Urinary Protein Biomarkers Research Articles

Urinary Metabolomic and Proteomic Analyses in a Mouse Model of Prostatic Inflammation.

Lower urinary tract symptoms (LUTS) are common among aging men. Since prostatic inflammation is one of its etiologies, it is plausible that urinary metabolite and protein biomarkers could be identified and used to diagnose inflammation-induced LUTS. We characterized the urine metabolome and proteome in a mouse model of bacterial-induced prostatic inflammation. Mass Spectrometry (MS)-based multi-omics analysis was employed to discover urinary protein and metabolite-based biomarkers. The investigation of isobaric dimethylated leucine (DiLeu) labeling on metabolites allowed metabolomics and proteomics analysis on the same liquid chromatography (LC)-MS platform. In total, 143 amine-containing metabolites and 1058 urinary proteins were identified and quantified (data are available via ProteomeXchange with identifier PXD018023); among them, 14 metabolites and 168 proteins were significantly changed by prostatic inflammation. Five metabolic pathways and four inflammation-related biological processes were potentially disrupted. By comparing our findings with urinary biomarkers identified in a mouse model of genetic-induced prostate inflammation and with those previously found to be associated with LUTS in older men, we identified creatine, haptoglobin, immunoglobulin kappa constant and polymeric Ig receptor as conserved biomarkers for prostatic inflammation associated with LUTS. These data suggest that these putative biomarkers could be used to identify men in which prostate inflammation is present and contributing to LUTS.

Elucidation of protein biomarkers in plasma and urine for epsilon toxin exposure in mouse model

Epsilon toxin (ETX) is the major virulence determinant of C. perfringens type B or type D strains, causing diseases in animals, besides being a listed biological and toxin warfare (BTW) agent. Keeping in mind the high lethality and the rapid onset of clinical manifestations, early diagnosis of epsilon toxin exposure is of paramount importance for implementation of appropriate medical countermeasures. Using a 2DE-MS approach, the present study is the first comprehensive proteomic elucidation of ETX-induced protein markers in the mouse model, providing putative targets for early diagnosis of ETX exposure. A total of 52 unique proteins showing ETX-induced modulations were identified in plasma and urine samples. Fibrinogen, apolipoprotein, serum amyloid protein, plasminogen, serum albumin, glutathione peroxidase, transferrin, major urinary protein 2, haptoglobin, transthyretin, and vitamin D-binding protein were among the proteins observed in more than one dataset with altered abundance after the ETX-intoxication. The predicted localization, function, and interaction of the ETX-modulated proteins in the plasma and urine indicated involvement of multiple pathways; extracellular proteins, followed by macromolecular complexes associated with blood coagulation and plasminogen activating cascade, being the most prominent among others. The putative markers elucidated here warrants further validation and can be of immense value for the early diagnosis of ETX exposure.

Identification of Low-Abundance Urinary Biomarkers in Lupus Nephritis Using Electrochemiluminescence Immunoassays.

To investigate the utility of a sensitive platform using electrochemiluminescence (ECL) for the identification of low-abundance urinary protein biomarkers in lupus nephritis (LN). Forty-eight urine samples were obtained from subjects in 2 independent cohorts, each consisting of 3 groups (matched for age, sex, and race) of 8 patients with active LN (renal Systemic Lupus Erythematosus Disease Activity Index [SLEDAI] >0), 8 patients with inactive SLE (renal SLEDAI 0), and 8 healthy controls. Samples were tested using a preexisting 40-plex ECL panel. A custom 5-plex ECL panel was then developed for further validation studies and used to test 140 urine samples (from 44 patients with active LN, 41 patients with inactive SLE, 28 healthy controls, and 27 patients with other kidney diseases). Levels of 17 urinary proteins were elevated (P < 0.05 by 2-tailed Mann-Whitney U test) in samples from patients with active LN compared to samples from patients with inactive SLE and healthy controls in cohort 1, while 9 were similarly elevated in cohort 2. Of these, interleukin-7 (IL-7), IL-12p40, IL-15, interferon-γ-inducible protein 10 (IP-10), and thymus and activation-regulated chemokine (TARC) were chosen for further validation. These 5 proteins were undetectable by enzyme-linked immunosorbent assay (ELISA). Hence, a custom 5-plex ECL panel was developed and used to validate the results from the initial 40-plex screening panel. Urinary IL-7, IL-12p40, IL-15, IP-10, and TARC levels were again significantly elevated in patients with active LN compared to those with inactive SLE and healthy controls, and correlated well with the renal SLEDAI and physician's global assessment of disease activity (R > 0.67, P < 0.05). All 5 urinary proteins were more frequently elevated in LN compared to controls with other chronic kidney diseases, although overall group differences attained significance only for urinary IL-7 and IL-15. Urinary levels of IL-7, IL-12p40, IL-15, IP-10, and TARC are potentially useful diagnostic tools in LN. The use of ECL assays may allow detection of urinary biomarkers that are below ELISA detection limits.

