Kidney Function Biomarkers Research Articles

Analyses of Kidney Biomarkers in Patients With SARS-CoV-2 (COVID-19)

The new coronavirus was first reported in China and caused a widespread global outbreak of pneumonia that spread rapidly across this country and many other countries. Acute kidney injury is one of the important complications of COVID-19, which has been shown in some cases. Exploring the diagnostic features of biomarkers of kidney function in COVID-19 patients may lead to better patient management. We collected laboratory data from 206 people with confirmed COVID-19 disease and evaluated their renal biomarkers, Blood Urea Nitrogen (BUN), and creatinine. The age range of the patients was almost 62 years old. The mean age in the dead patients and recovered patients was 71 and 54 years old, respectively. The average LDH value was 755 U/L, and creatine phosphokinase (CPK) was 267 U/L in the patients. The average BUN was 59.1 U/L, and creatinine was 1.5 U/L in COVID-2019 patients. Among all 193 patients, laboratory results revealed that 163 (85.4 %) patients had an elevated BUN level. Based on creatinine levels for total patients, laboratory results revealed that 49 (25.4 %) patients had an elevated value. The average BUN value in dead patients was 85 mg/dL, while in recovered patients was 40.5 mg/dL (P<0.0001). Also, the average creatinine level in dead patients was 1.86 mg/dL, while in recovered patients was 1.24 mg/dL (P=0.0004). Inflammation following COVID-19 disease causes kidney damage and elevated urea and creatinine levels, which may increase the risk of death in these patients.

Efficacy and safety of modified fasting therapy for weight loss in 2054 hospitalized patients.

The aim of this study was to evaluate the efficacy and safety of modified fasting therapy, and a retrospective study was conducted to analyze changes in clinical indicators of hospitalized fasting patients. A total of 2054 hospitalized fasting patients were enrolled in this observational study. All participants underwent 7 days of modified fasting therapy. The clinical efficacy biomarkers, safety indicators, and body composition were measured before and after fasting. The modified fasting therapy reduced body weight, BMI, abdominal circumference, systolic blood pressure, and diastolic blood pressure significantly. Blood glucose and indicators of body composition were improved to various extents (all p < 0.05). There was a small increase in liver function, kidney function, uric acid, electrolytes, blood count, coagulation, and uric biomarkers. Subgroup analysis results showed that cardiovascular diseases benefited from modified fasting therapy. At present this study is the largest retrospective population-based study about modified fasting therapy. The results from 2054 patients showed that the modified fasting therapy lasting 7 days was efficient and safe. It led to improvements in physical health and body weight-associated indicators, as well as body composition and relevant cardiovascular risk factors.

Sex differences in associations between creatinine and cystatin C-based kidney function measures with stroke and major bleeding.

We sought to explore whether adding kidney function biomarkers based on creatinine (eGFRCr), cystatin C (eGFRCys) or a combination of the two (eGFRCr-Cys) could improve risk stratification for stroke and major bleeding, and whether there were sex differences in any additive value of kidney function biomarkers. We included participants from the UK Biobank who had not had a previous ischaemic or haemorrhagic stroke or major bleeding episode, and who had kidney function measures available at baseline. Cause-specific Cox proportional hazards models tested associations between eGFRCr, eGFRCys and eGFRCr-Cys (mL/min/1.73 m2) with ischaemic and haemorrhagic stroke, major bleeding (gastrointestinal or intracranial, including haemorrhagic stroke) and all-cause mortality. Among 452,879 eligible participants, 246,244 (54.4%) were women. Over 11.5 (IQR 10.8-12.2) years, there were 3706 ischaemic strokes, 795 haemorrhagic strokes, 26,025 major bleeding events and 28,851 deaths. eGFRCys was more strongly associated with ischaemic stroke than eGFRCr: an effect that was more pronounced in women (men - HR: 1.16, 95% CI: 1.12-1.19; female to male comparison - HR: 1.11, 95% CI: 1.05-1.16, per 10 mL/min/1.73 m2 decline in eGFRCys). This interaction effect was also demonstrated for eGFRCr-Cys, but not eGFRCr. eGFRCys and eGFRCr-Cys were more strongly associated with major bleeding and all-cause mortality than eGFRCr in both men and women. Event numbers were small for haemorrhagic stroke. To a greater degree than is seen in men, eGFRCr underestimates risk of ischaemic stroke and major bleeding in women compared to eGFRCys. The difference between measures is likely explained by non-GFR biology of creatinine and cystatin C. Enhanced measurement of cystatin C may improve risk stratification for ischaemic stroke and major bleeding and clinical treatment decisions in a general population setting, particularly for women.

