Kidney Function Biomarkers Research Articles

Proenkephalin A 119-159 in Perioperative and Intensive Care-A Promising Biomarker or Merely Another Option?

Acute kidney injury (AKI) is a severe and prevalent syndrome, primarily observed in intensive care units (ICUs) and perioperative settings. The discovery of a new biomarker for kidney function and injury, capable of overcoming the limitations of traditional markers, has the potential to improve the diagnosis and management of AKI. Proenkephalin A 119-159 (PENK) has emerged as a novel biomarker for AKI and has been validated in various clinical settings. It has demonstrated a faster response to AKI compared to creatinine and has been shown to predict successful weaning from renal replacement therapy in the ICU. PENK has also shown promise as an AKI biomarker in perioperative patients. Additionally, PENK has been proven to be effective in estimating mortality and morbidity in patients undergoing cardiac surgery, and those with traumatic brain injury or ischemic stroke. Incorporating PENK into a novel estimation of the glomerular filtration rate, referred to as the PENK-Crea equation, has yielded promising results.

Saroglitazar ameliorates 5- Fluorouracil-induced hepatorenal damage in rats

RationaleHepatotoxicity and nephrotoxicity are significant adverse effects caused in cancer patients treated with 5-Flurouracil (5-FU), a pyrimidine analogue anti-metabolite anticancer drug. The purpose of this research was to evaluate the impact of PPAR α/γ agonist (Saroglitazar; SARO) on 5-FU-induced hepatorenal damage in rats. MethodsMale rats were randomly assigned to four groups: control, 5-FU, 5-FU + SARO (2 mg/kg), and 5-FU + SARO (4 mg/kg). Rats received 75 mg/kg 5-FU intraperitoneally once weekly for three weeks. Saroglitazar (2 and 4 mg/kg/day) was orally supplied by oral syringe for three consecutive weeks. On day 22, rats were euthanized and their livers and kidneys were subjected to morphological, biochemical, histological, and immunohistochemical analysis. ResultsSaroglitazar treatment significantly decreased serum liver and kidney function biomarkers. In addition, it successfully modulated liver and kidney levels of inflammatory mediators and markers (NF-κB P65, TNF-α, cleaved caspase-1, IL-1β and p-p38 MAPK) and oxidative stress-related parameters (MDA, GSH, SOD, Keap1, Nrf-2 and HO-1) in a dose dependent manner. Furthermore, SARO could attenuate 5-FU-induced activation of cleaved caspase-3 as well as improved histopathological examination of both liver and kidney tissues. Significance: Saroglitazar may be a viable therapy option for 5-FU toxicity as it halts the interaction network of NF-kB and Nrf2 signaling pathways and apoptosis.

Phenotyping Kidney Function in Young Adults With High Blood Pressure: The African-PREDICT Study.

Biomarkers of kidney function, including glomerular, tubular, and fibrotic markers, have been associated with blood pressure in elderly populations and individuals with kidney and cardiovascular diseases. However, limited information is available in young adults. In this study, we compared levels of several kidney function biomarkers between normotensive and hypertensive young adults and explored the associations of these biomarkers with blood pressure within these groups. In this cross-sectional assessment, twenty-four-hour (24-h) blood pressure measurements of 1055 participants (mean age=24.6years) were used to classify hypertension as per the 2018 ESC/ESH guidelines. Biomarkers of kidney function included estimated glomerular filtration rate, urinary albumin, alpha-1 microglobulin (uA1M), neutrophil gelatinase-associated lipocalin (uNGAL), uromodulin (uUMOD), and the CKD273 classifier. All urinary biomarkers, except for the CKD273 classifier, were standardized for urinary creatinine (Cr). In the hypertensive group (61.0% White; 73.2% men), urinary albumin-to-creatinine ratio (uACR), uNGAL/Cr and uUMOD/Cr were lower than the normotensive group. In multiple regression analyses, 24-h systolic blood pressure (SBP) (β=0.14; p=0.042), 24-h diastolic blood pressure (DBP) (β=0.14; p=0.040), and 24-h mean arterial pressure (MAP) (β=0.16; p=0.020) associated positively with uA1M/Cr in the hypertensive group, while 24-h MAP positively associated with uACR (β=0.17; p=0.017). In exploratory factor analysis, positive associations of 24-h DBP and 24-h MAP with a factor pattern including tubular biomarkers were observed in the hypertensive group (24-h DBP: β=0.18; p=0.026, 24-h MAP: β=0.17; p=0.032). In the setting of hypertension, high perfusion pressure in the kidneys may play a role in the development of proximal tubule damage and promote early deterioration in kidney function in young adults. Trial Registration: ClinicalTrials.gov identifier: NCT03292094.

