scholarly journals Alpha-1 Acid Glycoprotein and Podocin mRNA as Novel Biomarkers for Early Glomerular Injury in Obese Children

2021 ◽  
Vol 10 (18) ◽  
pp. 4129
Author(s):  
Anna Medyńska ◽  
Joanna Chrzanowska ◽  
Katarzyna Kościelska-Kasprzak ◽  
Dorota Bartoszek ◽  
Marcelina Żabińska ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Negative Impact ◽  
Glomerular Injury ◽  
Obese Children ◽  
Urine Sediment ◽  
Acid Glycoprotein ◽  
Glomerular Lesions ◽  
Specific Proteins ◽  
Podocyte Proteins ◽  
End Stage

Introduction: Obesity, which is a serious problem in children, has a negative impact on many organs, including kidneys, and obesity-related glomerulopathy (ORG) is an increasingly common cause of ESKD (end-stage kidney disease) in adults. Early-detected and -treated glomerular lesions are reversible, so it is important to find a useful marker of early damage. The study aimed to evaluate the albumin-to-creatinine ratio (ACR), urinary alpha-1-acid glycoprotein (α1-AGP), and mRNA of podocyte-specific proteins as indicators of glomerular injury and their relationship with the degree of obesity and metabolic disorders. Materials and Methods: A total of 125 obese children and 33 healthy peers were enrolled. Patients were divided into two groups, depending on SDS BMI values. ACR, α1-AGP, mRNA expression of nephrin, synaptopodin, podocin, and C2AP protein in urine sediment were measured. Results: ACR values did not differ between groups and were within the normal range. α1-AGP and mRNA expression were significantly higher in obese children compared with controls. mRNA expression of the remaining podocyte proteins was similar in both groups. No significant differences concerning all examined parameters were found depending on the degree of obesity. There was a positive significant correlation between α1-AGP and ACR. Conclusions: Increased α1-AGP before the onset of albuminuria suggests its usefulness as a biomarker of early glomerular damage in obese children. An increased podocin mRNA expression also indicates podocyte damage and may be linked to ORG development. The lack of increase in expression of other podocyte proteins suggests that podocin mRNA may be a more specific and sensitive biomarker. The degree of obesity has no impact on the tested parameters, but further studies are needed to confirm it.

scholarly journals Nephrin and Podocalyxin - New Podocyte Proteins for Early Detection of Secondary Nephropathies

2016 ◽  
Vol 14 (1) ◽  
pp. 11-16 ◽  
Author(s):  
Irena Kostovska ◽  
Katerina Tosheska Trajkovska ◽  
Svetlana Cekovska ◽  
Goce Spasovski ◽  
Danica Labudovic
Keyword(s):  
Early Diagnosis ◽  
Hypertensive Nephropathy ◽  
Common Causes ◽  
Specific Proteins ◽  
Functional Features ◽  
Podocyte Proteins ◽  
Main Component ◽  
End Stage ◽  
And Function ◽  
Main Clinical Manifestation

AbstractIn the last two decades a great progress was observed in understanding of podocytes, their specific structure and function identifying many specific podocyte proteins, such as nephrin and podocalyxin. Podocytes form the final barrier to plasma proteins leakage. Nephrin as a main component of the filtration diaphragm forms a physical barrier while podocalyxin as sialoglycoprotein forms an electrostatic barrier. Podocyte damage, i.e. podocytopathies and their loss through urine-podocyturia, are crucial in pathogenesis and progression of nephropathies with proteinuria as main clinical manifestation. In podocytopathies, nephrin and podocalyxin appear in the urine before proteinuria and microalbuminuria which were previously considered as earliest markers of nephropathies. Nephrinuria and podocalyxuria indicate damage of the podocytes on glomerular level and/or presence of apoptotic and necrotic podocytes in urine. These urinary markers are also important in early diagnosis of secondary nephropathies such as diabetic, lupus and hypertensive nephropathy as the most common causes of end-stage renal failure (ESRF). These markers are also important in the prediction of preeclampsia, which is the most common complication in pregnancy. In this review we elaborate in dept the main structural and functional features of podocytes and their specific proteins, nephrin and podocalyxin, summarizing the recent literature data on their importance in the early diagnosis of the most common secondary nephropathies.

