Biomarkers Of Kidney Disease Research Articles

Transformative personalized oxalate biomarker analysis through a wrist-worn microneedle device integrated with duplex nanozyme toolbox

The interstitial fluid (ISF) is valuable for disease diagnosis due to its unique biomarkers. Microneedles (MNs) offer a painless method for ISF sampling, facilitating primary diagnostics. This study introduces a minimally invasive, biocompatible MN patch made from a swellable hydrogel of polyvinyl alcohol (PVA) and polyvinyl pyrrolidone (PVP), which effectively extracts ISF. The hydrogel selectively permits small molecules like oxalate, a kidney disease biomarker, while blocking large biomolecules. The MN patch is integrated with a multilayer sensor via microfluidic channels, featuring cotton fiber, agarose, and Mn3[Fe(CN)6]2, alongside Fe3[Fe(CN)6]3 (AGH-CP/MnFeCN/FeFeCN). These nanozymes exhibit oxidase-like activity, reacting with 3,3′,5,5′-tetramethylbenzidine (TMB) to indicate oxalate levels through a color change from green (no oxalate) to light or dark blue, based on concentration. The designed sensor demonstrates high performance with a detection limit of 0.897 μM and an RSD of 1.22 %, enabling accurate quantification via smartphone image analysis as readout platforms for more accessibility and user-friendliness which helps to reach personalized healthcare goals. This integration facilitates real-time, remote, precise disease detection, biochemical analysis and forsooth miniaturization, leading to the development of portable, flexible, and wearable sensors. The MN patch and integrated sensor show excellent stability, selectivity, sensitivity, reliability, and long-term durability. This minimally invasive sensing system, designed for wristband integration, opens new avenues for precision point-of-care monitoring, enhancing personal healthcare.

Associations between Kidney Disease Progression and Metabolomic Profiling in Stable Kidney Transplant Recipients-A 3 Year Follow-Up Prospective Study.

Background: kidney transplant recipients are exposed to multiple pathogenic pathways that may alter short and long-term allograft survival. Metabolomic profiling is useful for detecting potential biomarkers of kidney disease with a predictive capacity. This field is still under development in kidney transplantation and metabolome analysis is faced with analytical challenges. We performed a cross-sectional study including stable kidney transplant patients and aimed to search for relevant associations between baseline plasmatic and urinary metabolites and relevant outcomes over a follow-up period of 3 years. Methods: we performed a cross-sectional study including 72 stable kidney transplant patients with stored plasmatic and urinary samples at the baseline evaluation which were there analyzed by nuclear magnetic resonance in order to quantify and describe metabolites. We performed a 3-year follow-up and searched for relevant associations between renal failure outcomes and baseline metabolites. Between-group comparisons were made after classification by observed estimated glomerular filtration rate slope during the follow-up: positive slope and negative slope. Results: The mean estimated GFR (glomerular filtration rate) was higher at baseline in the patients who exhibited a negative slope during the follow-up (63.4 mL/min/1.73 m2 vs. 55.8 mL/min/1.73 m2, p = 0,019). After log transformation and division by urinary creatinine, urinary dimethylamine (3.63 vs. 3.16, p = 0.027), hippuric acid (7.33 vs. 6.29, p = 0.041), and acetone (1.88 vs. 1, p = 0.023) exhibited higher concentrations in patients with a negative GFR slope when compared to patients with a positive GFR slope. By computing a linear regression, a significant low-strength regression equation between the log 2 transformed plasmatic level of glycine and the estimated glomerular filtration rate was found (F (1,70) = 5.15, p = 0.026), with an R2 of 0.069. Several metabolites were correlated positively with hand grip strength (plasmatic tyrosine with r = 0.336 and p = 0.005 and plasmatic leucine with r = 0.371 and p = 0.002). Other urinary metabolites were found to be correlated negatively with hand grip strength (dimethylamine with r = -0.250 and p = 0.04, citric acid with r = -0.296 and p = 0.014, formic acid with r = -0.349 and p = 0.004, and glycine with r = -0.306 and p = 0.01). Conclusions: some metabolites had different concentrations compared to kidney transplant patients with negative and positive slopes, and significant correlations were found between hand grip strength and urinary and plasmatic metabolites.

