scholarly journals Comparative quantitation of aquaporin-2 and arginine vasopressin receptor-2 localizations among chronic kidney disease and healthy kidney in dogs

2021 ◽  
pp. 2773-2781
Author(s):  
Pitchaya Matchimakul ◽  
Wanpitak Pongkan ◽  
Piyamat Kongtung ◽  
Raktham Mektrirat
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Protein Expression ◽  
Arginine Vasopressin ◽  
Basolateral Membrane ◽  
Kidney Tissue ◽  
Vasopressin Receptor ◽  
Water Homeostasis ◽  
Principal Cells ◽  
Aquaporin 2

Background and Aim: Aquaporin-2 (AQP2) and arginine vasopressin receptor-2 (AVPR2) are proteins that control water homeostasis in principal cells. Chronic kidney disease (CKD) is defined as the impairment and irreversible loss of kidney function and/or structure, which causes water imbalances and polyuria. The study aimed to know the expression of AQPs and AVPR2 in the kidneys of a canine with CKD. Materials and Methods: The kidneys were collected from two dog carcasses from Small Animal Teaching Hospital, Faculty of Veterinary Medicine, Chiang Mai University. The kidney tissue was prepared for immunohistochemistry and investigated the expression and localization of tissue's AQP2 and AVPR2. For statistical analysis, the Mann–Whitney U-test was applied to the data. Results: By immunohistochemistry, AQP2 was expressed strongly in the basolateral and apical membranes of the principal cells, whereas AVPR2 was localized in the principal cell's basolateral membrane in both renal cortex and renal medulla. In the normal kidney, the semi-quantitative immunohistochemistry for the percentage of protein expression of AQP2 and AVPR2 was 5.062±0.4587 and 4.306±0.7695, respectively. In contrast, protein expression of AQP2 and AVPR2 in CKD was found to be 1.218±0.1719 and 0.8536±0.1396, respectively. The data shows that the percentage of AQP2 and AVPR2 expression was decreased, corresponding to a 4-fold and 5-fold in CKD (p<0.001). Conclusion: Our findings revealed that CKD was a marked decrease in AQP2 and AVPR2 expression. The central role of specific AQP2 and AVPR2 in regulating water homeostasis will provide correlations in case of CKD with polyuria.

Tubular cell-enriched subpopulation of primary renal cells improves survival and augments kidney function in rodent model of chronic kidney disease

2010 ◽  
Vol 299 (5) ◽  
pp. F1026-F1039 ◽  
Author(s):  
Rusty Kelley ◽  
Eric S. Werdin ◽  
Andrew T. Bruce ◽  
Sumana Choudhury ◽  
Shay M. Wallace ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Kidney Function ◽  
Transforming Growth Factor ◽  
Kidney Tissue ◽  
Tubular Cell ◽  
Acute Injury ◽  
Treatment Modalities ◽  
Histological Evaluation ◽  
Renal Cells

Established chronic kidney disease (CKD) may be identified by severely impaired renal filtration that ultimately leads to the need for dialysis or kidney transplant. Dialysis addresses only some of the sequelae of CKD, and a significant gap persists between patients needing transplant and available organs, providing impetus for development of new CKD treatment modalities. Some postulate that CKD develops from a progressive imbalance between tissue damage and the kidney's intrinsic repair and regeneration processes. In this study we evaluated the effect of kidney cells, delivered orthotopically by intraparenchymal injection to rodents 4–7 wk after CKD was established by two-step 5/6 renal mass reduction (NX), on the regeneration of kidney function and architecture as assessed by physiological, tissue, and molecular markers. A proof of concept for the model, cell delivery, and systemic effect was demonstrated with a heterogeneous population of renal cells (UNFX) that contained cells from all major compartments of the kidney. Tubular cells are known contributors to kidney regeneration in situ following acute injury. Initially tested as a control, a tubular cell-enriched subpopulation of UNFX (B2) surprisingly outperformed UNFX. Two independent studies (3 and 6 mo in duration) with B2 confirmed that B2 significantly extended survival and improved renal filtration (serum creatinine and blood urea nitrogen). The specificity of B2 effects was verified by direct comparison to cell-free vehicle controls and an equivalent dose of non-B2 cells. Quantitative histological evaluation of kidneys at 6 mo after treatment confirmed that B2 treatment reduced severity of kidney tissue pathology. Treatment-associated reduction of transforming growth factor (TGF)-β1, plasminogen activator inhibitor (PAI)-1, and fibronectin (FN) provided evidence that B2 cells attenuated canonical pathways of profibrotic extracellular matrix production.