Relationship between phthalate exposure and kidney function in Taiwanese adults as determined through covariate-adjusted standardization and cumulative risk assessment

Few studies have investigated the associations between phthalate exposure and kidney function indicators in adults by simultaneously performing covariate-adjusted creatinine standardization, cumulative risk assessment, and mixture analysis. Thus, we applied these methods simultaneously to investigate the aforementioned associations in an adult population. This cross-sectional study analyzed data (N = 839) from a community-based arm of the Taiwan Biobank. The levels of 10 urinary phthalate metabolites were measured and calculated as the sum of the molar concentrations of the dibutyl phthalate metabolite (ΣDBPm) and di(2-ethylhexyl) phthalate (DEHP) metabolite (ΣDEHPm). The hazard index (HI) and daily intake (DI) were estimated by measuring the urinary levels of the phthalate metabolite. Kidney function biomarkers were assessed by measuring the following: blood urea nitrogen (BUN), uric acid, the albumin-to-creatinine ratio (ACR), and the estimated glomerular filtration rate (eGFR). Generalized linear models were implemented to examine the associations between exposure to individual phthalates, HI scores, and kidney function biomarkers. We also employed Bayesian kernel machine regression (BKMR) to analyze the relationships between exposure to various combinations of phthalates and kidney function. ΣDEHPm levels were significantly and positively associated with BUN and ACR levels, and ΣDBPm levels were positively associated with ACR levels. In addition, eGFR was negatively associated with ΣDBPm and ΣDEHPm levels. In the BKMR model, a mixture of 10 phthalate metabolites was significantly associated with BUN, uric acid, ACR, and eGFR results. Higher DIDEHP and higher DIDnBP values were significantly associated with lower eGFRs and higher ACRs, respectively. Higher DIDiBP and DIDEP values were significantly associated with higher uric acid levels. A higher HI was significantly associated with lower eGFRs and higher ACRs. Our results suggest that exposure to environmental phthalates is associated with impaired kidney function in Taiwanese adults.

Association of dementia with impaired kidney function and plasma biomarkers: A population-based study.

Emerging evidence has linked impaired kidney function with dementia in older adults, but the neuropathological pathways underlying their association remain poorly understood. We sought to examine the relationships of kidney function with dementia and plasma biomarkers in a Chinese rural population. This population-based study used data from the baseline examination of the Multimodal Interventions to Delay Dementia and Disability in rural China (MIND-China) cohort (March-September 2018; n = 5715). Kidney function was assessed using estimated glomerular filtration rate (eGFR) based on serum creatinine level. Dementia, Alzheimer's disease (AD) and vascular dementia (VaD) were diagnosed according to the international criteria. Plasma biomarkers were measured using the SIMOA platform in a subsample (n = 1446). Data were analyzed using logistic, general linear, and mediation models. Of the 5715 participants, 306 were diagnosed with dementia, including 195 with AD and 100 with VaD. Impaired kidney function (eGFR <60 vs. ≥90 mL/min/1.73 m2) was associated with multivariable-adjusted odds ratios of 2.24 (95% confidence interval [CI] 1.44-3.46) for all-cause dementia, 1.85 (1.07-3.18) for AD, and 2.49 (1.16-5.22) for VaD. In the biomarker subsample, impaired kidney function was significantly associated with higher plasma amyloid-β (Aβ)40 (β-coefficient = 54.36, 95% CI 43.34-65.39), Aβ42 (β-coefficient = 3.14, 95% CI 2.42-3.86), neurofilament light chain (β-coefficient = 10.62, 95% CI 5.62-15.62), and total tau (β-coefficient = 0.68, 95% CI 0.44-0.91), and a lower Aβ42/Aβ40 ratio (β-coefficient = -4.11, 95% CI -8.08 to -0.14). The mediation analysis showed that plasma total tau significantly mediated 21.76% of the association between impaired kidney function and AD (p < 0.05). Impaired kidney function is associated with dementia and plasma biomarkers among rural-dwelling older Chinese adults, and the association with AD is partly mediated by plasma biomarkers for neurodegeneration.

Understanding Cisplatin Pharmacokinetics and Toxicodynamics to Predict and Prevent Kidney Injury.

