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urinary biomarkers for nephrotic syndrome

Joichi Usui, Chie Yokoyama, Masahiro Hagiwara, Kai Hirayasu, Takahiro Kojima, Takayuki Yoshino, Hiroyuki Nishiyama, Masanori Hara, Kunihiro Yamagata
BACKGROUND: Focusing on glomerular thrombotic microangiopathy (TMA), we detected urinary podocytes to evaluate podocyte damage following glomerular endothelial cell injury. METHODS: We analyzed the relationship between urinary podocytes as biomarkers for podocyte injuries and clinical manifestations in five patients of anti-cancer-drug-induced glomerular TMA. RESULTS: Cancer in all five patients was advanced, including 4 cases of renal cell carcinoma treated with tyrosine kinase inhibitor, and one with intrahepatic bile duct carcinoma treated with gemcitabine...
December 1, 2016: Clinical Laboratory
Vincent P O'Reilly, Limy Wong, Claire Kennedy, Louise A Elliot, Shane O'Meachair, Alice Marie Coughlan, Eoin C O'Brien, Michelle M Ryan, Diego Sandoval, Emma Connolly, Gerjan J Dekkema, Jiaying Lau, Wayel H Abdulahad, Jan-Stephan F Sanders, Peter Heeringa, Colm Buckley, Cathal O'Brien, Stephen Finn, Clemens D Cohen, Maja T Lindemeyer, Fionnuala B Hickey, Paul V O'Hara, Conleth Feighery, Sarah M Moran, George Mellotte, Michael R Clarkson, Anthony J Dorman, Patrick T Murray, Mark A Little
A specific biomarker that can separate active renal vasculitis from other causes of renal dysfunction is lacking, with a kidney biopsy often being required. Soluble CD163 (sCD163), shed by monocytes and macrophages, has been reported as a potential biomarker in diseases associated with excessive macrophage activation. Thus, we hypothesized that urinary sCD163 shed by crescent macrophages correlates with active glomerular inflammation. We detected sCD163 in rat urine early in the disease course of experimental vasculitis...
September 2016: Journal of the American Society of Nephrology: JASN
Yeawon Kim, Heedoo Lee, Scott R Manson, Maria Lindahl, Bradley Evans, Jeffrey H Miner, Fumihiko Urano, Ying Maggie Chen
Endoplasmic reticulum (ER) stress and disrupted proteostasis contribute to the pathogenesis of a variety of glomerular and tubular diseases. Thus, it is imperative to develop noninvasive biomarkers for detecting ER stress in podocytes or tubular cells in the incipient stage of disease, when a kidney biopsy is not yet clinically indicated. Mesencephalic astrocyte-derived neurotrophic factor (MANF) localizes to the ER lumen and is secreted in response to ER stress in several cell types. Here, using mouse models of human nephrotic syndrome caused by mutant laminin β2 protein-induced podocyte ER stress and AKI triggered by tunicamycin- or ischemia-reperfusion-induced tubular ER stress, we examined MANF as a potential urine biomarker for detecting ER stress in podocytes or renal tubular cells...
October 2016: Journal of the American Society of Nephrology: JASN
Yun Pang, Ying Tan, Yongzhe Li, Jianchun Zhang, Yongbing Guo, Zhiling Guo, Chengying Zhang, Feng Yu, Ming-Hui Zhao
Lupus nephritis always elicits immune inflammatory tissue damages in kidney. Pentraxin 3 (PTX3), mainly produced at inflammatory sites, is known to be involved in the regulation of the innate immunity system. The aim of this study was to investigate the serum and urine levels of PTX3, and the expression of PTX3 in renal tissues in lupus nephritis patients from a large Chinese cohort.The study used cross-sectional survey and 288 active lupus nephritis patients, including discovery cohort and validation cohort, 115 systemic lupus erythematosus (SLE) patients without clinical renal involvement and 46 healthy controls were enrolled...
