Urinary Protein Concentration Research Articles

Urinary Epidermal Growth Factor Level as a Noninvasive Indicator of Tubular Repair in Patients with Acute Kidney Injury.

Epidermal growth factor (EGF), an essential factor for the proliferation and survival of renal tubular cells, is expressed by distal tubules and normally excreted via urine. Previous studies in rats demonstrated that acute tubular injury reduces urinary EGF levels. However, it is unclear whether urinary EGF is a suitable monitoring marker of tubular repair status after acute kidney injury (AKI) in humans. To address this question, we measured serum and urinary EGF in patients with AKI (n = 99) using ELISA and investigated whether urinary EGF levels were associated with the severity of tubular injury and renal prognosis. Urinary EGF was abundant in healthy controls but showed a significant decrease in AKI patients (14,522 ± 2190 pg/mL vs. 3201 ± 459.7 pg/mL, p < 0.05). The urinary EGF level in patients with renal AKI was notably lower than that in patients with pre-renal AKI. Furthermore, the urinary EGF level in patients with AKI stage 3 was significantly lower than that in patients with AKI stage 1. Urinary EGF levels were negatively correlated with urinary β-2MG and serum creatinine levels but positively correlated with hemoglobin levels and eGFR. Urinary EGF was not significantly correlated with urinary NAG, α-1MG, L-FABP, NGAL, KIM-1, or urinary protein concentrations. No significant correlation was observed between serum and urinary EGF levels, suggesting that urinary EGF is derived from the renal tubules rather than the blood. In living renal transplantation donors, the urinary EGF/Cr ratio was approximately half the preoperative urinary EGF/Cr ratio after unilateral nephrectomy. Collectively, these data suggest that urinary EGF is a suitable noninvasive indicator of not only the volume of functional normal renal tubules but also the status of tubular repair after AKI.

Concomitant use of interleukin-2 and tacrolimus suppresses follicular helper T cell proportion and exerts therapeutic effect against lupus nephritis in systemic lupus erythematosus-like chronic graft versus host disease.

Defective interleukin-2 (IL-2) production contributes to immune system imbalance in patients with systemic erythematosus lupus (SLE). Recent clinical studies suggested that low-dose IL-2 treatment is beneficial for SLE and the therapeutic effect is associated with regulatory T cell (Treg) expansion. Pharmacological calcineurin inhibition induces a reduction in the number of Tregs because they require stimulation of T cell receptor signaling and IL-2 for optimal proliferation. However, the activation of T cell receptor signaling is partially dispensable for the expansion of Tregs, but not for that of conventional T cells if IL-2 is present. We examined whether addition of IL-2 restores the Treg proportion even with concurrent use of a calcineurin inhibitor and if the follicular helper T cell (Tfh) proportion is reduced in an SLE-like murine chronic graft versus host disease model. Using a parent-into-F1 model, we investigated the effect of IL-2 plus tacrolimus on Treg and Tfh proportions and the therapeutic effect. Treatment with a combination of IL-2 and tacrolimus significantly delayed the initiation of proteinuria and decreased the urinary protein concentration, whereas tacrolimus or IL-2 monotherapy did not significantly attenuate proteinuria. Phosphorylation of signal transducer and activator of transcription 3, a positive regulator of Tfh differentiation, was reduced by combination treatment, whereas phosphorylation of signal transducer and activator of transcription 5, a negative regulator, was not reduced. Addition of calcineurin inhibitors as adjunct agents may be beneficial for IL-2-based treatment of lupus nephritis.

Effect of Carnosine on Oxidative Damage to the Kidneys in Experinental Diabetes Mellitus

The article presents the results of a study into the effect of carnosine on oxidative damage to the kidneys in experimental diabetes mellitus. The experiment was carried out using two groups of Wistar rats: control (n=8) and experimental (n=11). In both groups, streptozotocin-induced diabetes mellitus was simulated for eight weeks. Experimental animals were intragastrically injected with carnosine (15 mg/kg) from weeks 4 to 8. The concentration of glucose, protein and creatinine excretion in urine were determined. At the end of eight weeks, the kidneys were removed from the rats to determine the indicators of oxidative stress severity (concentration of thiobarbiturate-reactive products, total antioxidant activity, activity of catalase, superoxide dismutase, glutathione peroxidase) and to conduct morphometry of the size of the renal glomeruli, the area of the vascular bed, capillaries and mesangium in the glomeruli, the number of podocytes. A comparison with the control showed the use of carnosine led to a 1.5-fold decrease in the concentration of thiobarbiturate-reactive products (p&lt;0.001), a 2.2-fold increase in the total antioxidant activity (p&lt;0.001), and a 1.2-fold increase in catalase activity (p=0.039). The area of the renal glomeruli and the mesangium in this group decreased by 1.6 times (p&lt;0.001 and p=0.04, respectively). The total area of blood flow increased by 2.4 times (p&lt;0.001), the area of one capillary, and the number of podocytes in the glomerulus increased by 1.9 times (p&lt;0.001 and p=0.001). A 3.5-fold decrease in protein concentration in urine was also noted (p=0.007). Therefore, inhibition of the formation of advanced glycation end products by carnosine in experimental diabetes mellitus attenuates oxidative damage to the kidneys. This is evidenced by a decrease in proteinuria, an increase in the number of podocytes, a decrease in the area of the renal glomeruli, and an improvement in the condition of the glomerular vascular system.

