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Nowadays, kidney dysfunction is a common health issue due to the modernized lifestyle. Even though medications are commercially available to treat kidney diseases, early diagnosis is crucial and challenging. Clinically, measuring urine creatinine and pH has gained significant interest as a way to diagnose kidney diseases early. In the present work, we attempted to develop a low-cost, robust, accurate and naked-eye colorimetric method to determine both creatinine levels and pH variations in artificial urine samples using a simple 3D-printed hybrid microfluidic device. Creatinine was detected by the incorporation of the traditional Jaffe test onto the hybrid paper-PMMA microfluidic device and pH (4-8) was measured by a simple anthocyanin test. Notably, the tests were established without employing any sophisticated or costly instrument clusters. The developed 3D-printed microfluidic probe showed a limit of detection (LOD) of 0.04 mM for creatinine over a concentration range of 1-10 mM, with a regression coefficient ( R ) of 0.995 in laboratory conditions. Interestingly, the experimental data obtained with artificial urine exhibited a wide linear range from 0.1 mM to 5 mM under different pH values ranging from 4 to 8 in the presence of matrices commonly found in urine samples other than proteins, indicating the potential use of this method in pre-clinical analysis. Since the wide linear range of urine creatinine in artificial urine samples falls well below the clinically relevant concentrations in humans (0.07-0.27 mM), the developed lab-on-chip device is further suitable for clinical evaluation with proper ethical clearance. This 3D-printed hybrid microfluidic colorimetry-based creatinine detection and pH indicator platform can be beneficial in the healthcare sector due to the on-site testing capability, cost-effectiveness, ease of use, robustness, and instrument-free approach.2 ) of 0.995 in laboratory conditions. Interestingly, the experimental data obtained with artificial urine exhibited a wide linear range from 0.1 mM to 5 mM under different pH values ranging from 4 to 8 in the presence of matrices commonly found in urine samples other than proteins, indicating the potential use of this method in pre-clinical analysis. Since the wide linear range of urine creatinine in artificial urine samples falls well below the clinically relevant concentrations in humans (0.07-0.27 mM), the developed lab-on-chip device is further suitable for clinical evaluation with proper ethical clearance. This 3D-printed hybrid microfluidic colorimetry-based creatinine detection and pH indicator platform can be beneficial in the healthcare sector due to the on-site testing capability, cost-effectiveness, ease of use, robustness, and instrument-free approach.

In this work, a microfluidic paper-based analytical device (μPAD) for simultaneous multiple-point standard addition assay was fabricated by rubber stamping the hydrophobic barrier pattern onto a laboratory filter paper. The μPAD has a central zone from which an applied sample flows into eight surrounding narrow channels to which had been added the standard solutions. Each channel is connected to a circular area loaded with the reagent. The opposite end of this reagent zone is connected by second narrow channel to the final circular detection zone. The μPAD was applied to the measurement of creatinine in human urine. After addition of a urine sample, the orange-colored product arising from the Jaffé reaction is formed at the eight detection zones. A digital image of the μPAD is then recorded and the ratio of the red/green (R/G) intensity obtained using the ImageJ™ program is used in the quantitation of creatinine. The normal standard addition calibration line is constructed using the intensity ratio against the added creatinine concentrations (50-1000 mg L -1 ). Good linearity was achieved (r 2 ˃ 0.99). There were no significant differences between the creatinine content using an HPLC method (paired t-test at 95% confidence, t stat  = 1.78, t critical  = 2.26, n = 10). The use of simultaneous multiple-point standard addition calibration allows rapid determination of creatinine in urine with elimination of matrix interference., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A paper-based analytical device (PAD) with an integrated composite electrode for non-enzymatic creatinine sensing was developed. The electrode was produced and optimization was efficiently accomplished using a rapid digital dispensing approach. The electrochemical sensor was fabricated using an HP D300 digital dispenser to deliver a copper oxide and ionic liquid composite onto an electrochemically reduced graphene modified screen-printed carbon electrode (CuO/IL/ERGO/SPCE) on a PAD. The modified electrode was characterized using electrochemical and microscopic techniques. Electrochemical detection of creatinine was performed on the SPCE using amperometry at a constant potential. Under optimized conditions, the paper-based sensor exhibited a linear range of 0.01-2.0 mM (R 2  = 0.99) and the limit of detection was 0.22 μM (S/N = 3, IUPAC definition) for creatinine. The simple fabrication process, low cost, and clinically appropriate creatinine sensitivity make this device applicable for point-of-care use., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Proteinuria is a condition in which an excessive amount of protein is excreted in urine. It is, among others, an indicator of kidney disease or risk of cardiovascular disease. Rapid and reliable diagnosis and monitoring of proteinuria is of great importance for both patients and their physicians. For that reason, a paper-based sensor for proteinuria diagnosis was designed, optimized, and validated utilizing smartphone-assisted signal acquisition. In the first step, a few commonly employed protein assays were optimized and compared in terms of analytical performance on paper matrix. The tetrabromophenol blue method was selected as the one providing a sufficiently low limit of detection (39 mg·L -1 ) on the one hand and appropriate long-term stability (up to 3 months) on the other hand. The optimized assay was employed for protein-to-creatinine ratio (PCR) determination on a single paper-based sensor. For both analytes the linear ranges were within the clinically relevant range. The analytical usefulness of the developed sensors was demonstrated by a PCR recovery study in artificial urine. The obtained PCR recoveries were from ca. 80 to 150%.

