scholarly journals Proteomic approaches in kidney disease biomarker discovery

2018 ◽  
Vol 315 (6) ◽  
pp. F1817-F1821 ◽  
Author(s):  
Robert A. Fenton
Keyword(s):  
Kidney Disease ◽  
Posttranslational Modifications ◽  
Biomarker Discovery ◽  
State Of The Art ◽  
Kidney Diseases ◽  
Kidney Tissue ◽  
Tissue Samples ◽  
Disease Biomarker ◽  
Unbiased Manner ◽  
Potential Biomarkers

Biomarkers have the potential to greatly facilitate diagnosis and treatment of patients with various forms of kidney disease. State-of-the-art mass spectrometry-based methods possess the capability, on a proteome scale and in an unbiased manner, to detect alterations in protein abundances and/or posttranslational modifications in plasma, urine, or tissue. Such approaches can provide a large, unbiased database to facilitate identification of potential biomarkers. In the diagnosis of kidney diseases, urine is usually a more favorable specimen than plasma and kidney tissue due to its noninvasive collection and simplicity of processing. However, whether analysis of proteins in urine faithfully reflects their changes in the kidney tissue remains unclear. The use of proteomics to analyze kidney tissue samples collected during late-stage kidney diseases has also recently gathered pace. The goal of this minireview is to provide an overview of the proteomic technologies currently applied to studies of kidney and their limitations, present existing kidney and urine proteome databases, and highlight a few applications of such approaches in kidney disease biomarker discovery.

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 Vanderbilt O'Brien Kidney Center

2020 ◽  
Author(s):  
Ambra Pozzi ◽  
Raymond C Harris
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Scientific Community ◽  
State Of The Art ◽  
Kidney Diseases ◽  
The United States ◽  
Outreach Program ◽  
Personalized Care ◽  
Education And Outreach ◽  
The Right

The Vanderbilt O'Brien Kidney Center (VOKC) is one of the eight NDDK-P30 funded Centers in the United States. The mission of these core-based Centers is to provide technical and conceptual support to enhance and facilitate research in the field of kidney diseases. The goal of the VOKC is to provide support to understand mechanisms and identify potential therapies for acute and chronic kidney disease. The services provided by the VOKC are meant to help the scientific community to have the right support and tools as well as to select the right animal model, statistical analysis, and clinical study design to perform innovative research and translate discoveries into personalized care to prevent, diagnose and cure kidney disease. To achieve these goals, the VCKD has in place a program to foster collaborative investigation into critical questions of kidney disease; to personalize diagnosis and treatment of kidney disease; and to disseminate information about kidney disease and the benefits of the VOKC services and research. The Center is complemented by state-of-the art Cores and an Education and Outreach program whose goals are to provide an educational platform to enhance the study of kidney disease; to publicize information about services available through the VOKC; and to provide information about kidney disease to patients and other interested members of the community. In this review we highlight the major services and contributions of the VOKC.

Large-Scale Proteomic Assessment of Urinary Extracellular Vesicles Highlights Their Reliability in Reflecting Protein Changes in the Kidney

2021 ◽  
pp. ASN.2020071035
Author(s):  
Qi Wu ◽  
Søren Poulsen ◽  
Sathish Murali ◽  
P. Richard Grimm ◽  
Xiao-Tong Su ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Animal Studies ◽  
Large Scale ◽  
Biomarker Discovery ◽  
Kidney Tissue ◽  
Absolute Quantification ◽  
Protein Levels ◽  
Cytoplasmic Proteins ◽  
High K ◽  
Unbiased Manner