scholarly journals Role of miRNA-671-5p in Mediating Wnt/β-Catenin-Triggered Podocyte Injury

2022 ◽  
Vol 12 ◽  
Author(s):  
Chunhong Wang ◽  
Jiafeng Liu ◽  
Xiaoyao Zhang ◽  
Qiyan Chen ◽  
Xiaoyan Bai ◽  
...  
Keyword(s):  
Wilms Tumor ◽  
Luciferase Reporter ◽  
Glomerular Injury ◽  
Bioinformatics Analyses ◽  
Podocyte Injury ◽  
Specific Proteins ◽  
Underlying Mechanisms ◽  
End Stage

Podocyte injury and proteinuria are the most common features of glomerular disease, which is the leading cause of end-stage renal failure. Hyperactivated Wnt/β-catenin signaling is closely associated with podocyte injury, but the underlying mechanisms are incompletely understood. Here we show that miRNA-671-5p (miR-671-5p) plays a crucial role in mediating β-catenin-triggered podocyte injury by targeting Wilms tumor 1 (WT1). Microarray-based expression profiling revealed that miR-671-5p was the most upregulated miRNA in podocytes after β-catenin activation. MiR-671-5p was colocalized with β-catenin in the glomeruli of proteinuric CKD in vivo. Bioinformatics analyses and luciferase reporter assays confirmed that miR-671-5p targeted WT1 mRNA. Overexpression of miR-671-5p mimics inhibited WT1 and impaired podocyte integrity, whereas miR-671-5p antagomir preserved the expression of WT1 and other podocyte-specific proteins under basal conditions or after β-catenin activation. In mouse remnant kidney model, overexpression of miR-671-5p aggravated podocyte injury, worsened kidney dysfunction and exacerbated renal fibrosis after 5/6 nephrectomy. In contrast, miR-671-5p antagomir alleviated podocyte injury and attenuated proteinuria and renal fibrotic lesions after glomerular injury in vivo. These studies underscore a pivotal role of miR-671-5p in mediating WT1 depletion and podocyte injury induced by β-catenin. Targeting miR-671-5p may serve as a new approach to prevent podocyte injury and proteinuria in proteinuric CKD.

Glomerular injury in end-stage liver disease — role of circulating IgG and IgM immune complexes

1993 ◽  
Vol 7 (1) ◽  
pp. 6-10 ◽  
Author(s):  
Lawrence S. Milner ◽  
Mark T. Houser ◽  
Peter C. Kolbeck ◽  
Dean L. Antonson ◽  
Thomas L. McDonald ◽  
...  
Keyword(s):  
Liver Disease ◽  
Immune Complexes ◽  
Glomerular Injury ◽  
End Stage Liver Disease ◽  
End Stage

DIABETIC RETINOPATHY, CLASSIFIED USING THE LESION-AWARE DEEP LEARNING SYSTEM, PREDICTS DIABETIC END-STAGE RENAL DISEASE IN CHINESE PATIENTS

2020 ◽  
Vol 26 (4) ◽  
pp. 429-443 ◽  
Author(s):  
Lijun Zhao ◽  
Honghong Ren ◽  
Junlin Zhang ◽  
Yana Cao ◽  
Yiting Wang ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Deep Learning ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Learning System ◽  
Chinese Patients ◽  
Glomerular Lesions ◽  
Stage Renal Disease ◽  
End Stage

