Increased Blood Urea Nitrogen Levels Research Articles

Effects of rosmarinic acid on cyclophosphamide-induced nephrotoxicity in rats

Purpose: Cyclophosphamide (CP) is an antineoplastic agent. It is used in the treatment of many types of cancer. Rosmarinic acid (RA) exhibits remarkable biological activities such as anti-inflammatory, antitumor, antibacterial, and antimicrobial effects. This study aimed to evaluate the effect of rosmarinic acid against CP-induced nephrotoxicity.
 Materials and Methods: Eighteen male Sprague Dawley rats were randomly divided into 3 equal groups; Sham group (n=6): 0.9% saline solution/8 days/oral gavage + 0.9% saline solution/8th day/intraperitoneal, CP group (n=6): 0.9% saline solution/8 days/oral gavage + 200 mg/kg/8th day/intraperitoneal CP, and CP+RA group (n=6): 100 mg/kg/8 days/oral gavage RA + 200 mg/kg/8th day/intraperitoneal CP was applied. Hematoxylin and Eosin, Periodic Acid-Schiff, and Masson’s Trichrome staining were performed on the collected tissues 
 Results: Histopathological evaluation revealed tubular atrophy, glomerular damage, vascular congestion, vacuolization, and interstitial inflammation in the CP group. Histopathological scores were significantly lower in the CP+RA group compared to the CP group. Intertubular fibrosis was observed in the CP group compared to the Sham group. Fibrosis decreased with rosmarinic acid. PAS-stained sections from the CP group showed tubular epithelial vacuolization, brush border, and basal membrane disruption. These findings decreased with rosmarinic acid. The increased blood urea nitrogen level in the CP group was lower in the CP+RA group, while the decreased SOD level in the CP group was higher in the CP+RA group. 
 Conclusion: RA has protective effects against CP causing tubular atrophy, glomerular damage, vascular congestion, vacuolization, and interstitial inflammation in the kidney

The Worsening Renal Perfusion Index Predicts the Prognoses of Heart Failure Patients Treated with Sacubitril/Valsartan

Introduction: Sacubitril/valsartan (S/V) reduces all-cause mortality in patients with heart failure with reduced ejection fraction (HFrEF), but it may decline their estimated glomerular filtration rates (eGFR). In addition to eGFR, this clinical study aimed to develop a blood urea nitrogen (BUN)-based index to evaluate the status of renal perfusion and then identify predictors of all-cause death or heart transplant in patients with HFrEF receiving S/V. Methods: From the recruited 291 patients with HFrEF who were prescribed S/V from March 2017 to March 2019, we collected demographic, drug history, laboratory, echocardiographic, and clinical data from 1 year before S/V initiation until December 2020. Regression analysis was conducted by fitting Cox’s models with time-dependent covariates for the survival time and applying the modern stepwise variable selection procedure. The smoothing spline method was used to detect nonlinearity in effect and yield optimal cut-off values for continuous covariates. Results: In the Cox’s model, decreased hemoglobin level, decreased mean left ventricular ejection fraction, declined daily dose of S/V, decreased eGFR within 3 months, and increased BUN levels within 1 month and 9 months over time were significantly associated with an increased risk of all-cause death or heart transplant in patients with HFrEF. Conclusions: Adequate maintenance of renal perfusion is crucial for the continuous use of S/V and to avoid worsening renal function in patients with HFrEF. We defined the maximum increase in BUN levels within a specified period as the Worsening Renal Perfusion Index (WRP_SV Index) to capture the prognostic effect of renal hypoperfusion in patients with HFrEF.

Whey protein positively alters inflammatory markers and metabolic parameters of overweight and obese adults

