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Keywords = urine albumin–creatinine ratio (UACR)

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13 pages, 853 KiB  
Article
Comparative Effects of Dulaglutide and Semaglutide on Renal Function Decline and Proteinuria Reduction in Diabetic Patients: A Retrospective Cohort Study
by Yuh-Mou Sue, De-En Lu, Te-I Chang, Chun-You Chen, Cheng-Hsien Chen, Shih-Chang Hsu, Yen-Ling Chu, Nai-Jen Huang, Tso-Hsiao Chen, Feng-Yen Lin, Chun-Ming Shih, Po-Hsun Huang, Hui-Ling Hsieh and Chung-Te Liu
J. Clin. Med. 2025, 14(12), 4287; https://doi.org/10.3390/jcm14124287 - 16 Jun 2025
Viewed by 774
Abstract
Background: GLP-1 receptor agonists (GLP-1 RAs) lower glucose and reduce cardiovascular events in type 2 diabetes, with noted renal benefits. Few studies directly compare GLP-1 RAs. This study aims to compare the effects of semaglutide and dulaglutide on renal function decline and proteinuria [...] Read more.
Background: GLP-1 receptor agonists (GLP-1 RAs) lower glucose and reduce cardiovascular events in type 2 diabetes, with noted renal benefits. Few studies directly compare GLP-1 RAs. This study aims to compare the effects of semaglutide and dulaglutide on renal function decline and proteinuria reduction in diabetic patients. Methods: The present study was conducted at Wanfang Hospital, Taipei Medical University. Diabetic patients using either semaglutide or dulaglutide for more than 1 year in the outpatient department from 1 January 2022 to 30 September 2024 were enrolled retrospectively. The outcome events in the present study included a decline in the estimated glomerular filtration rate (eGFR), an increase in the urine albumin–creatinine ratio (UACR), and patient death. Results: A total of 268 patients on dulaglutide and 747 on semaglutide were included. Baseline eGFR levels were similar in both groups. After 12 months, eGFR levels did not significantly decline in both groups. However, the dulaglutide group showed significantly higher UACR increases than the semaglutide group (p < 0.01). More death events also occurred in the dulaglutide group (p < 0.01). Multivariate logistic regression revealed a higher risk of UACR increase with dulaglutide (p < 0.01). Subgroup analysis found dulaglutide associated with higher UACR in patients younger than 60, males, those with hypertension, without heart failure, those using angiotensin receptor blockers, biguanides, and statins, and those not using sodium-glucose cotransporter-2 inhibitors. Conclusions: Dulaglutide and semaglutide had comparable effects on slowing eGFR decline. However, dulaglutide was less effective in reducing UACR, particularly in the subgroups mentioned above. Full article
(This article belongs to the Section Nephrology & Urology)
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13 pages, 2979 KiB  
Article
The Underdiagnosis of Chronic Kidney Disease in Patients with a Documented Estimated Glomerular Filtration Rate and/or Urine Albumin–Creatinine Ratio in Germany
by Karel Kostev, Martina Lang, Sven-Oliver Tröbs, Sophia Urbisch and Maximilian Gabler
Medicina 2025, 61(5), 843; https://doi.org/10.3390/medicina61050843 - 2 May 2025
Viewed by 734
Abstract
Background and Objectives: The underdiagnosis of chronic kidney disease (CKD) is a critical issue worldwide. This present study aimed to explore the CKD subpopulation regarding underdiagnosed CKD in individuals with a pathological estimated glomerular filtration rate (eGFR) and/or urine albumin–creatinine ratio (UACR) values [...] Read more.
Background and Objectives: The underdiagnosis of chronic kidney disease (CKD) is a critical issue worldwide. This present study aimed to explore the CKD subpopulation regarding underdiagnosed CKD in individuals with a pathological estimated glomerular filtration rate (eGFR) and/or urine albumin–creatinine ratio (UACR) values in Germany. Materials and Methods: This analysis used data from the IQVIATM Disease Analyzer database and included adult outpatients with at least two pathological consecutive eGFR and/or UACR values, documented at least 60 days apart between October 2018 and September 2023 in 758 general practices. According to the 2024 KDIGO clinical practical guidelines, CKD was defined based on both eGFR and UACR values. UACR values were used when no pathological eGFR values were documented. The main outcome of the study was the proportion of patients with a documented CKD in the total population as well as in defined subgroups. Results: A total of 113,996 CKD patients (mean age: 76.5 (SD: 10.1) years; 60.2% female; 71.5% with mildly to moderately, 21.1% with moderately to severely, and 4.6% with a severely decreased eGFR value; and 1.0% with end-stage kidney disease) were available for analyses. CKD diagnosis was documented in 46.9% of CKD patients and was more frequent in male than in female patients (53.3% versus 42.7%). The highest proportion was observed in patients with heart failure (57.0%), followed by patients with type 2 diabetes (52.7%). In patients without diabetes and heart failure, CKD was documented in 38.2%. The proportion of CKD diagnoses increased with decreasing eGFR values, from 22.0% in patients with nonpathological eGFR but moderately or severely increased UACR to 87.7% in patients with end-stage kidney disease. Conclusions: The study provides valuable insights into the subpopulation of underdiagnosed CKD patients among a large patient population. These results underscore the need for improved screening, timely diagnosis documentation, and treatment strategies for CKD, particularly among high-risk populations. Moreover, it raises the need to increase awareness of micro- and macroalbuminuria as diagnostic criteria for CKD independent of eGFR. Full article
(This article belongs to the Section Urology & Nephrology)
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13 pages, 1807 KiB  
Article
Urinary Albumin-to-Creatinine Ratio (uACR) Point-of-Care (POC) Device with Seamless Data Transmission for Monitoring the Progression of Chronic Kidney Disease
by Artitaya Thiengsusuk, Napaporn Youngvises, Runtikan Pochairach, Rehab Osman Taha, Kridsada Sirisabhabhorn, Nadda Muhamad, Wanchai Meesiri, Wanna Chaijaroenkul and Kesara Na-Bangchang
Biosensors 2025, 15(3), 145; https://doi.org/10.3390/bios15030145 - 24 Feb 2025
Cited by 2 | Viewed by 2203
Abstract
Chronic kidney disease (CKD) continues to pose a critical global health challenge, making ongoing monitoring vital for effective management and preventing its progression to end-stage renal disease. The urinary albumin-to-creatinine ratio (uACR) stands out as a reliable biomarker. MyACR was developed and validated [...] Read more.
