Prevention Of Acute Kidney Injury Research Articles

RHABDOMYOLYSIS: HOW MUCH DO WE KNOW ABOUT IT? MODERN CLINICAL CONSENSUS (Literature review)

The article presents a review of the world data on modern approaches to the treatment of patients with rhabdomyolysis according to the principles of evidence-based medicine. Rhabdomyolysis is a condition occurring in critically ill and injured patients. But only 20 % of all cases of rhabdomyolysis are usually related to direct trauma. Diagnosis is made based on a combination of clinical and laboratory findings, determining the need for surgical intervention to stop any processes causing muscle damage and to prevent or treat known complications of the disease. Careful examination of patients and identification of potential risk factors associated with myocyte damage and release of breakdown products (myoglobin, creatinine, potassium, phosphorus) into the systemic bloodstream, which can lead both to asymptomatic elevations of muscle enzymes in the blood and to life-threatening acute renal damage and severe electrolyte disturbances. Although early volume resuscitation for rhabdomyolysis is a well-established principle for improving renal tubular function, diluting nephrotoxins such as myoglobin, and providing adequate renal perfusion to prevent acute kidney injury (AKI), choosing the best type of crystalloid for this purpose. Existing protocols and benefits of infusion therapy, rate of administration, target recommendations, and diuresis rate to prevent ARF in rhabdomyolysis are analyzed. The appropriateness of diuretics and/or bicarbonate administration for the prevention of AKI is considered. Whether extracorporeal removal of myoglobin can be an effective preventive strategy and taking into account the molecular weight of myoglobin or effective use of different dialysis regimens, filters and flow types to treat and prevent AKI.

Akutní poškození ledvin vlivem antimikrobiální terapie

One of the common causes of acute kidney injury (AKI) is drug nephrotoxicity. A large group of drugs associated with AKI includes a considerable number of antimicrobials. Clinical manifestations range from mild forms of tubular damage to significant deterioration of renal function requiring renal replacement therapy. Several mechanisms have been described, although the most common are acute interstitial nephritis, acute tubular necrosis, crystalic nephropathy or proximal/distal tubulopathy with electrolyte abnormalities. General risk factors for antimicrobial-induced AKI include pre-existing chronic kidney disease and concomitant use of drugs with nephrotoxic potential. Prevention and early recognition of AKI are the standard approach to mitigate AKI and avoid morbidity.

LncRNA IRAR regulates chemokines production in tubular epithelial cells thus promoting kidney ischemia-reperfusion injury

Increasing evidence demonstrates that long noncoding RNAs (lncRNAs) play an important role in several pathogenic processes of the kidney. However, functions of lncRNAs in ischemic acute kidney injury (AKI) remain undefined. In this study, global lncRNA profiling indicated that many lncRNA transcripts were deregulated in kidney after ischemia reperfusion (IR). Among them, we identified IRAR (ischemia-reperfusion injury associated RNA) as a potential lncRNA candidate, which was mostly expressed by the tubular epithelial cells (TECs) after IR, involved in the development of AKI. GapmeR-mediated silencing and viral-based overexpression of IRAR were carried out to assess its function and contribution to IR-induced AKI. The results revealed that in vivo silencing of IRAR significantly reduced IR-induced proinflammatory cells infiltration and AKI. IRAR overexpression induced chemokine CCL2, CXCL1 and CXCL2 expression both in mRNA and protein levels in TECs, while, silencing of IRAR resulted in downregulation of these chemokines. RNA immunoprecipitation and RNA pulldown assay validated the association between IRAR and CCL2, CXCL1/2. Further examination revealed that specific ablation of CCL2 in TECs reduced macrophages infiltration and proinflammatory cytokine production, attenuated renal dysfunction in IR mice. Inhibition of CXC chemokine receptor 2 (receptor of CXCL1/2) reduced neutrofils infiltration, but had no overt effect on kidney function. To explore the mechanism of IRAR upregulation in kidney during IR, we analyzed promoter region of IRAR and predicted a potential binding site for transcription factor C/EBP β on IRAR promoter. Silencing of C/EBP β reduced IRAR expression in TECs. A dual-luciferase reporter assay and chromatin immunoprecipitation (ChIP) confirmed that IRAR was a transcriptional target of the C/EBP β. Altogether, our findings identify IRAR as a new player in the development of ischemic AKI through regulating chemokine production and immune cells infiltration, suggesting that IRAR is a potential target for prevention and/or attenuation of AKI.

