Urinary Creatinine Levels Research Articles

Radiofrequency Electromagnetic and Pulsed Magnetic Fields Protected the Kidney Against Lipopolysaccharide-Induced Acute Systemic Inflammation, Oxidative Stress, and Apoptosis by Regulating the IL-6/HIF1α/eNOS and Bcl2/Bax/Cas-9 Pathways

Background/Objectives: Sepsis-associated acute kidney injury caused by lipopolysaccharide (LPS) is related to hypoxia, amplification of the inflammatory response, oxidative stress, mitochondrial dysfunction, and apoptosis. This study aims to explore the protective effects of a radiofrequency electromagnetic field (RF-EMF) and a pulsed magnetic field (PMF) on acute kidney injury in rats. Materials and methods: Forty female Wistar albino rats were randomly divided into five groups (each containing eight rats): control, LPS, RF-EMF, PMF, and RF-EMF + PMF groups. Six hours after LPS application, blood and tissues were removed for histopathological, immunohistochemical, biochemical, and genetic analysis. Results: Histopathological findings, caspase-3, inducible nitric oxide synthase and tumor necrosis factor-alpha immunoexpressions, total oxidant status and oxidative stress index levels, and interleukin-6, hypoxia-inducible factor alpha, Bcl-2-associated X protein, and caspase 9 gene expression in kidney tissue and blood urine nitrogen and creatinine levels in blood were increased, whereas endothelial nitric oxide synthase and B-cell lymphoma 2 gene expression were decreased in the LPS groups. Both RF-EMF and PMF reversed all these findings and recovered renal tissues. Conclusions: Noninvasive, nontoxic, low-cost PMF and RF-EMF, both single and combined, have been demonstrated to have renoprotective anti-inflammatory, antioxidant, and antiapoptotic effects.

Integrating an Extended-Gate Field-Effect Transistor in Microfluidic Chips for Potentiometric Detection of Creatinine in Urine

Monitoring creatinine levels in urine helps to recognize kidney dysfunction. In this research, we developed a photocurable membrane for the detection of serum creatinine. Using a system based on field-effect transistors, we carried out creatinine quantification in synthetic urine. The device was able to cover values between 3 and 27 mmol L−1. The current sensitivity was 0.8529 (mA)1/2 mmol−1 L with 91.8% linearity, with the LOD and LOQ being 5.3 and 17.5 mmol L−1, respectively. The voltage sensitivity was 0.71 mV mmol−1 L with a linearity of 96.2%, with the LOD and LOQ being 4.2 and 14.0 mmol L−1, respectively. These data were obtained under flow conditions. The system performed very well during the measurements, with a hysteresis of about 1.1%. Up to 90 days after manufacture, the sensor still maintained more than 70% of its initial response. Even when used periodically during the first week and then stored unused at −18 °C, it was able to maintain 96.7% of its initial response. The device used in the flow setup only had a useful life of three days due to membrane saturation, which was not reversible. In the interference test, the membrane was also shown to respond to the urea molecule, but in a different response window, which allowed us to discriminate urea in synthetic urine. EGFETs can be used to identify variations in the creatinine concentration in urine and can help in therapeutic decision-making.

Non-linear relationship between urinary creatinine and diabetic kidney disease: implications for clinical practice

ObjectiveThis study aims to investigate the relationship between urinary creatinine (UCr) and the risk and severity of Diabetic Kidney Disease (DKD) in patients with Type 2 Diabetes Mellitus (T2DM). The goal is to establish UCr as a potential biomarker for early DKD detection and severity assessment.MethodsA retrospective cross-sectional analysis was conducted using medical records of T2DM patients. Patients were classified into groups with and without DKD, and relevant clinical data, including demographic, blood, and urine parameters, were collected. Logistic regression and receiver operating characteristic (ROC) curve analysis evaluated the association between UCr levels and DKD. Curve fitting and threshold effect model were used to further evaluate the relationship between UCr and the incidence and severity of DKD.ResultsA total of 302 T2DM patients were analyzed, with 137 diagnosed with DKD. Significant differences in clinical parameters were observed between the DKD and non-DKD groups, particularly in UCr, urine albumin levels, and eGFR. UCr levels demonstrated a strong association with DKD. Moreover, a non-linear relationship was identified, with specific inflection points indicating different correlation patterns of UCr with DKD occurrence and progression.ConclusionThe findings of this study highlight the potential of UCr as a valuable biomarker for early detection and assessment of DKD in T2DM patients. Incorporating UCr measurements into routine clinical practice could enhance early identification of patients at risk for kidney complications, leading to timely intervention and improved patient outcomes.

