Urea Nitrogen Research Articles

Risk Factor Analysis Including Inflammatory Markers for ICU Admission and Survival After Pneumonectomy

Background and Objectives: To assess the impact of preoperative inflammatory parameters on the necessity for intensive care unit (ICU) admission and survival after pneumonectomy. Materials and Methods: We enrolled 207 adult patients who underwent pneumonectomy between December 2016 and January 2022. We collected data from patients’ electronic medical records. Results: The preoperative albumin level was statistically lower, need for blood transfusion was higher, and length of hospital stay was longer in ICU-admitted patients (p = 0.017, p = 0.020, and p = 0.026, respectively). In multivariate analysis, intra-pericardial pneumonectomy and postoperative complications were predictive factors for ICU admission (OR = 3.46; 95%CI: 1.45–8.23; p = 0.005 and OR = 5.10; 95%CI: 2.21–11.79; p < 0.001, respectively). Sleeve or pericardial pneumonectomy (p = 0.010), intraoperative vascular injury (p = 0.003), the need for mechanical ventilation (p < 0.001), acute renal failure (p = 0.018), sepsis (p = 0.008), respiratory failure (p < 0.001), pneumonia (p = 0.025), the need for blood transfusion (p = 0.047), elevated blood urea nitrogen (BUN) (p = 0.046), and elevated creatinine levels (p = 0.004) were more common in patients who died within 28 days. Patients who died within 90 days exhibited higher preoperative neutrophil-to-lymphocyte ratio (NLR) values (p = 0.019) and serum creatinine levels (p = 0.008), had a greater prevalence of sleeve or intra-pericardial pneumonectomy (p = 0.002), the need for mechanical ventilation (p < 0.001), intraoperative vascular injury (p = 0.049), sepsis (p < 0.001), respiratory failure (p = 0.019), and contralateral pneumonia (p = 0.008) than those who did not. Conclusions: Intra-pericardial pneumonectomy and postoperative complications are independent predictors of ICU admission after pneumonectomy. Tracheal sleeve and intra-pericardial procedures, intraoperative and postoperative complications, the need for blood transfusion, preoperative NLR ratio, BUN and creatinine levels may also be potential risk factors for mortality.

Interpretable machine learning model for new-onset atrial fibrillation prediction in critically ill patients: a multi-center study

BackgroundNew-onset atrial fibrillation (NOAF) is the most common arrhythmia in critically ill patients admitted to intensive care and is associated with poor prognosis and disease burden. Identifying high-risk individuals early is crucial. This study aims to create and validate a NOAF prediction model for critically ill patients using machine learning (ML).MethodsThe data came from two non-overlapping datasets from the Medical Information Mart for Intensive Care (MIMIC), with MIMIC-IV used for training and subset of MIMIC-III used as external validation. LASSO regression was used for feature selection. Eight ML algorithms were employed to construct the prediction model. Model performance was evaluated based on identification, calibration, and clinical application. The SHapley Additive exPlanations (SHAP) method was used for visualizing model characteristics and individual case predictions.ResultsAmong 16,528 MIMIC-IV patients, 1520 (9.2%) developed AF post-ICU admission. A model with 23 variables was built, with XGBoost performing best, achieving an AUC of 0.891 (0.873–0.888) in validation and 0.769 (0.756–0.782) in external validation. Key predictors included age, mechanical ventilation, urine output, sepsis, blood urea nitrogen, percutaneous arterial oxygen saturation, continuous renal replacement therapy and weight. A risk probability greater than 0.6 was defined as high risk. A friendly user interface had been developed for clinician use.ConclusionWe developed a ML model to predict the risk of NOAF in critically ill patients without cardiac surgery and validated its potential as a clinically reliable tool. SHAP improves the interpretability of the model, enables clinicians to better understand the causes of NOAF, helps clinicians to prevent it in advance and improves patient outcomes.

Suppression of ferroptosis through the SLC7A11/glutathione/glutathione peroxidase 4 axis contributes to the therapeutic action of the Tangshenning formula on diabetic renal tubular injury

