Inulin Reduces Kidney Damage in Type 2 Diabetic Mice by Decreasing Inflammation and Serum Metabolomics.

This study is aimed at assessing the impact of soluble dietary fiber inulin on the treatment of diabetes-related chronic inflammation and kidney injury in mice with type 2 diabetes (T2DM). The T2DM model was created by feeding the Institute of Cancer Research (ICR) mice a high-fat diet and intraperitoneally injecting them with streptozotocin (50 mg/kg for 5 consecutive days). The thirty-six ICR mice were divided into three dietary groups: the normal control (NC) group, the T2DM (DM) group, and the DM + inulin diet (INU) group. The INU group mice were given inulin at the dose of 500 mg/kg gavage daily until the end of the 12th week. After 12 weeks, the administration of inulin resulted in decreased serum levels of fasting blood glucose (FBG), low-density lipoprotein cholesterol (LDL-C), blood urea nitrogen (BUN), and creatinine (CRE). The administration of inulin not only ameliorated renal injury but also resulted in a reduction in the mRNA expressions of inflammatory factors in the spleen and serum oxidative stress levels, when compared to the DM group. Additionally, inulin treatment in mice with a T2DM model led to a significant increase in the concentrations of three primary short-chain fatty acids (SCFAs) (acetic acid, propionic acid, and butyric acid), while the concentration of advanced glycation end products (AGEs), a prominent inflammatory factor in diabetes, exhibited a significant decrease. The results of untargeted metabolomics indicate that inulin has the potential to alleviate inflammatory response and kidney damage in diabetic mice. This beneficial effect is attributed to its impact on various metabolic pathways, including glycerophospholipid metabolism, taurine and hypotaurine metabolism, arginine biosynthesis, and tryptophan metabolism. Consequently, oral inulin emerges as a promising treatment option for diabetes and kidney injury.

Hematological and renal toxicity in mice after three cycles of high activity [177Lu]Lu-PSMA-617 with or without human α1-microglobulin.

Radioligand therapy with [177Lu]Lu-PSMA-617 can be used to prolong life and reduce tumor burden in terminally ill castration resistant prostate cancer patients. Still, accumulation in healthy tissue limits the activity that can be administered. Therefore, fractionated therapy is used to lower toxicity. However, there might be a need to reduce toxicity even further with e.g. radioprotectors. The aim of this study was to (i). establish a preclinical mouse model with fractionated high activity therapy of three consecutive doses of 200 MBq [177Lu]Lu-PSMA-617 in which we aimed to (ii). achieve measurable hematotoxicity and nephrotoxicity and to (iii). analyze the potential protective effect of co-injecting recombinant α1-microglobulin (rA1M), a human antioxidant previously shown to have radioprotective effects. In both groups, three cycles resulted in increased albuminuria for each cycle, with large individual variation. Another marker of kidney injury, serum blood urea nitrogen (BUN), was only significantly increased compared to control animals after the third cycle. The number of white and red blood cells decreased significantly and did not reach the levels of control animals during the experiment. rA1M did reduce absorbed dose to kidney but did not show significant protection here, but future studies are warranted due to the recent clinical studies showing a significant renoprotective effect in patients.

Aortic Stenosis and Renal Function: A Bidirectional Mendelian Randomization Analysis.

BACKGROUND: Large observational studies have demonstrated a clear inverse association between renal function and risk of aortic stenosis (AS). Whether this represents a causal, reverse causal or correlative relationship remains unclear. We investigated this using a bidirectional 2-sample Mendelian randomization approach. METHODS AND RESULTS: We collected summary statistics for the primary analysis of chronic kidney disease (CKD) and AS from genome-wide association study meta-analyses including 480 698 and 653 867 participants, respectively. We collected further genome-wide association study summary statistics from up to 1 004 040 participants for sensitivity analyses involving estimated glomerular filtration rate (eGFR) derived from creatinine, eGFR derived from cystatin C, and serum urea nitrogen. Inverse-variance weighted was the primary analysis method, with weighted-median, weighted-mode, Mendelian randomization-Egger, and Mendelian randomization-Pleiotropy Residual Sum and Outlier as sensitivity analyses. We did not find evidence of a causal relationship between genetically predicted CKD liability as the exposure and AS as the outcome (odds ratio [OR], 0.94 per unit increase in log odds of genetic liability to CKD [95% CI, 0.85-1.04], P=0.26) nor robust evidence of AS liability as the exposure and CKD as the outcome (OR, 1.04 per unit increase in log odds of genetic liability to AS [95% CI, 0.97-1.12], P=0.30). The sensitivity analyses were neutral overall, as were the analyses using eGFR derived from creatinine, eGFR derived from cystatin C, and serum urea nitrogen. All positive controls demonstrated strong significant associations. CONCLUSIONS: The present study did not find evidence of a substantial effect of genetically predicted renal impairment on risk of AS. This has important implications for research efforts that attempt to identify prevention and treatment targets for both CKD and AS.