Background: Urinary extracellular vesicles (uEVs) are secreted into urine by cells from the kidneys and urinary tract. Although changes in uEV proteins are used for quantitative assessment of protein levels in the kidney or biomarker discovery, whether they faithfully reflect (patho)physiological changes in the kidney is a matter of debate. Methods: Mass spectrometry was used to compare in an unbiased manner the correlations between protein levels in uEVs and kidney tissue from the same animal. Studies were performed on rats fed a normal or a high K+ diet. Results: Absolute quantification determined a positive correlation (Pearson R=0.46 or 0.45, control or high K+ respectively, p<0.0001) between the ~ 1000 proteins identified in uEVs and corresponding kidney tissue. Transmembrane proteins had greater positive correlations relative to cytoplasmic proteins. Proteins with high correlations (R>0.9), included exosome markers Tsg101 and Alix. Relative quantification highlighted a monotonic relationship between altered transporter/channel abundances in uEVs and the kidney following dietary K+ manipulation. Analysis of genetic mouse models also revealed correlations between uEVs and kidney. Conclusion: This large-scale unbiased analysis identifies uEV proteins that track the abundance of the parent proteins in the kidney. The data form a novel resource for the kidney community and support the reliability of using uEV protein changes to monitor specific physiological responses and disease mechanisms.

Increased tubulointerstitial recruitment of human CD141hi CLEC9A+ and CD1c+ myeloid dendritic cell subsets in renal fibrosis and chronic kidney disease

2013 ◽  
Vol 305 (10) ◽  
pp. F1391-F1401 ◽  
Author(s):  
Andrew J. Kassianos ◽  
Xiangju Wang ◽  
Sandeep Sampangi ◽  
Kimberly Muczynski ◽  
Helen Healy ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Transforming Growth Factor ◽  
Interstitial Fibrosis ◽  
Kidney Diseases ◽  
Kidney Tissue ◽  
Transforming Growth Factor Β ◽  
Healthy Tissue ◽  
Lectin Domain ◽  
Immune Mediated

Dendritic cells (DCs) play critical roles in immune-mediated kidney diseases. Little is known, however, about DC subsets in human chronic kidney disease, with previous studies restricted to a limited set of pathologies and to using immunohistochemical methods. In this study, we developed novel protocols for extracting renal DC subsets from diseased human kidneys and identified, enumerated, and phenotyped them by multicolor flow cytometry. We detected significantly greater numbers of total DCs as well as CD141hi and CD1c+ myeloid DC (mDCs) subsets in diseased biopsies with interstitial fibrosis than diseased biopsies without fibrosis or healthy kidney tissue. In contrast, plasmacytoid DC numbers were significantly higher in the fibrotic group compared with healthy tissue only. Numbers of all DC subsets correlated with loss of kidney function, recorded as estimated glomerular filtration rate. CD141hi DCs expressed C-type lectin domain family 9 member A (CLEC9A), whereas the majority of CD1c+ DCs lacked the expression of CD1a and DC-specific ICAM-3-grabbing nonintegrin (DC-SIGN), suggesting these mDC subsets may be circulating CD141hi and CD1c+ blood DCs infiltrating kidney tissue. Our analysis revealed CLEC9A+ and CD1c+ cells were restricted to the tubulointerstitium. Notably, DC expression of the costimulatory and maturation molecule CD86 was significantly increased in both diseased cohorts compared with healthy tissue. Transforming growth factor-β levels in dissociated tissue supernatants were significantly elevated in diseased biopsies with fibrosis compared with nonfibrotic biopsies, with mDCs identified as a major source of this profibrotic cytokine. Collectively, our data indicate that activated mDC subsets, likely recruited into the tubulointerstitium, are positioned to play a role in the development of fibrosis and, thus, progression to chronic kidney disease.

scholarly journals Pathogenic and protective role of macrophages in kidney disease

2013 ◽  
Vol 305 (1) ◽  
pp. F3-F11 ◽  
Author(s):  
Qi Cao ◽  
Yiping Wang ◽  
David C. H. Harris
Keyword(s):  
Kidney Disease ◽  
Kidney Diseases ◽  
Kidney Tissue ◽  
Human Kidney ◽  
Protective Role ◽  
Therapeutic Use ◽  
Disease Type ◽  
Dual Role ◽  
Murine Models

