Humans ; Child ; COVID-19/complications* ; Brain Diseases ; Myositis/complications* ; Kidney ; Liver Failure, Acute/complications* ; Acute Kidney Injury/complications*

OBJECTIVE: To evaluate the protective effect of recombinant Schistosoma japonicum cystatin (rSj-Cys) against acute kidney injury induced by acute liver failure and unravel the underlying mechanism, so as to provide insights into the clinical therapy of acute kidney injury. METHODS: Twenty-four male C57BL/6J mice at ages of 6 to 8 weeks were randomly divided into the normal control group, rSj-Cys control group, lipopolysaccharide (LPS)/D-galactosamine (D-GaIN) model group and LPS/D-GaIN + rSj-Cys treatment group, of 6 mice each group. Mice in the LPS/D-GaIN group and LPS/D-GaIN + rSj-Cys group were intraperitoneally injected with LPS (10 μg/kg) and D-GaIN (700 mg/kg), and mice in the LPS/D-GaIN + rSj-Cys group were additionally administered with rSj-Cys (1.25 mg/kg) by intraperitoneal injection 30 min post-modeling, while mice in the rSj-Cys group were intraperitoneally injected with rSj-Cys (1.25 mg/kg), and mice in the normal control group were injected with the normal volume of PBS. All mice were sacrificed 6 h post-modeling, and mouse serum and kidney samples were collected. Serum creatinine (Cr) and urea nitrogen (BUN) levels were measured, and the pathological changes of mouse kidney specimens were examined using hematoxylin-eosin (HE) staining. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were detected using enzyme-linked immunosorbent assay (ELISA), and the expression of inflammatory factors and pyroptosis-related proteins was quantified in mouse kidney specimens using immunohistochemistry. In addition, the expression of pyroptosis-related proteins and nuclear factor-kappa B (NF-κB) signaling pathway-associated proteins was determined in mouse kidney specimens using Western blotting assay. RESULTS: HE staining showed no remarkable abnormality in the mouse kidney structure in the normal control group and the rSj-Cys control group, and renal tubular injury was found in LPS/D-GaIN group, while the renal tubular injury was alleviated in LPS/D-GaIN+rSj-Cys treatment group. There were significant differences in serum levels of Cr (F = 46.33, P < 0.001), BUN (F = 128.60, P < 0.001), TNF-α (F = 102.00, P < 0.001) and IL-6 (F = 202.10, P < 0.001) among the four groups, and lower serum Cr [(85.35 ± 32.05) μmol/L], BUN [(11.90 ± 2.76) mmol/L], TNF-α [(158.27 ± 15.83) pg/mL] and IL-6 levels [(56.72 ± 4.37) pg/mL] were detected in the in LPS/D-GaIN + rSj-Cys group than in the LPS/D-GaIN group (all P values < 0.01). Immunohistochemical staining detected significant differences in TNF-α (F = 24.16, P < 0.001) and IL-10 (F = 15.07, P < 0.01) expression among the four groups, and lower TNF-α [(106.50 ± 16.57)%] and higher IL-10 expression [(91.83 ± 5.23)%] was detected in the LPS/D-GaIN + rSj-Cys group than in the LPS/D-GaIN group (both P values < 0.01). Western blotting and immunohistochemistry detected significant differences in the protein expression of pyroptosis-related proteins NOD-like receptor thermal protein domain associated protein 3 (NLRP3) (F = 24.57 and 30.72, both P values < 0.001), IL-1β (F = 19.24 and 22.59, both P values < 0.001) and IL-18 (F = 16.60 and 19.30, both P values < 0.001) in kidney samples among the four groups, and lower NLRP3, IL-1β and IL-18 expression was quantified in the LPS/D-GaIN + rSj-Cys treatment group than in the LPS/D-GaIN group (P values < 0.05). In addition, there were significant differences in the protein expression of NF-κB signaling pathway-associated proteins p-NF-κB p-P65/NF-κB p65 (F = 71.88, P < 0.001), Toll-like receptor (TLR)-4 (F = 45.49, P < 0.001) and p-IκB/IκB (F = 60.87, P < 0.001) in mouse kidney samples among the four groups, and lower expression of three NF-κB signaling pathway-associated proteins was determined in the LPS/D-GaIN + rSj-Cys treatment group than in the LPS/D-GaIN group (all P values < 0.01). CONCLUSIONS rSj-Cys may present a protective effect against acute kidney injury caused by acute liver failure through inhibiting inflammation and pyroptosis and downregulating the NF-κB signaling pathway.
Mice ; Male ; Animals ; Interleukin-10 ; Tumor Necrosis Factor-alpha/genetics* ; NF-kappa B/therapeutic use* ; Interleukin-18/therapeutic use* ; Schistosoma japonicum/metabolism* ; Interleukin-6/therapeutic use* ; Lipopolysaccharides/therapeutic use* ; NLR Family, Pyrin Domain-Containing 3 Protein ; Mice, Inbred C57BL ; Acute Kidney Injury/drug therapy* ; Liver Failure, Acute ; Cystatins/therapeutic use*