January 2016: Medicine (Baltimore)
Michael R Bennett, Angad Pordal, Christopher Haffner, LaTawnya Pleasant, Qing Ma, Prasad Devarajan
BACKGROUND: Idiopathic nephrotic syndrome (NS) is one of the most common glomerular disorders of childhood and is associated with increased urinary vitamin D-binding protein (uVDBP) excretion. We tested the hypothesis that uVDBP represents a biomarker to differentiate steroid-resistant nephrotic syndrome (SRNS) from the more benign forms of steroid-sensitive nephrotic syndrome (SSNS). METHODS: This cross-sectional study included children with SRNS (n = 24), SSNS (n = 28), and normal controls (n = 5)...
2016: Biomarker Insights
C P Suresh, Abhijeet Saha, Manpreet Kaur, Ritesh Kumar, N K Dubey, Trayambak Basak, Vinay Singh Tanwar, Gaurav Bhardwaj, Shantanu Sengupta, Vineeta Vijay Batra, Ashish Datt Upadhyay
BACKGROUND: We performed a discovery phase of urinary proteomic profile in children with idiopathic nephrotic syndrome and validated selected biomarkers. METHODS: Urinary proteomic profile was performed using isobaric tags for relative and absolute quantitation labeling, coupled with liquid chromatography-matrix assisted laser desorption and ionization analysis. Validation of biomarkers apolipoprotein A1, alpha 2 macroglobulin, orosomucoid 2, retinol binding protein 4 and leucine-rich alpha 2-glycoprotein 1 was done by enzyme-linked immunosorbent assay...
April 2016: Clinical and Experimental Nephrology
M Iu Shvetsov, A Zheng, L V Kozlovskaia, A G Serova, E V Travkina, N A Mukhin
AIM: To study the urinary excretion of the molecular factors regulating angiogenesis, such as vascular endothelial growth factor type A (VEGF-A), thrombospondin 1 (THBS1), and angiopoietin 2 (ANGPT2), versus that of the urinary markers of renal injury and fibrogenesis, such as neutrophil gelatinase-associated lipocalin (NGAL), type IV collagen (COL4), and known clinical risk factors for accelerated disease progression to estimate the prognostic value of urinary excretion in patients with chronic glomerulonephritis (CGN)...
2015: Terapevticheskiĭ Arkhiv
N V Chebotareva, I N Bobkova, N V Neprintseva, L V Kozlovskaia, Z T Malkandueva
AIM: To estimate the degree of podocyte injury in patients with different types of chronic glomerulonephritis (CGN) from the urinary level of podocyte markers and to determine the significance of these indicators as criteria for disease activity and prognosis. SUBJECTS AND METHODS: Seventy-three patients with CGN, including 20 with inactive nephritis (Group 1), 23 with obvious urological syndrome (Group 2), 30 with nephrotic syndrome (NS) (Group 3), among them there were 7 patients with severe NS and 7 with NS concurrent with acute nephritic syndrome, were examined...
2015: Terapevticheskiĭ Arkhiv
Patrick Hamilton, Jenny Myers, Joanna Gillham, Gwen Ayers, Nina Brown, Michael Venning
Significant proteinuria in pregnancy can indicate the presence of serious conditions requiring investigation and treatment. The nephrotic syndrome in pregnancy presents a multitude of difficulties and is a relative contraindication of renal biopsy, particularly in the third trimester. We present a case of nephrotic syndrome of unknown cause presenting at 33 weeks of pregnancy. With renal biopsy contraindicated, we used the urine protein selectivity test, a largely discarded test predicting steroid-responsive nephrotic syndrome, to help inform the decision to give steroids...
December 2014: Clinical Kidney Journal
Yogavijayan Kandasamy, Roger Smith, Eugenie R Lumbers, Donna Rudd
Nephrin is a 180 KD trans-membrane protein expressed in glomerular podocytes. It was first identified in children with congenital nephrotic syndrome of the Finnish type (NPHS1). Nephrin forms an integral part of podocytes, which-together with endothelial cells and the basement-form the glomerular filtration barrier. Podocytopathies result in the detection of nephrin in the urine. We reviewed the literature to determine if urine nephrin measurements could become useful as a biomarker to detect early podocyte injury...