Introduction: The effects of prolonged consumption of whey protein on health are controversial. This study aimed to determine whether whey protein positively alters health parameters of overweight and obese adults. Methods: Randomised controlled trial was conducted. Fifty-eight participants, aged 30-50 years, were randomly allocated into four groups and supplemented with 50 g protein for eight weeks (group 1: plant-based protein (PBP), group 2: whey protein isolate (WPI) with cocoa powder, group 3: PBP with whey protein concentrate (WPC), and group 4: WPI with milk powder). Body composition and biochemical parameters (kidney and liver functions, inflammation, oxidative stress, and antioxidant capacity) were evaluated at pre-intervention and 8 weeks after intervention. Results: At Week 8, group 3 had lower diastolic blood pressure, waist circumference, visceral fat, and risk of insulin resistance (p<0.05 for all). Group 2 had decreased levels of total cholesterol and low-density lipoprotein cholesterol (p<0.05 for all). A drop in triglyceride was seen in group 4 (p=0.026). Whey protein decreased alanine aminotransferase level (p=0.028), while PBP increased aspartate aminotransferase level (p=0.034). PBP or WPI with milk powder increased blood urea nitrogen level (p>0.05 for all). Interleukin-6 and lactoferrin levels fell in all groups (p<0.05), while hs-CRP increased in the PBP group (p=0.043). Group 2 experienced increased antioxidant capacity. However, levels of oxidative stress markers were significantly decreased in the PBP group and WPI with milk powder group. Conclusion: Whey protein revealed positive effects on anthropometric parameters and biochemical markers of overweight and obese adults. Therefore, proper supplementation of whey protein can potentially promote health.

Protein arginine methyltransferase 3 inhibits renal tubulointerstitial fibrosis through asymmetric dimethylarginine.

Mammalian protein arginine methyltransferase 3 (PRMT3) catalyzes the monomethylation and dimethylation of the arginine residues of proteins. The role of PRMT3 in renal fibrosis is currently unknown. We aimed to study the role of PRMT3 in renal fibrosis and explored its underlying mechanisms. Quantitative PCR analysis and Western blotting analysis showed that the expression of PRMT3 was up-regulated in unilateral ureteral obstruction (UUO) mouse kidneys. Knockout of Prmt3 gene enhanced interstitial fibrosis in UUO kidneys as shown by Masson staining and Western blotting analysis the expression of pro-fibrotic markers. The production of asymmetric dimethylarginine (ADMA) was increased in wide type UUO kidneys but not further increased in Prmt3 knockout UUO kidneys. Administration of exogeneous ADMA in UUO kidneys blocked the enhanced renal interstitial fibrosis in Prmt3 mutant mice. Moreover, genetic deletion of Prmt3 gene increased blood urea nitrogen levels and renal deposition of collagen in folic acid injected mice. We conclude that PRMT3 inhibits renal tubulointerstitial fibrosis through elevating renal ADMA levels.

Safety of [177Lu]Lu-NeoB treatment: a preclinical study characterizing absorbed dose and acute, early, and late organ toxicity

PurposeThe radiolabeled gastrin-releasing peptide receptor (GRPR)-targeting antagonist NeoB is a promising radioligand for imaging and therapy of GRPR-expressing malignancies. In the current study, we aimed to discover the target organs of toxicity and the radiotoxic effects to these organs, when repeated dosages of [177Lu]Lu-NeoB are administered to healthy female and male mice.MethodsAnimals received either 3 injections, with a 7-day interval, of vehicle (control group 1), 1200 pmol [175Lu]Lu-NeoB (control group 2) or 40 MBq/400 pmol, 80 MBq/800 pmol, and 120 MBq/1200 pmol [177Lu]Lu-NeoB (treatment groups 1, 2, and 3, respectively). At week 5, 19, and 43 after the first injection acute, early, and late organ toxicity, respectively, was determined. For this, histopathological and blood analyses were performed. To correlate the observed toxicity to absorbed dose, we also performed extensive biodistribution and dosimetry studies.ResultsThe biodistribution study showed the highest absorbed doses in GRPR-expressing pancreas, the liver, and the kidneys (the main organs of excretion). Both control groups and almost all animals of treatment group 1 did not show any treatment-related toxicological effects. Despite the high absorbed doses, no clear microscopic signs of toxicity were found in the pancreas and the liver. Histological analysis indicated kidney damage in the form of hydronephrosis and nephropathy in treatment groups 2 and 3 that were sacrificed at the early and late time point. In the same groups, increased blood urea nitrogen levels were found.ConclusionIn general, repeated administration of [177Lu]Lu-NeoB was tolerated. The most significant radiotoxic effects were found in the kidneys, similar to other clinically applied radioligands. The results of this study underline the potential of [177Lu]Lu-NeoB as a promising option for clinical therapy.

Correlation between blood urea nitrogen level and cochlear outer hair cell function in non-dialysis chronic kidney disease patients.