Weekly administration of betulinic acid prevents development of chronic renal failure from acute renal failure in folic acid-induced mouse model of kidney injury.

Betulinic acid (BA) has been shown to exhibit various pharmacological activities and it has shown the protective effect on acute renal failure (ARF) and chronic renal failure (CRF); however, no reports are available on its effect on ARF-CRF transition. Therefore, we aimed to investigate the effects of BA on ARF-CRF transition. A single dose of250 mg/kg body weight (BW) intraperitoneal injection of folic acid was given in mice for inducing ARF-CRF transition (injury group; I) on day 1. Further, excess of these mice received BA at 30 mg/kg BW dose for 3 days (on days 1, 2, 3) in one group (IT3) and for 7 days (on days 1, 2, 3, 7, 14, 21, 28) in another group (IT7). All mice were sacrificed on day 28. Mice in injury group (I) showed elevated serum creatinine along with oxidative stress markers like urine nitrite, tissue lipid peroxidation, nitrotyrosine and fibrotic markers such as tissue α-smooth muscle actin and matrix metalloproteinase-2 activity. They had attenuated levels of urine creatinine and tissue reparative cytokines viz. interleukin-4 and interleukin-13. Excess of fibroblasts and extracellular matrix in the interstitia and periglomerular area in microscopy further support these findings. Seven days of BA treatment regimen (IT7) significantly improved serum and urine parameters accompanied by reduced oxidative stress, improved reparative cytokines and lesser maladaptive matrix deposition. The above findings reveal that weekly BA treatment regimen has potential to prevent development of CRF after ARF.

Biochemical markers of renal functions in hypothyroidism – A study in Indian population

The global burden of hypothyroidism is significant among the disorders of thyroid gland. In the developed world, hypothyroidism prevalence is approximately 4-5% and that of subclinical hypothyroidism is approximately 4-15%.The present study was done to evaluate the association between thyroid function and renal parameters among euthyroid, subclinical and overt hypothyroid individuals. To evaluate the renal functions in hypothyroid patients. To estimate & compare, freeT3, freeT4, TSH, serum creatinine, urea and uric acid, eGFR, urinary microalbumin, urinary creatinine levels in euthyroid (control group) & hypothyroid patients (study group).To calculate & compare urinary albumin to creatinine ratio (UACR) in both groups (control group and study group). This is a Cross sectional analytical study carried out at Clinical Chemistry Laboratory, at Sir Sayajirao General Hospital (S.S.G.H) and Medical College Baroda, Vadodara. Study subjects were divided into three groups depending upon the levels of the TSH and free T4.The Chemiluminescent Immunoassay (CLIA) was used to measure: S.TSH, fT4 and fT3 levels by micro particle enzyme immunoassays.The Fully automatic Erba XL 640 was used to measure-Serum Creatinine, Serum Urea, Serum Uric acid were measured on Erba XL 640. The semiautomatic Microlab RX-50V was used to measure-Urinary Microalbumin.All statistical analysis was done by using MedCalc statistical software. ANOVA comparison analysis, we found significant differences in mean results of several parameters in three thyroid groups. In overt hypothyroid subjects, free T4 levels showed significantly moderate strong negative correlations (p=0.002, r= -0.412 & p<0.001, -0.539) with UACR & urinary microalbumin. In overt hypothyroid group, Serum TSH: levels showed weak positive correlations (p=0.04, r=0.28) with urinary creatinine, moderately strong positive correlations with UACR and urinary microalbumin (p=<0.001, r=0.57 & p=<0.001, r=0.72). Serum TSH: In subclinical hypothyroid groups, TSH levels showed positive correlations with serum uric acid urinary creatinine, UACR, and urinary microalbumin (p=0.01, r= 0.32, p=0.00, r= 0.46, & p=<0.001, 0.43). Present study were found increased levels of serum creatinine, uric acid, urine albumin creatinine ratio, urinary microalbumin and decreased eGFR levels in hypothyroid group as compared to euthyroid group. The prevalence of microalbuminuria and urine albumin creatinine ratio is high in overt hypothyroidism.