Abstract 188: Loss of Renal Prolyl Carboxypeptidase in Mice With Chronic Kidney Disease

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Orly Leiva ◽  
Khalid M Elased ◽  
Mariana Morris ◽  
Nadja Grobe
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Protein Expression ◽  
Western Blot ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Left Renal Artery ◽  
Renal Tubules ◽  
Ang Ii ◽  
Chronic Kidney Injury

There are 26 million adults with chronic kidney disease (CKD) in the U.S. and the incidence continues to increase. It is well documented that the activation of the renin angiotensin system and the elevated formation of angiotensin (Ang) II both contribute to renal pathophysiology in CKD. Emerging evidence suggests that the Ang II degrading protease prolyl carboxypeptidase (PCP) is renoprotective. Thus, we investigated protein expression and activity of renal PCP using immunofluorescence, western blot and mass spectrometry in a mouse model of CKD. Renal injury in male C57Bl6 mice was caused by constriction of the left renal artery using silver clips (2K1C-method). Blood pressure measurements by radiotelemetry revealed a significant increase of 36.1 ± 3.9 mm Hg in 2K1C animals compared with control animals 1 week after clip placement (p<0.0001). Using immunofluorescence and confocal microscopy, PCP was localized in the Bowman’s capsule of the glomerulus and in proximal and distal renal tubules. Western blot analysis showed PCP was significantly reduced in clipped 2K1C kidneys compared to unclipped kidneys of the 2K1C mice or compared to control mice (clipped 0.04 ± 0.02 vs unclipped 0.58 ± 0.16 vs control 0.65 ± 0.18, p < 0.05). In addition, renal PCP enzyme activity was found to be markedly reduced in 2K1C kidneys as assessed by mass spectrometric based enzyme assays (clipped 37.1 ± 4.3 pmol Ang-(1-7)/h/μg vs unclipped 77.3 ± 12.3 pmol Ang-(1-7)/h/μg vs control 120.7 ± 14.7 pmol Ang-(1-7)/h/μg, p < 0.01). In contrast, protein expression of prolyl endopeptidase, another enzyme capable of converting Ang II into Ang-(1-7), was not affected. Notably, renal pathologies were exacerbated in the 2K1C model as revealed by a significant increase in mesangial expansion (clipped 34.6 ± 3.1 vs unclipped 52.1 ± 4.0 vs control 1.2 ± 2.1, p < 0.0001) and renal fibrosis (clipped 57.5 ± 0.9 vs unclipped 33.0 ± 0.7 vs control 3.3 ± 0.2, p < 0.0001). Results suggest that PCP is suppressed in chronic kidney injury and that this downregulation may attenuate renoprotective effects via impaired Ang II degradation by PCP. Therefore, Ang II processing by PCP may have clinical implications in patients with renal pathologies.