Shenkang injection for the treatment of acute kidney injury: a systematic review and meta-analysis.

OBJECTIVE: Shenkang injection (SKI) has been widely used in China for many years for the treatment of kidney disease. The objective of this systematic review was to assess the efficacy of Shenkang injection for the treatment of acute kidney injury (AKI). METHODS: A search was conducted across seven databases, encompassing data from the inception of each database through October 8th, 2023. Randomized controlled trials comparing SKI-treated AKI patients with control subjects were extracted. The main outcome measure was serum creatinine (SCr) levels. Secondary outcomes included blood urea nitrogen (BUN), serum cystatin C (CysC), 24-h urine protein (24 h-Upro) levels, APACHE II score and adverse reactions. RESULTS: This meta-analysis included eleven studies, and the analysis indicated that, compared with the control group, SKI significantly decreased SCr [WMD = -23.31, 95% CI (-28.06, -18.57); p < 0.001]; BUN [WMD = -2.07, 95% CI (-2.56, -1.57); p < 0.001]; CysC [WMD = -0.55, 95% CI (-0.78, -0.32), p < 0.001]; 24-h urine protein [WMD = -0.43, 95% CI (-0.53, -0.34), p < 0.001]; and the APACHE II score [WMD = -3.07, 95% CI (-3.67, -2.48), p < 0.001]. There was no difference in adverse reactions between the SKI group and the control group [RR = 1.32, 95% CI (0.66, 2.63), p = 0.431]. CONCLUSION: The use of SKI in AKI patients may reduce SCr, BUN, CysC, 24-h Upro levels, and APACHE II scores in AKI patients. The incidence of adverse reactions did not differ from that in the control group. Additional rigorous clinical trials will be necessary in the future to thoroughly evaluate and establish the effectiveness of SKI in the treatment of AKI.

Attenuating Renal Interstitial Fibrosis by Shenqi Pill via Reducing Inflammation Response Regulated by NF-κB Pathway In Vitro and In Vivo.

INTRODUCTION: One of the most significant clinical features of chronic  kidney disease is renal interstitial fibrosis (RIF). This study aimed  to investigate the role and mechanism of Shenqi Pill (SQP) on RIF. METHODS: RIF model was established by conducting unilateral  ureteral obstruction (UUO) surgery on rat or stimulating human  kidney-2 (HK-2) cell with transforming growth factor ß1 (TGFß1).  After modeling, the rats in the SQP low dose group (SQP-L), SQP  middle dose group (SQP-M) and SQP high dose group (SQP-H)  were treated with SQP at 1.5, 3 or 6 g/kg/d, and the cells in the  TGFß1+SQP-L/M/H were treated with 2.5%, 5%, 10% SQP-containing  serum. In in vivo assays, serum creatinine (SCr) and blood urea  nitrogen (BUN) content were measured, kidney histopathology  was evaluated., and α-smooth muscle actin (α-SMA) expression  was detected by immunohistochemistry. Interleukin-1ß (IL-1ß),  interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) content,  inhibitor of kappa B alpha (IKBα) and P65 phosphorylation were  assessed. Meanwhile, cell viability, inflammatory cytokines content,  α-SMA expression, IKBα and P65 phosphorylation were detected  in vitro experiment.  Results. SQP exhibited reno-protective effect by decreasing SCr  and BUN content, improving renal interstitial damage, blunting  fibronectin (FN) and α-SMA expression in RIF rats. Similarly, after  the treatment with SQP-containing serum, viability and α-SMA  expression were remarkably decreased in TGFß1-stimulated HK-2  cell. Furthermore, SQP markedly down-regulated IL-1ß, IL-6, and  TNF-α content, IKBα and RelA (P65) phosphorylation both in vivo and in vitro.  Conclusion. SQP has a reno-protective effect against RIF in vivo and in vitro, and the effect is partly linked to nuclear factor-kappa  B (NF-κB) pathway related inflammatory response, which indicates  that SQP may be a candidate drug for RIF. DOI: 10.52547/ijkd.7546.