Protein biomarkers in serum and urine for determining presence or absence of hip dysplasia in a canine model.

This study compares serum and urine concentrations of relevant protein biomarkers among adult dogs with or without radiographic canine hip dysplasia (CHD). Adult (≥2 years of age), client-owned dogs (n = 74) radiographically categorized as having at least "good" hips (n = 49) or having "mild," "moderate," or "severe" hip dysplasia (n = 25) by the Orthopedic Foundation for Animals (OFA). Urine and serum samples were obtained from each dog at a single time-point and processed and analyzed for relevant protein biomarkers. Urinary concentrations of CTX-II (p < 0.001) and TIMP-1 (p = 0.002) were significantly lower in dogs with CHD compared to dogs with no CHD. ROC curve analyses were successful in establishing a panel of four biomarkers (urinary CTX-I and II, serum MMP-9, and serum PIICP) with high discriminatory capability for the presence or absence of hip dysplasia in adult dogs (AUC = 0.89). Urine and serum biomarkers can distinguish adult dogs with radiographic CHD from those with no CHD with a sensitivity of 0.95 and specificity of 0.77 using ROC analysis with AUC 0.89. Clinical Significance: This finding suggests that this simple, minimally invasive diagnostic technique has potential for discriminating dysplastic dogs from dogs with normal hips, with possible translational application to humans based on similar etiopathogenesis. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-5, 2019.

ESTABLISHMENT OF NOVEL URINARY KIDNEY DISEASE NEW BIOMARKERS AND THERAPEUTIC EFFECT OF METHANOL FRACTION OF TERMINALIA ARJUNA ON ACETAMINOPHEN INDUCED KIDNEY DISEASE IN RATS

Objective: There were main two objectives, first was the identification of best biomarkers for early screening of kidney diseases whether plasma urea and creatinine or novel urinary low molecular weight protein biomarkers Interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and cystatin-C. Second was the therapeutic efficacy of methanol fraction of Terminalia arjuna (MFTA) on urinary novel biomarkers.&#x0D; Methods: A total of 35 adult male rats were divided into three Groups (n=5), Group 1 was fed normal food, Group 2, normal food with administration of acetaminophen (APAP) for 5 days, 10 days, and 15 days, and Group 3, normal food with administration of APAP and coadministration of MFTA for 5 days, 10 days, and 15 days. All rats were sacrificed at 15th day of the experiment.&#x0D; Results: Results showed 5 days, 10 days, and 15 days administrations of APAP increased novel urinary biomarkers as IL-18, KIM-1 near two-folds and cystatin-C near six-folds increased than old biomarkers plasma urea and plasma creatinine. Administration of APAP with coadministration of MFTA represented the protective effect by decreasing old and new novel biomarkers with superoxide dismutase and catalase but malondialdehyde level increased. Sodium dodecyle sulphate-polyacrylamide gel electrophoresis showed new low molecular weight urinary protein bands in APAP administration rats, the protective effect of MFTA presents no band at this molecular level as normal rats.&#x0D; Conclusion: MFTA is the most potent nephroprotective agent, and urinary low molecular proteins are the best thing diagnostic tools for early detection of kidney disease over common plasma urea and creatinine.

Investigating the Value of Urine Volume, Creatinine, and Cystatin C for Urinary Biomarkers Normalization for Drug Development Studies.