To maintain homeostasis of the cardiovascular system, the heart and kidney act bidirectionally. Therefore, acute or chronic dysfunction of one organ can cause dysfunction in the other. This phenomenon is characterized as cardiorenal syndrome (CRS). Concurrent dysfunction of the heart and kidney adversely affects one another and eventually worsens patient outcomes through a vicious cycle. Although a CRS classification system has been proposed, the underlying pathophysiology is multifactorial and clinical access continues to be difficult. Although several therapies, including agents that target the renin-angiotensin-aldosterone system, have been utilized, there is not enough evidence to demonstrate their effectiveness for CRS. Thus, more effort should be made to optimize the diagnosis and treatment strategies for CRS patients. This review will introduce CRS as it is currently understood, discuss the pathophysiology, and examine management strategies.
Acute Kidney Injury ; Cardio-Renal Syndrome ; Cardiovascular System ; Classification ; Diagnosis ; Heart ; Heart Failure ; Homeostasis ; Humans ; Kidney ; Renal Insufficiency, Chronic ; Renin-Angiotensin System

BACKGROUND: Femoral neck fracture is common in the elderly population. Acute kidney injury (AKI) is an important risk factor for mortality in patients who have had such fracture. We evaluated the incidence of AKI in patients who had femoral neck fracture and identified risk factors for AKI and mortality. METHODS: This was an observational cohort study including 285 patients who were ≥ 65 years of age and who underwent femoral neck fracture surgery between 2013 and 2017. RESULTS: The mean age was 78.63 ± 6.75 years. A total of 67 (23.5%) patients developed AKI during the hospital stay: 57 (85.1%), 5 (7.5%), and 5 (7.5%) patients were classified as having stage 1, 2, and 3 AKI, respectively. Patients with AKI had a lower baseline estimated glomerular filtration rate and higher left atrial dimension, left ventricular mass index, pulmonary artery pressure, and the ratio of early mitral inflow velocity to early diastolic mitral annulus velocity (E/e’) and were more likely to have diabetes or hypertension (HTN) (P < 0.05). The presence of HTN (odds ratio [OR], 4.570; 95% confidence interval [CI], 1.632–12.797) higher E/e’ (OR, 1.105; 95% CI, 1.019–1.198), and lower hemoglobin (OR, 0.704; 95% CI, 0.528–0.938) were independently associated with a higher risk for developing AKI. Severe AKI (OR, 24.743; 95% CI, 2.822–212.401) was associated with a higher risk of mortality. CONCLUSION: Elderly patients with femoral neck fracture had a high incidence of AKI. Diastolic dysfunction was associated with AKI. Severe AKI was associated with in-hospital mortality.
Acute Kidney Injury ; Aged ; Cohort Studies ; Femoral Neck Fractures ; Femur Neck ; Glomerular Filtration Rate ; Heart Failure, Diastolic ; Hospital Mortality ; Humans ; Hypertension ; Incidence ; Length of Stay ; Mortality ; Pulmonary Artery ; Risk Factors