Objective: To characterize the relationship between diabetic retinopathy (DR) and diabetic nephropathy (DN) in Chinese patients and to determine whether the severity of DR predicts end-stage renal disease (ESRD). Methods: Bilateral fundic photographs of 91 Chinese type 2 diabetic patients with biopsy-confirmed DN, not in ESRD stage, were obtained at the time of renal biopsy in this longitudinal study. The baseline severity of DR was determined using the Lesion-aware Deep Learning System (RetinalNET) in an open framework for deep learning and was graded using the Early Treatment Diabetic Retinopathy Study severity scale. Cox proportional hazard models were used to estimate the hazard ratio (HR) for the effect of the severity of diabetic retinopathy on ESRD. Results: During a median follow-up of 15 months, 25 patients progressed to ESRD. The severity of retinopathy at the time of biopsy was a prognostic factor for progression to ESRD (HR 2.18, 95% confidence interval 1.05 to 4.53, P = .04). At baseline, more severe retinopathy was associated with poor renal function, and more severe glomerular lesions. However, 30% of patients with mild retinopathy and severe glomerular lesions had higher low-density lipo-protein-cholesterol and more severe proteinuria than those with mild glomerular lesions. Additionally, 3% of patients with severe retinopathy and mild glomerular changes were more likely to have had diabetes a long time than those with severe glomerular lesions. Conclusion: Although the severity of DR predicted diabetic ESRD in patients with type 2 diabetes mellitus and DN, the severities of DR and DN were not always consistent, especially in patients with mild retinopathy or microalbuminuria. Abbreviations: CI = confidence interval; DM = diabetic mellitus; DN = diabetic nephropathy; DR = diabetic retinopathy; eGFR = estimated glomerular filtration rate; ESRD = end-stage renal disease; HbA1c = hemoglobin A1c; HR = hazard ratio; NPDR = nonproliferative diabetic retinopathy; PDR = proliferative diabetic retinopathy; SBP = systolic blood pressure; T2DM = type 2 diabetes mellitus; VEGF = vascular endothelial growth factor

scholarly journals Differential expression of CD11b/CD18 (Mo1) and myeloperoxidase genes during myeloid differentiation

Blood ◽  
1989 ◽  
Vol 73 (1) ◽  
pp. 131-136 ◽  
Author(s):  
AG Rosmarin ◽  
SC Weil ◽  
GL Rosner ◽  
JD Griffin ◽  
MA Arnaout ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mrna Expression ◽  
Cell Adhesion Molecule ◽  
Surface Expression ◽  
Cell Surface Expression ◽  
Myeloid Differentiation ◽  
Mrna Levels ◽  
Acute Nonlymphocytic Leukemia ◽  
Specific Proteins ◽  
Early Human

During the course of differentiation of early human myeloid cells toward monocytes and granulocytes, cell surface expression of the cell adhesion molecule, CD11b/CD18 (Mo1) increases dramatically and expression of myeloperoxidase (MPO), a bacteriocidal enzyme, decreases markedly. Using the inducible promyelocytic cell line HL-60 as a model, we studied the mRNA expression of these genes. Differentiation of these cells along both a monocytic and a granulocytic pathway demonstrated that the mRNA levels of the two subunits of CD11b/CD18 increased in a pattern temporally and quantitatively similar to the increase in cell surface expression of this heterodimer. In contrast, the expression of MPO mRNA decreased in a temporal and quantitative pattern similar to the known decrease in MPO protein during differentiation, suggesting that regulation of these myeloid-specific proteins may occur at the level of mRNA expression. These findings have important implications with regard to the nature of the block in differentiation in acute nonlymphocytic leukemia and the regulation of myeloid gene expression.

scholarly journals Evaluation of Tryptic Podocin Peptide in Urine Sediment Using LC-MS-MRM Method as a Potential Biomarker of Glomerular Injury in Dogs with Clinical Signs of Renal and Cardiac Disorders