An auto-photoacoustic melanin-based drug delivery nano-platform for self-monitoring of acute kidney injury therapy via a triple-collaborative strategy

Rhabdomyolysis-induced acute kidney injury (AKI) is closely related to toxic reactive oxygen species (ROS), apoptosis, and inflammation. Excessive activation of poly (ADP-ribose) polymerase-l (PARP-1) by ROS can cause mitochondrial dysfunction and release of the proapoptotic protein AIF, which triggers an intrinsic PARP-1-dependent cell death program. Considering these characteristics of rhabdomyolysis-induced AKI, we developed a targeting nanodrug delivery platform by loading PJ34 and coupling anti-GPR97 with melanin nanoparticles (GMP nanoparticles) that could realize photoacoustic self-monitoring and triple-collaborative treatment (antioxidant, antiapoptotic, and anti-inflammatory). The nanoparticles exhibited good dispersibility, solubility, and broad-spectrum ROS scavenging ability. In vitro experiments revealed high biocompatibility of the GMP nanoparticles and strong ability of scavenging multiple toxic ROS, antiapoptotic activity, and anti-inflammatory activity. Because melanin nanoparticles possess inherent photoacoustic (PA) imaging capability, they can not only serve as a drug carrier but also perform self-monitoring for real-time tracking of GMP biodistribution and renal uptake in a murine AKI model through PA imaging. In vivo experiments showed that the GMP nanoparticles could effectively reduce oxidative stress, apoptosis, and inflammatory response in mice with rhabdomyolysis-induced AKI, and the mechanism of alleviation was verified through western blot experiments. These results indicated that the nanoplatform could realize the targeted delivery and curative effect monitoring under the guidance of PA imaging, which is of great significance for the prevention and treatment of AKI. Statement of significanceA targeting nanodrug delivery platform was developed by loading PJ34 and coupling anti-GPR97 with melanin nanoparticles (GMP nanoparticles) for photoacoustic self-monitoring and triple-collaborative treatment (antioxidant, antiapoptotic, and anti-inflammatory) of acute kidney injury (AKI). Further studies indicated that the Keap-1/Nrf2/HO-1 and PARP-1/AIF signaling pathways are involved in the therapeutic mechanisms to alleviate AKI. Immunohistochemical staining and routine blood test confirmed the anti-inflammatory performance of GMP nanoparticles. Compared to exogenous nanomaterials, we used endogenous melanin with broad ROS scavenging capacity as the nanocarrier and antioxidant, which not only overcomes the defects of high specificity, potential toxicity, low loading capacity, and high cost but also shows good biosafety and photoacoustic imaging performance in vivo.

Multidisciplinary basic and clinical research of acute kidney injury with COVID-19: Pathophysiology, mechanisms, incidence, management and kidney transplantation.

Acute kidney injury (AKI) linked to coronavirus disease 2019 (COVID-19) has been identified in the course of the disease. AKI can be mild or severe and that is dependent on the presence of comorbidities and the severity of COVID-19. Among patients who had been hospitalized with COVID-19, some were admitted to intensive care unit. The etiology of AKI associated with COVID-19 is multifactorial. Prevention of severe AKI is the prime task in patients with COVID-19 that necessitates a battery of measurements and precautions in management. Patients with AKI who have needed dialysis are in an increased risk to develop chronic kidney disease (CKD) or a progression of their existing CKD. Kidney transplantation patients with COVID-19 are in need of special management to adjust the doses of immunosuppression drugs and corticosteroids to guard against graft rejection but not to suppress the immune system to place the patient at risk of developing a COVID-19 infection. Immunosuppression drugs and corticosteroids for patients who have had a kidney transplant has to be adjusted based on laboratory results and is individualized aiming at the protection of the transplanted from rejection.