BACKGROUND: Although some strategies are used for prophylaxis of contrast induced nephropathy, their efficacy is not fully established. Sarpogrelate can relieve vasospasm and have anti-inflammatory action. This study examined whether sarpogrelate reduces the incidence of contrast induced nephropathy (CIN) or subsequent renal impairment during four weeks after coronary angiography compared with a control group. METHODS: Seventy-four participants with chronic renal failure were randomly assigned to the sarpogrelate or control group. Patients assigned to the sarpogrelate group received oral saporogelate from 24 hours before contrast exposure up to one month after contrast exposure. The primary outcome of this study was the incidence of CIN within 48 hours after exposure to the contrast agent. RESULTS: Thirty-one subjects in the control group and 35 subjects in the sarpogrelate group were used for the analysis. Cumulative CIN occurred numerically more at 48 hours in the sarpogrelate group and less at one month without statistical significance (11.4% vs. 6.5% at 48 hours and 11.4% vs. 16.1% at one month, respectively). Baseline renal function was similar in both groups, but the estimated glomerular filtration rate (eGFR) was lower in the sarpogrelate group at 12 and 48 hours compared with the control group (45.6 vs. 54.7 mL/min/1.73m²; P = 0.023 and 39.9 vs. 50.6 mL/min/1.73m²; P = 0.020, respectively). At one month, the eGFR became comparable between the two groups because the eGFR was aggravated in the control group and maintained in the sarpogrelate group. CONCLUSION: This study failed to demonstrate that sarpogrelate has a renoprotective effect against contrast induced acute kidney injury. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01165567
Acute Kidney Injury ; Coronary Angiography ; Glomerular Filtration Rate ; Humans ; Incidence ; Kidney Failure, Chronic ; Prospective Studies ; Renal Insufficiency ; Serotonin

OBJECTIVE: To explore the predicting performance of renal resistive index (RRI), semi quantitative power Doppler ultrasound (PDU) score and serum cystatin C (Cys C) for acute kidney injury (AKI) in patients with cardiac failure or sepsis. METHODS: A prospective, observational study was conducted. Critically ill patients with acute cardiac failure or sepsis admitted to the emergency intensive care unit (ICU) of Cangzhou Central Hospital from January 1st to December 31st in 2018 were enrolled. In addition to the demographic data, serum Cys C, RRI, and PDU score were measured within 6 hours after admission to ICU. Renal function was assessed on day 5 according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Patients who proceeded to AKI stage 2 or 3 within 5 days from admission were defined as the AKI 2-3 group; other patients were classified into the AKI 0-1 group. The differences of each index were compared in all patients, cardiac failure patients and sepsis patients between the two groups. Multivariate binary Logistic regression was carried out to identify the independent risk predictors of AKI 2-3. Receiver operator characteristic (ROC) curves were plotted to examine the values of Cys C, RRI, PDU score, and RRI+PDU in predicting AKI 2-3. RESULTS: Thirty-seven patients with cardiac failure (11 with no AKI, 10 with AKI stage 1, 3 with AKI stage 2, and 13 with AKI stage 3) and 26 patients with sepsis (8 with no AKI, 2 with AKI stage 1, 7 with AKI stage 2, and 9 with AKI stage 3) were recruited. In all patients as well as the subgroup of cardiac failure, compared with the AKI 0-1 group, acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, rate of continuous renal replacement therapy (CRRT), 28-day mortality, serum creatinine (SCr), Cys C and RRI were higher in AKI 2-3 group, and urine output, PDU score were lower; in the subgroup of sepsis, rate of CRRT, SCr, and Cys C were higher in AKI 2-3 group, and urine output was lower. Multivariate Logistic regression analysis found that Cys C and PDU score were independent risk factors for AKI 2-3 in all patients [Cys C: odds ratio (OR) = 11.294, 95% confidence interval (95%CI) was 2.801-45.541, P = 0.001; PDU score: OR = 0.187, 95%CI was 0.056-0.627, P = 0.007]; RRI and PDU score were independent risk factors for AKI 2-3 in patients with cardiac failure [RRI (×10): OR = 6.172, 95%CI was 0.883-43.153, P = 0.067; PDU score: OR = 0.063, 95%CI was 0.007-0.584, P = 0.015]; Cys C was the independent risk factor for AKI 2-3 in patients with sepsis (OR = 22.830, 95%CI was 1.345-387.623, P = 0.030). It was shown by ROC curve analysis that: in the subgroup of cardiac failure, the predictive values of RRI, PDU score and Cys C were well [area under the curve (AUC) and 95%CI was 0.839 (0.673-0.942), 0.894 (0.749-0.971), 0.777 (0.610-0.897), all P < 0.01]. RRI+PDU performed best in predicting AKI (AUC = 0.956, 95%CI was 0.825-0.997, P < 0.01), and the predictive value was higher than Cys C [AUC (95%CI): 0.956 (0.825-0.997) vs. 0.777 (0.610-0.897), P = 0.034]. In the subgroup of sepsis, the predictive value of Cys C was well (AUC = 0.913, 95%CI was 0.735-0.987, P < 0.01), however, the predictive value of RRI, PDU, RRI+PDU were poor. CONCLUSIONS RRI and PDU score effectively predict AKI stage 2 or 3 in cardiac failure patients, but not in patients with sepsis. The predictive values of Cys C for AKI are similar in patients with cardiac failure or sepsis.
Acute Kidney Injury/diagnosis* ; Cystatin C/metabolism* ; Heart Failure ; Humans ; Intensive Care Units ; Prognosis ; Prospective Studies ; ROC Curve ; Sepsis ; Ultrasonography