Novel urinary protein biomarkers have recently been identified and qualified in rats for the early detection of renal injury in drug development studies. However, there seems to be no standardized normalization method for analyzing these urinary biomarkers, as some users normalize with urinary creatinine (uCr), urine volume (uVol), or leave biomarker un-normalized. More recently, urinary cystatin C is also emerging as a urinary biomarker normalizer, given some of its characteristics as a glomerular filtration marker. The purpose of this study was to identify an optimal drug-induced kidney injury biomarker normalization method that can be adopted more uniformly in the field. To this end, we compared the variability of uVol, urinary cystatin C, and Cr in healthy rats; we evaluated the sensitivity of the renal biomarkers to renal injury after normalization with uVol, uCr, and cystatin C in rats with cisplatin-induced renal injury. We showed that, over time, uCr was less variable than urinary cystatin C and uVol. When the renal biomarkers were normalized with the 3 normalizing end points, the biomarkers showed (1) least variability following normalization with Cr in healthy animals and (2) poor sensitivity when normalized with urinary cystatin C in animals with renal injury. Overall, the results suggested that uCr is better than urinary cystatin C and uVol for normalizing renal biomarkers in rats under controlled preclinical conditions. To our knowledge, this is the first report that compared the variability of uVol, cystatin C, and Cr in the context of renal biomarkers' normalization.

The significance of calprotectin, CD147, APOA4 and DJ-1 in non-invasive detection of urinary bladder carcinoma.

Aim of the study is to define the diagnostic accuracy of selected urinary protein biomarkers in the non-invasive detection of primary and recurrent urothelial carcinoma of the urinary bladder. The urinary levels of calprotectin, CD147, APOA4 and protein deglycase DJ-1 were examined in 255 individuals, including 60 controls with non-malignant urological disease, 61 patients with a history of urinary bladder cancer with negative cytology and negative cystoscopy and 134 patients with urinary bladder cancer. Urinary concentrations of biomarkers were determined by Enzyme-Linked Immunosorbent Assay (ELISA). During the follow-up of patients with non-muscle invasive bladder cancer (NMIBC), a group of 44 patients with cancer recurrence was compared to the group of 61 patients with a history of NMIBC but with no evidence of disease. Urinary concentrations of the evaluated markers did not reveal any significant difference between these groups. During the primary diagnosis, a group of 90 patients with primary bladder cancer and 60 subjects with benign disease were compared. Urinary levels of CD147 were not significantly higher in patients with tumors. The greatest diagnostic accuracy was observed in APOA4 (sensitivity 55.6, specificity 83.3, AUC 0.75), and lesser in calprotectin (sensitivity 39.4, specificity 87.7, AUC 0.66) and in DJ-1 (sensitivity 61.1, specificity 66.7, AUC 0.64), respectively. Apolipoprotein A4 may be used potentially as a supplemental urinary marker in the diagnosis of primary bladder cancer.

New Insights in Bladder Cancer Diagnosis: Urinary miRNAs and Proteins.

Bladder cancer is the 10th-most common cancer worldwide. The diagnosis and follow-up of patients require costly invasive methods and due to these expenses, bladder cancer continues to be one of the expensive malignancies. Early diagnosis is crucial in bladder cancer as it is in other cancers; therefore, non-invasive biomarkers for early diagnosis are very important. In this review, we aimed to focus on the most recent investigations on potential urinary micro RNA (miRNA) and protein biomarkers for bladder cancer diagnosis and their associated pathways. Studies performed by different groups were compiled and the biomarker properties of various proteins and miRNAs in the urine of bladder cancer patients were evaluated. Key studies were obtained by searching keywords “bladder cancer, urinary miRNA, urinary protein, urinary biomarker”. Targets and the pathways of the miRNAs and proteins were analyzed according to mirBase Catalogue and Panther Database. The major pathways that are targeted by aberrantly expressed miRNAs are Cholecystokinin receptor (CCKR), p53, Wnt signaling pathway, and feedback loops. We hereby conclude that urinary micro RNAs and proteins are promising candidates for bladder cancer diagnosis. It should be noted that urine collection, storage conditions, choice of fraction, and normalization strategies should be standardized.