Background: Hearing loss due to impaired cochlear function, which results from increased blood urea nitrogen (BUN) level, is one of the important clinical problems in chronic kidney disease (CKD) patients with uremia. This study aims to determine correlation between blood urea nitrogen (BUN) levels and cochlear outer hair cell (OHC) dysfunction in non-dialysis stage 3-5 CKD patients so that the BUN levels may also be used to determine the presence of cochlear OHC dysfunction.Design and methods: An observational analytic study with a cross sectional design and consecutive sampling. This study was conducted from November 2019 to February 2020 at the Department of Internal Medicine, Soetomo Hospital, Surabaya, Indonesia, and Otorhinolaryngology-Head and Neck Surgery Department, Soetomo Hospital, Surabaya, Indonesia. Non-dialysis CKD patients who met the inclusion and exclusion criteria were subjected to a Distortion Product Otoacoustic Emissions (DPOAE) test to assess cochlear OHC function at the Otorhinolaryngology- Head and Neck Surgery, Soetomo Hospital, Surabaya.Results: Female patients were in larger number than male patients in a ratio of 1 : 2. Most of the patients were between 51-60 years of age. DPOAE distribution was refer in 25 patients (83.3%) and pass in 5 patients (16.7%). The highest pass was at 2000 Hz in 24 patients (80.0%), while the refer results were mostly at 12,000 Hz in 29 patients (96.7%). The highest average signal to noise ratio (SNR) was at 2000 Hz and 4000 Hz (12.77 dB and 11.13 dB), while the lowest at 11,000 Hz and 12,000 Hz (1.60 dB and 1.03 dB). Pearson’s correlation test on DPOAE results did not show a significant correlation (p>0.05) between BUN levels and impaired cochlear OHC function.Conclusions: There was no correlation between increased blood urea nitrogen levels and cochlear outer hair cell function disorders in non-dialysis patients with CKD stage 3-5. Significance for public health One of the most commonly found disabilities in the world is hearing loss, which has a prevalence of 5% of the world population or affecting 466 million people. One that contributes to the prevalence of hearing loss is Chronic Kidney Disease (CKD). Its contribution to hearing loss prevalence may reach 45% to 80%. This is because CKD itself may cause malfunctions of some organs, including auditory organs. Therefore, early detection of hearing loss among patients with CKD is necessary by determining correlation of a kidney disease marker, the blood urea nitrogen (BUN), and cochlear Outer Hair Cell (OHC) dysfunction. The otoacoustic emission examination (OAE) should be used to detect cochlear dysfunction as it has 95% sensitivity and 90% specificity. It was expected that by the finding of correlation between BUN levels and cochlear OHC dysfunction in CKD patients, possible hearing loss of these patients can be anticipated early.

Clinical Characteristics, Outcomes, and Risk Factors of Disease Severity in Patients With COVID-19 and With a History of Cerebrovascular Disease in Wuhan, China: A Retrospective Study.

Background and Purpose: Coronavirus disease 2019 (COVID-19) rapidly resulted in a pandemic. Information on patients with a history of cerebrovascular disease (CVD) infected with severe acute respiratory syndrome coronavirus 2 (SARS-COV-2) is limited. This study investigated the clinical features and the risk factors of developing adverse outcomes in patients with COVID-19 and with previous CVD.Methods: This was a single-center retrospective clinical study including all the confirmed cases of COVID-19 at Wuhan Huoshenshan Hospital from February 4 to April 7, 2020. Differences in clinical characteristics were compared between patients with and without a history of CVD. The incidences of severe events comprising all-cause death, intensive care unit admission, shock, and mechanical ventilation usage during hospitalization in two groups were compared using propensity score matching analysis and multivariate logistic regression analyses. Besides, the risk factors of developing severe events in patients with COVID-19 who also have history of CVD were analyzed.Results: A total of 2,554 consecutive patients were included in our study, of whom 109 (4.27%) had a medical history of CVD. Patients with CVD tend to be older and with more comorbidities, including hypertension, diabetes, coronary heart disease, and chronic obstructive pulmonary disease. The levels of white blood cell, neutrophil, C-reactive protein, creatine kinase isoenzymes, and lactate dehydrogenase were higher, whereas the levels of lymphocyte and albumin were lower in the CVD group. Compared to those without CVD, patients with CVD were more likely to have severe events after age matching (12.8 vs. 5.7%, P = 0.012). After adjusting for the confounding effects of age, sex, smoking, and comorbidities, the odds ratio for developing severe events with a history of CVD was 2.326 (95% CI, 1.168–4.630; P = 0.016). Besides, patients with CVD, either with decreased lymphocyte count (OR 9.192, 95% CI, 1.410–59.902, P = 0.020) or increased blood urea nitrogen (OR 5.916, 95% CI, 1.072–32.641, P = 0.041), had a higher risk of developing severe events during hospitalization.Conclusions: Patients with CVD history tend to have adverse clinical outcomes after being infected with SARS-COV-2. Decreased lymphocyte counts and increased blood urea nitrogen levels may be risk factors for adverse outcomes in patients with COVID-19, and had CVD.

