scholarly journals Value of ultrasound elastography in the diagnosis of native kidney fibrosis.

2016 ◽  
Vol 18 (3) ◽  
pp. 362 ◽  
Author(s):  
Ileana Peride ◽  
Daniela Rădulescu ◽  
Andrei Niculae ◽  
Vladimir Ene ◽  
Ovidiu Gabriel Bratu ◽  
...  
Keyword(s):  
Shear Wave ◽  
Hepatic Fibrosis ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Ultrasound Elastography ◽  
Normal Kidney ◽  
Chronic Kidney Diseases ◽  
Kidney Fibrosis ◽  
Native Kidney ◽  
Deep Location

In the last decade, ultrasound elastography, an already widely used technique in the diagnosis of hepatic fibrosis, has raised the attention of nephrologists as a potential valuable noninvasive tool for the diagnosis of renal fibrosis. Due to renal deep location and anatomic complexity, the shear wave techniques are the most appropriate elastography methods for exploring native kidneys. Recent research offers promising results, but further larger studies are required for a better standardization of this method and also for establishing reference values of normal kidney elasticity. This article reviews the studies conducted for exploring the native kidney, highlighting the advantages and limitations of ultrasound elastography for assessing fibrosis development in chronic kidney diseases.

scholarly journals Extracellular Matrix in Kidney Fibrosis: More Than Just a Scaffold

2019 ◽  
Vol 67 (9) ◽  
pp. 643-661 ◽  
Author(s):  
Roman David Bülow ◽  
Peter Boor
Keyword(s):  
Extracellular Matrix ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Dynamic Structure ◽  
Renal Diseases ◽  
Chronic Kidney Diseases ◽  
Kidney Fibrosis ◽  
Non Invasive ◽  
Ecm Proteins ◽  
Diagnostic Approaches

Kidney fibrosis is the common histological end-point of progressive, chronic kidney diseases (CKDs) regardless of the underlying etiology. The hallmark of renal fibrosis, similar to all other organs, is pathological deposition of extracellular matrix (ECM). Renal ECM is a complex network of collagens, elastin, and several glycoproteins and proteoglycans forming basal membranes and interstitial space. Several ECM functions beyond providing a scaffold and organ stability are being increasingly recognized, for example, in inflammation. ECM composition is determined by the function of each of the histological compartments of the kidney, that is, glomeruli, tubulo-interstitium, and vessels. Renal ECM is a dynamic structure undergoing remodeling, particularly during fibrosis. From a clinical perspective, ECM proteins are directly involved in several rare renal diseases and indirectly in CKD progression during renal fibrosis. ECM proteins could serve as specific non-invasive biomarkers of fibrosis and scaffolds in regenerative medicine. The gold standard and currently only specific means to measure renal fibrosis is renal biopsy, but new diagnostic approaches are appearing. Here, we discuss the localization, function, and remodeling of major renal ECM components in healthy and diseased, fibrotic kidneys and the potential use of ECM in diagnostics of renal fibrosis and in tissue engineering.

scholarly journals Elastin imaging enables noninvasive staging and treatment monitoring of kidney fibrosis

2019 ◽  
Vol 11 (486) ◽  
pp. eaat4865 ◽  
Author(s):  
Qinxue Sun ◽  
Maike Baues ◽  
Barbara M. Klinkhammer ◽  
Josef Ehling ◽  
Sonja Djudjaj ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Matrix Protein ◽  
Kidney Diseases ◽  
Therapeutic Interventions ◽  
Extracellular Matrix Protein ◽  
Imaging Method ◽  
Chronic Kidney Diseases ◽  
Kidney Fibrosis ◽  
Common Endpoint ◽  
Routine Assessment