Molecules ◽  
2019 ◽  
Vol 24 (17) ◽  
pp. 3088 ◽  
Author(s):  
Barbara Szczepankiewicz ◽  
Remigiusz Bąchor ◽  
Robert Pasławski ◽  
Natalia Siwińska ◽  
Urszula Pasławska ◽  
...  
Keyword(s):  
Clinical Signs ◽  
Cardiorenal Syndrome ◽  
Specific Protein ◽  
Glomerular Injury ◽  
Model Peptide ◽  
Diagnostic Challenge ◽  
Urine Sediment ◽  
Heart Insufficiency ◽  
Potential Biomarker ◽  
Potential Applicability

The early asymptomatic stage of glomerular injury is a diagnostic challenge in the course of renal and extra-renal disease, e.g., heart insufficiency. It was found that podocin, a podocyte-specific protein present in the urine, may serve as a biomarker in the diagnosis of glomerular disease in humans and animals including glomerulonephritis, glomerulosclerosis, amyloidosis, or nephropathy. Therefore, there is a need of development of the sensitive and straightforward method of urinary podocin identification. In this work, we report our extended research under the glomerular injury investigation in dogs by application of clinical examination and LC-MS-MRM method in the identification of canine podocin in urine samples. The LC-MS-MRM method is based on the identification of podocin tryptic peptide with the 218H-AAEILAATPAAVQLR-OH232 sequence. The model peptide was characterized by the highest ionization efficiency of all the proposed model podocin tryptic peptides in a canine urine sediment according to the LC-MS/MS analysis. The obtained results revealed the presence of the model peptide in 40.9% of dogs with MMVD (active glomerular injury secondary to heart disease = cardiorenal syndrome-CRS) and 33.3% dogs with chronic kidney disease. The potential applicability of the developed methodology in the analysis of podocin in canine urine sediments was confirmed.

Schistosomiasis

2018 ◽  
Author(s):  
Rashad S. Barsoum
Keyword(s):  
Urinary Tract ◽  
Lower Urinary Tract ◽  
Immunoglobulin A ◽  
Class Ii ◽  
Acute Onset ◽  
Pathogenic Factors ◽  
Glomerular Lesions ◽  
End Stage ◽  
Focal Segmental Sclerosis ◽  
Lower Urinary

The urinary system is the primary target of Schistosoma haematobium infection, which leads to granuloma formation in the lower urinary tract that heals with fibrosis and calcification. While the early lesions may be associated with distressing acute or subacute symptoms, it is the late lesions that constitute the main clinical impact of schistosomiasis. The latter include chronic cystitis, ureteric fibrosis, ureterovesical obstruction or reflux which may lead to chronic pyelonephritis. Secondary bacterial infection and bladder cancer are the main secondary sequelae of urinary schistosomiasis.The kidneys are also a secondary target of S. mansoni infection, attributed to the systemic immune response to the parasite. Specific immune complexes are responsible for early, often asymptomatic, possibly reversible, mesangioproliferative lesions which are categorized as ‘class I’. Subsequent classes (II–VI) display different histopathology, more serious clinical disease, and confounding pathogenic factors. Class II lesions are encountered in patients with concomitant salmonellosis; they are typically exudative and associated with acute-onset nephrotic syndrome. Classes III (mesangiocapillary glomerulonephritis) and IV (focal segmental sclerosis) are progressive forms of glomerular disease associated with significant hepatic pathology. They are usually associated with immunoglobulin A deposits which seem to have a significant pathogenic role. Class V (amyloidosis) occurs with long-standing active infection with either S. haematobium or S. mansoni. Class VI is seen in patients with concomitant HCV infection, where the pathology is a mix of schistosomal and cryoglobulinaemic lesions, as well as amyloidosis which seems to be accelerated by the confounded pathogenesis.Early schistosomal lesions, particularly those of the lower urinary tract, respond to antiparasitic treatment. Late urological lesions may need surgery or endoscopic interventions. As a rule, glomerular lesions do not respond to treatment with the exception of class II where dual antiparasitic and antibiotic therapy is usually curative. Patients with end-stage kidney disease may constitute specific, yet not insurmountable technical and logistic problems in dialysis or transplantation. Recurrence after transplantation is rare.

