Efficacy and safety of enavogliflozin vs. dapagliflozin as add-on therapy in patients with type 2 diabetes mellitus based on renal function: a pooled analysis of two randomized controlled trials.

BACKGROUND: We assessed the efficacy and safety of enavogliflozin (0.3 mg), a newly developed SGLT-2 inhibitor, in patients with type 2 diabetes mellitus based on kidney function via pooled analysis of two 24-week, randomized, double-blind phase III trials. METHODS: Data from 470 patients were included (enavogliflozin: 0.3 mg/day, n = 235; dapagliflozin: 10 mg/day, n = 235). The subjects were classified by mildly reduced (60 ≤ eGFR < 90 mL/min/1.73 m², n = 247) or normal eGFR (≥ 90 mL/min/1.73 m², n = 223). RESULTS: In the mildly reduced eGFR group, enavogliflozin significantly reduced the adjusted mean change of HbA1c and fasting plasma glucose levels at week 24 compared to dapagliflozin (- 0.94% vs. -0.77%, P = 0.0196). Enavogliflozin exhibited a more pronounced glucose-lowering effect by HbA1c when combined with dipeptidyl peptidase-4 inhibitors than that observed in their absence. Enavogliflozin showed potent blood glucose-lowering effects regardless of renal function. Conversely, dapagliflozin showed a significant decrease in the glucose-lowering efficacy as the renal function decreased. Enavogliflozin showed a higher urinary glucose excretion rate in both groups. The homeostatic model assessment showed that enavogliflozin markedly decreased the insulin resistance. The blood pressure, weight loss, or homeostasis model assessment of beta-cell function values did not differ significantly between enavogliflozin and dapagliflozin. Adverse events were similar between both drugs. CONCLUSIONS: The glucose-lowering efficacy of enavogliflozin is superior to that of dapagliflozin in patients with type 2 diabetes mellitus with mild renal function impairment; this is attributed to its potent urinary glucose excretion-promoting ability. The emergence of new and potent SGLT-2 inhibitors is considered an attractive option for patients with inadequate glycemic control and decreased renal function. TRIAL REGISTRATION: Not applicable (pooled analysis).

Non-diabetic urine glucose in idiopathic membranous nephropathy.

This study aims to analyze the characteristics of idiopathic membranous nephropathy (iMN) with nondiabetic urine glucose during the follow-up. We retrospectively analyzed the data of 1313 patients who were diagnosed iMN. The prevalence of nondiabetic urine glucose during follow-up was 10.89%. There were significant differences between the patients with nondiabetic urine glucose and those without urine glucose in gender, hypertension ratio, proteinuria, N-acetyl-ß-glucosaminidase, retinol binding protein, serum albumin, serum creatinine (Scr), cholesterol, triglyceride and positive anti-phospholipase A2 receptor antibody ratio, glomerular sclerosis ratio, acute and chronic tubular injury lesion at baseline. To exclude the influence of the baseline proteinuria and Scr, case control sampling of urine glucose negative patients was applied according to gender, baseline proteinuria and Scr. The proteinuria nonremission (NR) ratio was 45.83 versus 12.50% of the urine glucose positive group and case control group. Partial remission (PR) ratio of the two groups was 36.46 versus 23.96% and complete remission (CR) ratio was 19.79% versus 63.54%, respectively. Patients with urine glucose had higher risk of 50% estimated glomerular filtration rate (eGFR) reduction. Cox regression showed that urine glucose and baseline Scr were risk factors of 50% reduction of eGFR. Urine glucose remission ratio of the patients with proteinuria NR, PR, and CR was 13.33, 56.25, and 94.73% (p < 0.005). Patients who got urine glucose remission also had better renal survival. In conclusion, non-diabetic urine glucose was closely related to proteinuria. It could be applied as a tubular injury marker to predict renal function.

Microbe-Based Sensor for Long-Term Detection of Urine Glucose.