Clinical Analysis of Kidney Injury in Elderly Patients with COVID-19

Objective:The aim of the study was to analyze the clinical features of elderly patients with coronavirus disease 2019 (COVID-19) and to explore the relationship between COVID-19 patients and kidney injury.Methods:A total of 188 elderly patients with confirmed COVID-19 enrolled in this study were hospitalized for at least 1 week in the Central Theater Command General Hospital of Chinese People's Liberation Army from January 3, 2020 to March 14, 2020. The recorded information included clinical data and results of kidney-related laboratory tests. Retrospective analysis was performed.Results:The median age of the patients was 69 years (interquartile range 65–78, range: 60–97 years); 31.4% were 60–74 years old, and 68.6% were over 75 years old. A total of 12.8% and 18.6% of the patients were in critical and severe stages of COVID-19, respectively. The proportions of patients using mechanical ventilators and deaths were 9.5% and 8.5%, respectively. A total of 26.1% and 8.5% of the patients showed mild elevation of blood urea nitrogen (BUN) and serum creatinine (SCr) levels at admission. A total of 18.6% and 5.9% of the patients had elevated BUN and SCr 1 week after admission, respectively. A total of 3.1% of the patients were diagnosed with acute kidney injury, and 75% of those patients had chronic kidney disease before admission. Compared with the patients aged 60–74 years, those over 75 years exhibited significantly increased proportions of elevated BUN levels, critical illness, use of mechanical ventilated, and death. Multivariate logistic regression analysis revealed that an elevated BUN level at admission and 1 week after admission were independent risk factors for death in the elderly patients with COVID-19.Conclusion:There were more critical cases and a high mortality in elderly patients with COVID-19. An increased BUN level was an independent risk factor for death in elderly patients with COVID-19.

Hyperglycemia exacerbates cadmium-induced glomerular nephrosis.

Current research suggests that cadmium (Cd) exposure may be associated with the progression of diabetic nephropathy; however, the details of this relationship are insufficiently understood. The present study investigated the effects of elevated glucose on Cd-induced toxicity to glomerular cells using in vitro and in vivo models, and it demonstrated that Cd exposure and the hyperglycemia of diabetes acting together increased the risk of developing glomerular nephrosis. In vitro, human podocytes were exposed to a DMEM low-glucose media without (control), or with Cd (as CdCl2), or a high-glucose media plus Cd. The CCK-8, ROS, apoptosis, and mitochondrial transmembrane potential (ΔΨm) assays showed that human podocytes exposed to Cd in a high-glucose media had greater degrees of injury compared with cells treated with Cd at low (euglycemic)-glucose levels. In vivo, diabetic hyperglycemia was induced by streptozotocin in 8-week-old male C57BL/6 mice to which either CdCl2 or saline (control) was intraperitoneally injected twice weekly for 24weeks. Compared with euglycemic saline-treated controls, the diabetic mice exposed to Cd demonstrated decreased body weight and increased blood urea nitrogen levels along with histopathological renal architecture changes including collagen fiber accumulation. The results of this study supported the hypothesis that hyperglycemia plus Cd exposure increases the risk of damage to glomerular podocytes compared with Cd exposure in euglycemia.

Renal-Protective Activity of Dried Gel of Aloe barbadensis (Elwa) on Gentamicin- Induced Nephrotoxicity in Albino Rats

