Upconversion Nanoparticle-Based Dot-Blot Immunoassay for Quantitative Biomarker Detection.

Dot-blot immunoassays are widely used for the user-friendly detection of clinical biomarkers. However, the majority of dot-blot assays have only limited sensitivity and are only used for qualitative or semiquantitative analysis. To overcome this limitation, we have employed labels based on photon-upconversion nanoparticles (UCNPs) that exhibit anti-Stokes luminescence and can be detected without optical background interference. First, the dot-blot immunoassay on a nitrocellulose membrane was optimized for the quantitative analysis of human serum albumin (HSA), resulting in a limit of detection (LOD) of 0.19 ng/mL and a signal-to-background ratio (S/B) of 722. Commercial quantum dots were used as a reference label, reaching the LOD of 4.32 ng/mL and the S/B of 3, clearly indicating the advantages of UCNPs. In addition, the potential of UCNP-based dot-blot for real sample analysis was confirmed by analyzing spiked urine samples, reaching the LOD of 0.24 ng/mL and recovery rates from 79 to 123%. Furthermore, we demonstrated the versatility and robustness of the assay by adapting it to the detection of two other clinically relevant biomarkers, prostate-specific antigen (PSA) and cardiac troponin (cTn), reaching the LODs in spiked serum of 9.4 pg/mL and 0.62 ng/mL for PSA and cTn, respectively. Finally, clinical samples of patients examined for prostate cancer were analyzed, achieving a strong correlation with the reference electrochemiluminescence immunoassay (recovery rates from 89 to 117%). The achieved results demonstrate that UCNPs are highly sensitive labels that enable the development of dot-blot immunoassays for quantitative analysis of low-abundance biomarkers.

Cobalt oxide modified sulfur and phosphorus Co-doped g-C3N4 for screening of urinary human albumin.

The fabrication of a heteroatom-doped nanocomposite based on cobalt oxide modified sulfur, phosphorus co-doped carbon nitride (Co3O4/SP-CN) with increased active sites is reported. The synthesized nanocomposite offers surprisingly high electrocatalytic oxidation efficacy toward human albumin (HA) despite its agglomeration. This improved efficacy of Co3O4/SP-CN nanocomposite could be attributed to its increased adsorption sites and surface defects, fast charge transportation capability, and conductivity. Additionally, morphological and compositional analysis of the fabricated Co3O4/SP-CN material has been performed  through scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photon spectroscopy (XPS), and Raman spectroscopy. The fabricated electrode shows remarkable amperometric response against the HA with a limit of detection of 8.39 nM and linear range of 20-4000 nM at applied potential of 0.25 V versus Ag/AgCl in 0.1 M PBS (pH 8.2). The designed Co3O4/SP-CN electrode has been successfully applied to monitor HA in  urine samples of diabetic patient with recovery percentage from 94.1 and 92.1% and with relative standard deviation (RSD) values of 5.8 and 7.8%. According to the best of our knowledge, this is the first report to use a Co3O4/SP-CN-based graphitic pencil (GP) electrode for monitoring of HA for early diagnosis of diabetic nephropathy.

Simultaneous enrichment and separation based on ion concentration polarization effect on a paper based analytical device.

In this paper, simultaneous enrichment and separation of ions and amphoteric components were successfully demonstrated by using electric field (E) and pH gradient (double gradient) in the ion depletion zone of anion concentration polarization interface established on a paper fluid channel. Experimental results were visualized with colored ions (bright blue and amaranth) and protein probes (phycocyanin and cytochrome C). With optimization, colored phycocyanin and bovine hemoglobin with similar pI as that of albumin and immunoglobulin respectively were well separated in 900 s with 10-fold enrichment effect. Based on the separation and enrichment function of this paper-based analytical device (PAD) and rapid selective staining of human serum albumin (HSA) with bromophenol blue, a rapid colorimetric detection of HSA was implemented with smartphone camera. A limit of detection (LOD) of 5.2 mg·L-1 was achieved in the clinically significant range of 10-300 mg·L-1 (R2 = 0.99). This method was applied to real human urine samples with good agreement (ɑ = 0.01) to clinical detection method (immunoturbidimetry). With the separation and enrichment functions of PAD, both the specificity and sensitivity were enhanced, which provides a solid basis for point-of-care test of microalbuminuria. Therefore, this PAD device is potential for sample pretreatment and detection of target components from complex physiological samples.