2014: Biomarker Research
Rutger Jh Maas, Jan Ajg van den Brand, Femke Waanders, Esther Meijer, Harry Goor van, Hilde P Peters, Julia M Hofstra, Jack Fm Wetzels
BACKGROUND: Urinary excretion of alpha-1-microglobulin and beta-2-microglobulin reflects tubular damage and predicts outcome in patients with idiopathic membranous nephropathy with reasonable accuracy. Urinary kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin are novel biomarkers of tubular damage. We investigated if these markers could improve prediction of outcome in idiopathic membranous nephropathy. METHODS: We measured kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in urine samples from patients with idiopathic membranous nephropathy, who had nephrotic proteinuria and normal renal function...
January 2016: Annals of Clinical Biochemistry
Yen-Sung Huang, Hsin-Yi Hsieh, Hsiu-Ming Shih, Huey-Kang Sytwu, Chia-Chao Wu
Membranous nephropathy (MN), a type of glomerular nephritis, is the most common cause of nephrotic syndrome in human adults. Changes in gene expression as a result of epigenetic dysregulation through long noncoding RNAs (lncRNAs) are increasingly being recognized as important factors in disease. Using an experimental MN mouse model, we identify the first dysregulated lncRNAs, Xist and NEAT1, whose levels are significantly upregulated in both tubular epithelial and glomerular cells. MN is also often characterized by glomerular podocyte injury...
September 26, 2014: Biochemical and Biophysical Research Communications
Chen Ling, Xiaorong Liu, Ying Shen, Zhi Chen, Jianfeng Fan, Yeping Jiang, Qun Meng
BACKGROUND: Early diagnosis of minimal change disease (MCD) in nephrotic syndrome (NS) patients remains challenging. Doctors often make a diagnosis of MCD using invasive renal biopsy. CD80, a transmembrane protein, is present on podocytes in a number of experimental models of NS. Urinary CD80 levels are significantly elevated in MCD but not in focal segmental glomerulosclerosis (FSGS) or other glomerulopathies. The purpose of this study was to investigate the feasibility of using urinary CD80 levels as a biomarker for the diagnosis of MCD...
February 2015: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
A A Pulin, M Iu Brovko, T Iu Kustova, L V Kozlovskaia, V V Fomin, N A Mukhin
AIM: To determine the nature and magnitude of changes in the detectable serum and urinary biomarkers of water-salt metabolism in patients with proteinuric forms of chronic glomerulonephritis (CGN), their importance for assessing the activity and prognosis of the disease. SUBJECTS AND METHODS: Forty-seven patients with CGN were examined. Group 1 included 10 patients with nephrotic syndrome (NS) and decreased renal function; Group 2 comprised 16 patients with persistent NS and normal renal function; Group 3 consisted of 10 patients with partial remission of NS; Group 4 included 11 patients with active hematuric CGN...
2014: Terapevticheskiĭ Arkhiv
Shiva Kalantari, Mohsen Nafar, Shiva Samavat, Mostafa Rezaei-Tavirani, Dorothea Rutishauser, Roman Zubarev
BACKGROUND: Focal segmental glomerulosclerosis (FSGS) is a type of nephrotic syndrome which is diagnosed by renal biopsy. Degree of the proteinuria, renal dysfunction, histologic findings and the response to therapy are some factors used for evaluating the prognosis of FSGS. OBJECTIVES: In the present study, we attempted to discover some protein candidates for disease prognosis related to glomerular filtration rate (renal dysfunction). PATIENTS AND METHODS: Urine samples were collected from ten patients...