Reduced urinary corin levels in patients with chronic kidney disease

2013 ◽  
Vol 124 (12) ◽  
pp. 709-717 ◽  
Author(s):  
Chaodong Fang ◽  
Lei Shen ◽  
Liang Dong ◽  
Meng Liu ◽  
Sensen Shi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Human Urine ◽  
Animal Studies ◽  
Kidney Tissue ◽  
Renal Tubules ◽  
Tissue Samples ◽  
Protein Levels ◽  
Normal Individuals ◽  
Renal Tubular

Corin is a cardiac protease that regulates BP (blood pressure) by activating natriuretic peptides. Recent animal studies identified corin expression in the kidney where it may regulate renal function. In the present study, we tested the hypothesis that corin may be present in human urine and that urinary corin levels may be altered in patients with kidney disease. We obtained urine and kidney tissue samples from normal individuals and CKD (chronic kidney disease) patients. Using ELISA, we detected corin protein in human urine. In normal individuals, urinary corin levels did not correlate with that of plasma, indicating that urinary corin is probably of kidney origin. Compared with normal controls, CKD patients had markedly reduced urinary corin levels and this reduction correlated with disease severity. By immunostaining, human corin protein was identified on the epithelial cell surface in renal tubules. The renal corin mRNA and protein levels were significantly lower in CKD patients than non-CKD controls. The results indicate that renal tubular corin may be shed into urine and that urinary and renal corin levels were reduced in CKD patients. These data suggest that reduced corin levels in the kidney may reflect the underlying pathology in CKD.

scholarly journals Dietary Phosphorus Differentially Alters Uremic Toxin Production in a Rat Model of Chronic Kidney Disease

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 843-843
Author(s):  
Dennis Cladis ◽  
Kendal Schmitz ◽  
Amber Jannasch ◽  
Bruce Cooper ◽  
Kathleen Hill Gallant
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Rat Model ◽  
Kidney Tissue ◽  
Toxin Production ◽  
Sham Operation ◽  
Uremic Toxin ◽  
Sprague Dawley ◽  
Waste Products ◽  
Dietary Phosphorus

Abstract Objectives Chronic kidney disease (CKD) is characterized by declining kidney function, limiting the kidney's ability to efficiently remove metabolic waste products from circulation. Byproducts of gut microbial protein metabolism, termed uremic retention solutes (URS), accumulate in CKD patients and are associated with accelerating kidney decline. The gut microbes responsible for generating URS are dependent upon phosphorus (P) for growth and survival. As dietary P restriction is a cornerstone of CKD treatment, we hypothesized that changes in dietary P loads would alter URS production. Methods To evaluate this, 8-week-old male Sprague Dawley rats underwent 5/6th nephrectomy (Nx, n = 24) or sham operation (n = 20) and were maintained on a 0.6% P diet (w/w) for three weeks. Animals were then randomized to receive either low (0.1% (w/w)) or high (1.2% (w/w)) P diets for 4h/d for 7d. Blood was collected at the start and end of the 7d diet (baseline and sacrifice, respectively). Serum was analyzed for blood urea nitrogen (BUN) and URS, including trimethylamine oxide (TMAO), indoxyl sulfate (IS), and p-cresol sulfate (pCS), via LC-MS. Results Nx rats had significantly elevated BUN compared to sham controls (38.9 ± 5.9 vs 23.1 ± 5.1 mg/dL, p &lt; 0.0001). Additionally, the presence of significantly enlarged kidney tissue in Nx animals verified the progression of kidney decline. At sacrifice, all URS were elevated in Nx animals as compared to sham controls (p &lt; 0.0001), though changes in dietary P loads only affected IS production (low vs. high, p = 0.0003). When comparing baseline to sacrifice, TMAO decreased, IS remained consistent, and pCS increased in all rats. Conclusions Our results indicate that dietary P loads may differentially affect the production of some URS in a rat model of CKD. As dietary P restriction is one of the cornerstones of CKD treatment, we posit that this dietary strategy influences URS production, CKD progression, and, ultimately, health outcomes. Funding Sources ASBMR, NIH K01.

scholarly journals Multi-sample mass spectrometry-based approach for discovering injury markers in chronic kidney disease

2020 ◽  
pp. mcp.RA120.002159
Author(s):  
Ji Eun Kim ◽  
Dohyun Han ◽  
Jin Seon Jeong ◽  
Jong Joo Moon ◽  
Hyun Kyung Moon ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Quantitative Proteomics ◽  
Kidney Tissue ◽  
Protein S ◽  
Disease Stage ◽  
Tandem Mass ◽  
Ckd Progression ◽  
Proteomics Analysis

