Progression Of Kidney Disease Research Articles

Unveiling Kidney Disease Progression in Autosomal Recessive Polycystic Kidney Disease with Hypertension: Insights from the SS-PCK Rat Model

Unveiling Kidney Disease Progression in Autosomal Recessive Polycystic Kidney Disease with Hypertension: Insights from the SS-PCK Rat Model

Apigenin inhibits epithelial mesenchymal transition in renal tubular epithelial cells through PI3K/AKT and NF-κB pathways for treating renal fibrosis

Renal fibrosis is a crucial factor in the progression of chronic kidney diseases. Previous studies have suggested that apigenin (API) has potential in ameliorating renal fibrosis, but its therapeutic mechanism remains unclear. This study aims to elucidate the mechanisms by which API treats renal fibrosis using network pharmacology and experimental validation. Initially, we used the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database and GeneCards database to identify molecular targets of API and associated genes. Next, we constructed a network of API-renal fibrosis targets, followed by protein–protein interaction (PPI) analysis. Subsequent analyses, such as Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, were performed using the Database for Annotation, Visualization, and Integrated Discovery (DAVID). We also performed molecular docking studies to explore API’s interactions with key proteins. To validate API’s mechanism in treating renal fibrosis, we used a Human Kidney-2 (HK-2) cell model of epithelial-mesenchymal transition (EMT) induced by transforming growth factor-β1 (TGF-β1). We identified 77 API target genes, 8434 renal fibrosis target genes, and 64 intersection genes, which were primarily enriched in nuclear factor kappa-B (NF-κB) and Phosphatidylinositide 3-kinases/protein kinase B (PI3K-AKT) pathways. API significantly inhibited EMT in TGF-β1-induced HK-2 cells by regulating the expression of α-Smooth muscle actin (α-SMA) and E-cadherin and suppressing the protein expression of p-PI3K, p-AKT, and p-P65, which are related to the PI3K-AKT and NF-κB pathways. However, co-administration of the PI3K agonist 740Y-P counteracted API’s inhibitory effects on these protein expressions. In summary, these findings highlight API’s therapeutic potential in treating renal fibrosis by modulating EMT in renal tubular epithelial cells via the PI3K-AKT and NF-κB pathways.

Efficacy of oral AB070597 for the management of chronic kidney disease in cats: a prospective, randomised, controlled parallel-group study.

It has been reported that AB070597, which contains amino acids and peptides, may prevent the progression of chronic kidney disease (CKD) in cats. The aim of this study was to evaluate the effect of AB070597 on CKD in International Renal Interest Society (IRIS) stage 2 or 3 cats compared with a placebo. A prospective, randomised, controlled parallel-group study was conducted on 35 cats with CKD. The cats were randomly allocated to receive 300 mg of AB070597 or placebo for 180 days, and cats were re-examined every 30 days. Changes in the results were compared from baseline to endpoint in each group, and the efficacy of AB070597 in cats with CKD was assessed. A total of 35 cats met the inclusion criteria, of which 20 received AB070597 and 15 received a placebo. Blood urea nitrogen (BUN), creatinine (Cre) and phosphorus levels increased significantly in the placebo group at 180 days compared with those at baseline, 30 days and 60 days, whereas these values were not significantly changed in the AB070597 group during the study period. The IRIS stage was also stable in cats with AB070597 from the baseline to the end of the study, whereas the IRIS stage progressed from stage 2 to stage 3 in 26% of cats with placebo. Body weight did not change significantly in either group. The administration of AB070597 in cats with CKD may be effective in preventing CKD progression.

Mapping Progression of Diabetic Kidney Disease (DKD) in Renin Adeno-Associated Virus (AAV) UNx db/db Mice Utilizing Time-Series RNA Sequencing

Mapping Progression of Diabetic Kidney Disease (DKD) in Renin Adeno-Associated Virus (AAV) UNx db/db Mice Utilizing Time-Series RNA Sequencing

Cytochrome P450 Is a Metabolic Regulator of Diabetic Kidney Disease (DKD) Progression

Cytochrome P450 Is a Metabolic Regulator of Diabetic Kidney Disease (DKD) Progression

Quantifying preserved renal volume and function in patients undergoing standard partial nephrectomy vs. tumor enucleation for localized renal tumors

