Proteinuria Research Articles

Evaluation of some immunological and physiological parameters in patients with chronic kidney disease infected with Toxoplasma gondii

Abstract Background - Chronic kidney disease (CKD) is defined as a decrease in glomerular filtration rate, increased urinary albumin excretion, and, ultimately, complete loss of kidney function or kidney damage. Toxoplasma gondii is a protozoan parasite responsible for toxoplasmosis a significant disease that affects over a billion people worldwide in humans, toxoplasmosis spreads through two primary routes: horizontal transmission, which occurs through accidental ingestion of Toxoplasma gondii oocysts present in contaminated food or water and vertical transmission where the infection is passed from mother to baby via the placenta. The aim of the current study was to detect the effect of toxoplasmosis on kidney function and determining some immunological and physiological parameters in immunosuppressed patients (kidney failure patients) compared to healthy people Methods The study involved the analysis of 90 blood samples, comprising 80 samples from patients diagnosed with Chronic Kidney Disease (CKD) and 10 samples from healthy individuals who served as control subjects Results Results revealed decrease in the level of both CD4+ and CD8+ in infected CKD compared with the control group, The CD4+/CD8+ concentration ratio was increased in infected CKD As for biochemical tests, the results showed an increase in the concentration of urea, creatinine, phosphorus, and the liver enzyme ALT, and no significant differences were recorded in the concentration of the liver enzyme AST and Alk.phosphatase Conclusions: The study revealed a decrease in immunological parameters and an increase in physiological parameters in kidney failure patients .

Reproductive Implications and Management of Congenital Uterine Anomalies: Scientific Impact Paper No. 62.

Congenital uterine anomalies (CUAs) are malformations of the uterus (womb) that develop during fetal life. When a female baby is in her mother's uterus, her uterus develops as two separate halves from two tubular structures called Müllerian ducts, which fuse together before she is born. Anomalies that occur during the baby's development can be variable, from complete absence of the uterus through to more subtle anomalies, which are classified into specific categories. While conventional ultrasound is good at detecting CUAs, 3D ultrasound is used to confirm a diagnosis. If a complex uterine anomaly is suspected, additional investigations may be used, including MRI scanning, laparoscopy (where a camera is inserted into the cavity of the abdomen) and/or hysteroscopy (where a camera is placed in the uterine cavity). As there can be a link between CUAs and anomalies of the kidney and bladder, scans of these organs are also usually requested. Although CUAs are present at birth, adult women typically do not have any symptoms, although some may experience painful periods. Most cases of CUA do not cause difficulties in becoming pregnant, and the outcome of pregnancy, in most cases, is good. However, these uterine anomalies are often discovered during investigations for infertility or miscarriage. Moreover, depending upon the type and severity of CUA, there may be increased risk of first and second trimester miscarriages, preterm birth, fetal growth restriction (smaller and lighter babies for the stage of pregnancy), pre-eclampsia (development of high blood pressure and protein in urine after the 20th week of pregnancy) and fetal malpresentation (baby not facing head-first down the birth canal) at birth. Surgical treatment may be considered for those who have had recurrent miscarriages and have a septate uterus, i.e. the uterine cavity is divided by a partition. In this case, surgery may reduce the chances of miscarriage. However, women should be informed that there is inconclusive and conflicting evidence regarding the improved likelihood of live births in this context. Further evidence from large randomised controlled trials are required to provide conclusive evidence-based recommendations for surgical treatment for septate uterus. Surgical treatment for other types of CUAs is not usually recommended as the risks outweigh potential benefits, and evidence for any benefits is lacking. Women with CUAs may be at an increased risk of preterm birth even after surgical treatment for a septate uterus. These people, if suspected to be at an increased risk of preterm birth based on the severity of CUA, should be followed up using an appropriate protocol for preterm birth as outlined in UK Preterm Birth Clinical Network Guidance.

Integrated proteomics reveals enrichment of oxidative stress and inflammatory proteins in the urine and stone matrix of calcium oxalate stone formers.