Choroidal Vascularity Index and Choroidal Structural Changes in Children With Nephrotic Syndrome.

To investigate the choroidal vascularity index (CVI) and choroidal structural changes in children with nephrotic syndrome. This was a cross-sectional study involving 45 children with primary nephrotic syndrome and 40 normal controls. All participants underwent enhanced depth imaging-optical coherence tomography examinations. An automatic segmentation method based on deep learning was used to segment the choroidal vessels and stroma, and the choroidal volume (CV), vascular volume (VV), and CVI within a 4.5mm diameter circular area centered around the macular fovea were obtained. Clinical data, including blood lipids, serum proteins, renal function, and renal injury indicators, were collected from the patients. Compared with normal controls, children with nephrotic syndrome had a significant increase in CV (nephrotic syndrome: 4.132 ± 0.464 vs. normal controls: 3.873 ± 0.574; P = 0.024); no significant change in VV (nephrotic syndrome: 1.276 ± 0.173 vs. normal controls: 1.277 ± 0.165; P = 0.971); and a significant decrease in the CVI (nephrotic syndrome: 0.308 [range, 0.270-0.386] vs. normal controls: 0.330 [range, 0.288-0.387]; P < 0.001). In the correlation analysis, the CVI was positively correlated with serum total protein, serum albumin, serum prealbumin, ratio of serum albumin to globulin, and 24-hour urine volume and was negatively correlated with total cholesterol, low-density lipoprotein cholesterol, urinary protein concentration, and ratio of urinary transferrin to creatinine (all P < 0.05). The CVI is significantly reduced in children with nephrotic syndrome, and the decrease in the CVI parallels the severity of kidney disease, indicating choroidal involvement in the process of nephrotic syndrome. Our findings contribute to a deeper understanding of how nephrotic syndrome affects the choroid.

Features of Klotho Protein Expression in Rat Kidneys in Experimental Hyperglycemia Against the Background of Pharmacological Correction with GABA Derivatives

The aim is to identify the features of Klotho protein expression in the epithelium of the convoluted tubules of the kidney during prolonged experimental hyperglycemia and pharmacological correction with GABA derivatives. Material and methods. The study used 50 mongrel male rats (initial weight: 330,0–360,0 g) with streptozotocin diabetes lasting 6 months. 6 months after the injection of streptozotocin (60 mg/kg), animals with a glycemic level of ≥ 15 mmol/l were included in the study (after 4 hours of food deprivation), then GABA derivatives (aminalon, mefargine, succicard) were administered orally for 30 days. Proteinuria and serum creatinine concentrations were evaluated. After euthanasia, kidney tissue was fixed in buffered neutral formalin and examined using immunofluorescence microscopy. The intensity of the glow was evaluated based on a visual-analog scale. Results. In the group with chronic hyperglycemia without treatment, there was a significant increase in the protein content in daily urine and serum creatinine levels (p&lt;0,05). In the group of animals with chronic hyperglycemia without treatment, there was a significant decrease in the expression of Klotho protein compared to the group of intact animals during immunofluorescence analysis. In the group treated with the GABA derivative succicard, there was an improvement in the functional state of the kidneys, accompanied by a significant increase (p≤0,0001) in the area of Klotho-positive material in the epithelium of the convoluted tubules of the kidney in relation to the group of animals with prolonged hyperglycemia without treatment. Conclusion. Prolonged hyperglycemia causes severe renal dysfunction in rats with streptozotocin diabetes: an increase the proteinuria and serum creatinine levels is accompanied by a decrease in the expression of Klotho protein in the kidneys. The GABA derivative succicard with course administration improves kidney function and this effect is accompanied by an increase in the expression of Klotho protein.