Macrophages (MΦ) are located throughout kidney tissue, where they play important roles in homeostasis, surveillance, tolerance, and cytoprotection. MΦ are highly heterogeneous cells and exhibit distinct phenotypic and functional characteristics depending on their microenvironment and the disease type and stage. Recent studies have identified a dual role for MΦ in several murine models of kidney disease. In this review, we discuss the pathogenic and protective roles of the various MΦ subsets in experimental and human kidney diseases and summarize current progress toward the therapeutic use of MΦ in kidney diseases.

scholarly journals Urinary Peptidomic Biomarkers in Kidney Diseases

2019 ◽  
Vol 21 (1) ◽  
pp. 96 ◽  
Author(s):  
Vittorio Sirolli ◽  
Luisa Pieroni ◽  
Lorenzo Di Liberato ◽  
Andrea Urbani ◽  
Mario Bonomini
Keyword(s):  
Kidney Disease ◽  
Drug Targets ◽  
Biomarker Discovery ◽  
Kidney Diseases ◽  
Response To Treatment ◽  
Protein Signaling ◽  
Prognostic Assessment ◽  
Urine Albumin ◽  
Short And Long Term ◽  
Molecular Pathophysiology

In order to effectively develop personalized medicine for kidney diseases we urgently need to develop highly accurate biomarkers for use in the clinic, since current biomarkers of kidney damage (changes in serum creatinine and/or urine albumin excretion) apply to a later stage of disease, lack accuracy, and are not connected with molecular pathophysiology. Analysis of urine peptide content (urinary peptidomics) has emerged as one of the most attractive areas in disease biomarker discovery. Urinary peptidome analysis allows the detection of short and long-term physiological or pathological changes occurring within the kidney. Urinary peptidomics has been applied extensively for several years now in renal patients, and may greatly improve kidney disease management by supporting earlier and more accurate detection, prognostic assessment, and prediction of response to treatment. It also promises better understanding of kidney disease pathophysiology, and has been proposed as a “liquid biopsy” to discriminate various types of renal disorders. Furthermore, proteins being the major drug targets, peptidome analysis may allow one to evaluate the effects of therapies at the protein signaling pathway level. We here review the most recent findings on urinary peptidomics in the setting of the most common kidney diseases.

Macrophages in Kidney Injury, Inflammation, and Fibrosis

Physiology ◽  
2015 ◽  
Vol 30 (3) ◽  
pp. 183-194 ◽  
Author(s):  
Qi Cao ◽  
David C. H. Harris ◽  
Yiping Wang
Keyword(s):  
Kidney Disease ◽  
Tissue Injury ◽  
Kidney Diseases ◽  
Treatment Options ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Inflammatory Factors ◽  
Anti Inflammatory ◽  
Molecular Patterns ◽  
Inflammatory Macrophages

Macrophages are found in normal kidney and in increased numbers in diseased kidney, where they act as key players in renal injury, inflammation, and fibrosis. Macrophages are highly heterogeneous cells and exhibit distinct phenotypic and functional characteristics in response to various stimuli in the local microenvironment in different types of kidney disease. In kidney tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce pro-inflammatory macrophages, which contribute to further tissue injury, inflammation, and subsequent fibrosis. Apoptotic cells and anti-inflammatory factors in post-inflammatory tissues induced anti-inflammatory macrophages, which can mediate kidney repair and regeneration. This review summarizes the role of macrophages with different phenotypes in kidney injury, inflammation, and fibrosis in various acute and chronic kidney diseases. Understanding alterations of kidney microenvironment and the factors that control the phenotype and functions of macrophages may offer an avenue for the development of new cellular and cytokine/growth factor-based therapies as alternative treatment options for patients with kidney disease.

