Elevated Blood Urea Nitrogen Levels Research Articles

Nrf2 deficiency aggravates the kidney injury induced by subacute cadmium exposure in mice.

Cadmium (Cd) is a heavy metal pollutant that adversely effects the kidney. Oxidative stress and inflammation are likely major mechanisms of Cd-induced kidney injury. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is crucial in regulating antioxidant and inflammatory responses. To investigate the role of Nrf2 in the development of subacute Cd-induced renal injury, we utilized Nrf2 knockout (Nrf2-KO) and control mice (Nrf2-WT) which were given cadmium chloride (CdCl2, 1 or 2mg/kg i.p.) once daily for 7days. While subacute CdCl2 exposure induced kidney injury in a dose-dependent manner, after the higher Cd dosage exposure, Nrf2-KO mice showed elevated blood urea nitrogen (BUN) and urinary neutrophil gelatinase-associated lipocalin (NGAL) levels compared to control. In line with the findings, the renal tubule injury caused by 2mg Cd/kg, but not lower dosage, in Nrf2-KO mice determined by Periodic acid-Schiff staining was more serious than that in control mice. Further mechanistic studies showed that Nrf2-KO mice had more apoptotic cells and severe oxidative stress and inflammation in the renal tubules in response to Cd exposures. Although there were no significant differences in Cd contents of tissues between Cd-exposed Nrf2-WT and Nrf2-KO mice, the mRNA expression of Nrf2 downstream genes, including heme oxygenase 1 and metallothionein 1, were significantly less induced by Cd exposures in the kidney of Nrf2-KO compared with Nrf2-WT mice. In conclusion, Nrf2-deficient mice are more sensitive to kidney injury induced by subacute Cd exposure due to a muted antioxidant response, as well as a likely diminished production of specific Cd detoxification metallothioneins.

Influence of Renal Impairment on Serum Parathyroid Hormone and Vitamin D Status and their Association with Serum Creatinine in Patients Undergoing Haemodialysis: A Case-control Study

Introduction: A transition in the lifestyle of Saudi population over the past few decades has increased the burden of various metabolic disorders including, diabetes mellitus type 2, Chronic Kidney Disease (CKD), cardiovascular diseases, and vitamin D deficiency. Deficiency of vitamin D has been linked to the progression of kidney disease and many cardiovascular complications. Aim: The study focuses on the vitamin D status and associated changes in serum Parathyroid Hormone (PTH) in End Stage Renal Disease (ESRD) patients undergoing haemodialysis in the Northern Border Region (Arar city) of Saudi Arabia. The present study also investigated the relationship between serum creatinine, PTH and vitamin D levels in these patients. Materials and Methods: This case-control study was carried out for a period of five months (September 2019 to January 2020). It included 60 patients, suffering from ESRD on haemodialysis (cases) attending the Nephrology Centre of Prince Mohammed bin Saud Al Kabeer renal dialysis unit in Arar Central Hospital, Arar, Saudi Arabia. A control population (n=60) with normal kidney function, who visited the hospital for other reasons, was also identified. Their blood samples were collected for estimation of renal function parameters {Blood Urea Nitrogen (BUN) and creatinine}, serum calcium, phosphate, vitamin D and PTH. Statistical analysis was performed using the Statistical Package for the Social Sciences version 22.0. Results: The study included 60 patients (50% males and 50% females) undergoing haemodialysis and 60 healthy controls (50% males and 50% females) with a mean age of 46.83±14.19 (range 18-73 years) and 39.25±5.11 (range 30-54 years) years, respectively. The mean BMI of the patients was 27.3±3.4 kg/m2 and that of controls was 23.7±2.2 kg/m2. A significant elevation (p-value <0.001) of serum PTH showing hyperparathyroidism accompanied by significant (p-value <0.001) hypovitaminosis D and hypocalcaemia was observed in the patients as compared to controls. The results also demonstrated significantly elevated (p-value <0.001) levels of BUN and serum creatinine in ESRD patients. Results of correlation analysis exhibited a significant (p-value <0.05) positive correlation between serum creatinine and PTH whereas, there was a significant (p-value <0.05) negative correlation between serum creatinine and vitamin D; and serum PTH and vitamin D among the patients. Conclusion: This study highlights the importance of monitoring changes in PTH levels in patients with impaired renal function for the early detection and treatment of CKD. The study also showed a significant (p<0.05) positive association between serum creatinine and PTH followed by a significant (p<0.05) negative correlation between serum creatinine and vitamin D; and serum PTH and vitamin D.