KIDNEYS INVOLVEMENT INTO THE THYROID GLAND BURNING PATHOGENETIC MECHANISMS

Background. Burn injuries considered to be the most common and severe diseases in people, positioned second place after traffic injuries. The thyroid gland, taking into account the wide range of thyroid hormones physiological activity, its structural and functional organization and morpho-functional features as well as large-scale duplicative mechanisms of regulatory feedback, is one of the first which receives the alterative thermal influence. Thyroid gland and other organs of the body dysfunction or pathological dysregulation occurs as a result of thermal exposure “triggers” systemic dysfunctions via the “vicious circle” and positive feedback mechanisms and systemic-antisystemic regulation which cannot be ignored by the majority of internal organs and organ systems resulting ion their functional disorders. We decided to test the assumptions regarding the kidneys participation in thyroid burning pathological process manifestation.&#x0D; Aim: to investigate the changes in lipid peroxidation and antioxidant defense in erythrocytes and kidney tissue and to investigate the kidneys functional activity throughout the thyroid gland thermal.&#x0D; Materials and methods. The malondialdehyde concentration and antioxidant enzymes activity - glutathione, catalase, superoxide dismutase and glutathione peroxidase - were determined in white Wistar rats’ erythrocytes and kidney homogenate 1, 3, 7, 14, 21, and 30 days after the thyroid gland burning. Diuresis was calculated in rats during induced water diuresis and both the protein and creatinine content in urine was determined during the indicated periods after thyroid gland burning&#x0D; Results. The significant accumulation of lipoperoxidation intermediate products and the antioxidant enzymes activity suppression in erythrocytes and in the kidney parenchyma are registered in rats during the post-burn period. The postburn period course is characterized by diuresis decrease. The urine protein level increased and the rate of protein excretion also increased in conditions of thyroid gland burning&#x0D; Conclusion. Significant accumulation of lipoperoxidation intermediate products and the antioxidant enzymes activity suppression in erythrocytes and in the liver parenchyma is recorded in thyroid gland burning dynamics which we consider as evidence of erythrocytes and kidney involvement in the specified pathological process mediation. The expressed renal dysfunction develops with thyroid gland thermal damage which is manifested by kidneys both excretory and filtering functions impairment. The data obtained we consider as the experimental background for kidney involvement into the thyroid gland burning pathogenetic mechanisms and the pathological dysregulation of organs and organ systems formation in these pathological conditions.

Improvement in Clinical Features of L-NAME-Induced Preeclampsia-like Rats through Reduced SERPINA5 Expression.

Pre-eclampsia (PE) is a severe pregnancy disorder that poses a significant health risk to both mother and fetus, with no preventive or therapeutic measures. Our previous research suggested an association between elevated SERPINA5 levels and PE features. This study investigated whether SERPINA5 could be a potential therapeutic target for PE. We established PE-like features in pregnant rats using L-NAME (75 mg/kg/d) treatment. Adenoviruses carrying overexpressed or suppressed SERPINA5 genes were intravenously injected into these PE rats on the fifth and seventh days of pregnancy. We evaluated the rats' systolic blood pressure, urine protein concentration, and placental and fetal metrics and histology. Placental gene expression following SERPINA5 overexpression was evaluated using mRNA sequencing. The L-NAME-induced PE rat model observed a significant increase in placental and peripheral SERPINA5 levels. The overexpression of SERPINA5 exacerbated L-NAME-induced hypertension and proteinuria in pregnant rats. A histology examination revealed a smaller placental junctional zone in L-NAME + overexpressing rats. Placental gene expression analysis in the L-NAME + overexpressing group indicated increased coagulation activation. L-NAME-induced hypertension and proteinuria were mitigated when SERPINA5 expression was suppressed. Additionally, placental development was improved in the SERPINA5-suppressed group. Our findings suggested that SERPINA5 may worsen L-NAME-induced PE-like features by promoting the activation of the coagulation cascade. Therefore, reducing SERPINA5 expression could potentially serve as a therapeutic strategy for PE.

Serum and Urinary Matrix Metalloproteinase-9 Concentrations in Dehydrated Horses.