Urinary proteomics studies have primarily focused on identifying markers of chronic kidney disease (CKD) progression. Here, we aimed to determine urinary markers of CKD renal parenchymal injury through proteomics analysis in animal kidney tissues and cells and in the urine of patients with CKD. Label-free quantitative proteomics analysis based on liquid chromatography-tandem mass spectrometry was performed on urine samples obtained from 6 normal controls and 9, 11, and 10 patients with CKD stages 1, 3, and 5, respectively, and on kidney tissue samples from a rat CKD model by 5/6 nephrectomy. Tandem mass tag-based quantitative proteomics analysis was performed for primary cultured glomerular endothelial cells (GECs) and proximal tubular epithelial cells (PTECs) before and after inducing 24-h hypoxia injury. Upon hierarchical clustering, out of 858 differentially expressed proteins (DEPs) in the urine of CKD patients, the levels of 416 decreased and 403 increased sequentially according to the disease stage, respectively. Among 2965 DEPs across 5/6 nephrectomized and sham-operated rat kidney tissues, 86 DEPs showed same expression patterns in the urine and kidney tissue. After cross-validation with two external animal proteome datasets, 38 DEPs were organized; only 10 DEPs, including serotransferrin, gelsolin, poly ADP-ribose polymerase 1, neuroblast differentiation-associated protein AHNAK, microtubule-associated protein 4, galectin-1, protein S, thymosin beta-4, myristoylated alanine-rich C-kinase substrate, and vimentin were finalized by screening human GECs and PTECs data. Among these ten potential candidates for universal CKD marker, validation analyses for protein S and galectin-1 were conducted. Galectin-1 was observed to have a significant inverse correlation with renal function as well as higher expression in glomerulus with chronic injury than protein S. This constitutes the first multi-sample proteomics study for identifying key renal-expressed proteins associated with CKD progression. The discovered proteins represent potential markers of chronic renal cell and tissue damage and candidate contributors to CKD pathophysiology.

scholarly journals Chaphamaparvovirus Antigen and Nucleic Acids are not Detected in Kidney Tissues from Cats with Chronic Renal Disease or Immunosuppressive Diseases

2021 ◽  
Author(s):  
Adam Oliver Michel ◽  
Taryn Donovan ◽  
Ben Roediger ◽  
Quintin Lee ◽  
Christopher J Jolly ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
New York ◽  
Kidney Disease ◽  
Renal Disease ◽  
Chronic Renal Disease ◽  
Kidney Tissue ◽  
Antigen Expression ◽  
Geographic Region ◽  
Wild Mice ◽  
Immunodeficient Mice

Mouse Kidney Parvovirus (MKPV) was recently recognized as the cause of murine inclusion body nephropathy, a disease reported for over 40 years in laboratory mice. Immunodeficient mice are persistently infected with MKPV, leading to chronic renal disease, morbidity and mortality whereas immunocompetent mice seroconvert with mild renal pathology. Given the high incidence of MKPV infection in wild mice in the New York City area, the first goal of this study was to evaluate the possibility of MKPV involvement in feline chronic kidney disease (CKD) from the same geographic region. As MKPV and related parvoviruses recently described in other animal species appear to have a tropism for kidney tissue, the second goal was to investigate the possible role of a virus of this group, other than MKPV, in the development of feline CKD, Presence of MKPV and related viruses was investigated in feline renal samples using PCR, RNA in situ hybridization (ISH) and immunohistochemistry (IHC). Cats were divided into three groups: normal (N=25), CKD (N=25) and immune suppressed (N=25). None of the kidney tissues from any of the 75 cats revealed the presence of MKPV DNA, RNA or antigen expression. Nor was "fechavirus" detected using PCR in renal tissue from cats with chronic kidney disease. We conclude that MKPV is an unlikely cause or contributor to feline CKD.