Identification of common biomarkers in diabetic kidney disease and cognitive dysfunction using machine learning algorithms

Cognitive dysfunction caused by diabetes has become a serious global medical issue. Diabetic kidney disease (DKD) exacerbates cognitive dysfunction in patients, although the precise mechanism behind this remains unclear. Here, we conducted an investigation using RNA sequencing data from the Gene Expression Omnibus (GEO) database. We analyzed the differentially expressed genes in DKD and three types of neurons in the temporal cortex (TC) of diabetic patients with cognitive dysfunction. Through our analysis, we identified a total of 133 differentially expressed genes (DEGs) shared between DKD and TC neurons (62 up-regulated and 71 down-regulated). To identify potential common biomarkers, we employed machine learning algorithms (LASSO and SVM-RFE) and Venn diagram analysis. Ultimately, we identified 8 overlapping marker genes (ZNF564, VPS11, YPEL4, VWA5B1, A2ML1, KRT6A, SEC14L1P1, SH3RF1) as potential biomarkers, which exhibited high sensitivity and specificity in ROC curve analysis. Functional analysis using Gene Ontology (GO) revealed that these genes were primarily enriched in autophagy, ubiquitin/ubiquitin-like protein ligase activity, MAP-kinase scaffold activity, and syntaxin binding. Further enrichment analysis using Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) indicates that these biomarkers may play a crucial role in the development of cognitive dysfunction and diabetic nephropathy. Building upon these biomarkers, we developed a diagnostic model with a reliable predictive ability for DKD complicated by cognitive dysfunction. To validate the 8 biomarkers, we conducted RT-PCR analysis in the cortex, hippocampus and kidney of animal models. The results demonstrated the up-regulation of SH3RF1 in the cortex, hippocampus and kidney of mice, which was further confirmed by immunofluorescence and Western blot validation. Notably, SH3RF1 is a scaffold protein involved in cell survival in the JNK signaling pathway. Based on these findings, we support that SH3RF1 may be a common gene expression feature that influences DKD and cognitive dysfunction through the apoptotic pathway.

Reference gene panel for urinary exosome-based molecular diagnostics in patients with kidney disease.

Kidney disease is a severe complication of diabetes that often leads to end-stage renal disease. Early diagnosis is crucial for prevention or delay. However, the current diagnostic methods, with their limitations in detecting the disease in its early stages, underscore the urgency and importance of finding new solutions. miRNAs encapsulated inside urinary exosomes (UEs) have potential as early biomarkers for kidney diseases. The need for reference miRNAs for accurate interpretation currently limits their translational potential. To identify consistently expressing reference miRNAs from UEs of controls and patients with type 2 diabetesmellitus (T2DM) and biopsy-confirmed kidney diseases. miRNA profiling was performed on UEs from 31 human urine samples using a rigorous and unbiased method. The UEs were isolated from urine samples collected from healthy individuals (n = 6), patients with T2DM (n = 13), and T2DM patients who also had kidney diseases (including diabetic nephropathy, n = 5; membranous nephropathy, n = 5; and IgA nephropathy, n = 2) through differential ultracentrifugation. After characterizing the UEs, miRNA expression profiling using microarray technology was conducted. Microarray data analysis identified 14 miRNAs that were consistently expressed in UEs from 31 human samples, representing various kidney conditions: diabetic controls, diabetic nephropathy, membrane nephropathy, IgA nephropathy, and healthy controls. Through in silico analysis, we determined that 10 of these miRNAs had significant potential to serve as reference genes in UEs. We identified uniformly expressing UE miRNAs that could serve as reference genes kidney disease biomarkers.