IntroductionRenal parenchymal volume loss from standard partial nephrectomy (SPN) is a significant prognosticator for postoperative renal function. Tumor enucleation (TE) minimizes parenchymal loss compared to SPN. Little is known regarding discrete changes in renal function associated with volume loss. We sought to quantify the differences between SPN and TE in preserving parenchymal volume and estimated glomerular filtration rate (eGFR). MethodsWe identified 420 patients who underwent robotic partial nephrectomy (SPN or TE) at our tertiary care center from 2009 to 2022. Parenchymal volumes were calculated using TeraRecon 3D reconstruction software from axial imaging performed preoperatively and within 6 months postoperatively. Renal volume preserved and renal function were evaluated with multivariable linear and logistic regression models. ResultsAt 1 year, eGFR was 7% lower in patients undergoing SPN compared to TE (P < 0.01). Across both SPN and TE, only volume of preserved parenchyma was predictive of eGFR and chronic kidney disease (CKD) progression (both P < 0.01). TE preserved more healthy parenchymal volume compared to SPN (median percentage 97.6% vs 89.2%; P < 0.001). Each 1% of volumetric loss corresponded to a 0.35% decrease in eGFR at 1 year postoperatively (P < 0.01). ConclusionsVolume of preserved renal parenchyma was the strongest factor associated with preserved eGFR and reduced odds of CKD progression. TE preserved more parenchyma than SPN, which translated to higher eGFR preservation at 1 year postoperatively.

Projecting the Population Level Burden of CKD Progression According to Urine Albumin-to-Creatinine Ratio Categories

IntroductionUrinary albumin-creatinine ratio (uACR) is an independent predictor of chronic kidney disease (CKD) progression, however there is limited evidence on the burden of CKD according to uACR categories at a population level. This study estimates future clinical and financial burden of CKD according to uACR categories using the Inside CKD microsimulation. MethodsThe Inside CKD model is an individual patient level microsimulation that emulates national populations based on demographic, epidemiological and economic data. The analysis estimates clinical and economic outcomes over time according to KDIGO uACR categories (A1–A3) at a population level for 31 countries and regions. ResultsCKD populations (diagnosed and undiagnosed individuals, stages G3-5) were projected to be predominantly within uACR categories A1 and A2 in 2022. Projected cumulative incidence of CKD stage transitions (disease progression) and cardio-renal complications (heart failure, myocardial infarction, stroke, and all-cause mortality) occurred mostly in uACR categories A1 and A2 between 2022–2027. Patients in uACR categories A1 and A2, who represent the largest proportion of patients with CKD, were projected to incur most of the healthcare costs associated with CKD management and cardio-renal complications for the diagnosed population (prevalence 2027). ConclusionThis study highlights the disproportionate population-level clinical and economic burden associated with individuals within KDIGO uACR categories A1 and A2, who represent most of the CKD population. This awareness will help healthcare decision makers to appropriately allocate resource and interventions to the CKD population, including those with mildly to moderately increased albuminuria, to reduce clinical and economic burden associated with CKD.

Association of Podocyte Injury with Kidney Histopathologic Lesions and Disease Progression

Association of Podocyte Injury with Kidney Histopathologic Lesions and Disease Progression

Unveiling the role of transgelin as a prognostic and therapeutic target in kidney fibrosis via a proteomic approach

Chronic kidney disease (CKD) progression involves tubulointerstitial fibrosis, a process characterized by excessive extracellular matrix accumulation. To identify potential biomarkers for kidney fibrosis, we performed mass spectrometry-based proteomic profiling of human kidney tubular epithelial cells and kidney tissue from a 5/6 nephrectomy rat model. Multidisciplinary analysis across kidney fibrosis models revealed 351 differentially expressed proteins associated with kidney fibrosis, and they were enriched in processes related to the extracellular matrix, kidney aging, and mitochondrial functions. Network analysis of the selected proteins revealed five crucial proteins, of which transgelin emerged as a candidate protein that interacts with known fibrosis-related proteins. Concordantly, the gene expression of transgelin in the kidney tissue from the 5/6 nephrectomy model was elevated. Transgelin expression in kidney tissue gradually increased from intermediate to advanced fibrosis stages in 5/6 Nx rats and mice with unilateral ureteral obstruction. Subsequent validation in kidney tissue and urine samples from patients with CKD confirmed the upregulation of transgelin, particularly under advanced disease stages. Moreover, we investigated whether blocking TAGLN ameliorated kidney fibrosis and reduced reactive oxygen species levels in cellular models. In conclusion, our proteomic approach identified TAGLN as a potential noninvasive biomarker and therapeutic target for CKD-associated kidney fibrosis, suggesting its role in modulating mitochondrial dysfunction and oxidative stress responses.