scholarly journals The negative impact of the COVID-19 lockdown on pain and physical function in patients with end-stage hip or knee osteoarthritis

2020 ◽  
Vol 28 (8) ◽  
pp. 2435-2443 ◽  
Author(s):  
Franz Endstrasser ◽  
Matthias Braito ◽  
Markus Linser ◽  
Anna Spicher ◽  
Moritz Wagner ◽  
...  
Keyword(s):  
Knee Osteoarthritis ◽  
Physical Function ◽  
Negative Impact ◽  
End Stage

scholarly journals Effect of cardiac resynchronization therapy on left ventricular fibrosis-related mRNA expression profile in patients with end-stage heart failure

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A.A Sayour ◽  
A Olah ◽  
M Ruppert ◽  
B.A Barta ◽  
M Polos ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Expression Profile ◽  
Biventricular Pacing ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Resynchronization Therapy ◽  
Mrna Expression Profile ◽  
Reverse Remodelling ◽  
History Of ◽  
End Stage

Abstract Background When indicated, cardiac resynchronization therapy (biventricular pacing, CRT) decreases mortality in patients with heart failure (HF) and reduced ejection fraction, especially in those with non-ischemic cardiomyopathy. This is reflected by relatively rapid improvement of left ventricular (LV) end-diastolic diameter (LVEDD) and LV ejection fraction (LVEF) indicating reverse remodelling. These LV structural and functional improvements are accompanied by characteristic changes in LV gene expression profile. However, whether beneficial gene expression alterations related to biventricular pacing are sustained independently of structural and functional reverse remodelling is unclear. Purpose We aimed to compare LV fibrosis-related mRNA expression profile in end-stage HF patients with idiopathic dilated cardiomyopathy (DCM) who were not on CRT versus to those on CRT. Methods Left ventricular myocardial samples were harvested from end-stage HF patients undergoing heart transplantation (HTX). Inclusion criteria were negative family history of DCM, negative coronarography (i.e. non-ischemic), no relevant comorbidity (e.g. diabetes, hypertension) and no history of myocarditis. Accordingly, the following patient groups were included: 1.) DCM (n=12, 17% female, mean age [±standard deviation] 46.8±11.8 years) without CRT and 2.) CRT-DCM (n=12, 42% female, mean age 47.8±12.3 years) which comprised DCM patients on active CRT for mean 3.2±2.4 years until HTX. LV RNA was extracted and subjected to a commercially available mRNA expression panel interrogating 760 genes related to the development and regulation of fibrosis. Normalization to 10 housekeeping genes and batch corrections were conducted as per protocol. LV mRNA expression of atrial-natriuretic peptide (ANP) was quantified using qRT-PCR. Results Markers of reverse remodelling including LVEDD (73.4±8.3 mm vs 75.4±9.9 mm), LVEF (21.9±3.7% vs 18.5±6.8%) and LV ANP mRNA expression (arbitrary units: 1.05±1.80 vs 1.04±0.88) were comparable between DCM and CRT-DCM patients (all P>0.05), respectively. High-throughput mRNA expression screening revealed significant (all P<0.001) downregulation of 3 genes proven to be implicated in adverse LV remodelling: alpha catalytic subunit of protein phosphatase 2 (PPP2CA), interleukin 20 receptor subunit beta (IL20RB) and lipoprotein lipase (LPL). According to pathway analysis using directed significance scores, CRT was associated with collective upregulation of genes modifying complement activation (SERPING1, C1S, CFH) and collective downregulation of genes promoting cell proliferation (PPP2CA, ANAPC7, HSP90AA1, CSNK2B). Conclusions Independently of structural and functional reverse remodelling, CRT might be associated with slightly favourable LV expression profile of genes related to the regulation and development of fibrosis. This suggests that biventricular pacing might be beneficial on the molecular level beyond improvement of LV structure and function. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Research, Development and Innovation Fund of Hungary, Higher Education Institutional Excellence Programme of the Ministry of Human Capacities of Hungary

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