UBC® Rapid Test-A Urinary Point-of-Care (POC) Assay for Diagnosis of Bladder Cancer with a focus on Non-Muscle Invasive High-Grade Tumors: Results of a Multicenter-Study.

Objectives: UBC® Rapid Test measures soluble fragments of cytokeratins 8 and 18 in urine. We present results of a multicenter study using an updated version of UBC® Rapid Test in bladder cancer patients, patients with urinary bladder cancer positive history, and healthy controls. Material and Methods: In total 530 urine samples have been included in this study. Clinical urine samples were used from 242 patients with tumors of the urinary bladder (134 non-muscle-invasive low-grade tumors (NMI-LG), 48 non-muscle-invasive high-grade tumors (NMI-HG), and 60 muscle-invasive high-grade tumors (MI-HG)), 62 patients with non-evidence of disease (NED), and 226 healthy controls. Urine samples were analyzed by the UBC® Rapid point-of-care (POC) assay and evaluated by Concile Omega 100 POC Reader. All statistical analyses have been performed using R version 3.2.3. Results: Elevated levels of UBC® Rapid Test in urine are higher in patients with bladder cancer in comparison to the control group (p < 0.001). The sensitivity for the whole bladder cancer cohort was 53.3% (positive predictive value (PPV) 90.2%, negative predictive value (NPV) 65.2%) and was 38.8% (PPV 78.8%, NPV 72.1%) for non-muscle-invasive low-grade bladder cancer; 75.0% (PPV 72.0%, NPV 94.7%) for non-muscle-invasive high-grade bladder cancer and 68.3% (PPV 74.6%, NPV 91.8%) for muscle-invasive high-grade bladder cancer. The specificity for the statistical calculations was 93.8%. The cut-off value (10 µg/L) was evaluated for the whole patient cohort. The area under the curve of the quantitative UBC® Rapid Test using the optimal threshold obtained by receiver operating characteristics (ROC) analysis was 0.774. Elevated values of UBC® Rapid Test in urine are higher in patients with high-grade bladder cancer in comparison to low-grade tumors and the healthy control group. Conclusions: UBC® Rapid Test has potential to be a clinically valuable urinary protein biomarker for detection of high-grade bladder cancer patients and could be added in the management of NMI-HG tumors. UBC® Rapid results generated in both study centers in the present multicenter study are very similar and reproducible. Furthermore UBC® Rapid Test is standardized and calibrated and thus independent of used batch of test as well as study site.

Assessment of a Urinary Kidney MicroRNA Panel as Potential Nephron Segment-Specific Biomarkers of Subacute Renal Toxicity in Preclinical Rat Models.

Drug-induced kidney injury (DIKI) remains a significant concern during drug development. Whereas FDA-endorsed urinary protein biomarkers encounter limitations including the lack of translatability, there is a considerable interest surrounding the application of microRNAs (miRNAs) in the renal biomarker space. Current knowledge about the value of these novel biomarkers for subacute preclinical rodent studies is still sparse. In this work, Wistar rats were treated with three nephrotoxic compounds-cisplatin (CIS, proximal tubule, 2.5 mg/kg, intraperitoneal [i.p.]), puromycin (PUR, glomerulus, 20/10 mg/kg, i.p.) and N-phenylanthranylic acid (NPAA, collecting ducts, 500 mg/kg, per os)-for up to 28 days to evaluate the performance of a panel of 68 urinary miRNAs as potential nephron segment-specific biomarkers. Out of these 68 kidney injury associated-miRNAs, our selection strategy ultimately revealed rno-miR-34c-5p significantly dysregulated after CIS single administration, and rno-miR-335 and rno-miR-155-5p significantly dysregulated after PUR treatment. In contrast, NPAA daily administration strongly altered the expression profile of 28 miRNAs, with rno-miR-210-3p displaying the most robust changes. A thorough evaluation showed that these miRNA candidates could complement urinary protein biomarkers to detect CIS- or PUR-induced kidney injury in a subacute setting, with a mechanistic (based on rno-miR-34c-5p) and/or a kidney injury detection potential. Our results also provide the first evidence that urinary miRNAs could enhance the detection of collecting duct damage. Overall, these data improve our understanding of the utility of urinary miRNAs as DIKI biomarkers in a subacute DIKI preclinical setting and support the value of using urinary biomarker panels comprising proteins and miRNAs.