Novel Biomarkers for Kidney Disease: New Frontiers in Early Diagnosis and Monitoring

Kidney diseases pose a significant threat to global public health, with early diagnosis and accurate monitoring being crucial for improving patient outcomes. However, traditional kidney disease markers such as serum creatinine and blood urea nitrogen have limitations in sensitivity and specificity. In recent years, rapid advancements in molecular biology and proteomics have led to the discovery of a series of novel biomarkers that are gradually being applied in clinical practice. This review examines novel kidney disease biomarkers, including cystatin C (Cys-C), neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule-1 (KIM-1). These markers not only reflect kidney injury earlier and more accurately but may also provide important bases for kidney disease classification, severity assessment, and prognosis prediction. Additionally, this paper explores the potential of multi-marker combined detection strategies in improving diagnostic accuracy. Although these novel markers show immense potential, they still face challenges such as standardization and cost-effectiveness before widespread clinical application. Future research should focus on optimizing detection methods, establishing clinical decision thresholds, and evaluating the value of these markers in personalized medicine, thereby paving new paths for precise diagnosis and treatment of kidney diseases.

Angiopoietin-like 4 is a potential biomarker for diabetic kidney disease in type 2 diabetes patients.

The association between serum angiopoietin-like 4 (ANGPTL4) levels and the severity of diabetic kidney disease (DKD) in patients with type 2 diabetes mellitus remains unclear. A total of 1,115 type 2 diabetes mellitus patients were analyzed in this cross-sectional study. DKD index included DKD stages defined by estimated glomerular filtration rate, the albuminuria grades and DKD risk management grades. Serum levels of ANGPTL4 and other biomarkers were detected. Multivariable-adjusted linear and logistic analyses were used to study the association between ANGPTL4 and DKD. The protein levels of ANGPTL4 were assessed in the kidney. Renal tubular cells were stimulated with glucose to study ANGPTL4 expression. Compared with the participants in the third or fourth quantile of ANGPTL4, those in the first or second quantile of ANGPTL4 were younger, with lower glycated hemoglobin, triglycerides and urinary albumin creatinine ratio (all P < 0.05). There was a negative nonlinear relationship between ANGPTL4 and estimated glomerular filtration rate in type 2 diabetes mellitus patients. One standard deviation increased serum ANGPTL4 levels, the odds ratio of having DKD was 1.40 (95% confidence interval 1.08-1.80). The mediation analysis showed that triglycerides did not mediate the association between ANGPTL4 and DKD. Furthermore, ANGPTL4 could be the strongest among multiple panels of biomarkers in its association of DKD. Compared with mice at 8 weeks-of-age, db/db mice at 18 weeks-of-age had increased ANGPTL4 expression in glomeruli and tubular segments. In vitro, glucose could stimulate ANGPTL4 expression in tubular cells in a dose-dependent manner. ANGPTL4 could be a potential marker and therapeutic target for DKD treatment.

Heterostructures constructed by NiMoO4 functionalized 2D MoO3 nanosheets for ultrasensitive trimethylamine detection with ppb level detection

Trimethylamine (TMA) serves as an indicator for assessing seafood spoilage and a biomarker for kidney disease. Achieving this dual functionality necessitates the detection of TMA with a low detection limit and exceptional selectivity. Here, NiMoO4 functionalized MoO3 heterostructures were constructed and subjected to a systematic investigation of their sensing properties towards TMA. The 7 %-NiMoO4/MoO3 sensor could detect trace TMA at 200°C with a response value of 3.93 (0.1 ppm) and achieve detecting thresholds as low as 2.48 ppb (theoretical limit). Additionally, the sensor exhibits remarkable selectivity to TMA, an expansive adjustable concentration on detection range, and excellent long-term stability. The enhanced sensing properties may be ascribed to the forming p-n heterojunctions at the NiMoO4/MoO3 interface, effectively modulating the interfacial potential. Moreover, the NiMoO4/MoO3 heterostructures demonstrate excellent charge-transfer capability, high charge carrier density, and a substantial active surface area in electrochemical measurements, thereby enhancing the sensing ability of TMA. Additionally, the thin nanosheet structure facilitates efficient charge transportation along the length of the nanosheets, further enhancing the sensing response. These results indicate the potential of NiMoO4/MoO3 as a promising sensing material for TMA gas sensors.

Insights into non-coding RNAS: biogenesis, function and their potential regulatory roles in acute kidney disease and chronic kidney disease.