Hyaluronidase inhibitor sHA2.75 alleviates ischemia-reperfusion-induced acute kidney injury.

Hyaluronidases (HAases) are enzymes that degrade hyaluronic acid (HA) in the animal kingdom. The HAases-HA system is crucial for HA homeostasis and plays a significant role in biological processes and extracellular matrix (ECM)-related pathophysiological conditions. This study aims to explore the role of inhibiting the HAases-HA system in acute kidney injury (AKI). We selected the potent inhibitor "sHA2.75" to inhibit HAase activity through mixed inhibitory mechanisms. The ischemia-reperfusion mouse model was established using male BALB/c mice (7-9 weeks old), and animals were subjected to subcapsular injection with 50 mg/kg sHA2.75 twice a week to evaluate the effects of sHA2.75 on AKI on day 1, 5 and 14 after ischemia-reperfusion or sham procedure. Blood and tissue samples were collected for immunohistochemistry, biochemical, and quantitative analyses. sHA2.75 significantly reduced blood urea nitrogen (BUN) and serum creatinine levels in AKI mouse models. Expression of kidney injury-related genes such as Kidney injury molecule-1 (KIM-1), Neutrophil Gelatinase-Associated Lipocalin (NGAL), endothelial nitric oxide synthase (eNOS), type I collagen (Col1), type III collagen (Col3), alpha-smooth muscle actin (α-SMA) showed significant downregulation in mouse kidney tissues after sHA2.75 treatment. Moreover, sHA2.75 treatment led to decreased plasma levels of Interleukin-6 (IL-6) proteins and reduced mRNA levels in renal tissues of AKI mice. Inhibitor sHA2.75 administration in the AKI mouse model downregulated kidney injury-related biomarkers and immune-specific genes, thereby alleviating AKI in vivo. These findings suggest the potential use of HAase inhibitors for treating ischemic reperfusion-induced kidney injury.

Association between blood urea nitrogen levels and the risk of diabetes mellitus in Chinese adults: secondary analysis based on a multicenter, retrospective cohort study.

Background: As one of the recognized indicators of kidney function, blood urea nitrogen (BUN) is a key marker of metabolic diseases and other diseases. Currently, data on the relationship of BUN levels with the risk of diabetes mellitus (DM) in Chinese adults are sparse. This study aimed to investigate the correlation between BUN levels and DM risk in Chinese adults. Data and methods: This study is a secondary analysis of a multicenter, retrospective cohort study with data from the Chinese health screening program in the DATADRYAD database. From 2010 to 2016, health screening was conducted on 211833 Chinese adults over the age of 20 in 32 locations and 11 cities in China, and there was no DM at baseline. Cox proportional hazards regression analysis assessed an independent correlation between baseline BUN levels and the risk of developing DM. The Generalized Sum Model (GAM) and smoothed curve fitting methods were used to explore the nonlinear relationship. In addition, subgroup analyses were performed to assess the consistency of correlations between different subgroups and further validate the reliability of the results. Results: After adjusting for potential confounding factors (age, sex, etc.), BUN levels were positively correlated with the occurrence of DM (HR=1.11, 95% CI (1.00~1.23)). BUN level had a nonlinear relationship with DM risk, and its inflection point was 4.2mmol/L. When BUN was greater than 4.2mmol/L, BUN was positively correlated with DM, and the risk of DM increased by 7% for every 1 mmol/L increase in BUN (P<0.05). Subgroup analysis showed that a more significant correlation between BUN levels and DM was observed in terms of sex, BMI, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL), alaninetransaminase (ALT), aspartate transaminase (AST), creatinine (Cr) and smoking status (interaction P<0.05). Conclusion: High levels of BUN are associated with an increased risk of DM in Chinese adults, suggesting that active control of BUN levels may play an important role in reducing the risk of DM in Chinese adults.