Fluorogenic Detection of Human Serum Albumin Using Curcumin-Capped Mesoporous Silica Nanoparticles.

Mesoporous silica nanoparticles loaded with rhodamine B and capped with curcumin are used for the selective and sensitive fluorogenic detection of human serum albumin (HSA). The sensing mesoporous silica nanoparticles are loaded with rhodamine B, decorated with aminopropyl moieties and capped with curcumin. The nanoparticles selectively release the rhodamine B cargo in the presence of HSA. A limit of detection for HSA of 0.1 mg/mL in PBS (pH 7.4)-acetonitrile 95:5 v/v was found, and the sensing nanoparticles were used to detect HSA in spiked synthetic urine samples.

Fluorimetric method for specific detection of human serum albumin in urine using its pseudoesterase property.

Detection of microalbuminuria is an analytical challenge. There are dye-based methods and immunochemical methods. However, these methods are less specific and sensitive respectively. So, people are trying new approaches for microalbuminuria detection. In this context, we have developed a fluorescent spectroscopic method to detect human serum albumin using its pseudoesterase property. Recently, we had discovered that neostigmine does not inhibit Human serum albumin pseudoesterase activity. Using such a phenomenon, we have devised a specific fluorimetric detection method of HSA using 2NA as a substrate for the pseudoesterase activity. The developed method can sense as low as 0.1 µM of HSA in the urine matrix without dye or antibody. We have proposed a scheme of automation of the proposed method.

Detection of Urinary Albumin Using a "Turn-on" Fluorescent Probe with Aggregation-Induced Emission Characteristics.

Human serum albumin (HSA) is a broadly used biomarker for the diagnosis of various diseases such as chronic kidney disease. Here, a fluorescent probe TC426 with aggregation-induced emission (AIE) characteristics is reported as a sensitive and specific probe for HSA. This probe is non-emissive in aqueous solution, meanwhile it shows bright fluorescence upon interacting with HSA, which makes it applicable in detecting HSA with a high signal to noise ratio. Besides, the fluorescence of TC426 exhibits a high linear correlation with the concentration of albumin in the range of microalbumin (20-200 mg/L), which has a significant importance for the early diagnosis of glomerulus related diseases. Compared with previously reported HSA probes TPE-4TA and BSPOTPE, TC426 shows comparable anti-interference ability towards creatinine and other major components in urine but is excited by a longer excitation wavelength at the visible light range. Finally, with the established assay, TC426 shows excellent performance in detecting HSA in real human urine, indicating its great potential in practical urinalysis.

Protein-templated copper nanoclusters for fluorimetric determination of human serum albumin.

Copper nanoclusters (CuNCs) are attractive for their unique optical properties, providing sensitive fluorescent detection of several kinds of targets even in complex matrices. Their ability in growing on suitable protein and nucleic acid templates make CuNCs efficient optical reporters to be exploited in bioanalysis. In this work, we report the specific and sensitive determination of human serum albumin (HSA) in human serum (HS) and urine via CuNCs fluorescence. HSA is the most abundant protein in plasma, and plays a key role in the early diagnosis of serious pathological conditions such as albuminuria and albuminemia. Recently, HSA has become clinically central also as a biomarker to assess severity, progression, and prognosis of various cancers. We report the controlled and reproducible growth of CuNCs directly on the target analyte, HSA, which results in a fine dose-dependent fluorescent emission at 405 nm. The protocol is optimized in water, and then applied to serum and urine specimens, without matrix pretreatment. The method linearly responds within the whole concentration of clinical interest, with a sensitivity of 1.8 ± 0.1 × 10-3 g L-1 and 0.62 ± 0.03 × 10-3 g L-1 in serum and urine, respectively, and excellent reproducibility (CVav% ca. 3% for both). The assay is designed to have a single protocol working for both matrices, with recovery of 95% (HS) and 96% (urine). The stability of the fluorescence after CuNCs formation was tested over 3 days, displaying good results (yet higher in urine than in serum).

Polydopamine-based quantitation of albuminuria for the assessment of kidney damage.