Chronic kidney disease (CKD) continues to pose a critical global health challenge, making ongoing monitoring vital for effective management and preventing its progression to end-stage renal disease. The urinary albumin-to-creatinine ratio (uACR) stands out as a reliable biomarker. MyACR was developed and validated as a novel point-of-care (POC) device for identifying and monitoring the progress of CKD. MyACR device operates using a colorimetric-based spectroscopy to quantify albumin and creatinine levels at 625 nm and 515 nm, respectively. Calculated uACR values were compared with results from the reference turbidimetry method using a dataset of 103 random urine samples from patients at high risk of advanced CKD. The device showed excellent performance in detecting severe nephropathy, with sensitivity, specificity, and accuracy of 100%, 100%, and 100%, respectively. The PPV (positive predictive value) was 100%, indicating perfect identification of patients with severe nephropathy (uACR > 300 mg/g creatinine). The NPV (negative predictive value) was 100%, suggesting a strong ability to rule out severe nephropathy, though a small risk of false negatives remained. Bland–Altman analysis confirmed a high level of agreement, with 96.11% (for all data) and 95.87% (for uACR > 300 mg/g creatinine) of MyACR measurements falling within the 95% confidence interval (−27 to +19). Correlation analysis revealed a significant alignment between MyACR and the reference method (r2 0.9720 to 0.9836). The ROC analysis suggested that combining uACR with the estimated glomerular filtration rate (eGFR) demonstrated strong predictive performance, yielding an area under the curve (AUC) of 0.933 (95% CI: 0.86–1.0). In conclusion, the MyACR device is a robust, affordable, and user-friendly tool for detecting nephropathy, showing performance comparable to the reference method. Its portability and cost-effectiveness make it particularly suitable for use in low-resource environments. Additionally, integrating uACR with eGFR enhances prognostic capabilities, offering a comprehensive approach to assessing kidney function and predicting CKD progression. Full article
(This article belongs to the Section Biosensors and Healthcare)
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14 pages, 2385 KiB  
Article
The Effect of Autologous Dendritic Cell Immunotherapy on Kidney Function and Endothelial Dysfunction of Patients with Diabetic Kidney Disease (DKD): An Open Label Clinical Trial
by Martina Lily Yana, Enda Cindylosa Sitepu, Jonny, Linda Chiuman, I Nyoman Ehrich Lister and Terawan Agus Putranto
Curr. Issues Mol. Biol. 2025, 47(1), 31; https://doi.org/10.3390/cimb47010031 - 6 Jan 2025
Cited by 1 | Viewed by 1135
Abstract
This study aimed to evaluate the effects of autologous dendritic cell (DC) immunotherapy on clinical outcomes (glomerular filtration rate/GFR and urine creatinine albumin ratio/UACR) and endothelial dysfunction (ICAM, VCAM, VEGF) in patients with diabetic kidney disease (DKD). Endothelial dysfunction induced by inflammation is [...] Read more.