Blood urea nitrogen to albumin ratio is associated with cerebral small vessel diseases.

Blood urea nitrogen (BUN) to albumin ratio (BAR) is a comprehensive parameter that reflects renal, inflammatory, nutritional, and endothelial functions. BAR has been shown to be associated with various cancers, pneumonia, sepsis, and pulmonary and cardiovascular diseases; however, few studies have been conducted on its association with cerebrovascular diseases. In this study, we evaluated the association between BAR and cerebral small vessel disease (cSVD) in health check-up participants. We assessed consecutive health check-up participants between January 2006 and December 2013. For the cSVD subtype, we quantitatively measured the volume of white matter hyperintensity (WMH) and qualitatively measured the presence of lacune and cerebral microbleeds (CMBs). The BAR was calculated by dividing BUN by albumin as follows: BAR = BUN (mg/dl)/albumin (g/dl). A total of 3012 participants were evaluated. In multivariable linear regression analysis, BAR showed a statistically significant association with WMH volume after adjusting for confounders [ß = 0.076, 95% confidence interval (CI): 0.027-0.125]. In multivariable logistic regression analyses, BAR was significantly associated with lacunes [adjusted odds ratio (aOR) = 1.20, 95% CI: 1.00-1.44] and CMBs (aOR = 1.28, 95% CI: 1.06-1.55). BAR was associated with all types of cSVD in the health check-up participants.

Blood-urea-nitrogen-to-serum-albumin ratio in predicting the value of patients with contrast-induced nephropathy for coronary heart disease.

BACKGROUND: The blood-urea-nitrogen (BUN)-to-serum-albumin (ALB) ratio (BAR) has been identified as a novel indicator of both inflammatory and nutritional status, exhibiting a correlation with adverse cardiovascular outcomes. This study aims to investigate the potential predictive value of BAR levels at admission for the development of CIN in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). METHODS: Retrospective data were collected from patients who were admitted and underwent CAG or PCI between January 2018 and December 2022 at the Cardiac Medical Center of Union Hospital of Fujian Medical University, and the patients were divided into CIN and non-CIN groups. The BAR was computed by dividing the BUN count by the ALB count. Using multiple variable logistic regression, risk variables associated with the development of CIN were found. RESULTS: A total of 156 patients developed CIN (7.78%). The development of CIN was predicted by a BAR ratio > 4.340 with a sensitivity of 84.0% and a specificity of 70.2%, according to receiver operating characteristic (ROC) analysis. BAR, female gender, diuretic use, and statin medication use were found to be independent predictors of CIN using multifactorial analysis. CONCLUSIONS: When patients are receiving CAG/PCI, BAR is a simple-to-use marker that can be used independently to predict the presence of CIN.

The Prognostic Value of Blood Urea Nitrogen to Albumin Ratio on Patients with Heart Failure.

This study aimed to investigate the relationship between blood urea nitrogen to albumin ratio (BAR) and the prognosis of heart failure (HF).A total of 2125 patients with HF were included in this single-center prospective cohort study between February 2012 and December 2017. Using a receiver operating characteristic curve, we determined the cutoff value of BAR as 0.24. All patients were divided into two groups according to the cutoff value of BAR.Among 2125 HF patients, the mean age was 56.7 ± 14.3. During a median follow-up time of 22 months, 516 end-point events occurred. Compared with patients in the low BAR group, those in the high BAR group were older; more likely to be male; had a higher percentage of hypertension, diabetes, smoking, and ß-blocker use; and higher levels of alanine aminotransferase, glycosylated hemoglobin, creatinine, log-transformed NTproBNP, and Blood urea nitrogen but lower levels of albumin, triglycerides, high-density lipoprotein, ApoA1, and hemoglobin. Prognosis analysis indicated that high BAR was associated with increased mortality risk of HF (Hazard Ratio = 1.497, 95% CI = 1.234-1.816; P < 0.001) in the multivariate Cox proportional hazard regression model. Subgroup analysis revealed that stratification by age, gender, history of hypertension, diabetes, smoking, ß-blocker use, and levels of hemoglobin, glycosylated hemoglobin, and creatinine have no obvious effect on the association between BAR ratio and the prognosis of HF. Furthermore, patients with high BAR represented a decreased left ventricular ejection fraction and increased left ventricular end-diastolic diameter.High BAR was an independent predictor for the mortality risk of HF.