Proteinuria is considered indicative of kidney damage that can be related to various adverse outcomes. Nowadays, there is a huge demand for routine urine screening methods to assess health risks in clinical setting without expensive procedures and long pretreatment of the sample. To address this issue, a polydopamine-based colorimetric assay to determine urinary albumin concentration in real samples is proposed here. The core of this approach relies on the established competitive adsorption of polydopamine film and human serum albumin onto the polystyrene surface of ELISA plates. Herein, we investigated the influence of temperature and the Tris-HCl buffer concentration on the polydopamine film growth. The absorbance of polydopamine film, after 24 h at 25 °C, decreases with the increase of HSA concentration, allowing the selective detection of HSA down to 0.036 ± 0.001 g L-1 in untreated urine. This simple and low-cost bioanalytical assay exhibited very good reproducibility, %CVmean = 2 in human urine, and was superior in terms of analytical performances to some standard methods available on the market, especially in comparison to the Bradford assay, for early screening and assessment of kidney damage.

Development and validation of point-of-care testing of albuminuria for early screening of chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD) is a significant global health issue. As the prevalence of renal replacement therapy (RRT) in Thailand is increasing, early detection and management of CKD is the most important step to prevent CKD progression and the need for RRT. Current diagnostic tests for CKD are non-specific and expensive. We aimed to develop and validate antibody-based-albumin point-of-care testing (POCT) to detect patients with impaired kidney function at early stage. METHODS: The prototype strip test was developed under the concept of competitive lateral flow immunochromatography assay, or strip test. Monoclonal antibodies (MAbs) to human serum albumin (HSA) were harvested from the hybridomas of spleen cells from immunized mice and mouse myeloma cells. Presence of MAbs was detected by enzyme-linked immunosorbent assay (ELISA). Spot urine was obtained from patients with kidney disease, type I, or type II Diabetes Mellitus upon their visit at King Chulalongkorn Memorial Hospital during 2018-2019. All samples were analyzed for urine albumin with our POCT (CU microalbumin) and the other two commercial POCTs (Microalbu PHAN and MICRAL). The results were validated against standard method for urine microalbumin measurement. A urine microalbumin concentration of less than 20 ug/ml was defined as normal. The sensitivity, specificity, and predictive values were calculated in comparison with the standard laboratory method. RESULT: A total of 100 adult patients were included. CU microalbumin had a sensitivity of 86%, a specificity of 94%, and a positive predictive value of 96%. Our POCT showed good correlation with the laboratory results. CONCLUSION: CU microalbumin correlated well with the standard method for quantitative measurement of urine albumin. Therefore, it has the potential for early screening of CKD, especially in primary health care facilities in resource limited settings.

Simultaneous Detection of Human Serum Albumin and Sulfur Dioxide in Living Cells Based on a Catalyzed Michael Addition Reaction.

As vital important bioactive species, human serum albumin (HSA) and sulfur dioxide (SO2) are essential molecules in the organisms and act a pivotal part in many biological events. Although studies have shown that SO2-induced HSA radicals can cause oxidative damage, the underlying mechanism of the synergistic effect of HSA and SO2 in various diseases is obscure, mainly because of the lack of powerful tools that can simultaneously detect HSA and SO2 in living systems. In this work, we report a novel single-site, double-sensing fluorescent probe 1 for the simultaneous detection of HSA and SO2. The probe is based on our finding that HSA can catalyze a Michael addition reaction between the probe and SO2, which induces a change in fluorescence. Probe 1 can effectively entered the endoplasmic reticulum and can be used to image exogenously introduced and de novo synthesis of HSA in endoplasmic reticulum. Furthermore, the simultaneous detection of HSA and SO2 was realized for the first time with probe 1. More important, we observed that HSA still retains its activity to catalyze the Michael addition reaction of 1 and SO2 in living cells, which may provide a significant boost in the study of the role of HSA in medicine and pharmacy.

A novel hydrazide Schiff base self-assembled nanoprobe for selective detection of human serum albumin and its applications in renal disease surveillance.

