Determination of Uromodulin as a Potential Biomarker of Diabetic Kidney Disease
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Diabetic Nephropathy
- Sponsor
- Tanta University
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Determine the urinary exosomal UMODmRNA gene expression
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
Detecting diabetes-related kidney diseases early is crucial to prevent end-stage renal disease (ESRD). Existing biomarkers' specificity and sensitivity vary, emphasizing the need for novel markers. This research assesses urinary uromodulin levels and its gene expression, aiming to identify a potential marker for early diabetic nephropathy (DN) detection in type 2 diabetes patients. Uromodulin, encoded by the UMOD gene, is expressed mainly in the thick ascending limb of Henle's loop epithelial cells, making it a promising candidate for early DN detection and progression towards ESRD, potentially reducing chronic kidney disease prevalence.
Detailed Description
Introduction: Diabetes mellitus (DM) is a metabolic disorder characterized by elevated blood glucose levels resulting from deficiencies in insulin secretion, insulin action, or both. Prolonged hyperglycemia associated with diabetes can lead to lasting damage and dysfunction in various organs, including the eyes, kidneys, nerves, heart, and blood vessels (American Diabetes Association, 2008). Among the complications of diabetes, diabetic nephropathy (DN) stands out as a significant contributor to chronic kidney disease (CKD) (Macisaac et al., 2014). Pathophysiologically, DN progresses from an early phase featuring glomerular hypertrophy, hyperfiltration, and microalbuminuria to an advanced phase marked by progressive glomerulosclerosis, increased urinary albumin excretion (UAE), and impaired renal function (Schrijvers et al., 2004). Traditionally, DN severity is assessed by measuring urine albumin levels, with persistent microalbuminuria (30-300 mg/24 hr) or macroalbuminuria (\>300 mg/24 hr) serving as markers and predictors of DN and its progression to end-stage renal disease (Adler et al., 2003). Current practices in biomarker use for DN diagnosis show conflicting results regarding sensitivity and specificity in recent studies. Therefore, it is imperative to identify novel biomarkers for early DN detection and progression to reduce the prevalence of chronic kidney diseases in the population (Carole et al., 2017). Uromodulin, also known as Tamm-Horsfall protein, is an 85 kDa glycoprotein normally secreted by epithelial cells lining the thick ascending limb (TAL) of Henle's loop and early distal tubule. It is released through proteolytic cleavage of glycosylphosphatidylinositol (GPI)-anchored protein, primarily localized to the apical plasma membrane. Uromodulin levels undergo significant changes in urinary excretion during pathological conditions, making it a valuable marker for renal disease
Investigators
Shaimaa Ibrahim Barr
Tanta, Egypt
Ain Shams University
Eligibility Criteria
Inclusion Criteria
- •Type 2 diabetic patients with not no album in ur is, micoalbuminuria and macroalbuminuria
Exclusion Criteria
- •prescence of non diabetic or obstructive kidney disease,
Outcomes
Primary Outcomes
Determine the urinary exosomal UMODmRNA gene expression
Time Frame: 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
Determination the level of urinary uromodulin as a potential biomarker for early prediction of DN
Time Frame: 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