The development of a reusable and low-cost urine glucose sensor can benefit the screening and control of diabetes mellitus. This study focused on the feasibility of employing microbial fuel cells (MFC) as a selective glucose sensor for continuous monitoring of glucose levels in human urine. Using MFC technology, a novel cylinder sensor (CS) was developed. It had a quick response time (100 s), a large detection range (0.3-5 mM), and excellent accuracy. More importantly, the CS could last for up to 5 months. The selectivity of the CS was validated by both synthetic and actual diabetes-negative urine samples. It was found that the CS's selectivity could be significantly enhanced by adjusting the concentration of the culture's organic matter. The CS results were comparable to those of a commercial glucose meter (recovery ranged from 93.6% to 127.9%) when the diabetes-positive urine samples were tested. Due to the multiple advantages of high stability, low cost, and high sensitivity over urine test strips, the CS provides a novel and reliable approach for continuous monitoring of urine glucose, which will benefit diabetes assessment and control.

Renal glucosuria in schoolchildren: Clinical characteristics.

BACKGROUND: We conducted an annual urine glucose screening program at schools, and diagnosed schoolchildren with diabetes at an early stage of the disease. We also identified some cases of renal glucosuria (RG), based on positive urine glucose with normal glucose tolerance. METHODS: During 2000-2015, 3 309 631 schoolchildren participated in the screening program. The positive rate for glucosuria in the first test was approximately 0.1%, whereas on repeat urine test it was approximately 0.05%. In total 350 schoolchildren were positive for glucosuria on detailed examination. Oral glucose tolerance test (OGTT) was also used to evaluate glucose intolerance. RESULTS: One hundred and two schoolchildren (29.7%) were diagnosed with diabetes, whereas RG was identified in 246 (70.3%) with normal glucose metabolism. In regard to the characteristics of RG, the percentage of boys was 50.3%, and the mean age at diagnosis was 11.2 ± 2.4 years. Twenty-eight children (11.4%) were overweight (body mass index standard deviation score [BMI-SDS] > +2.0 SD), whereas five (2.0%) were underweight (BMI-SDS < -2.0 SD). First-degree family history was suspected in 176 cases (71.5%). All RG subjects had normal glucose tolerance in the absence of insulin resistance and decreased insulin secretion (homeostasis model assessment for ß-cell function, 78.8 ± 59.5%) on OGTT. CONCLUSIONS: RG is not rare in Japanese schoolchildren with glucosuria. This disorder seems to have a strong genetic background, and to involve less growth retardation and weight loss than expected despite continuous excretion of glucose in urine.

A nanocomposite prepared from FeOOH and N-doped carbon nanosheets as a peroxidase mimic, and its application to enzymatic sensing of glucose in human urine.

A method is described for the synthesis of a nanocomposite containing FeOOH and N-doped carbon nanosheets. The nanocomposite was synthesized by a hydrothermal method using a Fe3O4/chitosan nanocomposite as the precursor. The nanocomposite displays peroxidase-like activity and catalyzes the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2. This results in the formation of a blue colored product with an absorption maximum at 652 nm in the UV-vis spectra. Based on these findings, colorimetric assays were worked out for both hydrogen peroxide and glucose. The H2O2 assay works in the 5 to 19 µM concentration range, and the limit of detection is 5 nM. The glucose assay works in the 8 µM to 0.8 mM concentration range and has a 0.2 µM detection limit. The method was successfully applied to the determination of glucose in human urine. Graphical abstract Schematic of the hydrothermal synthesis of a FeOOH/N-doped carbon nanocomposite. It was used to replace peroxidase enzyme for the catalytic oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) in a visual colorimetric test for glucose in human urine.

A Pediatric Case of Graves' Hyperthyroidism with Associated Glucose Intolerance Detected by a Urine Glucose Screening Program at School.

