Urinary complement factor D is increased in primary malignant hypertension: a single-center, cross-sectional study.

Kidney injury is one of the detrimental consequences of primary malignant hypertension (pMHTN). There is a paucity of non-invasive biomarkers to enhance diagnosis and elucidate the underlying mechanisms. This study aims to explore urine protein biomarkers for pMHTN associated renal damage. In the discovery phase, urine samples were collected from 8 pMHTN, 19 disease controls (DCs), and 5 healthy controls (HCs). In-gel digestion combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach was used for identification of proteins associated with pMHTN. In the validation phase, the differentially expressed proteins were validated by ELISA assay in cohort with 10 pMHTN patients, 37 DCs, and 30 HCs. Compared to DCs and HCs, a specific band between 15 and 25 kDa was found in 7 out of 8 patients with pMHTN. Further LC-MS/MS analysis revealed 5 differentially expressed proteins. ELISA validation demonstrated that urinary complement factor D (CFD) was significantly up regulated in pMHTN. By receiver operating characteristic curve analysis, urinary CFD/Cr showed moderate potential in discriminating pMHTN from DCs (the area under curve: 0.822, 95% CI 0.618-0.962). Urinary CFD may be a potential biomarker for pMHTN with its elevation indicative of the activation of the alternative complement pathway in pMHTN.

ELISA for leptospiral 3-hydroxyacyl-CoA dehydrogenase in urine is a promising screening tool for acute leptospirosis.

Introduction. Leptospirosis is a zoonotic disease that is prevalent worldwide. Leptospiral 3-hydroxyacyl-CoA dehydrogenase (3-HADH) is excreted in the urine of infected individuals. However, the potential use of 3-HADH as a biomarker for the diagnosis of leptospirosis using enzyme-linked immunosorbent assay (ELISA) has not been investigated. A technique that identifies Leptospira in a patient in urine sample will be valuable in regular diagnostics and epidemic scenarios, as opposed to existing serological approaches. This study aimed to develop and evaluate an ELISA that can detect 3-HADH in the urine of patients with confirmed acute leptospirosis and to assess its potential as a screening test for leptospirosis. Methods. Laboratory confirmation of acute leptospirosis was done by flaB-nested polymerase chain reaction (PCR) of plasma samples from suspected patients. ELISA-based determination of the presence of 3-HADH in the urine of PCR-positive patients versus PCR-negative patients matched for fever date was performed by coating ELISA plates with urine supernatants and using rabbit anti-3-HADH as the primary antibody. Receiver operating characteristic curve analysis was used to determine the cutoff values for the ELISA. The diagnostic measures between the PCR-positive and PCR-negative patients were compared using the Mann-Whitney U test. Results. In total, 158 febrile patients were assessed, of whom 121 (76.6 %) were male. Of the 15 flaB-nested PCR-positive patients, 12 were in the acute phase of the febrile illness. The best cutoff was an average optical density (ODav) value of 0.2200 for febrile patients. Sensitivity and specificity were 83.33% [95 % confidence interval (CI), 51.59-97.91 %) and 83.33 % (95 % CI, 76.05-89.13 %), respectively. The ODav values for PCR-positive patients in the acute phase of the disease (≤7 days of fever) were significantly higher than those for PCR-negative patients (P<0.001, U=114.0, z=-4.946). Conclusion. Detection of 3-HADH in urine by ELISA appears to be promising for the screening of acute leptospirosis in suspected patients.

Urinary biomarkers in diabetic nephropathy.

Diabetic nephropathy (DN), a significant consequence of diabetes, is associated with adverse cardiovascular and renal disease as well as mortality. Although microalbuminuria is considered the best non-invasive marker for DN, better predictive markers are needed of sufficient sensitivity and specificity to detect disease in general and in early disease specifically. Even prior to appearance of microalbuminuria, urinary biomarkers increase in diabetics and can serve as accurate nephropathy biomarkers even in normoalbuminuria. In this review, a number of novel urine biomarkers including those reflecting kidney damage caused by glomerular/podocyte damage, tubular damage, oxidative stress, inflammation, and intrarenal renin-angiotensin system activation are discussed. Our review also includes emerging biomarkers such as urinary microRNAs. These short noncoding miRNAs regulate gene expression and could be utilized to identify potential novel biomarkers in DN development and progression. .