This study aimed to evaluate the effects of autologous dendritic cell (DC) immunotherapy on clinical outcomes (glomerular filtration rate/GFR and urine creatinine albumin ratio/UACR) and endothelial dysfunction (ICAM, VCAM, VEGF) in patients with diabetic kidney disease (DKD). Endothelial dysfunction induced by inflammation is one of the key factors in the pathogenesis of DKD. In this one-group pretest–posttest quasi-experimental study, 69 subjects with DKD were administered a single dose of autologous DC immunotherapy ex vivo. UACR was measured at baseline and at weeks 1, 2, 3, and 4, while ICAM, VCAM, VEGF, and GFR were measured at baseline and at week 4 post-immunotherapy. The results showed a significant reduction in median UACR from 250 (IQR 71–668) mg/g at baseline to 164 (IQR 49–576) mg/g at week 4 (p < 0.05). GFR did not show any significant changes after immunotherapy. HbA1c (B = −33.270, p = 0.021) and baseline UACR (B = −0.185, p < 0.001) were identified as significant predictors of UACR change. Although there were no significant changes in ICAM, VCAM, and VEGF, subgroup analysis revealed a decrease in VCAM in macroalbuminuria patients and an increase in those with good glycemic control, suggesting differing endothelial responses. In conclusion, autologous DC immunotherapy effectively reduced UACR in DKD patients, and significant VCAM changes were found in macroalbuminuria and good glycemic control subjects. Further research is needed to understand the mechanisms behind UACR reduction and the long-term impact of this therapy. Full article
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15 pages, 933 KiB  
Article
The Influence of Concurrent Autoimmune Thyroiditis on the Cardiometabolic Consequences of Cabergoline in Postmenopausal Women
by Robert Krysiak, Marcin Basiak, Witold Szkróbka and Bogusław Okopień
Metabolites 2025, 15(1), 9; https://doi.org/10.3390/metabo15010009 - 1 Jan 2025
Viewed by 1273
Abstract
Background: Untreated hyperprolactinemia and autoimmune thyroiditis (Hashimoto’s disease) seem to increase cardiometabolic risk. The cardiometabolic effects of cabergoline were less significant in young women with concurrent euthyroid Hashimoto’s illness. This study sought to investigate if the detrimental effects of this condition on cabergoline [...] Read more.
Background: Untreated hyperprolactinemia and autoimmune thyroiditis (Hashimoto’s disease) seem to increase cardiometabolic risk. The cardiometabolic effects of cabergoline were less significant in young women with concurrent euthyroid Hashimoto’s illness. This study sought to investigate if the detrimental effects of this condition on cabergoline efficacy are also evident in postmenopausal women. Methods: The study comprised 50 postmenopausal women exhibiting increased prolactin levels, with half qualifying for euthyroid Hashimoto’s illness. The subjects with thyroid autoimmunity were matched with those without thyroid disease according to age, body mass index, and prolactin levels. In addition to prolactin, we assessed thyroid-stimulating hormone (TSH), thyroid antibodies, and glucose homeostasis markers: fasting glucose, the homeostatic model assessment 1 of insulin resistance ratio (HOMA1-IR), and glycated hemoglobin (HbA1c). Furthermore, we assessed plasma lipids, plasma uric acid levels, high-sensitivity C-reactive protein (hsCRP), fibrinogen, homocysteine, and the urine albumin-to-creatinine ratio (UACR). The decadal cardiovascular risk was assessed with the Framingham Risk Score (FRS). Results: Before therapy, disparities existed among groups in HOMA1-IR, HDL cholesterol, antibody titers, uric acid, hsCRP, fibrinogen, homocysteine, UACR, and FRS. After six months of treatment, cabergoline successfully corrected prolactin levels (both total and monomeric) in women without thyroid disorders. This normalization correlated with decreases in HOMA1-IR, triglycerides, uric acid, hsCRP, fibrinogen, homocysteine, UACR, and FRS, as well as an elevation in HDL cholesterol. In women diagnosed with Hashimoto’s disease, cabergoline’s effects were limited to a reduction in prolactin levels, HOMA1-IR, and UACR, as well as an elevation in HDL cholesterol, with these alterations being less pronounced compared to women without thyroid illness. Conclusions: The cardiometabolic benefits of cabergoline were associated with the degree of prolactin concentration reduction. In women diagnosed with Hashimoto’s disease, connections were noted between baseline levels and treatment-induced alterations in hsCRP. These data indicate that concurrent euthyroid autoimmune thyroiditis mitigates the cardiometabolic consequences of cabergoline. Full article
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12 pages, 244 KiB  
Article
Dulaglutide and Dapagliflozin Combination Concurrently Improves the Endothelial Glycocalyx and Vascular and Myocardial Function in Patients with T2DM and Albuminuria vs. DPP-4i
by Emmanouil Korakas, John Thymis, Evangelos Oikonomou, Konstantinos Mourouzis, Aikaterini Kountouri, Loukia Pliouta, Sotirios Pililis, George Pavlidis, Stamatios Lampsas, Konstantinos Katogiannis, Lina Palaiodimou, Georgios Tsivgoulis, Gerasimos Siasos, Ignatios Ikonomidis, Athanasios Raptis and Vaia Lambadiari
J. Clin. Med. 2024, 13(24), 7497; https://doi.org/10.3390/jcm13247497 - 10 Dec 2024
Viewed by 1299
Abstract
Background: The association between diabetic nephropathy and arterial elasticity and endothelial function is well established. In this study, we compared the effect of the combination of dulaglutide and dapagliflozin versus DPP-4 inhibitors on the endothelial glycocalyx, arterial stiffness, myocardial function, and albuminuria. [...] Read more.