March 2014: Nephro-urology Monthly
Cheuk-Chun Szeto
Nephrotic syndrome is a common problem in clinical nephrology. In general, nephrotic syndrome is pathognomonic of glomerular disease, but the underlying pathological etiology is highly variable. Although kidney biopsy is the standard method to classify the histology and determine the extent of renal scarring, it is an invasive procedure with potential complications, and is generally not suitable for serial monitoring. MicroRNAs (miRNAs) are short noncoding RNA molecules that regulate gene expression. Recent studies show that the urinary levels of several miRNAs are significantly changed in nephrotic syndrome; some appear to be disease specific, others being damage related...
September 25, 2014: Clinica Chimica Acta; International Journal of Clinical Chemistry
Abdulrahman L Al-Malki
OBJECTIVES: Microalbuminuria has been clinically used for noninvasive evaluation of renal dysfunctions. However, it is a nonspecific marker of diabetic nephropathy (DN). METHODS: This study was conducted from March 2012 to April 2013 at Biochemistry Unit, King Fahd Medical Research Center (KFMRC). In this study, urinary osteopontin, podocytes number, and levels of immunoglobulin M (IgM) were determined in 60 patients (diabetic normoalbuminuria, diabetic microalbuminuria, and nephritic syndrome) compared with healthy subjects...
2014: Disease Markers
Vanessa Pérez, Meritxell Ibernón, Dolores López, María Cruz Pastor, Maruja Navarro, Maribel Navarro-Muñoz, Josep Bonet, Ramón Romero
BACKGROUND: Minimal change disease (MCD) and primary focal segmental glomerulosclerosis (FSGS) are the main causes of primary idiopathic nephrotic syndrome in children and adults, with diagnosis being essential for the appropriate choice of therapy and requiring renal biopsy. However, the presence of only normal glomeruli on renal biopsy of FSGS patients may lead to the misclassification of these patients as having MCD. The aim of this study was to (i) compare the peptide profile of MCD and FSGS patients with that of a group of healthy subjects, (ii) generate and validate a class prediction model to classify MCD and FSGS patients and (ii) identify candidate biomarkers of these glomerular entities by analysis of the urinary peptidome...
2014: PloS One
Tara K Sigdel, Nathan Salomonis, Carrie D Nicora, Soyoung Ryu, Jintang He, Van Dinh, Daniel J Orton, Ronald J Moore, Szu-Chuan Hsieh, Hong Dai, Minh Thien-Vu, Wenzhong Xiao, Richard D Smith, Wei-Jun Qian, David G Camp, Minnie M Sarwal
Early transplant dysfunction and failure because of immunological and nonimmunological factors still presents a significant clinical problem for transplant recipients. A critical unmet need is the noninvasive detection and prediction of immune injury such that acute injury can be reversed by proactive immunosuppression titration. In this study, we used iTRAQ -based proteomic discovery and targeted ELISA validation to discover and validate candidate urine protein biomarkers from 262 renal allograft recipients with biopsy-confirmed allograft injury...
February 2014: Molecular & Cellular Proteomics: MCP
Marie C Hogan, Kenneth L Johnson, Roman M Zenka, M Cristine Charlesworth, Benjamin J Madden, Doug W Mahoney, Ann L Oberg, Bing Q Huang, Alexey A Leontovich, Lisa L Nesbitt, Jason L Bakeberg, Daniel J McCormick, H Robert Bergen, Christopher J Ward
Urinary exosome-like vesicles (ELVs) are a heterogenous mixture (diameter 40-200 nm) containing vesicles shed from all segments of the nephron including glomerular podocytes. Contamination with Tamm-Horsfall protein (THP) oligomers has hampered their isolation and proteomic analysis. Here we improved ELV isolation protocols employing density centrifugation to remove THP and albumin, and isolated a glomerular membranous vesicle (GMV)-enriched subfraction from 7 individuals identifying 1830 proteins and in 3 patients with glomerular disease identifying 5657 unique proteins...
May 2014: Kidney International
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