A novel paper-based analytical device (PAD) was fabricated and developed for the simple and rapid determination of the albumin to creatinine ratio (ACR) in urine samples. The detection was based on a colorimetric reaction using bromocresol green (BG) in a phosphate buffer (PB) at pH 4 for the determination of albumin (AL) and creatinine (CR). BG changes color from greenish-yellow to bluish-green in the presence of AL and/or CR. Picric acid (PA) in 0.25 M NaOH was used to detect CR, and PA changes color from yellow to orange. Under the optimal conditions, the working range was 10 to 350 mg dL-1 with a detection limit of 7.1 and 5.4 mg dL-1 for AL + CR and CR detection, respectively. The repeatability was evaluated, and the %RSD value was less than 8.23 (n = 10). The ACR was obtained by calculating the AL and CR colorimetric results. Finally, the proposed devices were applied to the determination of AL, CR, and ACR in urine samples. The results obtained by the developed PADs were in good agreement with the standard method and demonstrated the method could reliably measure AL, CR, and ACR. The proposed method provides a low-cost, simple, sensitive, and promising tool for diagnostic identification assay for chronic kidney disease (CKD).

Simple, low-cost and portable microfluidic paper-based analytical devices (μPADs) for determination of creatinine in urine samples were developed. The methodology was based on Jaffé reaction between the creatinine and picric acid in alkaline conditions, generating a colorimetric creatinine-alkaline picrate complex. The product exhibits an orange color that is clearly visible on the μPADs. The color intensity of the complex, which is indicative of the concentration of creatinine, is then quantitatively determined using ImageJ software. Various experimental parameters were optimized to achieve the best performance of the μPADs. Under the optimum conditions, a wide linear range was obtained in the range of 0.2 - 1 mM with a limit of detection and limit of quantitation of 0.08 and 0.26 mM, respectively. The accuracy of the proposed method was in good agreement with the standard Jaffé method. Finally, the developed devices were successfully applied for the determination of creatinine in urine samples.

This chapter describes the development of paper-based microchip electrophoresis (pME) devices for the separation of clinically relevant compounds. pME were fabricated by laser cut and thermal lamination process using polyester pouches. In addition, hand-drawn pencil electrodes were integrated to the device to perform capacitively coupled contactless conductivity detection (C 4 D). Finished device costs less than US$ 0.10 and did not require either sophisticated instrumentation or clean room facilities. Furthermore, pME is lightweight, easy to handle, flexible, and robust. pME-C 4 D device revealed an excellent capacity to separate BSA and creatinine in less than 150 s with baseline resolution. The device proposed in this chapter has proven to be a good alternative as a platform for the diagnosis of diseases from renal disorders such as diabetes mellitus and heart disease.

A new disposable microfluidic electrochemical paper-based device (ePAD) consisting of two spot sensors in the same working electrode for the simultaneous determination of uric acid and creatinine was developed. The spot 1 surface was modified with graphene quantum dots for direct uric acid oxidation and spot 2 surface modified with graphene quantum dots, creatininase and a ruthenium electrochemical mediator for creatinine oxidation. The ePAD was employed to construct an electrochemical sensor (based on square wave voltammetry analysis) for the simultaneous determination of uric acid and creatinine in the 0.010-3.0 µmol L -1 range. The device showed excellent analytical performance with a very low simultaneous detection limit of 8.4 nmol L -1 to uric acid and 3.7 nmol L -1 to creatinine and high selectivity. The ePAD was applied to the rapid and successful determination of those clinical biomarkers in human urine samples., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Creatinine is one of many markers used to investigate kidney function. This paper describes a low-cost enzymatic paper-based analytical device (enz-PAD) for determining urine creatinine. The disposable dead volumes of creatinine enzyme reagents from an automatic analyser cassette were utilised. Whatman No. 3 paper was cut into long rectangular shapes (4×40 mm(2)) on which the enzyme reagents, R1 and R2, were adsorbed in two consecutive regions. The assay was performed by immersing test strips into urine samples contained in microwells to allow creatinine in the sample to react with immobilised active ingredients and, then, traverse via capillary action to the detection area where chromogen products accumulated. The method is based on hydrogen peroxide (H2O2) formation via creatinine conversion using creatininase, creatinase, and sarcosine oxidase. The liberated H2O2 reacts with 4-aminophenazone and 2,4,6-triiodo-3-hydroxybenzoic acid to form quinoneimine with a pink-red colour at the detection zone. The linear range of the creatinine assay was 2.5-25 mg dL(-1) (r(2)=0.983), and the detection limit was 2.0 mg dL(-1). The colorimetric enz-PAD for the creatinine assay was highly correlated with a conventional alkaline picrate method when real urine samples were evaluated (r(2)=0.977; n=40). This simple and nearly zero-cost paper-based device provides a novel alternative method for screening urinary creatinine and will be highly beneficial for developing countries., (Copyright © 2015 Elsevier B.V. All rights reserved.)