Cisplatin is a common platinum-based chemotherapeutic that induces acute kidney injury (AKI) in about 30% of patients. Pharmacokinetic/toxicodynamic (PKTD) models of cisplatin-induced AKI have been used to understand risk factors and evaluate potential mitigation strategies. While both traditional clinical biomarkers of kidney function [e.g. serum creatinine (SCr), blood urea nitrogen (BUN), estimated glomerular filtration rate (eGFR), and creatinine clearance (CrCl)] and newer subclinical biomarkers of kidney injury [e.g. urinary kidney injury molecule 1 (KIM-1), beta-2 microglobulin (B2M), neutrophil gelatinase-associated lipocalin (NGAL), calbindin, etc.] can be used to detect cisplatin-induced AKI, published PKTD models are limited to using only traditional clinical biomarkers. Previously identified risk factors for cisplatin nephrotoxicity have included dose, age, sex, race, body surface area, genetics, concomitant medications, and comorbid conditions. However, the relationships between concentrations and PK of platinum and biomarkers of kidney injury have not been well elucidated. This review discusses the evaluation of cisplatin-induced nephrotoxicity in clinical studies, mouse models, and in vitro models, and examines the available human PK and TD data. Improved understanding of the relationships between platinum PK and TD, in the presence of identified risk factors, will enable the prediction and prevention of cisplatin kidney injury. Significance Statement As cisplatin treatment continues to cause AKI in a third of patients, it is critical to improve the understanding of the relationships between platinum PK and nephrotoxicity as assessed by traditional clinical and contemporary subclinical TD markers of kidney injury. Prediction and prevention of cisplatin-induced nephrotoxicity will be advanced by the evolving development of PKTD models that incorporate kidney injury biomarkers with enhanced sensitivity and include covariates that can impact risk of developing cisplatin-induced AKI.

High-Performance Electrochemical Creatinine Sensors Based on β-Lead Dioxide/Single-Walled Carbon Nanotube Electrodes.

Creatinine is an important biomarker of kidney function and muscular metabolism. In this paper, we developed the β-lead dioxide/single-walled carbon nanotube (β-PbO2/CNT) and the β-PbO2/CNT ion-selective electrode (β-PbO2/CNT/ISE), which were used as highly sensitive potentiometric sensors for creatinine detection. The fabricated electrodes exhibited highly pH-sensitive characteristics due to the synergistic effect of the electrochemical properties of CNT and β-PbO2. Moreover, an ammonium-ion-selective membrane coating allowed the β-PbO2/CNT electrode to be NH4+-selective for direct detection of the ammonium ion. By exploiting the electrochemical characteristics of these electrodes, the creatinine assay was established through the one-step selective conversion of creatinine by creatinine deiminase, in which the OH- and NH4+ generated by the enzymatic reaction were detected using β-PbO2/CNT and β-PbO2/CNT/ISE electrodes as pH- and NH4+-responsive sensors, respectively. The total creatinine assay can be completed within ∼5 min. The assay results from β-PbO2/CNT and β-PbO2/CNT/ISE showed excellent sensitivity values of -75.56 and 64.62 mV in the detection range of 10-400 μM with a fast response (20 s), and the limits of detection were calculated to be 0.06 and 0.13 μM, respectively. Moreover, the developed creatinine sensor showed high selectivity against 11 interfering bio/chemical species with negligible interferences (selectivity coefficient <10-4) and excellent repeatability (>97% within 25 cycles) and long-term stability for 4 weeks of storage. In addition, the feasibility and practicality of the device were successfully demonstrated in human serum tests, with recoveries of 95-104% for PbO2/CNT and 92-110% for PbO2/CNT/ISE.

Effects of High-Intensity Training on Complete Blood Count, Iron Metabolism, Lipid Profile, Liver, and Kidney Function Tests of Professional Water Polo Players.

Our goal was to examine the effect of high-intensity physical activity on changes in the lipid profile, complete blood count (CBC), iron metabolism, and kidney and liver function tests of professional water polo players. This study included twenty professional male water polo players. Blood sampling was carried out at the beginning of the season and during periods of high-intensity training. CBCs were determined with a Siemens Advia 2120i hematology analyzer. A Beckman CoulterAU680 chemistry analyzer was used to determine the serum concentrations/activities of lipid profiles and liver and kidney function test analytes. The lipid athlete scores were also determined. The mean corpuscular volume (p = 0.006), platelet count (p = 0.008), and mean platelet volume (p < 0.001) significantly decreased during the high-intensity period, compared with the beginning of the season. The total iron-binding capacity increased (p = 0.001), and ferritin concentrations significantly declined (p = 0.017). The lipid profiles revealed a significant difference between phases, with slight increases in serum total (p = 0.025) and LDL cholesterol (p = 0.002) levels and a decrease in triglyceride concentrations (p = 0.040) in the high-intensity period. During the high-intensity period, the liver and kidney function tests showed a substantial positive effect on lactate dehydrogenase levels (p < 0.001), aspartate aminotransferase (p = 0.028) serum activity, and total protein concentrations (p = 0.033), compared with the beginning of the season. Water polo players might exhibit a decrease in some CBC parameters, an increase in LDL cholesterol, and a decrease in liver function biomarkers due to intense training at the peak of the competitive season. Kidney function biomarkers remain unchanged.