Human serum albumin (HSA) is considered as a biomarker for the early diagnosis of renal disease, therefore identifying and detecting HSA in biological fluids (especially urine) with an easy method is of great importance. Herein, we report a novel hydrazide Schiff base fluorescent probe N'-((7-(diethylamino)-2-oxo-2H-chromen-3-yl)methylene)pyrazine-2-carbohydrazide (NPC), which self-assembled into nanoparticles in aqueous solution. Based on disassembly-induced emission and the site-specific recognition mechanism, the binding of NPC with HSA resulted in a fluorescence "turn-on" response. Probe NPC exhibited superior selectivity and sensitivity toward HSA with a detection limit of 0.59 mg L-1 in PBS and 0.56 mg L-1 in the urine sample. The site-binding mechanism of NPC with HSA was explored by fluorescence quenching study, Job's plot analysis, HSA destruction, site marker displacement and molecular docking. Fluorescence imaging of HSA in MCF-7 cells was achieved by using a non-toxic NPC probe, suggesting that NPC could be applied to visualize the level of HSA in vivo. More importantly, further practical applications of probe NPC in human urine samples were achieved with satisfactory results by using a fluorometer or test paper, which could provide extensive application in clinical diagnosis.

Despite initial recovery of GFR, long-term renal functions deteriorate following short periods of unilateral ureteral obstruction.

Following the release of short periods of unilateral ureteral obstruction (UUO), glomerular filtration rate (GFR) recovers by time. However, research in experimental animal models has demonstrated the presence of an ongoing element of renal interstitial fibrosis a few weeks following UUO reversal. Interstitial fibrosis can cause deterioration in GFR, and it is not known whether it leads to an ongoing slow deterioration in other renal functions despite the apparent initial recovery postreversal. To investigate this, rats underwent a 72-h reversible UUO. Renal functions of nonobstructed and previously obstructed kidneys were measured 1, 4, and 18 mo postreversal. GFR in nonobstructed and previously obstructed kidneys was similar up to 18 mo postreversal. However, there was ongoing tubulointerstitial fibrosis, and the degree of tubular atrophy and dilatation deteriorated by time. This was associated with an increase in urinary albumin leakage and alterations in renal injury markers, proinflammatory and profibrotic cytokines, and p53 from 4 mo onward despite the recovery in GFR. In conclusion, several aspects of renal functions continue to deteriorate following reversal of relatively short periods of UUO despite the initial recovery in GFR. This might stimulate further research in this area and might have clinical implications in terms of determining the best time for intervention following acute ureteral obstruction and long-term monitoring of these individuals.

The findings of corneal specular microscopy in patients with type-2 diabetes mellitus.

BACKGROUND: We aimed to compare the morphological characteristics of corneal endothelial cells in type 2 diabetic patients and age-matched healthy subjects by specular microscopy. We also aimed to determine the association of corneal morphological features with the general characteristics and laboratory data of diabetic patients, including disease duration, haemoglobin A1c (HbA1c) levels and urine albumin creatinine ratio. METHODS: A total of 195 diabetic patients and 100 healthy controls were enrolled in the study. All participants underwent a complete ophthalmological examination. Corneal endothelial measurements were performed using a noncontact specular microscopy. Laboratory data including serum fasting glucose, haemoglobin A1c levels, creatinine levels, and the urinary albumin-to-creatinine ratio were recorded. Diabetic patients were further subdivided into 3 groups according to the presence and stage of diabetic retinopathy. Specular microscopy findings and central corneal thickness of all patients were compared. RESULTS: The ECD and hexagonal cell ratio were significantly lower, while the average cell size, CV%, and central corneal thickness were determined to be significantly higher in diabetic patients than in healthy controls (p = 0.001). With the presence and advancement of diabetic retinopathy, the ECD and hexagonal cell ratio decreased, while the average cell size, CV%, and central corneal thickness increased. When correlation analysis was performed between corneal morphological features and laboratory data of diabetic patients, ECD showed a significant negative correlation with diabetes duration (p = 0.028). HbA1c levels, urinary albumin-creatinine ratio (p = 0.041), average cell size and CV showed a positive correlation with these parameters. CONCLUSION: In conclusion, keratopathy is an important complication of type 2 diabetes. With an increase in the stage of diabetic retinopathy, alterations in corneal findings also increased. In that respect, we can suggest that keratopathy should be evaluated more cautiously in diabetic patients.

Monitoring cellulose oxidation for protein immobilization in paper-based low-cost biosensors.