Matrix metalloproteinase-9 is increased in renal tissue in human kidney disease, but its role as a biomarker for kidney disease has not been fully evaluated yet. The aim of this study was to evaluate serum MMP-9 (sMMP-9) and urinary MMP-9 (uMMP-9) concentrations in dehydrated horses. Dehydrated horses were prospectively included. Blood and urinary samples were taken at admission, and after 12, 24, and 48 h (t0, t12, t24, t48), an anti-equine MMP-9 sandwich ELISA was used. Four healthy horses served as the controls. Serum creatinine, urea, symmetric dimethylarginine (SDMA), urine-specific gravity, urinary protein concentration, fractional sodium excretion, and urinary gamma-glutamyl transferase/creatinine ratio (uGGT/Cr) were measured. Statistical analysis included a repeated measures ANOVA and mixed linear regression model. Overall, 40 dehydrated horses were included (mild dehydration 13/40, moderate 16/40, severe 11/40). Acute kidney injury was found in 1/40 horses; 7/40 horses showed elevated serum creatinine, 11/40 horses elevated serum SDMA, and 5/28 elevated uGGT/Cr at presentation. In dehydrated horses, sMMP-9 concentrations were significantly higher on t0 (median: 589 ng/mL, range: 172-3597 ng/mL) compared to t12 (340 ng/mL, 132-1213 ng/mL), t24 (308 ng/mL, 162-1048 ng/mL), and t48 (258 ng/mL, 130-744 ng/mL). In healthy horses, sMMP-9 (239 ng/mL, 142-508 ng/mL) showed no differences over time or compared to patients. uMMP-9 and uMMP-9/creatinine did not differ over time or to the controls. No differences were found between dehydration groups. Urinary casts (p = 0.001; estimate = 135) and uGGT/Cr (p = 0.03; estimate = 6.5) correlated with sMMP-9. Serum urea was associated with uMMP-9/Cr (p = 0.01, estimate 0.9). In conclusion, sMMP-9 was elevated at arrival in dehydrated patients compared to later measurements. Correlations to uGGT/Cr and urinary casts need further evaluation.

A Pilot Study for the Kidney Effects of Voxelotor in Sickle Cell Anemia

The kidneys are among the most commonly affected organ systems in sickle cell anemia (SCA) and an estimated 15% of deaths in patients with SCA are attributed to kidney failure (PMID 7993409). Angiotensin converting enzyme-inhibitors and angiotensin receptor blockers have been adopted to treat SCA-related chronic kidney disease (CKD) from the non-SCA literature, although demonstrated efficacy in SCA CKD has been marginal in a limited number of small, short-term studies (PMID 28589652). Therapies that directly target the pathophysiology of SCA-related kidney disease may stabilize or improve kidney function. Both the rate of hemolysis and the degree of anemia are associated with the development and progression of CKD in SCA (PMID 24329963, 21523807). Voxelotor inhibits hemoglobin polymerization in SCA red blood cells in the deoxygenated state, leading to a reduction in the rate of hemolysis and an increase in hemoglobin concentration. We conducted a pilot study to determine whether voxelotor can improve kidney function in adults with SCA (NCT 04335721). SCA (HbSS or HbSβ 0-thalassemia) patients ≥ 18 years old and with urine dipstick-defined hemoglobinuria (+ for blood &amp; ≤ 2 red blood cells/high power field), CKD stage 1 or 2 (urine albumin-to-creatinine ratio [ACR] ≥ 30 mg/g &amp; estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73m 2), and hemoglobin concentrations of 5.5 - 10.5 g/dL were eligible. The eGFR was calculated using the CKD-EPI 2009 creatinine-based equation without the race coefficient and the 2012 cystatin C-based equation. Patients were randomized to voxelotor 1,500mg/day for 48 weeks or standard of care, as defined by their primary SCA provider. First or second void urines were collected for urine ACR measurements. The primary endpoint was the change in urine ACR from the mean values at baseline and screening versus the mean values at 47 and 48 week visits. One patient randomized to standard of care was started on voxelotor at week 24 by his provider to improve his hemoglobin concentration. This patient is included in the voxelotor treatment group in combined analysis; the change in laboratory measures in this patient is based upon changes from the mean of values at week 12 and 24 to week 47 and 48 visits. Median and range values are provided. Between 3/2021 and 6/2022, 8 SCA patients with hemoglobinuria and urine ACR &amp;gt; 30mg/g crt observed during routine clinic visits were screened and 6 met the inclusion criteria. The median age of the enrolled cohort was 36 (27 - 63) years, 4 were male, 4 were on stable doses of hydroxyurea (median dose 1000mg/day; 500 - 1500mg/day) and 2 were on stable doses of lisinopril (5, 20mg/day) for at least 90 days before screening. Two other patients had been on lisinopril in the past but developed hyperkalemia prior to enrollment. The median values of kidney function measures at screening and baseline study visits were as follows: urine ACR, 251 (32 - 3132) and 392 (80 - 3101) mg/g crt; creatinine-based eGFR, 109 (93 - 136) and 115 (88 - 137) mL/min/1.73m 2; and cystatin C-based eGFR, 82 (61 - 141) and 85 (61 - 128) mL/min/1.73m 2, respectively. SCA patients who received voxelotor (n = 4) had a median increase in hemoglobin concentration of +0.9 g/dL (-0.4 - +2.6 g/dL) and reductions in indirect bilirubin concentration of -2.2 mg/dL (0 - -4 mg/dL) and reticulocyte % of -2.7% (-1.2 - -4.9%). Urine ACR (-59%, -21% - -100%) improved in SCA patients treated with voxelotor but worsened in those who received standard of care without voxelotor (n = 2) (+86.3%, 64 - 108%) (P=0.009) (Figure 1A). 24-hour urine protein concentrations also improved in those that received voxelotor (-45%, -25% - -100%) but increased in those who did not receive voxelotor (+122%, 113 - 131%) (P = 0.002) (Figure 1B). Changes in creatinine- and cystatin-C based eGFR from baseline were not significantly different between patients who received voxelotor and those who did not. This pilot study demonstrates that SCA patients with hemoglobinuria and early stages of CKD treated with voxelotor may have significant improvements in urine ACR and proteinuria after 24 - 48 weeks of therapy. These preliminary results support the concept that improving hemolytic anemia could be a targeted therapeutic approach to reduce biomarkers of kidney dysfunction, and they warrant larger, prospective clinical studies.