In this paper, we describe a validated paper-based microfluidic analytical device for the simultaneous quantification of two important biomarkers of renal function in urine. This paper platform provides an inexpensive, simple, and easy to use colorimetric method for the quantification of creatinine (CRN) and uric acid (UA) in urine samples. The microfluidic paper-based analytical device (μPAD) consists of a main channel with three identical arms, each containing a circular testing zone and a circular uptake zone. Creatinine detection is based on the Jaffé reaction, in which CRN reacts with picrate to form an orange-red product. Uric acid quantification is based on the reduction of Fe 3+ to Fe 2+ by UA, which is detected in a colorimetric reaction using 1,10-phenanthroline. Under optimum conditions, obtained through chemometrics, the concentrations of the analytes showed good linear correlations with the effective intensities, and the method presented satisfactory repeatability. The limits of detection and the linear ranges, respectively, were 15.7 mg L -1 and 50-600 mg L -1 for CRN and 16.5 mg L -1 and 50-500 mg L -1 for UA. There were no statistically significant differences between the results obtained using the μPAD and a chromatographic comparative method (Student's t-test at 95% confidence level)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A new paper platform was developed for the colorimetric detection of creatinine. The filter paper was coated with 3-propylsulfonic acid trimethoxysilane and used as the platform. Creatinine in a cationic form was extracted onto the paper via an ion-exchange mechanism and detected through the Jaffé reaction, resulting in a yellow-orange color complex. The color change on the paper could be observed visually, and the quantitative detection of creatinine was achieved through monitoring the color intensity change. The color intensity of creatinine complexes on the paper platform as a function of the creatinine concentration provided a linear range for creatinine detection in the range of 10 - 60 mg L(-1) and a detection limit of 4.2 mg L(-1). The accuracy of the proposed paper-based method was comparable to the conventional standard Jaffé method. This paper platform could be applied for simple and rapid detection of creatinine in human urine samples with a low consumption of reagent.

This paper introduces the concept of "Drawing-PADs" (Drawing paper-based microfluidic analytical devices) allowing to intuitively evaluate the urinary albumin (Alb) index, a clinically important parameter used for the early detection of renal deficiencies related to diabetes, among others. To enable regular monitoring of the Alb index, a simple examination method suitable for self-diagnosis is highly desirable. The Drawing-PADs rely on the simultaneous naked eye detection of Alb and creatinine (Cre) on a single device according to the distance-based microfluidic PAD (μPAD) approach. The Alb index is visualized by simply drawing a straight line connecting the top of two color-changed assay channel sections (Alb and Cre channels), followed by visually confirming the position of the intercept of the drawn straight line. The semiquantitative Alb index evaluation performed with Drawing-PADs does not require any equipment such as a camera, software, or a color reference chart. The obtained results are independent of the sample volume and are not influenced by changes in the absolute Alb and Cre concentrations caused by urine excretion variations, making spot urine assays possible. Classification of Alb index values according to clinically relevant criteria (normoalbuminuria, microalbuminuria, and macroalbuminuria) is readily achieved within 15 min and has been validated for 15 human urine samples including diabetic patients and healthy volunteers.

Patients with kidney disease require frequent blood tests to monitor their kidney function, which is particularly difficult for young children and the elderly. For these people, the standard method is to evaluate serum creatinine or cystatin C or drug levels through venous sampling, but more recently, evaluation using dried blood spots has been used. This narrative review reports information from the literature on the use of dried blood spots to quantify the main markers used to detect kidney diseases. The ScienceDirect and PubMed databases were searched using the keywords: "dried blood on filter paper," "markers of renal function," "renal function," "creatinine," "cystatin C," "urea," "iohexol," and "iotalamate." Studies using animal samples were excluded, and only relevant articles in English or Spanish were considered. Creatinine was the most assessed biomarker in studies using dried blood spots to monitor kidney function, showing good performance in samples whose hematocrit levels were within normal reference values. According to the included studies, dried blood spots are a practical monitoring alternative for kidney disease. Validation parameters, such as sample and card type, volume, storage, internal patterns, and the effects of hematocrit are crucial to improving the reliability of these results.

Aim: To develop a bioassay for estimation of sodium, potassium and creatinine in dried urine strips and comparing with their respective concentration in liquid urine samples. Materials & methods: Urine was collected on filter paper strips, dried at room temperature and, eluted for estimation of sodium, potassium by indirect ion selective electrode method and creatinine by Jaffé method. Result: This bioassay was validated based on the US FDA guidelines for bioanalytical method validation and was linear, sensitive, accurate and precise with acceptable recovery and matrix effects. Analytes were stable in dried urine strips during 1 year of storage at 4°C. Conclusion: We conclude that the dried urine is suitable for analysis of sodium, potassium and creatinine and offers a convenient alternative for monitoring dietary salt intake.

