Article Delayed recovery from ertapenem induced encephalopathy: case-report and a possible mechanism. https://doi.org/10.1378/chest.128.3.1674. As a library, NLM provides access to scientific literature. Li X, Liu C, Mao Z, Li Q, Zhou F. Timing of renal replacement therapy initiation for acute kidney injury in critically ill patients: a systematic review of randomized clinical trials with meta-analysis and trial sequential analysis. Up-regulation of TLR-4 in the brain after ischemic kidney-induced encephalopathy in the rat. Zhang J, Crichton S, Dixon A, Seylanova N, Peng ZY, Ostermann M. Cumulative fluid accumulation is associated with the development of acute kidney injury and non-recovery of renal function: a retrospective analysis. Pain Med. As with other organs affected by AKI, the pathogenesis of AKI-associated delirium is multifactorial, and hypothesized to be due to direct and indirect pathways, mediated by toxin and drug accumulations [25], electrolyte imbalances [28], impaired volume homeostasis [29], neuroinflammation [13], and imbalances in neurotransmitters [30] (Fig. 2017;56(8):893913. https://doi.org/10.1164/rccm.201603-0476OC. Terrando N, Eriksson LI, Ryu JK, et al. Delirium - Neurologic Disorders - Merck Manuals Ann Emerg Med. Thus, such agents must be used with caution in patients with renal disease given that serum levels of glucuronidated metabolites of tricyclic antidepressants accumulate with kidney dysfunction. The pro-inflammatory cytokines, IL-6, TNF-, IL-1, IL-1, have been implicated in delirium-like behavioral changes, such as impaired concentration, diminished motivation, and psychomotor retardation in critically ill patients [52, 58,59,60]. Thus, a reasonable approach to fluid status in a patient with AKI is to avoid hypervolemia, which not only protects the kidneys from further injury [87], but also protects the brain. A summary of clinical studies that have evaluated AKI as a risk factor in the development of delirium is presented in Table 1. In a prospective study of 1487 patients, Zipser et al. 2007;167:162934. 2003;14:154958. Siew ED, Fissell WH, Tripp CM, et al. Neurobiol Aging. Further investigations into the cognitive effects of fluid overload in the setting of AKI are warranted. Further clinical evidence of AKIs potential role in contributing to delirium was provided by Wan et al. Another potential mechanism of AKI-associated delirium is fluid overload, which can occur in 40% of patients in the ICU [83]. Although the underlying mechanisms for AKI-associated delirium remain largely unknown, several pathobiological processes have been proposed, including accumulation of neurotoxins or deliriogenic drugs due to impaired renal clearance, upregulation of systemic cytokine-mediated neuroinflammatory processes, and volume overloaded conditions. https://doi.org/10.1093/ndt/gfm713. Pre-operative, high-IL-6 blood level is a risk factor of post-operative delirium onset in old patients. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Antibiotic-associated encephalopathy. Trzepacz PT. BBB leakage thus promotes brain edema and allows for movement of neurotoxic substances into the brain [86], resulting in delirium. 2012;25(3):2536. Springer; 2019. p. 397404. Kidney Int. Concordantly, a study by Nguyen et al. Grams ME, Rabb H. The distant organ effects of acute kidney injury. While studies using NMDA receptor antagonists to reduce postoperative delirium have yielded mixed results, further research is needed to assess the role of NMDA receptor agonists specifically in AKI-associated delirium. Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study. Before Delirium is a confused mental state that includes changes in awareness, thinking, judgment, sleeping patterns, as well as behavior. It is now understood that delirium independently contributes to long-term cognitive decline [19], rather than merely an unmasking of a vulnerable brain substrate. Prescribing non-opioid drugs in end-stage kidney disease. Lab Invest. J Am Soc Nephrol. During its entire course, it may disappear and come back again. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Adachi N, Lei B, Deshpande G, et al. 1999;55:23627. This hypothesis comes from studies of AKI in canines, which identified biochemical alternations in the brain, whereby calcium contents in gray and white matter markedly increased 3days after the onset of AKI along with a modest increment of magnesium in delirium-relevant regions of the brain. Current evidence suggests that, when possible, gradual normalization of kidney function may ameliorate delirium; however, optimization of other clinical contributors, such as deliriogenic drugs, including analgosedation and antibiotics, provides additional opportunities to mitigate delirium. Interleukin-6 mediates delirium-like phenotypes in a murine model of urinary tract infection. Kelly KJ. WebDelirium typically goes away in a few hours to a few days or several weeks or months. J Neurosci Res. In this study, patients with KDIGO stage 3 AKI were five times more likely to develop hyperactive delirium (OR 5.40, 95% CI 2.3312.51) than those without AKI and that less severe stages of AKI, i.e., KDIGO stage 1 or 2 AKI, were not independently associated with hyperactive delirium [25]. The author(s) received no financial support for the research, authorship, and/or publication of this article. 2006;290(5):F1187-1193. Despite the relative renal safety of lorazepam, a side effect of the solvent used in intravenous lorazepam can produce propylene glycol toxicity, which can lead to proximal tubular necrosis resulting in AKI, in addition to metabolic acidosis, serum hyperosmolality, and elevated anion gap [102]. Bhattacharyya S, Darby RR, Raibagkar P, Gonzalez Castro LN, Berkowitz AL. Long-term cognitive impairment after critical illness. J Pain Symptom Manag. Nephrol Dial Transplant. Encephalopathy Google Scholar. Serum S-100beta as a possible marker of blood-brain barrier disruption. We further identify critical knowledge gaps in understanding of underlying biological mechanisms and clinical contributors to inform design of future studies that address novel preventative and therapeutic discoveries. As noted earlier, uremic guanidino compounds may play a central role in AKI-associated delirium by promoting NMDA receptor-mediated depolarization of hippocampal neurons, therefore minimizing epileptiform discharges, and hippocampal damage [33]. Therefore, future studies are needed to assess the role of NMDA receptor antagonists to prevent or treat AKI-associated delirium. This point was suggested by findings by Liu et al. Cibelli M, Fidalgo AR, Terrando N, et al. Lieberman JA, Cooper TB, Suckow RF, et al. Anesthesiology. Another common explanation for delirium in the setting of AKI is the accumulation of drugs that are frequently administered in the ICU setting. Kapural M, Krizanac-Bengez L, Barnett G, et al. As noted earlier, uremic guanidino compounds may play a central role in AKI-associated delirium by promoting NMDA receptor-mediated depolarization of hippocampal neurons, therefore minimizing epileptiform discharges, and hippocampal damage [33]. 1985;37(3):3017. WebAcute kidney injury (AKI), also known as acute renal failure (ARF), is a sudden episode of kidney failure or kidney damage that happens within a few hours or a few days. Opioid dosing in renal and hepatic impairment. Although delirium has not been specifically evaluated in prior studies using ultrafiltration, prior studies have shown improved rates of extracerebral organ dysfunction with lower compared to higher rates of ultrafiltration [96]. Androsova G, Krause R, Winterer G, Schneider R. Biomarkers of postoperative delirium and cognitive dysfunction. [. In https://doi.org/10.1097/01.ASN.0000064946.94590.46. Cytokines and postoperative delirium in older patients undergoing major elective surgery. 10.1007/978-3-030-06067-1_31. Wilcock A, Charlesworth S, Twycross R, et al. Intensive Care Med. Opioids that undergo significant clearance through the kidneys should be avoided. The optimization of clinical contributors and normalization of renal function are reviewed as pragmatic management strategies in addition to potential and emerging therapeutic approaches. The pro-inflammatory cytokines, IL-6, TNF-, IL-1, IL-1, have been implicated in delirium-like behavioral changes, such as impaired concentration, diminished motivation, and psychomotor retardation in critically ill patients [52, 5860]. 2013;17(6):R278. Acute toxic-metabolic encephalopathy (TME), which encompasses delirium and the acute confusional state, is an acute condition of global cerebral dysfunction in the absence of primary structural brain disease [ 1 ]. Cibelli M, Fidalgo AR, Terrando N, et al. Delirium WebWhat is delirium? Therefore, in the setting of AKI, it seems reasonable to use dexmedetomidine over other types of sedatives [114]. https://doi.org/10.1016/j.jpainsymman.2017.08.014. 