Bladder cancer (BC) is the second most common type of cancer of the urinary system. Approximately 75% of the cases are non-muscle invasive bladder cancer (NMIBC), which has a high recurrence and progression rate. Current diagnosis and surveillance methods present challenges, including risks to the patients. For this reason, urinary biomarkers have been proposed as alternatives to the methods. The goal of this mini-review is to describe urinary mRNA-based biomarkers available in current literature for NMIBC tumors, using the PubMed database. The search included the following keywords: \"biomarkers\" AND \"bladder cancer\" AND \"urine\" and \"RNA\" and \"non-muscle\". The search yielded 11 original researchers utilizing mRNA-based urinary biomarkers. Although there is a wide variety of biomarkers described, the cohorts of the studies were not exclusively NMIBC, which is the subtype of BC that would mostly benefit from the introduction of a good follow-up biomarker, highlighting the need for randomized interventional trials for NMIBC.

Background: Programmed death-ligand 1 (PD-L1) expression has been recognized as a potential biomarker for various cancers, yet its diagnostic and prognostic significance in urothelial bladder cancer (BCa) requires further investigation. Methods: In this prospective single-center study, we aimed to assess the feasibility and diagnostic adequacy of PD-L1 expression analysis using cytoinclusion in BCa patients. We enrolled consecutive patients undergoing endoscopic transurethral resection of bladder tumor (TURBT), repeat TURBT, or robot-assisted radical cystectomy. Urinary and tissue specimens were collected from these patients for cytoinclusion and histopathological analysis to evaluate PD-L1 expression. Results: Out of 29 patients, PD-L1 expression was detected from cytoinclusion in 42.8% (3 out of 7), 10% (1 out of 10), and 66.8% (8 out of 12) of patients with negative/papilloma, low-grade, and high-grade tumors, respectively. Conversely, histopathological analysis identified PD-L1 expression in 57.2% (4 out of 7), 30% (3 out of 10), and 83.3% (10 out of 12) of patients with negative/papilloma, low-grade, and high-grade tumors, respectively. The diagnostic concordance between cytoinclusion and histopathology was 85.7%, 80%, and 83.3% in patients with negative/papilloma, low-grade, and high-grade tumors, respectively. Conclusions: Our study underscores the promise of cytoinclusion as a minimally invasive method for quantifying urinary PD-L1 percentages. This approach could serve as both a potential prognostic and diagnostic indicator, easily obtainable from urine samples. Standardizing this technique could facilitate its widespread use as a valuable tool.

Acute kidney injury (AKI) prevalence in surgical patients is high, emphasizing the need for preventative measures. This study addresses the insufficient evidence on nephroprotective intraoperative fluid resuscitation and highlights the drawbacks of relying solely on serum creatinine/urine output to monitor kidney function. This study assessed the impact of intraoperative fluid management on AKI in female breast cancer patients undergoing autologous breast reconstruction, utilizing novel urinary biomarkers (TIMP-2 and IGFBP-7). In a monocentric prospective randomized controlled trial involving 40 patients, liberal (LFA) and restrictive (FRV) fluid management strategies were compared. TIMP-2 and IGFBP-7 biomarker levels were assessed using the NephroCheck (bioMerieux, France) test kit at preoperative, immediate postoperative, and 24-h postoperative stages. FRV showed significantly higher immediate postoperative biomarker levels, indicating renal tubular stress. FRV patients had 21% (4/19) experiencing AKI compared to 13% (2/15) in the LFA group according to KDIGO criteria (p = 0.385). Restrictive fluid resuscitation increases the risk of AKI in surgical patients significantly, emphasizing the necessity for individualized hemodynamic management. The findings underscore the importance of urinary biomarkers in early AKI detection.