Several Alkaloids in Chinese Herbal Medicine Exert Protection in Acute Kidney Injury: Focus on Mechanism and Target Analysis

Objectives Acute kidney injury (AKI) is a loose set of kidney diseases accompanied by a variety of syndromes, which is a serious threat to human life and health. Some alkaloids are derived from various Chinese herbs have been widely concerned in the improvement of AKI. This review provides the research progress of alkaloids in AKI experimental models and discusses the related molecular mechanisms. Key Findings. Alkaloids can protect AKI through various mechanisms including antioxidant stress, improvement of mitochondrial damage, reduction of cell death, induction of autophagy, and inhibition of inflammation. These mechanisms are mainly related to the activation of Nrf2/HO-1 signaling pathway, inhibition of ferroptosis and apoptosis, regulation of PINK1/Parkin pathway, inhibition of TLR4/NF-κB pathway and NLRP3 inflammatory bodies, upregulation of Klotho protein level and so on. In addition, there are a few alkaloids that have certain toxicity on the kidney. Conclusion Alkaloids have been shown to significantly improve AKI, but only in pharmacological studies. This paper summarizes the main experimental models currently used in AKI research and describes some representative alkaloids based on recent research. Their potential roles in the prevention and treatment of AKI through different mechanisms are highlighted.

Preventive Effect of Collagen Peptides from Acaudina molpadioides on Acute Kidney Injury through Attenuation of Oxidative Stress and Inflammation.

The protective effect of collagen peptide from Acaudina molpadioides (Amp) on acute kidney injury (AKI) in mice and its mechanism were explored. The results showed that Amp-fed could effectively improve the renal mass index and histopathological morphology. The levels of serum creatinine and urea nitrogen decreased significantly, while the antioxidant enzyme catalase (CAT) and superoxide dismutase (SOD) increased significantly in Amp-fed groups. Western blot results disclosed that Amp significantly upregulates the levels of heme oxygenase-1 (HO-1), Nrf2, p-PI3K, and p-AKT in the kidney. In addition, Amp could significantly downregulate the levels of nuclear factor NF-kappa-B (NF-κB), tumor necrosis factor α (TNF-α), inflammatory cytokines interleukin 6 (IL-6) and interleukin 1β (IL-1β). These findings provide evidence that Amp plays a protective role in AKI via attenuation of oxidative stress and inflammation mediated by PI3K/AKT/Nrf2 and PI3K/AKT/NF-κB pathways. This study laid a foundation for the application of Amp in the prevention of AKI.

MO339: The Effect of Pre-Admission Angiotensin-Converting Enzyme Inhibitor (ACEI) and Angiotensin Receptor Blocker (ARB) Use on the Incidence of Acute Kidney Injury and Mortality in Patients With Septic Shock

Abstract BACKGROUND AND AIMS In the early stages of sepsis, the renin–angiotensin–aldosteron system (RAAS) is activated despite adequate volume resuscitation. Overactivity of RAAS might contribute to an inferior outcome in patients with severe sepsis, therefore modulation of RAAS could be beneficial in preventing organ failure and reducing mortality. Recommendation to discontinue angiotensin convertase enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) for the prevention of acute kidney injury (AKI) in these patients is currently controversial. In this retrospective cohort study, we aimed to study the potential effect of pre-hospital ACEI or ARB use on the incidence of AKI and mortality in patients admitted to the intensive care unit (ICU) with septic shock. METHOD A total of 536 patients admitted to a single ICU for septic shock during a 5-year period were selected for inclusion in the study. Pre-admission ACEi/ARB exposure was extracted from the admission documents. Propensity score matching based on age, gender, diabetes, hypertension and cardiovascular disease (CVD) was used to control for baseline differences between ACEi/ARB treated and control patients. Stages of AKI were defined according to the KDIGO criteria, using the first available creatinine level as a baseline. Since ACEi/ARB therapy was discontinued after admission, AKI was only considered within the first 3 days of admission. The incidence of AKI stages was compared between treated and control patients. In addition, multivariate logistic regression models were used to assess the association between ACEi/ARB use and mortality in the ICU. RESULTS A total of 241 treated and 274 control patients were identified after matching. The mean age was 71 ± 9 years, 42% were female, the prevalence of diabetes and CVD were 36% and 72%, respectively. As expected, baseline GFR on admission in the treated group was lower compared with control: 37 mL/min versus 49 mL/min; P = .005. The incidence of AKI was similar in both groups: 25 versus 28%; P = .593. The somewhat higher proportion of patients with AKI stage 1 in the treated group (6.6% versus 3.3%) did not reach statistical significance (P = .170). This most likely reflects the glomerular hemodynamic effect of RAS inhibition. The incidence of stage 2 and 3 AKI was comparable in treated (19.1%) and control groups (25.4%, P = .233). Patient survival was similar in both groups: 63.1% versus 58.6%; P = .461. In the whole cohort of 536 patients, only baseline GFR remained an independent predictor of AKI stage 2 or 3 (OR 1.6 for 10 mL/min decline; P < .001) in the multivariate analysis. AKI stage 2 and 3 (OR 3.324; P < .001) and cardiovascular disease (OR 2.288; P = 0.003) were independent predictors of mortality. ACEi/ARB exposure was not associated with patient outcome in our cohort. CONCLUSION In this retrospective cohort study, we confirmed that pre-admission ACEi/ARB use was not associated with a higher risk of AKI in patients with septic shock admitted to the ICU. Our results suggest that ACEi/ARB treatment could be continued until the patient's blood pressure allows in early stages of sepsis.