Membranous nephropathy after multiple Hymenoptera stings: a case report.

An association between Hymenoptera (bee and wasp) stings and nephrotic syndrome has been rarely reported. We report a case of nephrotic syndrome after multiple Hymenoptera stings, and membranous nephropathy was later diagnosed by a kidney biopsy. The patient was a 79-year-old woman who was stung by Hymenoptera at seven sites on her body. A weight gain of 3.7kg was observed in the patient at 1week after being stung, and she had considerable edema in both lower extremities. A urine protein concentration of 14.8g/g creatinine and a serum albumin concentration of 1.7g/dL led to the diagnosis of nephrotic syndrome. A percutaneous kidney biopsy 8days after the Hymenoptera stings showed stage I membranous nephropathy. She was in complete remission 1week after the administration of oral prednisolone 40mg/day, which was started 14days after Hymenoptera stings, and had no relapse of nephrotic syndrome. To the best of our knowledge, this is the first report of biopsy-proven membranous nephropathy caused by Hymenoptera stings.

Urinary extracellular vesicle dynamics in Parkinson's disease patients with urinary dysfunction.

Parkinson's disease (PD) presents with severe motor manifestations and a plethora of non-motor symptoms. Urinary dysfunctions are one of the most common non-motor symptoms of PD patients responsible for reduced quality of life. Urinary extracellular vesicles (EVs) are mostly considered to originate from the cells in the urogenital tract. In this study, we have performed urinary EV analysis in 29 PD cases with varied severity of urinary dysfunction and correlated it with the EV dynamics in 29 age-matched controls. In the studied cases, apart from urinary dysfunction, symptoms of depression, anxiety, cognitive dysfunction, sleep, and wakefulness were observed in >75% of the cases. No significant difference in urinary EV size, concentration and urinary EV protein concentration was observed between PD cases with urinary dysfunction and controls. However, a significant positive association was observed between urinary EV concentration and motor scores (p = 0.042), while no association was observed between urinary EV concentration and urinary dysfunction scores. Chronic stress induced by motor symptoms could be one of the reasons for excessive EV production in PD patients with urinary dysfunctions. Large-scale studies on the association of urinary EV dynamics with motor and non-motor symptoms may provide additional information on urinary dysfunction in PD.