BACKGROUND: An important reason for the high health care costs associated with bladder cancer is the need for frequent cystoscopy for detection and surveillance of this disease. Cytologic analysis of voided urine specimens can assist, but is too inaccurate to replace cystoscopy. In an effort to create reliable, objective, noninvasive mechanisms for detecting bladder cancer, a number of urine-based molecular tests have been developed with the ultimate goal of reducing the frequency of cystoscopy.
OBJECTIVE: To summarize the performance of urine-based biomarker tests, currently commercially available in the US, as part of the initial workup for hematuria and for bladder cancer surveillance.
METHODS: In accordance with PRISMA guidelines we performed a systematic review of the literature on the performance of NMP22, BTA, UroVysion, ImmunoCyt/uCyt, CxBladder, and Bladder EpiCheck. Median sensitivity, specificity, negative (NPV) and positive predictive values (PPV) were calculated for each test based on the included studies.
RESULTS: Twenty-eight studies met inclusion criteria for the performance of five urine-based biomarker tests in the setting hematuria workup. Median sensitivity ranged from 65.7% -100% and specificity ranged from 62.5% -93.8%. Median NPV ranged from 94.2% -98.3% and PPV ranged from 29% -58.7%. Fourteen studies met inclusion criteria for the performance of six tests in the setting of bladder cancer surveillance. Median sensitivity ranged from 22.6% -92.0% and specificity from 20.5% -97.9%. Median NPV ranged from 52.9% -96.5% and PPV ranged from 48.1% -75.7%.
CONCLUSIONS: Our analysis finds that while these tests may provide some clinical utility, none of the assays have thus far demonstrated objective evidence to supplant the gold diagnostic standard.

UNASSIGNED: The urinary biomarker response precedes the appearance of any renal structural or functional derangement. Transforming growth factor-β1 (TGF-β1), neutrophil gelatinase associated lipocalin (NGAL), and Cystatin C (CysC) can act as the early prognostic markers in posterior urethral valve (PUV) patients.
UNASSIGNED: To compare the urinary levels of TGF-β1, NGAL, and CysC between PUV cases and age matched controls and to correlate these with renal structural and functional parameters.
UNASSIGNED: This prospective study included children with PUV diagnosed using the standard investigations and an equal number of age-matched controls with nonurological problems. For the study subjects, the urinary samples were collected at three different time points (pre- and postoperatively at 3 and 6 months), whereas for controls, only single-voided samples were studied. The urinary levels of TGF-β1, NGAL, and CysC were estimated by the standardized techniques using the ELISA kits. Statistical methods were used to drive the comparisons between cases and controls.
UNASSIGNED: Fifteen children with a median age of 10 (5-48) months were enrolled in each of the two groups. The mean uTGF-β1 in the case group was significantly higher at all three time points (43.20 ± 6.13 pg/ml, 43.33 ± 11.89 pg/ml and 40.71 ± 9.01 pg/ml) as compared to the control group (29.12 ± 8.31 pg/ml) (P ≤ 0.001). The median uNGAL in the case group was also higher (17.78 ng/ml, 2.35 ng/ml and 2.536 ng/ml) as compared to the control group (1.31 ng/ml). However, the difference was significant only preoperatively (P = 0.02). The median uCysC in case group was similarly higher (0.347 μg/ml, 0.439 μg/ml, and 0.382 μg/ml) than the control group (0.243 μg/ml) (P > 0.05). Serum creatinine in the case group (0.49 mg/dl) showed no significant rise above that of control (0.24 mg/dl). A cutoff value of uTGF-β1 = 36.55 pg/ml (P < 0.001), uNGAL = 0.879 ng/ml (P = 0.02), and uCysC = 0.25 μg/ml (P = 0.22) was found to be associated with renal damage in PUV. A significant correlation was found between uNGAL and S. creatinine at 3 months (r = 0.43, P = 0.017) and 6 months (r = 0.47, P = 0.08).
UNASSIGNED: The elevated uTGF-β1, a decline in uNGAL and an increase in uCysC suggests ongoing inflammation, improvement in hydronephrosis and a prolonged proximal tubular dysfunction in PUV patients, respectively.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer often diagnosed at advanced stages, highlighting the urgent need for early detection strategies. This systematic review explores the potential of fecal and urinary biomarkers for early PDAC detection. A comprehensive search identified eight relevant studies investigating various biomarkers, including proteins, metabolites, microbial profiles, DNA mutations, and non-coding RNAs. Promising findings suggest that urinary biomarkers related to metabolic alterations, inflammatory processes, fecal microbiome profiles, and fecal miRNAs hold diagnostic potential even at early stages of PDAC. Combining biomarkers into panels may enhance diagnostic accuracy. Challenges such as validation in larger cohorts, standardization of protocols, and regulatory approval must be addressed for clinical translation. Despite these hurdles, non-invasive urinary and fecal biomarkers represent a promising avenue for improving PDAC outcomes through early detection.