2007;18(1):15564. Prommer E. Midazolam: an essential palliative care drug. J Neurol Sci. Clin Neurol Neurosurg. ICU delirium: a diagnostic and therapeutic challenge in the intensive care unit. https://doi.org/10.1016/j.expneurol.2007.01.037. Up-regulation of TLR-4 in the brain after ischemic kidney-induced encephalopathy in the rat. AKI may also lead to changes in the hormonal balance and neurotransmitter turnover in the brain which may contribute to delirium. Distant effects of experimental renal ischemia/reperfusion injury. https://doi.org/10.4103/psychiatry.IndianJPsychiatry_583_18. Google Scholar. Hoke TS, Douglas IS, Klein CL, et al. Methods. Nguyen et al. The site is secure. Jckel M, Aicher N, Rilinger J, et al. Delirium - Brain, Spinal Cord, and Nerve Disorders - Merck Causes of Delirium | American Geriatrics Society Cross-talk between the nervous system and the kidney. Calcium metabolism of brain in acute renal failure. End Stage Renal Disease (ESRD There is mounting preclinical evidence that AKI induces systemic inflammation, which is considered a key contributing mechanism of delirium [47]. Animal models demonstrate that the structural areas of the brain disproportionately affected by AKI-induced inflammatory mediators include the CA1 region of the hippocampus [13], which is consistent with the semiology of delirium and the hippocampus established involvement in learning and memory as well as anxiety and depression [71]. BMJ. Kidney failure. Delirium epidemiology in critical care (DECCA): an international study. 2018;144:17285. King S, Forbes K, Hanks G, Ferro C, Chambers E. A systematic review of the use of opioid medication for those with moderate to severe cancer pain and renal impairment: a European Palliative Care Research Collaborative opioid guidelines project. Barrientos RM, Higgins EA, Biedenkapp JC, et al. on the comparative risk of delirium with different opioids found the highest risk of delirium with meperidine and tramadol, likely due to the high anticholinergic properties of the opioids and their metabolites [44]. Serum S100B in elderly patients with and without delirium. https://doi.org/10.1093/bja/aer461. 2012;81:9428. Furthermore, the CA1 neurons of the hippocampus are vulnerable to damage in several other conditions that result in neurodegeneration, including global cerebral ischemia, Alzheimers disease, and prion diseases [72,73,74]. Many disorders cause delirium. 2019;23(1):352. https://doi.org/10.1186/s13054-019-2626-z. Crit Care 26, 258 (2022). Heldt S, Stanek L, Chhatwal J, Ressler K. Hippocampus-specific deletion of BDNF in adult mice impairs spatial memory and extinction of aversive memories. Endpoint: 48h, Readout: motor activity and brain monoamine turnover, Turnover of DA in the striatum, mesencephalon and hypothalamus, UTI, urinary tract infection; cDNA, complementary deoxyribonucleic acid; TLR-4, toll-like receptor-4; AKI, acute kidney injury; IL-6, interleukin-6; mRNA, messenger RNA; G-CSF, granulocyte colony-stimulating factor; and DA, dopamine. The disorder Introduction Delirium occurs in approximately 60% of patients with acute kidney injury (AKI) [ 1 ]. For instance, the metabolites of tramadol, morphine, codeine, and meperidine are renally cleared [45, 104] and thus justify caution or dose adjustment in the setting of AKI. In addition to the important problems related to renal Ann Neurol. Increased risk of dementia in patients hospitalized with acute kidney injury: a nationwide population-based cohort study. Delirium Am J Respir Cell Mol Biol. Cytokines and postoperative delirium in older patients undergoing major elective surgery. This pro-inflammatory milieu precipitated by AKI is hypothesized to contribute to multi-organ injury, including the brain [50,51,52]. Trzepacz PT. Among various cytokines, IL-6 has been frequently studied as a potential predictor of delirium in urinary tract infection, sepsis, acute lung injury, and perioperative animal models [53, 6166]. Crit Care. Nephrol Dial Transplant Off Publ Eur Dial Transpl Assoc Eur Ren Assoc. For instance, it has been found that orthopedic surgery disrupts the BBB and promotes infiltration of bone marrow-derived monocytes [68] and activation of microglia [69] in rodents. 2008;65(3):22938. Effect of renal impairment and hemodialysis on lorazepam kinetics. Int J Mol Sci. https://doi.org/10.1681/ASN.2006050494. 2008;42(12):184350. Received 2022 Apr 28; Accepted 2022 Aug 20. PubMed Central Am J Physiol Renal Physiol. volume26, Articlenumber:258 (2022) Findings persisted when using an alternative definition for AKI, Limitations: Single-center population. Ethics approval and consent to participate. 