An analysis of lactate/albumin, procalcitonin/albumin, and blood urea nitrogen/albumin ratios as a predictor of mortality in uroseptic patients.

OBJECTIVE: The aim of this study was to investigate the ratios of lactate/albumin, procalcitonin/albumin, and blood urea nitrogen/albumin to predict 14- and 28-day mortality in uroseptic patients. Urosepsis is a disease with high mortality, and early diagnosis and treatment are important. METHODS: Patients with urosepsis who were admitted to the intensive care unit between January 2021 and September 2022, had a follow-up of at least 28 days, and met the inclusion criteria were evaluated retrospectively. RESULTS: The mean age was 70.23 (15.66) years and 84 (53.85%) were males. The number of non-survivors were 75 (48%) in the 14-day mortality group and 97 (62.1%) in the 28-day mortality group. Based on the 14-day mortality data, the blood urea nitrogen/albumin ratio was higher in non-survivors vs. survivors (median, 15.88 vs. 9.62), and the lactate/albumin ratio was higher (median, 0.96 vs. 0.52, p<0.01, all). Based on the 28-day mortality data, the blood urea nitrogen/albumin ratio was higher in non-survivors vs. survivors (median, 14.78 vs. 8.46), and the lactate/albumin ratio was higher (median, 0.90 vs. 0.50, p<0.01, all). CONCLUSION: It is very difficult to determine the prognosis of patients admitted to the emergency department with the diagnosis of urosepsis. The lactate/albumin ratio and the blood urea nitrogen/albumin ratio can be used as early prognostic markers for both 14-day and 28-day mortality until more reliable markers are identified.

Renogrit attenuates Vancomycin-induced nephrotoxicity in human renal spheroids and in Sprague-Dawley rats by regulating kidney injury biomarkers and creatinine/urea clearance.

Vancomycin, is widely used against methicillin-resistant bacterial infections. However, Vancomycin accumulation causes nephrotoxicity which leads to an impairment in the filtration mechanisms of kidney. Traditional herbal medicines hold potential for treatment of drug-induced nephrotoxicity. Herein, we investigated protective properties of plant-based medicine Renogrit against Vancomycin-induced kidney injury. Phytometabolite analysis of Renogrit was performed by UHPLC. Spheroids formed from human proximal tubular cell (HK-2) were used for in vitro evaluation of Vancomycin-induced alterations in cell viability, P-gp functionality, NAG, KIM-1 levels, and mRNA expression of NGAL and MMP-7. The in vivo efficacy of Renogrit against Vancomycin-induced nephrotoxicity was further evaluated in Sprague-Dawley (SD) rats by measurement of BUN, serum creatinine, and their respective clearances. Moreover, eGFR, kidney-to-body weight ratio, GSH/GSSG ratio, KIM-1, NAG levels and mRNA expression of KIM-1 and osteopontin were also analyzed. Changes in histopathology of kidney and hematological parameters were also observed. Renogrit treatment led to an increase in cell viability, normalization of P-gp functionality, decrease in levels of NAG, KIM-1, and reduction in mRNA expression of NGAL and MMP-7. In Vancomycin-challenged SD rats, Renogrit treatment normalized altered kidney functions, histological, and hematological parameters. Our findings revealed that Renogrit holds a clinico-therapeutic potential for alleviating Vancomycin-associated nephrotoxicity.

BUN level is associated with cancer prevalence.

Blood urea nitrogen (BUN) was an important biomarker for the development and prognosis of many diseases. Numerous studies had demonstrated that BUN had a strong relationship with long-term mortality, survival and the prevalence of some diseases. The diagnosis and treatment, prognosis and long-term survival rate of cancer were the focus of clinical research at present. However, the relationship between BUN level and cancer prevalence was not clear. To investigate the relationship between BUN level and cancer prevalence, we performed a statistical analysis of population data from the National Health and Nutrition Examination Survey (NHANES) database. The results of the study showed that BUN level were positively correlated with cancer prevalence, and the correlation was more pronounced in breast cancer.