Correlation between salivary and serum biomarkers of kidney function in chronic kidney disease patients attending the nephrology clinics at Teaching Hospital Karapitiya, Sri Lanka

The present study was designed to determine the correlation between salivary and serum levels of creatinine and urea in patients with chronic kidney disease (CKD) and to propose the use of saliva as an alternative medium for the analysis of biochemical parameters of kidney function. Accordingly, an analytical cross-sectional study was carried out using 100 CKD patients attending the Nephrology Clinics at Teaching Hospital Karapitiya, Sri Lanka. Saliva and serum samples were collected from the patients for the estimation of creatinine and urea using spectrophotometric assay kits. Of the total, the majority of the patients were found within CKD stage 3 (82%). The salivary and serum concentrations of creatinine varied within the range of 0.20 - 2.10 mg/dL and 1.54 – 11.6 mg/dL, whereas the salivary and serum concentrations of urea varied within the range of 68.04 – 127.59 mg/dL and 60.14 – 168.25 mg/dL respectively within the study population. Significant positive correlations were observed between the salivary and serum concentrations of creatinine (r= 0.985, p=0.01), and urea (r= 0.942, p=0.01), and between salivary concentrations of creatinine and urea (r=0.887, p=0.01). A significant difference was observed in the salivary biomarkers between mild to moderate stages of CKD patients and severe to end-stage CKD patients. No significant association was observed in the salivary markers with the age and sex of the patients. The area under curve values in the receiver operating characteristic analysis was&gt;0.9 (95% CI). These findings revealed high levels of diagnostic accuracy in salivary biomarkers suggesting the potential use of saliva for the assessment of kidney function in CKD patients.

Acute changes in kidney function and outcomes following an acute myocardial infarction: Insights from PARADISE-MI.

Pharmacologic blockade of neurohormonal pathways in patients with acute myocardial infarction (MI) can result in acute changes in biomarkers of kidney function. We evaluated the effect of sacubitril/valsartan versus ramipril on initial changes in serum creatinine and the association of these changes with longer-term outcomes among participants in PARADISE-MI. In this randomized, double-blind, active-controlled, event-driven trial, 5661 patients with an acute MI were assigned to receive sacubitril/valsartan or ramipril, with no run-in. The frequency of an initial pre-specified increase in serum creatinine (≥26.5 or ≥44 μmol/L) from baseline to week 1 was compared between arms. Multivariable Cox regression models were fit to examine the association of acute changes in serum creatinine with the primary cardiovascular composite outcome (cardiovascular death, first heart failure hospitalization, or outpatient heart failure), all-cause mortality, and longer-term changes in estimated glomerular filtration rate (eGFR). An initial increase in serum creatinine ≥26.5 μmol/L occurred in 155 of 2604 (6.0%) patients assigned to sacubitril/valsartan and 120 of 2603 (4.6%) patients assigned to ramipril (odds ratio [OR] 1.32; 95% confidence interval [CI] 1.03-1.68). The corresponding numbers for an increase ≥44 μmol/L were 57 (2.2%) and 42 (1.6%), respectively (OR 1.37; 95% CI 0.92-2.05). A higher odds of increased serum creatinine ≥26.5 and ≥44 μmol/L for sacubitril/valsartan versus ramipril appeared to be restricted to patients who had a greater decline in systolic blood pressure over the same period (p-interaction = 0.05 and 0.001, respectively). In multivariable analyses, neither an acute increase in serum creatinine ≥26.5 or ≥44 μmol/L was associated with a higher risk of cardiovascular outcomes, all-cause mortality, or differences in longer-term eGFR slope. Findings were similar across the randomized treatment arms (p-interaction >0.6 for all). Following acute MI, patients assigned to sacubitril/valsartan had a higher frequency of initial increases in serum creatinine at 1 week, compared with ramipril. In adjusted models, initial increases in serum creatinine with either treatment were not associated with adverse cardiovascular outcomes or changes in longer-term kidney function.