Clinical biochemistry profile of Leptospira IgG seropositive trade horses

Background: Trade horses in Nigeria are not vaccinated against leptospirosis. Clinical biochemistry profile of Leptospira IgG (LEP-IgG) seropositive trade horses, alongside the effect of physiological factors (age, sex and pregnancy) were determined in this study. Methods and materials: Blood samples were collected via jugular veins of 129 horses of varying ages and sex at the Obollo Afor horse lairage. The harvested sera were subjected to qualitative test for LEP-IgG antibodies by sandwich ELISA method, and serum biochemistry evaluation which followed standard procedures. Results: A total number of 16 (12.4%) trade horses were recorded to be Leptospira seropositive. A significant association was recorded between the presence of LEP-IgG antibodies and age (p = 0.025), sex (p = 0.005), and pregnancy (p = 0.009). The mean serum total protein, albumin and total cholesterol values of the Leptospira seropositive trade horses were significantly (p < 0.05) lower than those of seronegative horses. Also, the mean blood urea nitrogen (BUN) level was significantly (p < 0.05) higher than those of seronegative horses. The mean serum ALT, AST, ALP and total protein values of the seropositive stallions were significantly (p < 0.05) lower than those of the Leptospira seropositive mares. The mean serum albumin and creatinine values of the Leptospira seropositive stallions were significantly (p < 0.05) higher than those of the Leptospira seropositive mares. The serum ALP of the seropositive young horses was significantly (p < 0.05) lower than those of the adult and horses. The mean serum albumin of young horses was significantly (p < 0.05) higher than those of old trade horses. The mean serum ALP value of the pregnant mares was significantly (p < 0.05) higher than that of the non-pregnant mares. The mean serum albumin value of seropositive pregnant mares was significantly (p < 0.05) lower than those of the non-pregnant seropositive mares. Also, the serum globulin and creatinine values of seropositive pregnant mares were significantly (p < 0.05) higher than those of the non-pregnant seropositive mares. Conclusion: Therefore, it was concluded that the seroprevalence of leptospirosis in trade horses was 12.4%. LEP-IgG seropositive horses were hypoproteinaemic, hypoalbuminaemic, hypocholesterolemic, with elevated levels of BUN. This suggests that the level of anti-LEP IgG is less protective and leptospirosis in horses is more associated with hepatic than renal involvement.

Kidney Function Indicators Predict Adverse Outcomes of COVID-19

BackgroundThe coronavirus disease 2019 (COVID-19) is a recently emerged respiratory infectious disease with kidney injury as a part of the clinical complications. However, the dynamic change of kidney function and its association with COVID-19 prognosis are largely unknown.MethodsIn this multicenter retrospective cohort study, we analyzed clinical characteristics, medical history, laboratory tests, and treatment data of 12,413 COVID-19 patients. The patient cohort was stratified according to the severity of the outcome into three groups: non-severe, severe, and death.FindingsThe prevalence of elevated blood urea nitrogen (BUN), elevated serum creatinine (Scr), and decreased blood uric acid (BUA) at admission was 6.29%, 5.22%, and 11.66%, respectively. The trajectories showed the elevation in BUN and Scr levels, as well as a reduction in BUA level for 28 days after admission in death cases. Increased all-cause mortality risk was associated with elevated baseline levels of BUN and Scr and decreased levels of BUA.ConclusionsThe dynamic changes of the three kidney function markers were associated with different severity and poor prognosis of COVID-19 patients. BUN showed a close association with and high potential for predicting adverse outcomes in COVID-19 patients for severity stratification and triage.FundingThis study was supported by grants from the National Key R&D Program of China (2016YFF0101504), the National Science Foundation of China (81630011, 81970364, 81970070, 81970011, 81870171, and 81700356), the Major Research Plan of the National Natural Science Foundation of China (91639304), the Hubei Science and Technology Support Project (2019BFC582, 2018BEC473, and 2017BEC001), and the Medical Flight Plan of Wuhan University.