Background: The association between diabetic nephropathy and arterial elasticity and endothelial function is well established. In this study, we compared the effect of the combination of dulaglutide and dapagliflozin versus DPP-4 inhibitors on the endothelial glycocalyx, arterial stiffness, myocardial function, and albuminuria. Methods: Overall, 60 patients were randomized to combined dulaglutide and dapagliflozin treatment (n = 30) or DPP-4 inhibitors (DPP-4i, n = 30) (ClinicalTrials.gov: NCT06611904). We measured at baseline and 4 and 12 months post-treatment: (i) the perfused boundary region of the sublingual arterial microvessels, (ii) pulse wave velocity (PWV) and central systolic blood pressure (cSBP), (iii) global left ventricular longitudinal strain (GLS), and (iv) urine albumin-to-creatinine ratio (UACR). Results: After twelve months, dual therapy showed greater improvements vs. DPP-4i in PBR (2.10 ± 0.31 to 1.93 ± 0.23 μm vs. 2.11 ± 0.31 to 2.08 ± 0.28 μm, p < 0.001), UACR (326 ± 61 to 142 ± 47 mg/g vs. 345 ± 48 to 306 ± 60 mg/g, p < 0.01), and PWV (11.77 ± 2.37 to 10.7 ± 2.29 m/s vs. 10.64 ± 2.44 to 10.54 ± 2.84 m/s, p < 0.001), while only dual therapy showed improvement in cSBP (130.21 ± 17.23 to 123.36 ± 18.42 mmHg). These effects were independent of glycemic control. Both treatments improved GLS, but the effect of dual therapy was significantly higher compared to DPP-4i (18.19% vs. 6.01%, respectively). Conclusions: Twelve-month treatment with dulaglutide and dapagliflozin showed a greater improvement in arterial stiffness, endothelial function, myocardial function, and albuminuria than DPP-4is. Early initiation of combined therapy as an add-on to metformin should be considered in these patients. Full article
9 pages, 674 KiB  
Article
Prediction of Possible Adverse Effects of Gestational Diabetes Mellitus on Maternal and Fetal Glomeruli by Urine and Amniotic Fluid Podocyte Degradation Products
by Fatma Tanilir Cagiran, Nihal Mavral, Zercan Kali and Pinar Kirici
Diagnostics 2024, 14(24), 2771; https://doi.org/10.3390/diagnostics14242771 - 10 Dec 2024
Viewed by 906
Abstract
Objectives: To compare the levels of podocyte damage markers nephrin and podocalyxin in urine samples taken at the time of gestational diabetes mellitus (GDM) diagnosis and at birth. Amniotic fluid podocalyxin (pdx) and nephrin levels were also analyzed to determine whether GDM had [...] Read more.
Objectives: To compare the levels of podocyte damage markers nephrin and podocalyxin in urine samples taken at the time of gestational diabetes mellitus (GDM) diagnosis and at birth. Amniotic fluid podocalyxin (pdx) and nephrin levels were also analyzed to determine whether GDM had an impact on fetal glomeruli. Methods: A total of 50 patients, including 24 patients diagnosed with gestational diabetes and 26 healthy pregnant women whose gestational weeks were matched, were included in the study. GDM was diagnosed with a 75 g oral glucose tolerance test (OGTT). Fresh morning urine samples from patients diagnosed with GDM were collected. The second urine sample was collected with the help of a catheter during birth. Amniotic fluid samples were taken from patients who gave birth by cesarean section. The urinary podocalyxin and nephrin levels were measured via the quantitative sandwich enzyme immunoassay. Albumin–creatinine ratio (uACR) was also calculated in urine samples. Results: Urinary nephrin and pdx levels on the day of GDM diagnosis were similar in the GDM and control groups. Microalbuminuria was detected in only one patient from each group at the time of GDM diagnosis. In the urine samples taken from the time of birth, pdx and nephrin levels of the GDM group were significantly higher than the control group (p < 0.001 for each). While microalbuminuria was detected in five patients (20.8%) at the time of birth in the GDM group, it was detected in only two patients (7.7%) in the control group. In the GDM group, a significant increase was detected between the urine pdx and nephrin levels measured at diagnosis and those measured at birth. In the control group, measurements at baseline and at birth were similar. There was no significant difference between the GDM and control groups in terms of amniotic fluid pdx and nephrin levels. A positive and significant correlation was detected between urinary pdx, nephrin, SBP, and uACR. Conclusions: While GDM triggers podocyte damage in maternal glomeruli, it does not cause significant change in fetal glomeruli. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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8 pages, 388 KiB  
Article
The Association Between Diabetic Nephropathy and Triglyceride/Glucose Index and Triglyceride/High-Density Lipoprotein Cholesterol Ratio in Patients with Type 2 Diabetes Mellitus
by Abbas Ali Tam, Feride Pınar Altay, Pervin Demir, Didem Ozdemir, Oya Topaloglu, Reyhan Ersoy and Bekir Cakır
J. Clin. Med. 2024, 13(22), 6954; https://doi.org/10.3390/jcm13226954 - 18 Nov 2024
Cited by 1 | Viewed by 1419
Abstract
Background: In this study, we aimed to investigate the relationship between diabetic nephropathy (DN) and triglyceride/glucose (TyG) index and triglyceride/high-density lipoprotein cholesterol ratio (Tg/HDL-C) as surrogate markers of insulin resistance. Method: Medical records of 15,378 individuals between February 2019 and May 2024 were [...] Read more.