Nephrolithiasis is a multifactorial disease associated with urinary and matrix proteins that become a focal point of research for diagnostic and preventative strategies. The functional relevance of these proteins in lithogenesis, along with their origins and impacts, remains a major subject of ongoing lithogenic research. Here, an integrated analysis was done on multiple proteome datasets compiled from various studies of normal urine (NU), urine from calcium oxalate stone formers (SFU), and calcium oxalate stone matrix (SM). Functional annotation and network analysis revealed the profound enrichment of proteins associated with oxidative stress and inflammation only in the stone-related samples (both "SFU but not NU" and "SM but not NU" cohorts). The oxidative stress and inflammation-related proteins were most abundant in the "SM but not NU" cohort and had higher proportions in the "SFU but not NU" cohort than the "NU only" cohort. KEGG pathway analysis corroborated such observation and highlighted the inclusion of proteins in the complement and coagulation pathways, particularly in SM. The findings of this study inform some mechanistic insights into the roles of calcium oxalate stone-related proteins and may help develop effective prevention and treatment strategies for nephrolithiasis.

Case of maternal uniparental isodisomy with autosomal recessive Alport syndrome combined with congenital myasthenia and Oguchi disease.

Uniparental isodisomy (UPiD) is a genetic condition in which an individual inherits two identical copies of a chromosome, or part of a chromosome, from one parent. UPiD can result in the development of autosomal recessive disorders if the chromosome inherited from one parent has a pathogenic variant. Herein, we present a 20year-old female patient who had no significant family history including kidney, muscular, or ocular diseases. She had muscle weakness since infancy and was suspected with congenital myasthenia. She was diagnosed with Oguchi disease, a congenital condition characterized by night blindness, by an ophthalmologist. At 3years of age, hematuria was noted, and gross hematuria was occasionally observed thereafter. Exome analysis revealed homozygous variants in the COL4A4, CHRND, and SAG genes on chromosome 2, which are the causative genes of Alport syndrome, congenital myasthenic syndrome, and Oguchi disease, respectively. Array comparative genomic hybridization analysis and microsatellite analysis revealed maternal UPiD. At approximately 18years of age, she presented with proteinuria withmild kidney impairment, and kidney biopsy was performed at 20years of age. Type IV collagen α5 chain staining showed a weak but positive image in the glomerular basement membrane. However, thinning and irregular thickening of the glomerular basement membrane and reticular changes in the dense layer were observed, which were consistent with Alport syndrome. Angiotensin II receptor blocker (candesartan) was administered, and her urinary protein levels decreased. She had a homozygous missense variant, positive α5 chain staining, and a mild phenotype.

Constructing a machine learning model for systemic infection after kidney stone surgery based on CT values

This study aims to develop a machine learning model utilizing Computed Tomography (CT) values to predict systemic inflammatory response syndrome (SIRS) after endoscopic surgery for kidney stones. The goal is to identify high-risk patients early and provide valuable guidance for urologists in the early diagnosis and intervention of post-operative urosepsis. This study included 833 patients who underwent retrograde intrarenal surgery (RIRS) or percutaneous nephrolithotomy (PCNL) for kidney stones. Five machine learning algorithms and ten preoperative or intraoperative variables were used to develop a predictive model for SIRS. The SHapley Additive exPlanations (SHAP) method was used to explain the distribution of feature importance in the model’s predictions. Among the 833 patients, 126 (15.1%) developed SIRS postoperatively. All five machine learning models demonstrated strong discrimination on the validation set (AUC: 0.690–0.858). The eXtreme Gradient Boosting (XGBoost) model was the best performer [AUC: 0.858; sensitivity: 0.877; specificity: 0.981; accuracy: 0.841; positive predictive value: 0.629; negative predictive value: 0.851]. The characteristic importance of the Machine Learning model (ML model) and SHAP results indicated Hounsfield Unit (HU), Urinary protein, Stone burden, and Serum uric acid as important predictors for the model. A machine learning model utilizing CT values was developed to predict postoperative SIRS in endoscopic kidney stone surgery. The model demonstrates strong predictive performance and can assist in assessing the risk of urosepsis in postoperative patients.