S2102 Color Vision Deficiency and Gastrointestinal Hemorrhage: A Synergistically Lethal Combination

INTRODUCTION: Color Vision Deficiency (CVD), also known as color blindness, is most often a congenital abnormality with a male predominance. The medical care of patients with color blindness involves awareness of such color discrimination issues, including preparatory advice and prophylactic action to avoid potentially dangerous situations, such as detecting sunburns from the sun's UV radiation, or food handling and cooking poultry to a safe level. In patients with deficiencies in identifying the color red, there represents a unique issue revolving around the detection of blood. We present a case of a patient admitted for hemorrhagic shock secondary to a gastrointestinal bleed, with a delay in presenting for medical evaluation due to the patient’s inability to detect bright red blood per rectum. CASE DESCRIPTION/METHODS: A 65 year-old male with coronary artery disease, on dual antiplatelet therapy, presented with weakness, lightheadedness, and loose stools for 10 days. He denied a history of excessive alcohol or non-steroidal anti-inflammatory drug use. Physical exam was notable for a mean arterial blood pressure of 52 mm Hg, tachycardia to 135 beats per minute, diaphoresis, pale complexion, and guaiac positive maroon stool. His laboratory studies revealed a hemoglobin concentration of 4.8 g/dL with a normal baseline level, lactic acid level of 6.6 mg/dL, and an elevated blood urea nitrogen level of 53 mg/dL. After admission to the intensive care unit and multiple packed red blood cell transfusions, the patient underwent endoscopic evaluation, revealing multiple duodenal ulcers with biopsies positive for H. pylori organisms. The patient later divulged he had congenital red/green color blindness, preventing him from recognizing his stool’s bright red blood color at symptom onset. The patient was educated on early recognition of blood loss, treated with triple-therapy for H. pylori, and discharged home with close follow-up. DISCUSSION: The literature on CVD in relation to gastrointestinal bleeding is scarce, with only two case reports identified on review. CVD is a common medical condition, with an estimated prevalence of 8%. Screening for CVD is through different optical tests, the most common of which is the Isihara test, utilizing multiple colors to compose either a number or pattern, usually only visible to a person with full color vision. The potential dangers of an inability to detect life-threatening bleeding makes it an essential topic to reinforce among physicians caring for patients with color blindness.Figure 1.: Endoscopic Evaluation.Figure 2.: Endoscopic Evaluation 2.Figure 3.: Ishihara Test For Color Vision Deficiency.

Diagnostic performance of initial blood urea nitrogen combined with D-dimer levels for predicting in-hospital mortality in COVID-19 patients

The crude mortality rate in critical pneumonia cases with coronavirus disease 2019 (COVID-19) reaches 49%. This study aimed to test whether levels of blood urea nitrogen (BUN) in combination with D-dimer were predictors of in-hospital mortality in COVID-19 patients. The clinical characteristics of 305 COVID-19 patients were analysed and were compared between the survivor and non-survivor groups. Of the 305 patients, 85 (27.9%) died and 220 (72.1%) were discharged from hospital. Compared with discharged cases, non-survivor cases were older and their BUN and D-dimer levels were significantly higher (P < 0.0001). Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression analyses identified BUN and D-dimer levels as independent risk factors for poor prognosis. Kaplan-Meier analysis showed that elevated levels of BUN and D-dimer were associated with increased mortality (log-rank, P < 0.0001). The area under the curve for BUN combined with D-dimer was 0.94 (95% CI 0.90-0.97), with a sensitivity of 85% and specificity of 91%. Based on BUN and D-dimer levels on admission, a nomogram model was developed that showed good discrimination, with a concordance index of 0.94. Together, initial BUN and D-dimer levels were associated with mortality in COVID-19 patients. The combination of BUN ≥ 4.6 mmol/L and D-dimer ≥ 0.845 μg/mL appears to identify patients at high risk of in-hospital mortality, therefore it may prove to be a powerful risk assessment tool for severe COVID-19 patients.

