Elevated Blood Urea Nitrogen Levels Research Articles

Causal Links Between Renal Function and Cardiac Structure, Function, and Disease Risk.

Chronic kidney disease (CKD) increases the risk of adverse cardiovascular outcomes. However, the causal relationships between renal function and cardiovascular diseases (CVD) remain incompletely understood. This study aimed to determine the causal relationships between genetic susceptibility to impaired renal function and the risk of CVD endpoints, as well as cardiac structure and function detectable by cardiac magnetic resonance imaging (CMR). Bidirectional Mendelian randomization (MR) analyses were conducted using summary-level data from genome-wide association studies. The exposures were blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), urine albumin-to-creatinine ratio (UACR), and CKD. The outcomes included atrial fibrillation, coronary artery disease (CAD), myocardial infarction, heart failure, stroke, and various CMR parameters. Sensitivity analyses, multivariable MR adjusting for cardiometabolic traits, and replication in the FinnGen cohort were performed. Elevated BUN levels (OR 1.505; 95% CI 1.077 to 2.103; P = 0.017) were causally associated with increased CAD risk, but this relationship was attenuated after adjusting for cardiometabolic traits. Increased UACR was causally linked to higher risks of CAD (OR 1.260; 95% CI 1.042 to 1.523; P = 0.017), myocardial infarction (OR 1.424; 95% CI 1.137 to 1.783; P = 0.002), and stroke (OR 1.182; 95% CI 1.012 to 1.379; P = 0.035), with the association for stroke remaining significant after multivariable adjustment. Reduced eGFR was causally related to decreases in ascending aorta diameter, proximal pulmonary artery diameter, right atrial size, left ventricular stroke volume, and right ventricular volumes, even after accounting for potential confounders. CKD was causally associated with a reduced pulmonary artery-to-aorta ratio and proximal pulmonary artery diameter. This comprehensive MR study establishes causal roles of genetic susceptibility to impaired renal function influencing cardiovascular outcomes and cardiac structure.

Nutritional Status Impact on Hip Fracture Patients in a Rural Environment.

(1) Background: Hip fractures are highly prevalent traumatic events with significant functional consequences, particularly among the older population. These fractures are associated with increased mortality, postoperative complications, and functional dependence. Medical and nutritional factors such as malnutrition and sarcopenia are crucial for predicting functional outcomes and mortality in these patients. This study aimed to assess the nutritional status, vitamin D levels, and sarcopenia, as well as their relationship with mortality, mean hospital stay, and 30-day-readmission rate, in patients with hip fracture who underwent surgery in a rural hospital setting. (2) Methods: A longitudinal retrospective study involving 124 patients who underwent hip fracture surgery in 2021 was conducted. Sociodemographic, surgical, and nutritional data, including vitamin D, albumin, and blood urea nitrogen (BUN) levels, were collected. (3) Results: The average age of the sample was 89.1 years, with a postoperative 30-day-mortality rate of 8.1% and an average hospital stay of 10.4 days. Vitamin D deficiency was present in 79.7% of patients, and a high prevalence of malnutrition was indicated by low albumin and elevated BUN levels. Elevated BUN levels and low vitamin D levels were associated with higher mortality. (4) Conclusions: Adequate nutritional assessment in patients with hip fracture is vital for identifying the risks of complications and mortality. Understanding the current nutritional status and its associated complications will aid in developing strategies to improve health and reduce complications in the future.

Value of Maternal Renal Function Indicators in Predicting Small for Gestational Age Infants in Patient with Severe Preeclampsia

Background: Severe preeclampsia poses significant health risks to both pregnant patients and their newborns. Our goal was to explore the association between serum renal function related indicators in pregnant patients with severe preeclampsia and the occurrence of small for gestational age (SGA) infants, as well as to further identify independent risk factors for SGA based on these indicators. Methods: This was a retrospective case-control study. We evaluated the renal function indicators of 127 severe preeclampsia pregnant patients and 127 normal pregnant patients antenatally who delivered in Shijiazhuang Fourth Hospital from January 2022 to December 2022. Mann-Whitney U test and Chi-square test were used to compare the differences in clinical data between two groups. Spearman correlation analysis was used to determine the correlation between renal function indicators and newborn weight in severe preeclampsia pregnant patients. Receiver operating characteristic (ROC) curve was used to determine the optimal critical values of the above indicators, and multivariate logistic regression analysis was used to determine the independent risk factors for severe preeclampsia combined with SGA. Results: Blood urea nitrogen (BUN), serum creatinine (SCr) and serum uric acid (SUA) in severe preeclampsia patients with SGA were higher than severe preeclampsia without SGA (p < 0.05 vs. all groups). In the severe preeclampsia group, these indicators were significantly negatively correlated with birth weight (p < 0.001 vs. all groups), whereas no correlation was observed in the control group. In the severe preeclampsia group, a ROC analysis was performed based on whether the infants were small for gestational age, and the indicators were divided into two groups according to the optimal cut-off value. After adjusting for confounding factors, elevated BUN (≥4.9 mmol/L) served as an independent risk factor for severe preeclampsia patients with SGA (odds ratio (OR) = 4.336, 95% confidence interval (95% CI): 1.781–10.552, p = 0.001), and the corresponding area under the curve was 0.661 (0.572, 0.743). Conclusions: Serum renal function indicators in pregnant patients with severe preeclampsia were significantly associated with the occurrence of small for gestational age (SGA) infants. Moreover, elevated maternal BUN levels (≥4.9 mmol/L) prior to delivery may indicate the occurrence of SGA. However, we also acknowledge that the predictive power of this single marker is limited.