Association between early blood urea nitrogen-to-albumin ratio and one-year post-hospital mortality in critically ill surgical patients: a propensity score-matched study.

BACKGROUND: Blood urea nitrogen to albumin ratio (BAR) is increasingly recognized as an early predictor for short-term outcomes in critically ill patients, but the association of BAR with long-term outcomes in critically ill surgical patients remains underexplored. METHODS: We enrolled consecutive patients who were admitted to surgical intensive care units (ICUs) at Taichung Veterans General Hospital between 2015 and 2020, and the dates of death were retrieved from Taiwan's National Health Insurance Research Database. In addition to Cox regression, we also used propensity score matching to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for one-year post-hospital mortality of the variables. RESULTS: A total of 8,073 eligible subjects were included for analyses. We found that age, male gender, high Charlson Comorbidity Index, high Acute Physiology and Chronic Health Evaluation II score, positive microbial culture, and leukocytosis were predictors for mortality, whereas high body mass index, scheduled surgery, and high platelet counts were protective factors against long-term mortality. The high BAR was independently associated with increased post-hospital mortality after adjustment for the aforementioned covariates (adjHR 1.258, 95% CI, 1.127-1.405). Notably, the association tended to be stronger in females and patients with fewer comorbidities and lower disease severity of critical illness. The propensity score matching, dividing subjects by BAR higher or lower than 6, showed a consistent association between week-one BAR and post-hospital mortality (adjHR 1.503, 95% CI 1.247-1.811). CONCLUSIONS: BAR is a newly identified predictor of short-term outcome, and we identified long-term outcome-relevant factors, including BAR, and the identified factors may be useful for risk stratification of long-term outcomes in patients discharged from surgical ICUs.

A randomized controlled comparative study of different fluid exchange modes in urgent-start peritoneal dialysis in patients with end-stage renal disease: automated peritoneal dialysis combined with manual fluid exchange vs. manual fluid exchange alone.

During urgent-start peritoneal dialysis (USPD) in end-stage renal disease (ESRD) patients, both adequate dialysis and skill training for fluid exchange are essential. However, automated peritoneal dialysis (APD) alone or manual fluid exchange peritoneal dialysis (MPD) alone could meet the above demands. Therefore, our study combined APD with MPD (A-MPD), and compared A-MPD with MPD, aiming to find the most appropriate treatment mode. This was a single-center, prospective, randomized controlled study. All eligible patients were randomized into the MPD and A-MPD groups. All patients underwent a five-day USPD treatment 48 h after catheter implantation, and they were followed up for six months after discharge. Overall, 74 patients were enrolled in this study. Among these, 14 and 60 patients quit due to complications during USPD and completed the study (A-MPD = 31, MPD = 29), respectively. Compared with MPD, the A-MPD treatment mode had a better effect on removing serum creatinine, blood urea nitrogen, and potassium and improving serum carbon dioxide combining power levels; it had less time expenditure on the fluid exchange by nurses (p < 0.05). In addition, patients in the A-MPD group had higher scores on the skill tests than those in the MPD group (p = 0.002). However, no significant differences in short-term peritoneal dialysis (PD) complications, PD technical survival rate, or mortality were found between the two groups. Therefore, the A-MPD mode could be recommended as an adoptable and suitable PD modality for USPD in the future.

Reduced glutathione ameliorates acute kidney injury by inhibiting ferroptosis.