Role of microvascular pericyte dysfunction in antibody-mediated rejection following kidney transplantation

Objective To investigate the role of microvascular pericyte dysfunction in antibody-mediated rejection (ABMR) of transplanted kidneys. Methods A total of 160 patients who underwent kidney transplantation in our hospital from 2004 to 2020 were enrolled, divided into 4 groups: ABMR group (n = 79), TCMR group (n = 20), mixed rejection group (n = 25) and control group (n = 36). Postoperative renal function indicators were compared, and immunohistochemical and immunofluorescence staining was performed on graft tissues and mice models using the pericyte marker PDGFR-β. An in vitro pericyte dysfunction model was co-cultured with vascular endothelial cells for functional assessment through Western blotting, PCR, and wound healing tests. KEGG pathway analysis from the GEO database identified gene expression changes in pericytes, which were further analyzed using electron microscopy and Western blot techniques. Results There were statistically significant differences in creatinine, urea nitrogen, urine protein, and eGFR among the groups over time, with ABMR displaying the poorest outcomes. Immunohistochemistry revealed lower pericyte expression in ABMR, which was confirmed in mouse model studies showing reduced PDGFR-β expression in ABMR. KEGG analysis highlighted decreased autophagy in pericyte dysfunction, supported by electron microscopy and Western blot findings indicating reduced autophagy and pericyte damage, which could be reversed by chloroquine. Conclusion ABMR episodes worsened the long-term prognosis of transplanted kidneys. pericyte dysfunction appears to be one of the crucial causes of poor prognosis in ABMR patients. In vitro studies demonstrated that dysfunction of microvascular pericytes can result in damage to vascular endothelial cells, with autophagy impairment being a significant mechanism contributing to pericyte dysfunction.

Comprehensive management application of sulodexide on proteinuria: 2 case reports

Proteinuria is an important sign of kidney function decline and one of the common clinical manifestations in patients with chronic kidney disease and diabetic kidney disease, which are often accompanied by a gradual decline in kidney function. Therefore, effective management of proteinuria is of great significance for delaying the progression of kidney disease and protecting kidney function. Sulodexide is a mixture of fast-moving heparin and dermatan sulfate with anticoagulant, thrombolytic, anticardiovascular, lipid-lowering, and renal-protective effects. It has potential application value in the comprehensive management of proteinuria. This study reported two different chronic disease cases to explore the comprehensive management application of sulodexide in patients with long-term poor proteinuria control. Case 1 is a 45 years-old male with type 2 diabetes mellitus and hypertension accompanied by persistent proteinuria and intermittent edema in both legs. Case 2 is a 52 years-old female with chronic nephritis and rheumatoid arthritis accompanied by persistent proteinuria and edema in both legs. Two patients showed a decrease in urinary protein levels and stable control of the remaining signs of disease after the addition of sulodexide to their comprehensive treatment regimens, indicating that sulodexide plays an important role in the comprehensive management of proteinuria.

Urinary Dickkopf-related protein 3 as a novel biomarker for kidney function decline in children with Alport syndrome.

Chronic kidney disease (CKD) seriously affects the well-being and shortens the life expectancy of children and adolescents, but its progression is challenging to predict. Therefore, there is an urgent need for biomarkers that can identify children at risk of faster CKD progression. Alport syndrome (AS) is the most common monogenetic glomerular kidney disease. Urinary Dickkopf-related protein 3 (DKK3) is associated with a decline in estimated glomerular filtration rate (eGFR) in adults and children with advanced CKD. However, its potential for early detection of CKD and its prognostic value in children with AS remain unknown. Urine samples from 49 children enrolled in the EARLY PRO-TECT Alport trial were analyzed to evaluate whether DKK3 could identify children with AS to be at risk for faster CKD progression. DKK3 levels in patients with AS were higher than those of healthy individuals reported in the literature. DKK3 levels were more elevated in patients with later stages of AS. Furthermore, children who were not treated with renin angiotensin system inhibitors (RASi) had higher DKK3 levels than treated children. Children with above-average DKK3 levels were more likely to have increased albuminuria after 2years of follow-up than children with below-average DKK3 levels. Urinary DKK3 is significantly elevated in children at early stages of AS. There was a potential association between higher DKK3 levels, worsening albuminuria, and a decline in kidney function. These findings suggest that DKK3 may be a prognostic marker for predicting the risk of kidney damage in children with AS.

The relationship between water intake and the progression of urine albumin-creatinine ratio in patients with chronic kidney disease: A cohort-prospective study.