Acute hyperbilirubinemia determines an early subclinical renal damage: Evaluation of tubular biomarkers in cholemic nephropathy.

BACKGROUND AND AIMS: Cholemic nephropathy is a cause of acute kidney injury occurring in patients with jaundice. The aim of this study was to evaluate early renal function impairment in patients with mild acute hyperbilirubinemia in the absence of alterations of the common parameters used in clinical practice (serum creatinine or urea) and with normal renal morphology. We studied urinary biomarkers of tubular damage urinary neutrophil gelatinase-associated lipocalin (u-NGAL), urinary beta-2-microglobulin (u-B2M), urinary osteopontin (u-OPN), urinary trefoil factor 3 (u-TFF3) and urinary Cystatin C (u-Cys). METHODS: This is a case-control study investigating the following urinary biomarkers of tubular damage: u-NGAL, u-B2M, u-OPN, u-TFF3 and u-Cys, in patients with mild acute hyperbilirubinemia. Seventy-four patients were included in this study: 36 patients with jaundice and 38 patients without jaundice. RESULTS: Subjects with jaundice (total bilirubin 12.4 ± 7.3 mg/dL) showed higher u-NGAL, u-B2M, u-OPN, u-TFF3 and u-Cys compared with controls. After logistic regression analyses, including the following independent variables: age, estimated Glomerular Filtration Rate (eGFR), haemoglobin, diabetes, hypertension and jaundice, we observed a higher risk of elevated u-NGAL values (OR = 3.8, 95% CI 1.07-13.5, p = .03) and u-B2M (OR = 9.4, 95% CI 2.3-38.9, p = .0018) in jaundiced subjects. Moreover, urinary biomarkers had a direct correlation with serum cholestasis indexes. CONCLUSIONS: This study demonstrated increased urinary biomarkers of tubular damage (u-NGAL, u-B2M, u-OPN, u-TFF3, and u-Cys) in patients with mild hyperbilirubinemia in comparison with a control group. These findings suggest early renal tubular damage in the absence of alterations of the normal parameters used in clinical practice (eGFR, serum urea and renal morphology).

The long noncoding RNA SUMO1P3 as urinary biomarker for monitoring bladder cancer progression.

Introduction: Urothelial Bladder Cancer (BC) is the ninth most common cancer worldwide. It is classified into Non Muscle Invasive (NMIBC) and Muscle Invasive Bladder Cancer (MIBC), which are characterized by frequent recurrences and progression rate, respectively. The diagnosis and monitoring are obtained through invasive methods as cystoscopy and post-surgery biopsies. Thus, a panel of biomarkers able to discriminate BC based on grading or staging represents a significant step forward in the patients' workup. In this perspective, long non-coding RNAs (lncRNAs) are emerged as reliable candidates as potential biomarker given their specific and regulated expression. In the present work we propose two lncRNAs, the Small Ubiquitin Modifier 1 pseudogene 3 (SUMO1P3), a poorly characterized pseudogene, and the Urothelial Carcinoma Associated 1 (UCA1) as candidates to monitor the BC progression. Methods: This study was a retrospective trial enrolling NMIBC and MIBC patients undergoing surgical intervention: the expression of the lncRNA SUMO1P3 and UCA1 was evaluated in urine from 113 subjects (cases and controls). The receiver operating characteristic curve analysis was used to evaluate the performance of single or combined biomarkers in discriminating cases from controls. Results: SUMO1P3 and UCA1 expression in urine was able to significantly discriminate low grade NMIBC, healthy control and benign prostatic hyperplasia subjects versus high grade NMIBC and MIBC patients. We also demonstrated that miR-320a, which binds SUMO1P3, was reduced in high grade NMIBC and MIBC patients and the SUMO1P3/miR-320a ratio was used to differentiate cases versus controls, showing a statistically significant power. Finally, we provided an automated method of RNA extraction coupled to ddPCR analysis in a perspective of clinical application. Discussion: We have shown that the lncRNA SUMO1P3 is increased in urine from patients with high grade NMIBC and MIBC and that it is likely to be good candidate to predict bladder cancer progression if used alone or in combination with UCA1 or with miRNA320a.