Iodine deficiency is a world-wide health problem. A simple, convenient, and inexpensive method to monitor urine iodine levels would have enormous benefit in determining an individual's recent iodine intake or in identifying populations at risk for iodine deficiency or excess. Current methods used to monitor iodine levels require collection of a large volume of urine and its transport to a testing laboratory, both of which are inconvenient and impractical in parts of the world lacking refrigerated storage and transportation. To circumvent these limitations we developed and validated methods to collect and measure iodine and creatinine in urine dried on filter paper strips. We tested liquid urine and liquid-extracted dried urine for iodine and creatinine in a 96-well format using Sandell-Kolthoff and Jaffe reactions, respectively. Our modified dried urine iodine and creatinine assays correlated well with established liquid urine methods (iodine: R(2)=0.9483; creatinine: R(2)=0.9782). Results demonstrate that the dried urine iodine and creatinine assays are ideal for testing the iodine status of individuals and for wide scale application in iodine screening programs., (Copyright © 2012 Elsevier B.V. All rights reserved.)

A paper-based analytical device (PAD) with an integrated composite electrode has been designed and fabricated for non-enzymatic creatinine sensing. Reduced graphene oxide (rGO) was employed to modify the PAD so that it could function as a solid-contact transducer. A new macrocyclic pyrido-hexapeptide derivative was made and used as a special ionophore in the creatinine membrane sensor. The synthesized PAD showed a detection limit of 1.0 µM (S/N = 3) and a potentiometric response towards creatinine throughout a log-linear range of 2.0 µM–10 mM (R2 = 0.9998). The sensor shows significant selectivity for a few related substances, including ephedrine, codeine, ketamine, caffeine, urea, urate, carbinoxamine, and dextromethorphan. It has been established that the testing method is appropriate for the direct potentiometric detection of creatinine in a variety of human urine sample types. When an indicating electrode and a reference electrode are put on the same flexible disposable, this lets applications with a small sample volume be done. For point-of-care creatinine measurement, the developed paper-based analytical equipment is a good choice because it is affordable, easily accessible, and self-pumping (especially when combined with potentiometric detection). [ABSTRACT FROM AUTHOR]

Creatinine is one of the most important biomarkers to detect renal failures. The electrochemical detection of creatinine has been performed using complex enzymatic and non-enzymatic electrode arrays hindering their commercialization. In this work, a new and practical non-enzymatic electrochemical sensor was fabricated depositing copper on carbon paper electrodes by physical vapor deposition (namely Cu/CP). Surface and cross-sectional SEM images demonstrated the deposition of copper over the 3D structure of carbon paper. A thin film was found on the surface, while Cu nanowires with diameters of 180 ± 30 nm were found inside the 3D structure of CP. The thickness of the Cu film on the tubular structures of CP was of 390 ± 40 nm. High-resolution TEM images indicated that the Cu film was integrated by hierarchical structures containing terminal Cu hemispheres of 17.6 ± 2.2 nm. Additionally, interplanar distances from the selected-area electron diffraction pattern demonstrated the presence of Cu0, while Cu2O was also found. Creatinine concentrations in saliva between 16 and 400 µM indicate kidney failure. The Cu/CP electrochemical sensor detected creatinine with linear concentration ranges from 0 to 1000 µM with a r2 = 0.9936. Outstandingly, this sensor presented good reproducibility (RSD = 7.3%), and selectivity to detect creatinine in artificial saliva using interferents like urea, glucose, glycine, ascorbic and uric acids. [ABSTRACT FROM AUTHOR]

Patients with kidney disease require frequent blood tests to monitor their kidney function, which is particularly difficult for young children and the elderly. For these people, the standard method is to evaluate serum creatinine or cystatin C or drug levels through venous sampling, but more recently, evaluation using dried blood spots has been used. This narrative review reports information from the literature on the use of dried blood spots to quantify the main markers used to detect kidney diseases. The ScienceDirect and PubMed databases were searched using the keywords: "dried blood on filter paper," "markers of renal function," "renal function," "creatinine," "cystatin C," "urea," "iohexol," and "iotalamate." Studies using animal samples were excluded, and only relevant articles in English or Spanish were considered. Creatinine was the most assessed biomarker in studies using dried blood spots to monitor kidney function, showing good performance in samples whose hematocrit levels were within normal reference values. According to the included studies, dried blood spots are a practical monitoring alternative for kidney disease. Validation parameters, such as sample and card type, volume, storage, internal patterns, and the effects of hematocrit are crucial to improving the reliability of these results. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is a widespread condition with considerable health and economic impacts globally. However, existing methodologies for serum creatinine assessment often involve prolonged wait times and sophisticated equipment, such as spectrometers, hindering real-time diagnosis and care. Innovative solutions like point-of-care (POC) devices are emerging to address these challenges. In this context, there is a recognized need for remote, regular, automated, and low-cost analysis of serum creatinine levels, given its role as a critical parameter for CKD diagnosis and management. This study introduces a miniaturized system with integrated heater elements designed for precise serum creatinine measurement. The system operates based on the Jaffe method and accurate serum creatinine measurement within a microreservoir chip. Smartphone-based image processing using the hue-saturation-value (HSV) color space was applied to captured images of microreservoirs. The creatinine analyses were conducted in serum with a limit of detection of ~ 0.4 mg/dL and limit of quantification of ~ 1.3 mg/dL. Smartphone-based image processing employing the HSV color space outperformed spectrometric analysis for creatinine measurement conducted in serum. This pioneering technology and smartphone-based processing offer the potential for decentralized renal function testing, which could significantly contribute to improved patient care. The miniaturized system offers a low-cost alternative ($87 per device), potentially reducing healthcare expenditures (~ $0.5 per test) associated with CKD diagnosis and management. This innovation could greatly improve access to diagnosis and monitoring of CKD, especially in regions where access to sophisticated laboratory equipment is limited., (© 2024. The Author(s).)