Fibrosis is the common endpoint and currently the best predictor of progression of chronic kidney diseases (CKDs). Despite several drawbacks, biopsies remain the only available means to specifically assess the extent of renal fibrosis. Here, we show that molecular imaging of the extracellular matrix protein elastin allows for noninvasive staging and longitudinal monitoring of renal fibrosis. Elastin was hardly expressed in healthy mouse, rat, and human kidneys, whereas it was highly up-regulated in cortical, medullar, and perivascular regions in progressive CKD. Compared to a clinically relevant control contrast agent, the elastin-specific magnetic resonance imaging agent ESMA specifically detected elastin expression in multiple mouse models of renal fibrosis and also in fibrotic human kidneys. Elastin imaging allowed for repetitive and reproducible assessment of renal fibrosis, and it enabled longitudinal monitoring of therapeutic interventions, accurately capturing anti-fibrotic therapy effects. Last, in a model of reversible renal injury, elastin imaging detected ensuing fibrosis not identifiable via routine assessment of kidney function. Elastin imaging thus has the potential to become a noninvasive, specific imaging method to assess renal fibrosis.

Fate alteration of bone marrow-derived macrophages ameliorates kidney fibrosis in murine model of unilateral ureteral obstruction

2018 ◽  
Vol 34 (10) ◽  
pp. 1657-1668 ◽  
Author(s):  
Ying Yang ◽  
Xiaojian Feng ◽  
Xinyan Liu ◽  
Ying Wang ◽  
Min Hu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Ureteral Obstruction ◽  
Renal Fibrosis ◽  
Kidney Diseases ◽  
Unilateral Ureteral Obstruction ◽  
Immunofluorescent Staining ◽  
Enzyme Linked Immunosorbent Assay ◽  
Pathological Feature ◽  
Kidney Fibrosis ◽  
Anti Inflammatory

AbstractBackgroundRenal fibrosis is a key pathological feature and final common pathway leading to end-stage kidney failure in many chronic kidney diseases. Myofibroblast is the master player in renal fibrosis. However, myofibroblasts are heterogeneous. Recent studies show that bone marrow-derived macrophages transform into myofibroblasts by transforming growth factor (TGF)-β-induced macrophage–myofibroblast transition (MMT) in renal fibrosis.MethodsTGF-β signaling was redirected by inhibition of β-catenin/T-cell factor (TCF) to increase β-catenin/Foxo in bone marrow-derived macrophages. A kidney fibrosis model of unilateral ureteral obstruction was performed in EGFP bone marrow chimera mouse. MMT was examined by flow cytometry analysis of GFP+F4/80+α-SMA+ cells from unilateral ureteral obstruction (UUO) kidney, and by immunofluorescent staining of bone marrow-derived macrophages in vitro. Inflammatory and anti-inflammatory cytokines were analysis by enzyme-linked immunosorbent assay.ResultsInhibition of β-catenin/TCF by ICG-001 combined with TGF-β1 treatment increased β-catenin/Foxo1, reduced the MMT and inflammatory cytokine production by bone marrow-derived macrophages, and thereby, reduced kidney fibrosis in the UUO model.ConclusionsOur results demonstrate that diversion of β-catenin from TCF to Foxo1-mediated transcription not only inhibits the β-catenin/TCF-mediated fibrotic effect of TGF-β, but also enhances its anti-inflammatory action, allowing therapeutic use of TGF-β to reduce both inflammation and fibrosis at least partially by changing the fate of bone marrow-derived macrophages.

Single-Nucleus RNA Sequencing Identifies New Classes of Proximal Tubular Epithelial Cells in Kidney Fibrosis

2021 ◽  
pp. ASN.2020081143
Author(s):  
Yueh-An Lu ◽  
Chia-Te Liao ◽  
Rachel Raybould ◽  
Bnar Talabani ◽  
Irina Grigorieva ◽  
...  
Keyword(s):  
Rna Sequencing ◽  
Renal Fibrosis ◽  
High Performance ◽  
Genome Mapping ◽  
Gene Expression Signature ◽  
Metabolic Reprogramming ◽  
Normal Kidney ◽  
Kidney Fibrosis ◽  
Proximal Tubular ◽  
Single Nucleus