Introduction:: Elwa (Aloe barbadensis / Aloe vera) also known as Sibr in Unani medicine which is dried juice obtained by the inspissations and used to treat many diseases, especially digestive disorders, arthritis, gastric ulcer, jaundice, amenorrhoea, kidney diseases, diseases of spleen and liver, constipation, nervine disorders, wounds, burns, scalds and other skin diseases. Methods:: The aim of this study was to evaluate the nephroprotective activity of Aloe barbadensis gel (ABG) on gentamicin-induced nephrotoxicity in rats. Wistar rats were divided into four groups of six animals in each. Group I (control); group II, III and IV were administered gentamicin 100 mg/kg/d subcutaneously from day four to eight. The lower (350 mg/kg) and higher doses (1260 mg/kg) of crude ABG were co-administrated orally in group III and group IV from day 1. On 9th day animals were sacrificed and serum was studied for blood urea nitrogen and serum creatinine and kidneys were prepared for histo-pathological analysis. Gentamicin alone treated group showed increased levels of blood urea nitrogen (118.76  0.90) and creatinine (3.42  0.13) were significantly inhibited in groups pretreated with lower [blood urea nitrogen (40.130.56); creatinine (1.640.13)] and higher [blood urea nitrogen (55.79  0.71); creatinine (2.50  0.06)] doses of crude Aloe barbadensis gel. Results:: The histopathological analysis also showed the protective nature of Aloe barbadensis gel in gentamicin-induced renal damage. Discussion:: In conclusion, the biochemical parameters and histopathological results confirmed nephroprotective effect of the crude Aloe barbadensis gel against gentamicin induced renal damage.

Elevated mean platelet volume in oral lichen planus and increased blood urea nitrogen level in its red-form: an observational study

BackgroundThis retrospective observational study aims to assess platelet count, mean platelet volume (MPV), blood biochemical tests for liver and kidney function in Chinese oral lichen planus (OLP) patients.MethodsEighty pathologically confirmed OLP patients and 51 healthy controls were enrolled. Data on full blood count and biochemical tests were obtained from the electronic medical record system of the hospital.ResultsMPV was elevated in OLP patients compared to controls (10.68 ± 0.97 fL versus 10.33 ± 0.89 fL, P = 0.042) while platelet count showed no difference between them. Red-form OLP group had increased blood urea nitrogen (BUN, 5.24 ± 1.15 mmol/L versus 4.69 ± 0.98 mmol/L, P = 0.036) than white-form OLP group. By contrast, there were no differences between those two groups in the other variables including MPV, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and creatinine. In terms of C-reactive protein (CRP), 92.5% of the OLP patients had a value of less than 3.48 mg/L. Besides, 75% of the OLP patients were overweight with body mass index (BMI) more than 25 kg/m2.ConclusionsThese findings indicate MPV might play roles in inflammation in OLP. The red-form OLP might be associated with damage or reduction of kidney function.

The association of blood urea nitrogen levels upon emergency admission with mortality in acute exacerbation of chronic obstructive pulmonary disease.

Background and purposeHigh blood urea nitrogen (BUN) is associated with an elevated risk of mortality in various diseases, such as heart failure and pneumonia. Heart failure and pneumonia are common comorbidities of acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, data on the relationship of BUN levels with mortality in patients with AECOPD are sparse. The purpose of this study was to evaluate the correlation between BUN level and in-hospital mortality in a cohort of patients with AECOPD who presented at the emergency department (ED).MethodsA total of 842 patients with AECOPD were enrolled in the retrospective observational study from January 2018 to September 2020. The outcome was all-cause in-hospital mortality. Receiver operating characteristic (ROC) curve analysis and logistic regression models were performed to evaluate the association of BUN levels with in-hospital mortality in patients with AECOPD. Propensity score matching was used to assemble a cohort of patients with similar baseline characteristics, and logistic regression models were also performed in the propensity score matching cohort.ResultsDuring hospitalization, 26 patients (3.09%) died from all causes, 142 patients (16.86%) needed invasive ventilation, and 190 patients (22.57%) were admitted to the ICU. The mean level of blood urea nitrogen was 7.5 ± 4.5 mmol/L. Patients in the hospital non-survivor group had higher BUN levels (13.48 ± 9.62 mmol/L vs. 7.35 ± 4.14 mmol/L, p < 0.001) than those in the survivor group. The area under the curve (AUC) was 0.76 (95% CI 0.73–0.79, p < 0.001), and the optimal BUN level cutoff was 7.63 mmol/L for hospital mortality. As a continuous variable, BUN level was associated with hospital mortality after adjusting respiratory rate, level of consciousness, pH, PCO2, lactic acid, albumin, glucose, CRP, hemoglobin, platelet distribution width, D-dimer, and pro-B-type natriuretic peptide (OR 1.10, 95% CI 1.03–1.17, p=0.005). The OR of hospital mortality was significantly higher in the BUN level ≥7.63 mmol/L group than in the BUN level <7.63 mmol/L group in adjusted model (OR 3.29, 95% CI 1.05–10.29, p=0.041). Similar results were found after multiple imputation and in the propensity score matching cohort.ConclusionsIncreased BUN level at ED admission is associated with hospital mortality in patients with AECOPD who present at the ED. The level of 7.63 mmol/L can be used as a cutoff value for critical stratification.