Screen-printed carbon electrodes (SPCE) functionalized with MXene-based three-dimensional nanomaterials are reported for rapid determination of creatinine. Ti 3 C 2 T X MXene with in situ reduced AuNPs (MXene@AuNP) were used as a coreactant accelerator for efficient immobilization of enzymes. Creatinine could be oxidized by chitosan-embedded creatinine amidohydrolase, creatine amidinohydrolase, or sarcosine oxidase to generate H 2 O 2 , which could be electrochemically detected enhanced by Prussian blue (PB). The enzyme@CS/PB/MXene@AuNP/SPCE detected creatinine within the range 0.03-4.0 mM, with a limit of detection of 0.01 mM, with an average recovery of 96.8-103.7%. This indicates that the proposed biosensor is capable of detecting creatinine in a short amount of time (4 min) within a ± 5% percentage error, in contrast with the standard clinical colorimetric method. With this approach, reproducible and stable electrochemical responses could be achieved for determination of creatinine in serum, urine, or saliva. These results demonstrated its potential for deployment in resource-limited settings for early diagnosis and tracking the progression of chronic kidney disease (CKD)., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

In this work, a new microfluidic paper-based analytical device (µPAD) was developed for on-hand creatinine quantification in urine samples. When compared to conventional methods, this innovative paper device is more accessible and portable, it provides low-cost analysis (cost of consumables of 40 cents), and it is applicable to non-invasive biological fluids. Furthermore, the paper-based approach is used within an environmentally friendly assembly with no need for wax printing and small amounts of reagents resulting in low waste production and easy disposal by incineration. Its assembly method includes cutting paper discs arranged into several reading units within a plastic pouch, enabling effective creatinine quantification with accuracy based on a vertical flow approach. The method is based on the colourimetric reaction between creatinine and alkaline picric acid, where the solution colour changes from yellow to orange/red. Under optimal conditions, the developed method allowed creatinine quantification in the dynamic range of 2.20–35.0 mg/dL, with a limit of detection (LOD) of 0.66 mg/dL and a limit of quantification (LOQ) of 2.20 mg/dL. The colour intensity developed was processed in ImageJ software, based on digital image scanning, performed in 20 min (up to 4 h) after the sample insertion. The device is stable for up to one week when stored in a vacuum at 4 °C. The method was validated by comparing the results with a batch-wise procedure, where there were no statistically significant differences between both methods. [ABSTRACT FROM AUTHOR]

Albuminuria is a clinical condition associated with poor kidney function, diagnosed by determining the ratio of albumin to creatinine concentrations in patient urine samples. We present a high-throughput paper spray mass spectrometry (PS-MS) method for simultaneous quantitation of urinary albumin and creatinine for potential diagnosis of albuminuria. Minimal (urine dilution) or no sample preparation is required. The analytical performance of the method was evaluated, achieving linear calibration curves (R2 > 0.99) with little inter-day variability in the slope (N = 5 days), exhibiting coefficient of variation (CV) of 8% and 3% for albumin and creatinine, respectively. LOD and LOQ for albumin were 2.1 and 7.0 mg L−1, and for creatinine were 0.01 and 0.03 mmol L−1, respectively. Intra- and inter-day (N = 5) precisions (%CV) and accuracies (%bias) were <10% and ±11%, respectively, for both analytes. The method was applied to determine albumin-to-creatinine ratios in anonymous human patient urine samples (N = 56), and a correlation of R2 = 0.9744 was achieved between the PS-MS results and validated clinical method results. This work demonstrates the utility of PS-MS to simultaneously quantify a large (albumin) and a small (creatinine) molecule directly in patient urine samples, and its potential as a tool for clinical albuminuria diagnostics. [ABSTRACT FROM AUTHOR]

A novel assay platform consisting of a microfluidic sliding double-track paper-based chip and a hand-held Raspberry Pi detection system is proposed for determining the albumin-to-creatine ratio (ACR) in human urine. It is a clinically important parameter and can be used for the early detection of related diseases, such as renal insufficiency. In the proposed method, the sliding layer of the microchip is applied and the sample diffuses through two parallel filtration channels to the reaction/detection areas of the microchip to complete the detection reaction, which is a simple method well suited for self-diagnosis of ACR index in human urine. The RGB (red, green, and blue) value intensity signals of the reaction complexes in these two reaction zones are analyzed by a Raspberry Pi computer to derive the ACR value (ALB and CRE concentrations). It is shown that the G + B value intensity signal is linearly related to the ALB and CRE concentrations with the correlation coefficients of R2 = 0.9919 and R2 = 0.9923, respectively. It is additionally shown that the ALB and CRE concentration results determined using the proposed method for 23 urine samples were collected from real suffering chronic kidney disease (CKD) patients are in fine agreement with those acquired operating a traditional high-reliability macroscale method. Overall, for point-of-care (POC) CKD diagnosis and monitoring in clinical applications, the results prove that the proposed method offers a convenient, real time, reliable, and low-spending solution for POC CKD diagnosis.