BackgroundTangshenning (TSN) is a safe and effective formula to treat diabetic nephropathy (DN), and clinical studies have demonstrated that its therapeutic effects are related to oxidative stress improvements in patients. Herein, this study aims to explore the potential mechanism of how TSN alleviates diabetic renal tubular injury.MethodsThe ultrahigh pressure liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS) was used to identify the chemical composition and serum components of TSN. KK-Ay mice served to investigate the protective effects and regulatory mechanisms of TSN on tubular damage in DN. Furthermore, inhibitors and inducers of ferroptosis were employed in high glucose-cultured tubular epithelial cells (TECs) to verify the potential mechanisms of TSN. The expressions of proteins related to renal tubular injury, ferroptosis and solute carrier family 7, member 11 (SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis were analyzed by western blot and immunofluorescence. Mitochondrial ultrastructure was observed in kidney tissues and TECs by a transmission electron microscope. Pathological changes in the renal tissues were observed by HE, PAS, and Prussian blue staining. Ferroptosis-related reactive oxygen species (ROS), malondialdehyde (MDA), ferrous ion, the intake of cystine, GSH, and oxidized glutathione (GSSG) were evaluated and contrasted in vivo or in vitro.Results51 compounds of TSN powder and 11 components in TSN-containing serum were identified by UPLC-QTOF/MS method. Administration of TSN ameliorated the elevated levels of proteinuria, serum creatinine, blood urea nitrogen, abnormal expression of renal tubular injury markers, and pathological damage to the renal tubules in DN mice model. Intriguingly, a strong inhibition of ferroptosis after TSN treatment occurred in both DN mice model and high glucose-cultured TECs. Notably, induction of ferroptosis by erastin attenuated the protective effect of TSN in high glucose-cultured TECs, while the ferroptosis inhibition by ferrostatin-1 treatment protected renal tubular, which was similar to TSN, suggesting the contribution of TSN-mediated by the inhibition of ferroptosis in DN progression. Mechanistically, TSN upregulated the SLC7A11/GSH/GPX4 axis to inhibit ferroptosis.ConclusionTSN may delay the DN progression and attenuate the renal tubular injury by inhibiting the ferroptosis regulated by the SLC7A11/GSH/GPX4 axis.

An early HMGB1 rise 12 hours before creatinine predicts acute kidney injury and multiple organ failure in a smoke inhalation and burn swine model.

Acute kidney injury (AKI) and multiple organ failure (MOF) are leading causes of mortality in trauma injuries. Early diagnosis of AKI and MOF is vital to improve outcomes, but current diagnostic criteria rely on laboratory markers that are delayed or unreliable. In this study, we investigated whether damage associated molecular patterns such as high-mobility group box 1 (HMGB1), syndecan-1 (SDC-1) and C3a correlate with the development of trauma-induced AKI and MOF. Thirty-nine swine underwent smoke inhalation and severe burns, then received critical care for 72 hours or until death. AKI was defined by the KDIGO (Kidney Disease: Improving Global Outcomes) criteria, which labels AKI when a 1.5-fold increase in blood creatinine levels from baseline or a urine output < 0.5 mL/kg/h for 6 hours or more occurs. MOF was defined by the presence of both AKI and acute respiratory distress syndrome (PaO2/FiO2<300 for 4 hours). Eight of 39 pigs developed AKI and seven of those developed MOF. Pathological analysis revealed that polytrauma induces significantly higher kidney injury scores compared to sham controls. The average time from injury to KDIGO AKI was 24 hours (interquartile range: 22.50-32.25). Twelve hours after injury, HMGB1 levels were significantly increased in animals that went on to develop AKI compared to those that did not (73.07 ± 18.66 ng/mL vs. 31.64 ± 4.15 ng/mL, p<0.01), as well as in animals that developed MOF compared to those that did not (81.52±19.68 ng/mL vs. 31.19 ± 3.972 ng/mL, p<0.05). SDC-1 and C3a levels were not significantly different at any time point between groups. ROC analysis revealed that HMGB1 levels at 12 hours post-injury were predictive of both AKI and MOF development (AKI: AUROC=0.81, cut-off value=36.41 ng/mL; MOF: AUROC=0.89, cut-off value=36.41 ng/mL). Spearman's correlation revealed that HMGB1 levels at 12 hours correlated with multiple parameters of AKI, including blood urea nitrogen, blood creatinine, and blood myoglobin. Twelve-hour post-injury HMGB1 levels predict AKI and MOF in a smoke inhalation and burn swine model. Further research is needed to validate this result in other polytrauma models and in critical combat causalities.

Dietary full-fat or defatted black soldier fly larvae can replace protein sources with no detrimental effect on growth performance or intestinal health of nursery pigs.

This work aimed to determine the effects of dietary full-fat or defatted black soldier fly larvae (BSFL) to replace protein sources on growth performance, blood parameters, intestinal morphology, and intestinal microbiota in nursery pigs and to investigate the effects of dietary defatted BSFL at up to 30% at the expense of protein sources on growth performance in nursery pigs. In Exp. 1, a total of 36 barrows with an initial body weight of 7.0kg (standard deviation = 0.8) were allotted to 3 dietary treatments in a randomized complete block design with 4 replicate pens per treatment and 3 barrows per pen. A corn-soybean meal (SBM)-whey-based control diet was prepared with soy protein concentrate and fish meal as additional protein supplements. Two additional diets were prepared to include 20% full-fat BSFL or 20% defatted BSFL to replace soy protein concentrate and fish meal to maintain the same energy and nutrient concentrations in all diets. In the 28-day feeding trial, pigs fed the diet containing defatted BSFL tended to consume more feeds (P < 0.10) than other groups during days 14 to 28 and the overall period. On day 28, the serum blood urea nitrogen in pigs fed the control diet was less (P < 0.05) than that fed the full-fat or defatted BSFL, but fecal score and jejunal morphology did not differ among the treatment groups. Relative abundance of Mycoplasma in the ileal digesta was less (P < 0.05) in the pigs fed the diet containing full-fat or defatted BSFL compared with the control group. In Exp. 2, a total of 192 pigs with an initial body weight of 7.8 (standard deviation = 1.2kg) were randomly allotted to one of 4 dietary treatments in a randomized complete block design with 6 replicate pens per treatment and 4 barrows and 4 gilts per pen. A control diet was mainly based on corn, SBM, fermented SBM, fish meal, and spray-dried plasma protein. Three additional diets were prepared to contain 10%, 20%, and 30% defatted BSFL to replace SBM, fermented SBM, fish meal, and spray-dried plasma protein to maintain for the same energy and nutrient concentrations. Average daily gain, average daily feed intake, gain:feed, and fecal score were not affected by increasing dietary defatted BSFL. Overall, dietary black soldier fly larvae did not compromise growth performance or intestinal health in nursery pigs. Black soldier fly larvae can be used in nursery pig diets to replace other protein sources without negative effects.