2019;10:712. https://doi.org/10.3389/fpsyt.2019.00712. Clinical Considerations in Renal Failure, Depression, and Delirium Thus, the activation of central immune cells leading to neuronal injury and dysfunction [82] may contribute to post-AKI delirium (Fig. J Affect Disord. 2012;116:113948. 2008;19(6):110615. Although delirium can happen at the end of life, many episodes of delirium are caused by medicine or dehydration and are reversible.. In this comprehensive review of clinical and basic research studies, we detail the epidemiology, clinical implications, pathogenesis, and management strategies of patients with acute kidney injury-associated delirium. Miller A, Price G. Gabapentin toxicity in renal failure: the importance of dose adjustment. Acute kidney failure - Symptoms and causes - Mayo Clinic Consider the use of renal replacement therapy to reduce risk of delirium, Systematic review and meta-analysis on dexmedetomidine, Overall incidence of delirium in the dexmedetomidine group was significantly lower compared to placebo, standard sedatives, and opioids, Preferential use of dexmedetomidine for sedation, which may also potentially be renally protective (Liu et al. Posterior reversible encephalopathy syndrome is an increasingly recognized disorder, with a wide clinical spectrum of both symptoms and triggers, and yet it remains poorly understood. In the short term, delirium is well known to be strongly associated with increased mortality, prolonged hospitalization, and need for intensive medical interventions [1], while persistent cognitive decline is a feared long-term sequela [19]. 2021. https://doi.org/10.1093/ndt/gfab283. By using this website, you agree to our Lee SA, Cozzi M, Bush EL, Rabb H. Distant organ dysfunction in acute kidney injury: a review. This is evidenced by mouse models of AKI that demonstrated extravasation of Evans blue dye into the brain, indicating breakdown of the BBB [13]. Zar T, Graeber C, Perazella MA. Popkov VA, Silachev DN, Zalevsky AO, Zorov DB, Plotnikov EY. There is mounting preclinical evidence that AKI induces systemic inflammation, which is considered a key contributing mechanism of delirium [47]. First to examine admission risk factors, Limitations: Missing data on risk factors, specifically liver function test and arterial pH. Therefore, future studies are needed to assess the role of NMDA receptor antagonists to prevent or treat AKI-associated delirium. Perhaps intuitively, it is hypothesized that AKI precipitates delirium due to impaired renal clearance of drugs and toxic metabolic waste products. Article Cefepime-induced neurotoxicity is a relatively commonly precipitant of delirium, imposing up to a tenfold greater risk of neurotoxicity when compared to meropenem, and occurring in up to 15% of ICU patients treated with cefepime [42]. Grill MF, Maganti R. Cephalosporin-induced neurotoxicity: clinical manifestations, potential pathogenic mechanisms, and the role of electroencephalographic monitoring. Morrison G, Chiang ST, Koepke HH, Walker BR. 2009;301(5):48999. Dean M. Opioids in renal failure and dialysis patients. Genetic variations in the interleukin-6 and interleukin-8 genes and the interleukin-6 receptor gene in delirium. TLR-4, toll-like receptor-4; KC, keratinocyte-derived chemokine; G-CSF, granulocyte colony-stimulating factor; MCP-1, monocyte chemoattractant protein-1; and GFAP, glial fibrillary acidic protein. It results in confused thinking and a lack of awareness of someone's surroundings. Delirium is a sudden and severe change in brain function that causes a person to appear confused or disoriented, or to have difficulties maintaining focus, thinking clearly, and remembering recent events, typically with a fluctuating course. 2003;14(6):154958. Weerink MAS, Struys MMRF, Hannivoort LN, Barends CRM, Absalom AR, Colin P. Clinical pharmacokinetics and pharmacodynamics of dexmedetomidine. Eldehni MT, McIntyre CW. JAMA. The neuroinflammatory hypothesis of delirium. Annual update in intensive care and emergency medicine. 