In January 2013, the international recommendations of the KDIGO (for "Kidney Disease: Improving Global Outcomes") to define chronic kidney disease (CKD) and classify patients in CKD stages have been published. In this opinion article, we will review and discuss the most important guidelines proposed about CKD staging and glomerular filtration rate (GFR) estimating. In particular, we question the choice of fixed knot values at 60 mL/min/1.73 m² to define CKD. We also question the strategies proposed to measure and use cystatin C results.

Proteinuria is a condition in which an excessive amount of protein is excreted in urine. It is, among others, an indicator of kidney disease or risk of cardiovascular disease. Rapid and reliable diagnosis and monitoring of proteinuria is of great importance for both patients and their physicians. For that reason, a paper-based sensor for proteinuria diagnosis was designed, optimized, and validated utilizing smartphone-assisted signal acquisition. In the first step, a few commonly employed protein assays were optimized and compared in terms of analytical performance on paper matrix. The tetrabromophenol blue method was selected as the one providing a sufficiently low limit of detection (39 mg·L−1) on the one hand and appropriate long-term stability (up to 3 months) on the other hand. The optimized assay was employed for protein-to-creatinine ratio (PCR) determination on a single paper-based sensor. For both analytes the linear ranges were within the clinically relevant range. The analytical usefulness of the developed sensors was demonstrated by a PCR recovery study in artificial urine. The obtained PCR recoveries were from ca. 80 to 150%.

Background: The Schwartz equation is the most widely used serum creatinine (SCr)-based formula to estimate the glomerular filtration rate (GFR) in children of European descent, but whether this applies to African children is unclear., Methods: In a cross-sectional study, 513 apparently healthy African children aged 6 to 16 years were randomly recruited in school area of Kinshasa, the Democratic Republic of Congo (DRC). SCr was measured using calibrated enzymatic method. SCr was normalized using Q-values designed for European descent children, due to the absence of Q-values for African children. Commonly used eGFR equations were applied in this population., Results: Normalization of SCr using Q-values for European descent children was effective in this cohort. The majority of African children (93.4%) have normalized SCr (SCr/Q) values within the reference interval (0.67-1.33) of children of European descent. The bedside-Schwartz equation was associated with significant age and sex dependency. However, the FAS-Age formula showed no sex and age dependency. The new CKiDU25 equation did not show a significant sex dependency. The recently introduced EKFC and LMR18 equations also showed no age and sex dependency, although the distribution of eGFR-values was not symmetrical. On the other hand, the FAS-Height and the Schwartz-Lyon equations showed significant sex dependency but no age dependency., Conclusions: The reference interval for SCr designed for European descent children can be applied to African children. Of all the equations studied, FAS-Age performed best and is most suitable because no height measurements are required. Establishment of specific Q-values for the widespread Jaffe-measured creatinine in Africa can further broaden applicability., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

• This Research advances paper-based sensors, optimizing hydrophobic microchannel (µPAD) fabrication. • The approach employs a modified DIY RepRap 3D printer combined with a technical drawing pen loaded with PDMS-hexane mixture. • The colorimetric detection of creatinine concentrations in artificial urine spans from 5 mg/dL to 450 mg/dL, with naked eye. • The limiting concentration of 500 mg/dL and an estimated Limit of Detection (LOD) of 61.4 mg/dL. • Nylon 6,6 membrane microfluidic domains display concentration-dependent Janovsky complexes, demonstrating high selectivity. Paper-based microfluidic sensors for point-of-care applications represent an exceptional strategy for facilitating rapid sensing within clinical settings. Despite their considerable promise, the ongoing research objective lies in efficiently printing hydrophobic microfluidic channels (µPADs) onto hydrophilic paper while minimizing expenditure. This research paper introduces an advanced, economic, and efficient method for the rapid fabrication of µPADs on paper substrates, enabling immediate colorimetric detection of creatinine in artificial urine using Jaffe's reagent. The process involves a modified DIY RepRap 3D printer with an integrated technical drawing pen filled with the solution of Polydimethylsiloxane (PDMS) and hexane. This solution creates hydrophobic domain barriers on a flexible nylon-based paper substrate, effectively confining the aqueous medium within the microfluidic channels. We report visual detection of a broad spectrum of creatinine concentrations ranging from 5 mg/dL to 450 mg/dL through the vibrant Janovsky complex appearance on the microfluidic domains. The study identifies the limiting concentration on µPADs as 500 mg/dL. The innovative procedure demonstrates exceptional selectivity, exhibiting a maximum interference of only 0.97 % from potentially interfering substances. This rapid, naked-eye detection of creatinine on nylon 6,6 membranes offers a user-friendly and economical approach, enhancing the capabilities of colorimetric visualization in point-of-care applications. [ABSTRACT FROM AUTHOR]