Evaluation of TNF-α and TNF-R1 immunomarkers in Renal Failure Patients in Karbala province

Renal failure is characterized by height level of pro-inflammatory cytokines, mainly Tumor necrosis factor-alpha (TNF-α) and its receptor TNF-R1. The aim was to investigate the association of TNF-α and TNF-R1 levels in Renal Failure.This study was carried out from February 2022 to March 2023 in the labs of Thi-Qar University's Col1ege of Education for Pure Sciences. In partnership with Al-Hussein Teaching Hospital, Nasiriyah General Hospital, and Thi-Qar Center for Nephrology and Dialysis in Thi-Qar Province .The study comprised (100) patients for both sex : (40 patients with diabetes mellitus), (40 patients without diabetes mellitus) whose serum urea level and serum creatinine level were examined, and (40 healthy).The level of biochemical indicators were measured, which included urea, creatinine, albumin and total protein where the study discovered a considerable rise in urea and creatinine levels compared to healthy subjects and standard rates, and this increase is related 'with a decrease GFR', while there is decrease in rate of albumin and total protein. The statistical analysis' findings revealed a considerable difference (p &lt;0.05) in patients with RF in concentration of the TNF-α and TNF-R1, where they were examined for 80 samples of RF patients, and 40 healthy samples in the control group. The number of RF patients in Thi-Qar province showed a marked increase in the yearly rate of hemodialysis. A third of all patients had a considerable prevalence of RF linked to hypertension. The study concluded that a significant effect of TNF-α is associated with markers of kidney disease severity and distant organ dysfunction among patients with RF. In addition, this study found a correlation between the effects of TNF- α on end-stage renal disease. Extensive studies are needed to confirm these relationships.

Mizhuo Guanchangye enema delays the decline of renal function in rats with chronic kidney disease by intervening in the TLR4/MyD88/NF-κB pathway.

Chronic kidney disease (CKD) is a prevalent chronic condition that poses a significant threat to human health. There is a close connection between the gut and kidneys, jointly influencing the onset and progression of CKD through the "gut-kidney axis." Traditional Chinese medicine has shown potential in CKD treatment, but the specific mechanisms require further investigation. This study aims to explore the protective effects of Mizhuo Enema (MZGCY) on kidney function in CKD rats by regulating the TLR4/MyD88/NF-κB signaling pathway. The researcher employed a CKD rat model, which was divided into four groups: Control, Model, half-dose Mizhuo Guanchangye (1/2 MZGCY), and full-dose Mizhuo Guanchangye (MZGCY). Post enema administration, assessments were conducted on kidney function indicators, which included blood urea nitrogen (BUN), serum creatinine (SCR), and 24-h urinary protein. Additionally, measurements were taken for intestinal toxic substances such as indoxyl sulfate (IS) and lipopolysaccharide (LPS), as well as inflammatory factors interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Examinations of pathological changes in both the intestines and kidneys were also performed. During this process, immunofluorescence was utilized to detect the expression levels of proteins toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), and nuclear factor kappa B (NF-κB) in the intestinal tissues. It was found that after enema treatment, the BUN, SCR, and 24-h urinary protein levels in the MZGCY and 1/2 MZGCY groups significantly decreased, indicating notable improvement in kidney function. Compared to the model group, the IS, LPS, IL-6, and TNF-α levels in the MZGCY and 1/2 MZGCY groups were significantly reduced. Immunofluorescence showed a marked decrease in the expression of TLR4, MyD88, and NF-κB proteins in the intestines of the MZGCY group. MZGCY significantly reduces the levels of intestinal toxins and inflammatory factors in the serum of CKD rats by interfering with the TLR4/MyD88/NF-κB signaling pathway, thereby improving intestinal and renal pathological changes and delaying CKD progression. This study demonstrates that MZGCY has significant renal protective effects, providing a new potential approach for CKD treatment.