Background: In this study, we aimed to investigate the relationship between diabetic nephropathy (DN) and triglyceride/glucose (TyG) index and triglyceride/high-density lipoprotein cholesterol ratio (Tg/HDL-C) as surrogate markers of insulin resistance. Method: Medical records of 15,378 individuals between February 2019 and May 2024 were examined. Serum glucose, Tg, HDL-C, HbA1c, estimated glomerular filtration rate (eGFR), and urine albumin/creatinine ratio (UACR) were evaluated and the TyG index and TG/HDL-C ratios were calculated for each individual. DN was defined as a UACR ≥ 30 mg/g and/or eGFR <60 mL/min/1.73 m2. Results: Of 10,714 patients, DN was detected in 3763 (35.1%). Females had 10% higher odds of developing DN compared to males. A TyG index at or above the determined cutoff point (9.58) indicated a risk of DN and the sensitivity and specificity values were 44.01% and 71.28%, respectively. The risk of DN was 1.95 times higher in individuals with a TyG index value of ≥9.58 compared to those with a TyG index <9.58. While the Tg/HDL ratio was significant in detecting DN in the univariate analysis (odds ratio (OR) 1.59; 95% confidence interval 1.46–1.73), this significance was not found in the multivariate analysis (OR 1.15; 95% confidence interval 0.94–1.40). Conclusions: A high TyG index is associated with DN in patients with type 2 diabetes and it might be a potential marker in predicting DN. Full article
(This article belongs to the Section Endocrinology & Metabolism)
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13 pages, 2555 KiB  
Article
Polycystic Ovary Syndrome Accompanied by Hyperandrogenemia or Metabolic Syndrome Triggers Glomerular Podocyte Injury
by Kagan Gungor, Nur D. Gungor, Onder Celik, Aynur Ersahin, Nilufer Celik, Meltem Yardim, Arzu Yurci, Murat Kobaner and Ivan Ilkov Maslarski
Diagnostics 2024, 14(19), 2197; https://doi.org/10.3390/diagnostics14192197 - 1 Oct 2024
Cited by 1 | Viewed by 1352
Abstract
Objective: To determine whether the urinary excretion of podocyte degradation products varies according to PCOS phenotype and metabolic syndrome (MetS). Methods: The concentrations of podocalyxin (PDX) and nephrin, chronic markers of podocyte damage, and neutrophil gelatinase-associated lipocalin (NGAL), a marker of acute glomerular [...] Read more.
Objective: To determine whether the urinary excretion of podocyte degradation products varies according to PCOS phenotype and metabolic syndrome (MetS). Methods: The concentrations of podocalyxin (PDX) and nephrin, chronic markers of podocyte damage, and neutrophil gelatinase-associated lipocalin (NGAL), a marker of acute glomerular damage, were analyzed in the morning urine samples of 50 PCOS patients and 50 healthy controls matched by age and BMI. Albuminuria was assessed by calculating the urine albumin–creatinine ratio (uACR). Results: The PDX, nephrin and NGAL concentrations of PCOS participants were significantly higher than those of the control group. While PDX, nephrin and NGAL levels of classic phenotypes were similar, they were higher than ovulatory and non-hyperandrogenic phenotypes. Significant increases in urinary levels of each podocyte protein were detected in PCOS patients with MetS compared to patients without MetS. A positive significant correlation between podocyte proteins and BMI, systolic blood pressure, testosterone, glucose, HOMA-IR and uACR. After adjusting for age and BMI, podocyte proteins were an independent risk factor for microalbuminuria. The incidence of microalbuminuria in PCOS increased 6-fold compared to controls. The frequency of microalbuminuria was higher in classical phenotypes than in ovulatory phenotype. The frequency of microalbuminuria in PCOS patients with MetS was 6.5 times higher than in PCOS patients without MetS. Conclusions: In PCOS accompanied by hyperandrogenemia or metabolic syndrome, leakage of acute and chronic podocyte breakdown products into the urine becomes more pronounced. Full article
(This article belongs to the Section Clinical Laboratory Medicine)
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13 pages, 2703 KiB  
Article
Portable Electrochemical System and Platform with Point-of-Care Determination of Urine Albumin-to-Creatinine Ratio to Evaluate Chronic Kidney Disease and Cardiorenal Syndrome
by Shuenn-Yuh Lee, Ding-Siang Ciou, Hao-Yun Lee, Ju-Yi Chen, Yi-Chieh Wei and Meng-Dar Shieh
Biosensors 2024, 14(10), 463; https://doi.org/10.3390/bios14100463 - 27 Sep 2024
Cited by 1 | Viewed by 1960
Abstract
Abstract: The urine albumin (Alb)-to-creatinine (Crn) ratio (UACR) is a sensitive and early indicator of chronic kidney disease (CKD) and cardiorenal syndrome. This study developed a portable and wireless electrochemical-sensing platform for the sensitive and accurate determination of UACR. The developed platform consists [...] Read more.