In vivo experimentally study the effect of Nigella Sativa silver nanoparticles for treatment of salmonella species causing diarrhea in ruminants

Salmonellais one of the main etiological agents of infectious diarrhea in large and small ruminants but emergence of multidrug-resistant (MDR) strains faster rate than previously, leads to develop of MDR strains among animals needs different alternative therapeutic strategies. Our study was aimed to evaluate the effects of Nigella sativa silver nanoparticles (NS AgNPs) on specific pathogen-free (SPF) Wister rats. Nigella sativa silver nanoparticles were prepared and confirmed their formation by optical observations, UV–Vis spectroscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Rats in group G2 were infected experimentally with Salmonella spp and treated with ciprofloxacin orally for duration of 6 days at a dose rat 10 mg/kg. On the other hand, rats in group G1 were infected with salmonella and treated for 20 days with NS AgNPs in oral dose of (10 mg/kg rats), and the results were compared to control groups G3 which received bacterial infection without treatment and G4 control negative. The results of optical observation, UV–Vis spectroscopy, TEM, and SEM revealed typical characteristics of prepared NS AgNPs. Liver, kidney function biomarkers, hematologic analysis, and histological examination the tissues of liver, kidney, and stomach of rat's model improved that NS AgNPs has antimicrobial effect and has the ability to decrease the inflammatory reaction caused by Salmonella spp infection. The results of our study indicate that NS AgNPs are effective in controlling MDR Salmonella spp in vivo without causing any adverse effects. Moreover, our findings suggest that reducing the use of antimicrobials could be a key factor in the fight against antimicrobial resistance and can provide valuable insights into identifying the most appropriate treatment strategies to tackle this issue effectively in the future.

Association of Kidney Tubule Biomarkers With Cardiac Structure and Function in the Multiethnic Study of Atherosclerosis

Markers of glomerular disease, estimated glomerular filtration rate (eGFR) and albuminuria, are associated with cardiac structural abnormalities and incident cardiovascular disease (CVD). We aimed to determine whether biomarkers of kidney tubule injury, function, and systemic inflammation are associated with cardiac structural abnormalities. Among 393 Multi-Ethnic Study of Atherosclerosis participants without diabetes, CVD, or chronic kidney disease, we assessed the association of 12 biomarkers of kidney tubule injury, function, and systemic inflammation with the left ventricular mass/volume ratio (LVmvr) and left ventricular ejection fraction (LVEF) on cardiac magnetic resonance imaging using linear regression. The average age was 60 ± 10years; 48% were men; mean eGFR was 96±16ml/min/1.73m2; mean LVmvr was 0.93±0.18g/ml, and mean LVEF was 62±6%. Each twofold greater concentration of plasma soluble urokinase plasminogen activator receptor was associated with a 0.04g/ml (95% confidence interval [CI] 0.01 to 0.08 g/ml) higher LVmvr and 2.1% (95% CI 0.6 to 3.5%) lower LVEF, independent of risk factors for CVD, eGFR, and albuminuria. Each twofold greater plasma monocyte chemoattractant protein 1 was associated with higher LVmvr with a similar coefficient to that of plasma soluble urokinase plasminogen activator receptor. Each twofold greater concentration of plasma chitinase-3-like protein 1 and urine alpha-1-microglobulin was associated with a 1.1% (95% CI 0.4 to 1.7%) and 1.2% (95% CI 0.2 to 2.2%) lower LVEF, respectively. In conclusion, abnormal kidney tubule health may lead to cardiac dysfunction above and beyond eGFR and albuminuria.

Investigation of N,N,N-Trimethyl-L-alanyl-L-proline Betaine (TMAP) as a Biomarker of Kidney Function.