Machine learning identification of risk factors for ischaemic stroke in patients with heart failure with reduced ejection fraction but without atrial fibrillation: A report from WARCEF trial

Abstract Background The prediction of ischaemic stroke in patients with heart failure with reduced ejection fraction (HFrEF) but without atrial fibrillation (AF) remains challenging and risk stratification based clinical factors alone has limited discrimination. Our aim was to evaluate the performance of machine learning (ML) to identify risk factors for ischaemic stroke in such HFrEF patients. Methods We performed a post-hoc analysis of the WARCEF trial, only including patients without prior history of AF, and censoring those who developed incident AF during follow-up. We evaluated the performance of 9 ML models to identify risk factors for incident stroke, using metrics including area under the curve (AUC), precision, specificity, and decision curve analysis. The importance of each feature in constructing the model was quantified using SHapley Additive exPlanations (SHAP) values. Results We included 2,213 patients with HFrEF but without AF (mean age 59±12 years; 79% male). Of these, 74 (3.3%) had an ischaemic stroke during mean follow-up of 3.5±1.8 years. Out of the 29 patient-demographics variables, 12 were selected for the ML training. All ML models demonstrated high AUC values, outperforming the CHA2DS2-VASc score (Figure 1). The logistic regression model exhibited a slight deviation from this trend. The XGBoost model achieved an AUC of 0.86 (95% confidence interval [CI]: 0.72-0.99), while the Random Forest model showed an AUC of 0.85 (95% CI: 0.74-0.96). Similarly, the Support Vector Machine and Light Gradient Boosting Machine models recorded AUCs of 0.85 (95% CI: 0.72-0.97) and 0.83 (95% CI: 0.70-0.96), respectively. Each of these models attained precision and specificity scores of 1.0, indicating high performance. These models consistently provided significant net clinical benefits. Key risk factors for stroke identified across these models were creatinine clearance and blood urea nitrogen. The use of warfarin appears to be protective. Conclusions Machine-learning models can identify risk factors for ischaemic stroke in patients with HFrEF but without AF. Worsening renal failure was predictive of an incident stroke, while warfarin use was protective against stroke (Figure 2).Figure 1Figure 2

Preclinical Evidence of Mulberry Leaf Polysaccharides on Diabetic Kidney Disease: a Systematic Review and Meta-Analysis.

Mulberry leaf polysaccharides (MLPs) have a variety of biological activities. Preliminary scattered evidence of preclinical studies have reported their potenzial effects on diabetic kidney disease (DKD). Here, we intended to assess the preclinical evidence of MLPs and explore their potenzial mechanisms on DKD, offering a scientific reference for the therapeutic use of MLPs. The study has been registered under the CRD42022309117 registration number at PROSPERO. Comprehensive search was conducted across eight databases from their establishment till January 2024, and eight studies with 270 animals were included in the meta-analysis. The primary outcome measurements in the MLP group, including serum creatinine (Scr) (P = 0.0005), blood urea nitrogen (BUN) (P = 0.02), 24-hour urinary protein (UP) (P = 0.001), and urinary microalbumin (UAlb) (P < 0.0001), were significantly reduced compared to the control group. Additionally, MLP treatment was significantly correlated with fasting blood glucose (FBG), total cholesterol (TC), protein expression of TGF-β1, CTGF mRNA, and the kidney index (all P values < 0.05) and delayed the progression of local pathological changes in the kidney. Subgroup analysis revealed significant species differences in the efficacy of MLPs. Also, it showed that the dosage of streptozotocin potenzially affected the Scr and UAlb results, while the duration of MLP treatment influenced UAlb results. MLPs may exert potenzial renal protection by delaying renal fibrosis, inhibiting inflammatory reactions, suppressing the growth hormone-insulin-like growth factor-insulin-like growth factor binding protein axis, and regulating the insulin receptor pathway. In summary, MLPs have multifaceted renal protective effects, suggesting their potenzial for treating DKD.

Blood urea monitoring in heart failure patients - an important predictor of mortality

Abstract Background Recent ESC position statement regarding worsening renal failure recommends the use of blood urea monitoring of patients with heart failure with reduced ejection fraction (HFrEF). Although both serum creatinine and blood urea nitrogen are markers for renal dysfunction, blood urea nitrogen levels are also affected by reabsorption in the renal tubules, a process modulated by renin-angiotensin-aldosterone activity, sympathetic nervous activity and arginine-vasopressin activity. Thus, neurohormonal activity is reflected in the BUN/creatinine ratio (bUCR) which effectively ‘normalizes’ BUN for the degree of renal dysfunction, as measured by the creatinine level. Previous studies have demonstrated increased mortality at bUCR &amp;gt;100mmol/l. however, most of the prognostic data has come from patients admitted with acute heart failure. The use of bUCR in patients with chronic HFrHF receiving intensive titration of guideline directed medical therapy (GDMT) has not been studied. Purpose To identify the extent of blood urea monitoring in primary care in HFrEF and whether bUCR remains a significant prognostic indicator despite intensive GDMT. Methods We analysed the electronic health records of all patients referred to the Heart Failure Nurse Service (HFNS) in an NHS population approx. 400,000 in 2022. Inclusion criteria consists of patients with symptomatic heart failure NYHA II-IV with echocardiogram demonstrating HFrEF. Patients were segregated into two cohorts, with a urea/creatinine ratio greater or less than 100mmol/l and analysed. Results Data from 338 patients [mean age 72.3 ± 15.6 years; 218 (64.5%) males; 143 (42.3%) ischaemic cardiomyopathy; 141 (41.7%) AF; 49 (14.5%)] were analysed. Of these, 112 (33.1%) had chronic kidney disease (CKD) with eGFR &amp;lt;60 ml/min/1.73m2 at the time of HF diagnosis and 181 (53.6%) had CKD on discharge from the HFNS. During follow-up, 132 (39%) had further admission with HF and 76 (22.5%) died. Sixty-eight (20.1%) patients did not have blood urea checked despite the availability of serum creatinine. While an eGFR &amp;lt; 60 ml/min/1.73m2 at discharge was associated with a twofold increased risk of death (OR 2.4, 95% CI 1.1-5.3, p=0.029), a bUCR &amp;gt; 100mmol/l at discharge was associated with a four-times greater risk of death (OR 4.2, 95% CI 2.2-7.9, p &amp;lt;0.001). Conclusion Blood urea/creatinine ratio is an important predictor of outcome and can be utilised to help identify at-risk patients with HFrEF despite intensive GDMT.Survival from diagnosis bUCR