Association between hypertension duration and chronic kidney disease in residents in China

Objective: To evaluate the association between hypertension duration and risk for chronic kidney disease in residents in China. Methods: Participants aged 18-74 years from the sixth round of China Chronic Disease and Risk Factor Surveillance in 2018 were included. The age/date at hypertension diagnosis was reported by them, and hypertension duration was calculated based on the age at diagnosis and the age at survey. The hypertension duration was calculated as 0 year (i.e., normotensive participants), 0.1- year, 5.0- years, 10.0- years, and ≥15.0 years. Serum creatinine, urinary albumin, and urinary creatinine levels were measured, and chronic kidney disease was diagnosed when glomerular filtration rate was <60 ml·min-1·(1.73 m2)-1 and/or urine albumin-to-creatinine ratio was ≥30 mg/g. Multivariable logistic regression analysis, which took intra-group correlation into account, was used to evaluate the association of hypertension duration with chronic kidney disease. Results: A total of 140 662 residents were finally included in the analysis. After adjusting the confounders, including blood pressure, the odds ratio of chronic kidney disease was 1.16 (95%CI: 1.09-1.23), 1.33 (95%CI: 1.20-1.48), 1.33 (95%CI: 1.18-1.49), and 1.43 (95%CI: 1.29-1.60) in study subjects with hypertension durations of 0.1-4.9 years, 5.0-9.9 years, 10.0-14.9 years, and ≥15.0 years, respectively, in comparison with normotensive people. This result was further supported by the positive association between hypertension duration and chronic kidney disease in people with previously diagnosed hypertension. The results of restricted cubic spline suggested that the risk for chronic kidney disease showed a steep increase within 0.1- 4.9 years after hypertension diagnosis, then showed neither increase nor decrease. The above association seemed to be stronger in those with hypertension diagnosed age <45 years. Compared with those with hypertension duration of 0.1-4.9 years, the odds ratio was 1.38 (95%CI: 1.04-1.84), 1.22 (95%CI: 0.91-1.65), and 1.47 (95%CI: 1.04-2.07) in those with hypertension durations of 5.0-9.9 years, 10.0-14.9 years, and ≥15.0 year, respectively. In those with hypertension diagnosis at ≥45 years, the corresponding odds ratio was 1.08 (95%CI: 0.98-1.19), 1.08 (95%CI: 0.97-1.21), and 1.16 (95%CI: 1.02-1.32), respectively. Conclusions: Hypertension duration is positively associated with the risk for chronic kidney disease in residents in China, and this association is independent of blood pressure level. Early diagnosis of hypertension and long-term control of blood pressure are effective strategies for secondary prevention of hypertension-related chronic kidney disease.

Safety and Efficacy of Nusinersen Focusing on Renal and Hematological Parameters in Spinal Muscular Atrophy.

Spinal muscular atrophy (SMA) is a motor neuron disease caused by mutations in the SMN1 gene. Nusinersen, an antisense oligonucleotide, has been shown to improve motor function in SMA patients. However, concerns regarding its renal safety remain as previous studies have linked similar treatments to renal toxicity. The aim of this study was to evaluate the effects of the nusinersen treatment on platelet counts and renal functions, specifically urine protein excretion, in SMA patients and to estimate safe urinary protein levels before administration of each intrathecal injection. This retrospective study examined data from 33 patients with SMA to assess the effects of nusinersen on motor functions and laboratory parameters including platelet count, serum creatinine, urine protein, and urine creatinine. Measurements were taken at baseline andprior to each maintenance dose, after the completion of four initial loading doses. The baseline values were compared between SMA Type 1 and Type 2 patients, while the changes in these values over time were analyzed within each group. No significant adverse effects on platelet counts or renal functions were observed. Urine creatinine and protein levels were significantly higher in SMA Type 2 patients compared to SMA Type 1 at baseline; these parameters remained stable in SMA Type 2 but increased significantly after the loading doses in SMA Type 1. Motor function improvements were observed in both groups, with the most significant gains in SMA Type 1 after the loading doses. Thus, improvement in motor functions was associated with increase in urine creatinine. Nusinersen treatment did not cause significant renal toxicity or affect platelet counts. Urine creatinine levels may serve as a potential biomarker for assessing treatment response in SMA Type 1.

Non-invasive detection of urinary creatinine levels using a non-enzymatic electrochemical sensor with pectin-assisted Cu electrodeposition

Non-invasive detection of urinary creatinine levels using a non-enzymatic electrochemical sensor with pectin-assisted Cu electrodeposition

Volatile organic compounds (VOC) metabolites in urine are associated with increased systemic inflammation levels, and smokers are identified as a vulnerable population

BackgroundPrevious studies indicated that exposure to VOCs was linked to increased systemic inflammation levels. However, the dose-response relationships between urine VOCs metabolites and systemic inflammation have not been established, and the key metabolite of the toxic compounds has not been identified. MethodsWe used data in 7007 US adults in the NHANES cycles (2011–2018) across 8 years. Urinary VOC metabolites were measured using ultra-performance liquid chromatography and electrospray tandem mass spectrometry (UPLC-ESI/MSMS). VOC metabolites were adjusted by urinary creatinine level before analysis. Systemic inflammation was assessed by systemic immune-inflammation index (SII) and systemic inflammation response index (SIRI) indices. Generalized linear models, restricted cubic splines (RCS), and weighted quantile sum (WQS) regression were applied to evaluate the associations, exposure-response (E-R) curve and identify the key contributor compound, adjusting for gender, age, race, BMI, marital condition, education level, smoking level, alcohol consumption and physical activity. Smoking status was assessed as an effect modifier. ResultsSignificant and robust positive correlations were found between 8 VOC metabolites and both SII and SIRI. They were N-Acetyl-S-(2-carboxyethyl)-L-cysteine (CEMA), N-Acetyl-S-(2-cyanoethyl)-L-cysteine (CYMA), N-Acetyl-S-(3,4-dihydroxybutyl)-L-cysteine (DHBMA), N-Acetyl-S-(3-hydroxypropyl)-L-cysteine (3HPMA), mandelic acid (MA), N-Acetyl-S-(4-hydroxy-2-butenyl)-L-cysteine (MHBMA3), phenylglyoxylic acid (PGA), and N-Acetyl-S-(3-hydroxypropyl-1-methyl)-L-cysteine (HPMMA). The RCS curves showed J-shaped or exponential shaped E-R relationships for most VOC metabolites. WQS regression found that exposure to the mixture of VOC metabolites was related to increased systemic inflammation, and MA was the key VOC metabolite contributing most to systemic inflammation levels. Smokers exhibited higher levels of urinary VOCs and larger susceptibility to VOC-related increases in SII and SIRI compared to non-smokers. ConclusionThis study demonstrated a strong link between urinary VOC metabolites and increased systemic inflammation, and smokers were more susceptible. Our findings highlighted the significance of reducing VOC exposure to mitigate the inflammation levels, particularly for smokers.

Loss of the Endothelial Glycocalyx Component EMCN Leads to Glomerular Impairment.

EMCN (endomucin), an endothelial-specific glycocalyx component, was found to be highly expressed by the endothelium of the renal glomerulus. We reported an anti-inflammatory role of EMCN and its involvement in the regulation of VEGF (vascular endothelial growth factor) activity through modulating VEGFR2 (VEGF receptor 2) endocytosis. The goal of this study is to investigate the phenotypic and functional effects of EMCN deficiency using the first global EMCN knockout mouse model. Global EMCN knockout mice were generated by crossing EMCN-floxed mice with ROSA26-Cre mice. Flow cytometry was used to analyze infiltrating myeloid cells in the kidneys. The ultrastructure of the glomerular filtration barrier was examined by transmission electron microscopy, whereas urinary albumin, creatinine, and total protein levels were analyzed from freshly collected urine samples. Expression and localization of EMCN, EGFP, CD45, CD31, CD34, podocin, and albumin were examined by immunohistochemistry. Mice were weighed regularly, and their systemic blood pressure was measured using a noninvasive tail-cuff system. Glomerular endothelial cells and podocytes were isolated by fluorescence-activated cell sorting for RNA sequencing. Transcriptional profiles were analyzed to identify differentially expressed genes in both endothelium and podocytes, followed by gene ontology analysis. Protein levels of EMCN, albumin, and podocin were quantified by Western blot. The EMCN-/- mice exhibited increased infiltration of CD45+ cells, with an increased proportion of Ly6GhighLy6Chigh myeloid cells and higher VCAM-1 (vascular cell adhesion molecule 1) expression. EMCN-/- mice displayed albuminuria with increased albumin in the Bowman's space compared with the EMCN+/+ littermates. Glomeruli in EMCN-/- mice revealed fused and effaced podocyte foot processes and disorganized endothelial fenestrations. We found no significant difference in blood pressure between EMCN knockout mice and their wild-type littermates. RNA sequencing of glomerular endothelial cells revealed downregulation of cell-cell adhesion and MAPK (mitogen-activated protein kinase)/ERK (extracellular signal-regulated kinase) pathways, along with glycocalyx and extracellular matrix remodeling. In podocytes, we observed reduced VEGF signaling and alterations in cytoskeletal organization. Notably, there was a significant decrease in both mRNA and protein levels of podocin, a key component of the slit diaphragm. Our study demonstrates a critical role of the endothelial marker EMCN in supporting normal glomerular filtration barrier structure and function by maintaining glomerular endothelial tight junction and homeostasis and podocyte function through endothelial-podocyte crosstalk.