Abstract: The urine albumin (Alb)-to-creatinine (Crn) ratio (UACR) is a sensitive and early indicator of chronic kidney disease (CKD) and cardiorenal syndrome. This study developed a portable and wireless electrochemical-sensing platform for the sensitive and accurate determination of UACR. The developed platform consists of a carbon nanotube (CNT)-2,2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)(ABTS)-based modified UACR sensor, a miniaturised potentiostat, a cup holder embedded with a magnetic stirrer and a smartphone app. The UACR sensing electrode is composed of two screen-printed carbon working electrodes, one screen-printed carbon counter electrode and a screen-printed AgCl reference electrode. The miniaturised potentiostat, which is controlled by the developed app, performs cyclic voltammetry and amperometry to detect Alb and Crn, respectively. Clinical trials of the proposed system by using spot urine samples from 30 diabetic patients indicate that it can accurately classify all three CKD risk statuses within 30 min. The high accuracy of our proposed sensing system exhibits satisfactory agreement with the commercial biochemical analyser TBA-25FR (Y = 0.999X, R2 = 0.995). The proposed UACR sensing system offers a convenient, reliable and affordable solution for personal mobile health monitoring and point-of-care urinalysis. Full article
(This article belongs to the Special Issue Electrochemical Biosensors for Disease Detection)
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15 pages, 4251 KiB  
Article
Proteomic Analysis Identifies Dysregulated Proteins in Albuminuria: A South African Pilot Study
by Siyabonga Khoza, Jaya A. George, Previn Naicker, Stoyan H. Stoychev, June Fabian and Ireshyn S. Govender
Biology 2024, 13(9), 680; https://doi.org/10.3390/biology13090680 - 30 Aug 2024
Cited by 1 | Viewed by 2397
Abstract
Albuminuria may precede decreases in the glomerular filtration rate (GFR) and both tests are insensitive predictors of early stages of kidney disease. Our aim was to characterise the urinary proteome in black African individuals with albuminuria and well-preserved GFR from South Africa. This [...] Read more.
Albuminuria may precede decreases in the glomerular filtration rate (GFR) and both tests are insensitive predictors of early stages of kidney disease. Our aim was to characterise the urinary proteome in black African individuals with albuminuria and well-preserved GFR from South Africa. This case-controlled study compared the urinary proteomes of 52 normoalbuminuric (urine albumin: creatinine ratio (uACR) < 3 mg/mmol) and 56 albuminuric (uACR ≥ 3 mg/mmol) adults of black African ethnicity. Urine proteins were precipitated, reduced, alkylated, digested, and analysed using an Evosep One LC (Evosep Biosystems, Odense, Denmark) coupled to a Sciex 5600 Triple-TOF (Sciex, Framingham, MA, USA) in data-independent acquisition mode. The data were searched on SpectronautTM 15. Differentially abundant proteins (DAPs) were filtered to include those with a ≥2.25-fold change and a false discovery rate ≤ 1%. Receiver–operating characteristic curves were used to assess the discriminating abilities of proteins of interest. Pathway analysis was performed using Enrichr software. As expected, the albuminuric group had higher uACR (7.9 vs. 0.55 mg/mmol, p < 0.001). The median eGFR (mL/min/1.73 m2) showed no difference between the groups (111 vs. 114, p = 0.707). We identified 80 DAPs in the albuminuria group compared to the normoalbuminuria group, of which 59 proteins were increased while 21 proteins were decreased in abundance. We found 12 urinary proteins with an AUC > 0.8 and a p < 0.001 in the multivariate analysis. Furthermore, an 80-protein model was developed that showed a high AUC ˃ 0.907 and a predictive accuracy of 91.3% between the two groups. Pathway analysis found that the DAPs were involved in insulin growth factor (IGF) functions, innate immunity, platelet degranulation, and extracellular matrix organization. In albuminuric individuals with a well-preserved eGFR, pathways involved in preventing the release and uptake of IGF by insulin growth factor binding protein were significantly enriched. These proteins are indicative of a homeostatic imbalance in a variety of cellular processes underlying renal dysfunction and are implicated in chronic kidney disease. Full article
(This article belongs to the Special Issue Applications of Proteomics in Biological Fluids and Biopsies)
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11 pages, 728 KiB  
Article
Urine Protein to Creatinine Ratio for the Assessment of Bevacizumab-Associated Proteinuria in Patients with Gynecologic Cancers: A Diagnostic and Quality Improvement Study
by Kuan-Ju Huang, Wen-Chun Chang, Chi-Hau Chen, Wei-Chen Lin, William Wei-Lin Pan, Hao-I. Hsieh, Yu-Hsiung Hsieh, Lin-Hung Wei and Bor-Ching Sheu
Diagnostics 2024, 14(17), 1852; https://doi.org/10.3390/diagnostics14171852 - 24 Aug 2024
Cited by 1 | Viewed by 2562
Abstract
Proteinuria is a common adverse event arising from treatment with bevacizumab, requiring diagnostic testing via 24-h urine collection. However, this method is cumbersome. We assessed urine screenings in gynecologic cancer patients from February 2021 to May 2022. Along with a simple urine dipstick [...] Read more.