Introduction: The urine albumin-creatinine ratio (uACR) is a key biomarker for assessing kidney function in patients with chronic kidney disease (CKD), with elevated levels indicating kidney damage. Water and protein metabolism significantly impact kidney function. Proper hydration influences vasopressin feedback and osmolality regulation, while excessive protein intake exacerbates kidney stress through hyperfiltration and increased urea production. This study aims to investigate the relationship between daily water and protein intake and uACR levels in CKD patients. Methods: A cohort study was conducted on 10 non-dialysis CKD patients at Dr. Wahidin Sudirohusodo Hospital, Makassar, Indonesia. Demographic and clinical data were collected, and average daily water and protein intake were assessed. The Spearman correlation test was used to analyze the relationship between water and protein intake and changes in uACR, albumin, and creatinine levels. Results: A strong negative correlation was found between daily water intake and uACR (ρ=-0.891, p=0.001), indicating that higher water consumption reduces uACR. Conversely, protein intake showed a strong positive correlation with uACR (ρ=0.770, p=0.009) and urine albumin levels (ρ=0.806, p=0.005), suggesting that higher protein consumption increases both uACR and albumin excretion. No significant correlation was found between water or protein intake and urine creatinine levels. Conclusion: This study highlights the importance of hydration and dietary protein regulation in managing CKD progression. Increased water intake may reduce uACR, while excessive protein intake can exacerbate kidney damage, emphasizing the need for dietary management in CKD patients.

Relation of volatile organic compounds to renal function in American adolescents: three statistical models

ABSTRACT This study was conducted to evaluate the relationship between 17 urinary metabolites of volatile organic compounds (mVOCs) in adolescents and renal function parameters (estimated glomerular filtration rate (eGFR), albumin-to-creatinine ratio (ACR), urinary albumin, serum uric acid (SUA), and blood urea nitrogen (BUN)). In adjusted generalised linear models (GLM), mVOCs were positively correlated with eGFR, urinary albumin, and BUN, and mVOCs were negatively correlated with ACR and SUA. Weighted Quartile Sum (WQS) index correlated with eGFR [β(95%CI): 0.040 (0.028, 0.052)], urine albumin [β(95%CI): 0.275 (0.203, 0.622)], SUA [β(95%CI): 0.040 (0.025, 0.055)] and BUN [β(95%CI): 0.102 (0.082, 0.122)]. In Bayesian Kernel Machine Regression (BKMR) model, total compound effect was positively correlated with eGFR, positive associations were observed in high concentration of the mixture with urine albumin and ACR. Findings suggest that single and mixed exposures to mVOCs may affect renal parameters in adolescents.

Short-term efficacy of rituximab in children with calcineurin inhibitor resistant steroid resistant nephrotic syndrome

Objective: To investigate the short-term efficacy and safety of rituximab (RTX) in children with calcineurin inhibitor (CNI) resistant steroid resistant nephrotic syndrome (SRNS). Methods: A retrospective case analysis was conducted. Thirteen children with CNI resistant SRNS who were regularly treated with RTX (375 mg/m2 per dose (maximum dose 500 mg), 1 dose per week, a total of 4 doses) in Department of Nephrology, Children's Hospital of Fudan University from January 2016 to December 2023 were enrolled. The general data, disease related information, urinary protein/creatinine, serum albumin, blood creatinine before RTX treatment, immunosuppressants, adverse events, and monthly urinary protein/creatinine, serum albumin, and blood creatinine indexes within 6 months after RTX treatment were collected. The changes of urinary protein/creatinine, serum albumin and estimated glomerular filtration rate (eGFR) before and after RTX at 3 and 6 months were analyzed by using paired sample t test and Wilcoxon signed-rank test. Results: Among the 13 patients, 8 were male and 5 were female. The age of disease onset was 4.0 (2.9, 6.8) years and the age of RTX treatment was 9.8 (5.9, 13.6) years. There were 8 cases of focal segmental glomerulosclerosis, 3 cases of minimal change disease and 2 cases of mesangial proliferative glomerulonephritis. No clinically significant gene variation was detected in 12 cases and the other one did not receive gene test. Before RTX treatment, 11 cases were in chronic kidney disease stage G1, and 1 case each was in stage G2 and stage G3. Ten children completed 4 doses of RTX treatment, 1 patient completed 3 doses, and 2 patients completed 2 doses. Urinary protein/creatinine in 13 children at 3 and 6 months after RTX treatment was significantly lower than baseline (0.60 (0.13, 2.04), 0.49 (0.28, 1.10) vs. 1.44 (0.76, 4.11) mg/mg, Z=-2.34, -2.34, both P<0.05), and serum albumin was significantly higher than baseline ((35±8), (34±7) vs. (30±6) g/L, t=2.30, 2.60, both P<0.05). The eGFR at 6 months after RTX treatment was not significantly different from the baseline ((110±32) vs. (113±35) ml/(min·1.73 m2),t=-0.76,P>0.05)). No serious adverse reactions occurred in this study. Conclusion: RTX could reduce urinary protein and increase serum albumin in short-term treatment in children with CNI resistant SRNS without significant side effects.