scholarly journals FcER1: A Novel Molecule Implicated in the Progression of Human Diabetic Kidney Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Swastika Sur ◽  
Mark Nguyen ◽  
Patrick Boada ◽  
Tara K. Sigdel ◽  
Hans Sollinger ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Target Genes ◽  
Kidney Tissue ◽  
Kidney Injury ◽  
Rational Drug Design ◽  
Transcriptional Analysis ◽  
Peripheral Blood Mononuclear ◽  
Tissue Samples ◽  
Diabetic Kidney

Diabetic kidney disease (DKD) is a key microvascular complication of diabetes, with few therapies for targeting renal disease pathogenesis and progression. We performed transcriptional and protein studies on 103 unique blood and kidney tissue samples from patients with and without diabetes to understand the pathophysiology of DKD injury and its progression. The study was based on the use of 3 unique patient cohorts: peripheral blood mononuclear cell (PBMC) transcriptional studies were conducted on 30 patients with DKD with advancing kidney injury; Gene Expression Omnibus (GEO) data was downloaded, containing transcriptional measures from 51 microdissected glomerulous from patients with DKD. Additionally, 12 independent kidney tissue sections from patients with or without DKD were used for validation of target genes in diabetic kidney injury by kidney tissue immunohistochemistry and immunofluorescence. PBMC DKD transcriptional analysis, identified 853 genes (p &lt; 0.05) with increasing expression with progression of albuminuria and kidney injury in patients with diabetes. GEO data was downloaded, normalized, and analyzed for significantly changed genes. Of the 325 significantly up regulated genes in DKD glomerulous (p &lt; 0.05), 28 overlapped in PBMC and diabetic kidney, with perturbed FcER1 signaling as a significantly enriched canonical pathway. FcER1 was validated to be significantly increased in advanced DKD, where it was also seen to be specifically co-expressed in the kidney biopsy with tissue mast cells. In conclusion, we demonstrate how leveraging public and private human transcriptional datasets can discover and validate innate immunity and inflammation as key mechanistic pathways in DKD progression, and uncover FcER1 as a putative new DKD target for rational drug design.

scholarly journals Familial nephropathy in Bracchi Italiani: 8 cases (2012–2019)

2021 ◽  
pp. 1-6
Author(s):  
Amanda L. Inman ◽  
Ashley E. Allen-Durrance ◽  
Rachel E. Cianciolo ◽  
Autumn N. Harris
Keyword(s):  
Kidney Disease ◽  
Clinical Presentation ◽  
Kidney Tissue ◽  
Clinical Signs ◽  
Descriptive Statistics ◽  
Test Results ◽  
Health Records ◽  
Tissue Samples ◽  
Hereditary Nephropathy ◽  
Familial Nephropathy

Abstract OBJECTIVE To characterize the signalment, clinical signs, clinical pathological and histologic findings, and outcome in 8 related Bracchi Italiani with proteinuric kidney disease. ANIMALS 8 client-owned Bracchi Italiani. PROCEDURES Health records submitted to the Bracco Italiano Health Foundation and the Bracco Italiano Club of America between 2012 and 2019 were reviewed for dogs with evidence of nephropathy for which histologic diagnoses were obtained. Pedigree, signalment, clinical signs, diagnostic test results (including microscopic examination of kidney tissue samples collected ante- or postmortem), and outcome were acquired. Results were presented as descriptive statistics. RESULTS The most common clinical sign in affected dogs was inappetence. All dogs were proteinuric, and 4 dogs were azotemic. Seven dogs developed clinical signs of kidney disease and were euthanized a median of 75 days postdiagnosis. Six dogs had glomerular amyloidosis, and 1 dog each had nephrosclerosis and nonamyloidotic fibrillar glomerulopathy. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the clinical presentation may vary in affected dogs, and proteinuria in young or middle-aged Bracchi Italiani should raise the concern for hereditary nephropathy. Prognosis is likely poor once clinical signs are noted.

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