Use of Bladder Epicheck® in the follow-up of high-risk non-muscle-invasive Bladder cancer: A systematic literature review.

INTRODUCTION: In recent years, different urinary markers such as the Bladder Epicheck® have been developed in an attempt to reduce the number of cystoscopies in the follow-up of non-muscle invasive bladder cancer (NMIBC). AIM: To provide a systematic review of Bladder Epicheck® and its current clinical utility in the follow-up and detection of recurrence of NMIBC. MATERIAL AND METHODS: Systematic review based on a literature search of PubMed, Web of Science and Scopus databases until October 2023, according to PRISMA and Quadas-2 criteria. Sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of the marker were calculated. Diagnostic performance was evaluated by the area under the curve (AUC). RESULTS: Fifteen studies were analyzed (n = 3761) including 86.7% prospective studies. Of the patient series, 53.2% had received previous intravesical instillations. The mean Se of the biomarker in the detection of recurrence varied according to tumor grade (87.9%-high grade/HG vs. 44.9%-low grade/LG, respectively). Their weighted mean Se and Sp were 71.6% and 84.5%, respectively. The mean recurrence rate was 29.1%. The weighted mean PPV and NPV were 56.4% and 92.8% (97.7% non-LG), respectively. The mean AUC was 85.63%. CONCLUSION: Bladder Epicheck® is a useful urinary marker in the follow-up of NMIBC, with significantly high Se and NPV in the detection of recurrences, especially in cases of HG disease. Its use can reduce the number of cystoscopies required in the follow-up of NMIBC, improving the quality of life of patients and potentially increasing health economic savings.

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 ß-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.

Sucrose-Powered Liposome Nanosensors for Urinary Glucometer-Based Monitoring of Cancer.

Timely detection of early-stage cancer holds immense potential in enhancing prognostic outcomes. There is an increasing desire for versatile tools to enable simple, sensitive, and cost-effective cancer detection. By exploiting the extraintestinal metabolic inertness and efficiency renal clearance of sucrose, we designed a liposome nanosensor using sucrose as a messenger to convert tumor-specific esterase activity into glucose meter readout, enabling economical and sensitive urinalysis for cancer detection in point-of-care testing (POCT). Our results demonstrate that the nanosensors exhibited significant signal differences between tumor-bearing and healthy mice in both orthotopic and metastatic tumor models. Additionally, efficient elimination of the nanosensors through the hepatobiliary pathway was observed with no significant toxicity. Such a non-invasive diagnostic modality significantly assists in personalized pharmacological treatment and follow-up efficacy assessment. We envision that this modular liposome nanosensor platform might be applied for economically detecting diverse diseases via a simple urinary test.

Noninvasive biomarkers for lupus nephritis.

Lupus nephritis (LN) is one of the most severe clinical manifestations of systemic lupus erythematosus (SLE). Notably, the clinical manifestations of LN are not always consistent with the histopathological findings. Therefore, the diagnosis and activity monitoring of this disease are challenging and largely depend on invasive renal biopsy. Renal biopsy has side effects and is associated with the risk of bleeding and infection. There is a growing interest in the development of novel noninvasive biomarkers for LN. In this review, we summarize most of the LN biomarkers discovered so far by correlating current knowledge with future perspectives. These biomarkers fundamentally reflect the biological processes of kidney damage and repair during disease. Furthermore, this review highlights the role of urinary cell phenotype detection in the diagnosis, monitoring, and treatment of LN and summarizes the limitations and countermeasures of this test.

Polycyclic Aromatic Hydrocarbons and Pancreatic Cancer: An Analysis of the Blood Biomarker, r-1,t-2,3,c-4-Tetrahydroxy-1,2,3,4-tetrahydrophenanthrene and Selected Metabolism Gene SNPs.

