Markers of Vascular Calcification in Diabetic Nephropathy in Patients With Diabetic Nephropathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT03820635

Recruitment Status : Unknown

Verified January 2019 by Ahmed Mahmoud ahmed ali, Assiut University.
Recruitment status was: Not yet recruiting

First Posted : January 29, 2019

Last Update Posted : January 29, 2019

Sponsor:

Information provided by (Responsible Party):

Ahmed Mahmoud ahmed ali, Assiut University

Study Description

Brief Summary:

The study will be conducted at Assiut University Hospital. Eligible subjects will be screened for vascular calcification by Doppler ultrasound examination. A correation between the level of serum Osteopontin (OPN) level and the extent of vascular calcification will be evaluated.

Condition or disease	Intervention/treatment
Diabetic Nephropathies Vascular Calcification	Diagnostic Test: Osteopontin (OPN)

Show detailed description

Detailed Description:

Osteopontin (OPN) is one of integrin-binding N-linked glycoproteins, which is produced by activated mononuclear cells and is linked to increasing evidence about the role of OPN in vascular calcification[1].

Recent clinical studies have shown that vascular calcification is a pathological process leading to mechanical rigidity and stiffness of vascular wall, endothelial dysfunction, development and accelerating atherosclerosis even in the absence of established cardiovascular (CV) disease . Ectopic calcification is explained by several mutually counteracting molecular mechanisms, i.e. oxidative stress, microvascular inflammation, immune cell-to-cell cooperation, accumulation of lipids and extracellular proteins, vascular reparative systems, and metabolic disorders All these processes are under tight regulation of vitamin D, parathyroid hormone-related peptides (fibroblast growth factor, transcription factor Sox2, beta-catenin, etc) and matricellular proteins such as OPN. [2].

OPN was found to have relation with vascular calcification, atherosclerosis, and CV disease associated with severe vascular remodelling including hypertension, chronic kidney disease, diabetes mellitus . In this context, OPN is a promising biomarker of vascular remodelling closely related to inflammation intensity, glucose level and pro-thrombotic state with promising predictive value for CV events [3].

It is a matricellular protein that was first identified in 1995 by Heingard et al. as sialoprotein derived from bovine bone matrix . During the last decade a number of studies analysed the role of OPN in the pathogenesis of diabetic nephropathy. This proposed association needs confirmation and detailed description by further research [4].

At first, OPN has been reported to be highly expressed in the tubular epithelium of the renal cortex and in glomeruli in rat and mouse models of diabetic nephropathy [5]. This was associated with extensive macrophage accumulation in the kidney interstitium indicating that OPN upregulation and macrophage recruitment may play a role in the tubulo-interstitial injury in diabetic nephropathy [6]. Consistently, OPN/mice are protected from diabetes-induced albuminuria and renal damage, possibly by modulating podocyte signaling and motility [7]. In humans, plasma OPN levels are independently associated with presence and severity of diabetic nephropathy [8] Compelling evidence in the literature provides interesting clues about a link between the rennin-angiotensin system (RAS) and OPN in diabetic kidney disease. Diabetes-induced OPN expression and macrophage accumulation in the kidney interstitium of diabetic rats are significantly ameliorated after treatment with the long acting ACE inhibitor [9]. Showing that treatment with ramipril for nine month improves creatinine clearance rate and decreases urinary protein excretion, systolic blood pressure, development of glomerulosclerosis, tubulo-interstitial fibrosis and inflammatory cell infiltration in a diabetics. Of note, all these effects of ACE inhibition were associated with markedly suppressed OPN expression, suggesting that blockade of the RAS by ramipril may confer renoprotection by decreasing OPN secretion in diabetic nephropathy [10]. Liver X receptors (LXRs) have been identified as important lipid-dependent regulators of glucose metabolism and immune functions in leukocytes [11]. Synthetic LXR ligands can inhibit cytokine-induced OPN expression in macrophages [12]. Tachibana and colleges recently observed decreased urinary albumin excretion and substantially attenuated macrophage infiltration, mesangial matrix accumulation and interstitial fibrosis in streptozotocin-induced diabetics following administration of the LXR agonist T0901317. Notably, this was paralleled by diminished OPN expression in the kidney cortex indicating that inhibition of renal OPN by LXR activation may provide a potential therapeutical approach for diabetic nephropathy [13].

Osteopontin (OPN) is a multifunctional protein expressed by several different cell types, although the bone is known to be a major source [14].The exact excretion pathway of OPN from the body is not known. OPN is involved in a number of physiological and pathological conditions, including (1), urinary stones (2), wound healing (3), chronic inflammatory and autoimmune diseases (4), obesity-related chronic inflammation, and insulin resistance. However, OPN was originally found in bone and shown to regulate the formation and calcification of bone tissue. [15].

Notably, OPN has also been linked to vascular remodelling and calcification, especially in diabetic arteries, and has been shown to associate with diabetic retinopathy and nephropathy in patients with type 2 diabetes (T2D), as well as cardiovascular disease (CVD) events in diabetic subjects with history of long standing diabetes. [16]

Study Design

Layout table for study information

Study Type :	Observational
Estimated Enrollment :	20 participants
Observational Model:	Case-Control
Time Perspective:	Cross-Sectional
Official Title:	Relation Between Plasma Concentration of Osteopontin Level and Vascular Calcification in Patients With Diabetic Nephropathy
Estimated Study Start Date :	March 1, 2019
Estimated Primary Completion Date :	July 1, 2020
Estimated Study Completion Date :	September 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Diabetic Kidney Problems Kidney Diseases Minerals

U.S. FDA Resources

Groups and Cohorts

Group/Cohort	Intervention/treatment
Calcified those with evidence of vascular calcification	Diagnostic Test: Osteopontin (OPN) the serum level of Osteopontin (OPN) will be measured in the subject's blood sample
Non-calcified those with no evidence of vascular calcification	Diagnostic Test: Osteopontin (OPN) the serum level of Osteopontin (OPN) will be measured in the subject's blood sample

Outcome Measures

Primary Outcome Measures :

correlation coefficient between serum level of osteoponton and the rate of different aspects of vascular affection as discussed previously [ Time Frame: 6 months ]
the correlation coefficient

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

all patients diagnosed with diabetic nephropathies

Criteria

Inclusion Criteria:

adult patients diagnosed clinically as diabetic nephropathy within 5 years

Exclusion Criteria:

patients with any previous macrovascular complication: coronary heart disease, cerebrovascular stroke, peripheral ischaemia

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03820635

Locations

Layout table for location information

Egypt
Assiut University
Asyūţ, Egypt, 71515
Contact: Ahmed MA Ali, MSc +201006918718 drahmedmosaed2016@gmail.com

Sponsors and Collaborators

Assiut University

More Information

Layout table for additonal information

Responsible Party:	Ahmed Mahmoud ahmed ali, Doctor, Assiut University
ClinicalTrials.gov Identifier:	NCT03820635
Other Study ID Numbers:	MVasCDN
First Posted:	January 29, 2019 Key Record Dates
Last Update Posted:	January 29, 2019
Last Verified:	January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Layout table for additional information

Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Additional relevant MeSH terms:

Layout table for MeSH terms

Kidney Diseases Diabetic Nephropathies Calcinosis Vascular Calcification Urologic Diseases	Diabetes Complications Diabetes Mellitus Endocrine System Diseases Calcium Metabolism Disorders Metabolic Diseases

To Top