PPP2R2B Variant Reduces Protein Phosphatase 2A (PP2A) Complexity and Worsens Diabetic Kidney Disease (DKD) Progression

PPP2R2B Variant Reduces Protein Phosphatase 2A (PP2A) Complexity and Worsens Diabetic Kidney Disease (DKD) Progression

Impact of Carbamylation on the Association of Glycated Albumin and Diabetic Kidney Disease (DKD) Progression

Impact of Carbamylation on the Association of Glycated Albumin and Diabetic Kidney Disease (DKD) Progression

Mesoporous activated carbon derived from Chinese herbal medicine residues for hemoperfusion removal of uremia toxins from progressive chronic kidney diseases patients

Hemoperfusion is one of the most important therapies for progressive chronic kidney disease (CKD) and is effective at removing toxins from the blood. Increasing the efficiency of adsorbents applied in hemoperfusion is crucial. In the present study, shell of areca nut, one of the most common waste Chinese herb medicine residue with a porous structure was carbonized and activated at different temperatures to obtain two kinds of porous materials. The biocompatibility of the as-prepared porous materials was estimated via a hemolytic test, and the removal efficiency of the materials toward toxins was tested via an adsorption experiment in solution and blood samples from CKD patients, simulated hemoperfusion and in vivo hemoperfusion. After 4 h of adsorption, free and protein-bound toxins in solution were efficiently removed by the prepared porous materials, and the removal efficiency was better than that of commonly used hemoperfutor adsorbents. Most of the tested toxins can be removed from CKD blood samples and simulated hemoperfusion samples. Blood uremic toxins from CKD mice were also efficiently and safely removed after in vivo hemoperfusion using the as-prepared adsorbent. This work highlights promising adsorbents for hemoperfusion that could increase the therapeutic efficacy in patients with progressive CKD.

MRI-Based Kidney Volume and Resistive Index in Patients with Progressive vs. Stable Diabetic Kidney Disease (DKD)

MRI-Based Kidney Volume and Resistive Index in Patients with Progressive vs. Stable Diabetic Kidney Disease (DKD)

Glucagon-like peptide-1 receptor agonists and kidney outcomes.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have gained increasing attention for their potential benefits in people with type 2 diabetes mellitus (T2DM) with chronic kidney disease (CKD). Most supportive evidence of a kidney-protective effect of the GLP-1RA class of medications has been derived from kidney-related outcomes reported from cardiovascular outcome trials (CVOTs). GLP-1RAs have been shown to reduce albuminuria, mitigate cardiovascular risk, and possibly attenuate estimated glomerular filtration rate (eGFR) decline. The kidney-protective effects of GLP-1RAs are thought to be attributed to their anti-inflammatory, antioxidant, and vasodilatory properties. Despite these promising findings, the use of GLP-RAs has yet to be definitively shown to slow progression to chronic kidney failure in people with T2DM. The Research Study to See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease (FLOW trial) is the first major trial assessing the potential of a GLP-1RA to slow progression of kidney disease in people with established CKD to clinically important kidney end points. On March 5, 2024, the top line result from FLOW was announced with semaglutide 1.0 mg being reported to reduce the primary end point of the trial by a significant 24% compared with placebo. Here, we summarize the kidney outcomes reported from CVOTs for the GLP-1RA class of medication and briefly describe kidney outcomes from other major GLP-1RAs trials. We also discuss a potential role of the dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, tirzepatide, as a kidney-protective agent.

Combination of Renin AAV and L-NAME Accelerates the Progression of Kidney Disease in Diabetic Mice

Combination of Renin AAV and L-NAME Accelerates the Progression of Kidney Disease in Diabetic Mice

Urine Biomarkers for Diabetic Kidney Disease Progression

Urine Biomarkers for Diabetic Kidney Disease Progression

Identification and Validation of Pivotal Genes Driving Diabetic Kidney Disease Progression through Weighted Gene Co-Expression Network Analysis

Identification and Validation of Pivotal Genes Driving Diabetic Kidney Disease Progression through Weighted Gene Co-Expression Network Analysis

Value of Post-AKI Protein-to-Creatinine Ratio (PCR) in Discriminating Risk of Kidney Disease Progression: Insights from the CRIC Study

Value of Post-AKI Protein-to-Creatinine Ratio (PCR) in Discriminating Risk of Kidney Disease Progression: Insights from the CRIC Study

Effects of Type of Protein Intake on Risk of Kidney Disease Progression among Patients with Nondialysis-Dependent CKD: A Systematic Review

Effects of Type of Protein Intake on Risk of Kidney Disease Progression among Patients with Nondialysis-Dependent CKD: A Systematic Review

Dapagliflozin in Addition to Ramipril Ameliorates Kidney Disease Progression in Mice with Alport Syndrome

Dapagliflozin in Addition to Ramipril Ameliorates Kidney Disease Progression in Mice with Alport Syndrome