Acute generalized exanthematous pustulosis (AGEP) is rarely caused by radiocontrast media (RCM). The role of skin tests for the diagnosis and evaluation of cross-reactivity in a delayed type of RCM-induced hypersensitivity have yet to be determined. Here, we report a case of iodixanol-induced AGEP where we safely administered alternative RCM using patch tests. A 44-year-old woman had coronary artery angiography (CAG) for the evaluation of ischemic heart disease. She was on regular hemodialysis because of end-stage renal disease. She was given iodixanol (Visipaque) during CAG. Approximately 1 day after CAG, she developed AGEP. The patient was rehospitalized for CAG again after 1 year. We performed skin tests to choose safe alternative RCM. Intradermal tests with iodixanol, iohexol (Bonorex) and Iopamidol (Pamiray) showed negative responses. Patch tests showed a positive response to iodixanol, equivocal to iohexol, and negative to Iopamidol. We finally chose Iopamidol and performed CAG successfully without any adverse reaction. Patch tests may be a useful tool for the diagnosis and choice of safe alternatives in RCM-induced delayed-type hypersensitivity reactions such as AGEP.
Acute Generalized Exanthematous Pustulosis* ; Adult ; Angiography ; Contrast Media* ; Coronary Vessels ; Diagnosis ; Female ; Humans ; Hypersensitivity ; Intradermal Tests ; Iohexol ; Iopamidol ; Kidney Failure, Chronic ; Myocardial Ischemia ; Patch Tests* ; Renal Dialysis ; Skin Tests

BACKGROUND/AIMS: The true incidence of aristolochic acid nephropathy (AAN) is thought to be underestimated because numerous ingredients known or suspected to contain aristolochic acid (AA) are used in traditional medicine in Korea. METHODS: We collected data on cases of AAN since 1996 via a database in Korea. We evaluated the year of AAN development, route to obtaining AA-containing herbal medicine, gender, reason for taking AA-containing herbal medicine, clinical manifestations, histological findings, phytochemical analysis, and prognosis of patients with AAN. RESULTS: Data on 16 cases of AAN were collected. Thirteen cases developed AAN before and three cases after the prohibition of AA-containing herbal medicine by the Korea Food and Drug Administration. Patients were prescribed AA-containing herbal medicine from oriental clinics or had purchased it from traditional markets. AAN was distributed in all age groups. Young females were most commonly exposed to AA-containing herbal medicine for slimming purposes and postpartum health promotion, while older adults took AA-containing compounds for the treatment of chronic diseases. The most common symptoms presented at hospitalization were nausea and vomiting, and acute kidney injury was accompanied by Fanconi syndrome in almost half of the patients. Phytochemical analysis of AA in herbal medicine was available in six cases. Progression to end stage renal disease (ESRD) was observed in seven patients (43.8%), and five patients (31.3%) had progressed to ESRD within 6 months of diagnosis. CONCLUSIONS: Our report shows that patients were still exposed to AA-containing herbal medicine and that there is a possibility of underdiagnosis of AAN in Korea. A stronger national supervision system of herbal ingredients and remedies in oriental medicine is needed to prevent AAN.
Acute Kidney Injury ; Adult ; Chronic Disease ; Diagnosis ; Fanconi Syndrome ; Female ; Health Promotion ; Herbal Medicine ; Hospitalization ; Humans ; Incidence ; Kidney Failure, Chronic ; Korea* ; Medicine, East Asian Traditional ; Medicine, Traditional ; Nausea ; Organization and Administration ; Postpartum Period ; Prognosis ; United States Food and Drug Administration ; Vomiting