Effects of dietary supplementation with Vitamin A, D3, E, and Garlic on heat detection, pregnancy rate, and serum profile in anestrus dairy cows

Anestrus poses substantial challenges for dairy industries worldwide. This research aims to evaluate the effect of oral supplementation with garlic alone, vitamins A, D3, E alone, and their combination on heat detection, pregnancy rate and serum profile in anestrus dairy cows. Using a completely randomized design, this study, conducted over 327 days, evaluated 72 anestrus-affected cows, which were divided into four groups. T0 (Control) received only normal saline; T1 with vitamin A,D3,E; T2 with Garlic and T3 integrated with A, D3, E + Garlic in drinking water. Results demonstrated that the treatment groups exhibited significantly higher estrus signs (p<0.05) compared to the control. The pregnancy rate was also increased (P=0.059), especially in the T3 group which had the highest heat detection (55.55%), conception (70%), and pregnancy (38.88%). In comparison, the heat detection rate for T1 was 44.44%, while the conception rate for T2 was 66.66%. Additionally, T0 exhibited the least proportion across all parameters. Additionally, the elevated BUN (Blood Urea Nitrogen) and blood glucose levels observed in non-responsive (those not showing signs of heat) cows at 32.51 and 43.65 mg/dl respectively, compared to responsive cows (those showing signs of heat) with levels of 22.40 and 51.34 mg/dl. These findings suggest a potential association between these blood parameters and the cyclicity of dairy cows. These findings highlight that oral supplementation with vitamin AD3E+Garlic significantly improves the heat detection rate and pregnancy rate than only administering vitamin AD3E or Garlic with anestrus in dairy cattle.

Association between blood urea nitrogen-to-potassium ratio and 30-day all-cause mortality in patients with non-traumatic subarachnoid hemorrhage

BackgroundThe mortality risk is exceptionally high in non-traumatic subarachnoid hemorrhage (SAH). Elevated blood urea nitrogen (BUN) levels and hypokalemia are prevalent issues in patients with non-traumatic SAH. To explore the correlation between the blood urea nitrogen-to-potassium ratio (BPR) and 30-day all-cause mortality in non-traumatic SAH patients. MethodsWe systematically extracted specific clinical data from the Medical Information Mart for Intensive IV (MIMIC-IV) database. To assess the prognostic relevance of the BPR, we categorized patients into those experiencing in-hospital mortality within 30 days and those surviving, subjecting them to both univariate and multivariate Cox regression analyses. The optimal BPR cut-off value was identified using Receiver Operating Characteristic (ROC) curve analysis, employing the maximum Youden index to predict survival status. Furthermore, we employed Kaplan–Meier (K–M) analysis to illustrate survival curves. ResultsA cohort comprising 608 patients with non-traumatic SAH was enrolled in the investigation. Multivariate Cox regression analysis identified the BPR as an independent predictor of all-cause mortality within 30 days of admission for patients with non-traumatic SAH (Hazard Ratio [HR], 1.13; 95 % Confidence Interval [CI], 1.04–––1.23; P<0.05). Further refinement resulted in the establishment of an optimized prediction model (AUC=83.61 %, 95 % CI: 79.73 % − 87.49 %) for forecasting all-cause mortality at 30 days post-hospital admission in patients with non-traumatic SAH. ConclusionThe BPR emerges as an independent prognostic indicator for all-cause mortality within the initial 30 days of admission among non-traumatic SAH patients.

Mitochondrial Pathogenic Mutations and Expression Pattern of Oxidative Phosphorylation Genes in COVID-19 Patients.