Glomerular filtration rate (GFR) is the most widely used tool for the measurement of kidney function, but endogenous biomarkers such as cystatin C and creatinine have limitations. A previous metabolomic study revealed N,N,N-trimethyl-L-alanyl-L-proline betaine (TMAP) to be reflective of kidney function. In this study, we developed a quantitative LCMS assay for the measurement of TMAP and evaluated TMAP as a biomarker of GFR. An assay to measure TMAP was developed using liquid chromatography-mass spectrometry. After validation of the method, we applied it to plasma samples from three distinct kidney disease patient cohorts: nondialysis chronic kidney disease (CKD) patients, patients receiving peritoneal and hemodialysis, and living kidney donors. We investigated whether TMAP was conserved in other mammalian and nonmammalian species, by analyzing plasma samples from Wistar rats with diet-induced CKD and searching for putative matches to the m/z for TMAP and its known fragments in the raw sample data repository "Metabolomics Workbench". The assay can measure plasma TMAP at a lower limit of quantitation (100 ng/mL) with an interday precision and accuracy of 12.8 and 12.1%, respectively. In all three patient cohorts, TMAP concentrations are significantly higher in patients with CKD than in controls with a normal GFR. Further, TMAP concentrations are also elevated in rats with CKD and TMAP is present in the sap produced from Acer saccharum trees. TMAP concentration is inversely related to GFR suggesting that it is a marker of kidney function. TMAP is present in nonmammalian species suggesting that it is part of a biologically conserved process.

Cardiovascular risk and kidney function profiling using conventional and novel biomarkers in young adults: the African-PREDICT study

BackgroundLow- and middle-income countries experience an increasing burden of chronic kidney disease. Cardiovascular risk factors, including advancing age, may contribute to this phenomenon. We (i) profiled cardiovascular risk factors and different biomarkers of subclinical kidney function and (ii) investigated the relationship between these variables.MethodsWe cross-sectionally analysed 956 apparently healthy adults between 20 and 30 years of age. Cardiovascular risk factors such as high adiposity, blood pressure, glucose levels, adverse lipid profiles and lifestyle factors were measured. Various biomarkers were used to assess subclinical kidney function, including estimated glomerular filtration rate (eGFR), urinary albumin, uromodulin and the CKD273 urinary proteomics classifier. These biomarkers were used to divide the total population into quartiles to compare extremes (25th percentiles) on the normal kidney function continuum. The lower 25th percentiles of eGFR and uromodulin and the upper 25th percentiles of urinary albumin and the CKD273 classifier represented the more unfavourable kidney function groups.ResultsIn the lower 25th percentiles of eGFR and uromodulin and the upper 25th percentile of the CKD273 classifier, more adverse cardiovascular profiles were observed. In multi-variable adjusted regression analyses performed in the total group, eGFR associated negatively with HDL-C (β= -0.44; p < 0.001) and GGT (β= -0.24; p < 0.001), while the CKD273 classifier associated positively with age and these same risk factors (age: β = 0.10; p = 0.021, HDL-C: β = 0.23; p < 0.001, GGT: β = 0.14; p = 0.002).ConclusionAge, lifestyle and health measures impact kidney health even in the third decade.

Actinidia deliciosa as a complemental therapy against nephropathy and oxidative stress in diabetic rats

This study aimed to evaluate the anti-hyperglycemic and antioxidant role of Actinidia deliciosa (kiwifruits) aqueous extract in streptozotocin-treated rats. Animals were distributed into; control, A. deliciosa aqueous extract (ADAE; 1 g/kg orally), streptozotocin (STZ; 50 mg/kg, i.p, single dose), and STZ plus ADAE, respectively. Results showed that ADAE had high antioxidant and radical scavenging potency. Elevation in blood sugar level, lipid peroxidation (LPO), kidney function biomarkers, and perturbations in hematological parameters were observed in diabetic rats. While, enzymatic and non-enzymatic antioxidants, protein content, and alkaline phosphatase (ALP) activity declined. Furthermore, histological, immunohistochemical alpha-smooth muscle actin immunoreactivity (α-SMA-ir) and histochemical (collagen, total protein, DNA, and RNA) alterations were observed in rat kidneys. Moreover, STZ produced upregulation of inflammatory associated genes (tumor necrosis factor-alpha; TNF-α and transforming growth factor β1; TGF-β1) and triggered apoptosis by upregulating apoptotic related gene [Bcl2-associated X protein (Bax)] and downregulating anti-apoptotic related gene B-cell lymphoma-2 (Bcl-2) based on real-time PCR data. Moreover, diabetic rats administered with ADAE showed significant restoration in LPO, antioxidant status, and biochemical indices besides tissue architecture, and genes improvement regarding STZ group. Conclusively, A. deliciosa has a valuable ameliorative influence and can restore glucose levels and improve kidney dysfunction in diabetic rats.

Apocynin abrogates methotrexate-induced nephrotoxicity: role of TLR4/NF-κB-p65/p38-MAPK, IL-6/STAT-3, PPAR-γ, and SIRT1/FOXO3 signaling pathways.