Involvement of mitochondrial dysfunction and oxidative stress in the nephrotoxicity induced by high-fat diet in Sprague-Dawley rats.

The prevalence of obesity-associated kidney injury has increased, yet the precise extent of the injury and its underlying mechanisms remain unclear. This study used a Sprague-Dawley (SD) rat model to simulate human exposure scenarios, with the objective of investigating the involvement of mitochondria in obesity-induced renal toxicity. Biochemical analysis revealed significant increases in serum creatinine, cystatin C, urinary protein, urinary microalbumin, and urinary α1-microglobulin levels in rats fed a high-fat diet, indicating a notable decline in glomerular filtration function. Histopathological examination showed mild to moderate degeneration in renal tubular epithelial cells, slight glomerular enlargement, fusion and disappearance of pedunculated cell, and decreased electron density of mitochondrial matrix and cristae, indicating the impaired filtration function of kidney. Furthermore, the study found reduced mitochondrial membrane potential and superoxide dismutase (SOD) levels, along with increased malondialdehyde (MDA) levels, signifying elevated mitochondrial oxidative stress in the kidneys of high-fat diet-fed rats. Additionally, a decrease in the number of mitochondrial proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) and uncoupling protein-2 (UCP-2)-positive cells, as well as reduced protein expression levels in the mitochondria, suggests a reduced renal mitochondrial resistance to oxidative stress. Collectively, these findings indicate that a high-fat diet triggers abnormalities in both renal filtration and structural functionality in SD rats. The observed reduction in renal mitochondrial density and the elevation in oxidative stress levels could potentially serve as underlying mechanisms.

Clinicopathological characteristics of patients with low titer anti-phospholipase A2 receptor antibodies verified by indirect immunofluorescence assay

Laboratory extensively applied enzyme-linked immunosorbent assay (ELISA) to measure anti-phospholipase A2 receptor antibodies (PLA2R-abs) since its diagnostic significance on PLA2R related primary membranous nephropathy (PLA2R-related pMN) was discovered. However, PLA2R-abs determined by ELISA (PLA2R-ELISA) could infrequently yield inconclusive results, specifically a grey-zone defined as PLA2R-abs ranging from 2 to 20 RU/mL. Recently, researchers suggested that double-check grey-zone PLA2R-abs by indirect immunofluorescence (IIF) could improve diagnostic accuracy. We evaluated the diagnostic performance of PLA2R-IIF in assessing PLA2R-related pMN and summarized clinicopathological characteristics of grey-zone population to provide more evidence for clinical practice. Data on demographics, serology and pathology of patients with PLA2R-ELISA grey-zone results and a native kidney biopsy at Peking Union Medical College Hospital from September 2020 to April 2023 were reviewed. Grey-zone samples were analyzed using PLA2R-IIF. Negative results were defined as no fluorescence and positive results were graded according to fluorescence intensity. This study included a total of 52 grey-zone patients divided into pMN group (n=36, 69%) and non-pMN group (n=16, 31%) according to renal pathology reports. The pMN patients had higher PLA2R-abs and lower serum creatinine compared to the non-pMN patients (P=0.003, P<0.001). No statistically significant differences were observed in 24-hour urine protein and albumin between the two groups. Multiple pathological types were identified in the non-pMN group. The sensitivity and specificity of PLA2R-IIF in PLA2R-ELISA grey-zone population were 72% and 88%, respectively, with a total consistent rate of 77% and a positive predictive value of 93%. Both pMN and non-pMN patients presented grey-zone PLA2R-ELISA results. It was necessary to perform PLA2R-IIF to assist in the diagnosis of patients with PLA2R-ELISA grey-zone results.