[Display omitted] • This review advances in the development of colorimetric and fluorometric paper-based devices (PADs) • PADs with metal nanoparticles and quantum dots employed as sensing probes in the point-of-care diagnosis. • PADs are integrated with desktop scanners and smartphones measure the grey scale/RGB values for quantitative measurement. • This innovative paper-based detection platforms for diverse diagnostic scenarios and their utility in resource-limited settings. This review paper comprehensively explores recent advancements in the development of colorimetric and fluorometric paper-based analytical devices (PADs) for rapid point-of-care diagnosis of specific disease biomarkers. The paper elucidates the principles of colorimetry and fluorometry, focusing on their application in the detection of various biomolecules. Notably, metal nanoparticles (NPs) and quantum dots (QDs) emerge as versatile sensing probes in these platforms. The fabrication of nanomaterials (NMs) on paper substrates is extensively discussed, covering techniques such as dip-coating, drop-casting, wax printing, inkjet printing and screen printing. The integration of PADs with portable devices is explored, including gray scale and RGB measurements using desktop scanners, smartphones and color detector apps for enhanced colorimetric and fluorometric analysis. The application of PADs with metal NPs for the detection of a wide array of biomolecules is highlighted. The versatility of these devices is demonstrated in detecting nucleic acids, proteins, amino acids, bio thiols, urea, uric acid, antigens, antibodies, glucose, creatinine, bilirubin, vitamins and bacteria. The potential for point-of-care diagnosis in diverse healthcare settings is underscored, emphasizing the simplicity, cost-effectiveness and rapidity of these paper-based diagnostic platforms. This review provides an overview of the NMs-enabled colorimetric and fluorometric PADs, offering insights into the fabrication techniques, integration with portable devices and diverse applications in the field of biomarker detection. The amalgamation of metal nanoparticles and quantum dots with paper-based devices holds promising prospects for advancing point-of-care diagnostics of specific disease biomarkers. [ABSTRACT FROM AUTHOR]

Paraquat intoxication is characterized by acute kidney injury and multi-organ failure, causing substantial mortality and morbidity. This study aims to develop a 2-in-1 paper-based analytical device to detect the concentrations of paraquat and creatinine in human serum, which can help clinicians diagnose patients with paraquat poisoning in a more rapid and geographically unrestricted manner. The procedure involves fabrication of a paper-based analytical device, i.e., printing of design on a filter paper, heating of wax-printed micro zone plates so as molten wax diffusing into and completely through the paper to the other side, forming hydrophobic boundaries that could act as detection zones for the paraquat colorimetric assay, and finally analysis using ImageJ software. The paper employed a colorimetric sodium dithionite assay to indicate the paraquat level in a buffer or human serum system in less than 10 min. In this study, colorimetric changes into blue color could be observed by the naked eye. By curve fitting models of sodium dithionite in normal human serum, we evaluated the serum paraquat levels for five paraquat patients. In the sodium dithionate assay, the measured serum paraquat concentrations in patients 1⁻5 were 22.59, 5.99, 26.52, 35.19 and 25.00 ppm, respectively. On the other hand, by curve fitting models of the creatinine assay in normal human serum, the measured serum creatinine concentrations were 16.10, 12.92, 13.82, 13.58 and 12.20 ppm, respectively. We found that the analytical performance of this device can compete with the standard of Clinical Laboratory of Chang Gung Memorial Hospital, with a less complicated sample preparation process and more rapid results. In conclusion, this 2-in-1 paper-based analytical device has the advantage of being simple and cheap, enabling rapid detection of paraquat intoxication as well as assessment of renal prognosis.

Purpose of Review: Serum creatinine reflects both muscle mass and kidney function. Serum cystatin C has recently been recommended as an additional marker for estimating kidney function, and use of both markers together may provide an index of muscle mass. This review aims to describe the biological basis for and recent research examining the relationship of these markers to muscle mass in a range of adult populations and settings., Recent Findings: This review identified 67 studies, 50 of which had direct measures of muscle mass, and almost all found relationships between serum creatinine and cystatin C and muscle mass and related outcomes. Most studies have been performed in older adults, but similar associations were found in general populations as well as in subgroups with cancer, chronic kidney disease (CKD), and other morbid conditions. Creatinine to cystatin C ratio was the measure examined the most often, but other measures showed similar associations across studies., Summary: Measures of serum creatinine and cystatin C together can be an index of muscle mass. They are simple and reliable measures that can be used in clinical practice and research. Further study is needed to determine actionable threshold values for each measure and clinical utility of testing and intervention., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