Magnetic vagus nerve stimulation ameliorates contrast-induced acute kidney injury by circulating plasma exosomal miR-365-3p

BackgroundContrast-induced acute kidney injury (CI-AKI) is manifested by a rapid decline in renal function occurring within 48–72 h in patients exposed to iodinated contrast media (CM). Although intravenous hydration is currently the effective method confirmed to prevent CI-AKI, it has several drawbacks. Some investigations have demonstrated the nephroprotective effects of vagus nerve stimulation (VNS) against kidney ischemia-reperfusion injury, but no direct research has investigated the use of VNS for treating CI-AKI. Additionally, most current VNS treatment applies invasive electrical stimulator implantation, which is largely limited by the complications. Our recent publications introduce the magnetic vagus nerve stimulation (mVNS) system pioneered and successfully used for the treatment of myocardial infarction. However, it remains uncertain whether mVNS can mitigate CI-AKI and its specific underlying mechanisms. Therefore, we herein evaluate the potential therapeutic effects of mVNS on CM-induced nephropathy in rats and explore the underlying mechanisms.ResultsmVNS treatment was found to significantly improve the damaged renal function, including the reduction of elevated serum creatinine (Scr), blood urea nitrogen (BUN), and urinary N-acetyl-β-D-glucosaminidase (NAG) with increased urine output. Pathologically, mVNS treatment alleviated the renal tissue structure injury, and suppressed kidney injury molecule-1 (KIM-1) expression and apoptosis in renal tubular epithelial cells. Mechanistically, increased circulating plasma exosomal miR-365-3p after mVNS treatment enhanced the autophagy and reduced CM-induced apoptosis in renal tubular epithelial cells by targeting Ras homolog enriched in brain (Rheb).ConclusionsIn summary, we demonstrated that mVNS can improve CI-AKI through enhanced autophagy and apoptosis inhibition, which depended on plasma exosomal miR-365-3p. Our findings highlight the therapeutic potential of mVNS for CI-AKI in clinical practice. However, further research is needed to determine the optimal stimulation parameters to achieve the best therapeutic effects.Graphical abstract

Interpretable machine learning model for predicting long-term cardiovascular mortality risk in chronic kidney disease patients using SHAP explainers

Abstract Background Patients with chronic kidney disease (CKD) exhibited a pronounced burden of cardiac mortality. However, early prediction of cardiovascular mortality risk in CKD patients remains an unmet medical need. Purpose This study aimed to evaluate the performance of machine learning (ML) algorithms and identify the most influential factors in predicting long-term cardiac mortality among CKD patients. Methods Six ML models were developed, with the most effective one chosen for predicting and categorising patients into high-risk and low-risk groups based on the maximal Youden’s index. Differences in survival rates were assessed using the log-rank test on Kaplan-Meier curves. Cox regression analysis was employed to investigate the relationship between ML-predicted risk scores and mortality. Furthermore, the SHapley Additive exPlanations (SHAP) method was implemented to provide personalised explanations for model decisions. Results The auto-encoder (AE) model achieved the highest AUC of 0.94, with a sensitivity of 80.95% and specificity of 96.34%. Compared to individuals in low-risk group, those in high-risk group exhibited a significantly elevated risk of cardiovascular mortality (adjusted hazard ratio [HR]: 48.24; P &amp;lt;0.001). According to the SHAP model, age, C-reactive protein, blood urea nitrogen and hypertension were identified as the four most influential factors in the AE model. Conclusions Our study successfully developed an AE machine learning model for predicting 10-year cardiovascular mortality among CKD patients. The combination of ML model and SHAP aids doctors in understanding key features in the model, improving their insight into decision-making related to disease severity assessment, thus facilitating early preventive strategies in clinical practice.