Towards clinical translation of urinary vitronectin for non-invasive detection and monitoring of renal fibrosis in kidney transplant patients

BackgroundInterstitial fibrosis and tubular atrophy (IFTA) is a critical factor in the prognosis of kidney health. Currently, IFTA quantitation in kidney biopsy samples is crucial for diagnosis and assessing disease severity, but the available non-invasive biomarkers are not satisfactory. Proteomic studies identified urinary vitronectin (VTN) as a potential biomarker for kidney fibrosis. As mass spectrometry techniques are not practical for use in clinical settings, we tested whether evaluation of urinary VTN levels through enzyme-linked immunosorbent assay (ELISA) can help monitor fibrotic changes in kidney transplant recipients and prove the clinical viability of the assay.MethodsA total of 58 kidney transplant (KTx) patients who underwent renal biopsy were included in the study. Patients were categorized into two groups referred as no fibrosis (0%) or with fibrosis (≥ 5%) based on their histological findings. In a subsequent/follow-up analysis, the time elapsed from transplantation was also considered. The urinary levels of VTN were measured using ELISA.ResultsVTN (p = 0.0180) and VTN normalized by urinary creatinine levels (p = 0.0037), were significantly increased in patients with fibrotic grafts. When focusing on patients with long-term grafts (> 3 years from transplantation, n = 36), VTN exhibited superior potential in identifying fibrotic grafts compared to albuminuria (VTN p = 0.0040 vs. albuminuria p = 0.0132). Importantly, in this group, while albuminuria correctly identified 71% of fibrotic patients, the combination of VTN plus albuminuria correctly classified 89% of fibrotic grafts detected by renal biopsy.ConclusionsVTN has emerged as a valid indicator of renal fibrosis. Of interest, urinary levels of VTN in combination with conventional clinical parameters (such as albuminuria) significantly improved the non-invasive detection of renal fibrosis in kidney transplant patients.

Long-term effects of IVF on offspring kidneys: observations from adolescence to adulthood

Research questionWhat is the effect of in-vitro fertilization (IVF) on long-term health of offspring kidney? DesignWe established an IVF mouse model and subsequently observed renal structure, function, and cortical oxidative stress from the age of 2 months to ascertain any disparities compared to natural conceived (NC) offspring. And this kind of process continued until the mice reached 5 months old. ResultsWe found no significant difference in the body weight of mice aged 2 to 5 months between IVF and NC offspring. However, the renal/weight ratio of IVF offspring was higher than that of NC offspring at 2 months and 3 months, but this difference disappeared in offspring aged 4 to 5 months. IVF offspring at 5 months of age had lower urine creatinine (Ucr) levels compared to NC offspring. Moreover, The expression of ACE2 was observed to decrease in the kidneys of 4 to 5-month-old IVF mice, and the expression of AGTR1A was higher in 5-month-old IVF mice compared to NC mice. The malondialdehyde (MDA) level in 5-month-old IVF offspring was higher than in NC offspring. ConclusionOur study indicated that microvascular thickness in the kidneys of IVF offspring remains unchanged, but minor alterations in kidney function, RAS gene expression, and renal cortical oxidative stress were evident by 5 months of age.

The influence of the daily salt-intake on the antihypertensive action and atrial natriuretic peptide level in patietns with angiotensin receptor neprilysin inhibition

