Clinical trial NCT05695573: Assessment of Urinary Uromodulin and the Corresponding Gene Expression as a Biomarker of Diabetic Nephropathy
Official title: Determination of Uromodulin as a Potential Biomarker of Diabetic Kidney Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Diabetic Nephropathy
Lead sponsor: Tanta University
Sponsor class: OTHER
Collaborators: name: Ain Shams University
First posted: 2023-01-25
Enrollment: 100
Sex: ALL
Minimum age (years): 40
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Patients were selected from those admitted to the Internal Medicine Department and outpatients of Tanta University Hospital

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

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,

Primary outcomes:
measure: Determination the level of urinary uromodulin as a potential biomarker for early prediction of DN
timeFrame: June, 2022
measure: Determine the urinary exosomal UMODmRNA gene expression
timeFrame: June, 2022
Secondary outcomes:
Other outcomes:
Locations:
city: Tanta
country: Egypt
facility: Tanta university hospital, faculty of science, tanta university
state: Al Gharbia
Study officials:
affiliation: Faculty of science, tanta university
name: Tarek M mohamed, prof
role: STUDY_DIRECTOR
affiliation: faculty of science, Ain shams University
name: Eman M Abd elAzeem, prof
role: STUDY_DIRECTOR
References: