Urinary Excretion Rate Research Articles

Relationship Between Postprandial Blood Glucose, Fasting Insulin, and Glycated Hemoglobin Levels and Early Diabetic Nephropathy in Patients with Type 2 Diabetes Mellitus

Objective: To investigate the relationship between postprandial blood glucose (PBG), fasting insulin (FINS), and glycated hemoglobin (HbA1c) levels and early diabetic nephropathy in patients with type 2 diabetes. Methods: 96 cases of type 2 diabetes mellitus treated in our hospital from May 2021 to May 2022 were selected as the research subjects. The patients were divided into two groups according to the urinary albumin excretion rate (UAER), with 53 cases in the type 2 diabetes group (UAER < 30 ?g/min) and 43 cases in the early diabetic nephropathy group (30 ?g/min ? UAER < 300 ?g/min). PBG, FINS, and HbA1c levels were detected in 87 healthy patients. Results: The levels of PBG, FINS, and HbA1c in the early diabetic nephropathy group were higher than those in the control group (P < 0.01) and the type 2 diabetes group (P < 0.01). Conclusion: PBG, FINS, and HbA1c are factors affecting the occurrence of diabetic nephropathy in patients with type 2 diabetes; thus, controlling the levels of PBG, FINS, and HbA1c can effectively prevent the occurrence of diabetic nephropathy in type 2 diabetes mellitus.

Glycolate oxidase inhibition by lumasiran varies between patients with primary hyperoxaluria type 1

Glycolate oxidase inhibition by lumasiran varies between patients with primary hyperoxaluria type 1

Comparison of in vivo plasma pharmacokinetics and urine excretion of main components in Xihuang Formula in rats with precancerous lesions of breast cancer

The UPLC-MS/MS was established for the determination of acetyl-11-keto-beta-boswellic acid(AKBA) and β-boswellic acid(β-BA), the main active components of Olibanum and Myrrha extracts in Xihuang Formula, in rat plasma and urine. The effects of compatibility on the pharmacokinetic behaviors of AKBA and β-BA in rats were investigated, and the differences in pharmacokinetic behaviors between healthy rats and rats with precancerous lesions of breast cancer were compared. The results showed that compared with RM-NH and RM-SH groups, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05 or P<0.01), T_(max) decreased(P<0.05 or P<0.01), and C_(max) increased(P<0.01) after compatibility. The trends of AKBA and β-BA were the same. Compared with RM-SH group, the T_(max) decreased(P<0.05), C_(max) increased(P<0.01), and the absorption rate increased in the normal group of Xihuang Formula. The results of urinary excretion showed that there was a decreasing trend in the urinary excretion rate and total urinary excretion of β-BA and AKBA after compatibility, but there was no statistical difference. Compared with normal group of Xihuang Formula, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05), T_(max) increased(P<0.05), and the clearance rate decreased in the breast precancerous lesion group. AUC_(0-t) and AUC_(0-∞) of AKBA showed an increasing trend, the in vivo retention time was prolonged, and the clearance rate was reduced, but there was no significant difference compared with the normal group. The cumulative urinary excretion and urinary excretion rate of β-BA and AKBA decreased under pathological conditions, indicating that pathological conditions could affect the in vivo process of β-BA and AKBA, and reduce their excretion in the form of prototype drugs, showing different pharmacokine-tic characteristics from normal physiological conditions. In this study, UPLC-MS/MS analysis method was established, which was sui-table for in vivo pharmacokinetic analysis of β-BA and AKBA. This study laid a foundation for the development of new dosage forms of Xihuang Formula.

Обмен кальция и остеопороз у больных ишемической болезнью сердца в пожилом и старческом возрасте

im. To analyze the relationship between calcium and various clinical and laboratory parameters in old and very old patients with coronary artery disease (CAD) based on the determination of the blood concentration of ionized calcium and daily excretion of calcium in the urine. Materials and methods. This work was a cross-sectional study enrolled 102 patients (84 women and 18 men) with coronary artery disease with a mean age of 83.0±5.9 years. The blood level of ionized calcium (N 1.16–1.32 mmol/l), daily excretion of calcium in the urine (N 2.5– 7.5 mmol/l) and concentration of 25-hydroxycalciferol (25(OH)D) were determined in all patients. Along with this, the bone mineral density of the lumbar spine and proximal femur was analyzed using dual-energy x-ray absorptiometry. Results. The mean daily excretion of calcium in the urine was 1.39±1.1 mmol/l (0.17–7.44 mmol/l). 84.4% of patients had low calcium content in daily urine. The mean blood concentration of ionized calcium was 1.26±0.05 mmol/l (1.16–1.53 mmol/l). Hypercalcemia was observed in 8.3% of patients. Osteoporosis in the proximal femur was registered in 32.9% of patients, in the lumbar spine – in 18.1% of patients. In patients with normal vitamin D level the mean urinary calcium excretion was 1.77±1.2 mmol/l, with vitamin D deficiency – 1.1±0.7 mmol/l (p=0.07). In patients with low calcium excretion in the urine, the mean blood concentration of vitamin D was 18.7±7.7, with normal excretion – 28.5±10.8 ng/ml (p=0.007). Significant inverse relationships were registered between urinary calcium excretion and creatinine (r=-0.36; p<0.0001). In the group of patients with low urinary calcium excretion the mean creatinine level reached 102.3±23.9 µmol/l, with normal excretion – 84.9±11.2 µmol/l (p<0.0001). There was a significant direct correlation between daily urinary calcium excretion and glomerular filtration rate, estimated using the CKD-EPI formula (r=0.39; p<0.0001) and an inverse correlation between blood calcium and GFR (r=-0.26; p=0.01). Significant direct relationship was registered between the blood concentration of ionized calcium and the creatinine (r=0.2; p=0.05) and urea (r=0.32; p=0.04) concentration. Conclusion. The study results demonstrate a low level of calcium excretion in the urine in old and very old patients with coronary artery disease. The urine calcium excretion is primarily due to impaired renal function and low vitamin D concentration.

The Metabolite Profile of Radioisotope-Labeled Biotin in Rats Indicates that Rat Biotin Metabolism is Similar to that in Humans

The egg white-fed rat is the most commonly used animal model of human biotin deficiency. We sought to determine whether the urinary excretion rates of biotin and biotin metabolites in rats are similar to those reported in humans. D-(Carbonyl-14C)biotin was injected intraperitoneally at physiologic doses in 6- to 10-wk-old rats; HPLC and radiometric flow detection were used to specifically identify and quantify biotin and metabolites in urine. Substantial amounts of bisnorbiotin and biotin sulfoxide, the two principal human metabolites, were detected. The excretion rates of biotin and metabolites were strikingly dependent on the dose of biotin. When the dose of [14C]biotin was 30% of the daily dietary intake (a physiologic dose), 50% of the administered 14C was excreted within 24 h; more than half of the excretion was the unchanged vitamin. After d 1, [14C]bisnorbiotin was the major form excreted. For the cumulative 5-d excretion, [14C]biotin accounted for 46 ± 9%, [14C]bisnorbiotin accounted for 47 ± 11%, and [14C]biotin sulfoxide accounted for 8 ± 4% of the total of biotin, bisnorbiotin, and biotin sulfoxide recovered radioactivity (mean ± 1 SD, n = 6). These proportions are similar to those reported in humans: biotin = 52 ± 12%, bisnorbiotin = 35 ± 9%, and biotin sulfoxide = 13 ± 4% of total biotin plus metabolites (mean ± 1 SD, n = 10). Thus, these, studies confirm the earlier identification of bisnorbiotin and biotin sulfoxide as the two principal biotin metabolites and provide evidence that the rat is an appropriate model for human biotin metabolism.

Association between Urinary Creatinine Excretion and Hypothyroidism in Patients with Chronic Kidney Disease.

While hypothyroidism increases serum creatinine (Cr) levels, it is uncertain whether the elevation is mediated via a decline in the glomerular filtration rate (GFR) or the reflection of enhanced Cr production from the muscles or both. In the present study, we explored an association between urinary Cr excretion rate (CER) and hypothyroidism. A total of 553 patients with chronic kidney disease were enrolled in a cross-sectional study. Multiple linear regression analysis was performed to explore the association between hypothyroidism and urinary CER. The mean urinary CER was 1.01 ± 0.38 g/day and 121 patients (22%) had hypothyroidism. The multiple linear regression analysis revealed explanatory variables with urinary CER, including age, sex, body mass index, 24 h Cr clearance (24hrCcr), and albumin while hypothyroidism was not considered an independent explanatory variable. In addition, scatter plot analysis with regression fit line representing the association between estimated GFR calculated using s-Cr (eGFRcre) and 24hrCcr revealed that eGFRcre and 24hrCcr had strong correlations with each other in hypothyroid patients as well as euthyroid patients. Collectively, hypothyroidism was not considered an independent explanatory variable for urinary CER in the present study and eGFRcre is a useful marker to evaluate kidney function regardless of the presence of hypothyroidism.

Effectiveness of Mycophenolate Mofetil Among Patients With Progressive IgA Nephropathy

The role of mycophenolate mofetil (MMF) in management of immunoglobulin A nephropathy (IgAN) remains highly controversial. To evaluate the efficacy and safety of MMF in patients with IgAN at high risk of kidney function loss. This randomized clinical trial with open-label, blinded end-point design was conducted among adults with IgAN, proteinuria greater than 1.0 g/d, and estimated glomerular filtration rate (eGFR) greater than 30 and less than 60 mL/min/1.73m2 or with persistent hypertension from September 2013 to December 2015. During a 3-month run-in period, 238 patients received optimized supportive care (SC), including losartan. Patients with a urinary protein excretion rate of 0.75 g/d or greater despite of 3 months optimized SC were enrolled into the trial for 3 years. Survivors of the trial who did not receive dialysis or transplant were followed up after the trial for a median (IQR) of 60 (47-76) months. Data were analyzed from March through June 2022. A total of 170 participants were randomized in a 1:1 ratio to receive MMF (initially, 1.5 g/d for 12 months, maintained at 0.75-1.0 g for at least 6 months) plus SC or SC alone. The primary outcomes were (1) a composite of doubling of serum creatinine, end-stage kidney disease (dialysis, transplant, or kidney failure without receiving kidney replacement therapy), or death due to kidney or cardiovascular cause and (2) progression of chronic kidney disease. Among 170 randomized patients (mean [SD] age 36.6 [9.4] years; 94 [55.3%] male patients), 85 patients received MMF with SC and 85 patients received SC alone. The mean (SD) eGFR was 50.1 (17.9) mL/min/1.73m2 and mean (SD) proteinuria level was 1.9 (1.7) g/d; 168 patients (98.8%) completed the trial, and 157 participants (92.4%) survived and did not receive dialysis or transplant. Primary composite outcome events occurred in 6 patients (7.1%) in the MMF group and 18 patients (21.2%) in the SC group (adjusted hazard ratio [aHR], 0.23; 95% CI, 0.09-0.63). Progression of chronic kidney disease occurred in 7 participants (8.2%) in the MMF group and 23 participants (27.1%) in the SC group (aHR, 0.23; 95% CI, 0.10-0.57). The effect of MMF treatment on primary outcomes was consistent across prespecified subgroups, with no significant interaction per subgroup. During posttrial follow-up, annual loss of eGFR accelerated after discontinuation of MMF; mean (SD) annual eGFR loss during the study period was 2.9 (1.0) mL/min/1.73m2 in the MMF group and 6.1 (1.2) mL/min/1.73m2 among 66 patients in the MMF group who discontinued MMF after the trial. Serious adverse events were not more frequent with MMF vs SC alone. This study found that addition of MMF to SC compared with SC alone significantly reduced risk of disease progression among patients with progressive IgAN. ClinicalTrials.gov Identifier: NCT01854814.

Urine 24-Hour Sodium Excretion Decreased between 1953 and 2014 in Japan,but Estimated Intake Still Exceeds the WHO Recommendation

Background: Accurate monitoring of sodium intake is necessary for evaluating strategies used to reduce sodium intake. However, no repeat survey has been conducted in representative populations in Japan to examine trends in sodium intake with the use of 24-h urinary sodium excretion, a standard evaluation method for sodium intake monitoring.Objective: The objective of this study was to examine potential trends in sodium intake by examining previous reports of 24-h urinary sodium excretion in healthy Japanese adult populations.Methods: We systematically searched for reports of 24-h urinary sodium excretion in healthy Japanese adult populations (mean age range: 18-69 y). We searched PubMed and Web of Science for English-language articles and hand-searched 7 Japanese scientific journals for Japanese-language articles. Trends in urinary sodium excretion were examined with the use of weighted linear regression and random-effects meta-regression analyses, with adjustment or stratification to address study characteristics (population mean age, percentage of men, and sample size) and study assessment for completeness of urine collection.Results: We identified 68 reports of urinary sodium excretion from 53 articles published from 1953 through 2014 that showed high rates of urinary sodium excretion in healthy Japanese adult populations (weighted mean: 4900 mg/d). The rate of urinary sodium excretion significantly decreased between 1953 and 2014, by 4350 mg/d (P < 0.001); however, the rate of reduction in urinary sodium excretion was variable and decreased with time (P-linear trend <0.001 and P-quadratic trend <0.001). In the random-effects meta-regression analysis of studies that assessed completeness of urine collection with creatinine excretion, no significant relation between urinary sodium excretion and year was observed from 1978 to 2014 (β = -16, P = 0.40).Conclusion: Despite a decrease in urinary sodium excretion in healthy Japanese adult populations between 1953 and 2014, sodium intake still exceeds the WHO recommendation for adults. This review was registered at PROSPERO as CRD42016035452.

Diagnosis by Microbial Culture, Breath Tests and Urinary Excretion Tests, and Treatments of Small Intestinal Bacterial Overgrowth.

Small intestinal bacterial overgrowth (SIBO) is characterized as the increase in the number and/or alteration in the type of bacteria in the upper gastrointestinal tract and accompanies various bowel symptoms such as abdominal pain, bloating, gases, diarrhea, and so on. Clinically, SIBO is diagnosed by microbial culture in duodenum/jejunum fluid aspirates and/or the breath tests (BT) of hydrogen/methane gases after ingestion of carbohydrates such as glucose. The cultural analysis of aspirates is regarded as the golden standard for the diagnosis of SIBO; however, this is invasive and is not without risk to the patients. BT is an inexpensive and safe diagnostic test but lacks diagnostic sensitivity and specificity depending on the disease states of patients. Additionally, the urinary excretion tests are used for the SIBO diagnosis using chemically synthesized bile acid conjugates such as cholic acid (CA) conjugated with para-aminobenzoic acid (PABA-CA), ursodeoxycholic acid (UDCA) conjugated with PABA (PABA-UDCA) or conjugated with 5-aminosalicylic acid (5-ASA-UDCA). These conjugates are split by bacterial bile acid (cholylglycine) hydrolase. In the tests, the time courses of the urinary excretion rates of PABA or 5-ASA, including their metabolites, are determined as the measure of hydrolytic activity of intestinal bacteria. Although the number of clinical trials with this urinary excretion tests is small, results demonstrated the usefulness of bile acid conjugates as SIBO diagnostic substrates. PABA-UDCA disulfate, a single-pass type unabsorbable compound without the hydrolysis of conjugates, was likely to offer a simple and rapid method for the evaluation of SIBO without the use of radioisotopes or expensive special apparatus. Treatments of SIBO with antibiotics, probiotics, therapeutic diets, herbal medicines, and/or fecal microbiota transplantation are also reviewed.

Clinical significance of vascular endothelial growth factor and endothelin-1 in serum levels as novel indicators for predicting the progression of diabetic nephropathy

Objective: Early diagnosis and intervention of diabetic nephropathy (DN) is necessary to optimize therapy in order to delay the progression of diabetes. This research aimed to reveal the change of vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1) in patients with DN, and to assess possible correlations with glycated hemoglobin (HbAlc) values. Methods: The present study was a retrospective, single-center study conducted at a teaching hospital in the northeast China. A total of 120 patients were divided into proteinuria-positive group ( n = 40), the microalbuminuria group ( n = 40), and the high proteinuria group ( n = 40) according to the urinary albumin excretion rate (UAER), and 40 healthy volunteers were selected as the control group. The levels of VEGF, ET-1 and HbA1c were measured in all subjects and principal component analysis (PCA) was performed to classify and reveal correlations between VEGF, ET-1 and HbA1c. Results: Compared to the control group, a significant difference in the increase of HbA1c was detected in group I, II and III. A significant increase in the concentrations of serum VEGF and ET-1 was also observed. HbA1c in DN patients had proven to be positively correlated with VEGF (r = 0.7941; p &lt; 0. 0001) and ET-1 (r = 0.8504; p &lt; 0.0001) respectively. Conclusion: The elevated levels of VEGF and ET-1 in serum have been proposed as being able to supplement the additional information about the progression of DN. These data suggest that the decrease in endothelial function may be related to poor glycemic control.

Baseline anxiety disorders are associated with progression of diabetic kidney disease in type 2 diabetes

Background Diabetic kidney disease (DKD) is a leading cause of kidney failure worldwide. Anxiety has been associated with disease progression in non-diabetes patients. We aimed to examine the prospective association between anxiety and progression of DKD in type 2 diabetes. Methods We conducted a prospective cohort study of 2040 participants with type 2 diabetes at the Diabetes Center of Shanghai General Hospital between May 2017 and June 2020. Anxiety disorders at baseline were diagnosed by a structured clinical interview based on the 10th Revision of International Classification of Disease (ICD). Progression of DKD was identified as the transition from one urinary albumin excretion rate (AER) stage to the next or the development of kidney failure during the follow-up period. Results At baseline, 403 (19.8%) had a diagnosis of anxiety disorders, of whom 107 (26.6%) also received a depression diagnosis. During a median follow-up time of 3.2 years, deterioration of the kidney status occurred in 340 (16.7%) individuals. After adjustment for potential confounders including depression or an anxiety × depression interaction term, anxiety disorders were independently related to an increased risk of progression of DKD (HR 1.539, 95% CI 1.130–2.095, p = 0.006; HR 1.536, 95% CI 1.111–2.122, p = 0.009, respectively). Conclusions Anxiety disorders at baseline, independent of possible confounders, were associated with the progression of DKD in type 2 diabetes. Whether therapeutic interventions for anxiety reduce the risk needs to be investigated.

Effects of lipopolysaccharide stimulation during pregnancy on kidneys and blood vessels in offspring rats

Objective: To investigate the effect of lipopolysaccharide (LPS) inflammatory stimulation during pregnancy on offspring rats. Methods 20 SD pregnant rats were randomly divided into control and LPS groups, with 10 rats in each group. Rats in LPS group received intraperitoneal injection of LPS 0.79 mg/kg on the Days 8th, 10th, and 12th of gestation, and rats in control group received intraperitoneal injection of the same volume of sterile saline. The blood pressure of offspring rats was measured once every two weeks from 8 weeks of age to 16 weeks of age. Protein expression of NF-κB and NOX2 was detected by immunohistochemistry. ROS and NO levels in vascular tissues were observed by staining with DHE and DAF-2DA cular tissues were observed by staining with DHE and DAF-2DA fluorescent probes, respectively. Results At 8, 10, 12, 14 and 16 weeks of age,the systolic blood pressure of offspring in the LPS group was higher than that of the control group at the same age (P< 0.01).The urine volume and urinary sodium excretion rate of the LPS group were significantly lower than those of the control group (P < 0.05), while the urine creatinine and urine protein were not statistically significant as compared with those of the control group. Compared with the control group, the expression of NF-κB, NOX2, Ang II in thoracic aorta, and ROS in mesenteric artery were higher in LPS group. However, mesenteric artery NO expression was lower (P < 0.01) Conclusion LPS inflammatory stimulation during pregnancy causes kidneys inflammation and increased oxidative stress in blood vessels in offspring rats.

PS-C33-11: FACTORS RELATED TO DETERIORATED KIDNEY FUNCTION IN RESISTANT HYPERTENSION PATIENTS

Objectives: To determine the factors associated with renal function deterioration in resistant hypertension (RH) patients Methods: The study included 152 patients aged 28 to 79 years with RH. They underwent measurement of office and ambulatory blood pressure monitoring (ABPM). Blood level of potassium, sodium, glucose, creatinine, uric acid, citrulline, C-reactive protein (CRP), matrix metalloproteinase-12 (MMP-12), aldosterone-renin ratio and 24-h excretion of metanephrine and 24-h urinary albumin excretion rate (AER) were determined. Glomerular filtration rate (GFR) was estimated by the CKD-EPI formula. Results: Chronic kidney disease (CKD) was diagnosed in 32.3% of patients with RH (gr.1 pts), gr.2 pts - those without CKD. Spearman's correlation analysis showed a negative relationship between GFR and office diastolic BP (DBP) and 24 hours mean DBP (r = -0.233; r = -0.373; P &lt; 0.01, respectively). Significant negative correlation was revealed between GFR and daytime systolic BP variability (r = -0.275; P &lt; 0.01). GFR was inversely related to AER (r = -0.412; P &lt; 0.01), uric acid (r = -0.311; P &lt; 0.05), CRP (r = -0.314; P &lt; 0.05), MMP-12 (r = -0.385; P &lt; 0.01), citrulline (r = -0.375; P &lt; 0.01), sodium (r = -0.284; P &lt; 0.05), aldosterone and urinary metanephrine level (r = -0.225; P &lt; 0.05 and r = - 0.210; P &lt; 0.05). In gr.1pts. level of CRP, MM-12 and citrulline was significantly (P &lt; 0.01) higher than in the gr.2 pts. Factors independently and most closely related to reduced GFR in RH patients are 24 hours mean DBP (β; = -0.449, P &lt; 0.001), CRP (β; = -0.354, P &lt; 0.01), MMP-12 (β; = -0.248; P &lt; 0.01) and citrulline (β; = -0.232; P &lt; 0.05). Conclusions: Revealed associations, in addition to elevated blood pressure, indicate the possible pathogenic role of low-grade systemic inflammation biomarkers in the renal function deterioration in RH patients. Targeting low-grade systemic inflammation may improve BP control in resistant hypertension patients with CKD.

Histological Manifestations of Diabetic Kidney Disease and its Relationship with Insulin Resistance.

Histological manifestations of diabetic kidney disease (DKD) include mesangiolysis, mesangial matrix expansion, mesangial cell proliferation, thickening of the glomerular basement membrane, podocyte loss and foot process effacement, hyalinosis of the glomerular arterioles, interstitial fibrosis and tubular atrophy. Glomerulomegaly is a typical finding. Histological features of DKD may occur in the absence of clinical manifestations, having been documented in patients with normal urinary albumin excretion and normal glomerular filtration rate. Furthermore, the histological picture progresses over time while clinical data may remain normal. Conversely, histological lesions of DKD improve with metabolic normalization, following effective pancreas transplantation. Insulin resistance has been associated with the clinical manifestations of DKD (nephromegaly, glomerular hyperfiltration, albuminuria, and kidney failure). Likewise, insulin resistance may underlie the histological manifestations of DKD. Morphological changes of DKD are absent in newly diagnosed type 1 diabetes patients (with no insulin resistance), but appear afterwards when insulin resistance develops. In contrast, structural lesions of DKD are typically present before the clinical diagnosis of type 2 diabetes. Several heterogeneous conditions that share the occurrence of insulin resistance, such as aging, obesity, acromegaly, lipodystrophy, cystic fibrosis, insulin receptor dysfunction, and Alström syndrome, also share both clinical and structural manifestations of kidney disease, including glomerulomegaly and other features of DKD, focal segmental glomerulosclerosis, and C3 glomerulopathy, which might be ascribed to reduction in the synthesis of factor H binding sites (such as heparan sulfate) that leads to uncontrolled complement activation. Alström syndrome patients show systemic interstitial fibrosis markedly similar to that present in diabetes.

Type 2 diabetics presumed to be normotensive: Masked hypertension, urinary albumin excretion rate and echocardiographic screening

Type 2 diabetics presumed to be normotensive: Masked hypertension, urinary albumin excretion rate and echocardiographic screening

Correlation of Blood Pressure with Microalbuminuria and Dyslipidaemia in Patients with Essential Hypertension: A Case-control Study

Introduction: Hypertension (HTN) is one of the most common disease affecting the people around the world. Microalbuminuria and dyslipidaemia has been considered as an early indicator of vascular damage, endothelial dysfunction and renal disease. Studies, conducted to evaluate microalbuminuria, dyslipidaemia in essential hypertensive patients are scarce. Aim: To assess the microalbuminuria, dyslipidaemia in essential hypertensive patients and also, to correlate these parameters with Blood Pressure (BP). Materials and Methods: This case-control study was conducted in the Department of Biochemistry at Veer Surendra Sai Institute of Medical Sciences and Research (VIMSAR), Sambalpur, Odisha, India, from January 2020 to February 2021. The study included 70 healthy individuals as controls and 70 essential hypertensive patients as cases in the age group of 25 to 55 years. According to Joint National Committee (JNC) 7 guidelines, out of 70, 20 cases were categorised as stage I (BP≥140-159/90-99 mmHg) and 50 as stage II (BP≥160/100 mmHg). Renal profile, lipid profile, total protein and albumin, microalbumin and Albumin-creatinine Ratio (ACR) were evaluated. Pearson correlation coefficient was applied to statistically analyse the data. Results: In the present study, 38 (54.3%) were males and 32 (45.7%) were females. Whereas, in controls, 44 (62.8%) were males and 26 (37.2%) were females. The mean age in cases 44.4±8.58 years, Systolic Blood Pressure (SBP) 156.0±35.1 mmHg, Diastolic Blood Pressure (DBP) 101±12.9 mmHg, serum creatinine 1.08±0.29 mg/dL, serum uric acid 7.37±1.8 mg/dL, serum total cholesterol 171±44.7 mg/dL, serum triglycerides 173±48.4 mg/dL, Low-density Lipoprotein Cholesterol (LDL-C) 107±38.8 mg/dL, Very Low-density Lipoprotein Cholesterol (VLDL-C) 35.1±10.2 mg/dL, microalbuminuria 75±31.9 mg/L, and urinary ACR 78±44.1 were significantly increased and serum High-density Lipoprotein Cholesterol (HDL-C) 31.7±7.07 mg/dL levels were decreased in cases than controls. Urinary ACR was significantly increased in stage II. ACR was positively correlated with SBP, DBP, creatinine, uric acid, total cholesterol, triglycerides, VLDL-C and negatively correlated with HDL-C. Conclusion: Blood pressure was positively correlated with lipid profile parameters, except HDL-C. Increased urinary albumin excretion rate may be useful and inexpensive marker for the identification of patients with higher cardiovascular risk and organ damage.

Clinical efficacy and safety of Xuefu Zhuyu decoction in the treatment of diabetic kidney disease: A protocol for systematic review and meta-analysis.

Diabetic kidney disease (DKD) is one of the common complications of diabetes, the most crucial cause of end-stage renal disease, and a significant cause of death in diabetes patients. In recent years, Xuefu Zhuyu decoction has also been widely used in treating diabetic nephropathy. However, there need to be more systematic reviews that comprehensively describe the effectiveness and safety of Xuefu Zhuyu decoction in treating DKD. Therefore, we will conduct a systematic review and meta-analysis to evaluate the indicators of Xuefu Zhuyu decoction in the treatment of DKD to provide evidence-based support. Eligible published randomized controlled trials from January 2005 to October 2022 will be obtained by searching PubMed, Cochrane Library, EMBASE, Web of Science, CNKI, Wanfang, and VIP in Chinese and English. The Cochrane Collaboration Risk of bias tool will be used for methodological quality assessment and risk of bias. The meta-analysis will be performed using Cochrane RevMan 5.4 software. This study will compare the following indicators: the primary outcomes: urinary albumin excretion rate and urea nitrogen. Secondary outcomes: blood creatinine; 24 hours urine protein quantification; glycosylated hemoglobin; fasting blood glucose; 2-hour postprandial blood glucose; total cholesterol; triglycerides; total effective rate; incidence of adverse events. The results of this systematic review will provide an objective, evidence-based basis for judging the efficacy and safety of Xuefu Zhuyu decoction in treating DKD.

Toxicological and hygienic study of imidourea as antibacterial preservative for pharmaceutical and cosmetic products

Introduction. Imidourea is widely used as an antibacterial preservative in the pharmaceutical and cosmetic industries. There are literature data on the toxicity and specific effect of the substance, but there are no hygienic standards in the air of the working area necessary to protect the health of workers. The study aims to substantiate the approximate safe level of exposure (ASLE) of imidourea in the air of the working area based on the study of the nature of biological action in various ways of entry into the body. Materials and methods. The researchers chose the methods for studying the functions of organs and systems of experimental animals after a single inhalation of the substance at concentrations of 35.3±5.7 mg/m3 and 6.1±1.7 mg/m3 taking into account the literature data on the biological effect of the compound under study. We studied the antimicrobial effect of the substance on the intestinal microbiota of rats after 24 hours and 144 hours after inhalation exposure. Results. During inhalation of the substance in both concentrations, the researchers observed disturbances in the balance of the intestinal microflora, which were characterized by changes in the number of individual representatives of the normal microbiota, which corresponds to the initial signs of dysbiosis of the 1st degree. 144 hours after exposure, the microflora balance was almost restored. Inhalation exposure to imidourea at a concentration of 35.3 mg /m3 also revealed changes in the functional parameters of the liver (decreased activity of alkaline phosphatase and glucose concentration in blood serum) and kidneys (decreased content and rate of protein excretion in urine). Conclusion. Imidourea in the inhalation route of admission has a general toxic, sensitizing, weak antimicrobial effect. We recommend to use the ASLE of imidourea in the air of the working area of 1.5 mg/m3 (aerosol). Ethics. The Ethics Commission of JSC "VNC BAS" adopted and approved the imidourea research program (Protocol No. 3 of 11.02.2020).