Chlorogenic acid prevents vancomycin-induced nephrotoxicity without compromising vancomycin antibacterial properties.

Vancomycin (VCM) is an effective chemotherapeutic agent commonly used against gram-positive microorganisms but has serious nephrotoxic side effects that limit its effectiveness. New therapeutics and strategies are urgently needed to combat VCM associated nephrotoxicity. In this study, we determined the protective effect of chlorogenic acid (CA) in a rat model of VCM-induced nephrotoxicity. VCM administration led to markedly elevated blood urea nitrogen and serum creatinine levels that could be prevented with CA co-administration. VCM-mediated oxidative stress was also significantly attenuated by CA as reflected by decreased malondialdehyde and nitric oxide in VCM-treated kidneys. CA administration also prevented the VCM-mediated decrease in the renal antioxidative enzyme activities of glutathione reductase, glutathione peroxidase, and catalase and led to increased levels of reduced glutathione that had been depleted by VCM. Moreover, CA administration clearly inhibited VCM-induced expression of nuclear factor-kappa B, inducible nitric oxide synthase and the downstream pro-inflammatory mediators tumor necrosis factor-α and interleukins 1β and 6. Apoptotic markers were also markedly down-regulated with CA. Overall, CA treatment mitigated VCM-induced oxidative and nitrosative stresses and countered the apoptotic and inflammatory effects of VCM. Notably, CA did not affect the antibacterial activity of VCM in vitro.

Who's at Risk? A Prognostic Model for Severity Prediction in Pediatric Acute Pancreatitis.

Objectives:The aim of the study was to validate and optimize a severity prediction model for acute pancreatitis (AP) and to examine blood urea nitrogen (BUN) level changes from admission as a severity predictor.Study Design:Patients from 2 hospitals were included for the validation model (Children’s Hospital of the King’s Daughters and Children’s National Hospital). Children’s Hospital of the King’s Daughters and Cincinnati Children’s Hospital Medical Center data were used for analysis of BUN at 24 to 48 hours.Results:The validation cohort included 73 patients; 22 (30%) with either severe or moderately severe AP, combined into the all severe AP (SAP) group. Patients with SAP had higher BUN (P = 0.002) and lower albumin (P = 0.005). Admission BUN was confirmed as a significant predictor (P = 0.005) of SAP (area under the receiver operating characteristic [AUROC] 0.73, 95% confidence interval [CI] 0.60–0.86). Combining BUN (P = 0.005) and albumin (P = 0.004) resulted in better prediction for SAP (AUROC 0.83, 95% CI 0.72–0.94). A total of 176 AP patients were analyzed at 24–48 hours; 39 (22%) met criteria for SAP. Patients who developed SAP had a significantly higher BUN (P < 0.001) after 24 hours. Elevated BUN levels within 24 to 48 hours were independently predictive of developing SAP (AUROC: 0.76, 95% CI: 0.66–0.85). Patients who developed SAP had a significantly smaller percentage decrease in BUN from admission to 24 to 48 hours (P = 0.002).Conclusion:We externally validated the prior model with admission BUN levels and further optimized it by incorporating albumin. We also found that persistent elevation of BUN is associated with development of SAP. Our model can be used to risk stratify patients with AP on admission and again at 24 to 48 hours.