We report here a 13-year-old female with Graves' disease, whose diagnostic clue was glycosuria, which was detected by a urine glucose screening program at school. She had had mild general malaise, and a physical examination revealed a slightly enlarged thyroid gland. Hyperthyroidism (thyroid-stimulating hormone (TSH) < 0.01 µU/ml, free triiodothyronine (fT3) 23.57 pg/ml, free thyroxine (fT4) 3.38 ng/dl) and anti-thyroid autoantibodies (TRAb 43.6%) were detected in laboratory tests, and her plasma glucose at 120 minutes was 142 mg/dl in a 75 g oral glucose tolerance test. She was diagnosed as having borderline diabetes. These findings revealed a diagnosis of Graves' hyperthyroidism with associated impaired glucose tolerance. Although it is reported that many adults with hyperthyroidism develop disorders of glucose metabolism, pediatric patients rarely have complications of glucose intolerance or diabetes mellitus, and there are no previous reports of Graves' disease diagnosed by a urine glucose screening program at school. This case suggests a possibility of abnormalities in glucose metabolism even in pediatric cases of Graves' disease. To avoid overlooking the diagnosis of glucose intolerance associated with hyperthyroidism, a careful medical interview and examination should be performed even if the clinical features are mild.

A non-enzymatic urine glucose sensor with 2-D photonic crystal hydrogel.

A novel polymerized crystalline colloidal array (PCCA) sensing material for the detection of urine glucose was developed by embedding a two-dimensional (2-D) polystyrene crystalline colloidal array (CCA) in 3-acrylamidophenylboronic acid (3-APBA)-functionalized hydrogel. After adjusting the cross-linker concentration, this material showed significant sensitivity for glucose under lab conditions, the particle spacing of the PCCA changed from 917 to 824 nm (93 nm) within 3 min as the glucose concentration increased from 0 to 10 mM, and the structural color of the PCCA changed from red through orange, to green, and finally, to cyan. In further experiments, this material was used to semi-quantitatively detect glucose in 20 human urine (HU) samples. Compared with the traditional dry-chemistry method, which was applied widely in clinical diagnosis, the PCCA method was more accurate and cost-effective. Moreover, this method can efficiently avoid the errors induced by most of the urine-interfering elements like vitamin C and ketone body. With a homemade portable optical detector, this low-cost intelligent sensing material can provide a more convenient and efficient strategy for the urine glucose detection in clinical diagnosis and point-of-care monitoring.

Review on the screening of urine glucose for early diagnosis of type 2 diabetes mellitus in school children and adolescents with obesity in Hong Kong.

OBJECTIVES: Obesity and type 2 diabetes mellitus (T2DM) are growing health concerns. Since 2005, Student Health Service (SHS) and Hong Kong Paediatric Society formulated a protocol on urine glucose screening (UGS) for early diagnosis of T2DM in students with obesity in Hong Kong. This study reviews students with T2DM captured by this screening program and compare the data with the Hong Kong Children Diabetes Registry (HKCDR) database, to see if the UGS program facilitates early diagnosis of T2DM. METHODS: Students between the ages of 10-18 years old with age- and sex-specific body mass index (BMI) >97th percentile who attended SHS between the school years from 2005/06 to 2017/18 were recruited for UGS. Those tested positive for random urine glucose underwent diagnostic testing for T2DM according to ADA guidelines. Demographic data and investigatory results from UGS and HKCDR within the same time period were compared. RESULTS: A total of 216,526 students completed UGS in the said period; 415 (0.19 %) students were tested positive for urine glucose of which 121 students were diagnosed with T2DM. UGS picked up 23 % of the newly diagnosed T2DM cases. When compared to the HKCDR database, students diagnosed via UGS were significantly younger, less obese, and had fewer diabetic related complications. The negative predictive value of UGS is high and can effectively rule out T2DM. CONCLUSIONS: Urine glucose screening is an inexpensive and simple test that allows for early diagnosis of T2DM among obese school students. Other methods including POCT HbA1c can be explored to improve program effectiveness.

Clinical characteristics in children with maturity-onset diabetes of the young detected by urine glucose screening at schools in the Tokyo Metropolitan Area.