UGT1A1 and BLVRA allele and genotype variants in neonatal patients with hyperbilirubinemia in southern China

We explore the allele and genotype distribution of UGT1A1 and BLVRA variants in individuals affected by neonatal hyperbilirubinemia in southern China. Blood specimens were collected from 240 neonates: 126 cases of hyperbilirubinemia and 114 healthy controls. Serum levels of total protein, albumin, bilirubin (total and direct), urea nitrogen, creatinine, and other biochemical parameters were quantified using a biochemical analyzer. Nine UGT1A1 and five BLVRA genetic variants were genotyped using flight time mass spectrometry. The allele and genotype frequencies of these variants and their associations with neonatal hyperbilirubinemia were analyzed. The genotype frequencies of CC and CG for the UGT1A1 variant rs11888492 in the hyperbilirubinemia group were 90.48% and 9.52%, respectively (P = 0.001), in comparison with the control group. The C and G allele frequencies of rs11888492 in the hyperbilirubinemia group were 95.24% and 4.76%, respectively (P = 0.023). Similarly, in the hyperbilirubinemia group, the genotype frequencies for the UGT1A1 variant rs4148325 were 90.48% CC, 8.73% CT, and 0.79% TT (P = 0.001), with corresponding allele frequencies of 94.84% for C and 5.16% for T (P = 0.002). No notable distinctions were detected for other variants. Newborns carrying the CC genotype of rs11888492 exhibited higher total bilirubin (TBIL) levels than those carrying the GG genotype (P = 0.034), whereas newborns carrying the CC genotype of rs4148325 displayed higher TBIL levels than those carrying the CT genotype (P = 0.003). The presence of the G allele at rs11888492 was found to be significantly correlated with a decreased likelihood of developing neonatal hyperbilirubinemia (odds ratio [OR]: 0.363; 95% confidence interval [CI] 0.169–0.777). Furthermore, a substantial reduction in the risk of neonatal hyperbilirubinemia associated with the CT genotype of rs4148325 were revealed (OR = 0.242; 95% CI 0.102–0.574). Additionally, an inverse relationship was identified between TBIL concentration and the quantity of genetic variants. The UGT1A1 variants rs11888492 and rs4148325 are strongly associated with neonatal hyperbilirubinemia in southern China.

Nephroprotective role of resveratrol in renal ischemia-reperfusion injury: a preclinical study in Sprague-Dawley rats.

Renal ischemia-reperfusion injury (IRI) is a significant contributor to renal dysfunction, acute kidney injury (AKI), and associated morbidity and mortality. Resveratrol, a polyphenol and phytoalexin, is known for its anti-inflammatory, antioxidant, and anti-cancer properties. This study investigates the nephroprotective potential of resveratrol in a rat model of renal IRI. Twenty-eight male Sprague-Dawley rats were divided into four groups: Sham, IRI, DMSO, and Resveratrol. The Sham group underwent identical procedures without renal pedicle clamping, while the IRI group experienced 30min of ischemia followed by 2h of reperfusion. The DMSO group received dimethyl sulfoxide (DMSO) intraperitoneally 30min before ischemia, and the Resveratrol group received 30mg/kg resveratrol intraperitoneally 30min before ischemia. Biochemical parameters (Urea, creatinine, IL-1β, NF-κβ, SOD, GSH, Bcl-2, and caspase-3) and histopathological changes were assessed. IRI caused a substantial increase in serum creatinine, Urea, IL-1β, NF-κβ, and caspase-3 levels, while simultaneously decreasing SOD, GSH, and Bcl-2 levels. Resveratrol treatment mitigated these effects by lowering inflammatory and apoptotic markers, enhancing antioxidant defenses, and improving histological outcomes. Resveratrol demonstrates significant nephroprotective effects in renal IRI, primarily through its antioxidant, anti-inflammatory, and anti-apoptotic properties.

Association of thyroid hormones with the severity of chronic kidney disease: a cross-sectional observational study at Tabuk, Saudi Arabia.

The interplay between chronic kidney disease (CKD) and thyroid dysfunction is becoming more evident in the biomedical community. However, the intricacies of their relationship warrant deeper investigation to understand the clinical implications fully. This study aims to systematically evaluate the correlation between thyroid hormone levels, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), and thyroxine (T4), and markers of renal disease severity. These markers include serum creatinine, urea, and parathyroid hormone (PTH) levels in individuals diagnosed with CK). We conducted a cross-sectional observational study involving a cohort of 86 participants with CKD recruited from the renal clinic at King Fahad Hospital in Tabuk. Biochemical parameters, encompassing plasma electrolytes and thyroid hormone concentrations, were quantitatively assessed. These measurements were performed with the aid of a Roche Cobas E411 analyzer. The Pearson correlation coefficient was employed to delineate the strength and direction of the associations between the thyroid function markers and renal disease indicators. The statistical analysis highlighted a generally weak correlation between the concentrations of thyroid hormones and the indicators of renal disease severity, with Pearson correlation coefficients between -0.319 and 0.815. Critically, no significant correlation was found between creatinine and thyroid hormones (TSH, T3, T4), nor was any substantial correlation between urea and thyroid hormones. Conversely, a robust positive correlation was noted between the levels of parathyroid hormone and serum creatinine (r=0.718, p<0.001). The data suggests that thyroid hormone levels have a minimal correlation with the severity of renal disease markers. In contrast, the pronounced correlation between PTH and creatinine underscores the importance of considering PTH as a significant factor in managing and therapeutic intervention of CKD complications. These initial findings catalyze further research to thoroughly investigate the pathophysiological relationships and potential therapeutic targets concerning thyroid dysfunction in patients with renal impairment.