Synthesis, characterization, and intraperitoneal biochemical studies of zinc oxide nanoparticles in Rattus norvegicus

In the present work, zinc oxide nanoparticles (ZnO-NPs) were synthesized in the presence of poly(ethylene glycol) which is a biocompatible agent in living systems. The sub-chronic effects of ZnO-NPs were investigated based on biochemical parameters and histological changes applied to Rattus norvegicus. The structural, morphology, and size characterization of nanoparticles were studied by applying techniques as XRD, SEM, FTIR, and TEM. 8-week intraperitoneal injection of ZnO-NPs at a dose of 100 mg/kg leads to significant changes in liver enzymes, malondialdehyde (MDA) content, and tissue histopathological changes. The animal group which was treated with 50 mg/kg of ZnO-NPs presented elevated blood urea nitrogen and creatinine levels, but the liver enzymes and liver histopathology were found to be in normal level. The rats exposed to increasing dose of ZnO-NPs (100 mg/kg) showed necrosis of germinal epithelium and sertoli cells in the seminiferous tubules. The current study clearly demonstrated the dose-dependent toxicity of zinc oxide nanoparticles.

Does Baseline BUN Have an Additive Effect on the Prediction of Mortality in Patients with Acute Pulmonary Embolism?

Background: In patients with heart failure, elevated levels of blood urea nitrogen (BUN) is a prognostic factor. In this study, we investigated the prognostic value of elevated baseline BUN in short-term mortality among patients with acute pulmonary embolism (PE). Methods: Between 2007 and 2014, cardiac biomarkers and BUN levels were measured in patients with acute PE. The primary endpoint was 30-day mortality, evaluated based on the baseline BUN (≥14 ng/L) level in 4 groups of patients according to the European Society of Cardiology’s risk stratification (low-risk, intermediate low-risk, intermediate high-risk, and high-risk). Results: Our study recruited 492 patients with a diagnosis of acute PE (mean age=60.58±16.81 y). The overall 1-month mortality rate was 6.9% (34 patients). Elevated BUN levels were reported in 316 (64.2%) patients. A high simplified pulmonary embolism severity index (sPESI) score (OR: 5.23, 95% CI: 1.43–19.11; P=0.012), thrombolytic or thrombectomy therapy (OR: 2.42, 95% CI: 1.01–5.13; P=0.021), and elevated baseline BUN levels (OR: 1.04, 95% CI: 1.01–1.03; P=0.029) were the independent predictors of 30-day mortality. According to our receiver-operating characteristics analysis for 30-day mortality, a baseline BUN level of greater than 14.8 mg/dL was considered elevated. In the intermediate-low-risk patients, mortality occurred only in those with elevated baseline BUN levels (7.2% vs. 0; P=0.008). Conclusion: An elevated baseline BUN level in our patients with PE was an independent predictor of short-term mortality, especially among those in the intermediate-risk group.

Renal protective effects of vicenin-2 and scolymoside in a mouse model of sepsis

This study was initiated to determine whether 2 structurally related flavonoids found in Cyclopia subternata-vicenin-2 (VCN) and scolymoside (SCL)-could modulate renal functional damage in a mouse model of sepsis, and to elucidate the relevant underlying mechanisms. The potential of VCN and SCL treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured via assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with either VCN or SCL resulted in elevated plasma levels of BUN and creatinine, and of protein in the urine of mice with CLP-induced renal damage. Moreover, both VCN and SCL inhibited nuclear factor κB activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. VCN and SCL treatment also reduced the plasma levels of interleukin-6, and tumor necrosis factor-α, reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. The present results suggest that VCN and SCL protect mice from sepsis-triggered renal injury.

HIGH ADMISSION PLASMA OSMOLALITY VALUE AS IN-HOSPITAL MAJOR ADVERSE CARDIOVASCULAR EVENTS PREDICTOR IN PATIENT WITH ACUTE MYOCARDIAL INFARCTION