Impacts of Plu kaow (Houttuynia cordata Thunb.) Ethanolic Extract on Diabetes and Dyslipidemia in STZ Induced Diabetic Rats: Phytochemical Profiling, Cheminformatics Analyses, and Molecular Docking Studies.

The increasing prevalence of diabetes and dyslipidemia poses significant health challenges, impacting millions of people globally and leading to high rates of illness and death. This study aimed to explore the potential antidiabetic and hypolipidemic effects of Plu kaow (Houttuynia cordata Thunb.) ethanolic extract (PK) in streptozotocin (STZ) induced diabetic rats, focusing on its molecular mechanisms. Diabetes was induced in fasting Long Evans rats using streptozotocin (65 mg/kg b. w.), with glibenclamide (5 mg/kg/day) used as the standard experimental drug. The treated groups received oral supplementation of PK (500 mg/kg/day) for 28 days. The study evaluated blood glucose levels, lipid status, body weight, liver, kidney, and heart function biomarkers, antioxidant activity, and histological examination of various organs. Additionally, untargeted metabolomics, cheminformatics, and molecular docking were employed to elucidate the probable mechanisms of action of PK. Based on metabolomic profiling data, the PK was found to contain various putative antidiabetic agents such as kaempferol 7-neohesperidoside, isochlorogenic acid C, rutin, datiscin, and diosmin and they have been proposed to significantly (p < 0.001) reduce blood glucose levels and modulated hyperlipidemia. PK also improved the tested liver, kidney, and heart function biomarkers and reversed damage to normal pancreatic, liver, kidney, and heart cells in histological analysis. In conclusion, PK shows promise as a potential treatment or management option for diabetes and hyperlipidemia, as well as their associated complications in diabetic rats.

A longitudinal assessment of heat exposure and biomarkers of kidney function on heat shock protein 70 and antibodies among agricultural workers

BackgroundExposure to extreme heat impacts millions of people worldwide and outdoor workers are among the populations most affected by hot temperatures. Heat stress induces several biological responses in humans, including the production of heat shock proteins (HSP) and antibodies against HSP (anti-HSP) which may play a central role in the body’s cellular response to a hot environment.ObjectiveThis longitudinal study investigated the impact of elevated temperatures and humidity on the presence of HSP70 and anti-HSP70 and examined relationships with markers of kidney function in an at-risk workforce under conditions of extreme heat and exertion in Guatemala.MethodsWe collected ambient temperature and relative humidity data as well as biomarkers and clinical data from 40 sugarcane workers at the start and the end of a 6-month harvest. We used generalized mixed-effects models to estimate temperature effects on HSP70 and anti-HSP70 levels. In addition, we examined trends between HSP70 and anti-HSP70 levels and markers of kidney function across the harvest.ResultsAt the end of the harvest, temperatures were higher, and workers had, on average, higher levels of HSP70 and anti-HSP70 compared to the beginning of the season. We observed significant increasing trends with temperature indices, heat index, and HSP70 levels. Maximum temperature was associated with HSP70 increments after controlling for age, systolic and diastolic blood pressure (β: 0.21, 95% Confidence Interval: 0.09, 0.33). Kidney function decline across the harvest was associated with both higher levels of anti-HSP70 levels at the end of the harvest as well as greater increases in anti-HSP70 levels across the harvest.ConclusionsThese results suggest that workplace heat exposure may increase the production of HSP70 and anti-HSP70 levels and that there may be a relationship between increasing anti-HSP70 antibodies and the development of renal injury. HSP70 holds promise as a biomarker of heat stress in exposed populations.

Protective effect of β-sitosterol against high-fructose diet-induced oxidative stress, and hepatorenal derangements in growing female sprague-dawley rats