Clinical efficacy and safety of astragalus injection combined with ACEI/ARB in the treatment of diabetic kidney disease: Protocol for a systematic review and meta-analysis.

Kidney disease is a common complication of diabetes and the main cause of end-stage renal disease. Astragalus (Huangqi) injection in combination with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARBs) have been widely used for the treatment of diabetic kidney disease (DKD) in China. However, no supporting evidence yet exists with regard to the safety and effectiveness of this approach. Here a protocol is outlined for use in systematic evaluation of the safety and effectiveness of astragalus injection combined with ACEI/ARB for the treatment of DKD. Randomised controlled trials will be retrieved from 8 scientific databases, including PubMed, Web of Science, EMBASE database, Cochrane Library, China National Knowledge Infrastructure, Wanfang, China Biomedical Literature CD-ROM Database and China Science Journal Database. Ongoing clinical trial databases will also be searched for studies published from the time of establishment of each database to September 1, 2022. that will include the Chinese Clinical Trial Registration Centre (www.chictr.org.cn/), the World Health Organisation International Trial Registration Platform (https://www.who.int/clinical-trials-registry-platform), Google Scholar (https://scholar.google.com/), Baidu Scholar (https://xueshu.baidu.com), etc. The main outcome indicators included urinary albumin excretion rate or 24-hour urinary albumin excretion rate, and renal function (blood urea nitrogen, serum creatinine concentration). The secondary outcome indicators mainly include the following 4 aspects: blood sugar, blood pressure, blood lipid levels and adverse events. Two researchers will independently select and extract data from randomized controlled trials and determine risks of bias. Meta-analysis will be performed using Revman5.4 then the quality of evidence from randomized clinical trials will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) System tool. This review will be the first to summarize meta-analysis results regarding the efficacy and safety of Huangqi injection combined with ACEI/ARB when administered during any stage of diabetic nephropathy rather than during only a single stage of the disease. It will provide high-quality guidance for the treatment of diabetic kidney disease and provide patients with more treatment options.

Torsemide Pharmacometrics in Healthy Adult Populations Including CYP2C9 Genetic Polymorphisms and Various Patient Groups through Physiologically Based Pharmacokinetic-Pharmacodynamic Modeling.

Torsemide is a widely used diuretic in clinical practice. In this study, pharmacokinetic (PK) and pharmacodynamic (PD) simulations of torsemide for various population groups and exposure scenarios were performed through human-scale physiologically-based PK-PD (PBPK-PD) modeling of torsemide. For PBPK-PD modeling of torsemide, invitro and clinical data of torsemide reported previously were used. After exposure to clinical doses of torsemide, observed plasma (or serum) concentration and urine torsemide excretion profiles were used as PK-data, and observed urinary sodium excretion rate was used as PD-data. The model was then extended to take into account physiological and biochemical factors according to different CYP2C9 phenotypes or patient populations. The established model captured various torsemide clinical results well. Differences in torsemide PKs and PDs between patient groups or CYP2C9 genetic polymorphisms were modelologically identified. It was confirmed that degrees of differences in torsemide PKs and PDs by disease groups were greater than those according to different CYP2C9 phenotypes. According to torsemide administration frequency or dose change, it was confirmed that although the difference in plasma PKs between groups (healthy adult and patient groups) could increase to 14.80 times, the difference in PDs was reduced to 1.01 times. Results of this study suggested that it is very important to consider disease groups in the setting of torsemide clinical therapy and that it is difficult to predict PD proportionally with only differences in PKs of torsemide between population groups. The PBPK-PD model established in this study is expected to be utilized for various clinical cases involving torsemide application in the future, enabling optimal drug therapy.