The oxidation of paper by periodate was investigated and systematically characterized by Fourier-transform infrared (FTIR) spectroscopy, scanning electron microscopy, X-ray diffraction, goniometry, and dynamic mechanical analysis. For the first time, in situ FTIR microscopy analysis was performed, yielding chemical images of carbonyl groups on the cellulose fibers. The enhancement of protein immobilization on oxidized paper was quantified by a colorimetric assay with Ponceau dye, demonstrating that 0.5-h oxidation suffices to functionalize the paper-based devices. The oxidized paper was applied as a sensor for protein quantification in urine, a test able to detect levels of proteinuria and even microalbuminuria. The quantification was based on the capture of proteins through covalent bonds formed with the carbonyl groups on the oxidized paper followed by the staining of the region with Ponceau dye. There is a linear dependency between human serum albumin (HSA) concentration and the length of the stained blot from 0.1 to 3 mg mL-1. This method correlated linearly with a reference method showing a higher sensitivity (0.866 cm mL mg-1) than the latter. The limit of quantification was 0.1 mg mL-1, three times lower than that of the commercial strip. Graphical abstract Paper oxidation with periodate and extensive characterization, including microspectroscopy. The conversion of cellulose hydroxyl groups to aldehyde enhances covalent immobilization of protein on paper for application as analytical device. The oxidized paper determined protein in urine, suitable for proteinuria diagnosis.

Ionic liquid decorated AIE luminogen for selective detection of HSA in biofluids and early disease screening.

The precise evaluation of human serum albumin (HSA) contents in biofluids is critical due to its important physiological functions. A fluorescent luminogen TPE-IL is facilely fabricated in present study by decorating the aggregation induced emission (AIE) dye E-1,2-bis(4-hydroxyphenyl)-1,2-diphenylethylene (TPE-OH) with ionic liquid (IL) HOOCMIMBr. The hydrophobic and hydrogen-bond interactions between the amino acid residues of HSA and TPE-IL lead to the spontaneous and energetically favorable docking of TPE-IL molecules in the hydrophobic subdomain of HSA, inducing the significant fluorescence enhancement of this sensor. Highly sensitive and selective detection of HSA is accomplished in the linear range of 0.02-10 µg/mL, with a detection limit of 0.007 µg/mL. The practicability of this sensor is validated by the accurate detection of HSA contents in human serum and urine samples. A glass slide-based visual sensing platform is also constructed to offer simple and fast HSA content evaluation in serum for early disease screening.

NGAL, albumin and cystatin C during cisplatin therapy.

Cisplatin is a commonly used chemotherapeutic drugs. It is known for its nephrotoxic side effects with an increased risk of acute kidney injury. Finding of clinically feasible cisplatin nephrotoxicity markers is of importance. In our study, we compared neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine, the estimated glomerular filtration rate (based on serum cystatin C) and urine albumin as markers of nephrotoxicity. The study involved 11 men and 9 women (mean ± SD age 58.2±9.5 years) with different malignancies treated with cisplatin in four cycles of chemotherapy (I - IV). Samples 0-4 were taken before, immediately after, in 3, 6 and 24 hours after administering chemotherapy. We detected significant increase of ACR in Sample 2 (p=0.03) and decrease of eGFR in Sample 4 (p=0.03) up to 24 hours after cisplatin administration in the first chemotherapy cycle only. When cumulative effect of cisplatin was assessed, significantly increased values of urine albumin (vs cycle I) were found in Sample 0 (p=0.00058), 1 (p=0.00256), 2 (p=0.00456), 3 (p=0.00006) and 4 (p=0.00319) in cycles II to IV. We found a correlation between values of urine NGAL and urine albumin (r=0.68, p<0.0001). In conclusion, urine albumin was the only measured marker that consistently and statistically significantly increased after cisplatin containing chemotherapy cycles.

Sensitive detection of albuminuria by graphene oxide-mediated fluorescence quenching aptasensor.

Albuminuria is a pathological condition wherein the human serum albumin (HSA) protein is present in abnormally excess amounts in the urine. A simple and sensitive graphene oxide-mediated fluorescence quenching aptasensor is developed to quantify albumin in urine samples and HSA in serum samples. The aptamer-bound HSA used in this aptasensor has hairpin structures, which are characteristic of the aptamer binding site. The limit of detection of the developed platform is 0.05 µg·mL-1 and the detection range is 0.1-14.0 µg·mL-1, which covers the albuminuria concentration range present in normal human urine and the urine of the patient with kidney diseases. This approach can be modified to measure HSA using a high-throughput quantification platform and portable point of care testing. In addition, the production cost for one reaction is cheaper than those for other standard automated methods. Therefore, this aptasensor has significant potential for commercialization and wide-scale public use.