Prognostic significance of Blood Urea Nitrogen in comparison to Creatinine levels in mortality assessment of patients at admission with Acute Coronary Syndrome in Shivamogga district, Karnataka

Introduction and Objectives: Several studies have hypothesized the relation of Blood Urea Nitrogen (BUN) and serum Creatinine level with the severity of coronary artery disease. The basis of this study is to show the prognostic significance of BUN and serum Creatinine levels at admission for assessing the risk of mortality in patients with acute coronary syndromes (ACS). This study also undertakes the comparative prognostic significance of BUN over serum creatinine as an indicator of risk of mortality in patients with ACS. Materials and Methods & Results:This was a prospective study of all patients admitted with suspected (n=1019) and retrospectively confirmed (n=65) Myocardial Infarction (MI) or Unstable Angina. The Receiver-operating characteristic curve analysis established that the area under the curve for BUN was higher than that of Creatinine 0.71 (95% CL 0.65 to 0.78) and 0.63 (95% CL 0.59 to 0.66), respectively (p=0.005). The threshold level was 8.6mmol/L for BUN and 110µmol/L for Creatinine. Sensitivity was 61% and 56% for threshold levels of BUN and Creatinine, and specificity was 84% and 78%, respectively. It is seen only an increase of BUN and a combination of increased BUN and Creatinine levels, as risk factors of mortality with ACS.Isolated increase in creatinine levels was not found to be significant. Separate inclusion of BUN and Creatinine as continuous variables in the regression model showed that both were associated with the risk of mortality. Odds Ratio (OR) 1.18 (95% CL 1.12 to 1.25) and 1.08 (95% CL 1.011 to 1.019) per unit increase (R2 =12.5 and 8.1% respectively). When both were simultaneously included, only the increased BUN level was persistent with the prognosis of ACS: OR after multivariate adjustment 1.14 (95% CL 1.04 to 1.18). Conclusion: An increased level of BUN is a more significant prognostic marker of mortality assessment at admission in ACS than that of serum Creatinine. Keywords: Blood Urea Nitrogen, Serum Creatinine, Acute Co

Blood urea nitrogen to albumin ratio is a predictor of in-hospital mortality in older emergency department patients

In this study, we aimed to evaluate the first measured blood urea nitrogen (BUN)/albumin ratio in the emergency department (ED) as a predictor of in-hospital mortality in older ED patients. This retrospective observational study was conducted at a university hospital ED. Consecutive patients aged 65 and over who visited the ED in a three-month period were included in the study. The BUN, albumin, creatinine, and estimated glomerular filtration rate (eGFR) of patients were recorded. The primary end point of the study was in-hospital mortality. A total of 1253 patients were included in the statistical analyses of the study. Non-survivors had increased BUN levels (32.9 (23.3-55.4) vs. 20.2 (15.4-28.3) mg/dL, p<0.001), decreased albumin levels (3.27 (2.74-3.75) vs. 3.96 (3.52-4.25) g/dL, p<0.001), and increased BUN/albumin ratios (10.19 (6.56-18.94) vs. 5.21 (3.88-7.72) mg/g, p<0.001) compared to survivors. An increased BUN/albumin ratio was a powerful predictor of in-hospital mortality with an area under the curve of 0.793 (95% CI: 0.753-0.833). Malignancy (OR: 2.39; 95% CI: 1.59-3.74, p<0.001), albumin level<3.5g/dL (OR: 2.75; 95% CI: 1.74-4.36, p<0.001), and BUN/albumin ratio>6.25 (OR: 2.82; 95% CI: 1.22-6.50, p<0.015) were found to be independent predictors of in-hospital mortality in older ED patients. According to our findings, older patients with a BUN level>23mg/dL, an albumin level<3.5g/dL, and a BUN/albumin ratio>6.25mg/g in the ED have a higher risk of in-hospital mortality. Additionally, the BUN/albumin ratio is a more powerful independent predictor of in-hospital mortality than the BUN level, albumin level, creatinine level, and eGFR in older ED patients.