Noncoding RNAs (ncRNAs) have emerged as pivotal regulators of gene expression, and have attracted significant attention because of their various roles in biological processes. These molecules have transcriptional activity despite their inability to encode proteins. Moreover, research has revealed that ncRNAs, especially microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), are linked to pervasive regulators of kidney disease, including anti-inflammatory, antiapoptotic, antifibrotic, and proangiogenic actions in acute and chronic kidney disease. Although the exact therapeutic mechanism of ncRNAs remains uncertain, their value in treatment has been studied in clinical trials. The numerous renal diseases and the beneficial or harmful effects of NcRNAs on the kidney will be discussed in this article. Afterward, exploring the biological characteristics of ncRNAs, as well as their purpose and potential contributions to acute and chronic renal disease, were explored. This may offer guidance for treating both acute and long-term kidney illnesses, as well as insights into the potential use of these indicators as kidney disease biomarkers.

Serum and Urinary Uromodulin in Dogs with Early Chronic Kidney Disease vs. Healthy Canine Population.

Serum and urinary uromodulin are evaluated as potential biomarkers of kidney disease. The aim of our research was to select a more appropriate form of uromodulin for the diagnosis of early stages of chronic kidney disease (CKD). We also focused on the influence of age and gender in one breed on uromodulin and on the possible interbreed differences. Serum uromodulin had the lowest values in dogs younger than 2 years but no effect of gender, breed, or CKD was observed. Urinary uromodulin indexed to urinary creatinine was significantly reduced in dogs in stage 2 of CKD (p = 0.003) in contrast to uromodulin converted to urine specific gravity. Urinary uromodulin with both corrections was significantly lower in Belgian shepherds compared to German shepherds (p < 0.0001, p = 0.0054) but was not influenced by gender or age. In stage 1 of CKD, urinary uromodulin correlated with kidney disease markers SDMA (p = 0.0424, p = 0.0214) and UPC (p = 0.0050, p = 0.0024). Urinary uromodulin appears to be more associated with CKD than serum uromodulin. Further studies with a larger number of patients are needed for the suitability of urinary uromodulin as a marker of early-stage disease.

In Situ Growth of COF/PVA-Carrageenan Hydrogel Using the Impregnation Method for the Purpose of Highly Sensitive Ammonia Detection.

Flexible ammonia (NH3) gas sensors have gained increasing attention for their potential in medical diagnostics and health monitoring, as they serve as a biomarker for kidney disease. Utilizing the pre-designable and porous properties of covalent organic frameworks (COFs) is an innovative way to address the demand for high-performance NH3 sensing. However, COF particles frequently encounter aggregation, low conductivity, and mechanical rigidity, reducing the effectiveness of portable NH3 detection. To overcome these challenges, we propose a practical approach using polyvinyl alcohol-carrageenan (κPVA) as a template for in the situ growth of two-dimensional COF film and particles to produce a flexible hydrogel gas sensor (COF/κPVA). The synergistic effect of COF and κPVA enhances the gas sensing, water retention, and mechanical properties. The COF/κPVA hydrogel shows a 54.4% response to 1 ppm NH3 with a root mean square error of less than 5% and full recovery compared to the low response and no recovery of bare κPVA. Owing to the dual effects of the COF film and the particles anchoring the water molecules, the COF/κPVA hydrogel remained stable after 70 h in atmospheric conditions, in contrast, the bare κPVA hydrogel was completely dehydrated. Our work might pave the way for highly sensitive hydrogel gas sensors, which have intriguing applications in flexible electronic devices for gas sensing.

BRD4 plays an antiaging role in the senescence of renal tubular epithelial cells.