Evaluation of the effect of Ela tablets in the treatment of diabetic nephropathy based on rat experiments and screening strategy for quality markers of Ela tablets targeting aldose reductase.

Ela tablets (ALP) is a traditional Uyghur medicinal formulation comprising 9 herbs. Clinical applications have demonstrated its potential in treating diabetic nephropathy (DN). However, its specific medicinal effects and pharmacodynamic components have not been elucidated. This research aims to investigate the efficacy of ALP in treating DN and to explore the quality markers (Q-markers) for its exertion of efficacy. Using the UHPLC-Q-Orbitrap HRMS technique, a total of 60 compounds were identified within ALP. Animal experiments were conducted to investigate the effect of ALP intervention at doses of 80, 160, and 320mg/kg in Sprague-Dawley rats. Then, fingerprints of ten batches of ALP extracts were established using UPLC-DAD. Spectrum-effect relationship analysis of these fingerprints and aldose reductase (AR) activity was conducted by chemometric analysis methods. The results were further validated by molecular docking and cellular experiments. The animal experiments indicated that ALP had a therapeutic effect on DN. Specifically, ALP reduced biochemical indexes such as serum creatinine (SCr), 24-hour urinary total protein (24h UTP), uric acid (UA), blood urea nitrogen (BUN), triglycerides (TG), and total cholesterol (TC). ALP stabilized body weight and fasting blood glucose, enhanced the antioxidant capacity of kidneys, and improved renal pathology. Comprehensive analysis indicated that crocin-I and gallic acid may be used as Q-markers for ALP. In summary, ALP has been identified as a treatment for DN, and gallic acid and crocin-I can be used as its Q-markers.

WCN25-2110 Adverse Childhood Experiences and Urinary Protein Creatinine Ratio in a cohort of unselected Mexican participants

WCN25-2110 Adverse Childhood Experiences and Urinary Protein Creatinine Ratio in a cohort of unselected Mexican participants

Urinary NGAL and KIM-1 in Canine Monocytic Ehrlichiosis

Glomerulonephritis, caused by the deposition of immune complexes, can lead to kidney damage in dogs with canine monocytic ehrlichiosis (CME). The early diagnosis of renal insult is important to prevent severe kidney disease in infected dogs by Ehrlichia canis. This study aimed to investigate urinary biomarkers of renal function, neutrophil gelatinase (uNGAL), and kidney injury molecule-1 (uKIM-1) using the Luminex® xMAP® platform, and the proportion of mixed or high molecular weight proteinuria in dogs with CME. This study included blood samples of thirty dogs with clinical signs of CME and amplified DNA for E. canis (CME group) and six dogs of different breeds and both sexes, aged 3 to 7 years, that showed no clinical-laboratory alterations or tick parasitism and were tested negative for E. canis via PCR (control group). The total calcium, phosphorus (p &lt; 0.05), urea (p &lt; 0.001), creatinine (p &lt; 0.05), urinary density (p &lt; 0.05), urinary protein creatinine ratio (p &lt; 0.001), uNGAL (p &lt; 0.05), and uKIM-1 (p &gt; 0.05), as well as the proportion of high molecular weight proteinuria and mixed proteinuria (p &lt; 0.01), were measured. Elevated serum concentrations of creatinine, urea, and phosphorus combined with reduced urinary density, increased urinary creatinine–protein ratio, urinary NGAL, and mixed proteinuria detected renal damage in dogs with CME, while KIM -1 remained unchanged. uNGAL can detect early renal lesions, reflecting renal damage before a significant increase in serum creatinine occurs, and appears to be an early diagnostic biomarker in renal disease in dogs with CME.

WCN25-3705 Scored Salt Questionnaire and Urinary Albumin Creatinine Ratio in a cohort of unselected Mexican participants

WCN25-3705 Scored Salt Questionnaire and Urinary Albumin Creatinine Ratio in a cohort of unselected Mexican participants

Targeted and non-targeted proteomics to identify the urinary protein biomarkers for Wilson disease.