Abstract Background The angiotensin receptor–neprilysin inhibitor (ARNI) is a drug which acts through angiotensin receptor blocking effect and the increase in atrail natriuretic peptide (ANP) through neprilysin inhibitor in hypertension (HT). These combined effects result in a reduced risk of hospitalization for heart failure or death from cardiovascular causes. ANP is also known for its various cardioprotective effects including vasodilator and natriuretic action. Acording to Guyton's pressure-natriuresis curve, the efficacy of angiotensin receptor blocker drugs is diminished in HT cases with high daily salt inatke. However, whether the effect of ARNI on HT is attenuated in patients with high daily salt intake remains unclear. Purpose The present study investigated the influence of a daily salt intake on the antihypertensive action and ANP level in patients with ARNI. Methods Fourty-four consecutive essential HT patients on ARNI were enrolled. Blood pressure and ANP level were measured at baseline (before taking ARNI) and 3 weeks later. ARNI (200mg) was prescribed and maintained during the study. In addtion, the daily salt intake was calculated using creatinine and natrium levels in urine, age, and body weight according to Japanese hypertensive guideline at baseline and 3 weeks later. Results The average age was 70±8 years old. About 50% (N=23) was male. The mean sytolic and diastolic blood pressure was 148±14mmHg and 89±10mmHg, respectively. The mean daily salt intake was 9.5±2.2 g/day at baseline. The mean ANP level was 529±300pg/ml. At follow up (3 weeks later), the mean systolic and diastolic blood pressure significanly went down to 132± 18 mmHg and 70± 9 mmHg, respectively (p=0.03). ANP level also increased from 529±300pg/ml to 793±580pg/ml. However, the mean daily salt intake was almost same as the baseline at 9.4±3.2 g/day. The patients were divided into 2 groups; high daily salt intake (N=20 with mean daily salt intake 10.5±1.7g/day)) and low daily salt intake (N=24 with 8.4±3.1g/day) groups compared to the baseline. The absolute and percentage changes in systolic blood pressure were almost same in the high and low daily salt intake groups (-12.7±15.8mmHg vs -13.7±14.2mmHg, p=0.75; -5.8±6.5% vs.-7.0±9.6%, p=0.58, respectively). However, the change rate in ANP level was significantly higer in the high daily salt intake group than in the low daily salt intake group (155±63 vs. 12±16%, p=0.01). Conclusion ARNI demonstrates effectiveness in lowering the blood pressure even in patients with higher salt intake, unlike angiotensin receptor blocker. In cases with high salt intake, the notable increase in ANP levels may contribute to decreasing blood pressure through vasodilator and natriuretic action.

Correlation of urinary glutathione S-transferase with serum creatinine in sepsis-induced acute kidney injury: A prospective and observational study.

Sepsis-induced acute kidney injury (AKI) is difficult to prevent because most patients are diagnosed after they develop it. Standard serum and urine creatinine levels are insensitive and nonspecific for detecting kidney injury in its early stages. Glutathione S-transferase (GST) has received little attention as a biomarker in AKI. This study included 65 adult patients with sepsis who developed oliguria within 72 h of admission. Baseline serum creatinine values were recorded at least 1 month before or after intensive care unit (ICU) admission. The clinical endpoints were defined as the occurrence of advanced AKI stages 2 or 3 according to the KDIGO classification. Serum creatinine and urinary GST levels were measured every 6 h from admission until 72 h postoliguria development. The primary objective was to assess the correlation between urinary GST and serum creatinine levels in patients with sepsis-induced AKI. Among the 65 patients, 13 (20%) progressed to AKI Grade I, while 52 (80%) progressed to AKI Grade II or III. Both groups exhibited an increasing trend in serum creatinine and urinary GST levels up to 72 h. Significant mean differences between the two AKI groups were observed at 48 and 72 h for serum creatinine (P = 0.021 and P = 0.007, respectively) and at 18 h for urinary GST levels (P = 0.044). Urinary GST levels demonstrated an earlier elevation than serum creatinine levels in critically ill sepsis patients, underscoring their utility as a valuable tool for the early diagnosis and predicting AKI following admission to the ICU.

Effect of age, sex, and chronic kidney disease on urinary creatinine excretion in Japanese patients.

Urinary creatinine levels are used to estimate the excretion rates of certain analytes from the respective analyte-to-creatinine ratios. We clarified the influence of age and sex on estimated daily urinary creatinine excretion (eUCrE) based on the urinary creatinine level and daily urine volume. All inpatients aged ≥ 18years who attended the Kochi Medical School Hospital with serum and urinary creatinine measurement results were enrolled. Serum and urinary creatinine concentrations were extracted from the database and fluctuations with sex and age were investigated. The eUCrE was calculated for patients with early morning spot urine protein excretion (UPE), and daily urine volume was measured on the same day. Overall, 643 participants (322 men, 321 women) were enrolled. The eUCrE levels of men and women aged 18 - 64 and 18 - 44years, respectively, significantly exceeded 1g/day. Those of women aged 65-74 and ≥ 75years were significantly lower than 1g/day. Each age group was further categorised into Groups A (patients with eGFR ≥ 30mL/min/1.73 m2 and UPE < 0.5g/gCr), B (eGFR ≥ 30mL/min/1.73 m2 and UPE ≥ 0.5g/gCr), and C (eGFR < 30mL/min/1.73 m2 and UPE ≥ 0.5g/gCr). The eUCrE levels were the highest in Group A, followed by Groups B and C. This study revealed age-, sex-, and renal function-related biases in adjusted values using urinary biomarkers, including proteinuria and creatinine ratio.

