD-2 (illness severity) scores. Specimens were analyzed for plasma and urine complement activation fragments of factor B, C3a, C4a, and sC5b-9. The primary outcomes were MAKE30 and severe AKI rates. Results:14 patients with stage 3 AKI (5 requiring renal replacement therapy [RRT]) were matched to 14 patients without AKI. Urine factor Ba and plasma C4a levels increased stepwise as severity of AKI increased, from no AKI to stage 3 AKI, to stage 3 AKI with RRT need. Plasma C4a levels were independently associated with increased risk of MAKE30 outcomes (OR 3.2; IQR 1.1-8.9), and urine Ba and plasma Bb, C4a, and C3a were independently associated with risk of severe stage 2-3 AKI on day 3 of admission. Conclusions:Multiple complement fragments increase as magnitude of AKI severity increases. Very high levels of urine Ba or plasma C4a may identify patients at risk for severe AKI, hemodialysis, and MAKE30 outcomes. The fragments may be useful as a functional biomarker of complement activation and may identify those patients to study complement inhibition to treat or prevent AKI in critically ill children. These findings suggest the need for further specific investigations of the role of complement activation in critically ill children at risk of AKI.

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