Effects of post-renal anemia treatment with the HIF-PHD inhibitor molidustat on adenine-induced renal anemia and kidney disease in mice

The kidneys are the major organs for erythropoietin (EPO) production in adults, and thus, kidney damage results in reduced EPO levels and anemia. Inhibitors of Hypoxia-inducible factor-prolyl hydroxylase domain-containing protein (HIF-PHD) are awaited as new therapeutic options for renal anemia. It can be predicted that most patients who receive HIF-PHD inhibitors have renal dysfunction as a cause of anemia. Therefore, in the present study, we investigated the effects of the HIF-PHD inhibitor molidustat on anemia and renal dysfunction when initiated after the onset of renal anemia. Male C57BL/6J mice received adenine orally to induce nephropathy. After the onset of nephropathy, the mice were treated with either vehicle or molidustat. After 4 weeks of administration, vehicle-treated mice displayed significant anemia, and molidustat ameliorated this anemia. Vehicle-treated mice exhibited reduced creatinine clearance and body weight, increased blood urea nitrogen levels, histopathological changes, immune cell infiltration, and dehydration. Molidustat reversed immune cell infiltration, dehydration, and renal fibrosis without improving renal functional parameters. In conclusion, molidustat treatment initiated after the onset of nephropathy and renal anemia reversed anemia in mice. Molidustat improved some parameters of renal abnormality, but it did not restore renal function.

The Preventive Effect of Rome Beauty Variety Apple Skin Extract on Blood Urea Nitrogen (BUN) levels of Rat (Rattus norvegicus) Induced by Lead (Pb)

Lead (Pb) is a heavy metal that can cause poisoning in living things. Pb contamination that enters the body through the digestive system will bind to erythrocytes and trigger an increase in ROS the body resulting in a decrease in organ function such as the kidneys followed by an increase in levels of BUN. Apple is an example of a fruit that rich in antioxidant. Apple skin contains flavonoids which act as antioxidants and as chelating agent for metal ion. The parameters observed in this study were BUN levels. This study consist of 5 groups with each group consisting of 4 white rats, namely negative control, positive control with 10 mg Pb / head / day of Pb administration for 14 days, and preventive therapy group with Rome Beauty apple skin extract 28 mg/200g, 56 mg/200g, and 112 mg/200g for 21 days and giving lead at a dose of 10 mg/rat/day for 14 days. BUN levels were analyzed using one way ANOVA method which was followed by Turkey. The results showed that the preventive group of apple skin extract of Rome Beauty variety with a dose of 112 mg/200g was able to prevent an increase in BUN levels.

Abstract P144: Integrin β1 in Tubular Epithelium Protects From Acute Injury Induced Fibrosis

Acute kidney injury (AKI) results in the sudden loss of renal function primarily due to renal tubular injury. Repeated injury or maladaptive recovery lead to chronic kidney diseases. All forms of chronic kidney disease are characterized by excessive extracellular matrix (ECM) accumulation. The proximal tubule cells that are injured but not detached from the basement membrane are critical for the restoration of renal functions after the injury incidence. Renal tubular epithelial cell adhesion, migration, and proliferation are required for the kidney to recover from sub-lethal injury. These processes require the ability of cells to interact with the ECM. Integrin, which exists as a complex of α and β subunits, are the principal receptors for ECM proteins. Integrin β1 is the major integrin subunit present in kidney and critically regulates renal epithelial cell functions. We investigated the importance of Integrin β1 in kidney proximal tubule epithelial cells. Integrin β1 was deleted from these cells using the γ-gt cre. These KO mice had no morphological abnormalities but have a higher urine osmolality (2369±881 mΩ) compared to WT (2098±945 mΩ). By using a nephrotoxic injury model, we investigated the role of integrin β1 in AKI. Samples were collected on 3, 5, 7 and 14 days after injury to assess the nature of injury and recovery. Integrin β1 KO mice were more susceptible to injury as evident by protein casts and tubule dilation of tubules. The blood urea nitrogen (BUN) from the plasma showed increased BUN level in KO animals compared to WT controls (26.78±8.23 and 34.05±7.11). After the injury the level was increased to 52.26±18.37 in WT and 60.34±11.58 KO suggesting both were injured to a similar extent. After 14 days the WT recovered better than KO animals (BUN 37.33±10.12 and 48.73±15.92). After 14 KO mice had more collagen deposition compared to WT animals. This data suggests the importance of integrin β1 in the tubular epithelium in promoting the recovery from injury and preventing its progression to chronic kidney disease.