Background: Proximal tubular cells (PTCs) are the most abundant cell type in the kidney. PTCs are central to normal kidney function and to regeneration versus organ fibrosis following injury. This study used single-nucleus RNA sequencing (snRNA-seq) to describe the phenotype of PTCs in renal fibrosis. Methods: Kidneys were harvested from naïve mice and from mice with renal fibrosis induced by chronic aristolochic acid administration. Nuclei were isolated using Nuclei EZ Lysis buffer. Libraries were prepared on the 10X platform and snRNA-seq completed using the Illumina NextSeq 550 System. Genome mapping was carried out with high-performance computing. Results: A total of 23,885 nuclei were analysed. PTCs were found in five abundant clusters, mapping to S1, S1-2, S2, S2-cortical S3, and medullary S3 segments. Additional cell clusters ("new PTC clusters") were at low abundance in normal kidney and in increased number in kidneys undergoing regeneration/fibrosis following injury. These clusters exhibited clear molecular phenotypes, permitting labelling as proliferating, New-PT1, New-PT2, and (present only following injury) New-PT3. Each cluster exhibited a unique gene expression signature, including multiple genes previously associated with renal injury response and fibrosis progression. Comprehensive pathway analyses revealed metabolic reprogramming, enrichment of cellular communication and cell motility, and various immune activations in new PTC clusters. In ligand-receptor analysis, new PTC clusters promoted fibrotic signaling to fibroblasts and inflammatory activation to macrophages. Conclusion: These data identify unrecognized PTC phenotype heterogeneity and reveal novel PTCs associated with kidney fibrosis.

scholarly journals SOX9 is required for kidney fibrosis and regulates NAV3 to control renal myofibroblast function in mice and humans

2019 ◽  
Author(s):  
Sayyid Raza ◽  
Elliot Jokl ◽  
James Pritchett ◽  
Katherine Martin ◽  
Kim Su ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Kidney Diseases ◽  
Pharmacological Intervention ◽  
Chronic Kidney Diseases ◽  
Kidney Fibrosis ◽  
Genome Wide ◽  
Common Endpoint ◽  
Vitro Model ◽  
Novel Target

AbstractRenal fibrosis is a common endpoint for many chronic kidney diseases. Extracellular matrix (ECM) from myofibroblasts causes progressive scarring and organ failure. The mechanisms underlying fibrogenesis and how it is sustained are incompletely understood. Here, we show that the transcription factor, Sex determining region Y-box 9 (SOX9), is required for kidney fibrosis. From genome-wide analysis we identify Neuron navigator 3 (NAV3) downstream of SOX9. NAV3 was upregulated in kidney disease in patients and following renal injury in mice colocalised with SOX9. By establishing an in vitro model of renal pericyte transition to myofibroblast we demonstrated that NAV3 is required for multiple aspects of fibrogenesis including actin polymerization linked to cell migration and sustaining SOX9 and active YAP1 levels. In summary, our work discovers novel SOX9-NAV3-YAP1/SOX9 circuitry as a new mechanism to explain the progression of kidney fibrosis and points to NAV3 as a novel target for pharmacological intervention.

scholarly journals Mesenchymal stem cells ameliorate renal fibrosis by galectin-3/Akt/GSK3β/Snail signaling pathway in adenine-induced nephropathy rat

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Huajun Tang ◽  
Peiyue Zhang ◽  
Lianlin Zeng ◽  
Yu Zhao ◽  
Libo Xie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Renal Fibrosis ◽  
Lentiviral Vector ◽  
Kidney Diseases ◽  
Collagen Type I ◽  
Type I ◽  
Chronic Kidney Diseases ◽  
Galectin 3 ◽  
Tgf Β1 ◽  
Sirius Red