Mitochondrial missense mutations and pathogenic variants have been implicated in the pathogenesis of COVID-19. This study evaluated the role of mitochondrial DNA (mtDNA) mutations and changes in gene expression in the progression of COVID-19 and their correlation with clinical characteristics. Next-generation sequencing with high throughput was used to identify mtDNA mutations in 30 COVID-19 patients compared to 20 healthy controls. The potential impact of identified mutations on protein structure and stability was predicted using bioinformatic tools. Quantitative real-time polymerase chain reaction was employed to assess the expression levels of mtDNA-encoded genes involved in oxidative phosphorylation in COVID-19 patients and healthy controls. Correlations between gene expression levels, clinical parameters, including leukocyte, lymphocyte, neutrophil, and platelet count, as well as creatinine, alanine transaminase (ALT), aspartate transaminase (AST), and blood urea nitrogen (BUN) levels, and disease severity were analyzed. We found 8 different mtDNA mutations in ND1, ND5, CO3, ATP6, and CYB genes, which were predicted to alter amino acids and decrease protein stability. Two missense unique mutations, C9555T in CO3 and A12418T in ND5 were identified and correlated with Complexes I and IV, respectively. This downregulation was correlated with age, elevated levels of leukocytes, lymphocytes, neutrophils, platelets, creatinine, ALT, AST, and BUN, as well as disease severity. These findings suggest that mtDNA mutations and altered expression of oxidative phosphorylation genes contribute to mitochondrial dysfunction in COVID-19. Targeting mitochondrial dysfunction may represent a promising therapeutic strategy for COVID-19 treatment.

Juzentaihoto alleviates cisplatin‐induced renal injury in mice

AbstractAimCisplatin is a highly effective anti‐cancer agent, but its clinical use is restricted due to severe renal toxicity. This study aimed to investigate the alleviative effects of juzentaihoto (JTT) in a mouse model of cisplatin‐induced renal injury.MethodsFour groups of seven‐week‐old male C57BL/6J mice (control, JTT, cisplatin, and JTT + cisplatin groups) were used in the study. The JTT and JTT + cisplatin groups received oral JTT (500 mg/kg) once a day for three days. After 24 h, the cisplatin, and JTT + cisplatin groups were intraperitoneally injected with cisplatin (15 mg/kg). The mice in each group were euthanized 72 h after cisplatin administration, and blood and kidney samples were collected.ResultsCisplatin injection decreased body weight and elevated plasma blood urea nitrogen and creatinine levels, while also increasing renal oxidative stress, inflammation, and cell death. These changes were alleviated by JTT administration. We also found that platinum accumulation in the kidneys following cisplatin injection was attenuated by JTT treatment. Furthermore, Mate1 expression levels (a cisplatin efflux transporter) were upregulated by JTT injection.ConclusionOur results demonstrated that JTT mitigated cisplatin‐induced renal injury in mice by alleviating oxidative stress, inflammation, and cell death, achieved through the upregulation of the cisplatin efflux transporter Mate1.

HL156A, an AMP-Activated Protein Kinase Activator, Inhibits Cyst Growth in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most prevalent genetic kidney disorder. While metformin has demonstrated the ability to inhibit cyst growth in animal models of ADPKD via activation of adenosine monophosphate-activated protein kinase (AMPK), its effectiveness in humans is limited due to its low potency. This study explored the impact of HL156A, a new and more potent AMPK activator, in a mouse model of ADPKD. To investigate whether HL156A inhibits the proliferation of renal cyst cells in ADPKD in vitro, exogenous human telomerase reverse transcriptase (hTERT)-immortalized renal cyst cells from ADPKD patients were treated with HL156A, and an MTT (dimethylthiazol-diphenyltetrazolium bromide) assay was performed. To assess the cyst-inhibitory effect of HL156A in vivo, we generated Pkd1 conditional knockout (KO) mice with aquaporin 2 (AQP2)-Cre, which selectively expresses Cre recombinase in the collecting duct. The effectiveness of HL156A in inhibiting cyst growth and improving renal function was confirmed by measuring the number of cysts and blood urea nitrogen (BUN) levels in the collecting duct-specific Pkd1 KO mice. When cyst cells were treated with up to 20 µM of metformin or HL156A, HL156A reduced cell viability by 25% starting at a concentration of 5 µM, whereas metformin showed no effect. When AQP2-Cre male mice were crossed with Pkd1flox/flox female mice, and when AQP2-Cre female mice were crossed with Pkd1flox/flox male mice, the number of litters produced by both groups was comparable. In collecting duct-specific Pkd1 KO mice, HL156A was found to inhibit cyst growth, reducing both the number and size of cysts. Furthermore, it was confirmed that kidney function improved as HL156A treatment led to a reduction in elevated BUN levels. Lastly, it was observed that the increase in AMPK phosphorylation induced by HL156A decreased ERK phosphorylation and α-SMA expression. HL156A has potential as a drug that can restore kidney function in ADPKD patients by inhibiting cyst growth.