Current Management and Treatment for Patients with Chronic Kidney Disease

The incidence of chronic kidney disease (CKD) is rising in many parts of the world and primary care providers are poised to be the first point of contact for these patients. The optimal management of patients with CKD include early detection, cause identification, CKD progression retardation (including dietary support, blood pressure control, drug therapeutics), management of comorbid conditions, acute kidney injury prevention, and knowing when to refer for specialist care. In general, the concept of CKD progression retardation involves patient education on topics such as lifestyle modification measures, e.g., diet, to reduce burden on the kidneys and use of medications that can confer renoprotection while causing little if any side effects. The advent of SGLT2 inhibitors, nonsteroidal mineralocorticoid receptor antagonists, and new potassium binders provides our patients with new hope to further lengthen the time to end-stage kidney failure. It is therefore necessary that stakeholders involved in the care of patients with CKD understand the latest evidence to optimise care and patient wellbeing.

The incidence of acute kidney injury in hospitalized patients receiving aminoglycoside antibiotics: a retrospective study.

Our aim is to investigate the incidence and risk factors of acute kidney injury (AKI) in hospitalized patients who received aminoglycoside antibiotics. A retrospective analysis was performed on the electronic medical record information of inpatients who received aminoglycoside (AG) antibiotics in our center from January 2018 to December 2020. The diagnosis of AKI was based on serum creatinine changes. Several statistical methods, including chi square test and two sample Wilcoxon rank sum test, were used to evaluate the epidemiological characteristics of aminoglycosides associated AKI. The multivariate logistic regression analysis was used to screen the risk factors. Finally, 8,040 patients who received AGs were included in the study. Among them, 494 patients (6.14%) were judged as incidence with AKI, while only 29 patients were diagnosed with AKI in the medical record. The multiple logistic regression analysis suggested that admission to ICU, complicated with diabetes mellitus, heart failure, anemia, shock, combined use of diuretics, β-lactam antibiotics, proton pump inhibitors were independent risk factors for AKI related to aminoglycosides. It is urgent to improve the understanding and attention of AKI for medical workers, and the assessment of risk factors before the use of aminoglycosides should be contributed to the early prevention, diagnosis, and treatment of AKI.

Perioperative management of adult living donor liver transplantation: Part 1 - recipients.

Living donor liver transplantation was first developed to mitigate the limited access to deceased donor organs in Asia in the 1990s. This alternative liver transplantation option has become an established and widely practiced transplantation method for adult patients suffering from end-stage liver disease. It has successfully addressed the shortage of deceased donors. The Society for the Advancement of Transplant Anesthesia and the Korean Society of Transplant Anesthesia jointly reviewed published studies on the perioperative management of live donor liver transplant recipients. The review aims to offer transplant anesthesiologists and critical care physicians a comprehensive overview of the perioperative management of adult live liver transplantation recipients. We feature the status, outcomes, surgical procedure, portal venous decompression, anesthetic management, prevention of acute kidney injury, avoidance of blood transfusion, monitoring and therapeutic strategies of hemodynamic derangements, and Enhanced Recovery After Surgery protocols for liver transplant recipients.

MicroRNA-214-3p aggravates ferroptosis by targeting GPX4 in cisplatin-induced acute kidney injury.