The high mortality rates associated with acute kidney injury are mainly due to extra-renal complications that occur following distant-organ involvement. Damage to these organs, which is commonly referred to as multiple organ dysfunction syndrome, has more severe and persistent effects. The brain and its sub-structures, such as the hippocampus, are vulnerable organs that can be adversely affected. Acute kidney injury may be associated with numerous brain and hippocampal complications, as it may alter the permeability of the blood-brain barrier. Although the pathogenesis of acute uremic encephalopathy is poorly understood, some of the underlying mechanisms that may contribute to hippocampal involvement include the release of multiple inflammatory mediators that coincide with hippocampus inflammation and cytotoxicity, neurotransmitter derangement, transcriptional dysregulation, and changes in the expression of apoptotic genes. Impairment of brain function, especially of a structure that has vital activity in learning and memory and is very sensitive to renal ischemic injury, can ultimately lead to cognitive and functional complications in patients with acute kidney injury. The objective of this review was to assess these complications in the brain following acute kidney injury, with a focus on the hippocampus as a critical region for learning and memory.
Acute Kidney Injury* ; Blood-Brain Barrier ; Brain Diseases ; Brain* ; Hippocampus* ; Humans ; Inflammation ; Learning ; Memory ; Mortality ; Multiple Organ Failure ; Neurotransmitter Agents ; Permeability ; Uremia

Chronic silica nephropathy has been associated with tubulointerstitial disease, immune-mediated multisystem disease, chronic kidney disease, and end-stage renal disease. On the other hand, acute intentional exposure is extremely rare. The authors' experienced a 44-year-old man who took rapid cement hardener (sodium silicate) in a suicide attempt whilst in a drunken state. He visited the emergency department approximately 1 hour after ingestion. Information on the material was obtained after 3 L gastric lavage. The patient complained of a sore throat, epigastric pain, and swollen to blood tinged vomitus. Proton pump inhibitors, hemostats, steroid, and fluids were administered. Nine hours after ingestion, he was administered 200 mL hematochezia. Immediately after, a gastroenterologist performed an endoscopic procedure that revealed diffuse hyperemic mucosa with a color change and variable sized ulceration in the esophagus, whole stomach, and duodenal 2(nd) portion. Approximately 35 hours later, persistent oligouria and progressive worsening of the renal function parameters (BUN/Cr from 12.2/1.2 to 67.5/6.6 mg/dL) occurred requiring hemodialysis. The patient underwent 8 sessions of hemodialysis for 1 month and the BUN/Cr level increased to 143.2/11.2 mg/dL and decreased to 7.6/1.5 mg/dL. He was discharged safely from the hospital. Follow up endoscopy revealed a severe esophageal stricture and he underwent endoscopic bougie dilatation. Acute cement hardener (sodium silicate) intoxication can cause renal failure and strong caustic mucosal injury. Therefore, it is important to consider early hemodialysis and treatment to prevent gastrointestinal injury and remote esophageal stricture.
Acute Kidney Injury* ; Adult ; Caustics ; Dilatation ; Drug Overdose ; Eating ; Emergency Service, Hospital ; Endoscopy ; Esophageal Stenosis ; Esophagus ; Follow-Up Studies ; Gastric Lavage ; Gastrointestinal Hemorrhage ; Hand ; Humans ; Kidney ; Kidney Failure, Chronic ; Mucous Membrane ; Pharyngitis ; Proton Pump Inhibitors ; Renal Dialysis ; Renal Insufficiency ; Renal Insufficiency, Chronic ; Silicates ; Silicon Dioxide ; Stomach ; Suicide ; Tolnaftate ; Ulcer