This study aimed to examine the clinical characteristics of young children diagnosed with maturity-onset diabetes (MODY) using urine glucose screening at schools. The study participants were 70 non-obese children who were clinically diagnosed with type 2 diabetes through urine glucose screening at schools in Tokyo between 1974 and 2020. Of these children, 55 underwent genetic testing, and 21 were finally diagnosed with MODY: MODY2 in eight, MODY3 in eight, MODY1 in four and MODY5 in one. A family history of diabetes was found in 76.2% of the patients. Fasting plasma glucose levels did not differ between the different MODY subtypes, while patients with MODY 3, 1, and 5 had significantly higher levels of glycosylated hemoglobin and 2-hour glucose in an oral glucose tolerance test than those with MODY2. In contrast, most patients exhibit mild insulin resistance and sustained ß-cell function. In the initial treatment, all patients with MODY2 were well controlled with diet and exercise, whereas the majority of those with MODY3, 1, and 5 required pharmacological treatment within one month of diagnosis. In conclusion, urine glucose screening in schools appears to be one of the best opportunities for early detection of the disease and providing appropriate treatment to patients.

Refined protocol for newly onset identification in non-obese diabetic mice: an animal-friendly, cost-effective, and efficient alternative.

BACKGROUND: Therapeutic interventions for diabetes are most effective when administered in the newly onset phase, yet determining the exact onset moment can be elusive in practice. Spontaneous autoimmune diabetes among NOD mice appears randomly between 12 and 32 weeks of age with an incidence range from 60 to 90%. Furthermore, the disease often progresses rapidly to severe diabetes within days, resulting in a very short window of newly onset phase, that poses significant challenge in early diagnosis. Conventionally, extensive blood glucose (BG) testing is typically required on large cohorts throughout several months to conduct prospective survey. We incorporated ultrasensitive urine glucose (UG) testing into an ordinary BG survey process, initially aiming to elucidate the lag period required for excessive glucose leaking from blood to urine during diabetes progression in the mouse model. RESULTS: The observations unexpectedly revealed that small amounts of glucose detected in the urine often coincide with, sometimes even a couple days prior than elevated BG is diagnosed. Accordingly, we conducted the UG-based survey protocol in another cohort that was validated to accurately identified every individual near onset, who could then be confirmed by following few BG tests to fulfill the consecutive BG + criteria. This approach required fewer than 95 BG tests, compared to over 700 tests with traditional BG survey, to diagnose all the 37-38 diabetic mice out of total 60. The average BG level at diagnosis was slightly below 350 mg/dl, lower than the approximately 400 mg/dl observed with conventional BG monitoring. CONCLUSIONS: We demonstrated a near perfect correlation between BG + and ultrasensitive UG + results in prospective survey with no lag period detected under twice weekly of testing frequency. This led to the refined protocol based on surveying with noninvasive UG testing, allowing for the early identification of newly onset diabetic mice with only a few BG tests required per mouse. This protocol significantly reduces the need for extensive blood sampling, lancet usage, labor, and animal distress, aligning with the 3Rs principle. It presents a convenient, accurate, and animal-friendly alternative for early diabetes diagnosis, facilitating research on diagnosis, pathogenesis, prevention, and treatment.

Knockout of the aryl hydrocarbon receptor results in distinct hepatic and renal phenotypes in rats and mice.

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor which plays a role in the development of multiple tissues and is activated by a large number of ligands, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). In order to examine the roles of the AHR in both normal biological development and response to environmental chemicals, an AHR knockout (AHR-KO) rat model was created and compared with an existing AHR-KO mouse. AHR-KO rats harboring either 2-bp or 29-bp deletion mutation in exon 2 of the AHR were created on the Sprague-Dawley genetic background using zinc-finger nuclease (ZFN) technology. Rats harboring either mutation type lacked expression of AHR protein in the liver. AHR-KO rats were also insensitive to thymic involution, increased hepatic weight and the induction of AHR-responsive genes (Cyp1a1, Cyp1a2, Cyp1b1, Ahrr) following acute exposure to 25 µg/kg TCDD. AHR-KO rats had lower basal expression of transcripts for these genes and also accumulated ~30-45-fold less TCDD in the liver at 7 days post-exposure. In untreated animals, AHR-KO mice, but not AHR-KO rats, had alterations in serum analytes indicative of compromised hepatic function, patent ductus venosus of the liver and persistent hyaloid arteries in the eye. AHR-KO rats, but not AHR-KO mice, displayed pathological alterations to the urinary tract: bilateral renal dilation (hydronephrosis), secondary medullary tubular and uroepithelial degenerative changes and bilateral ureter dilation (hydroureter). The present data indicate that the AHR may play significantly different roles in tissue development and homeostasis and toxicity across rodent species.

