Assessment of Urinary Uromodulin and the Corresponding Urinary Exosomal UMOD mRNA Gene Expression as a Potential Biomarker of Diabetic Nephropathy
Study Details
Study Description
Brief Summary
Diabetes is a major health problem prolonged untreated diabetes cause kidney diseases that can leads to end stage renal disease (ESRD). There are several biomarkers to access the DN severity but there are conflicting regarding the specifity and sensitivity of these biomarkers. So it is important to identify novel biomarker for early detection DN and progression toward ESRD to minimize the prevelance of CKD in human population. Uromodulin is a tubular protein encoded by UMOD gene which expressed predominantly in the epithelial cells of thick ascending limb (TAL) of henel's loop. This study was conducted to evaluate the level of urinary uromodulin and its corresponding exosomal mRNA gene expression as a potentional marker for early detection of DN in type 2 diabetic patients
| Condition or Disease | Intervention/Treatment | Phase |
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Detailed Description
Introduction Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia resulting from defect in insulin secretion, insulin action or both. The chronic hyperglycemia of diabetes is associated with long term damage, dysfunction and failure of various organs especially the eyes, kidneys, nerves, heart and blood vessels (American Diabetes Association., 2008) Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes and represents an important cause of chronic kidney disease (CKD) that frequently leads to end-stage renal disease (ESRD) (Macisaac et al., 2014).
DN is characterized pathophysiologically by an early phase with glomerular hypertrophy, hyperfiltration and microalbuminuria that over the course of years leads to an advanced phase with progressive glomerulosclerosis, rise in the urinary albumin excretion (UAE), and abnormal renal function (Schrijvers et al., 2004).
Conventionally, DN severity is accessed by measuring urine albumin levels (albumin-to-creatinine ratio) persistent microalbuminuria (between 30-300 mg/24 hr) or macroalbuminuria (levels >300 mg/24 hr) is considered a marker and predictor of DN and its progression to ESRD (Adler et al., 2003).
Recent studies are conflicting regarding the sensitivity and the specificity of biomarkers currently used in practice for DN diagnosis. The identification of novel biomarkers of early stages of DN and progression toward ESRD is thus mandatory to reduce the burden of chronic kidney diseases in the human population (Carole et al., 2017).
Uromodulin also called Tamm-Horsfall protein is a 85 kDa glycoprotein normally secreted by epithelial cells lining thick ascending limb (TAL) of Henle's loop and early distal tubule, released by proteolytic cleavage of glycosylphosphatidylinositol (GPI)-anchored protein that is predominant localized to the apical plasma membrane.
The gene for human uromodulin is called UMOD gene, located on chromosome 16p12.3, coding for 616 amino acid and contains 15 exons. The levels of uromodulin had marked change in urinary excretion in pathological conditions. Therefore, uromodulin was useful as a marker of renal disease (Neng et al., 2017 ).
Uromodulin has diverse functions including prevention of ascending urinary tract infections by binding type-I toxin of bacteria Escherichia coli, prevention of calcium oxalate aggregation and kidney stones formation, regulating sodium, potassium, chloride transport and it has immunomodulatory properties as it activates granulocytes and mediates monocytes cytotoxicity (Chia et al., 2017).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Controlgroup 25 healthy subjects as a control group. |
Diagnostic Test: ACR, fasting, postprandial blood glucose ,HbA1c, creatinine, cystatin-C, BUN, Na, K , lipid profile
Use the ACR to divide diabetic patients to 3groups not normoalbuminuria, microalbuminuria, macroalbuminuria to evaluate the urinary uromodulin level and its exosomal umod mRNA as a potential biomarker of Diabetic nephropathy diagnosis
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| diabetic patients with normoalbuminuria Consisted of 25 type 2 diabetic patients with normoalbuminuria (levels <30 mg/g creatinine) |
Diagnostic Test: ACR, fasting, postprandial blood glucose ,HbA1c, creatinine, cystatin-C, BUN, Na, K , lipid profile
Use the ACR to divide diabetic patients to 3groups not normoalbuminuria, microalbuminuria, macroalbuminuria to evaluate the urinary uromodulin level and its exosomal umod mRNA as a potential biomarker of Diabetic nephropathy diagnosis
|
| diabetic patients with microalbuminuria Consisted of 25 type 2 diabetic patients with microalbuminuria (between 30-300 mg/g creatinine). |
Diagnostic Test: ACR, fasting, postprandial blood glucose ,HbA1c, creatinine, cystatin-C, BUN, Na, K , lipid profile
Use the ACR to divide diabetic patients to 3groups not normoalbuminuria, microalbuminuria, macroalbuminuria to evaluate the urinary uromodulin level and its exosomal umod mRNA as a potential biomarker of Diabetic nephropathy diagnosis
|
| diabetic patients with macrolbuminuria Consisted of 25 type 2 diabetic patients with macroalbuminuria (levels >300 mg/g creatinine) |
Diagnostic Test: ACR, fasting, postprandial blood glucose ,HbA1c, creatinine, cystatin-C, BUN, Na, K , lipid profile
Use the ACR to divide diabetic patients to 3groups not normoalbuminuria, microalbuminuria, macroalbuminuria to evaluate the urinary uromodulin level and its exosomal umod mRNA as a potential biomarker of Diabetic nephropathy diagnosis
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Outcome Measures
Primary Outcome Measures
- Determination the level of urinary uromodulin as a potential biomarker for early prediction of DN [June, 2022]
Evaluate the level of urinary uromodulin in the 3 diabetic group comparing with each other and compare them to the control group and correlate these results with other kidney biomarker
- Determine the urinary exosomal UMODmRNA gene expression [June, 2022]
Isolation of urinary exosomes and extraction the UMOD mRNA from these exosoms and determine the fold change of the exosomal UMOD mRNA between the diabetic groups and control group and correlate it with the urinary uromodulin level and other kidney biomarker
Eligibility Criteria
Criteria
Inclusion Criteria:
- Type 2 diabetic patients with not no album in ur is, micoalbuminuria and macroalbuminuria
Exclusion Criteria:
- History or existence of non diabetic or obstructive kidney disease, urinary tract infection, liver disease, autoimmune, inflammatory or neoplastic diseases will be excluded from the study.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Tanta university hospital, faculty of science, tanta university | Tanta | Al Gharbia | Egypt | 31515 |
Sponsors and Collaborators
- Tanta University
- Ain Shams University
Investigators
- Study Director: Tarek M mohamed, prof, Faculty of science, tanta university
- Study Director: Eman M Abd elAzeem, prof, faculty of science, Ain shams University
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- DN UMOD