SEX-SPECIFIC ASPECTS OF TYPE 2 DIABETES MELLITUS IN COMORBIDITY WITH HYPERTENSION

The purose of this investigation is to study individual clinical and diagnostic characteristics in patients with type 2 diabetes mellitus with comorbid essential hypertension (DM + HD) with consideration for sex difference. Participants and methods. We examined 41 patients with comorbidity of type 2 diabetes and hypertension (21 men and 20 women) and 30 patients without diabetes, but having a history of hypertension (14 men and 16 women) and 20 healthy individuals. Results. Systolic and diastolic blood pressure (SBP), (DBP) is significantly higher in patients with comorbidity of DM+HD compared with HD (in men, only DBP), while the heart rate did not change. The protein content in urine was below normal values that indicates an early stage of the pathological condition. Women showed a high level of creatinine compared to normal value in both groups, although this indicator is lower compared to men and is statistically significant in DM + HD. In both groups, there were high numbers of left atrium size, end diastolic size (EDS) compared to normal value, while sex differences were noted: EDS was higher in men. The increased size of left atrium directly correlated with the end-diastolic size (higher in men), the thickness of the interventricular septum (TIVS), and thickness of posterior wall (TPW) (with DM + HD, higher in men). In men with DM + HD, the E / A was lower and the thickness of the intima-media complex (IMC) of the right common carotid artery (CCA) was higher than in the HD group. There were no statistically significant differences in the state of right and left common carotid arteries. The ejection fraction was lower compared to normal values. Conclusion. In patients with diabetes mellitus + hypertension and hypertension, the semi-dimorphic differences of TIVS, TPW, E / A, IMC of right CCA can be used to predict the development of pathological process. A decrease in level of protein in urine indicates absence of proteinuria, glomerular filtration disorders, which is due to early stage of formation of DM + HD pathological state in this category of patients. Absence of changes in urea is associated with a sufficient excretory function of kidneys.

Smoker Detection Using Machine Learning

Smoking remains a persistent global public health challenge, posing severe health risks and socioeconomic burdens. Early detection of smokers is crucial for implementing targeted interventions, public health campaigns, and personalized support to mitigate smoking-related illnesses. The dataset used in this research comprises extensive information on individual health, encompassing age, height, weight, waist circumference, visual acuity in both eyes, hearing capability in both ears, systolic and diastolic blood pressure, cholesterol levels (HDL, LDL, and triglycerides), haemoglobin levels, urine protein content, liver enzymes (AST, ALT, and GTP), presence of dental caries, and fasting blood sugar. Four For the smoking identification job, cutting-edge machine learning methods including logic regression, Gaussian Naive Bayes, Random Forest Classifier, and XGBoost Classifier are used. Each algorithm is tested using a variety of efficiency indicators after being trained on the data set used for training., including accuracy, ROC-AUC scores, and confusion matrices.The outcomes show the efficiency of the Random Forest Classifier, demonstrating an excellent precision of around 79.4% in correctly identifying smokers. This model outperforms the other algorithms and proves to be a robust approach for smoker detection based on the provided health parameters. Furthermore, the study delves into the interpretability of the models, analyzing the significance of different health parameters in predicting smoking behaviour. Insights gained from the feature importance analysis offer valuable guidance for public health practitioners and policymakers in designing targeted interventions.

Sex differences in FASN protein concentrations in urinary exosomes related to serum triglycerides levels in healthy adults

BackgroundDysregulation of lipid metabolism is the most prominent metabolic alteration observed in obesity, cancer, and cardiovascular diseases. The present study aimed to explore the sex differences associated with lipid metabolism in urinary exosome proteins, and evaluate the correlation of urinary exosome proteins with serum lipid biomarkers.MethodsThe key enzymes regulating lipid metabolism in healthy adults were screened using urinary exosome data. Urinary exosomes were isolated from 120 healthy subjects and the expression of urinary proteins was assessed by Western blotting and ELISA. The correlation between urinary protein concentrations and the levels of serum lipid biomarkers was analyzed using correlation analysis.ResultsThree urinary exosome proteins, namely fatty acid synthase (FASN), phosphoenolpyruvate carboxykinase (PCK1), and ATP-citrate synthase (ACLY) were identified, and only FASN showed sex differences. Sex differences were also observed in the serum triglyceride (TG) levels. Healthy males had higher FASN levels than females, and a moderate positive correlation was found between FASN concentrations and serum TG levels in healthy males (r = 0.479, P < 0.05). FASN concentrations in different age groups were positively correlated with the level of serum TG (18 ~ 30 years, r = 0.502; 31 ~ 44 years, r = 0.587; 45 ~ 59 years, r = 0.654; all P < 0.05). In addition, FASN concentrations was positively related to the increase in serum TG levels (range:1.0 ~ 1.7 mmol/L; r = 0.574, P < 0.05).ConclusionsSex differences were observed in urinary exosome FASN protein levels in healthy adults. FASN protein levels positively correlated with increased serum TG levels. FASN may serve as a novel biomarker to evaluate fatty acid synthesis in the human body.