A multi-calibration potentiometric sensing array based on diboronic acid-PtAu/CNTs nanozyme for home monitoring of urine glucose.

All-solid-state potentiometric sensors that are easily miniaturized and arrayed are widely used in home diagnostics. However, changes in sample matrix compositions tend to affect the basic potential of the potentiometric sensor, and pH of sample could change the response slope, thus affecting the detection reliability. This study takes the detection of glucose in urine as a model to increase the reliability of potentiometric sensors in home detection. PtAu/CNTs nanozyme modified by diboronic acid has been designed, showing better catalytic selectivity for glucose by experiments and theoretical calculations. Moreover, glucose electrode group in a multi-calibration glucose potentiometric sensing array can realize the basic potential calibration of sensing channel by the calibration channel. Meanwhile, the pH electrode group can not only measure the urine pH, but also calibrate the response slope of the glucose electrode group, thus improving the reliability of home detection.

Development of high sustained anti-drug antibody titers and corresponding clinical decline in a late-onset Pompe disease patient after 11+ years on enzyme replacement therapy.

A late-onset Pompe disease patient developed high sustained antibody titers (HSAT) of ≥51,200 after 11+ years on alglucosidase alfa and previous tolerance. There was a corresponding worsening of motor function and rise in urinary glucose tetrasaccharide (Glc4). Following immunomodulation therapy, HSAT were eliminated with improved clinical outcomes and biomarker trends. This report highlights the importance of continued surveillance of antibody titers and biomarkers, the negative impact of HSAT, and improved outcomes with immunomodulation therapy.

Investigational Agents Targeting SGLT1 and SGLT2 in the Treatment of Type 2 Diabetes Mellitus.

Targeting sodium-dependent glucose transporters (SGLT1 and SGLT2) represents a new class of pharmacotherapy for type 2 diabetes mellitus, a major global health issue with an increasing social and economic burden. Following recent successes in market approvals of SGLT2 inhibitors, the ongoing effort has paved the way for the discovery of novel agents via structure-activity relationship studies, preclinical and clinical testing, including SGLT2 inhibitors, SGLT1/2 dual inhibitors, and selective SGLT1 inhibitors. A growing understanding of the physiology of SGLTs allows drug developers to explore additional cardiovascular and renal protective benefits of these agents in T2DM patients at risk. This review provides an overview of the recent investigational compounds and discusses future perspectives of drug discovery in this area.

Selective colorimetric urine glucose detection by paper sensor functionalized with polyaniline nanoparticles and cell membrane.

For the diabetes diagnosis, noninvasive methods are preferred to invasive methods; urine glucose measurement is an example of a noninvasive method. However, conventional noninvasive methods for urine glucose measurement are not intuitive. Furthermore, such methods exhibit low selectivity because they can detect interfering molecules in addition to glucose. Herein, we fabricate a noninvasive, intuitive, and highly selective paper sensor consisting of polyaniline nanoparticles (PAni-NPs) and red blood cell membranes (RBCMs). The PAni-NPs (adsorbed on the paper) are highly sensitive to hydrogen ions and change color from emeraldine blue to emeraldine green within a few seconds. The RBCM (coated on the PAni-NP-adsorbed paper) having the glucose transporter-1 protein plays the role of a smart filter that transports glucose but rejects other interfering molecules. In particular, the selectivity of the RBCM-coated PAni-NP-based paper sensor was approximately improved ∼85%, compared to the uncoated paper sensors. The paper sensor could detect urine glucose over the range of 0-10 mg/mL (0-56 mM), with a limit of detection of 0.54 mM. The proposed paper sensor will facilitate the development of a highly selective and colorimetric urine glucose monitoring system.