BackgroundChronic consumption of a high-fructose diet causes oxidative stress that compromises kidney and liver health. β-sitosterol (Bst), a phytosterol, is a functional nutrient with health benefits. β-sitosterol antioxidant activity protects the liver and kidney from ROS-mediated damage and lipid peroxidation. We evaluated the potential renoprotective and hepatoprotective effects of orally administrated β-sitosterol in high-fructose diet-fed growing female rats. Thirty-five 21-day old female Sprague-Dawley rat pups were randomly assigned to and administered the following treatments for 12 weeks: group I- standard rat chow (SRC) + plain drinking water (PW) + plain gelatine cube (PC); group II- SRC + 20% w/v fructose solution (FS) as drinking fluid + PC; group III- SRC + FS + 100 mg/kg body mass (BM) fenofibrate in gelatine cube; group IV- SRC + FS + 20 mg/kg BM β-sitosterol gelatine cube (Bst) and group V- SRC + PW + Bst. The rats were fasted overnight, weighed then euthanised. Blood was collected, centrifuged and plasma harvested. Livers and kidneys were excised, weighed and samples preserved for histological assessments. Plasma biomarkers of oxidative stress, liver and kidney function and renal tubular injury were assessed.ResultsHigh fructose diet fed rats had increased plasma KIM-1, NGAL (p < 0.001) and MDA levels (p < 0.05). Dietary fructose caused microvesicular and macrovesicular steatosis, and reduced glomerular density, Bowman’s capsule area and urinary space. β-sitosterol protected against the high-fructose diet-induced hepatic steatosis and glomerular disturbances without adverse effects on liver and kidney function.Conclusionsβ-sitosterol, as a dietary supplement, could potentially be exploited to prevent high-fructose diet-induced NAFLD and to protect against high-fructose diet-induced renal tubular injury.

Enhanced eNOS/nitric oxide production by nebivolol interferes with TGF-β1/Smad3 signaling and collagen I deposition in the kidney after prolonged tacrolimus administration

AimsTacrolimus is an effective immunosuppressant commonly used post-transplantation and in certain autoimmune diseases. However, its long-term administration is associated with renal fibrosis through transforming growth factor-beta/suppressor of mother against decapentaplegic (TGF-β/Smad) signaling that could be partly attributed to endothelial dysfunction alongside decreased nitric oxide (NO) release. Our study aimed to investigate the prospective renal anti-fibrotic effect of enhanced NO production by nebivolol against tacrolimus-stimulated TGF-β1/Smad3 signaling. Materials and methodsTo illustrate the proposed mechanism of nebivolol, Nω-nitro-L-arginine methyl ester (L-NAME); nitric oxide synthase inhibitor; was co-administered with nebivolol. Rats were treated for 30 days as control, tacrolimus, tacrolimus/nebivolol, tacrolimus/L-NAME, and tacrolimus/nebivolol/L-NAME groups. Key findingsOur results revealed that renal NO content was reduced in tacrolimus-treated rats, while treatment with tacrolimus/nebivolol enhanced NO content via up-regulated endothelial nitric oxide synthase (eNOS), but down-regulated inducible nitric oxide synthase (iNOS) expression. That participated in the inhibition of TGF-β1/Smad3 signaling induced by tacrolimus, where the addition of L-NAME abolished the defensive effects of nebivolol. Subsequently, the deposition of collagen I and alpha-smooth muscle actin (α-SMA) was retarded by nebivolol, emphasized by reduced Masson's trichrome staining. In accordance, there was a strong negative correlation between eNOS and both TGF-β1 and collagen I protein expression. The protective effects of nebivolol were further confirmed by the improvement in kidney function biomarkers and histological features. SignificanceIt can be suggested that treatment with nebivolol along with tacrolimus could effectively suppress renal TGF-β1/Smad3 fibrotic signaling via the enhancement of endothelial NO production, thus curbing renal fibrosis development.

Potential protective effects of Acacia nilotica (L.) against gentamicin - induced nephrotoxicity by suppressing renal redox imbalance, inflammatory stress and caspase-dependent apoptosis in Wistar rats

Gentamicin-induced nephrotoxicity limits its therapeutic use as an effective aminoglycoside. Herbal drugs have a distinct place in the world of pharmaceuticals since they are safe, effective, and cost-efficient. Acacia nilotica (L.) has long been recognized for its antihypertensive, antioxidant, anti-inflammatory, and antiplatelet aggregatory benefits in traditional medicine. Still, the protective effect of Acacia nilotica on gentamicin-induced nephrotoxicity is still unknown. Thus, the goal of this research was to examine the protection of ethanolic extract of Acacia nilotica (ANE) against nephrotoxicity triggered by Gentamicin. Thirty-six rats were randomly divided into six groups containing six rats in each group. The distilled water were given in control group. The rats in groups two and three were administered metformin and gentamicin respectively. In groups five and six, rats were administered ANE at doses of 100 and 200 mg/kg. Ten days of daily treatments were given. The urea, creatinine, uric acid, and LDH levels were analyzed on serum, whereas histological evaluation, MDA, GSH, SOD, CAT, TNF-α, IL-6, and caspase-3, were performed on kidney tissue on day 11. The gentamicin-treated group exhibited a significantly elevated MDA, and lower levels of antioxidant enzymes. Kidney function markers, inflammatory markers and caspase-3 expression were significantly elevated in the gentamicin-treated group. ANE significantly restored kidney function biomarkers, upregulated biochemical levels, inhibited TNF-α, caspase-3, cytokine expression, and reduced histological lesions. In conclusion, ANE has the ability to prevent gentamicin-induced nephrotoxicity and reduce nephrotoxic damage. As such, it may represent an effective therapy for patients receiving gentamicin treatment.