Urine-Based Biomarkers for Alzheimer's Disease Identified Through Coupling Computational and Experimental Methods.

Alzheimer's disease (AD) is a chronic neurodegenerative disorder contributing to nearly 70% of dementia cases. However, no diagnostic protein biomarkers are available in urine. In this study, we combined computational and experimental methods to identify urinary biomarkers for AD. First, by analyzing brain tissue-based gene expression data of AD, 2,754 differentially expressed genes were identified, 559 of which were predicted to encode urine-excretory proteins that might act as candidate protein biomarkers of AD. GO enrichment analyses implied that they were mainly involved in microtubule-based process, myelin sheath, and calcium ion binding, suggesting that they might be associated with AD pathogenesis. In order to verify these proteins in urine, an iTRAQ experiment was carried out to analyze urine samples from AD patients and healthy controls, and 15 proteins were detected. Based on the expression changes of these proteins, 4 proteins were chosen for further validation by ELISA experiment, and SPP1, GSN, and IGFBP7 were found to be differentially expressed in the urine of AD patients. After a literature survey, we found that they were involved in AD pathophysiology and might serve as new urine biomarkers for AD. To our knowledge, this is the first time that urine biomarkers for AD were identified by combining computational and experimental methods. Furthermore, this is the first time SPP1, GSN, and IGFBP7 have been reported as potential urine protein biomarkers for AD. Therefore, our findings might provide significant guidance for finding early biomarkers of AD in urine.

Quantification of Urinary Protein Biomarkers of Autosomal Dominant Polycystic Kidney Disease by Parallel Reaction Monitoring.

Autosomal dominant polycystic kidney disease (ADPKD) is a life-long disease in which the genes responsible are known, but the pathogenesis of cyst formation and cyst growth are not understood. Cyst growth ultimately leads to end-stage renal failure in most patients. Analysis of the urinary proteome offers the potential to identify proteins that indicate the presence of cysts (and thus provides diagnosis) as well as the rates of cyst growth (providing prognostic information). A scheduled parallel reaction monitoring (sPRM) assay is performed on urine samples from 14 patients and 18 normal controls. For relative quantification, stable isotope-labeled synthetic peptides are spiked in the urinary protein digests prior to data collection. The data are subsequently normalized to creatinine and protein concentration in the respective urine samples to control for variations in water intake between individuals. Out of the 143 urinary proteins targeted for sPRM assay, 69 proteins are observed to be significantly dysregulated in ADPKD. The dysregulated proteins are used to cluster ADPKD patients into those who are more or less similar to normal controls. This study shows that sPRM is a promising approach to rapidly screen large numbers of proteins in urine in order to provide earlier diagnosis and potentially better understand the pathogenesis of ADPKD development and progression.

Discovery and Validation of Novel Protein Biomarkers in Ovarian Cancer Patient Urine.

For the vast majority of ovarian cancer patients, optimal surgical debulking remains a key prognostic factor associated with improved survival. A standardized, biomarker-based test, to preoperatively discriminate benign from malignant disease and inform appropriate patient triage, is highly desirable. However, no fit-for-purpose biomarkers have yet been identified. We conducted a pilot study consisting of 40 patient urine samples (20 from each group), using label-free quantitative (LFQ) mass spectrometry, to identify potential biomarker candidates in urine from individual ovarian cancer patients. To validate these changes, we used parallel reaction monitoring (PRM) to investigate their abundance in an independent validation cohort (n=20) of patient urine samples. LFQ analyses identified 4394 proteins (17027 peptides) in a discovery set of 20 urine samples. Twenty-three proteins were significantly elevated in the malignant patient group compared to patients with benign disease. Several proteins, including LYPD1, LYVE1, PTMA, and SCGB1A1 were confirmed to be enriched in the urine of ovarian cancer patients using PRM. We also identified the established ovarian cancer biomarkers WFDC2 (HE4) and mesothelin (MSLN), validating our approach. This is the first application of a LFQ-PRM workflow to identify and validate ovarian cancer-specific biomarkers in patient urine samples.

Role of Kidney Biopsies for Biomarker Discovery in Diabetic Kidney Disease.