Effect of Vitamin E Supplemented with Calcium in the Treatment of Hypertension During Pregnancy on Maternal and Infant Outcomes

Objective: To investigate the effect of vitamin E supplemented with calcium in the treatment of hypertension during pregnancy on maternal and infant outcomes. Methods: 60 patients with gestational hypertension admitted from January 2020 to December 2022 were recruited and randomly divided into the control group and the observation group, each group including 30 patients. The control group was given routine treatment, whereas the observation group was given routine treatment combined with vitamin E-supplemented calcium therapy, and both groups received treatment until delivery. The clinical effects of the observation group and the control group after treatment, systolic and diastolic blood pressure, mean arterial pressure, urine protein, blood lipid levels at different time points (before and after treatment), and maternal and child outcomes during treatment were uniformly compared and analyzed. Results: After treatment, the total clinical effective rate (93.33%) of the observation group was significantly higher than that of the control group (70.00%); compared with before treatment, the systolic blood pressure, diastolic blood pressure, mean arterial pressure, urine protein, TC, and TG levels of the two groups were all lower after treatment, and the observation group was at a lower level; there was no significant difference in the incidence of hemorrhage (P &gt; 0.05). Conclusion: Vitamin E supplemented with calcium has a significant effect on the treatment of hypertension during pregnancy, which can help reduce blood pressure and blood lipid levels, reduce urinary protein content, improve maternal and child outcomes, and improve safety.

Progression of Type 2 Diabetic Nephropathy and Serum Monocyte Chemoattractant Protein-1 (MCP-1) Levels

Diabetic nephropathy is an important complication that develops from diabetes mellitus. The chemotactic cytokine Monocyte Chemoattractant Protein-1 (MCP-1) exhibits selective binding and activation of the C-C motif Chemokine Receptor 2 (CCR2). MCP-1 has been consistently observed to play a role in the pathogenesis of chronic and diabetic renal disease in clinical settings, regardless of the different stages and phenotypes. The main goal of this study was to assess and contrast the levels of monocyte chemoattractant protein-1 (MCP-1/CCL2) in individuals with diabetic nephropathy and those who show healthy state to examine the possibility of the usefulness of MCP-1/CCL2 as a biomarker of prognosis for early identification in patients developing albuminuria. The study involved the study of a sample of ninety patients diagnosed with type 2 diabetic nephropathy, while a control group of thirty individuals was also included for comparison purposes. The study recruited participants requesting from Baghdad and Maysan in Iraq. Urine specimens were obtained to determine the urinary protein concentration. Samples of blood and serum were collected to measure the levels of serum creatinine (s-Cr), fasting plasma glucose (F.P.G.), glycohemoglobin A1c (Hba1c) and serum MCP-1. The results of the statistical analysis indicate that there were significant differences (P &lt; 0.001) in the levels of MCP-1 between the microalbuminuric (stage 2) and macroalbuminuric (stage 3) when compared with the control group and between the stage 2 and stage 3 groups. Based on these findings, it can be concluded that MCP-1 levels may serve as biochemical indicators for disease progression of D.N.

Study on risk factors of diabetic peripheral neuropathy and establishment of a prediction model by machine learning

BackgroundDiabetic peripheral neuropathy (DPN) is a common complication of diabetes. Predicting the risk of developing DPN is important for clinical decision-making and designing clinical trials.MethodsWe retrospectively reviewed the data of 1278 patients with diabetes treated in two central hospitals from 2020 to 2022. The data included medical history, physical examination, and biochemical index test results. After feature selection and data balancing, the cohort was divided into training and internal validation datasets at a 7:3 ratio. Training was made in logistic regression, k-nearest neighbor, decision tree, naive bayes, random forest, and extreme gradient boosting (XGBoost) based on machine learning. The k-fold cross-validation was used for model assessment, and the accuracy, precision, recall, F1-score, and the area under the receiver operating characteristic curve (AUC) were adopted to validate the models’ discrimination and clinical practicality. The SHapley Additive exPlanation (SHAP) was used to interpret the best-performing model.ResultsThe XGBoost model outperformed other models, which had an accuracy of 0·746, precision of 0·765, recall of 0·711, F1-score of 0·736, and AUC of 0·813. The SHAP results indicated that age, disease duration, glycated hemoglobin, insulin resistance index, 24-h urine protein quantification, and urine protein concentration were risk factors for DPN, while the ratio between 2-h postprandial C-peptide and fasting C-peptide(C2/C0), total cholesterol, activated partial thromboplastin time, and creatinine were protective factors.ConclusionsThe machine learning approach helped established a DPN risk prediction model with good performance. The model identified the factors most closely related to DPN.