Age-related kidney failure is often induced by a decrease in the bioavailability of tubular epithelial cells in elderly chronic kidney disease (CKD) patients. BRD4, an epigenetic regulator and a member of the bromodomain and extraterminal (BET) protein family, acts as a super-enhancer (SE) organizing and regulating genes expression during embryogenesis and cancer development. But the physiological function of BRD4 in normal cells has been less studied. This study aimed to research certain biological roles of BRD4 in the process of normal cell aging and discuss the potential mechanisms. In this study, we investigated the biological functions of BRD4 proteins in the aging of renal tubular cells. At first, we used a D-galactose (D-gal) and BRD4 inhibitor (Abbv-075) to replicate kidney senescence in vivo. D-gal and Abbv-075 were then used to measure the aging-related changes, such as changes in cell cycle, β-galactosidase activity, cell migration, and p16 protein expression in vitro. At last, we knocked down and over-expressed BRD4 to investigate the aging-related physiological phenomena in renal tubular cells. In vitro, D-gal treatment induced noticeable aging-related changes such as inducing cell apoptosis and cell cycle arrest, increasing β-galactosidase activity as well as up-regulating p16 protein expression in primary human tubular epithelial cells. In the aging mice model, D-gal significantly induced renal function impairment and attenuated BRD4 protein expression. At the same time, the BRD4 inhibitor (Abbv-075) was able to mimic D-gal-induced cell senescence. In vivo, Abbv-075 also decreased kidney function and up-regulated p21 protein expression. When we knocked down the expression of BRD4, the senescence-associated β-galactosidase (SA-β-gal) activity increased dramatically, cell migration was inhibited, and the proportion of cells in the G0/G1 phase increased. Additionally, the knockdown also promoted the expression of the senescence-related proteins p16. When the renal tubular cells were overexpressed with BRD4, cell aging-related indicators were reversed in the D-gal-induced cell aging model. BRD4 appears to have an active role in the aging of renal tubular cells in vivo and in vitro. The findings also suggest that BRD4 inhibitors have potential nephrotoxic effects for oncology treatment. BRD4 may be a potential therapeutic biomarker and drug target for aging-related kidney diseases, which warrants additional studies.

Amino-functionalized MOF-based fluorescent sensor for efficient detection of 3-nitrotyrosine in serum

Sensitive and rapid detection of biomarker is an important but challenging task for diagnosis, treatment and monitoring of diseases. Herein, this study reports an amino-functionalized MOF-based fluorescent sensor (FJU-40-NH2), which is selectively and significantly quenched by 3-nitrotyrosine (3-NT), a key biomarker of kidney disease, featuring ultra-fast detection time (<15 s), high quenching efficiency, superior anti-interference capability and low detection limit (0.55 µM). More importantly, this fluorescent sensor is successfully employed for the determination of 3-NT in both healthy and acute kidney injury mice serums with recoveries of 96.3–103.3 %. The fluorescence quenching mechanism is attributed to the synergistic effect of the photoinduced electron transfer and internal filtration effect, as confirmed by UV–vis spectra and theoretical calculations.

Serum angiopoietin-2: a promising biomarker for early diabetic kidney disease in children and adolescents with type 1 diabetes

Albuminuria has been considered the golden standard biomarker for diabetic kidney disease (DKD), but appears once significant kidney damage has already occurred. Angiopoietin-2 (Angpt-2) has been implicated in the development and progression of DKD in adults. We aimed to explore the association of serum Angpt-2 levels with DKD in children and adolescents with type 1 diabetes mellitus (T1DM) of short duration (3–5 years) and to evaluate the predictive power of serum Angpt-2 in the early detection of DKD prior to the microalbuminuric phase. The current cross-sectional study included 90 children divided into three age and sex-matched groups based on urinary albumin-to-creatinine ratio (UACR): microalbuminuric diabetic group (n = 30), non-albuminuric diabetic group (n = 30), and control group (n = 30). All participants were subjected to anthropometric measurements, serum Angpt-2 and fasting lipid profile (total cholesterol, triglycerides, LDL-C, HDL-C, and Non-HDL-C) assessment. Glomerular filtration rate was estimated based on serum creatinine (eGFR-Cr). Higher serum Angpt-2 levels were detected in both diabetic groups compared to controls and in microalbuminuric compared to non-albuminuric diabetic group. There was no detected significant difference in eGFR-Cr values across the study groups. Serum Angpt-2 was positively correlated with triglycerides, LDL, Non-HDL-C, HbA1c, and UACR, while UACR, HbA1c, and Non-HDL-C were independent predictors for serum Angpt-2. Serum Angpt-2 at level of 137.4 ng/L could discriminate between microalbuminuric and non-albuminuric diabetic groups with AUC = 0.960 and at level of 115.95 ng/L could discriminate between the non-albuminuric diabetic group and controls with AUC = 0.976.Conclusion: Serum Angpt-2 is a promising potent biomarker for the detection of early stage of DKD in childhood T1DM before albuminuria emerges.What is Known?• Urine albumin-to-creatinine ratio (UACR) and glomerular filtration rate (GFR) are the golden standard but late biomarkers for DKD.• Angiopoietin-2 has been implicated in the development and progression of DKD in adults with diabetes, but has not been explored in T1DM children with DKD.What is New?• Higher serum angiopoietin-2 was detected in diabetic groups compared to controls and in microalbuminuric compared to non-albuminuric group.• Angiopoietin-2 correlated positively with triglycerides, LDL, Non-HDL-C, HbA1c, and UACR.• Serum angiopoietin-2 is a promising early diagnostic biomarker for DKD in children with T1DM.