Abstract Background Tubulointerstitial fibrosis (TIF) is one of the main pathological features of various progressive renal damages and chronic kidney diseases. Mesenchymal stromal cells (MSCs) have been verified with significant improvement in the therapy of fibrosis diseases, but the mechanism is still unclear. We attempted to explore the new mechanism and therapeutic target of MSCs against renal fibrosis based on renal proteomics. Methods TIF model was induced by adenine gavage. Bone marrow-derived MSCs was injected by tail vein after modeling. Renal function and fibrosis related parameters were assessed by Masson, Sirius red, immunohistochemistry, and western blot. Renal proteomics was analyzed using iTRAQ-based mass spectrometry. Further possible mechanism was explored by transfected galectin-3 gene for knockdown (Gal-3 KD) and overexpression (Gal-3 OE) in HK-2 cells with lentiviral vector. Results MSCs treatment clearly decreased the expression of α-SMA, collagen type I, II, III, TGF-β1, Kim-1, p-Smad2/3, IL-6, IL-1β, and TNFα compared with model rats, while p38 MAPK increased. Proteomics showed that only 40 proteins exhibited significant differences (30 upregulated, 10 downregulated) compared MSCs group with the model group. Galectin-3 was downregulated significantly in renal tissues and TGF-β1-induced rat tubular epithelial cells and interstitial fibroblasts, consistent with the iTRAQ results. Gal-3 KD notably inhibited the expression of p-Akt, p-GSK3β and snail in TGF-β1-induced HK-2 cells fibrosis. On the contrary, Gal-3 OE obviously increased the expression of p-Akt, p-GSK3β and snail. Conclusion The mechanism of MSCs anti-renal fibrosis was probably mediated by galectin-3/Akt/GSK3β/Snail signaling pathway. Galectin-3 may be a valuable target for treating renal fibrosis.

scholarly journals Renal Ultrasound Elastography: A Review of the Previous Reports on Chronic Kidney Diseases

2021 ◽  
Vol 11 (20) ◽  
pp. 9677
Author(s):  
Takuji Iyama ◽  
Takaaki Sugihara ◽  
Tomoaki Takata ◽  
Hajime Isomoto
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Shear Wave ◽  
Malignant Tumors ◽  
Interstitial Fibrosis ◽  
Kidney Diseases ◽  
Shear Wave Elastography ◽  
Ultrasound Elastography ◽  
Renal Ultrasound

The early detection of a kidney injury is essential to protect against the progression of kidney damage owing to the progressive nature of chronic kidney disease. A renal biopsy is the gold standard for the assessment of pathological alterations such as interstitial fibrosis and glomerulosclerosis. However, there are concerns regarding potential complications including bleeding and a reduction in renal function. Ultrasound elastography is an ideal modality for assessing the alterations in various organs and diagnosing malignant tumors. This technique has the potential to help detect early changes in renal function and pathological alterations. However, the careful application and interpretation of this technique in the kidney is required because of its complex hemodynamics and architecture. Shear wave elastography is the most widely investigated technique among ultrasound elastography. This review aims to summarize the previous investigations of the kidney using shear wave elastography, particularly for renal malignancy, kidney transplantation, and chronic kidney disease. Additionally, we have highlighted the influencing factors concerning the practical measurement of renal elasticity.

scholarly journals Targeting TGF-β Signaling in Kidney Fibrosis

2018 ◽  
Vol 19 (9) ◽  
pp. 2532 ◽  
Author(s):  
Yoshitaka Isaka
Keyword(s):  
Intracellular Signaling ◽  
Renal Fibrosis ◽  
Matrix Protein ◽  
Transforming Growth Factor ◽  
Kidney Diseases ◽  
Transforming Growth Factor Β ◽  
Cell Interaction ◽  
Common Pathway ◽  
Kidney Fibrosis ◽  
Fibrotic Diseases

Renal fibrosis is the final common pathway of numerous progressive kidney diseases, and transforming growth factor-β (TGF-β) has an important role in tissue fibrosis by up-regulating matrix protein synthesis, inhibiting matrix degradation, and altering cell-cell interaction. Many strategies targeting TGF-β, including inhibition of production, activation, binding to the receptor, and intracellular signaling, have been developed. Some of them were examined in clinical studies against kidney fibrosis, and some are applied to other fibrotic diseases or cancer. Here, I review the approaches targeting TGF-β signaling in kidney fibrosis.

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