The Renoprotective Effect of Shikonin in a Rat Model of Diabetic Kidney Disease

In diabetes mellitus, diabetic nephropathy (DN) is a typical complication and pivotal cause of chronic kidney disease. The DN disease burden is among the highest in the world and is associated with high morbidity, mortality, and disease burden. Safe and effective medications are urgently needed for the treatment of DN. Interest has been increasing in Shikonin, extracted from the naphthoquinone plant, particularly in determining its renal protective effect. In this study, we explored Shikonin's effects and potential mechanisms on a streptozotocin (STZ)-induced DN experimental model. An STZ-induced rat diabetic model was established, and the rats were treated with different doses of Shikonin (10/50 mg/kg) for 4 weeks. Blood, urine, and renal tissue samples were collected after the last administration. Renal tissues were examined to detect each group's physiologic, biochemical, histopathologic, and molecular changes. The results showed that Shikonin administration could significantly alleviate the STZ-induced elevation of blood urea nitrogen, serum creatinine, urinary protein content, and renal pathologic injury. Furthermore, Shikonin significantly decreased oxidative stress, inflammation, and Toll-like receptor 4/myeloid differentiation primary response 88/nuclear factor-κB expression levels in DN kidney tissues. Shikonin showed a dose-dependent effect, with the best outcome at 50 mg/kg. Shikonin could effectively alleviate DN-related nephropathy damage and reveal the underlying pharmacologic mechanism. Based on the results, a Shikonin combination can be used in clinical treatment.

Intraindividual variations of urinary biomarkers in hospitalized children with glomerular diseases: a prospective observational study

This study aimed to assess the intraindividual variations of urinary biomarkers in hospitalized children with glomerular diseases. Hospitalized children with glomerular diseases participated in the study. For each patient, an overnight (9:00 p.m.–7:00 a.m.) urine was collected, followed by a 24-h urine (classified into four distinct periods: morning 7:00 a.m.–12:00 p.m., afternoon 12:00 p.m.–4:00 p.m., evening 4:00 p.m.–9:00 p.m., and overnight 9:00 p.m.–7:00 a.m.). The concentrations of protein, albumin, N-acetyl-beta-D-glucosaminidase, and epidermal growth factor (EGF) were measured and normalized by three correction factors (creatinine, osmolality, or specific gravity, respectively). Additionally, the 2nd overnight urine sample was grouped into different aliquots according to centrifugation, additives, storage temperature, or delayed processing. Twenty (14 boys, 6 girls) children were enrolled, with an average age of 11.3 years. Among the three correction factors, creatinine-normalized biomarkers provided the best agreements among different periods over 24 h. There were significant diurnal variations during 24 h in the concentrations of urinary protein, albumin, N-acetyl-beta-D-glucosaminidase, and EGF (p = 0.001, p = 0.003, p = 0.003, and p = 0.003, respectively). Evening urine overestimated 24-h urinary protein and albumin, while overnight urine underestimated 24-h urinary albumin. Urinary EGF showed low variability within a day or between the 2 days (coefficients of variation 10.2% and 10.6%, respectively) and excellent agreements (intraclass correlation coefficients > 0.9) with 24-h urinary concentration. Furthermore, urinary EGF was not affected by centrifugation, additives, storage temperature, or delayed processing of urine samples (all p > 0.05).  Conclusion: Given the diurnal variations of urinary biomarkers, urine samples should be collected during the same time period in clinical practice if possible. The results also extend the evidence for urinary EGF as a relatively stable biomarker applied in the future clinical practice.What is Known:• Urinary biomarkers have been widely used or discussed in making diagnoses and therapy regimens and estimating the prognosis of pediatric glomerular diseases. It remains unclear whether their levels would be affected by the time of sample collection, processing methods, and storage conditions in hospitalized children with glomerular diseases.What is New:• The levels of both commonly used biomarkers and novel biomarkers exhibited diurnal variations in hospitalized children with glomerular diseases.• Our results extend the evidence for urinary EGF as a relatively stable biomarker applied in the future clinical practice.

Albumin-to-protein ratio in spot urine samples for analysis of proteinuria selectivity in chronic kidney disease.

The albumin-to-creatinine ratio and total protein-to-creatinine ratio in spot urine samples have already been validated as surrogates for 24-hour albuminuria and proteinuria measurements. Thus, we hypothesized that the type of proteinuria, detected by the electrophoretic pattern of 24-hour urine, could be predicted by the simple proportion of albumin in the total urine protein content, using the albumin-to-protein ratio (APR). Our study sought to validate the use of APR as a cheaper substitute for urinary protein electrophoresis (UPE). Using different mathematical models, we compared, the albumin fraction in 24-hour urine samples by electrophoresis and the APR ratio in spot samples from 42 outpatients with chronic kidney disease (CKD). A strong log-order correlation r = 0.84 (0.75-0.92; 95% CI, p = 0.001) was observed between APR and the albumin fraction in the UPE. The APR can substitute electrophoresis in CKD outpatients.