Background: Elevated blood urea nitrogen (BUN), blood glucose, and alteration sodium levels are common among patients with acute myocardial infarction (AMI). These parameters to be widely investigated to assess the prognosis in AMI patients. However, the combination of these parameters (BUN, blood glucose, and sodium) calculated by a certain formula in the form of plasma osmolality has not been widely studied to assess the prognosis of patients with acute myocardial infarction. This study aims to assess plasma osmolality in predicting hospital major adverse cardiovascular events (MACEs) among AMI patients. Methods: Data were collected from 118 consecutive patients with AMI in Cardiac Centre Haji Adam Malik General Hospital Medan. We measured admission plasma osmolality [1,86 (Na+) + BUN/2,8 + Glucose/18+9]. Then we observed in hospital Major Adverse Cardiovascular Outcomes (MACEs) which consist of cardiovascular mortality, acute heart failure, malignant arrhythmia, and cardiogenic shock. Statistical analysis was performed using mean difference, logistic regression, and receiver operating curve (ROC). Result: Among 118 patients, MACEs were observed in 49 (41.5%) patients with the most common MACEs was acute heart failure (25.4%). Bivariate analysis showed a significant relationship between the plasma osmolality and in hospital MACEs (p &lt; 0.001). The plasma osmolality AUC prediction value was 78.9%. The optimal cut-off value was 279.9 mOsm/kg (sensitivity 81.6%; specificity 75.4%). In multivariate logistic regression analysis, the plasma osmolality was the strongest predictor with an OR value of 10.542 (95% CI 2.694-41.255; p-value &lt;0.001). Conclusions: Among AMI patients, high plasma osmolality value (≥280 mOsm/kg) is a better predictor of in-hospital MACEs than its components separately(BUN, glucose level, sodium).

Renal protective effects of zingerone in a mouse model of sepsis

Zingerone (ZGR), a phenolic alkanone isolated from ginger, has been reported to possess pharmacological activities such as anti-inflammatory and anti-apoptotic effects. This study was initiated to determine whether ZGR could modulate renal functional damage in a mouse model of sepsis and to elucidate the underlying mechanisms. The potential of ZGR treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured by assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with ZGR resulted in elevated plasma levels of BUN and creatinine, and of protein in urine in mice with CLP-induced renal damage. Moreover, ZGR inhibited nuclear factor-κB activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. ZGR treatment also reduced the plasma levels of interleukin-6 and tumor necrosis factor-α, reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. Our study showed renal suppressive effects of zingerone in a mouse model of sepsis, suggesting that ZGR protects mice against sepsis-triggered renal injury.

Impact of Elevated Preoperative Blood Urea Nitrogen (BUN) Levels on Outcomes in CF-LVAD Patients

Purpose Patients with advanced heart failure and cardiorenal syndrome can experience significantly elevation in blood urea nitrogen (BUN) levels. We evaluated the impact of preoperative elevated BUN levels on bleeding and survival in patients who underwent continuous flow - left ventricular assist device (CF-LVAD) implantation. Methods We performed a retrospective review of 737 patients who underwent implantation of CF-LVADs from December 1999 through August 2017 at our center. Preoperative hemodynamics, perioperative characteristics, and postoperative outcomes were compared between patients with BUN ≥60 mmol/L and those Results Of the 664 patients included in the study (73 were excluded due to incomplete data), 53 patients had a BUN ≥60 mmol/L (mean: 83±28) and 611 patients had a BUN Conclusion Preoperative elevation in BUN above 60 mmol/L was associated with higher mortality. Additional studies are warranted to determine whether preoperative optimization of the uremia with medical therapy and/or dialysis can impact the increased risk of mortality.

A quantitative exploration of gastrointestinal bleeding in intensive care unit patients.

BackgroundQuantitative assessments of the severity of bleeding in patients with bleeds within the gastrointestinal tract (GIB) are generally limited to blood tests like the hematocrit. The varied and irregular nature of the data collected during such observations makes it difficult in retrospective data analysis to characterize the complete course of bleeding. We intend to quantify the rate of blood loss over the course of an ICU stay, facilitating more precise analysis of retrospective data, and to use this quantification to examine questions about the effects of GIB.Methods and findingsA population of 2,445 intensive care admissions across 2,266 patients with a diagnosis of GIB was studied. Using statistical techniques for smoothing data and accepted medical approaches for calculating blood loss, we are able to convert collections of individual laboratory readings that are difficult to understand into a simple, interpretable overview of the patient’s bleeding status over time. To demonstrate this method, we compare patients’ standard vital signs while bleeding heavily to times when they are not bleeding, finding a 3.0 ± 0.5% increase in heart rate, a 1.3 ± 0.4% decrease in systolic blood pressure and a 0.9 ± 0.5% decrease in diastolic blood pressure. After considering the effect of bleeding on standard vital signs, we demonstrate that patients with upper GIB have significantly elevated blood urea nitrogen levels while bleeding heavily, with a mean increase of 11.7 ± 7.2%, while patients with lower GIB do not, with a mean increase of 4.2 ± 6.6%.ConclusionsThis study introduces a novel method of processing retrospective laboratory data to characterize the course of bleeds within the gastrointestinal tract. This method is used to examine the direct effects of bleeding on a patient and can be deployed in future studies of bleeding using retrospective data.