A noninvasive method of diagnosing membranous nephropathy using exosomes derived from urine.

Membranous nephropathy (MN) is a specific autoimmune disease affecting kidneys. It is characterized by the accumulation of immune complexes in the glomerular basement membrane. Renal biopsy is currently the standard procedure to confirm the diagnosis, although the presence of autoantibodies against the phospholipase A2 receptor (PLA2R) can also help diagnose. In this study, we aimed to investigate the potential of urinary exosomes as noninvasive markers for diagnosing MN. Exosomes were extracted from urine samples of five patients with MN and four healthy controls. The concentration of PLA2R was measured in both urine and isolated exosomes using enzyme-linked immunosorbent assay techniques. The measurements were adjusted based on the urine creatinine (UCr) level of each participant. The levels of PLA2R/UCr were investigated in urine and urine-derived exosomes from patients and controls. Results of the analysis revealed significantly higher expression of PLA2R/UCr in patients compared to the control group (p < 0.05). Furthermore, the expression level of PLA2R/UCr was higher in urine-derived exosomes than in urine samples. Additionally, a positive correlation was observed between the expression levels of PLA2R/UCr and the urine protein-to-creatinine ratio, with urine-derived exosomes exhibiting a stronger correlation than urine samples. Studies have indicated that measuring exosomal PLA2R/UCr levels in urine could be a noninvasive method for diagnosing MN. Using urine-derived exosomes could also reduce the burden of performing a biopsy on patients and facilitate follow-up treatment, such as monitoring for future recurrence.

From computational prediction to experimental validation: Hesperidin's anti-Urolithiatic activity in sodium oxalate-induced urolithiasis models in fruit flies and mice

Kidney stones have been a long-standing health issue, contributing to renal failure, especially in co-morbid patients. There is an increasing interest in exploring natural compounds with anti-urolithiatic properties. Our study utilized in-silico techniques followed by in vivo experiments to evaluate the anti-urolithiatic potential of selected phytoconstituents. Molecular docking studies were conducted on 11 different targets, including inhibitors of kidney stone formation, antioxidant enzymes, and biomarkers of kidney injury, to explore the potential of anti-urolithiatic effects of 38 phytoconstituents from medicinal plants possessing diuretic activity. Further, the anti-urolithiatic activity of the phytoconstituent was evaluated using a sodium oxalate-induced urolithiatic fruit fly and mouse model. Hesperidin emerged as a promising candidate, exhibiting binding interactions with a specific set of 11 target proteins involved in crystal formation with minimal free energy. Hesperidin demonstrated promising anti-urolithiatic potential in mitigating urolithiasis as evidenced by reduced crystal covered area of Malpighian tubules of fruit fly and reduced blood urea nitrogen (BUN), serum creatinine and serum sodium, potassium levels in mice. Moreover, it increased urine volume, preventing crystal deposition, and reduced urine urea nitrogen, creatinine, sodium, and potassium levels, enhancing urine flow and preventing crystal accumulation. Histopathological analysis further supported its efficacy by showing minimal crystal deposition and reduced kidney damage. Hesperidin exhibited superior effectiveness in reducing various serum and urine parameters, making it promising alternatives for urolithiasis management warranting further investigation to determine its safety and optimal dosages in human.

Urinary PYD/Creatinine Ratio Has Negative Correlation to Serum 25(OH)D and Positive Correlation to Chronic Lead Exposure Index