Surgical Treatment of a Perinephric Pseudocyst in a Five-Month-Old Female Cat

Introduction: A perinephric pseudocyst is characterized by the accumulation of fluid within fibrous sacs surrounding one or both kidneys, typically located in the sub-capsular or extracapsular areas. Histologically, these cysts lack an epithelial lining, thus earning the term "pseudocyst." This condition is uncommon in cats and is often associated with chronic kidney disease, particularly in older animals. Diagnosis relies heavily on imaging modalities, and prognosis varies based on the severity of renal impairment. The present case report aimed to detail the diagnosis and treatment of a rare perinephric pseudocyst in a 5-month-old female domestic short-haired cat. Case report: A left perinephric pseudocyst was diagnosed in a 5-month-old female domestic short-haired cat weighing 4.7 kg, presented to Guilan Pet Hospital, Guilan, Iran in January 2021 with a history of abdominal distention and anorexia. Physical examination revealed distension on the left side of the abdomen without any other significant findings. Complete blood count was within normal limits, while the biochemical profile showed elevated blood urea nitrogen (BUN) and serum creatinine (Cr) levels at the upper limits of the reference range, along with elevated glucose and alkaline phosphatase (ALP) levels above the reference range. Plain radiography revealed a large mass on the left side of the abdomen, and ultrasonography confirmed the presence of anechoic fluid surrounding the left kidney. Subsequently, a unilateral nephrectomy was performed. Following surgery, the cat owner reported satisfaction with the outcome, and the cat showed no signs of illness during follow-up examinations over the next six months. Both complete blood count and biochemical profiles remained within normal ranges. Conclusion: While perinephric pseudocyst is rare in young cats, it should be considered in cases of abdominal distention and renomegaly. Utilizing imaging is crucial for diagnosis, and nephrectomy proves to be a reliable treatment, ensuring both owner satisfaction and positive results for the cat's health.

Association of blood urea nitrogen with all-cause and cardiovascular mortality in hyperlipidemia: NHANES 1999–2018

ObjectiveAlthough blood urea nitrogen (BUN) has a crucial impact on many diseases, its effect on outcomes in patients with hyperlipidemia remains unknown. The study aimed to investigate the relationships between BUN levels and all-cause and cardiovascular disease (CVD) mortality in individuals with hyperlipidemia.MethodsThis analysis comprised 28,122 subjects with hyperlipidemia from the National Health and Nutrition Examination Survey (NHANES) spanning 1999 to 2018. The risk of BUN on mortality was evaluated using weighted Cox regression models. Additionally, to illustrate the dose-response association, the restricted cubic spline (RCS) was used.ResultsDuring the observation period, 4276 participant deaths were recorded, of which 1206 were due to CVD. Compared to patients with hyperlipidemia in the third BUN quintile, the hazard ratios (HRs) for all-cause mortality were 1.26 (95% CIs: 1.09, 1.45) and 1.22 (95% CIs: 1.09, 1.37) for patients in the first and fifth quintiles of BUN, respectively. The HRs for CVD mortality among patients in the fifth quintile of BUN were 1.48 (95% CIs: 1.14, 1.93). BUN levels were found to have a U-shaped association with all-cause mortality and a linear association with CVD mortality using restricted triple spline analysis.ConclusionsThis study revealed that both low and high BUN levels in patients with hyperlipidemia are associated with heightened all-cause mortality. Furthermore, elevated BUN levels are also associated with increased CVD mortality. The findings indicate that patients with hyperlipidemia may face an elevated risk of death if they have abnormal BUN levels.