2004;342(12):112. Reversible Encephalopathy and Delirium in Patients with found that at least chronic kidney disease was significantly associated with periodic epileptiform discharges. Continuous electroencephalography in the medical intensive care unit*. Clinical evidence of BBB disruption serving a pathophysiologic role in delirium is provided in one study that showed elevated serum levels of S100, the marker of BBB damage [56] in elderly patients with delirium [57]. Vutukuri R, Brunkhorst R, Kestner RI, et al. In persons with functioning kidneys, it is removed by the kidneys. Lee SA, Cozzi M, Bush EL, Rabb H. Distant organ dysfunction in acute kidney injury: a review. In: Vincent JL, editors. Cookies policy. Arulkumaran N, Montero RM, Singer M. Management of the dialysis patient in general intensive care. Springer Nature. 1992;112(1):96105. Additionally, a systematic review by Swart et al. Dexmedetomidines delirium-sparing effects in AKI may also be related to its hepatic clearance [112], and potential renoprotective effects [113] via stabilization of the sympathetic system, and anti-inflammatory toll-like receptor-4-mediated effects [113]. AKI is estimated to affect more than 10 million people worldwide annually and confer a 1.76.9-fold increased risk of hospital mortality [8, 9]. Federal government websites often end in .gov or .mil. Overall, the dose-dependent relationship between severity of AKI and delirium identified by these studies suggests a direct pathological role, though causality cannot be reasonably established with clinical studies that may be susceptible to the presence of multiple confounding factors including, but not limited to, heterogeneities in use of analgosedation, identification of patients with increased susceptibility to delirium, such as those with preexisting cognitive impairment, and varied environmental triggers of delirium. Overall, the dose-dependent relationship between severity of AKI and delirium identified by these studies suggests a direct pathological role, though causality cannot be reasonably established with clinical studies that may be susceptible to the presence of multiple confounding factors including, but not limited to, heterogeneities in use of analgosedation, identification of patients with increased susceptibility to delirium, such as those with preexisting cognitive impairment, and varied environmental triggers of delirium. Blood-brain barrier breakdown in septic encephalopathy and brain tumours. HP drafted the manuscript. In younger people, read more or kidney failure Overview of Kidney Failure Kidney Murugan R, Kerti SJ, Chang CCH, et al. Salluh JI, Soares M, Teles JM, Delirium Epidemiology in Critical Care Study Group et al. Incidence and predictors of delirium on the intensive care unit in patients with acute kidney injury, insight from a retrospective registry. Liu Y, Sheng B, Wang S, Lu F, Zhen J, Chen W. Dexmedetomidine prevents acute kidney injury after adult cardiac surgery: a meta-analysis of randomized controlled trials. Substantial clinical evidence suggests a direct pathological role for AKI in delirium. Sparrow NA, Anwar F, Covarrubias AE, et al. With the possible exception of renal replacement therapy, existing treatment paradigms are limited to lower, indirect evidence of benefit. A summary of the potential therapeutic approaches to AKI-associated delirium is provided in Table Table33. Strm T, Johansen RR, Prahl JO, Toft P. Sedation and renal impairment in critically ill patients: a post hoc analysis of a randomized trial. Association between systemic hemodynamics and septic acute kidney injury in critically ill patients: a retrospective observational study. Fluid buildup.Acute 1). 2023 BioMed Central Ltd unless otherwise stated. Accessed 26 Jan 2022. Ann Pharmacother. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Summary of evidence-based therapies, potentially useful therapies, and emerging therapies to prevent AKI-associated delirium, Renal replacement therapy is associated with a reduced odds of delirium in AKI, Future studies are needed to examine the mechanisms underlying these associations and the effects renal replacement therapy may have on AKI-associated delirium. 2013;12(5):5836. https://doi.org/10.1016/0304-3940(96)12615-X. Nguyen DN, Huyghens L, Parra J, Schiettecatte J, Smitz J, Vincen JL. 2021;65(4):40312. Acute Kidney Injury as a Risk Factor for Delirium and Coma during 10.1111/jgs.15767. Delirium Flkiger J, Hollinger A, Speich B, et al. Fluid overload is thought to increase capillary transmural hydrostatic pressure, resulting in fluid leak into brain interstitial tissue causing cerebral edema [83]. 2019;28(6):46270. Cognitive alterations in chronic kidney disease: an update Causes Risk factors Symptoms Diagnosis Treatment Outlook Delirium is a sudden change in your alertness and thinking. Convulsive action and toxicity of uremic guanidino compounds: behavioral assessment and relation to brain concentration in adult mice. Another potential mechanism of AKI-associated delirium is fluid overload, which can occur in 40% of patients in the ICU [83]. 