The present study was designed to evaluate the potential renoprotective impacts of apocynin (APC) against nephrotoxicity induced by methotrexate (MTX) administration. To fulfill this aim, rats were allocated into four groups: control; APC (100mg/kg/day; orally); MTX (20mg/kg; single intraperitoneal dose at the end of the 5th day of the experiment); and APC +MTX (APC was given orally for 5 days before and 5 days after induction of renal toxicity by MTX). On the 11th day, samples were collected to estimate kidney function biomarkers, oxidative stress, pro-inflammatory cytokines, and other molecular targets. Compared to the MTX control group, treatment with APC significantly decreased urea, creatinine, and KIM-1 levels and improved kidney histological alterations. Furthermore, APC restored oxidant/antioxidant balance, as evidenced by a remarkable alleviation of MDA, GSH, SOD, and MPO levels. Additionally, the iNOS, NO, p-NF-κB-p65, Ace-NF-κB-p65, TLR4, p-p38-MAPK, p-JAK1, and p-STAT-3 expressions were reduced, while the IκBα, PPAR-γ, SIRT1, and FOXO3 expressions were significantly increased. In NRK-52E cells, MTX-induced cytotoxicity was protected by APC in a concentration-dependent manner. In addition, increased expression of p-STAT-3 and p-JAK1/2 levels were reduced in MTX-treated NRK-52E cells by APC. The in vitro experiments revealed that APC-protected MTX-mediated renal tubular epithelial cells were damaged by inhibiting the JAK/STAT3 pathway. Besides, our in vivo and in vitro results were confirmed by predicting computational pharmacology results using molecular docking and network pharmacology analysis. In conclusion, our findings proved that APC could be a good candidate for MTX-induced renal damage due to its strong antioxidative and anti-inflammatory bioactivities.

Abstract P173: Proteomic Assessment of Progressive Chronic Renal Insufficiency Risk and Mortality in a Heart Failure Community Study

Introduction: Over six million U.S. adults have heart failure (HF). Evaluation of kidney function is critical to the care of patients with HF but may not be fully captured by traditional measures, such as estimated glomerular filtration rate (eGFR) or the Meta-Analysis Global Group in Chronic HF (MAGGIC) risk score. Identifying patients at highest risk of progressive chronic renal insufficiency (PCRI) may improve risk stratification in HF, beyond these traditional measures. High-throughput proteomics has allowed for the development of PCRI risk scores based on novel kidney function biomarkers. However, the prognostic value of a proteomic-based PCRI risk score in HF has not been explored. Hypothesis: Proteomic-based PCRI risk scores will improve risk stratification in HF. Methods: Clinical data and plasma were collected from 1,389 patients in a HF community cohort from Southeastern Minnesota (2003-2012). Results from the aptamer-based technology SomaScan® were used to derive PCRI risk scores using the SomaSignal™ Kidney Prognosis test, a protein-based algorithm developed to predict risk of PCRI within four years. Cox proportional hazard models were used to estimate the association between quintiles of PCRI and mortality, after adjustment for the MAGGIC score. Results: PCRI risk scores were available for 1,349 patients who were on average 75±13 years of age, 48% female, and had a median eGFR of 57 mL/min/1.73m 2 . There was a positive association with mortality across PCRI risk quintiles, after adjustment for the MAGGIC score. (Figure). Overall, the highest quintile was associated over a two-fold higher risk of mortality compared with the lowest quintile (HR 2.3, 95% CI 1.8,2.8). The higher risk of mortality remained in analyses stratified by patients with (HR 1.5, 95% CI 1.1,2.1) and without (HR 2.2, 95% CI 1.4,3.5) an eGFR &lt;60 mL/min/1.73 m 2 . Conclusions: In this community HF cohort, proteomic-based PCRI risk scores improve risk stratification, independent of traditional measures of kidney function.

Abstract P430: Role of Cystatin C-based Estimated Glomerular Filtration Rate for Direct Oral Anticoagulant Dosing in Patients With Atrial Fibrillation