Electrolyte Imbalance and Impaired Kidney Functions in COVID-19 Hospitalized Patients

Abstract Objective: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, is a pandemic infection that first appeared in Wuhan, China and is responsible for acute respiratory illness. The symptoms of this infection range from being mild and restricted to developing fever, cough, and loss of smell or taste, to severe life-threatening pneumonia and acute respiratory distress syndrome, and the severity could reach beyond that level and convert to a multi-organ failure or death. Angiotensin-converting enzyme 2 (ACE2) is known to be the receptor that used by coronavirus to enter the cells, and hence, multi-organ infection could result. From that point, renal involvement, including impaired kidney function and electrolyte imbalance, is one of the complications that might develop. Materials and Methods: A total of 60 patients, 29 males and 31 females, were recruited in this study, where blood urea nitrogen (BUN), serum creatinine, sodium, potassium, and chloride were evaluated. Results: The results revealed elevated levels of BUN and serum creatinine and decreased levels of sodium and chloride and to some extent, potassium levels. Few samples were diagnosed with increased levels of serum electrolytes. Conclusion: The results revealed the presence of electrolyte imbalance and kidney dysfunction associated with COVID-19 infection. Further investigations need to be carried out to estimate to what extent the changes in these biochemical parameters could be risk factors for developing acute kidney injury (AKI) and eventually death.

β-Hydroxybutyrate Protects Against Cisplatin-Induced Renal Damage via Regulating Ferroptosis

Cisplatin is a particularly potent antineoplastic drug. However, its usefulness is restricted due to the induction of nephrotoxicity. More recent research has indicated that β-hydroxybutyrate (β-HB) protects against acute or chronic organ damage as an efficient healing agent. Nonetheless, the therapeutic mechanisms of β-HB in acute kidney damage caused by chemotherapeutic drugs remain unclear. Our study developed a model of cisplatin-induced acute kidney injury (AKI), which involved the administration of a ketogenic diet or β-HB. We analyzed blood urea nitrogen (BUN) and creatinine (Cr) levels in serum, and used western blotting and immunohistochemical staining to assess ferroptosis and the calcium/calmodulin-dependent kinase kinase 2 (Camkk2)/AMPK pathway. The mitochondrial morphology and function were examined. Additionally, we conducted in vivo and in vitro experiments using selective Camkk2 inhibitor or activator to investigate the protective mechanism of β-HB on cisplatin-induced AKI. Exogenous or endogenous β-HB effectively alleviated cisplatin-induced abnormally elevated levels of BUN and Cr and renal tubular necrosis in vivo. Additionally, β-HB reduced ferroptosis biomarkers and increased the levels of anti-ferroptosis biomarkers in the kidney. β-HB also improved mitochondrial morphology and function. Moreover, β-HB significantly attenuated cisplatin-induced cell ferroptosis and damage in vitro. Furthermore, western blotting and immunohistochemical staining indicated that β-HB may prevent kidney injury by regulating the Camkk2-AMPK pathway. The use of the Camkk2 inhibitor or activator verified the involvement of Camkk2 in the renal protection by β-HB. This study provided evidence of the protective effects of β-HB against cisplatin-induced nephrotoxicity and identified inhibited ferroptosis and Camkk2 as potential molecular mechanisms.

Effect of verbascoside against acute kidney injury induced by rhabdomyolysis in rats.

Rhabdomyolysis is a pathological condition caused by muscle tissue degradation. In this condition, intracellular contents enter the bloodstream, and acute kidney injury (AKI) develops. Verbascoside (VB) is one of the most common phenylethanoid glycosides and has antioxidant and anti-inflammatory effects. This study investigated the effects of VB on AKI induced by rhabdomyolysis in rats. Male Wistar rats were divided into six groups (n = 6): (1) control group (normal saline), (2) 50% glycerol (10 ml/kg, IM, single injection, only on the first day), (3)-(5) 50% glycerol (same as group 2) + VB (30, 60, and 100 mg/kg, IP, 4 days), and (6) VB (100 mg/kg). Serum and kidney tissue samples were collected on day 5. Subsequently, serum creatinine (Cr), blood urea nitrogen (BUN), renal glutathione (GSH), malondialdehyde (MDA), lipocalin associated with neutrophil gelatinase (NGAL), tumor necrosis factor-alpha (TNF-α), and pathological changes were investigated. The injection of glycerol elevated levels of kidney damage markers, including Cr and BUN in serum, MDA, TNF-α, and NGAL, along with a reduction in GSH levels in the kidney tissue. The administration of VB (100 mg/kg) significantly lowered the levels of these markers, indicating the therapeutic effect of VB against AKI caused by rhabdomyolysis. Histopathological examinations revealed enhanced myoglobin cast formation and tubular necrosis in the glycerol group, which was reduced in rats that received VB, although this reduction did not reach statistical significance. VB can reduce rhabdomyolysis-induced AKI through its anti-inflammatory and antioxidant effects and decrease kidney damage severity.

Local antibiotic delivery via intra-articular catheter infusion for the treatment of periprosthetic joint infection: a systematic review.