scholarly journals A functional landscape of chronic kidney disease entities from public transcriptomic data

2018 ◽  
Author(s):  
Ferenc Tajti ◽  
Christoph Kuppe ◽  
Asier Antoranz ◽  
Mahmoud M. Ibrahim ◽  
Hyojin Kim ◽  
...  
Keyword(s):  
Gene Expression ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Gene Expression Data ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Kidney Tissue ◽  
Therapeutic Targets ◽  
Expression Data ◽  
Disease Entities

AbstractTo develop efficient therapies and identify novel early biomarkers for chronic kidney disease an understanding of the molecular mechanisms orchestrating it is essential. We here set out to understand how differences in CKD origin are reflected in gene expression. To this end, we integrated publicly available human glomerular microarray gene expression data for nine kidney disease entities that account for a majority of CKD worldwide. We included data from five distinct studies and compared glomerular gene expression profiles to that of non-tumor parts of kidney cancer nephrectomy tissues. A major challenge was the integration of the data from different sources, platforms and conditions, that we mitigated with a bespoke stringent procedure. This allowed us to perform a global transcriptome-based delineation of different kidney disease entities, obtaining a landscape of their similarities and differences based on the genes that acquire a consistent differential expression between each kidney disease entity and nephrectomy tissue. Furthermore, we derived functional insights by inferring activity of signaling pathways and transcription factors from the collected gene expression data, and identified potential drug candidates based on expression signature matching. We validated representative findings by immunostaining in human kidney biopsies indicating e.g. that the transcription factor FOXM1 is significantly and specifically expressed in parietal epithelial cells in RPGN whereas not expressed in control kidney tissue. These results provide a foundation to comprehend the specific molecular mechanisms underlying different kidney disease entities, that can pave the way to identify biomarkers and potential therapeutic targets. To facilitate this, we provide our results as a free interactive web application: https://saezlab.shinyapps.io/ckd_landscape/.Translational StatementChronic kidney disease is a combination of entities with different etiologies. We integrate and analyse transcriptomics analysis of glomerular from different entities to dissect their different pathophysiology, what might help to identify novel entity-specific therapeutic targets.

scholarly journals MO038SCARF EXPRESSION IN KIDNEY DISEASE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sol Carriazo ◽  
Maria Dolores Sanchez-Nino ◽  
Maria Vanessa Perez Gomez ◽  
Laura Castañeda-Infante ◽  
Catalina Martin ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Risk Factor ◽  
Kidney Disease ◽  
Single Cell ◽  
Kidney Tissue ◽  
Differentially Expressed ◽  
Tubular Cells ◽  
Risk Of Death ◽  
Increased Risk ◽  
The Impact

Abstract Background and Aims Chronic kidney disease (CKD) is the most common risk factor for lethal COVID19 and the risk factor that most increases the risk of death of COVID19 patients. Additionally, acute kidney injury (AKI) is frequent in COVID19 and AKI increases the risk of death. However, the underlying cellular and molecular mechanisms of such increased risk are unclear. SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) are required for and/or regulate (in a positive or negative manner) coronary cell entry and/or viral replication. We have now studied changes in the expression of genes encoding for SCARF in the context of acute and chronic kidney disease. Method Data mining of in-house (experimental models of AKI -folic acid nephropathy- and CKD -Unilateral ureteral obstruction- in mice) and publicly available databases (Nephroseq, published single cell transcriptomics studies) of kidney tissue transcriptomics as well as the Protein Atlas database. Results Out of 28 SCARF genes identified by Singh et al (Cell Reports 2020), 26 were represented in the experimental AKI database. Of them 7 (27%) were differentially expressed during AKI (FDR &lt;0.05), 4 of them upregulated and 3 downregulated (Figure 1.A). Additionally, 27 were represented in the experimental CKD database. Of them 17 (63%) were differentially expressed during experimental CKD, 6 of them upregulated and 11 downregulated (Figure 1.B). Two genes were consistently upregulated (Ctsl and Ifitm3) and two consistently downregulated (Tmprss2 and Top3b) in both experimental AKI and CKD (Figure 1.A and B). They encode cathepsin L, interferon induced transmembrane protein 3, transmembrane serine protease 2, DNA topoisomerase III beta, respectively. Single cell transcriptomics databases localized Ctsl expression mainly to podocytes and tubular cells while protein atlas showed clear tubular staining. The main site of Ifitm3 was endothelium in both datasets and it was also localized to leukocytes by single cell transcriptomics. Tmprss2 was mainly localized to tubular cells in both datasets while Top3b was widely expressed in parenchymal renal cells, endothelium and leucocytes in single cell transcriptomics. Increased kidney expression of Ifitm3 and decreased expression of Tmprss2 and Top3b were confirmed in diverse CKD datasets in Nephroseq. Conclusion Both AKI and CKD are associated with differential expression of SCARF genes in kidney tissue, the impact of CKD appearing to be larger. Characterization of these changes and their functional impact in kidney tissue and beyond the kidneys may provide clues to the increased risk of severe or lethal COVID19 in kidney disease patients. Kidney SCARF gene expression