412-P: Kidney Shape in Magnetic Resonance Imaging—A Possible Biomarker for Diabetic Kidney Disease?

412-P: Kidney Shape in Magnetic Resonance Imaging—A Possible Biomarker for Diabetic Kidney Disease?

Targeting pyruvate kinase M2 for the treatment of kidney disease.

Pyruvate kinase M2 (PKM2), a rate limiting enzyme in glycolysis, is a cellular regulator that has received extensive attention and regards as a metabolic regulator of cellular metabolism and energy. Kidney is a highly metabolically active organ, and glycolysis is the important energy resource for kidney. The accumulated evidences indicates that the enzymatic activity of PKM2 is disturbed in kidney disease progression and treatment, especially diabetic kidney disease and acute kidney injury. Modulating PKM2 post-translational modification determines its enzymatic activity and nuclear translocation that serves as an important interventional approach to regulate PKM2. Emerging evidences show that PKM2 and its post-translational modification participate in kidney disease progression and treatment through modulating metabolism regulation, podocyte injury, fibroblast activation and proliferation, macrophage polarization, and T cell regulation. Interestingly, PKM2 activators (TEPP-46, DASA-58, mitapivat, and TP-1454) and PKM2 inhibitors (shikonin, alkannin, compound 3k and compound 3h) have exhibited potential therapeutic property in kidney disease, which indicates the pleiotropic effects of PKM2 in kidney. In the future, the deep investigation of PKM2 pleiotropic effects in kidney is urgently needed to determine the therapeutic effect of PKM2 activator/inhibitor to benefit patients. The information in this review highlights that PKM2 functions as a potential biomarker and therapeutic target for kidney diseases.

Urinary complement biomarkers in immune-mediated kidney diseases.

The complement system, an important part of the innate system, is known to play a central role in many immune mediated kidney diseases. All parts of the complement system including the classical, alternative, and mannose-binding lectin pathways have been implicated in complement-mediated kidney injury. Although complement components are thought to be mainly synthesized in the liver and activated in the circulation, emerging data suggest that complement is synthesized and activated inside the kidney leading to direct injury. Urinary complement biomarkers are likely a better reflection of inflammation within the kidneys as compared to traditional serum complement biomarkers which may be influenced by systemic inflammation. In addition, urinary complement biomarkers have the advantage of being non-invasive and easily accessible. With the rise of therapies targeting the complement pathways, there is a critical need to better understand the role of complement in kidney diseases and to develop reliable and non-invasive biomarkers to assess disease activity, predict treatment response and guide therapeutic interventions. In this review, we summarized the current knowledge on urinary complement biomarkers of kidney diseases due to immune complex deposition (lupus nephritis, primary membranous nephropathy, IgA nephropathy) and due to activation of the alternative pathway (C3 glomerulopathy, thrombotic microangiography, ANCA-associated vasculitis). We also address the limitations of current research and propose future directions for the discovery of urinary complement biomarkers.