There is an increasing interest in the use of intra-articular (IA) antibiotic infusion as a stand-alone or adjuvant therapy to standard revision surgery for periprosthetic joint infection (PJI). The objective of this systematic review is to evaluate the evidence with respect to this up-and-coming treatment modality. A systematic review of studies published until April 2023 was conducted using PubMed, Embase, MEDLINE and Cochrane databases. Quality assessment was performed with the National Institute of Health quality assessment tool. Inclusion criteria were adult patients (≥ 18years) with a mean follow-up of ≥ 11months and a score ≥ 6 on the National Institute of Health quality assessment tool. Primary outcome was eradication of infection. 15 articles, encompassing 631 PJIs in 626 patients, were included in the final analysis, all level IV case series. The majority was treated with single-stage revision with adjuvant IA antibiotic infusion (79.1%). The remaining PJIs were treated with stand-alone IA antibiotic infusion (12.2%), DAIR (debridement, antibiotics and implant retention) with adjuvant IA antibiotic infusion (5.7%) or two-stage revision with adjuvant IA antibiotic infusion (3.0%). Mean duration of IA antibiotic infusion was 19days (range 3-50). An overall failure rate of approximately 11% was found. In total 117 complications occurred, 71 were non-catheter-related and 46 were catheter-related. The most common catheter-related complications were premature loss of the catheter (18/46) and elevated blood urea nitrogen (BUN) and creatinine levels (12/46). Due to the lack of comparative studies the (added) benefit of IA antibiotic infusion in the treatment of PJI remains uncertain. Based on the current evidence, we would advise against using it as a stand-alone treatment. A prospective randomized controlled trial using a well-described infusion protocol is needed to see if the potential benefits justify the increased costs and potential complications of this treatment modality.

Role of cAMP/pCREB and GSK-3β/NF-κB p65 signaling pathways in the renoprotective effect of mirabegron against renal ischemia-reperfusion injury in rats

Acute kidney injury and other renal disorders are thought to be primarily caused by renal ischemia-reperfusion (RIR). Cyclic adenosine monophosphate (cAMP) has plenty of physiological pleiotropic effects and preserves tissue integrity and functions. This research aimed to examine the potential protective effects of the β3-adrenergic receptors agonist mirabegron in a rat model of RIR and its underlying mechanisms. Male rats enrolled in this work were given an oral dose of 30 mg/kg mirabegron for two days before surgical induction of RIR. Renal levels of kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α), Interleukin-10 (IL-10), cAMP, cAMP-responsive element binding protein (pCREB), and glycogen synthase kinase-3 beta (GSK-3β) were assessed along with blood urea nitrogen and serum creatinine. Additionally, caspase-3 and nuclear factor-kappa B (NF-κB) p65 were explored by immunohistochemical analysis. Renal specimens were inspected for histopathological changes. RIR led to renal tissue damage with elevated blood urea nitrogen and serum creatinine levels. The renal KIM-1, MCP-1, TNF-α, and GSK-3β were significantly increased, while IL-10, cAMP, and pCREB levels were reduced. Moreover, upregulation of caspase-3 and NF-κB p65 protein expression was seen in RIR rats. Mirabegron significantly reduced kidney dysfunction, histological abnormalities, inflammation, and apoptosis in the rat renal tissues. Mechanistically, mirabegron mediated these effects via modulation of cAMP/pCREB and GSK-3β/NF-κB p65 signaling pathways. Mirabegron administration could protect renal tissue and maintain renal function against RIR.

Kidney Function Tests and Continuous eGFR Decrease at Six Months after SARS-CoV-2 Infection in Patients Clinically Diagnosed with Post-COVID Syndrome.

The long-term sequelae of SARS-CoV-2 infection are still under research, since extensive studies showed plenty of systemic effects of the viral infection, extending even after the acute phase of the infection. This study evaluated kidney function tests six months after SARS-CoV-2 infection in patients clinically diagnosed with Post-COVID Syndrome, hypothesizing persistent renal dysfunction evidenced by altered kidney function tests compared to baseline levels. Continuous eGFR decrease <30 at six months post-infection was considered the main study outcome. Conducted at the "Victor Babes" Hospital, this retrospective observational study involved adults with laboratory-confirmed SARS-CoV-2 infection and clinically-diagnosed Post-COVID Syndrome, excluding those with prior chronic kidney disease or significant renal impairment. Kidney function tests, including serum creatinine, blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), alongside markers of kidney damage such as proteinuria and hematuria, were analyzed. Among 206 participants, significant differences were observed between the control (n = 114) and the Post-COVID group (n = 92). The Post-COVID group exhibited higher serum creatinine (109.7 μmol/L vs. 84.5 μmol/L, p < 0.001), lower eGFR (65.3mL/min/1.73 m2 vs. 91.2 mL/min/1.73 m2, p < 0.001), and elevated BUN levels (23.7 mg/dL vs. 15.2 mg/dL, p < 0.001) compared to the control group. Regression analysis highlighted significant predictors of continuous eGFR decrease <30 at six months post-infection. The development of acute kidney injury (AKI) during the initial COVID-19 illness emerged as a strong predictor of reduced eGFR (β = 3.47, p < 0.001). Additional factors, including a creatinine increase (23 μmol/L above the normal range) and an elevated Albumin to Creatinine Ratio (ACR) (>11 mg/g above the normal range), were significantly associated with eGFR reduction. Patients with Post-COVID Syndrome demonstrate significant renal impairment six months post-SARS-CoV-2 infection. The study's findings stress the need for ongoing monitoring and intervention strategies for renal health in affected individuals, underscoring the persistent impact of COVID-19 on renal function.