Acute kidney injury (AKI) induced by cisplatin (cis-AKI) involves indicators such as inflammation and oxidative stress (OS) in proximal tubules, although its underlying mechanisms remain largely unknown so far. Exploration of the molecular mechanisms underlying cisplatin-induced AKI is of great significance for AKI prevention and also for preventing its progression into chronic kidney disease (CKD) or end-stage renal disease (ESRD). OS and ferroptosis are mutually causal; they finally lead to the regulatory cell injury and death induced by the accumulation of reactive oxygen species (ROS). GPX4 is critical not only in OS, but studies established as the key regulator of ferroptosis. In this context, the present study focused on determining the biological function of miR-214-3p in the cisplatin-induced ferroptosis of tubular epithelial cell (TEC) and the underlying molecular mechanism. The relationship between TEC ferroptosis and cisplatin-induced AKI was investigated in vitro and in vivo. Ferrostatin-1(Fer-1), an inhibitor of ferroptosis, was observed to confer a protective effect against the renal tubular injury and renal failure induced by cisplatin. MicroRNAs (miRNAs) regulate the genes that have important functions in the development of cis-AKI. In the present study, GPX4 was predicted as a target of miR-214-3p. Moreover, inhibiting miR-214-3p enhanced the expressions of GPX4 and SLC7A11 while decreasing the ACSL4 expression. Furthermore, miR-214-3p down-regulation protected against TEC death and renal tubule damage both in vitro and in vivo. According to these findings, inhibiting miR-214-3p would alleviate TEC ferroptosis in cis-AKI via GPX4.

Role of Urinary Kidney Stress Biomarkers for Early Recognition of Subclinical Acute Kidney Injury in Critically Ill COVID-19 Patients.

A high proportion of critically ill patients with COVID-19 develop acute kidney injury (AKI) and die. The early recognition of subclinical AKI could contribute to AKI prevention. Therefore, this study was aimed at exploring the role of the urinary biomarkers NGAL and [TIMP-2] × [IGFBP7] for the early detection of AKI in this population. This prospective, longitudinal cohort study included critically ill COVID-19 patients without AKI at study entry. Urine samples were collected on admission to critical care areas for determination of NGAL and [TIMP-2] × [IGFBP7] concentrations. The demographic information, comorbidities, clinical, and laboratory data were recorded. The study outcomes were the development of AKI and mortality during hospitalization. Of the 51 individuals that were studied, 25 developed AKI during hospitalization (49%). Of those, 12 had persistent AKI (23.5%). The risk factors for AKI were male gender (HR = 7.57, 95% CI: 1.28–44.8; p = 0.026) and [TIMP-2] × [IGFBP7] ≥ 0.2 (ng/mL)2/1000 (HR = 7.23, 95% CI: 0.99–52.4; p = 0.050). Mortality during hospitalization was significantly higher in the group with AKI than in the group without AKI (p = 0.004). Persistent AKI was a risk factor for mortality (HR = 7.42, 95% CI: 1.04–53.04; p = 0.046). AKI was frequent in critically ill COVID-19 patients. The combination of [TIMP-2] × [IGFBP7] together with clinical information, were useful for the identification of subclinical AKI in critically ill COVID-19 patients. The role of additional biomarkers and their possible combinations for detection of AKI in ritically ill COVID-19 patients remains to be explored in large clinical trials.

Modelling and Prevention of Acute Kidney Injury through Ischemia and Reperfusion in a Combined Human Renal Proximal Tubule/Blood Vessel-on-a-Chip.

Renal ischemia/reperfusion injury (rIRI) is one of the major causes of AKI. Although animal models are suitable for investigating systemic symptoms of AKI, they are limited in translatability. Human in vitro models are crucial in giving mechanistic insights into rIRI; however, they miss out on crucial aspects such as reperfusion injury and the multitissue aspect of AKI. We advanced the current renal proximal tubule-on-a-chip model to a coculture model with a perfused endothelial vessel separated by an extracellular matrix. The coculture was characterized for its three-dimensional structure, protein expression, and response to nephrotoxins. Then, rIRI was captured through control of oxygen levels, nutrient availability, and perfusion flow settings. Injury was quantified through morphologic assessment, caspase-3/7 activation, and cell viability. The combination of low oxygen, reduced glucose, and interrupted flow was potent to disturb the proximal tubules. This effect was strongly amplified upon reperfusion. Endothelial vessels were less sensitive to the ischemia-reperfusion parameters. Adenosine treatment showed a protective effect on the disruption of the epithelium and on the caspase-3/7 activation. A human in vitro rIRI model was developed using a coculture of a proximal tubule and blood vessel on-a-chip, which was used to characterize the renoprotective effect of adenosine. The robustness of the model and assays in combination with the throughput of the platform make it ideal to advance pathophysiological research and enable the development of novel therapeutic modalities.