Lipid Accumulation Product Combined With Urine Glucose Excretion Improves the Efficiency of Diabetes Screening in Chinese Adults.

Background: To compare the efficacy of lipid accumulation product (LAP) and urine glucose excretion (UGE) in predicting diabetes and evaluate whether the combination of LAP and UGE would help to improve the efficacy of using LAP alone or UGE alone in identifying diabetes. Methods: Data from 7485 individuals without prior history of diabetes who participated in a cross-sectional survey in Jiangsu, China, were analyzed. Each participant underwent an oral glucose-tolerance test. Operating characteristic curves (ROC) and logistic regression analyses were used to evaluate the performance of LAP and UGE in identification of newly diagnosed diabetes (NDM) and prediabetes (PDM). Results: For subjects with NDM, the area under the ROC curve was 0.72 for LAP and 0.85 for UGE, whereas for PDM, these values were 0.62 and 0.61, respectively. Furthermore, LAP exhibited a comparable sensitivity with UGE in detecting NDM (76.4% vs 76.2%, p = 0.31). In predicting PDM, LAP showed a higher sensitivity than UGE (66.4% vs 42.8%, p < 0.05). The combination of LAP and UGE demonstrated a significantly higher sensitivity than that of LAP alone and UGE alone for identification of NDM (93.6%) and PDM (80.1%). Moreover, individuals with both high LAP and high UGE had significantly increased risk of NDM and PDM than those with both low LAP and low UGE. Conclusions: The combination of LAP and UGE substantially improved the efficacy of using LAP and using UGE alone in detecting diabetes, and may be a novel approach for mass screening in the general population.

Basal glucose excretion in dogs: The impact of feeding, obesity, sex, and age.

BACKGROUND: The urine glucose (UG) measurements are an integral part of urinalyses, especially in dogs with polyuria and polydipsia. A positive dipstick result is considered pathologic for disease. This paradigm has been challenged by new ultrasensitive tests, where the manufacturers recommend tolerating slightly positive results. It implies that, as in other species, basal urine glucose losses can exceed the lower limits of detection using ultrasensitive glucose dipsticks in healthy dogs. OBJECTIVES: We aimed to determine whether glucose is routinely detectable using a sensitive quantitative wet chemistry method in the urine of nondiabetic, nonazotemic dogs, and investigate the impact of food intake, obesity, sex, castration status, and age. METHODS: Serial UG measurements were performed in healthy clinic-owned Beagle dogs that were randomly fasted or fed. Glucose was measured in morning urine samples from normal-weight healthy and obese dogs, and the university's electronic database was searched for quantitative UG measurements (Gluco-quant Enzyme Kit/Roche Diagnostics). RESULTS: Small amounts of glucose were detected in 555 (99.1%) of 560 urine samples analyzed. All urine samples from the clinic-owned Beagle dogs, as well as from privately owned obese and normal-weight healthy dogs that tested positive for glucose. The median (range) UG concentration obtained from the university's electronic database was 0.39 (0-1.55) mmol/L, and 2.2% of the samples tested negative. Feeding, obesity, gender, castration status, and age did not affect UG concentrations. CONCLUSIONS: Studies, including a larger number of healthy dogs, are warranted to define a cut-off between physiologic and pathologic glucosuria.

Urine Glucose Excretion Attenuates the Association Between Lipid Accumulation Product and Serum Uric Acid in Subjects with Prediabetes.