[Display omitted] • The accurate measurement of creatinine (Ctn) in human biofluid samples is a challenge. • A stable carboxyl (C=O, COOH) groups were introduced on the electrode surface during electrochemical activation. • ePAD* was applied for the selective non-enzymatic detection of Ctn. • ePAD* detects Ctn in blood serum and urine samples with high reliability. • ePAD* is economic and accurate compared to existing methods for Ctn detection. Selective detection of creatinine (Ctn) is crucial for the clinical diagnosis of early-stage kidney dysfunction. A non-enzymatic electrochemical method for a highly selective and sensitive detection of Ctn in blood serum and urine samples was developed using an electrochemically activated carbon-coated paper-based analytical device (ePAD*). During activation, the growth of stable carboxyl (C = O, COOH) groups on the edge planes of the carbon surface was observed. The prepared ePAD* was characterized using various microscopic, spectroscopic, and electrochemical techniques. The ePAD* was utilized as a medium exchanger, and the voltammetric response of Ctn detection in the linear concentration from 0.03 to 45 mM with a detection limit of 5.41 µM was achieved. In addition, the selective detection of Ctn in the presence of potential interferences (i.e., uric acid, ascorbic acid, ammonia, and urea) was examined. The examination revealed a remarkable selectivity toward Ctn detection. Real-time detection of Ctn in blood serum and urine samples was performed. The results were correlated with the classical Jaffé colorimetric method. Our ePAD* exhibited a better electrochemical response. Thus, it is a highly potential diagnostic method for further development as a rapid and precise detection platform for point-of-care (POC) devices for examining patients with kidney disease. [ABSTRACT FROM AUTHOR]

Background and Aims: Use the MDRD (Modification of Diet in Renal Disease) and 2021 CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equation void of race coefficients (CKD-EPI Crea , CKD-EPI Cys-C , and CKD-EPI Crea+Cys-C ) to estimate the BV (Biological variation) of eGFR (estimated glomerular filtration rate) within 24 h in a healthy population to help explain future studies using eGFR in the context of a known BV., Methods: Blood samples were collected from 30 healthy subjects at six time points within 24 h. Serum creatinine (S-Crea) and serum cystatin C (S-Cys-C) were measured, and the BV of eGFR was calculated. Outlier and variance homogeneity analyses were performed, followed by CV-ANOVA on trend-corrected data., Results: The eGFR CV I for the four equations (MDRD, CKD-EPI Crea , CKD-EPI Cys-C , and CKD-EPI Crea+Cys-C ) were 8.39% (7.50-9.51%), 3.90% (3.49-4.42%), 6.58% (5.88-7.46%), and 5.03% (4.50-5.71%), respectively. The corresponding II and RCV pos/neg values were 0.69, 0.48, 0.51, and 0.31, and (29.30%, - 22.66%), (12.69%, - 11.2 6%), (20.97%, - 17.33%), and (15.88%, - 13.70%), respectively; RCV pos /neg of eGFR was highest in the MDRD equation and lowest in the CKD-EPI Crea equation. Additionally, the RCV pos/neg values of the individual was highest in the MDRD equation and lowest in the CKD-EPI Crea+Cys-C equation; they are (56.51%, - 36.11%) and (5.01%, - 4.77%), respectively., Conclusions: We present data on the 24 h BV eGFR of the 2021 CKD-EPI equations. The presence of BV has impact on the interpretation of GFR results, affecting CKD disease grading. The RCV pos/neg differences were large among the individuals. When using eGFRs based on the MDRD and CKD-EPI equations, it is necessary to combine RCV pos/neg values before interpreting the results., (© 2024. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

An integrated system consisting of a paper-based chip and a smart detection device is proposed for determining the human serum creatinine concentration based on Jaffé reaction theory. In the proposed approach, the reaction zone of the paper-based chip is implanted with picric acid and NaOH reagent and dried at 35 °C for 20 min. Human serum creatinine is dripped onto the reaction zone of the chip. A Jaffé reaction is induced by heating the chip at 37 °C for 5 min and the creatinine concentration is then derived by analyzing the RGB (red, green and blue) intensity of the resulting Janovsky complex using self-written analysis software installed on a smartphone. The validity of the proposed method is demonstrated using control samples with creatinine concentrations ranging from 0.2~8 mg/dL. The detection results obtained for 32 real-world creatinine samples are shown to be in excellent agreement with those obtained using a standard macroscale method (R2 = 0.9994). Overall, the results show that the proposed system provides a compact, low-cost and reliable approach for human serum creatinine concentration detection.

Accurate quantification of blood creatinine is important to estimate the glomerular filtration rate. Existing techniques using liquid chromatography tandem mass spectrometry (LC–MS/MS) have a high accuracy and eliminate most interferences encountered in routine enzymatic and Jaffé methods. However, they require laborious and time-consuming sample treatment and data acquisition. The aim of this study is to develop a fast and simple method to enable a direct analysis of whole blood creatinine with performance measures that are comparable to conventional LC–MS/MS. 5μL whole blood is formed as a three-dimensional spheroid on hydrophobic silanized paper substrates which then undergoes paper-spray ionization—tandem mass spectrometry (PSI–MS/MS). The method is validated using real human samples and compared with LC–MS/MS. PSI–MS/MS whole blood analysis exhibited a lower limit of quantification of 2.5 μg/mL, precision ≤ 6.3%, recovery in the range of 88–94% and excellent linearity (R2 > 0.99; 2.5—20 μg/mL) covering the normal range for creatinine levels. Creatinine levels were comparable to those measured by LC–MS/MS with small deviations of less than 0.3 μg/mL. This simple, fast and accurate microsampling technique for direct analysis of creatinine from whole blood shows promise for routine clinical screening and monitoring. This approach can be readily extended for other analytes of interest and, due to inherent advantages relating to cost, storability, speed, and simplicity, it can be especially advantageous for use in resource-limited settings. [ABSTRACT FROM AUTHOR]