Rapid Conductometric Sensing of Chronic Kidney Disease Biomarkers: Specific and Precise Detection of Creatinine and Cystatin C in Artificial Saliva

AbstractChronic kidney disease (CKD) has asymptomatic early stages, whereby early detection is crucial to prevent its complications and progression. Creatinine and cystatin C (cysC) assays are known for assessing kidney function but there are limited point‐of‐care diagnostics which are rapid, precise, and easy to use. Here, high resistivity silicon conductometric sensors for detection of creatinine and cysC with a 10 min sample incubation is introduced. The sensors provide resistance‐based signals that can be quantified and measured wirelessly. The sensors successfully detect creatinine and cysC in both phosphate buffer saline (PBS) and artificial saliva in the nanomolar range, being able to distinguish their critical concentrations at 8.8 and 20 nm, respectively, for diagnosis of early stage of CKD. The detection limit for both creatinine and cysC is determined as 0.01 nm which is more than 500× and 1000× times lower than critical concentrations for the two biomarkers, respectively. Finally, these sensors are incorporated into a battery‐free, miniaturized electronic device for wireless biomarker detection as a proof‐of‐concept demonstration of a point‐of‐care tool for assessing kidney functionality.

Modified Citrus Pectin (MCP) Confers a Renoprotective Effect on Early-Stage Nephropathy in Type-2 Diabetic Mice.

Diabetic nephropathy (DN) is a significant global health concern with a high morbidity rate. Accumulating evidence reveals that Galectin-3 (Gal-3), a β-galactoside-binding lectin, is a biomarker in kidney diseases. Our study aimed to assess the advantageous impacts of modified citrus pectin (MCP) as an alternative therapeutic strategy for the initial and ongoing progression of DN in mice with type 2 diabetes mellitus (T2DM). The animal model has been split into four groups: control group, T2DM group (mice received intraperitoneal injections of nicotinamide (NA) and streptozotocin (STZ), T2DM+MCP group (mice received 100 mg/kg/day MCP following T2DM induction), and MCP group (mice received 100 mg/kg/day). After 4 weeks, kidney weight, blood glucose level, serum kidney function tests, histopathological structure alterations, oxidative stress, inflammation, apoptosis, and fibrosis parameters were determined in renal tissues. Our findings demonstrated that MCP treatment reduced blood glucose levels, renal histological damage, and restored kidney weight and kidney function tests. Additionally, MCP reduced malondialdehyde level and restored glutathione level, and catalase activity. MCP demonstrated a notable reduction in inflammatory and apoptosis mediators TNF-α, iNOS, TGF-βRII and caspase-3. Overall, MCP could alleviate renal injury in an experimental model of DN by suppressing renal oxidative stress, inflammation, fibrosis, and apoptosis mediators.