Online sample clean-up and enrichment of proteins from salty media with dynamic double gradients on a paper fluidic channel.

Paper-based analytical device (PAD) has received more and more attention in the field of point-of-care test (POCT) due to its low cost, portability and simple operation. Sensitivity and selectivity are two important aspects in clinical diagnostic analysis. However, low sensitivity of a PAD limits its wider application for POCT. Here we introduced a PAD that can clean and enrich the protein content from salty media with both electric field (E) and pH gradient (double E/pH gradients), with which 100-fold enrichment effect could be achieved within 70 s as demonstrated by fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) from artificial urine media. With post staining of the protein stacking band with bromophenol blue (BPB), selective colorimetric detection of human serum albumin (HSA) was achieved simply with smartphone camera in the clinically significant range of 10-300 mg‧L-1 (R2 = 0.99) with a limit of detection (LOD) of 4.9 mg‧L-1. Detection of microalbuminuria (MAU) of diabetic patients was demonstrated with this method without difference (ɑ = 0.01) to that by the clinical method (immunoturbidimetry). This work demonstrated the potential of this PAD method in online sample pretreatment and detection of target component from complex physiological samples.

Glyphosate exposures and kidney injury biomarkers in infants and young children.

The goal of this study was to assess biomarkers of exposure to glyphosate and assess potential associations with renal function in children. Glyphosate is used ubiquitously in agriculture worldwide. While previous studies have indicated that glyphosate may have nephrotoxic effects, few have examined potential effects on kidney function in children. We leveraged three cohorts across different phases of child development and measured urinary levels of glyphosate. We evaluated associations of glyphosate with three biomarkers of kidney injury: albuminuria (ACR), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury marker 1 (KIM-1). Multivariable regression analyses examined associations of glyphosate with kidney injury biomarkers controlling for covariates. We identified glyphosate in 11.1% of the total participants. The herbicide was detected more frequently in the neonate population (30%). Multivariable regression models failed to identify significant associations of log-transformed glyphosate with any of the kidney injury biomarkers, controlling for covariates age, sex, and maternal education. While we confirm detectability of glyphosate in children's urine at various ages and stages of life, there is no evidence in this study for renal injury in children exposed to low levels of glyphosate. Further studies of larger sample size are indicated to better understand putative deleterious effects of the herbicide after different levels of exposure.

Association of uric acid in serum and urine with subclinical renal damage: Hanzhong Adolescent Hypertension Study.

BACKGROUND AND OBJECTIVES: The aim of the study was to examine the associations of uric acid (UA) in blood and urine with subclinical renal damage (SRD) and its progression in a Chinese cohort. METHODS: 1) 2342 participants from our previously established cohort who were followed up in 2017 were included. Cross-sectional analysis was used to examine the relationships between serum and urinary UA and the risk of SRD. 2) A total of 266 participants were recruited from the same cohort in 2013, and followed up in 2017. Longitudinal analysis was used to determine the relationships of serum and urinary UA with progression of SRD, which was defined as urinary albumin-to-creatinine ratio (uACR) progression or estimated glomerular filtration rate (eGFR) decline. RESULTS: In cross-sectional analysis, higher levels of uACR were associated with higher levels of serum uric acid (SUA) and urinary uric acid/creatinine ratio (uUA/Cre). Lower eGFR was associated with higher levels of SUA and fractional excretion of uric acid (FEUA) but lower uUA/Cre levels in all subjects. In addition, the multivariate-adjusted odds ratios for SRD compared with non-SRD were 3.574 (2.255-5.664) for uUA/Cre. Increasing uUA/Cre levels were associated with higher risk of SRD. In longitudinal analysis, 4-year changes of uUA/Cre and SUA were significantly associated with eGFR decline. CONCLUSIONS: This study suggested that urinary UA excretion was significantly associated with the risk of SRD in Chinese adults. Furthermore, 4-year changes of serum and urinary UA were associated with SRD progression. These findings suggest that UA, especially urinary UA, may be used as a simple, noninvasive marker for early detection of decreased renal function in otherwise healthy subjects.