Introduction: Renal dose adjustment is imperative to appropriate direct oral anticoagulant (DOAC) prescribing among patients with atrial fibrillation (AF). Serum creatinine is routinely used to estimate GFR (eGFRcr) in clinical practice, but eGFRcr may be less accurate in certain settings. It is unknown whether other kidney function biomarkers, like cystatin C, is helpful to guide DOAC dosing. Hypothesis: Appropriate DOAC dosing by eGFRcr but supratherapeutic dosing by cystatin C-based eGFR (eGFRcys) is associated with bleeding, compared to appropriate dosing by both eGFRcr and eGFRcys. Methods: We conducted observational study from the SCREAM project, a healthcare utilization cohort of Stockholm, Sweden, during 2006-2018. We identified patients with AF on DOACs who had creatinine and cystatin C measured on the same day. We calculated eGFRcr with the 2021 Chronic Kidney Disease (CKD)-EPI and eGFRcys with 2012 CKD-EPI cystatin C equations. We estimated defined daily dose consumed per day and considered &lt;0.8 as a reduced dose. We separately classified supratherapeutic, subtherapeutic, and appropriate dosing by eGFRcr and eGFRcys, and examined the bleeding risk using Cox regression. Results: Among 5427 AF patients on DOACs, mean age (SD) was 76 (9) years and 43% were women. Compared to eGFRcr, eGFRcys identified more patients with CKD (61% for eGFRcys &lt;60 ml/min/1.73 m 2 vs. 35% for eGFRcr &lt;60 ml/min/1.73 m 2 ), as well as more patients with supratherapeutic dosing (7.9 vs. 2.4%). Among 3064 patients who were classified as appropriate dosing by eGFRcr, 312 (10.2%) were reclassified as supratherapeutic dosing by eGFRcys and had a higher risk of bleeding (hazard ratio=1.58, 95% CI: 1.03-2.42), compared with those who were classified as appropriate dosing by both eGFRcr and eGFRcys ( Table ). Conclusions: Appropriate DOAC dosing by eGFRcr but supratherapeutic dosing by eGFRcys was associated with a higher risk of bleeding. The findings suggest that eGFRcys may inform decisions on DOAC dosing.

Abstract P162: Sex Differences in Cardiometabolic Biomarkers During Pre-Diabetes

Background: Diabetes (DM) diminishes female protection against cardiovascular disease (CVD). Women with DM face excess CVD risk than men partly due to women’s greater deterioration in risk factors before DM. In this study, we compared sex differences in biomarkers that reflect distinct pathophysiological pathways during the pre-diabetes (pre-DM) stage. Method: A cross-sectional analysis was performed based on pooled data from Atherosclerosis Risk in Communities Study and the Jackson Heart Study. We used multivariable linear regressions to examine the associations between sex and biomarkers (log-transformed) representative of inflammation, lipoprotein, adipokine, kidney function, cardiac injury/stress, and thrombosis, adjusted for age, race, and BMI, among CVD-free individuals with pre-DM. We validated the results in a sensitivity analysis, including those that eventually progressed into DM during the follow-up. We used the false discovery rate method to adjust multiple comparisons. Results: Among 5975 individuals with pre-DM, the mean age was 54.2 years, 2853 (48%) were women, and 2022 (34%) were non-Hispanic blacks. In the adjusted models, inflammatory biomarkers, including high-sensitivity c-reactive proteins (β coefficient 0.2, P=2.9 x 10 -9 ), fibrinogen (β 0.19, P=2.8E-12), and absolute lymphocyte (β 0.25, P=2.54 x 10 -7 ), and cardiac injury/stress biomarker, NT-proBNT (β 0.14, P=0.0002) were higher in women than men with pre-DM. Additionally, lipoprotein(a) (β 0.19, P=4.96 x 10 -13 ) and apolipoproteins A1 (β 0.61, P=2.81x 10 -120 ), and adipokines including leptin (β 1.1, P=2.62 x 10 -123 ) and adiponectin (β 0.56, P=1.94 x 10 -12 ) were all higher in women with pre-DM. In contrast, kidney function markers, albumin (β -0.24, P=2.79 x 10 -9 ) and creatinine (β -1.1, P=1x 10 -100 ), and thrombosis biomarker, homocysteine (β -0.5, P=9.09 x 10 -19 ) were higher in men with pre-DM than in their women counterparts. These sex differences remained generally unchanged among 2320 individuals that progressed into DM. Conclusion: Biomarkers differ significantly between sexes during the pre-DM state. The inflammatory, lipoprotein, adipokine, and cardiac stress biomarkers were higher in women with pre-DM, while kidney function and thrombosis biomarkers were higher in men with pre-DM. Future mechanistic studies are warranted to delineate pathophysiological pathways characterized by these biomarkers contributing to sex disparities of CVD risk in DM.