Wilson disease (WD) is a genetic disorder of copper metabolism. Early diagnosis of WD is inherently challenging due to the absence of typical symptoms. This study aimed to identify urinary protein biomarkers for WD using targeted and nontargeted mass spectrometry-based approaches. Exploratory urinary proteomic research on WD patients was initially conducted and revealed some potential biomarkers (alpha-2-macroglobulin, alpha-1-antitrypsin, complement C3, prothrombin, and complement factor B). A multiple reaction monitoring (MRM) assay was subsequently developed and applied to an independent WD cohort for protein candidate validation. Finally, a Random Forest (RF) model constructed with five proteins was evaluated for its diagnostic capacity. The linear range of the MRM assay extended from 0.025ng/L to 155ng/L and the limit of quantification (LOQ) ranged from 0.0095 ng/L to 9.2308 ng/L. Alpha-2-macroglobulin, alpha-1-antitrypsin, and complement C3 exhibited significant increases (p<0.05) in WD patients compared to the controls, whereas prothrombin and complement factor B only showed variations in concentration. The physiology reference intervals (RIs) for alpha-2-macroglobulin, alpha-1-antitrypsin, complement C3, prothrombin, and complement factor B were estimated as 0-12.50, 0-123.08, 0-5.20, 0-16.59, 0-4.85ng/mol Cr, while the pathology RIs were 0-114.86, 0-600.98, 0-12.62, 0-22.16, and 0-10.83ng/mol Cr, respectively. The RF model demonstrated an area under the curve (AUC) of 0.99 for the training data and 0.83 for the testing data. Based on the proteomic results, the quantitative method was successfully applied for the validation of protein candidates in WD. Using supervised machine learning, the five-protein panel exhibited excellent accuracy in non-invasive diagnosis of WD.

Urine Protein Tests in Lupus: What do They Mean?

The development of nephritis in patients with lupus is associated with increased morbidity and mortality. Proteinuria is a key indicator of kidney involvement detecting and monitoring proteinuria is crucial as it acts as a surrogate marker for disease activity and has significant prognostic value. This review explores the general mechanisms of proteinuria and highlights the limitations of current measurement techniques. In the absence of specific urinary markers for LN disease activity, evaluating proteinuria involves considering its trajectory, amplitude of change, and the overall clinical status of the patient. Differentiating between acute disease versus proteinuria that may stem from scarring and glomerular basement membrane remodeling, can be challenging. Additionally, in the absence of other signs of active disease, the time to recovery and resolution of proteinuria may be prolonged.

IGSF8 impairs migration and invasion of trophoblast cells and angiogenesis in preeclampsia.

Insufficient trophoblast cell infiltration is implicated in the progression of preeclampsia (PE). The immunoglobulin superfamily member 8 (IGSF8) has been shown to promote cell migration, invasion, and epithelial mesenchymal transition (EMT). However, the specific impact of IGSF8 on trophoblast cells in PE has not been definitively demonstrated. To address this, placental tissues from PE patients and normal subjects was collected. A PE-like rat model was established by administering L-NAME (60mg/kg) intragastrically to pregnant rats from the 10th to the 19th day of gestation. Knockdown and overexpression plasmids of IGSF8 were transfected into JEG-3cells for further experiments. Clinical samples indicated impaired spiral artery remodeling, and high IGSF8 expression in the placental tissues of PE patients. PE rats exhibited increased mean arterial pressure, elevated 24-h urine protein levels, higher abortion rates, and decreased placental and fetal weight compared to rats of sham group. Failure of physiological transformation of spiral arteries was observed in PE rats, along with increased IGSF8 expression. IGSF8 overexpression inhibited JEG-3cell migration, invasion and EMT, as well as reduced release of VEGF in JEG-3cells, impairing HUVEC tube formation. mRNA-sequencing analysis of JEG-3cells transfected with shIGSF8 showed differentially expressed genes related to angiogenesis, and mesenchymal cell differentiation, with IGSF8 knockdown being associated with the activation of pathways involved in blood vessel development and cell migration. Overall, this study suggests that IGSF8 plays a role in the development of PE and provides new insights for potential treatments.