Cystatin C as a Marker of Kidney Function in Children.

This review examines the reliability of cystatin C as a biomarker for kidney function in paediatric populations. Chronic kidney disease (CKD) affects a significant number of children globally, leading to severe health complications such as anaemia, hypertension, and growth disorders. Traditionally, kidney function has been assessed using the estimated glomerular filtration rate derived from serum creatinine, though this method is flawed due to variability in muscle mass, age, gender, and diet. Cystatin C offers an alternative as it is less influenced by these factors. Evidence from various studies indicates that cystatin C provides a more accurate assessment of kidney function, especially in neonates and children with urinary tract malformations. Additionally, it is more reliable in early detection of acute kidney injury in paediatric intensive care units. Despite its potential, cystatin C is not yet widely adopted in clinical guidelines, primarily due to a lack of large-scale paediatric studies. Nonetheless, existing research supports its utility in providing a consistent and precise measure of kidney function across different paediatric age groups, suggesting that it could enhance early diagnosis and management of CKD in children if more extensive validation studies are conducted.

Ppb-Level Ammonia Sensor for Exhaled Breath Diagnosis Based on UV-DOAS Combined with Spectral Reconstruction Fitting Neural Network.

Ammonia (NH3) in exhaled breath (EB) has been a biomarker for kidney function, and accurate measurement of NH3 is essential for early screening of kidney disease. In this work, we report an optical sensor that combines ultraviolet differential optical absorption spectroscopy (UV-DOAS) and spectral reconstruction fitting neural network (SRFNN) for detecting NH3 in EB. UV-DOAS is introduced to eliminate interference from slow change absorption in the EB spectrum while spectral reconstruction fitting is proposed for the first time to map the original spectra onto the sine function spectra by the principle of least absolute deviations. The sine function spectra are then fitted by the least-squares method to eliminate noise signals and the interference of exhaled nitric oxide. Finally, the neural network is built to enable the detection of NH3 in EB at parts per billion (ppb) level. The laboratory results show that the detection range is 9.50-12425.82 ppb, the mean absolute percentage error (MAPE) is 0.83%, and the detection accuracy is 0.42%. Experimental results prove that the sensor can detect breath NH3 and identify EB in simulated patients and healthy people. Our sensor will serve as a new and effective system for detecting breath NH3 with high accuracy and stability in the medical field.

Correlation between Biomarkers and Severity of Clinical Categories in COVID-19 Patients: A Hospital-Based Study in Arunachal Pradesh, India

Background: The COVID-19 pandemic has brought about widespread effects on communities on a global scale, with impacts varying among different demographics. This study focuses on a unique cohort of COVID-19-positive patients from Arunachal Pradesh, a region in northeast India with a substantial indigenous population. This study aims to delve into the features and consequences of COVID-19 in this indigenous population within this distinct demographic region, with a special focus on assessing the effects on tribal communities. Out of a total of 1627 COVID-19 positive cases, 1392 belonged to various tribes of Arunachal Pradesh, categorized as the indigenous population of the region. Our research primarily focuses on examining the biochemical and inflammatory indicators that forecast the clinical results of COVID-19 patients, specifically within both indigenous and non-indigenous groups. Methods: Biochemical markers, including hematological parameters, liver and kidney function biomarkers, D-DIMER, and inflammatory markers, were assessed along with immune-inflammatory ratios: neutrophil-to-lymphocyte ratio (NLR) and lymphocyte-to-monocyte ratio (LMR). Differences in biomarker levels and ratios across disease severities were analyzed, and significant data were observed using descriptive statistics. Results: Elevated levels of Ferritin (CRP, IL-6, D-DIMER, Creatinine, Urea, AST/SGOT, and ALT/SGPT) were associated with increasing disease severity in COVID-19 cases, reflecting increased inflammation, multi-organ dysfunction, and coagulopathy in the severe COVID-19 category amongst the indigenous population. The data showed an aligned report with the non-indigenous population of India when compared with various other studies (using a Spearman rank correlation test). Similarly, an increase in the neutrophil-to-lymphocyte ratio (NLR) and a declining shift in the lymphocyte-to-monocyte ratio (LMR) indicated deregulated immune responses and systemic inflammation in the severe category of COVID-19. Conclusion: This population-based study from northeast India offers important perspectives into the pathophysiology of COVID-19 and its link with disease severity among indigenous and non-indigenous populations.