Evaluation of Antidiabetic Effect of Luteolin in STZ Induced Diabetic Rats: Molecular Docking, Molecular Dynamics, In Vitro and In Vivo Studies

Despite the existence of modern antidiabetic medications, diabetes still affects millions of individuals worldwide, with a high death and disability rate. There has been a concerted search for alternative natural medicinal agents; luteolin (LUT), a polyphenolic molecule, might be a good choice, both because of its efficacy and because of it having fewer side effects, compared to conventional medicines. This study aims to explore the antidiabetic potential of LUT in diabetic rats, induced by streptozotocin (STZ; 50 mg/kg b.w.), intraperitoneally. The level of blood glucose, oral glucose tolerance test (OGTT), body weight, glycated hemoglobin A1c (HbA1c), lipidemic status, antioxidant enzymes, and cytokines were assessed. Also, its action mechanism was explored through molecular docking and molecular dynamics simulations. Oral supplementation of LUT for 21 days resulted in a significant decrease in the blood glucose, oxidative stress, and proinflammatory cytokine levels, and modulated the hyperlipidemia profile. LUT also ameliorated the tested biomarkers of liver and kidney function. In addition, LUT markedly reversed the damage to the pancreas, liver, and kidney cells. Moreover, molecular docking and molecular dynamics simulations revealed excellent antidiabetic behavior of LUT. In conclusion, the current investigation revealed that LUT possesses antidiabetic activity, through the reversing of hyperlipidemia, oxidative stress, and proinflammatory status in diabetic groups. Therefore, LUT might be a good remedy for the management or treatment of diabetes.

Electrolyte Imbalance Among Bangladeshi Patients With COVID-19.

Introduction Infection with SARS-CoV-2 begins in the lower respiratory tract, but COVID-19 often involves the renal system, resulting in serum electrolyte imbalance. Monitoring serum electrolyte levels and parameters of liver and kidney function is essential to understand disease prognosis. Objectives This study aimed to determine the effect of imbalances in serum electrolytes and other parameters on COVID-19 severity. Material and method This retrospective study comprised 241 patients, ages 14 years and older, including 186 patients who were moderately affected and 55 who were categorized as severely affected by COVID-19. Serum electrolytes (sodium (Na+), potassium (K+), and chloride (Cl-)) and biomarkers of kidney and liver function (creatinine and alanine aminotransferase (ALT)) were measured and correlated with disease severity. This research was conducted among admitted patients of Holy Family Red Crescent Medical College Hospital designated into two groups based on retrospective hospital records. Individuals with moderate illness had evidence of lower respiratory tract infection (cough, cold, breathless, etc.) during clinical assessment or imaging (chest X-ray and computed tomography (CT) scan of the lungs) and have an oxygen saturation by pulse oximetry (SpO2) ≥ 94% on room air at sea level. The severely ill group involved individuals with SpO2 ≤94% on room air at sea level and respiratory rate ≥ 30 breaths/minute, and critically ill patients are those who needed mechanical ventilation or required intensive care unit (ICU) care. This categorization was based on the Coronavirus Disease 2019 (COVID-19) Treatment Guidelines (https://www.covid19treatmentguidelines.nih.gov/about-the-guidelines/whats-new/). Results Average Na+and creatinine increased by 2.30 parts (95% confidence interval (CI) = 0.20, 4.81, P = 0.041) and 0.35 units (95% CI = 0.03, 0.68, P = 0.043) in severe cases compared with moderate cases. Older participants had relatively Na+lowered to -0.06 parts (95% CI = -0.12, -0.001, P = 0.045), significant Cl- reduction by 0.09 units (95% CI = -0.14, -0.04, P = 0.001), and ALT by 0.47 units (95% CI = -0.88, -0.06, P = 0.024), whereas serum creatinine was increased by 0.01 parts (95% CI = 0.001, 0.02, P = 0.024). The creatinine and ALT of COVID-19 participants were significantly higher in males by 0.34 units and 23.2 units, respectively,compared with females. In severe COVID-19 cases compared with moderate cases, the risks of hypernatremia, elevated chloride levels, and elevated serum creatinine levels were increased by 2.83-fold (95% CI = 1.26, 6.36, P = 0.012), 5.37-fold (95% CI = 1.90, 15.3, P = 0.002), and 2.00-fold (95% CI = 1.08, 4.31, P = 0.039), respectively. Conclusion Serum electrolyte and biomarker levels can serve as good indicators of the condition and disease prognosis of patients with COVID-19. Our purpose in this study was to determine the association between serum electrolyte imbalance and disease severity. We collected data from ex post facto hospital records and did not intend to assess the mortality rate. Consequently, this study expects that the prompt diagnosis of electrolyte disparity or disturbance possibly minimizes COVID-19-related morbidity and mortality.