Muscle Mass and Muscle Strength in Non-Dialysis-Dependent Chronic Kidney Disease Patients.

Background: Sarcopenia is a state with a progressive and generalized loss of skeletal muscle mass and strength. However, muscle strength and muscle mass are different features, which are usually not studied separately. The aim of the study was to investigate anthropometric and clinical correlates and sources of variation in both skeletal muscle mass and muscle strength in chronic kidney disease (CKD). Methods: The study sample consisted of 84 patients with an estimated glomerular filtration rate (eGFR) < 45 mL/min/1.73 m2. Muscle strength was estimated by measuring hand grip strength (HGS). Muscle quantity was measured with bioimpedance spectroscopy (BIS). Serum creatinine, urea, uric acid (UA), and albumin were measured as well. Results: Appendicular skeletal muscle mass (ASM) significantly and positively correlated with body mass, NH weight (normally hydrated weight), height, body mass index (BMI), lean tissue mass (LTM), lean tissue index (LTI), fat mass (FM), and fat tissue index (FTI), and was negatively associated with hydration status. HGS significantly and positively correlated with body mass, NH weight, height, LTM, LTI, and ASM, and was negatively associated with UA and urea. After adjustment for age, sex, and height, HGS remained significantly and negatively related with UA and hydration status. Conclusions: In CKD patients, ASM is determined by anthropometric parameters, but HGS is determined by both anthropometric and clinical variables specific for CKD. In order to study the determinants of HGS in CKD, relationships with HGS should be adjusted for anthropometric variables.

The use of allopurinol in prophylaxis against contrast-induced nephropathy in patients undergoing percutaneous coronary intervention

Abstract Background Contrast-induced nephropathy (CIN) is a serious complication after percutaneous coronary intervention (PCI). Inflammation and development of reactive oxygen species are among the postulated mechanisms of CIN. Allopurinol with anti-inflammatory action could be a preventive method of CI-AKI. Aim of the work To determine the effect of adding allopurinol to hydration in the prevention of CIN in patients undergoing PCI, with or without hyperuricemia. Methods One hundred and seven patients with moderate to high Mehran score undergoing elective PCI were randomly allocated to the allopurinol (n=52) or the control group (n=55). Those in the allopurinol group (hyperuricemic n=25, and normouricemic n= 27) received allopurinol 300 mg one day and one hour before PCI beside intravenous hydration (1 ml/kg/hour) normal saline, a maximum of 100 ml/hour for 12 hours pre and post coronary angiography. Patients in the control group (hyperuricemic n=26 and normouricemic n=29), received the same intravenous hydration only. Serum creatinine and urea were measured before and 48 hours after the procedure while the uric acid level was measured before the procedure only. CIN was defined by a percentage increase in serum creatinine of ≥25% or absolute serum creatinine ≥0.5 mg/dl, 48 hours after PCI. Results The mean age of the studied patients was 59.6 ± 9.1 years old, 59% were male. No difference between both groups regarding baseline characteristics or medications. Average Mehran score was 9.0 ± 1.2. CIN was observed in 5 patients in the allopurinol group (9.6%) and 15 patients in the control group (27.3%) (P = 0.017). There was no significant difference between both groups regarding the contrast volume (179.8 ± 68.1 vs. 153.8 ± 57.9 ml, p: 0.052). Hyperuricemia had no significant effect on increasing the incidence of CI-AKI either in patients with or without CKD (p=0.964). Conclusion Allopurinol on the top of hydration was found to decrease the incidence of CIN following PCI in patients with moderate to high Mehran score for CIN. The anti-inflammatory action of allopurinol could be the mechanism of this favorable effect, as baseline uric acid didn't affect the results. Further multi-center study with a larger sample size is needed to offer more definite results.

Rumen fermentation shifts and microbial dynamics in mid-lactating holstein dairy cows experiencing heat stress and subsequent recovery periods.