Exposure to polycyclic aromatic hydrocarbons (PAHs), byproducts of incomplete combustion, and their effects on the development of cancer are still being evaluated. Recent studies have analyzed the relationship between PAHs and tobacco or dietary intake in the form of processed foods and smoked/well-done meats. This study aims to assess the association of a blood biomarker and metabolite of PAHs, r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), dietary intake, selected metabolism SNPs, and pancreatic cancer. Demographics, food-frequency data, SNPs, treatment history, and levels of PheT in plasma were determined from 400 participants (202 cases and 198 controls) and evaluated based on pancreatic adenocarcinoma diagnosis. Demographic and dietary variables were selected based on previously published literature indicating association with pancreatic cancer. A multiple regression model combined the significant demographic and food items with SNPs. Final multivariate logistic regression significant factors (p-value < 0.05) associated with pancreatic cancer included: Type 2 Diabetes [OR = 6.26 (95% CI = 2.83, 14.46)], PheT [1.03 (1.02, 1.05)], very well-done red meat [0.90 (0.83, 0.96)], fruit/vegetable servings [1.35 (1.06, 1.73)], recessive (rs12203582) [4.11 (1.77, 9.91)], recessive (rs56679) [0.2 (0.06, 0.85)], overdominant (rs3784605) [3.14 (1.69, 6.01)], and overdominant (rs721430) [0.39 (0.19, 0.76)]. Of note, by design, the level of smoking did not differ between our cases and controls. This study does not provide strong evidence that PheT is a biomarker of pancreatic cancer susceptibility independent of dietary intake and select metabolism SNPs among a nonsmoking population.

Potential Utility of Urinary Follistatin as a Non-Invasive Indicator of Acute Tubular Damage in Patients with Acute Kidney Injury.

Activin A is known to impede tubular repair following renal ischemia, whereas exogenous follistatin, an activin A antagonist, has been shown to ameliorate kidney damage in rats. Despite these findings, the precise role of endogenous follistatin in the kidney has yet to be elucidated. In this study, we investigated the localization of follistatin in the normal human kidney and its potential utility as a marker for acute kidney injury (AKI). In a total of 118 AKI patients and 16 healthy adults, follistatin levels in serum and urine were quantified using ELISA, and correlations with clinical parameters were analyzed. Follistatin-producing cells were positive for Na-Cl co-transporter and uromodulin, but negative for aquaporin 1 and aquaporin 2. Unlike healthy adults, urinary follistatin significantly increased in AKI patients, correlating positively with AKI severity. Urinary follistatin levels were notably higher in patients needing renal replacement therapy. Significant correlations were observed with urinary protein, α1 microglobulin, and urinary NGAL, but not with urinary KIM-1, urinary L-FABP, urinary NAG, urinary ß2 microglobulin, or serum creatinine. Interestingly, no correlation between urinary and serum follistatin levels was identified, indicating a renal origin for urinary follistatin. In conclusion, follistatin, produced by distal tubules, is detectable in the urine of AKI patients, suggesting its potential as a valuable marker for monitoring acute tubular damage severity in AKI.

False positives and false negatives in benzene biological monitoring.

Benzene is a commonly used industrial chemical that is a significant environmental pollutant. Occupational health specialists and industrial toxicologists are concerned with determining the exact amount of exposure to chemicals in the workplace. There are two main approaches to assess chemical exposure; air monitoring and biological monitoring. Air monitoring has limitations, which biological monitoring overcomes and could be used as a supplement to it. However, there are several factors that influence biological monitoring results. It would be possible to assess exposure more accurately if these factors were taken into account. This study aimed to review published papers for recognizing and discussing parameters that could affect benzene biological monitoring. Two types of effects can be distinguished: positive and negative effects. Factors causing positive effects will increase the metabolite concentration in urine more than expected. Furthermore, the parameters that decrease the urinary metabolite level were referred to as false negatives. From the papers, sixteen influential factors were extracted that might affect benzene biological monitoring results. Identified factors were clarified in terms of their nature and mechanism of action. It is also important to note that some factors influence the quantity and quality of the influence of other factors. As a result of this study, a decision-making protocol was developed for interpreting the final results of benzene biological monitoring.

Urinary liver-type fatty acid binding protein is a biomarker reflecting renal damage and the ameliorative effect of drugs at an early stage of histone-induced acute kidney injury.

