scholarly journals Glomerular pathology and the progression of chronic kidney disease

2016 ◽  
Vol 310 (11) ◽  
pp. F1385-F1388 ◽  
Author(s):  
Kevin V. Lemley
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Glomerular Sclerosis ◽  
Structural Studies ◽  
Detailed Model ◽  
Viable Cells ◽  
Podocyte Detachment ◽  
Current Therapies ◽  
Novel Therapeutic Strategies ◽  
Glomerular Capillary Hypertension

Structural studies of the glomerulus, largely undertaken in animal models, have informed our understanding of the progression of chronic kidney disease (CKD) for decades. A fundamental tenet of that understanding is that a loss of podocytes underlies progression in many or most cases of progressive CKD. Recent attempts have been made to reconcile earlier findings from glomerular physiology (the primacy of glomerular capillary hypertension in causation of secondary glomerular sclerosis) with structural findings and have suggested a more detailed model of the mechanisms underlying podocyte detachment as viable cells. A new appreciation of the main locus of mechanical challenges to the podocyte (in the filtration slit) may both explain the renoprotective action of some current therapies and help to suggest novel therapeutic strategies.

scholarly journals Impacts of Indoxyl Sulfate and p-Cresol Sulfate on Chronic Kidney Disease and Mitigating Effects of AST-120

Toxins ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 367 ◽  
Author(s):  
Wen-Chih Liu ◽  
Yasuhiko Tomino ◽  
Kuo-Cheng Lu
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Large Scale ◽  
Interstitial Fibrosis ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Renal Diseases ◽  
Glomerular Sclerosis ◽  
Inflammatory Reactions

Uremic toxins, such as indoxyl sulfate (IS) and p-cresol, or p-cresyl sulfate (PCS), are markedly accumulated in the organs of chronic kidney disease (CKD) patients. These toxins can induce inflammatory reactions and enhance oxidative stress, prompting glomerular sclerosis and interstitial fibrosis, to aggravate the decline of renal function. Consequently, uremic toxins play an important role in the worsening of renal and cardiovascular functions. Furthermore, they destroy the quantity and quality of bone. Oral sorbent AST-120 reduces serum levels of uremic toxins in CKD patients by adsorbing the precursors of IS and PCS generated by amino acid metabolism in the intestine. Accordingly, AST-120 decreases the serum IS levels and reduces the production of reactive oxygen species by endothelial cells, to impede the subsequent oxidative stress. This slows the progression of cardiovascular and renal diseases and improves bone metabolism in CKD patients. Although large-scale studies showed no obvious benefits from adding AST-120 to the standard therapy for CKD patients, subsequent sporadic studies may support its use. This article summarizes the mechanisms of the uremic toxins, IS, and PCS, and discusses the multiple effects of AST-120 in CKD patients.

P0752THE EXPRESSION AND DIAGNOSTIC VALUE OF URINE ANGIOTENSINOGEN IN CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Qiuyan Huang ◽  
Junzhe Chen ◽  
Ying Tang ◽  
Yanchun Xu ◽  
Anping Xu
Keyword(s):  
Chronic Kidney Disease ◽  
Regression Analysis ◽  
Kidney Disease ◽  
Linear Regression ◽  
Predictive Value ◽  
Linear Regression Analysis ◽  
Diagnostic Value ◽  
Glomerular Sclerosis ◽  
Ckd Stage ◽  
Stage 1