Reduced glutathione (RGSH) can participate in the redox process in the body and inhibit damage to important organs caused by free radicals. Due to its broad biological effects, in addition to its clinical applications in treatment of liver diseases, RGSH is also used in the treatment of numerous other diseases, such as malignant tumors and nerve, urological and digestion diseases. However, there are few reports of RGSH being used in treatment of acute kidney injury (AKI), and the mechanism of its action in AKI is not clear. To assess the possible mechanism of RGSH inhibition in AKI, a mouse AKI model and HK­2 cell ferroptosis model were built to perform in vitro and in vivo experiments. The levels of blood urea nitrogen (BUN) and malondialdehyde (MDA) before and after the RGSH treatment were assessed, and the pathological changes of the kidneys were assessed using hematoxylin and eosin staining. Immunohistochemical (IHC) methods were used to evaluate the expressions of acyl­CoA synthetase long­chain family member 4 (ACSL4) and glutathione peroxidase (GPX4) in the kidney tissues, reverse transcription­quantitative PCR and western blotting were used to assess the levels of ferroptosis marker factors in the kidney tissues and HK­2 cells, and flow cytometry was used to assess cell death. The results indicated that, RGSH intervention reduced the BUN and serum MDA levels, and ameliorated glomerular damage and the level of renal structure damage in the mouse model. IHC results demonstrated that RGSH intervention could significantly reduce the ACSL4 mRNA expression level and inhibit iron accumulation, and significantly upregulate the GPX4 mRNA expression level. Moreover, RGSH could inhibit ferroptosis induced by ferroptosis inducers erastin and RSL3 in HK­2 cells. Cell assay results demonstrated that RGSH could improve the lipid oxide level and cell viability, and inhibit cell death, so as to ameliorate the effects of AKI. These results suggested that RGSH could ameliorate AKI by inhibiting ferroptosis, which indicates RGSH as a promising therapeutic strategy for the treatment of AKI.

Association of Bun/Cr ratio-based dehydration status with infarct volumes and stroke severity in acute ischemic stroke.

BACKGROUND: Only a few clinical research had previously investigated the dehydration status to predict the evolution of the ischemic core. The aim of this study is to clarify the association between blood urea nitrogen (BUN)/creatinine (Cr)ratio-based dehydration and infarct volume measured using DWI (Diffusion-weighted imaging) at admission in patients with AIS (Acute Ischemic Stroke). METHODS: We retrospectively recruited a total of 203 consecutive patients who were hospitalized through emergency or outpatient services within 72 h of acute ischemic stroke onset between October 2015 and September 2019. Stroke severity was measured by assessing the National Institutes of Health Stroke Scale (NIHSS) on admission. Infarct volume was measured using DWI with MATLAB software. RESULTS: In this study, 203 patients who met the study criteria were enrolled. Patients in the dehydration group (Bun/Cr ratio>15) had a higher median NIHSS score (6(IQR:4-10) VS. 5(3-7); P = 0.0015)and larger DWI infarct volume (1.55 ml (IQR:0.51-6.79) VS. (0.37 ml (0.05-1.22); P < 0.001) on admission compared with patients in normal group. Further, a statistically significant correlation was found between DWI infarct volumes and NIHSS score with nonparametric Spearman rank correlation (r = 0.77; P < 0.001). The median NIHSS scores for the DWI infarct volumes quartiles were 3 ml (IQR, 2-4), 5 ml (4-7), 6 ml (5-8), and12 ml (8-17) from lowest to highest. However, the second quartile group did not show any significant correlation with the third quartile group (P = 0.4268). Multivariable linear and logistic regression analyses were used to test dehydration (Bun/Cr ratio>15), representing a predictor of infarct volume and stroke severity. CONCLUSION: Bun/Cr ratio-based dehydration is associated with larger volumes of ischemic tissue measured using DWI and worse neurological deficit assessed by the NIHSS score in acute ischemic stroke.

A low BUN/creatinine ratio predicts histologically confirmed acute interstitial nephritis.

INTRODUCTION: In hospitalized patients with acute renal injury (AKI), acute tubulointerstitial nephritis (AIN) constitutes one of the leading etiologies. The objective of this study was to identify clinical and biochemical variables in patients with AKI associated with kidney biopsy-confirmed AIN. METHODS: For our prospective study, we recruited hospitalized patients aged 18 years and older who were diagnosed with AKI based on biochemical criteria. Prior to enrollment, each patient was assessed with a complete metabolic panel and a kidney biopsy. RESULTS: The study consisted of 42 patients (with a mean age of 45 years) and equal numbers of male and female patients. Diabetes and hypertension were the main comorbidities. Nineteen patients had histological findings consistent with AIN. There was a correlation between histology and the BUN/creatinine ratio (BCR) (r = -0.57, p = 0.001). The optimal Youden point for classifying AIN via a receiver operating characteristic (ROC) curve analysis was a BCR ≤ 12 (AUC = 0.73, p = 0.024). Additionally, in diagnosing AIN, BCR had a sensitivity of 76%, a specificity of 81%, a positive predictive value of 81%, a negative predictive value of 76%, and OR of 14 (95% CI = 2.6 to 75.7, p = 0.021). In the multivariable analysis, BCR was the sole variable associated with AIN. CONCLUSION: A BCR ≤ 12 identifies AIN in patients with AKI. This study is the first to prospectively assess the relationship between renal biopsy results and BCR.