AIM: Circulated histones play a crucial role in the pathogenesis of infectious diseases and severe trauma, and it is one of the potential molecular targets for therapeutics. Recently, we reported that histone is one of the causative agents for urinary L-FABP increase. However, the mechanism is still unclear, especially in severe cases. We further investigated the mechanism of urinary L-FABP increase using a more severe mouse model with histone-induced kidney injury. This study also aims to evaluate the therapeutic responsiveness of urinary L-FABP as a preliminary study. METHODS: Human L-FABP chromosomal transgenic mice were administrated 30 mg/kg histone from a tail vein with a single dose. We also performed a comparative study in LPS administration model. For the evaluation of the therapeutic responsiveness of urinary L-FABP, we used heparin and rolipram. RESULTS: The histological change with cast formation as a characteristic of the models was observed in proximal tubules. Urinary L-FABP levels were significantly elevated and these levels tended to be higher in those with more cast formation. Heparin and rolipram had the ameliorative effect of the cast formation induced by histone and urinary L-FABP levels significantly decreased. CONCLUSION: Histone is one of the causative agents for the increase of urinary L-FABP at an early stage of AKI. In addition, it suggested that urinary L-FABP may be useful as a subclinical AKI marker reflecting kidney damage induced by histone. Furthermore, urinary L-FABP reflected the degree of the damage after the administration of therapeutic agents such as heparin and PDE4 inhibitor.

Budgetary Impact of Including the Urinary Genomic Marker Cxbladder Detect in the Evaluation of Microhematuria Patients.

INTRODUCTION: Current AUA guidelines mandate a risk-stratified approach for the evaluation of microhematuria. Urine genomic tests with high negative predictive value could further reduce unnecessary diagnostic testing and morbidity, but the economic impact is unknown. This study modeled the financial impact of Cxbladder Detect on microhematuria evaluations. METHODS: A decision tree analysis was constructed by Coreva Scientific comparing 1-year costs of the standard microhematuria evaluation using the AUA guidelines vs an algorithm incorporating Cxbladder Detect. Cxbladder Detect-positive patients had cystoscopy and imaging, whereas patients with negative tests were reevaluated in 6 months. Patients with positive diagnostic testing underwent cystoscopy, and positive cystoscopies led to transurethral resection of bladder tumor. Test performance was based on published literature, and costs were based on Medicare allowable fees. RESULTS: Using the decision tree model, the average savings of using Cxbladder Detect was $559 compared with the standard of care, with an average reduction of 0.38 procedures per patient. Probabilistic analysis showed statistical significance with a median reduction in the total cost of $498 per patient (95% CrI [-1356, -2]) and a significant median reduction in diagnostic procedures per patient of 0.36 (95% CrI [-0.52, -0.16]) without impact on the number of cancers diagnosed. CONCLUSIONS: This model-based study demonstrates the potential economic value of using a Cxbladder-driven protocol for microhematuria evaluations.

Diagnostic Accuracy of Urinary N Terminal pro-B Type Natriuretic Peptides for Hemodynamically Significant-Patent Ductus Arteriosus in Preterm Infants.

BACKGROUND: Echocardiography is the gold standard for the diagnosis hemodynamically significant-patent ductus arteriosus (hs-PDA). It requires trained personnel and is not readily available. Urinary biomarkers can be used as an adjunct. OBJECTIVE: The objective of this study was to systematically review the diagnostic accuracy of urinary N terminal pro-B type natriuretic peptides (NT-proBNP) for hs-PDA in preterm neonates. METHODS: We included studies that evaluated urinary NT-proBNP and urinary NT-proBNP/creatinine ratio (index tests) in preterm neonates with hs-PDA (participants) in comparison with echocardiogram (reference standard). Methodological quality and certainty of evidence were assessed using Quality Assessment of Diagnostic-Accuracy Studies (QUADAS-2) and Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. RESULTS: Low quality of evidence suggests that urinary NT-proBNP has modest sensitivity and specificity for the diagnosis of a hs-PDA, with variation in accuracy based on assay and patient characteristics. CONCLUSION: Urinary NT-proBNP assays must be locally validated for specific patient populations and further studies to support its use must be performed.

Corrigendum: Urine L-selectin reflects clinical and histological renal disease activity and treatment response in lupus nephritis across multi-ethnicity.