In this study, we investigated the effects of heat stress (HS) on rumen fermentation, blood parameters, and ruminal microbial communities in mid-lactating Holstein dairy cows in Korea. Our study involved 12 mid-lactation Holstein dairy cows aged 55.54 months with 2.5 ± 0.65 parities and 100 to 200 days in milking (DIM), fed a total mixed ratio (TMR) diet. Samples were collected during HS (temperature-humidity index (THI) = 81.69) and recovery (RC) period (THI 69.84). The samples were analyzed for rumen fermentation, blood parameters, heat shock proteins, and microbial communities in dairy cows. The milk yield, milk fat, milk protein, and milk urea nitrogen (MUN) levels differed significantly between two -time points (p < 0.05). Rumen pH and volatile fatty acid (VFA) concentrations, the pH was not significantly different (p=0.619) between HS and RC periods; however, the ammonia nitrogen (NH3-N) levels increased during HS period ), however, there was no significant difference (p>0.05). Blood total protein significantly increased during HS period compared with that during RC period (p < 0.05), while no significant differences were observed in other parameters between the two periods. HSP27, HSP70, and HSP90 increased in dairy cows under HS conditions compared with those during the RC period. Taxonomic classification revealed that Firmicutes and Bacteroidetes dominated the bacterial community. PERMANOVA and PERMDISP showed significant differences in rumen bacterial diversity between HS and RC periods, based on Unifrac metrics (p=0.044 and p=0.015, respectively), indicating taxonomic variations. Microbial networks with correlations of > 0.8 (p < 0.05) showed a complex structure with equal positive and negative connections, indicating Anaerohabdus furcosa and Ruminiclostridium cellobioparum as key species during the HS and RC periods respectively. Heat stress significantly impacts Holstein dairy cows' physiological and metabolic processes, altering rumen fermentation, blood biochemistry, and gut microbiota during mid-lactation.

Glutathione s-transferase pi is a marker of loop diuretic resistance in patients with congestive heart failure exacerbation

Abstract Background Loop diuretic resistance (LDR) in patients with heart failure (HF) exacerbation is associated with worse clinical outcomes, greater symptom burden and mortality. Diagnosis and treatment of LDR remains a significant clinical dilemma. Purpose To assess the ability of different urine biomarkers to predict LDR in patients with HF exacerbation. Methods Consecutive patients with congestive HF exacerbation were prospectively included in the study. HF was diagnosed according to ESC 2021 HF Guidelines definition. Congestion was defined as a presence of one or more of the following signs: edema, ascites, pleural effusion. LDR was defined as persistent congestion on the 4th day of hospital stay despite high i.v. loop diuretic dose. Urine biomarkers released from different parts of the nephron (Kidney Injury Molecule-1 - KIM-1, N-acetyl-β-D-glucosaminidase - NAG, uromodulin, glutathione S-transferase Pi - pi-GST, aquaporin-2), transthoracic echo, clinical and biochemical parameters were evaluated on the 1st and 4th day of hospital stay. Results are presented as mean ±standard deviation or median (interquartile range). Results 40 patients were included in the study with median age 84 (72,8; 86) years, median left ventricle ejection fraction (EF) 35.3 (26,5; 49) %, median NT-proBNP 8967.5 (3024; 15241) pg/ml. LDR was found in 14 (35%) patients. Univariate analysis identified the following risk factors for LDR: urine pi-GST concentration on admission and on the 4th day, right ventricle to pulmonary circulation coupling index (TAPSE/PASP ratio), presence of mitral regurgitation, serum creatine concentration, serum urea concentration, serum LDL concentration. Logistic regression analysis identified pi-GST concentration as a significant independent risk factor for LDR in this population: odds ratio (OR) 5.75 [95% confidence interval (CI) 1.271–25.990]. Conclusions Urine pi-GST on admission and after 4 days of treatment might be a marker for a development of LDR in patients with congestive HF exacerbation.

Epidemiological Aspects, Clinicopathology, Hemato-biochemistry and Therapeutic Management of Viperine Snake Envenomation in Buffaloes (Bubalus bubalis)

Background: Poisonous snakebite is a neglected tropical disease, frequently reported in animals including buffaloes. Snakebites are responsible for considerable morbidity and mortality in animals causing economic losses to dairy farmers. Methods: To establish the baseline data of epidemiology, clinical syndrome, hemato-biochemistry and diagnosis of viper snakebites and to standardize the treatment of viper snakebite in buffaloes. Result: The highest incidence of viper envenomation was observed during the monsoon and post-monsoon season in female buffaloes above 4 years of age. The clinical signs such as tachycardia, increased respiration rate, ascending swelling of affected limbs, asymmetrical swelling with dyspnea in case of bite over face and bleeding at the site of bite were observed in envenomed buffaloes. Hemato-biochemical analysis revealed neutrophilic leukocytosis, thrombocytopenia, prolonged capillary blood clotting time, elevated values of blood urea nitrogen (BUN) and creatinine. Post-mortem examination showed hemorrhages and blood-stained serous fluid in subcutaneous tissue and skeletal muscles of the affected limbs. The histopathological changes such as extensive myonecrosis and hemorrhages with marked edema in skeletal muscles, widespread interstitial and intra-alveolar hemorrhages and fibrinous microthrombi in pulmonary vasculature, multifocal to coalescing areas of massive hemorrhages and coagulative necrosis within hepatic parenchyma and marked degeneration of renal tubular epithelium were evident. Therapeutic regimen consisting of polyvalent anti-snake venom, with antibiotics, diuretics, vitamin B complex, styptics, fluids and corticosteroids in non-pregnant while non-steroidal anti-inflammatory drugs in pregnant buffaloes was used. The present treatment strategy showed subsidence of clinical signs, restoration of platelet count, blood clotting time, urea nitrogen and creatinine values depicting clinical recovery with 88.15% survival rate in treated buffaloes.