PURPOSE: Obesity is known to be strongly associated with hyperuricemia. Moreover, the impact of urine glucose excretion (UGE) on serum uric acid (UA) levels has gained much more attention in recent years. Yet concern is raised about whether UGE influences the relationship between obesity and hyperuricemia. The aim of this study was to assess the effect of UGE on the association between lipid accumulation product (LAP), a novel marker of visceral adipose accumulation, and UA in subjects with prediabetes. MATERIALS AND METHODS: Data were obtained from a cross-sectional study. A total of 3645 subjects with prediabetes were included in the present study. The separate and joint associations of LAP and UGE with hyperuricemia were examined using logistic regression analyses. RESULTS: LAP was positively associated with UA in both genders. Subgroup analysis based on UGE revealed that the association was strongest in subjects with low UGE (r = 0.328, p < 0.001), whereas the positive association was weakened, but still remained significant in subjects with moderate and high UGE. High LAP was significantly associated with an increased odds ratio for hyperuricemia after adjustment for potential confounders in the overall population (OR = 2.07, 95% CI: 1.66-2.58, p < 0.001). However, a downward trend in odds ratios for hyperuricemia was observed across UGE categories. In addition, the joint association analysis confirmed that the relationship between LAP and hyperuricemia was attenuated by UGE. CONCLUSION: The positive association between LAP and UA appears to be attenuated by UGE, indicating that promoting UGE may be an effective strategy for controlling UA levels, especially for people with obesity who are at increased risk for hyperuricemia.

Comparison of clinicopathological patterns of renal tubular damage in dogs with acute kidney injury caused by leptospirosis and other aetiologies.

In humans, leptospiral acute kidney injury (AKI) is characterised by tubulointerstitial involvement and renal electrolyte losses, impacting clinical presentation and case management. The aim of this study was to evaluate urine chemistry findings in dogs with leptospirosis in order to identify characteristic patterns of tubular damage associated with this disease. Dogs with intrinsic AKI caused by leptospirosis and by other aetiologies were prospectively enrolled. Clinical and clinicopathological variables, including serum and urine chemistry, fractional excretion (FE%) of electrolytes, and urinary neutrophil gelatinase-associated lipocalin (NGAL), were evaluated in both groups and compared statistically. Dogs with leptospirosis (n = 38) had significantly higher serum creatinine concentration than dogs with AKI caused by other aetiologies (n = 37). Serum potassium and glucose concentrations were comparable between groups. Dogs with leptospiral AKI had significantly higher FE of potassium (median 100%, range 20-480 vs. median 68%, range 5-300; P = 0.048), as well as higher magnitude of glucosuria (urine glucose to creatinine ratio, median 0.64, range 0-26 vs. median 0.22, range 0-13; P = 0.023) and frequency of positive glucose dipstick reaction (59% vs. 18%; P = 0.002), than dogs with AKI of other aetiologies. Additional markers of tubular damage considered in this study, including FE of other electrolytes and urinary NGAL, did not differ between groups. In conclusion, when compared to other aetiologies of intrinsic AKI, canine leptospirosis was characterised by increased glucosuria and kaliuresis.

Ultrasensitive Visual Detection of Glucose in Urine Based on the Iodide-Promoted Etching of Gold Bipyramids.

Blood glucose monitoring is an essential but painful component of diabetes management, so it is urgent to develop simple, convenient, and noninvasive glucose monitoring methods as alternatives. Because the glucose level in urine is directly related to the blood glucose, urine can be an alternative for blood glucose monitoring. Herein, we report the development of a new and highly sensitive noninvasive colorimetric assay to detect the glucose content in urine samples using gold bipyramids (GBPs). The principle of this method is to utilize hydrogen peroxide (H2O2), the oxidation product of glucose, to etch GBPs, where the urine glucose will be quantified based on the displacement of the absorption peak of GBPs. The unique morphology (sharp tips) and etching mechanism (from tips) of GBPs determine the high sensitivity of this assay. Under optimal conditions, this colorimetric assay shows a dynamic range of 0.5-250 µM and a detection limit of 0.34 µM for artificial urine samples. This detection capability is ideal when sample dilution is necessary. Another advantage is that the color change of the GBP solution in this assay is convenient for the visual readout of the urine glucose semiquantitatively by the naked eye. Furthermore, it has been demonstrated here that the iodide ion has the horseradish peroxidase (HRP) activity and can be used alone to promote the reduction reaction of H2O2, which eliminates the use of HRP enzymes, simplifies the reaction, and reduces costs. The role of iodide ions has been studied and mainly attributed as a catalyst with I2 as the reaction intermediate, which reduced the activation energy for the reduction of H2O2.