BACKGROUND: The burden of disease due to lead exposure continues to increase. Lead interferes with 25(OH)D hydroxylation and calcium transport, increasing osteoclastic activity and bone resorption. Pyridinoline crosslinks (PYD), as an indicator of bone damage, can be seen earlier compared to imaging changes. Therefore, it is necessary to determine the correlation between serum 25(OH)D levels and the urinary PYD/creatinine ratio in workers exposed to lead, since up to now, there are only limited studies related to it.METHODS: This cross-sectional study involved 104 workers exposed to lead, selected from parents whose children had blood lead levels above 10 µg/dL. Questionnaires and physical examination were performed to obtain characteristic data from subjects. Data regarding blood lead levels, serum 25(OH)D levels, urinary PYD levels, and urinary creatinine levels were also obtained from various laboratory methods.RESULTS: Most subjects (86.5%) had inadequate serum 25(OH)D. Median blood lead levels was 6.3 (1.2-35.5) µg/dL, chronic lead exposure index was 35.3 (1.2-535.8) years µg/dL, serum 25(OH)D levels was 22 (8-52) ng/mL, and urinary PYD/creatinine ratio was 5.3 (3.6-28.1)×10-6. There was a significant negative correlation between serum 25(OH)D levels and urinary PYD/creatinine ratio in workers exposed to lead. There was also a significant positive correlation between chronic lead exposure index and the urinary PYD/creatinine ratio.CONCLUSION: Since urinary PYD/creatinine ratio is correlated with serum chronic lead exposure index and serum 25(OH)D levels, it suggests that pyridinoline might be a potential biomarker to detect bone metabolism disorder due to the chronic lead exposure. Vitamin D adequacy is also an important factor in preventing bone metabolism disorder amidst chronic lead exposure.KEYWORDS: 25(OH)D, bone resorption, pyridinoline, lead, worker

Serum and urinary biomarkers of vancomycin-induced acute kidney injury: A prospective, observational analysis.

Vancomycin, a first-line drug for treating methicillin-resistant Staphylococcus aureus infections, is associated with acute kidney injury (AKI). This study involved an evaluation of biomarkers for AKI detection and their comparison with traditional serum creatinine (SCr). We prospectively enrolled patients scheduled to receive intravenous vancomycin for methicillin-resistant S aureus infection. Blood samples for pharmacokinetic assessment and SCr and cystatin C (CysC) measurements were collected at baseline and on days 3, 7, and 10 from the initiation of vancomycin administration (day 1). Urinary biomarkers, including kidney injury molecule 1 (KIM-1), neutrophil gelatinase-associated lipocalin, and clusterin, were collected from days 1 to 7 and adjusted for urinary creatinine levels. The estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Of the 42 patients, 6 experienced vancomycin-induced AKI. On day 7, the change from baseline eGFR using CysC (ΔeGFRCysC) showed a stronger correlation with vancomycin area under the curve (r = -0.634, P < .001) than that using SCr (ΔeGFRSCr; r = -0.437, P = .020). ΔeGFRSCr showed no significant correlation with vancomycin pharmacokinetic in patients with body mass index ≥23. The median (interquartile range) level of KIM-1 (μg/mg) was significantly higher in the AKI group (0.006 [0.005-0.008]) than in the non-AKI group (0.004 [0.001-0.005]) (P = .039, Mann-Whitney U test), with area under the receiver operating characteristic curve (95% confidence interval) of 0.788 (0.587-0.990). Serum CysC, particularly in overweight individuals or those with obesity, along with urinary KIM-1 are important predictors of vancomycin-induced AKI. These results may aid in selecting better biomarkers than traditional SCr for detecting vancomycin-induced AKI.

Schisandrin A Attenuates Diabetic Nephropathy via EGFR/AKT/GSK3β Signaling Pathway Based on Network Pharmacology and Experimental Validation.

Diabetic nephropathy (DN) is one of the common complications of diabetes and the main cause of end-stage renal disease (ESRD) in clinical practice. Schisandrin A (Sch A) has multiple pharmacological activities, including inhibiting fibrosis, reducing apoptosis and oxidative stress, and regulating immunity, but its pharmacological mechanism for the treatment of DN is still unclear. In vivo, streptozotocin (STZ) and a high-fat diet were used to induce type 2 diabetic rats, and Sch A was administered for 4 weeks. At the same time, protein-protein interaction (PPI) networks were established to analyze the overlapping genes of DN and Sch A. Subsequently, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed to determine the hub pathway. In addition, molecular docking was used to preliminarily verify the affinity of hub proteins and Sch A. Further, H&E staining, Sirius red staining, immunohistochemistry, immunofluorescence, and western blot analysis were used to detect the location and expression of related proteins in DN. This study revealed the multi-target and multi-pathway characteristics of Sch A in the treatment of DN. First, Sch A could effectively improve glucose tolerance, reduce urine microprotein and urine creatinine levels, and alleviate renal pathological damage in DN rats. Second, EGFR was the hub gene screened in overlapping genes (43) of Sch A (100) and DN (2524). Finally, it was revealed that Sch A could inhibit the protein expression levels of EGFR and PTRF and reduced the expression of apoptosis-related proteins, and this effect was related to the modulation of the AKT/GSK-3β signaling pathway. In summary, Sch A has a protective effect in DN rats, EGFR may be a potential therapeutic target, throughout modulating AKT/GSK-3β pathway.