Proteinuria is a common adverse event arising from treatment with bevacizumab, requiring diagnostic testing via 24-h urine collection. However, this method is cumbersome. We assessed urine screenings in gynecologic cancer patients from February 2021 to May 2022. Along with a simple urine dipstick (UD), the urine microalbumin, total protein, and creatinine were measured and calculated as the urine albumin to creatinine ratio (UACR) and the urine protein to creatinine ratio (UPCR), which were further adjusted through the Modification of Diet in Renal Disease and Chronic Kidney Disease Epidemiology Collaboration equations to be estimated and correlated with 24-h urine total protein content. The incremental cost-effectiveness ratio was used for cost analysis. There were 129 urine samples from 36 patients. The sensitivity and specificity for the UACR were 0.56 and 0.97, and for the UPCR, 0.71 and 0.88, respectively. The 24-h TP correlated strongly with the UACR (r = 0.75; p < 0.001) and UPCR (r = 0.79; p < 0.001) and fair for the simple UD (r = 0.35; p < 0.001). The UPCR saves one unnecessary 24-h urine test for less than a dollar compared to a simple UD. The results indicate that using the UPCR could enhance diagnostic accuracy, lower costs, and reduce unnecessary 24-h urine sampling. Full article
(This article belongs to the Special Issue Advances in the Diagnosis and Management of Gynecological Cancers)
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15 pages, 1934 KiB  
Article
Higher Circulating Neutrophil Counts Is Associated with Increased Risk of All-Cause Mortality and Cardiovascular Disease in Patients with Diabetic Kidney Disease
by Ruiyan Xie, David M. Bishai, David T. W. Lui, Paul C. H. Lee and Desmond Y. H. Yap
Biomedicines 2024, 12(8), 1907; https://doi.org/10.3390/biomedicines12081907 - 20 Aug 2024
Cited by 4 | Viewed by 2190
Abstract
Background: Accumulating evidence has suggested the pathogenic roles of chronic inflammation and neutrophils in diabetic kidney disease (DKD). This study investigated the relationship between neutrophils, all-cause, and cardiovascular disease (CVD) mortality in type 2 diabetes mellitus (T2DM) patients with DKD. Methods: We used [...] Read more.
Background: Accumulating evidence has suggested the pathogenic roles of chronic inflammation and neutrophils in diabetic kidney disease (DKD). This study investigated the relationship between neutrophils, all-cause, and cardiovascular disease (CVD) mortality in type 2 diabetes mellitus (T2DM) patients with DKD. Methods: We used data from the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2020 to investigate the relationship between circulating neutrophils counts, kidney function indices, all-cause, and CVD mortality in adult T2DM patients with DKD. Clinical predictive models and risk scores for long-term mortality were constructed. Results: 44,332 patients [8034 with T2DM and 36,323 without T2DM] were included. Two thousand two hundred twenty patients had DKD, and 775 died (31.5% related to CVD) during a follow-up of 6.18 (range: 5.94–6.42) years. Higher neutrophil counts (Quartile 4, Q4) were associated with increased all-cause and CVD mortality [HR 1.73 (95% CI 1.34–2.25) and 1.81 (95% CI 1.14–2.89), respectively, p < 0.0001 and 0.01]. Neutrophil counts in Q4 showed a positive correlation with urine albumin-creatinine ratio (UACR) but a negative association with eGFR (p < 0.01 for all). Clinical predictive models incorporating neutrophil counts showed satisfactory performance in forecasting 5-year and 10-year CVD mortality-free survival (ROC AUC 0.824 and 0.842, respectively), and the nomogram-predicted survival demonstrated good concordance with observed survival. Conclusions: Higher levels of circulating neutrophil counts show a significant correlation with renal abnormalities and higher all-cause and CVD mortality in T2DM patients with DKD. The novel clinical predictive models and risk scores incorporating neutrophil counts may facilitate stratification and, hence, risk factor management in DKD patients. Full article
(This article belongs to the Section Endocrinology and Metabolism Research)
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15 pages, 1718 KiB  
Article
MyACR: A Point-of-Care Medical Device for Determination of Albumin–Creatinine Ratio (uACR) in Random Urine Samples as a Marker of Nephropathy
by Nadda Muhamad, Napaporn Youngvises, Tullayakorn Plengsuriyakarn, Wanchai Meesiri, Wanna Chaijaroenkul and Kesara Na-Bangchang
Diagnostics 2024, 14(16), 1702; https://doi.org/10.3390/diagnostics14161702 - 6 Aug 2024
Cited by 6 | Viewed by 2676
Abstract
Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the world’s population. Monitoring urine albumin-to-creatinine ratio (uACR) has become the gold standard for nephropathy diagnosis and control. The objective of the present study was to develop a simple, [...] Read more.