Tumor lysis syndrome following letrozole for locally advanced breast cancer: a case report

BackgroundLetrozole, an aromatase inhibitor, is used to treat breast cancer in postmenopausal women. Tumor lysis syndrome (TLS) is a complication that can trigger multiple organ failure caused by the release of intracellular nucleic acids, phosphate, and potassium into the blood due to rapid tumor cell disintegration induced by drug therapy. TLS is uncommon in solid tumors and occurs primarily in patients receiving chemotherapy. Herein, we report a rare occurrence of TLS that developed in a patient with locally advanced breast cancer following treatment with letrozole.Case presentationAn 80-year-old woman with increased bleeding from a fist-sized left-sided breast mass presented to our hospital. Histological examination led to a diagnosis of invasive ductal carcinoma of the luminal type. The patient refused chemotherapy and was administered hormonal therapy with letrozole. Seven days after letrozole initiation, she complained of anorexia and diarrhea. Blood test results revealed elevated blood urea nitrogen (BUN) and creatinine (Cr) levels, and she was admitted to our hospital for intravenous infusions. On the second day after admission, marked elevations of LDH, BUN, Cr, potassium, calcium, and uric acid levels were observed. Furthermore, metabolic acidosis and prolonged coagulation capacity were observed. We suspected TLS and discontinued letrozole, and the patient was treated with hydration, febuxostat, and maintenance hemodialysis. On the third day after admission, her respiratory status worsened because of acute respiratory distress syndrome associated with hypercytokinemia, and she was intubated. On the fourth day after admission, her general condition did not improve, and she died.ConclusionsAlthough TLS typically occurs after chemotherapy initiation, the findings from the present case confirm that this syndrome can also occur after hormonal therapy initiation and should be treated with caution.

Current status and clinical outcome of endoscopic hemostatic powder in gastrointestinal bleeding: a retrospective multicenter study.

Few multicenter studies have investigated the efficacy of hemostatic powders in gastrointestinal (GI) bleeding. We aimed to investigate the clinical outcomes of hemostatic powder therapy and the independent factors affecting rebleeding rates. We retrospectively recruited patients who underwent a new hemostatic adhesive powder (UI-EWD; Next-Biomedical) treatment for upper and lower GI bleeding between January 1, 2020 and March 1, 2023. We collected patients' medical records and bleeding lesions. The primary outcomes were clinical and technical success rates, and the secondary outcomes were early, delayed, and refractory bleeding, mortality, and factors affecting early rebleeding rates. This study enrolled 135 patients (age: 67.7±13.6 years, male: 74.1%) from five hospitals. Indications for UI-EWD were peptic ulcers (51.1%), post-procedure-related bleeding (23.0%), and tumor bleeding (19.3%). The clinical and technical success rates were both 97%. The early, delayed, and refractory rebleeding rates were 19.3%, 11.1%, and 12.8%, respectively. Initially elevated blood urea nitrogen (BUN) levels (p=0.014) and Forrest classification IA or IB compared with IIA or IIB (p=0.036) were factors affecting early rebleeding. UI-EWD showed high clinical and technical success rates; however, rebleeding after UI-EWD therapy in patients with initially high BUN levels and active bleeding, according to the Forrest classification, should be considered.

Toxicity evaluation of processing Evodiae fructus based on intestinal microbiota.