scholarly journals Shen Shuai II Recipe Attenuates Renal Interstitial Fibrosis by Improving Hypoxia via the IL-1β/c-Myc Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Liuyi Yang ◽  
Meng Wang ◽  
Yuan Zhou ◽  
Jing Yang ◽  
Chaoyang Ye ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Renal Function ◽  
Chronic Renal Failure ◽  
Kidney Disease ◽  
Protein Expression ◽  
Interstitial Fibrosis ◽  
Renal Interstitial Fibrosis ◽  
Related Factors

Background. Renal interstitial fibrosis is a pathological manifestation of progression of chronic kidney disease induced by various factors. Shen Shuai II Recipe (SSR) has been used in clinical practice for more than 20 years, and clinical studies have confirmed that SSR significantly improves the renal function of patients with chronic kidney disease. However, the specific mechanisms underlying its efficacy require further research. This study aims to explore the influencing factors of renal interstitial fibrosis in the context of hypoxia via the IL-1β/c-Myc pathway and the potential molecular mechanisms of SSR intervention in vivo and in vitro. Methods. A rat model of chronic renal failure was developed by performing 5/6 (ablation/infarction, A/I) surgery on randomly selected, male Sprague Dawley rats. Thirty-six successfully modeled rats were randomly divided into three groups: 5/6 (A/I), 5/6 (A/I) + SSR, and 5/6 (A/I) + losartan. Another 12 rats were used as the sham group. After 8 weeks of the corresponding intervention, renal function, liver function, and protein expression of renal-fibrosis-related factors, HIF-1α, IL-1β, and c-Myc, were detected. In vitro analysis was performed using hypoxia-induced rat renal tubular epithelial cells (NRK-52E) and IL-1β-stimulated rat renal interstitial fibroblasts (NRK-49F). IL-1β concentration in the culture medium and IL-1β protein expression in hypoxic NRK-52E treated with different concentrations of SSR were investigated. Furthermore, we also studied the changes in protein expression of c-Myc and fibrosis-related factors after c-Myc gene silencing in IL-1β-stimulated NRK-49F treated with SSR. Results. Shen Shuai II Recipe significantly reduced RIF and downregulated the expression of HIF-1α, c-Myc, and IL-1β proteins in 5/6 (A/I) rats with chronic renal failure. It also inhibited IL-1β secretion from NRK-52E induced by hypoxia, which in turn inhibited fibroblast activation mediated by the IL-1β/c-Myc pathway, and finally reduced the overproduction of the extracellular matrix. Conclusion. The renoprotective effects of SSR in rats with chronic renal failure may be related to its inhibition of hypoxia via the IL-1β/c-Myc pathway. Thus, SSR is a potentially effective drug for delaying the progression of renal interstitial fibrosis.

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