Assessment of Urinary Uromodulin and the Corresponding Gene Expression as a Biomarker of Diabetic Nephropathy

Determination of Uromodulin as a Potential Biomarker of Diabetic Kidney Disease

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Nephropathy
• Intervention / Treatment: Diagnostic test: ACR, fasting, postprandial blood glucose ,HbA1c, creatinine, cystatin-C, BUN, Na, K , lipid profile

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

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Egypt
  • Al Gharbia
    • Tanta, Al Gharbia, Egypt, 31515
      • Tanta university hospital, faculty of science, tanta university

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Patients were selected from those admitted to the Internal Medicine Department and outpatients of Tanta University Hospital

Description

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,

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
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
Controlgroup; 25 healthy volunteer as a control	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination the level of urinary uromodulin as a potential biomarker for early prediction of DN	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	June, 2022
Determine the urinary exosomal UMODmRNA gene expression	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	June, 2022

Collaborators and Investigators

• Sponsor: Tanta University
• Collaborators: 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

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2019
• Primary Completion (Actual): April 28, 2022
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: January 13, 2023
• First Submitted That Met QC Criteria: January 23, 2023
• First Posted (Actual): January 25, 2023

Study Record Updates

• Last Update Posted (Actual): December 22, 2023
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Diabetic Nephropathies; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Cysteine Proteinase Inhibitors; Cystatins
• Other Study ID Numbers: DN UMOD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No