Abstract Background and Aims This article aims to detect the expression of urine angiotensinogen (uAGT) in patients with chronic kidney disease (CKD) and its correlation with clinical and renal pathology. Method Patients who diagnosed with CKD and undergoing renal biopsy for the first visit to Sun Yat-sen Memorial Hospital from March 1st ,2018 to October 1st, 2019 were enrolled. First morning urine samples from CKD patients before renal biopsy and healthy volunteers as controls were collected during the same period. These samples were tested for uAGT by ELISA. Linear regression analysis was used to explore the correlation between uAGT and clinical indicators as well as renal pathology in CKD patients. The receiver operating curve (ROC curve) was used to explore the diagnostic value of uAGT for CKD stage 3 or above and glomerular sclerosis ratio>50%. Results A total of 133 CKD patients with 59 (44.4%) in stage 1, 31 (23.3%) in CKD stage 2, 17 (12.8%) in stage 3, 17 (12.8%) in stage 4 and 9 (6.7%) in stage 5 were included in our study. At the same time, 20 healthy volunteers were included as control. uAGT levels of CKD patients were significantly higher than healthy controls(275.0 vs 774.2,P<0.001). Compared with CKD stage 1-2 patients, uAGT levels in patients with stage CKD 3 or above were significantly increased, and the difference was statistically significant (P<0.001) (Table 1). The result of multivariate linear regression analysis showed that uAGT levels in CKD patients were positively correlated with 24h urine protein (beta = 0.193, P = 0.012) and negatively correlated with eGFR (beta = -0.489, P<0.001) (Table 2). We also demonstrated that uAGT was positively correlated with the ratio of glomerular sclerosis(P = 0.003) (Table 3). Our results showed that the area under the curve (AUC)of uAGT for the diagnosis of renal function with CKD stage 3 or above was 0.789 (Figure 1) with the cut-off value was1959.9pg/ml. The sensitivity and specificity were 51.2% and 97.3% respectively, Furthermore, the positive predictive value (PPV) was 88.0% and negative predictive value (NPV) was 82.95%.The AUC of uAGT for the diagnosis of renal pathological glomerular sclerosis ratio>50% was 0.677 (Figure 2).The cut-off value of uAGT was 2131.8pg/ml.The sensitivity and specificity were 50% and 89.5% respectively. Meanwhile, the PPV was 41.67% and the NPV was 92.25%. Conclusion uAGT was significantly increased in CKD patients, which is closely related with the urinary protein, eGFR, and renal pathology.The specific cut-off value of uAGT can be used as a predictive indicator of advanced CKD stage and severe glomerular sclerosis.

Fructose, but not dextrose, accelerates the progression of chronic kidney disease

2007 ◽  
Vol 293 (4) ◽  
pp. F1256-F1261 ◽  
Author(s):  
Michael S. Gersch ◽  
Wei Mu ◽  
Pietro Cirillo ◽  
Sirirat Reungjui ◽  
Li Zhang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Tissue Homogenate ◽  
Glomerular Sclerosis ◽  
Sprague Dawley ◽  
Tubular Atrophy ◽  
High Fructose Diet ◽  
The Metabolic Syndrome ◽  
High Fructose

The metabolic syndrome has recently been recognized as a risk factor for kidney disease, but the mechanisms mediating this risk remain unclear. High fructose consumption by animals produces a model of the metabolic syndrome with hypertension, hyperlipidemia, and insulin resistance. The present study was conducted to test the hypothesis that consumption of a high-fructose diet could accelerate the progression of chronic kidney disease. Three groups of 14 male Sprague-Dawley rats were pair fed a specialized diet containing 60% fructose (FRU) or 60% dextrose (DEX) or standard rat chow (CON). After the animals were fed their assigned diet for 6 wk, five-sixths nephrectomy was performed, and the assigned diet was continued for 11 wk. Proteinuria was significantly increased and creatinine clearance was decreased in the FRU group compared with the CON and DEX groups, and blood urea nitrogen was higher in the FRU group than in the CON and DEX groups. Kidneys from the FRU group were markedly larger than kidneys from the CON and DEX groups. Glomerular sclerosis, tubular atrophy, tubular dilatation, and cellular infiltration appeared markedly worse in kidneys from the FRU group than in kidneys from the DEX and CON groups. Monocyte chemoattractant protein-1 (MCP-1) was measured in renal tissue homogenate and found to be increased in the FRU group. In vitro studies were conducted to determine the mechanism for increased renal MCP-1, and fructose stimulation of proximal tubular cells resulted in production of MCP-1. In conclusion, consumption of a high-fructose diet greatly accelerates progression of chronic kidney disease in the rat remnant kidney model.

Colchicine attenuates renal injury in a model of hypertensive chronic kidney disease

2013 ◽  
Vol 305 (10) ◽  
pp. F1466-F1476 ◽  
Author(s):  
Tianxiu Guan ◽  
Bo Gao ◽  
Guang Chen ◽  
Xing Chen ◽  
Melissa Janssen ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Renal Fibrosis ◽  
Interstitial Fibrosis ◽  
Mechanical Strain ◽  
Tissue Growth ◽  
Glomerular Sclerosis ◽  
Glomerular Mesangial Cells ◽  
Rhoa Activation ◽  
Microtubule Disruption