#57 Tubular biomarkers in proteinuric kidney diseases

Abstract Background and Aims Proteinuria is not only a biomarker of chronic kidney disease (CKD) and a risk predictor of adverse outcomes but also a driver of kidney disease progression. The excessive filtration of plasma proteins through the glomerular filtration barrier exerts a toxic effect on tubular cells which ultimately leads to fibrosis and end-stage kidney disease (ESKD. The aim of this study was to assess the levels of various tubular biomarkers in both serum and urine in patients with biopsied glomerular and proteinuric kidney diseases, and correlate them with renal histology and kidney outcomes. Method A retrospective study and observational study was conducted at a single center from January 2016 to December 2021. Serum and urine samples were collected on the same day of renal biopsy and were correlated with histological data from a cohort of 156 patients with proteinuric kidney diseases. Kidney outcomes were registered during a median follow-up period of 26 months and defined as a decrease in eGFR ≥ 40% from baseline or the development of end-stage kidney disease. The following urinary markers, adjusted to urine creatinine, were analyzed: β2-mcg (beta 2 microglobulin), α1-mcg (alpha 1 microglobulin), NGAL (Neutrophil Gelatinase-Associated Lipocalin), uKIM-1 (Kidney Injury Molecule-1), MCP-1 (Monocyte Chemoattractant Protein-1), uDKK-3 (urinary Dickkopf-3), and uUMOD (uromodulin). Serum markers sKIM-1 and uUMOD were also collected. Results Regarding the etiology of proteinuric kidney disease, the majority corresponded to glomerular disease (68.6%) followed by diabetic kidney disease (12.8%). Higher levels of proteinuria were associated with increased values of β2-mcg and α1-mcg levels and low levels of uUMOD and sUMOD. A significant correlation between the extent of interstitial fibrosis and specific biomarkers was observed: uDKK3 (rho = 0.804, p &amp;lt; 0.001), sKIM-1 (rho = 0.472, p &amp;lt; 0.001), sUMOD (rho = −0.370, p &amp;lt; 0.001), uUMOD (rho = −0.317, p &amp;lt; 0.001), MCP-1 (rho = 0.374, p &amp;lt; 0.001), uKIM-1 (rho = 0.368, p &amp;lt; 0.001), and β2-mcg (rho = 0.392, p &amp;lt; 0.001). Multivariate regression analysis identified uDKK3 as an independent predictor of interstitial fibrosis (Beta 0.728, p &amp;lt; 0.001) adjusted for age, serum creatinine and proteinuria. Elevated levels of MCP-1 and uKIM-1 were associated with a higher risk of significant cortical interstitial inflammation &amp;gt;10% in the logistic regression analysis adjusted for eGFR, proteinuria, and microhematuria: MCP-1 OR = 5.14, 95% CI (2.27−11.62), p &amp;lt; 0.001 and uKIM-1 OR = 1.64, 95% CI (1.05−2.58), p = 0.031. Patients with higher tertiles of β2mcg, MCP1, uDKK3, and KIM1s, and lower tertiles of uUMOD and sUMOD experienced a significantly reduced renal event-free survival in the analysis of Kaplan-Meier model (Fig.). Moreover, of all the evaluated markers, uDKK3 was identified as the best predictor of renal events [HR = 1.03, 95% CI (1.01−1.06), p = 0.008], independently of age, baseline eGFR, proteinuria, and the extent of interstitial fibrosis at the time of renal biopsy. Conclusion Tubular biomarkers may offer prognostic value in proteinuric kidney diseases, particularly uDKK3, exhibiting a notable correlation with interstitial fibrosis and serving as a potential predictor of CKD progression.

#1466 Age- and kidney function-dependent life expectancy of patients after COVID-19

Abstract Background and Aims The life expectancy among survivors of SARS-CoV-2 infection may be influenced by age, pre-existing health conditions, and the severity of the initial infection. This study aimed to investigate the life expectancy in patients that survived the acute phase of COVID-19 and the association with kidney function. Method Survival data of 649 unvaccinated patients from our previous study “Prospective Validation of a Proteomic Urine Test for Early and Accurate Prognosis of Critical Course Complications in Patients with SARS-CoV-2 Infection” (CRIT-COV-U) [1] was collected until December 2023 in six different countries. These patients had been recruited within the first and second wave in 2020-2021 (mostly infected with wild-type virus) and had survived the acute phase of COVID-19 (CritCov-U study period 21 days after infection). The age dependent death rate in this cohort was compared to age- and sex-matched data of non-SARS-CoV-2 infected patients (n = 5192) extracted from human urinary database. The association of chronic kidney disease biomarker CKD273 with mortality was investigated in both cohorts using Kaplan-Meier analysis. Cox-regression analysis was used to assess variables associated with mortality in the COVID-19 population. Results Mortality was age dependent in both cohorts and markedly higher in patients who had survived the acute phase of COVID-19 in comparison to non-infected individuals (Fig. A-E). Within the first year after infection, mortality was up to 16.5 times higher in patients younger than 50 years in comparison to non-infected controls. Kidney status estimated by the CKD273 score was associated with a poor outcome in both COVID-19 patients and age- and sex-matched controls, respectively (Fig. F-G). The hazard ratio (HR) for mortality during the first year of follow-up for patients with the highest CKD273 score was 12.7, a huge increase in comparison to HR = 6.6 in the matched control group. In the Cox-regression model, CKD273 significantly contributed to death prediction, next to age and COVID-19 severity score at baseline. Conclusion SARS-CoV-2 infection during the first and second wave increased the risk of mortality in the follow-up period beyond the acute phase of the first 21 days. Kidney function appears to be a key element in the underlying molecular pathology of this process, indicating the importance of kidney-protective measures. Of note, among those who survived the acute phase of COVID-19, increase in mortality within the first year after infection compared to a non-infected control group was highest in the younger individuals.