The effects of hemodialysis on blood glutamate levels in chronic renal failure: Implementation for neuroprotection

Rogachev, Boris; Ohayon, Sharon; Saad, Amit; Vorobiovsky, Victoria; Gruenbaum, Benjamin F.; Leibowitz, Akiva; Boyko, Matthew; Shapira, Yoram; Shnaider, Alla; Zlotnik, Moshe; Azab, Abed N.; Zlotnik, Alexander

doi:10.1016/j.jcrc.2012.07.002

Cited by 23 publications

(33 citation statements)

References 47 publications

(70 reference statements)

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“…Because the clinical manifestation of TBI-ALI lacks specificity and is often obscured by the primary disease, there is an urgent need for an objective and easily quantifiable parameter to predict the disease; therefore, blood glutamate levels make sense for use in clinical practice. Additionally, several studies have confirmed that lowering blood glutamate levels by haemofiltration 30 or peritoneal dialysis 31 exerts a protective effect on the brain. Based on the evidence revealed in this study, we believe that in the future, blood glutamate levels might be a good therapeutic target not only for brain injury but also for complicated lung injury in clinical practice.…”

Section: Discussionmentioning

confidence: 96%

Dramatic increases in blood glutamate concentrations are closely related to traumatic brain injury-induced acute lung injury

Bai

Zhu

Ning

et al. 2017

Sci Rep

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Traumatic brain injury-induced acute lung injury (TBI-ALI) is a serious complication after brain injury for which predictive factors are lacking. In this study, we found significantly elevated blood glutamate concentrations in patients with TBI or multiple peripheral trauma (MPT), and patients with more severe injuries showed higher blood glutamate concentrations and longer durations of elevated levels. Although the increase in amplitude was similar between the two groups, the duration was longer in the patients with TBI. There were no significant differences in blood glutamate concentrations in the patients with MPT with regard to ALI status, but the blood glutamate levels were significantly higher in the patients with TBI-ALI than in those without ALI. Moreover, compared to patients without ALI, patients with TBI showed a clearly enhanced inflammatory response that was closely correlated with the blood glutamate levels. The blood glutamate concentration was also found to be a risk factor (adjusted odds ratio, 2.229; 95% CI, 1.082–2.634) and was a better predictor of TBI-ALI than the Glasgow Coma Scale (GCS) score. These results indicated that dramatically increased blood glutamate concentrations were closely related to the occurrence of TBI-ALI and could be used as a predictive marker for “at-risk” patients.

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Section: Discussionmentioning

confidence: 96%

Dramatic increases in blood glutamate concentrations are closely related to traumatic brain injury-induced acute lung injury

Bai

Zhu

Ning

et al. 2017

Sci Rep

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“…Similar to blood glutamate scavengers, extracorporeal methods would thereby increase the concentration gradient between the brain and blood and increase the brain-to-blood glutamate efflux. The efficacy of blood glutamate reduction with HD, PD and HF has been studied in humans and animals [7,43–45]. …”

Section: Extracorpeal Methods Of Blood Glutamate Reductionmentioning

confidence: 99%

“…Rogachev et al [43] recently investigated the efficacy of using HD to eliminate excess plasma glutamate in humans. The authors reported that blood glutamate concentrations were significantly reduced during HD, and that low concentrations were maintained during the first few hours of a standard HD session.…”

Section: Extracorpeal Methods Of Blood Glutamate Reductionmentioning

confidence: 99%

“…Interestingly, patients with ESRD on HD were shown to have higher concentrations of blood glutamate compared with healthy controls [43,51]. There are several factors that may account for this increased glutamate in patients with chronic renal failure on HD, including altered lipid metabolism, decreased muscle mass and insulin resistance [51].…”

Section: Extracorpeal Methods Of Blood Glutamate Reductionmentioning

confidence: 99%

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Extracorporeal methods of blood glutamate scavenging: a novel therapeutic modality

Zhumadilov

Boyko

Gruenbaum

et al. 2015

Expert Review of Neurotherapeutics

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Pathologically elevated glutamate concentrations in the brain's extracellular fluid are associated with several acute and chronic brain insults. Studies have demonstrated that by decreasing the concentration of glutamate in the blood, thereby increasing the concentration gradient between the brain and the blood, the rate of brain-to-blood glutamate efflux can be increased. Blood glutamate scavengers, pyruvate and oxaloacetate have shown great promise in providing neuroprotection in many animal models of acute brain insults. However, glutamate scavengers’ potential systemic toxicity, side effects and pharmacokinetic properties may limit their use in clinical practice. In contrast, extracorporeal methods of blood glutamate reduction, in which glutamate is filtered from the blood and eliminated, may be an advantageous adjunct in treating acute brain insults. Here, we review the current evidence for the glutamate-lowering effects of hemodialysis, peritoneal dialysis and hemofiltration. The evidence reviewed here highlights the need for clinical trials.

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“…It was recently demonstrated that compared with healthy controls, patients with end-stage renal failure on hemodialysis (HD) had higher concentrations of blood glutamate (Rogachev et al 2012). During HD (especially in the first hour), glutamate concentrations decreased regardless of the size of filter pores, blood flow rate, or gender.…”

Section: Other Factors Affecting Blood Glutamate Concentrationsmentioning

confidence: 99%

Brain to blood glutamate scavenging as a novel therapeutic modality: a review

Boyko

Gruenbaum

et al. 2014

J Neural Transm

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It is well known that abnormally elevated glutamate levels in the brain are associated with secondary brain injury following acute and chronic brain insults. As such, a tight regulation of brain glutamate concentrations is of utmost importance in preventing the neurodegenerative effects of excess glutamate. There has been much effort in recent years to better understand the mechanisms by which glutamate is reduced in the brain to non-toxic concentrations, and in how to safely accelerate these mechanisms. Blood glutamate scavengers such as oxaloacetate, pyruvate, glutamate–oxaloacetate transaminase, and glutamate-pyruvate transaminase have been shown to reduce blood glutamate concentrations, thereby increasing the driving force of the brain to blood glutamate efflux and subsequently reducing brain glutamate levels. In the past decade, blood glutamate scavengers have gained increasing international interest, and its uses have been applied to a wide range of experimental contexts in animal models of traumatic brain injury, ischemic stroke, subarachnoid hemorrhage, epilepsy, migraine, and malignant gliomas. Although glutamate scavengers have not yet been used in humans, there is increasing evidence that their use may provide effective and exciting new therapeutic modalities. Here, we review the laboratory evidence for the use of blood glutamate scavengers. Other experimental neuro-protective treatments thought to scavenge blood glutamate, including estrogen and progesterone, beta-adrenergic activation, hypothermia, insulin and glucagon, and hemodialysis and peritoneal dialysis are also discussed. The evidence reviewed here will hopefully pave the way for future clinical trials.

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The effects of hemodialysis on blood glutamate levels in chronic renal failure: Implementation for neuroprotection

Cited by 23 publications

References 47 publications

Dramatic increases in blood glutamate concentrations are closely related to traumatic brain injury-induced acute lung injury

Dramatic increases in blood glutamate concentrations are closely related to traumatic brain injury-induced acute lung injury

Extracorporeal methods of blood glutamate scavenging: a novel therapeutic modality

Brain to blood glutamate scavenging as a novel therapeutic modality: a review

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