Although estimated glomerular filtration rate and albuminuria are well-established biomarkers of diabetic kidney disease (DKD), additional biomarkers are needed, especially for the early stages of the disease when both albuminuria and estimated glomerular filtration rate may still be in the normal range and are less helpful for identifying those at risk of progression. Traditional biomarker studies for early DKD are challenging because of a lack of good early clinical end points, and most rely on changes in existing imprecise biomarkers to assess the value of new biomarkers. There are well-characterized changes in kidney structure, however, that are highly correlated with kidney function, always precede the clinical findings of DKD and, at preclinical stages, predict DKD progression. These structural parameters may thus serve as clinically useful end points for identifying new biomarkers of early DKD. In addition, investigators are analyzing tissue transcriptomic data to identify pathways involved in early DKD which may have associated candidate biomarkers measurable in blood or urine, and differentially expressed microRNAs and epigenetic modifications in kidney tissue are beginning to yield important observations which may be useful in identifying new clinically useful biomarkers. This review examines the emerging literature on the use of kidney tissue in biomarker discovery in DKD.

Impact of Hydrophobic Non-Specific Binding on Assay Recovery for Some Urinary Biomarkers of Acute Kidney Injury.

Several sensitive low-abundance urine protein biomarkers have emerged for the diagnosis of acute kidney injury (AKI)2, but preanalytical factors can negatively impact the accuracy of biomarker testing. In this study, we observed the effect of a hydrophobic nonspecific binding (HNB) inhibitor (ovalbumin) and protease inhibitors on the recovery of urine AKI biomarkers. The following 5 proteins were investigated: kidney injury molecule-1 (KIM-1) and retinol binding protein-4 (RBP-4), sandwich ELISA (RD β2-microglobulin (B2M; Siemens Healthcare Diagnostics), automated ligand-binding immunoassay (Immulite 2000); α1-microglobulin (A1M; Kamiya Biomedical), automated immunoturbidimetric assay (Roche Modular P); and N-acetyl-β-D-glucosaminidase (NAG; Roche …

Metal–Organic Framework Encapsulation for Biospecimen Preservation

Handling, transport and storage of biospecimens such as blood and urine without refrigeration are extremely challenging. This formidable challenge leads to an inevitable reliance on a “cold chain” for shipping, handling and storage of biospecimens throughout the world. The cold chain requirement precludes biospecimen procurement from underserved populations and resource-limited settings where refrigeration and electricity are not reliable or even available. Here, we introduce a universal biospecimen preservation approach based on nanoporous material encapsulation for preserving protein biomarkers in biofluids under normal (non-refrigerated) storage conditions. Using urinary NGAL and serum/plasma CA-125 as the model protein biomarkers, we demonstrate that zeolitic imidazolate framework-8 (ZIF-8), a nanoporous material, encapsulation can preserve protein biomarkers in urine, serum, plasma and blood at room temperature and 40°C, with comparable preservation efficacy to the “gold standard” method (freezing li...

Meta-analysis of a 10-plex urine-based biomarker assay for the detection of bladder cancer.

A 10-plex urine-based bladder cancer (BCa) diagnostic signature has the potential to non-invasively predict the presence of BCa in at-risk patients, as reported in various case-control studies. The present meta-analysis was performed to re-evaluate and demonstrate the robustness and consistency of the diagnostic utility of the 10-plex urine-based diagnostic assay. We re-analyzed primary data collected in five previously published case-control studies on the 10-plex diagnostic assay. Studies reported the sensitivity and specificity of ten urinary protein biomarkers for the detection of BCa, including interleukin 8, matrix metalloproteinases 9 and 10, angiogenin, apolipoprotein E, syndecan 1, alpha-1 antitrypsin, plasminogen activator inhibitor-1, carbonic anhydrase 9, and vascular endothelial growth factor A. Data were extracted and reviewed independently by two investigators. Log odds ratios (ORs) were calculated to determine how strongly the 10-plex biomarker panel and individual biomarkers are associated with the presence of BCa. Data pooled from 1,173 patients were analyzed. The log OR for each biomarker was improved by 1.5 or greater with smaller 95% CI in our meta-analysis of the overall cohort compared with each analysis of an individual cohort. The combination of the ten biomarkers showed a higher log OR (log OR: 3.46, 95% CI: 2.60–4.31) than did any single biomarker irrespective of histological grade or disease stage of tumors. We concluded that the 10-plex BCa-associated diagnostic signature demonstrated a higher potential to identify BCa when compared to any single biomarker. Our results justify further advancement of the 10-plex protein-based diagnostic signature toward clinical application.