With the development of healthcare services, drug efficacy, and safety have become the focus of drug use, and processing alters drug toxicity and efficacy, exploring the effects of processing on Evodiae fructus (EF) can guide the clinical use of drugs. Fifty male Kunming mice were randomly divided into the control group (CCN), raw small-flowered EF group (CRSEF), raw medium-flowered EF group (CRMEF), processing small-flowered EF group (CPSEF), and processing medium-flowered EF group (CPMEF). The CRSEF, CRMEF, CPSEF, and CPMEF groups were gavaged with aqueous extracts of raw small-flowered EF dry paste (RSEF), medium-flowered EF dry paste (RMEF), processing small-flowered EF dry paste (PSEF) and processing medium-flowered EF dry paste (PMEF), respectively, for 21 days at 5 times the pharmacopeial dosage. Upon concluding the experiment, histopathological sections of liver and kidney tissues were examined. Additionally, levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (SCr), and blood urea nitrogen (BUN) were determined. DNA from the intestinal contents of the mice was extracted, and 16S rRNA full-length high-throughput sequencing was performed. After fed EF 21 days, mice exhibited a decreasing trend in body weight. Comparative analysis with the CCN group revealed an upward trend in SCr, BUN, AST, and ALT levels in both CRSEF and CRMEF groups. The CRMEF group displayed notably elevated BUN and AST levels, with an observed increasing trend in Scr and ALT. Kidney sections unveiled cellular edema and considerable inflammatory cell infiltrates, whereas significant liver damage was not evident. Compared with CRSEF, Bun levels were significantly lower while AST levels were significantly higher in the CPMEF group. Additionally, the intestinal microbiota diversity and the relative abundance of Psychrobacter decreased significantly, and the relative abundance of Staphylococcus, Jeotgalicoccus, and Salinicoccus increased significantly in the CPMEF group. AST, ALT, and SCr were positively correlated with Staphylococcus, Jeotgalicoccus, and Salinicoccus. In conclusion, PMEF significantly increased harmful bacteria (Staphylococcus, Jeotgalicoccus, and Salinicoccu) and decreased beneficial bacteria. SEF with 5 times the clinical dose showed nephrotoxicity and SEF nephrotoxicity decreased after processing, but EF hepatotoxicity was not significant, which may be due to insufficient dose concentration and time.

Protective effects and mechanisms of dapagliflozin on renal ischemia/reperfusion injury

BackgroundRenal diseases have a significant negative impact on human health and the quality of life. Renal ischemia/reperfusion (I/R) injury is considered as one of the leading causes of renal dysfunction and tissue damage. Oxidative stress and inflammation are responsible for cellular apoptosis playing critical roles in renal I/R injury. Recent studies suggested that dapagliflozin—a medication used to treat Type 2 Diabetes—may exert protective effects on I/R injury in kidneys by alleviating oxidative stress and inflammation. Our study evaluated the protective effects of dapagliflozinon in renal I/R injury. MethodsA group of 32 male Sprague-Dawley rats were divided into four groups: 1) control group without any manipulation; 2) sham-operated control group with surgery but without I/R injury; 3) experimental group with 30-min I/R injury; and 4) therapeutic group with 30-min IR injury and dapagliflozin therapy. The fourth therapeutic group received 1 mg/kg dapagliflozin delivered once daily by oral gavage. All rats were evaluated by measurements of neutrophil gelatinase-associated lipocalin (NGAL), creatinine kinase (CR), blood urea nitrogen (BUN), kidney injury molecule-1 (KIM-1), myoglobin (MYO), creatinine kinase (CK), lactate dehydrogenase (LDH) LD, GSH, superoxide dismutase (SOD), MDA, interleukin-6 (IL-6), and tumor necrosis factor-a (TNF-a and glutathione peroxidase (GSH-Px) levels. TUNEL and flow cytometry assays evaluated apoptosis. ResultsOverall, the 30-min exposure to I/R injury significantly elevated levels of NGAL, CR, BUN, CK, LDH, KIM-1, and MYO (all p < 0.05). Inflammatory cytokine levels (IL-6 and TNF-a) were also increased after I/R injury (p > 0.05). At the same time, I/R injury decreased levels of SOD and GSH-Px (p > 0.05). In contrast, administration of dapagliflozin following I/R injury reduced renal damage, enhanced antioxidant capacity, and suppressed inflammatory responses (all p > 0.05), thus improving renal function, while reducing oxidative stress status and inflammatory responses. Further investigations revealed that dapagliflozin exerted its protective effects on renal tissues by activating the phosphatidylinositol 3-kinase-protein kinase B (PI3K-AKT) signaling pathway, inhibiting cellular apoptosis, and promoting proliferation and autophagy through bone morphogenetic protein 4 (BMP4). ConclusionThese findings documented that dapagliflozin protected kidneys from I/R injury suggesting its therapeutic potential.