Human Proenkephalin A 119-159 (penKid) in Extracorporeal Therapies: Ex vivo Sieving Coefficient, Diffusive Clearance, and Hemoadsorption Kinetics

Introduction: Enkephalins, endogenous opioid peptides, are involved in the regulation of renal function. One derived molecule, proenkephalin A, also known as penKid, has been demonstrated to be a reliable biomarker for kidney function and its plasma concentration correlates with measured glomerular filtration rate. penKid is used for prediction and diagnosis of AKI and need of renal replacement therapy (RRT). penKid has also been used to predict the successful weaning from RRT in patients with AKI. Whether the concentration of penKid is affected or not by RRT is a controversial point and there are no studies describing the kinetics of the molecule in such conditions. The low molecular weight (4.5 kDa) would imply free removal by the glomerulus and the dialysis membranes. During RRT, this reduction could not be detected in clinical practice due to the complex kinetics involving either low dialytic clearance or increased production in response to impaired kidney function. The aim of this study was to determine the sieving coefficient and the diffusive clearance of the penKid molecule in conditions of in vitro continuous veno-venous hemofiltration (CVVH) and continuous veno-venous hemodialysis (CVVHD), respectively, and also the penKid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous resin. Methods: Blood spiked with a lyophilized penKid peptide solved in 20 mm dipotassium phosphate and 6 mm disodium EDTA [pH 8] to reach target concentrations is used as testing solution. In each experiment, the blood batch was adjusted at a volume of 1,000 mL, maintained at 37°, and continuously stirred. Samples were collected from blood, ultrafiltrate, and spent dialysate at different times during the experiments. Sieving, clearance, and removal ratio were calculated. Results: Significant removal of penKid was observed in CVVH (sieving 1.04 ± 0.27), in CVVHD (clearance 23.08 ± 0.89), and in HA (removal ratio 76.1 ± 1% after 120 min). Conclusion: penKid is effectively removed by extracorporeal therapies. In presence of anuria, penKid generation kinetics can be calculated based on extracorporeal removal and volume variation. In steady state conditions, declining values may be the result of an initial renal function recovery and may suggest discontinuation and successful liberation from RRT.

Renoprotective effects of apocynin and/or umbelliferone against acrylamide-induced acute kidney injury in rats: role of the NLRP3 inflammasome and Nrf-2/HO-1 signaling pathways.

Acrylamide (ACR) is a toxic, probably carcinogenic compound commonly found in fried foods and used in the production of many industrial consumer products. ACR-induced acute kidney injury is mediated through several signals. In this research, we investigated, for the first time, the therapeutic effects of phytochemicals apocynin (APO) and/or umbelliferone (UMB) against ACR-induced nephrotoxicity in rats and emphasized the underlying molecular mechanism. To achieve this goal, five groups of rats were randomly assigned: the control group received vehicle (0.5% CMC; 1 ml/rat), ACR (40 mg/kg, i.p.), ACR + APO (100 mg/kg, P.O.), ACR + UMB (50 mg/kg, P.O.), and combination group for 10 days. In ACR-intoxicated rats, there was a significant reduction in weight gain while the levels of blood urea, uric acid, creatinine, and Kim-1 were elevated, indicating renal injury. Histopathological injury was also observed in the kidneys of ACR-intoxicated rats, confirming the biochemical data. Moreover, MDA, TNF-α, and IL-1β levels were raised; and GSH and SOD levels were decreased. In contrast, treatment with APO, UMB, and their combination significantly reduced the kidney function biomarkers, prevented tissue damage, and decreased inflammatory cytokines and MDA. Mechanistically, it suppressed the expression of NLRP-3, ASC, GSDMD, caspase-1, and IL-1β, while it upregulated Nrf-2 and HO-1 in the kidneys of ACR-intoxicated rats. In conclusion, APO, UMB, and their combination prevented ACR-induced nephrotoxicity in rats by attenuating oxidative injury and inflammation, suppressing NLRP-3 inflammasome signaling, enhancing antioxidants, and upregulating Nrf-2 and HO-1 in the kidneys of ACR-induced rats.