Exposure to oxyfluorfen-induced hematobiochemical alterations, oxidative stress, genotoxicity, and disruption of sex hormones in male African catfish and the potential to confront by Chlorella vulgaris

The present study evaluated the effect of chronic exposure to oxyfluorfen (OXY) on different physiological responses of male African catfish, Clarias gariepinus, and the ameliorative effect of Chlorella vulgaris. The fish (160 ± 5.10 g) were exposed to 1/20 LC50 of OXY (0.58 mg/L) for 60 consecutive days with or without co-administration of C. vulgaris (25 g/kg diet) in triplicate groups. The results revealed that chronic exposure to a sublethal level of OXY induced severe anemia and leukopenia. OXY-exposed fish experienced hypoproteinemia, marked lower AchE levels, and a significant increase in glucose, liver, and kidney function biomarkers. The DNA fragmentation of the liver increased by 15 % in fish compared to the control. On the other hand, lipid peroxidation, superoxide dismutase, and catalase activities were markedly increased in the liver and testes homogenates of the OXY-exposed fish. Meanwhile, total antioxidant capacity and glutathione S-transferase levels declined in the same tissues. Exposure to OXY induced a significant reduction in testosterone and luteinizing hormone levels and a significant increase in follicle stimulating hormone and estradiol. Meanwhile, C. vulgaris dietary supplementation succeeded in alleviating the negative impact of OXY on hematobiochemical parameters and restoring the antioxidant balance in the liver and testes. Furthermore, it ameliorated endocrine disruption and repaired sex hormone levels. In conclusion, exposure to OXY could induce systemic stress, oxidative stress, and endocrine disruption in male C. gariepinus. The dietary supplementation of C. vulgaris could be a potential protective strategy against the toxicity of OXY.

The Effect of Melissa officinalis Hydro Alcoholic Extract on Liver Enzymes, Markers of Kidney Function and Testosterone in Lead Poisoned Rats

Background: Lead, one of the most important environmental pollutants, can induce a broad range of physiological dysfunction. The aim of this study was to investigate the protective effect of the Melissa officinalis plant extract on biomarkers of liver and kidney function as well as serum testosterone concentration in lead-exposed male rats. Methods: We used 40 Wistar rats and divided them into 5 groups. The control group received saline (1 mL/kg) by gastric gavage and 30 minutes later received saline (1 mL/kg) through i.p injection. The lead group received saline (1 mL/kg) by gastric gavage and 30 minutes later received i.p injection of lead acetate (20 mg/kg). The treatment groups received different doses of M. officinalis alcoholic extract (20, 100, and 500 mg/kg, respectively) by gastric gavage and 30 min later received i.p injection of lead acetate (20 mg/kg). The rats were treated for 5 days and then twenty -four hours after the last injection, blood samples were collected for the measurement of urea, creatinine, uric acid, alanine transaminase (ALT), alkaline phosphatase (ALP), aspartate transaminase (AST) and testosterone. Data analysis was performed through SPSS (version 16). Results: Melissa extract (100 mg/kg) significantly reduced liver enzymes and kidney function markers when compared to the lead group. Treatment with Melissa extract (100 mg/kg and 500 mg/kg) significantly increased serum testosterone concentration compared to the lead group. Conclusion: The biochemical results of this study showed that M. officinalis may be beneficial in lead-induced liver and kidney dysfunction.

Investigation of admission serum creatinine as a predictor of hospital length of stay in triple-vaccinated COVID-19 inpatients.

This study assessed the association between admission kidney function and the duration of hospitalization in triple-vaccinated coronavirus disease 2019 (COVID-19) inpatients during the omicron surge in Larissa, central Greece. Regression analysis was used to estimate the effect of kidney function biomarkers on hospital length of stay (LoS) within a dataset from a cohort of 51 subjects. Sex- and age-adjusted admission serum creatinine was associated with hospital LoS (p=0.034). Serum creatinine concentration on admission should be further evaluated as a possible clinical predictor of hospital LoS among triple-vaccinated COVID-19 inpatients both at the country and global level.