Unique Clinical Characteristics and Prognosis of Allopurinol-Induced Severe Cutaneous Adverse Reactions

Allopurinol is the most common cause of severe cutaneous adverse reactions (SCARs) in Korea due to the relatively high prevalence of the HLA-B*58:01 genotype (8%-13%). We aimed to reveal the clinical characteristics and risk factors for death in allopurinol-induced SCARs in Korea. We retrospectively reviewed the medical records of 106 subjects with allopurinol-induced SCARs and 639 subjects with other drug-induced SCARs who were enrolled in the Korean SCARs Registry (collected from 34 nationwide medical institutions) from January 2010 to December2015. Subjects with allopurinol-induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) were older and had more comorbidities, longer latent periods, longer disease durations, more deranged laboratory findings, and increased disease severity resulting in a higher mortality rate (17.6% vs 7.6%; P= .020) compared with the subjects with other drug-induced SCARs. There was no significant difference in age or mortality in drug reaction with eosinophilia and systemic symptoms (DRESS). Subjects with allopurinol-induced SJS/TEN were older and had shorter latent periods and a higher mortality rate (17.6% vs 3.7%; P= .044) than those with allopurinol-induced DRESS. In allopurinol-induced SJS/TEN, significant risk factors for death included chronic renal insufficiency, intensive care unit (ICU) admission, increased blood urea nitrogen levels on admission day, serum peak eosinophil counts, baseline and peak creatinine levels, baseline and peak alanine aminotransferase levels, and decreased lowest platelet counts. In allopurinol-induced DRESS, significant risk factors for death included ICU admission and increased glucose levels on admission day. Allopurinol-induced SCARs have unique characteristics and poor prognoses with important predictive factors of death.

Histological and blood chemistry examination of the rodent kidney after exposure to flash-replenishment ultrasound contrast imaging

The purpose of this work is to investigate whether imaging sequences of flash-replenishment contrast enhanced ultrasound (CEUS) of the kidney result in chronic or acute bioeffects. Kidneys of female Fischer 344 rats were imaged using the flash-replenishment technique. Animals were separated into four groups (N = 31). Imaging was conducted with a 4C1 probe, driven by an Acuson Sequoia system with Definity microbubbles as the ultrasound contrast agent. During the flash phase of the imaging sequence, one kidney in each animal was exposed to either a mechanical index (MI) of 1.0 or 1.9. For each MI, half of the animals were sacrificed shortly after imaging (4 h) or after 2 weeks. A blinded veterinary nephropathologist reviewed the histopathology of both the imaged and control (non-imaged) kidney. Blood urea nitrogen (BUN) was measured for each animal prior to imaging and at the time of necropsy. Histopathology assessments in both the 1.0 and 1.9 MI groups revealed no signs of hemorrhage at either the 4-h or 2-week time point. BUN showed minor but statistically significant elevations in both the 1.0 and 1.9 MI groups, but no significant difference was present at the 2-week time point in the 1.0 MI group. All BUN levels (at both time points) remained in the normal range. In conclusion, CEUS with flash-replenishment imaging sequences did not result in kidney bioeffects observable with histology at early or late time points. Increases in BUN levels were observed after imaging, but were minimized when using a moderate MI (1.0).

Hypersensitivity to Cisplatin and Gentamycin Induced Nephrotoxicity in Mice with Decreased Expression of NADPH‐Cytochrome P450 Reductase

Cytochrome P450 reductase (CPR or POR) is an obligatory redox partner for all microsomal P450 enzymes. A large, global decrease in POR expression, in a Cpr‐low mouse model, was previously found to lead to altered sex steroid hormone homeostasis, female infertility, and decreased capacity for xenobiotic metabolism. The aim of this study was to further characterize the Cpr‐low mouse model, in order to identify additional phenotypes that may reveal vulnerability in people with low POR expression. Here, we report differences between wild‐type and Cpr‐low mice in their sensitivities to drug‐induced toxicity in the renal proximal tubules. We studied two drugs, the anticancer drug cisplatin and the antibiotic drug gentamycin, which are known as renal toxicants, but are not P450 substrates. Toxicity was assessed by blood urea nitrogen (BUN) levels and histopathology of the kidney. At drug doses that do not cause renal toxicity in wild‐type mice, cisplatin caused significant increases in BUN levels over vehicle control group in both male and female Cpr‐low mice, whereas gentamycin caused significant increases in BUN levels over vehicle control group in male but not female Cpr‐low mice. Corresponding histopathological changes, including appearance of extensive proximal tubule vacuolization, were found in the kidneys of drug‐treated Cpr‐low mice. These findings suggest that POR expression level could be a risk factor for drug‐induced nephrotoxicity in patients.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.