Hypertension is a risk factor for chronic kidney disease, particularly when associated with impaired renal autoregulation and thereby increased intraglomerular pressure (Pgc). Elevated Pgc can be modeled in vitro by exposing glomerular mesangial cells to mechanical strain. We previously showed that RhoA mediates strain-induced matrix production. Here, we show that RhoA activation is dependent on an intact microtubule network. Upregulation of the profibrotic cytokine connective tissue growth factor (CTGF) by mechanical strain is dependent on RhoA activation and inhibited by microtubule disruption. We tested the effects of the microtubule depolymerizing agent colchicine in 5/6 nephrectomized rats, a model of chronic kidney disease driven by elevated Pgc. Colchicine inhibited glomerular RhoA activation and attenuated both glomerular sclerosis and interstitial fibrosis without affecting systemic blood pressure. Upregulation of the matrix proteins collagen I and fibronectin, as well as CTGF, was attenuated by colchicine. Activity of the profibrotic cytokine TGF-β, as assessed by Smad3 phosphorylation, was also inhibited by colchicine. Microtubule disruption significantly decreased renal infiltration of lymphocytes and macrophages. Our studies thus indicate that colchicine modifies hypertensive renal fibrosis. Its protective effects are likely mediated by inhibition of RhoA signaling and renal infiltration of inflammatory cells. Already well-established in clinical practice for other indications, prevention of hypertension-associated renal fibrosis may represent a new potential use for colchicine.

scholarly journals Protective Effects and Metabolic Regulatory Mechanisms of Shenyan Fangshuai Recipe on Chronic Kidney Disease in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Xinqi Deng ◽  
Nan Jiang ◽  
Li Guo ◽  
Chunguo Wang ◽  
Jiaoyan Li ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
High Resolution Mass Spectrometry ◽  
Interstitial Fibrosis ◽  
Scientific Evidence ◽  
Ultra Performance Liquid Chromatography ◽  
Glomerular Sclerosis ◽  
Protective Effects ◽  
Cysteine Biosynthesis ◽  
Clinical Practices

Background. Chronic kidney disease (CKD) is one of the major causes of renal damage. Shenyan Fangshuai Recipe (SFR), a modified prescription of traditional medicine in China, showed potent effects in alleviating edema, proteinuria, and hematuria of CKD in clinical practices. In this study, we aimed to investigate scientific evidence-based efficacy as well as metabolic regulations of SFR in CKD treatment. Materials and Methods. The effect of SFR on CKD was observed in a rat model which is established with oral administration of adenine-ethambutol mixture for 21 days. Further, metabolites in serum were detected and identified with ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Metabolomics study was performed using Ingenuity Pathway Analysis (IPA) software. Results. With H&E staining and Masson’s trichrome, the results showed that chronic kidney damage is significantly rescued with SFR treatment and recovered to an approximately normal condition. Along with 44 differential metabolites discovered, the regulation of SFR on CKD was enriched in glycine biosynthesis I, mitochondrial L-carnitine shuttle pathway, phosphatidylethanolamine biosynthesis III, sphingosine-1-phosphate signaling, L-serine degradation, folate transformations I, noradrenaline and adrenaline degradation, salvage pathways of pyrimidine ribonucleotides, cysteine biosynthesis III (Mammalia), glycine betaine degradation, and cysteine biosynthesis/homocysteine degradation. Further, TGFβ-1 and MMP-9 were observed playing roles in this regulatory process by performing immunohistochemical staining. Conclusion. SFR exerts potent effects of alleviating glomerular sclerosis and interstitial fibrosis in the kidney, mainly via integrated regulations on metabolism and production of homocysteine, L-carnitine, and epinephrine, as well as the expression of TGFβ-1. This study provides evidence for SFR’s protective effects on CKD and reveals the metabolic mechanism behind these benefits for the first time.

Novel therapeutic strategies for cardiorenal protection in patients with type 2 diabetes and chronic kidney disease

2021 ◽  
Vol 19 ◽  
Author(s):  
Panagiotis I. Georgianos ◽  
Stefanos Roumeliotis ◽  
Theodoros Eleftheriadis ◽  
Vassilios Liakopoulos
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Early Stage ◽  
High Risk Population ◽  
Mineralocorticoid Receptor Antagonist ◽  
Novel Therapeutic Strategies ◽  
End Stage

: Type 2 diabetes mellitus (T2DM) is the leading cause of end-stage kidney disease (ESKD) worldwide [1]. The development of chronic kidney disease (CKD) in patients with T2DM substantially increases their risk for cardiovascular (CV) morbidity and mortality [2]. In fact, when T2DM and early-stage CKD co-exist, the risk for CV death is several times higher than the risk for progression to ESKD [3]. Therefore, there is a need for the development of novel therapies to improve CV and kidney failure outcomes in this high-risk population. In this brief perspective, we explore the role of sodium-glucose co-transporter type-2 (SGLT-2) inhibitors and the nonsteroidal mineralocorticoid-receptor-antagonist (MRA) finerenone, in the management of diabetic kidney disease (DKD).

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