2020;14:2632352419895527. https://doi.org/10.1177/2632352419895527. Renal ischemia/reperfusion leads to macrophage-mediated increase in pulmonary vascular permeability. Several studies have identified AKI as a principal risk factor for delirium. Impairment of cognitive functions occurs frequently in chronic kidney disease (CKD). Not all codes could be included and information may be skewed or lost in this process, (OR 10.01, CI 1.1388.73, p=0.039). An expanded discussion on the risks of delirium from analgosedatives in the setting of AKI will be reviewed below. https://doi.org/10.1111/j.1526-4637.2008.00492.x. Patients aged over 65 years admitted PubMed Critical Care The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. Springer; 2019. p. 397404. Future studies should consistently report whether the investigated mechanisms or risk factors relate to hypoactive, hyperactive, or both delirium phenotypes. Nelson RL, Guo Z, Halagappa VM, et al. Objectives: To examine Accumulation of normeperidine, an active metabolite of meperidine, in patients with renal failure or cancer. Dexmedetomidine vs midazolam for sedation of critically ill patients: a randomized trial. Bagshaw SM, Wald R, Adhikari NK, Bellomo R, da Costa BR, Dreyfuss D, Gallagher MP, Gaudry S, Hoste E, Lamontagne F, Joannidis M. Timing of initiation of renal-replacement therapy in acute kidney injury. Acute renal failure after bilateral nephrectomy is associated with cytokine-mediated pulmonary injury. HHS Vulnerability Disclosure, Help Fluid overload is thought to increase capillary transmural hydrostatic pressure, resulting in fluid leak into brain interstitial tissue causing cerebral edema [83]. Psychosomatics. IL-6 inhibition reduces neuronal injury in a murine model of ventilator-induced lung injury. Delirium Neurosci Lett. Delirium - Symptoms and causes - Mayo Clinic https://doi.org/10.1186/cc9333. Acute vs. chronic serum creatinine level>2 was not distinguished as being associated with delirium, Strength: Large sample size and prospective design. Pre-operative, high-IL-6 blood level is a risk factor of post-operative delirium onset in old patients. Kidney Int. https://doi.org/10.1002/ams2.508. Opioid dosing in renal and hepatic impairment. 2016;86(10):96371. Crit Care. Delirium is a sudden change in a persons mental function. This is concordant with clinical studies that have found that high levels of IL-6 preoperatively were significantly associated with postoperative delirium in patients admitted for elective and emergency surgery [62, 70]. IL-6 inhibition reduces neuronal injury in a murine model of ventilator-induced lung injury. If too many of these toxins are allowed to build up, they can alter brain function and lead to asterixis. Brown AS, Gershon S. Dopamine and depression. Future studies are needed to examine the viability of ultrafiltration in hypervolemic patients with AKI to mitigate delirium. SK, WE, MG, and SL read, edited, and approved the final manuscript. Retrospective design limited to data recorded in electronic health records, Strengths: At the time, the largest collection of data on delirium among older ICU patients. Distant effects of experimental renal ischemia/reperfusion injury. Introduction. The most common clinical manifestation of AKI-associated acute brain injury is delirium, which presents as an acute or fluctuating impairment in attention, executive, function, or short-term memory [3, 1418]. The pathogenesis of AKI-associated delirium is multifactorial and includes both inflammatory- and non-inflammatory-mediated processes, such as the accumulation of toxins and drugs, structural brain injury from systemic inflammation, impaired volume homeostasis, and hormonal and neurotransmitter effects. https://doi.org/10.1001/jamaneurol.2020.2273. Summary of experimental studies on the effects of inflammation on the central nervous system, Readout: behavioral and structural brain dysfunction, 60min bilateral ischemia reperfusion injury-induced AKI, Bilateral renal ischemia reperfusion injury in rats, Keratinocyte-derived chemoattractant and G-CSF in the cerebral cortex and hippocampus, acidic protein in astrocytes in the cortex and corpus callosum, Bilateral rat renal artery occlusion.
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