Metabolomics, especially urine-based studies, offers incredible promise for the discovery and development of clinically impactful biomarkers. However, due to the unique challenges of urine, a highly precise and reproducible workflow for NMR-based urine metabolomics is lacking. Using 1D and 2D non-uniform sampled (NUS) 1H-13C NMR spectroscopy, we systematically explored how changes in hydration or specific gravity (SG) and pH can impact biomarker discovery. Further, we examined additional sources of error in metabolomics studies and identified Navigator molecules that could monitor for those biases. Adjustment of SG to 1.002-1.02 coupled with a dynamic sum-based peak thresholding eliminates false positives associated with urine hydration and reduces variation in chemical shift. We identified Navigator molecules that can effectively monitor for inconsistencies in sample processing, SG, protein contamination, and pH. The workflow described provides quality assurance and quality control tools to generate high-quality urine metabolomics data, which is the first step in biomarker discovery.

More than half of patients hospitalized with liver cirrhosis are dealing with an episode of acute kidney injury; the most severe pattern is hepatorenal syndrome due to its negative prognosis. The main physiopathology mechanisms involve renal vasoconstriction and systemic inflammation. During the last decade, the definition of hepatorenal syndrome changed, but the validated criteria of diagnosis are still based on the serum creatinine level, which is a biomarker with multiple limitations. This is the reason why novel serum and urinary biomarkers have been intensively studied in recent years. Meanwhile, the imaging studies that use shear wave elastography are using renal stiffness as a surrogate for an early diagnosis. In this article, we focus on the physiopathology definition and highlight the novel tools used in the diagnosis of hepatorenal syndrome.

Prostate cancer is the most common non-cutaneous cancer among men in the UK, causing significant health and economic burdens. Diagnosis and risk prognostication can be challenging due to the genetic and clinical heterogeneity of prostate cancer as well as uncertainties in our knowledge of the underlying biology and natural history of disease development. Urinary extracellular vesicles (EVs) are microscopic, lipid bilayer defined particles released by cells that carry a variety of molecular cargoes including nucleic acids, proteins and other molecules. Urine is a plentiful source of prostate-derived EVs. In this narrative review, we summarise the evidence on the function of urinary EVs and their applications in the evolving field of prostate cancer diagnostics and active surveillance. EVs are implicated in the development of all hallmarks of prostate cancer, and this knowledge has been applied to the development of multiple diagnostic tests, which are largely based on RNA and miRNA. Common gene probes included in multi-probe tests include PCA3 and ERG, and the miRNAs miR-21 and miR-141. The next decade will likely bring further improvements in the diagnostic accuracy of biomarkers as well as insights into molecular biological mechanisms of action that can be translated into opportunities in precision uro-oncology.

The appropriate use of human biomonitoring data to model population chemical exposures is challenging, especially for rapidly metabolized chemicals, such as agricultural chemicals. The objective of this study is to demonstrate a novel approach integrating model predicted dietary exposures and biomonitoring data to potentially inform regulatory risk assessments. We use lambda-cyhalothrin as a case study, and for the same representative U.S. population in the National Health and Nutrition Examination Survey (NHANES), an integrated exposure and pharmacokinetic model predicted exposures are calibrated to measurements of the urinary metabolite 3-phenoxybenzoic acid (3PBA), using an approximate Bayesian computing (ABC) methodology. We demonstrate that the correlation between modeled urinary 3PBA and the NHANES 3PBA measurements more than doubled as ABC thresholding narrowed the acceptable tolerance range for predicted versus observed urinary measurements. The median predicted urinary concentrations were closer to the median measured value using ABC than using current regulatory Monte Carlo methods.