Chronic kidney disease (CKD) is a progressive condition that affects more than 10% of the world’s population. Monitoring urine albumin-to-creatinine ratio (uACR) has become the gold standard for nephropathy diagnosis and control. The objective of the present study was to develop a simple, accurate, sensitive, and rapid point-of-care test (PoCT) device, MyACR, for uACR measurement, intended for use in community healthcare to screen for the risk and monitor the progress of CKD. Albumin and creatinine concentrations in urine samples were determined using spectrophotometric dye (tetrabromophenol blue)-binding and colorimetric Jaffe assay, respectively. Urine samples were diluted with distilled water (1:80) and mixed separately with albumin and creatinine reaction mixture. The creatinine reaction was incubated at room temperature (25 °C) for 30 min before analysis. Optical density (OD) was measured at the wavelengths of 625 nm (albumin) and 515 nm (creatinine). All calibration curves (0–60 mg/L and 0–2 mg/dL for albumin and creatinine) yielded linear relationships with correlation coefficients (R2) of >0.997. Good accuracy (% deviation of mean value (DMV) ≤ 5.42%) and precision (% coefficients of variation (CV) ≤ 12.69%) were observed from both the intra- and inter-day assays for the determination of albumin and creatinine using MyACR. The limit of quantification (LOQ) of albumin and creatinine in urine samples determined using MyACR and a laboratory spectrophotometer were 5 mg/L and 0.25 mg/dL, respectively, using 37.5 μL urine spiked samples (n = 5). The device was well-applied with clinical samples from 20 CKD patients. The median (range) of %DMV of the central (hospital) laboratory method (immune-based assay) was 3.48 (−17.05 to 21.64)%, with a high correlation coefficient (R2 > 0.98). In conclusion, MyACR showed satisfactory test performance in terms of accuracy, reproducibility, and sensitivity. Cost-effectiveness and improvement in clinical decision making need to be proven in future multisite community and home studies. Full article
(This article belongs to the Section Point-of-Care Diagnostics and Devices)
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9 pages, 812 KiB  
Article
Real-Life Experience on the Effect of SGLT2 Inhibitors vs. Finerenone vs. Combination on Albuminuria in Chronic Kidney Disease
by Mohamad Hanouneh, Dustin Le, Bernard G. Jaar, Christina Tamargo and C. Elena Cervantes
Diagnostics 2024, 14(13), 1357; https://doi.org/10.3390/diagnostics14131357 - 26 Jun 2024
Cited by 4 | Viewed by 6598
Abstract
Background: There have been several recent advances in the care of patients with chronic kidney disease (CKD), including the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and selective mineralocorticoid receptor antagonists (MRAs). There are very few data reporting the outcomes of these [...] Read more.
Background: There have been several recent advances in the care of patients with chronic kidney disease (CKD), including the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and selective mineralocorticoid receptor antagonists (MRAs). There are very few data reporting the outcomes of these treatments in real-world experience. The aim of this retrospective study is to report the effects of SGLT2 inhibitors, finerenone, and their combination in CKD patients in our community-based setting. Methods: Ninety-eight patients with CKD with an estimated glomerular filtration rate (eGFR) between 25 and 90 mL/min per 1.73 m2 and a urine albumin-to-creatinine ratio (UACR) ≥ 30 mg/g were included. Patients were divided into three groups: two monotherapy groups of SGLT2 inhibitors or finerenone and a third combination group of therapy with SGLT2 inhibitors for the first 4 months and SGLT2 inhibitors and finerenone subsequently. The primary outcomes were the timing and percentage of patients achieving a >50% reduction in UACR from baseline. Results: Group 1 comprised 52 patients on SGLT2i, group 2 had 22 patients on finerenone, and group 3 had 24 patients on combination therapy. The baseline median UACR and mean eGFR were 513 mg/g and 47.9 mL/min per 1.73 m2 in group 1, 548.0 mg/g and 50.5 mL/min per 1.73 m2 in group 2, and 800 mg/g and 60 mL/min per 1.73 m2 in group 3. At baseline, 71 (72.4%) patients were on the angiotensin-converting enzyme inhibitor (ACEi) or the angiotensin receptor blocker (ARB), and 78 (79.5%) patients had type 2 diabetes. After 8 months of follow-up, a >50% decrease in albuminuria was achieved in 96% of patients in group 3, compared to 50% in group 1 and 59% in group 2 (p-values were <0.01 and <0.01, respectively). There was a statistically but not clinically significant change in mean potassium levels in group 2 (+0.4 mmol/L) compared to either group 1 (0.0 mmol/L with p-value: <0.01) or group 3 (−0.01 mmol/L with p-value: <0.01). However, there was no difference in potassium levels when comparing groups 1 and 3. At the end of the follow-up, the average difference in eGFR was −3.4 (8.8), −5.3(10.1), and −7.8 (11.2) mL/min per 1.73 m2 in groups 1, 2, and 3, respectively, without a statistically significant difference between groups. Conclusions: In this real-world experience in our community setting, the combination of SGLT2 inhibitors and finerenone in our adult patients with CKD was associated with a very significant and clinically relevant reduction in UACR, without an increased risk of hyperkalemia. Combination therapy of SGLT2 inhibitor and finerenone regarding background use of ACEi/ARB is feasible and should be encouraged for further albuminuria reductions in CKD patients. Full article
(This article belongs to the Special Issue Kidney Disease: Biomarkers, Diagnosis, and Prognosis: 3rd Edition)
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