Effect of 3-mercaptopyruvate Sulfurtransferase Deficiency on the Development of Multiorgan Failure, Inflammation, and Wound Healing in Mice Subjected to Burn Injury.

The gaseous transmitter hydrogen sulfide (H2S) has been implicated in various forms of critical illness. Here, we have compared the outcome of scald burn injury in wild-type mice and in mice deficient in 3-mercaptopyruvate sulfurtransferase (3-MST), a mammalian H2S-generating enzyme. Outcome variables included indices of organ injury, clinical chemistry parameters, and plasma levels of inflammatory mediators. Plasma levels of H2S significantly increased in response to burn in wild-type mice, but remained unchanged in 3-MST-/- mice. The capacity of tissue homogenates to produce H2S from 3-mercaptopyruvate was unaffected by burn injury. In 3-MST-/- mice, compared to wild-type controls, there was a significant enhancement in the accumulation of polymorphonuclear cells (as assessed by the quantification of myeloperoxidase) in the liver (but not heart, lung, or skin) at 7 days postburn. Oxidative tissue damage (as assessed by malon dialdehyde content) was comparable between wild-type and 3-MST-deficient mice in all tissues studied. 3-MST-/- and wild-type mice exhibited comparable burn-induced elevations in circulating plasma levels of hepatic injury; however, 3-MST-/- mice exhibited a higher degree of renal injury (as reflected by elevated blood urea nitrogen levels) at 7 days postburn. Inflammatory mediators (eg, TNF-α, IL-1β, IL-2, IL-6, IL-10, and IL-12) increased in burn injury, but without significant differences between the 3-MST-/- and wild-type groups. The healing of the burn wound was also unaffected by 3-MST deficiency. In conclusion, the absence of the H2S-producing enzyme 3-MST slightly exacerbates the development of multiorgan dysfunction but does not affect inflammatory mediator production or wound healing in a murine model of burn injury.

Pelargonidin Protects Against Renal Injury in a Mouse Model of Sepsis.

Pelargonidin (PEL) is a well-known red pigment found in plants, and it has been reported to have important biological activities that are potentially beneficial for human health. This study was initiated to determine whether PEL could modulate renal functional damage in a mouse model of sepsis, and to elucidate the underlying mechanisms. The potential of PEL treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured by assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase (GSH-Px) activity, catalase activity, and superoxide dismutase (SOD) activity. Treatment with PEL resulted in elevated plasma levels of BUN and creatinine, and of protein in urine in mice with CLP-induced renal damage. Moreover, PEL inhibited nuclear factor-κB activation and reduced the induction of nitric oxide synthase and excessive production of nitric acid. PEL treatment also reduced the plasma levels of interleukin-6 and tumor necrosis factor-α reduced lethality due to CLP-induced sepsis, increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of SOD, GSH-Px, and catalase in kidney tissues. These results suggested that PEL protects mice against sepsis-triggered renal injury.