Evaluation of the effect of bun/albumin ratio on in-hospital mortality in hypertensive COVID-19 patients.

OBJECTIVE: The impact of COVID-19 infection still continues all over the world and is an important cause of mortality. The mortality rate due to infection varies between 1-5%. The mortality rate is higher in those with cardiovascular risk factors, especially in cases with hypertension. Some studies have shown that blood urea nitrogen (BUN) and albumin levels are associated with worse prognosis in patients with COVID-19. In our study, we aimed to investigate whether the BUN/albumin (BAR) ratio has an effect on in-hospital mortality in hypertensive COVID-19 patients. PATIENTS AND METHODS: A total of 800 hypertensive COVID-19 patients, (618 of whom were alive and 182 died) were included in our study. Patients with a history of heart failure, malignancy, acute coronary syndrome, and myocarditis were excluded. RESULTS: The median age of the study population was 69 (60-77 IQR) years, and 305 (38%) of these patients were men. There was no statistically significant difference between the patients who died during follow-up and cases that remained alive in terms of comorbidities except chronic obstructive pulmonary disease (COPD) which was significantly lower in surviving group (p=0.014). Multivariable logistic regression analysis revealed that age [OR: 1.04, CI (1.01-1.06); p=0.002], male gender [OR: 1.85, CI (1.13-3.02); p=0.010], lymphocyte count [OR: 0.63, CI (0.40-0.98); p=0.038], SaO2 [OR: 0.82, CI (0.79-0.85); p<0.001] and BAR level [OR: 1.09, CI (1.04-1.16); p=0.001] were independent predictors of in-hospital mortality. ROC analysis yielded that BAR is a better predictor of in-hospital mortality compared to albumin and BUN alone. CONCLUSIONS: BUN, albumin, and BAR levels were found to be reliable predictors of in-hospital mortality in COVID-19 patients, and BAR was also found to be a more reliable predictor than BUN and albumin levels. Hypertension is one of the major risk factors for morbidity and mortality in COVID-19 and, BAR presents additional prognostic data in hypertensive COVID-19 patients that may direct physicians for treatment intensification.

Blood urea nitrogen to creatinine ratio is associated with physical frailty in older-aged Chinese: a cross-sectional study.

BACKGROUND: The relationship between the ratio of blood urea nitrogen to creatinine (BUN/Cr) and physical frailty in elderly patients remains unclear. The study aims to investigate the association between the BUN/Cr ratio and physical frailty in the elderly Chinese population. METHODS: In this cross-sectional analysis, the clinical data of 5213 participants from 2015 were selected from the China Health and Retirement Longitudinal Study (CHARLS). The demographic variables (including age and gender) and health behavior (including smoking and drinking history), anthropometric (including systolic and diastolic blood pressure, waist circumference (WC), etc.), physical performances (i.e., grip strength, repeated chair stands, etc.), and biochemical indicators (i.e., blood urea nitrogen (BUN), creatinine(Cr), total cholesterol (TC), triglycerides (TG), etc.) were measured. The association between the BUN/Cr ratio and physical frailty was analyzed. RESULTS: After adjusting for potential confounding factors, smooth curve fitting showed a linear relationship between the BUN/Cr ratio and grip strength, a non-linear relationship between the BUN/Cr ratio, and repeated chair-rising time. The fully adjusted linear regression results showed a negative association between the BUN/Cr ratio and grip strength. In the multivariate, piecewise linear regression, when the BUN/Cr ratio was greater than 18.60, the repeated chair-rising time increased with the increase in BUN/Cr ratio (ß = 0.046, 95%CI 0.025, 0.066; p < 0.001). However, we did not observe a significant correlation when the BUN/Cr ratio was less than 18.60 (ß = -0.007, 95%CI -0.046, 0.032; p = 0.717). CONCLUSION: This study demonstrated that the BUN/Cr ratio might be associated with physical frailty in older-aged Chinese, and this association requires further investigation.