Prevention and Early Detection of Acute Kidney Injury in Intensive Care Unit: A Systematic Review

Acute Kidney Injury (AKI) is often associated with Intensive Care Unit (ICU) admission and results in a higher mortality rate around the world. The AKI cases have been rising for the past decade alongside the mortality rate. Literature has shown that early detection helps in overcoming the problem. This systematic review aims to identify the identify the relevant literature and to summarize the prevention and early detection of AKI in the ICU setting to reduce the morbidity and mortality rate of patients. A total of 20 articles identified in this review. This systematic review also is in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Relevant studies were identified based on the inclusion criteria with language filters but were limited to articles published from the year 2010 to 2020. Two reviewers independently conducted the quality assessment, data extraction, and analysis on all included studies. The result indicates there are several biomarkers which are helpful in detecting AKI such as Neutrophil Gelatinase-Associated Lipocalin (NGAL), Interleukin-18 (IL-18), Tissue Inhibitor of Metalloproteinase 2 (TIMP-2), Insulin-Like Growth Factor Binding Protein 7 (IGFBP-7), Protein C (PC), and soluble thrombomodulin (sTM). This review also addressed nursing responsibilities for early detection and prevention of AKI. Thus, severe cases of AKI and mortality cases associated with AKI can be minimized with better predictive and proper management.

Clinical features and prognostic factors of acute kidney injury caused by adult secondary hemophagocytic lymphohistiocytosis

Hemophagocytic lymphohistiocytosis is a clinical syndrome caused by a cytokine storm and phagocytosis of blood cells. Acute kidney injury is typically associated with a poor prognosis in hemophagocytic lymphohistiocytosis. In the present study, a retrospective analysis of patient data was performed to identify risk factors associated with acute kidney injury in hemophagocytic lymphohistiocytosis. All patients included in the studywere diagnosed with hemophagocytic lymphohistiocytosis between January 2009 and July 2019. Acute kidney injury was diagnosed according to the Kidney Disease Improving Global Outcomes guidelines, according to the2012update. We collected the general information of the patients, clinical manifestations, treatments, as well as laboratory data from the electronic medical records. We analyzed 600 patients with hemophagocytic lymphohistiocytosis. Serum phosphorus, need forvasopressors, heart failure, gastrointestinal symptoms, disseminated intravascular coagulation, high heart rateat admission, total bilirubin and albumin levelswere independently associated with an increased risk of developing acute kidney injury. Independent risk factors for in-hospital mortality were administration of vasopressors, acute kidney injury stage III, baseline Cystatin-C, total bilirubin, number of days of glucocorticoid therapy, fibrinogen leveland presence ofmulti-organ failure. Patients with hemophagocytic lymphohistiocytosis usually exhibit high hospital mortality, particularly in the presence ofacute kidney injury. The risk factors for the occurrence of acute kidney injury and increased mortality identified in the study may assist clinicians in the prevention of acute kidney injury, and in its timelytreatment in patients affected byhemophagocytic lymphohistiocytosis, toultimately improve prognosis.

A goal-directed therapy protocol for preventing acute kidney injury after laparoscopic liver resection: a retrospective observational cohort study.

Postoperative acute kidney injury (AKI) remains a serious complication of liver resection with restrictive fluid therapy. However, unlike open hepatectomy, laparoscopic liver resection (LLR) does not have established anesthesia management strategies. We compared our goal-directed therapy (GDT) protocol for LLR with/without carperitide and the conventional restrictive method regarding AKI prevention. The GDT thresholds in this retrospective observational cohort study were as follows: stroke volume variation, ≤ 15%; pulse pressure variation, ≤ 13%; oxygen delivery index, ≥ 600mL/min/m2; and mean arterial pressure (MAP), ≥ 55mmHg. If the thresholds were not achieved, a 250mL infusion fluid bolus was administered. The MAP target was changed to > 65mmHg if the urine output was < 0.3mL/kg/h. Postoperative AKI within 48h and perioperative outcomes within 90days were analyzed. Forty-seven propensity score-matched pairs from 127 patients were investigated. We adjusted for AKI risk factors and surgical difficulty; 46.8% of the GDT group received carperitide. The GDT group had a lower postoperative AKI rate (10.6% vs. 27.7%, P = 0.04) and shorter overall (P = 0.04) and postoperative (P < 0.01) hospital stays than the conventional group. Furthermore, the GDT group received more intraoperative fluid (P = 0.001) and phenylephrine (P = 0.02), without significant increases in blood loss and transfusion volume, than the conventional group. GDT reduced the AKI rates post-LLR.