Sulforaphane Suppresses Sepsis-Mediated Renal Functions in Cecal Ligation and Puncture Mouse Model

Sulforaphane (SFN), a natural isothiocyanate present in cruciferous vegetables such as broccoli and cabbage, is effective in preventing carcinogenesis, diabetes, and inflammatory responses. This study was initiated to determine whether SFN could modulate renal functional damage in a mouse model of sepsis and to elucidate the underlying mechanisms. The potential of SFN treatment to reduce renal damage induced by cecal ligation and puncture (CLP) surgery in mice was measured by assessment of serum creatinine, blood urea nitrogen (BUN), lipid peroxidation, total glutathione, glutathione peroxidase activity, catalase activity, and superoxide dismutase activity. Treatment with SFN resulted in elevated plasma levels of BUN and creatinine, and of protein in urine in mice with CLP-induced renal damage. SFN treatment also reduced the plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α),▢increased lipid peroxidation, and markedly enhanced the antioxidant defense system by restoring the levels of superoxide dismutase, glutathione peroxidase, and catalase in kidney tissues. The present results suggested that SFN protects mice against sepsis-triggered renal injury.

Activated renal tubular Wnt/β-catenin signaling triggers renal inflammation during overload proteinuria

Imbalance of Wnt/β-catenin signaling in renal cells is associated with renal dysfunction, yet the precise mechanism is poorly understood. Previously we observed activated Wnt/β-catenin signaling in renal tubules during proteinuric nephropathy with an unknown net effect. Therefore, to identify the definitive role of tubular Wnt/β-catenin, we generated a novel transgenic "Tubcat" mouse conditionally expressing stabilized β-catenin specifically in renal tubules following tamoxifen administration. Four weeks after tamoxifen injection, uninephrectomized Tubcat mice displayed proteinuria and elevated blood urea nitrogen levels compared to non-transgenic mice, implying a detrimental effect of the activated signaling. This was associated with infiltration of the tubulointerstitium predominantly by M1 macrophages and overexpression of the inflammatory chemocytokines CCL-2 and RANTES. Induction of overload proteinuria by intraperitoneal injection of low-endotoxin bovine serum albumin following uninephrectomy for four weeks aggravated proteinuria and increased blood urea nitrogen levels to a significantly greater extent in Tubcat mice. Renal dysfunction correlated with the degree of M1 macrophage infiltration in the tubulointerstitium and renal cortical up-regulation of CCL-2, IL-17A, IL-1β, CXCL1, and ICAM-1. There was overexpression of cortical TLR-4 and NLRP-3 in Tubcat mice, independent of bovine serum albumin injection. Finally, there was no fibrosis, activation of epithelial-mesenchymal transition or non-canonical Wnt pathways observed in the kidneys of Tubcat mice. Thus, conditional activation of renal tubular Wnt/β-catenin signaling in a novel transgenic mouse model demonstrates that this pathway enhances intrarenal inflammation via the TLR-4/NLRP-3 inflammasome axis in overload proteinuria.

Factors associated with absent microhematuria in symptomatic urinary stone patients

IntroductionThe aim of this study was to identify factors associated with absent hematuria in patients with symptomatic urinary stones. MethodsThis retrospective study analyzed the clinical and imaging findings of emergency department patients who underwent computed tomography (CT) for suspected ureteral colic over the past 2years. All patients also underwent a microscopic urinalysis, and the presence of 4 or more red blood cells/high-power field was defined as microhematuria. ResultsA total of 798 patients were included in this study. Of these patients, 750 (94.0%) presented with hematuria, while 48 (6.0%) urine samples did not have evidence of hematuria. The group with an absence of hematuria was more likely to have a lower stone location (located in an area from the distal ureter to the bladder) and perinephric stranding on CT than the hematuria group (75.0% vs. 54.3%, p=0.005; 47.9% vs. 30.5%, p=0.012, respectively). The degree of hematuria at each stone location was significantly different (p=0.001). In multivariate analysis, perinephric stranding (odds ratios (OR) 1.87 [95% confidence interval (CI) 1.01–3.46], p=0.047), a lower stone location (OR 2.72 [95% CI 1.37–5.36], p=0.004), and elevated serum blood urea nitrogen (BUN) levels (OR 1.06 [95% CI 1.01–1.12], p=0.026) were associated with absent hematuria. ConclusionsIn this large cohort of patients with renal colic, 6% had no microhematuria. Although some CT findings and elevated BUN were independently associated with hematuria absence, there was no difference in the demographics, time of presentation and degree and location of pain between the groups.