Balancing renal Ang-II/Ang-(1–7) by xanthenone; an ACE2 activator; contributes to the attenuation of Ang-II/p38 MAPK/NF-κB p65 and Bax/caspase-3 pathways in amphotericin B-induced nephrotoxicity in rats

Despite the great importance of amphotericin B for the management of life-threatening systemic fungal infections, its nephrotoxic effect restricts its repeated administration. This study was designed to examine the prospective modulatory effects of xanthenone, an ACE2 activator, against amphotericin B nephrotoxicity. Male Wistar rats were allocated into four groups; control (1st), Xanthenone (2nd), Amphotericin B (3rd), and Xanthenone + Amphotericin B (4th). The second and fourth groups received xanthenone (2 mg/kg; s.c.) daily for 14 consecutive days. Amphotericin B (18.5 mg/kg; i.p.) was administered to the third and fourth groups daily starting from day 8. After two weeks, samples were withdrawn for analysis. The histopathological findings, molecular and biochemical markers showed that amphotericin B caused marked renal injury. Pretreatment with xanthenone ameliorated amphotericin B-induced deterioration in kidney function biomarkers (creatinine, urea, cystatin C, KIM-1) and guarded against the disturbance of serum electrolytes (Na+, K+, Mg2+) due to amphotericin B-induced tubular dysfunction. Besides, the ACE2 activator xanthenone balanced renal Ang-II/Ang-(1–7), and so the inflammatory signaling p38 MAPK/NF-κB p65 and its downstream inflammatory cytokines (TNF-α, IL-6) were attenuated. Meanwhile, the anti-oxidant signaling Nrf2/HO-1 and glutathione content were preserved, but the lipid peroxidation marker MDA was declined. These regulatory effects of xanthenone eventually enhanced Bcl-2 (anti-apoptotic), but reduced Bax (pro-apoptotic) and cleaved caspase-3 (apoptotic executioner) protein expressions. Collectively, the regulatory effects of xanthenone on renal Ang-II/Ang-(1–7) could at least partially contribute to the mitigation of amphotericin B nephrotoxicity by attenuating inflammatory signaling, oxidative stress, and apoptosis, thus improving the tolerability to amphotericin B.

Plasma Trimethylamine N-Oxide Levels Are Associated with Poor Kidney Function in People with Type 2 Diabetes

Previous studies have linked elevated plasma trimethylamine N-oxide (TMAO) levels to poor renal function. The relationship between TMAO and chronic kidney disease (CKD) in type 2 diabetes (T2D) is still unclear. We investigated the association between plasma TMAO levels and CKD in patients with T2D. A cross-sectional study of 133 patients with T2D with or without CKD has been conducted. Blood biomarkers of kidney function, diabetes, and inflammation were assessed in the study participants. Plasma TMAO levels were quantified using UPLC-MS/MS. People with T2D and CKD exhibited significantly higher plasma TMAO levels [10.16 (5.86-17.45) µmol/L] than those without CKD [4.69 (2.62-7.76) µmol/L] (p = 0.002). Participants in the highest quartile of TMAO levels (>8.38 µmol/L) presented relatively elevated serum creatinine levels and a higher number of people with CKD than those in the lower quartiles. TMAO levels were significantly correlated with kidney function biomarkers, including estimated glomerular filtration rate and urinary albumin to creatinine ratio. The association between TMAO and CKD was evident (p < 0.0001) and remained significant after adjusting for risk factors of kidney disease, including age, gender, body mass index, duration of diabetes, and smoking. These findings suggest the association between plasma TMAO and CKD in patients with T2D.

Sensitive electrochemical detection of creatinine based on electrodeposited molecular imprinting polymer modified screen printed carbon electrode

Creatinine (Crn) is an important biomarker for kidney function, and early detection could help to avoid end-stage renal disease. In this study, a label-free and ultra-selective platform was developed for Crn detection by modifying the screen-printed carbon electrode (SPCE) with the copper nanoparticle integrated with poly (methyl methacrylate-co-divinylbenzene) molecularly imprinted polymer (Cu2O@MIP) by the electrodeposition method. The synthesized Cu2O@MIP was investigated by transmission electron microscopy (TEM), atomic force microscopy (AFM), fourier transform infrared spectroscopy (FT-IR), cyclic voltammetry, and electrochemical impedance spectroscopy (EIS). In addition, response surface methodology (RSM) is used to optimize the effects of potential and time intervals to increase its sensitivity. Under optimized conditions, Crn was determined in the presence of other interferences to be 2.16 AnM−1cm−2 and the limit of detection (LOD) was 22 nM. The sensor platform showed a response in the nanomolar range of 0–75 nM. The developed non-enzymatic electrochemical sensing responded well to Crn, and is highly specific without any significant compromise to non-specific macromolecules found in urine which presents a promising platform for the development of potable kidney disease detectors.