[This corrects the article DOI: 10.3389/fimmu.2023.1200167.].

The Role of Checkpoint Inhibitor Expression Directly on Exfoliated Cells from Bladder Cancer: A Narrative Review.

Bladder cancer (BCa) is a common type of cancer that affects the urinary bladder. The early detection and management of BCa is critical for successful treatment and patient outcomes. In recent years, researchers have been exploring the use of biomarkers as a non-invasive and effective tool for the detection and monitoring of BCa. One such biomarker is programmed death-ligand 1 (PD-L1), which is expressed on the surface of cancer cells and plays a crucial role in the evasion of the immune system. Studies have shown that the PD-L1 expression is higher in BCa tumors than in healthy bladder tissue. Additionally, PD-L1 expression might even be detected in urine samples in BCa patients, in addition to the examination of a histological sample. The technique is being standardized and optimized. We reported how BCa patients had higher urinary PD-L1 levels than controls by considering BCa tumors expressing PD-L1 in the tissue specimen. The expression of PD-L1 in urinary BCa cells might represent both a diagnostic and a prognostic tool, with the perspective that the PD-L1 expression of exfoliate urinary cells might reveal and anticipate eventual BCa recurrence or progression. Further prospective and longitudinal studies are needed to assess the expression of PD-L1 as a biomarker for the monitoring of BCa patients. The use of PD-L1 as a biomarker for the detection and monitoring of BCa has the potential to significantly improve patient outcomes by allowing for earlier detection and more effective management of the disease.

Sixty years of conjecture over a urinary biomarker: a step closer to understanding the proposed link between anxiety and urinary pyrroles.

OBJECTIVE: For over 60 years there has been conjecture about the identity of an Ehrlich's test positive pyrrole (Mauve Factor) reputed to be a biomarker for psychological disorders, including anxiety. We reviewed studies that attempt to identify Mauve Factor and subjected authentic standards of the 2 main candidates, kryptopyrrole and hydroxypyrrole, to the Ehrlich's reaction. METHODS: Modified Ehrlich's test for kryptopyrrole and hydroxypyrrole were applied to urine samples from 10 volunteers, anxious and nonanxious. RESULTS: Based on the mechanistic chemistry of Ehrlich's reaction and reactions of the 2 compounds, Mauve Factor cannot be hydroxypyrrole. Analyses of urine samples from volunteers, identified by the Generalized Anxiety Disorder - 7 item scale (GAD-7 ≥10; n = 5) and control urine samples (GAD-7 <10; n = 5) using a kryptopyrrole calibration graph, show that concentrations are similar in both groups. CONCLUSION: Kryptopyrrole may be the elusive Mauve Factor. Its possible origin from stercobilin via gut microbiome-mediated metabolism, its link to gut-mediated neurological effects via γ-aminobutyric acid (GABA) receptors, and its predicted interaction with Zn2+ and consequent impact on zinc homeostasis are discussed. The GAD-7 scale does not differentiate between state and trait anxiety and as such, the minimal difference in pyrrole levels between volunteer groups requires further study.

Urine L-selectin reflects clinical and histological renal disease activity and treatment response in lupus nephritis across multi-ethnicity.

Objective: There is an urgent need for novel biomarkers in lupus nephritis (LN). We report a non-invasive urinary biomarker, L-selectin, in two independent multi-ethnic cohorts. Methods: uL-selectin was tested cross-sectionally in a Chinese cohort (n=255) and a US cohort (n=219) of SLE patients and controls using ELISA. A longitudinal cohort includes 20 active Chinese LN patients. Results: uL-selectin was significantly increased in active LN patients compared to active non-renal SLE, inactive LN, inactive non-renal SLE, chronic kidney disease patients, and healthy controls. uL-selectin positively correlated with global and renal disease activities as well as histological activity index and chronicity index (CI). Low uL-selectin was an independent predictor for high CI. During follow-up, uL-selectin levels decreased significantly in the complete renal remission group. Conclusion: uL-selectin is a novel biomarker of disease activity and renal histopathology in LN across multiple ethnicities. It also reflects treatment response in LN patients during follow up.