Identification of urinary biomarkers for the prediction of gestational diabetes mellitus in early second trimester of young gravidae based on iTRAQ quantitative proteomics.

Gestational Diabetes Mellitus (GDM) has brought great harm to maternal and fetus. Up to now, only a few plasma biomarkers for its early diagnosis have been reported; nevertheless, there is no report about identification of urinary biomarkers for prediction of GDM. Thus, it is necessary to correct this deficiency. In our study, urine samples were collected from 889 healthy young gravidae at the early second trimester (15 to 20 weeks), 69 of whom were subsequently diagnosed with GDM at 24 to 28 weeks. iTRAQ (the isobaric tags for relative and absolute quantification) quantitative proteomics was conducted on sixteen GDM (trial group) and an equal number of matched healthy young gravidae (control group). Validation was performed in 40 cases of each group by ELISA. A total of 1,901 proteins were identified in this study, including 119 significantly differential proteins (fold change ≧1.2 or ≦0.83 and p < 0.05). Compared with control group, 83 differential proteins were increased and 36 proteins were decreased in GDM group. The validation for expression of CD59 and IL1RA showed significant difference and the area under the receiver operating characteristic curve was 0.729 and 0.899, respectively (p < 0.05). The two candidate protein biomarkers (CD59 and IL1RA) in urine could be an early, noninvasive diagnostic predictors of young pravidae with GDM, and IL1RA is stronger diagnostic power than CD59.

Neonatal acute kidney injury: predictive and diagnostic value of urinary protein biomarkers

Neonatal acute kidney injury: predictive and diagnostic value of urinary protein biomarkers

Urinary protein biomarkers of kidney injury in patients receiving cisplatin chemotherapy.

Despite recent progress in the development of novel approaches to treat cancer, traditional antineoplastic drugs, such as cisplatin, remain a mainstay of regimens targeting solid tumors. Use of cisplatin is limited by acute kidney injury, which occurs in approximately 30% of patients. Current clinical measures, such as serum creatinine and estimated glomerular filtration rate, are inadequate in their ability to detect acute kidney injury, particularly when there is only a moderate degree of injury. Thus, there is an urgent need for improved diagnostic biomarkers to predict nephrotoxicity. There is also interest by the U.S. Food and Drug Administration to validate and implement new biomarkers to identify clinical and subclinical acute kidney injury in patients during the drug approval process. This minireview provides an overview of the current literature regarding the utility of urinary proteins (albumin, beta-2-microglobulin, N-acetyl-D-glucosaminidase, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, and cystatin C) as biomarkers for cisplatin-induced AKI. Many of the well-studied urinary proteins (KIM-1, NGAL, B2M, albumin) as well as emerging biomarkers (calbindin, monocyte chemotactic protein-1, and trefoil factor 3) display distinct patterns of time-dependent excretion after cisplatin administration. Implementation of these biomarker proteins in the oncology clinic has been hampered by a lack of validation studies. To address these issues, large head-to-head studies are needed to fully characterize time-dependent responses and establish accurate cutoff values and ranges, particularly in cancer patients. Impact statement There is growing interest in using urinary protein biomarkers to detect acute kidney injury in oncology patients prescribed the nephrotoxic anticancer drug cisplatin. We aim to synthesize and organize the existing literature on biomarkers examined clinically in patients receiving cisplatin-containing chemotherapy regimens. This minireview highlights several proteins (kidney injury molecule-1, beta-2-microglobulin, neutrophil gelatinase-associated lipocalin, calbindin, monocyte chemotactic protein-1, trefoil factor 3) with the greatest promise for detecting cisplatin-induced acute kidney injury in humans. A comprehensive review of the existing literature may aid in the design of larger studies needed to implement the clinical use of these urinary proteins as biomarkers of kidney injury.