AKI in Hospitalized Children: Poorly Documented (and Underrecognized).

Background: Acute kidney injury (AKI) is common in hospitalized children. We hypothesized that hospital-acquired AKI would be underrecognized and under-reported, with potential implications for prevention of future AKI and CKD risk stratification.Methods: Five hundred thirty-two cases of AKI occurring over a 1 year period in a tertiary children's hospital in the United States were studied. AKI documentation was defined as any mention of AKI in the admission history and physical note, progress notes, or discharge summary. Nephrology follow-up was defined as a completed outpatient clinic visit within 1 year of discharge. Logistic regression was used to assess factors associated with documentation, consultation, and follow-up.Results: AKI developed during 584/7,640 (7.6%) of hospitalizations: 532 cases met inclusion criteria. Documentation was present in 34% (185/532) of AKI cases and 90 (16.9%) had an inpatient nephrology consult. Among 501 survivors, 89 (17.8%) had AKI in their hospital discharge summary and 54 had outpatient nephrology follow up. Stage 3 AKI, peak creatinine >1 mg/dL and longer length of stay were associated with documentation. Stage 3 AKI and higher baseline creatinine were associated with inpatient nephrology consultation. Inpatient nephrology consultation was positively associated with outpatient nephrology follow up, but documentation in the discharge summary was not.Conclusion: Most cases of AKI were not documented and the proportion of children seen by a nephrologist was low, even among those with more severe injury. Increased severity of AKI was associated with documentation and inpatient consultation. Poor rates of documentation has implications for AKI recognition and appropriate management and follow up.

Kidney-Targeted Redox Scavenger Therapy Prevents Cisplatin-Induced Acute Kidney Injury.

Cisplatin-induced acute kidney injury (CI-AKI) is a significant co-morbidity of chemotherapeutic regimens. While this condition is associated with substantially lower survival and increased economic burden, there is no pharmacological agent to effectively treat CI-AKI. The disease is hallmarked by acute tubular necrosis of the proximal tubular epithelial cells primarily due to increased oxidative stress. We investigated a drug delivery strategy to improve the pharmacokinetics of an approved therapy that does not normally demonstrate appreciable efficacy in CI-AKI, as a preventive intervention. In prior work, we developed a kidney-selective mesoscale nanoparticle (MNP) that targets the renal proximal tubular epithelium. Here, we found that the nanoparticles target the kidneys in a mouse model of CI-AKI with significant damage. We evaluated MNPs loaded with the reactive oxygen species scavenger edaravone, currently used to treat stroke and ALS. We found a marked and significant therapeutic benefit with edaravone-loaded MNPs, including improved renal function, which we demonstrated was likely due to a decrease in tubular epithelial cell damage and death imparted by the specific delivery of edaravone. The results suggest that renal-selective edaravone delivery holds potential for the prevention of acute kidney injury among patients undergoing cisplatin-based chemotherapy.

Advances in the clinical value of tissue inhibitors of metalloproteinase-2 and insulin-like growth factor binding protein 7 in sepsis associated-acute kidney injury

Sepsis is an important cause of acute kidney injury (AKI). About 60% of sepsis patients will develop AKI. At present, the standard of clinical diagnosis of AKI is still based on the changes in serum creatinine and urine volume. Because of its lag in time, it may lead to delay in treatment and increase the mortality. To find a new biomarker similar to "troponin" for the diagnosis of AKI, and to achieve the early diagnosis and prevention of AKI, is of great significance to reduce the mortality of AKI. In recent years, it has been found that tissue inhibitors of metalloproteinase-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) can be used for early diagnosis of sepsis associated-acute kidney injury (SA-AKI). They also have important values in risk stratification, prognosis judgment, intervention and other aspects of SA-AKI. In this paper, the research progress of the application of TIMP-2 and IGFBP7 in SA-AKI is reviewed.