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

Tanta University

Status: Completed

Conditions: Diabetic Nephropathy

Treatments: Diagnostic Test: ACR, fasting, postprandial blood glucose ,HbA1c, creatinine, cystatin-C, BUN, Na, K , lipid profile

Study type: Observational

Funder types: Other

Identifiers

NCT05695573

DN UMOD

Details and patient eligibility

About

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.

Full 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

Enrollment: 100 patients

Sex: All

Ages: 40 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion 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,

Trial design

100 participants in 4 patient groups

Controlgroup

Description:

25 healthy volunteer as a control

Treatment:

Diagnostic Test: ACR, fasting, postprandial blood glucose ,HbA1c, creatinine, cystatin-C, BUN, Na, K , lipid profile

diabetic patients with normoalbuminuria

Description:

Consisted of 25 type 2 diabetic patients with normoalbuminuria (levels \<30 mg/g creatinine)

Treatment:

Diagnostic Test: ACR, fasting, postprandial blood glucose ,HbA1c, creatinine, cystatin-C, BUN, Na, K , lipid profile

diabetic patients with microalbuminuria

Description:

Consisted of 25 type 2 diabetic patients with microalbuminuria (between 30-300 mg/g creatinine).

Treatment:

Diagnostic Test: ACR, fasting, postprandial blood glucose ,HbA1c, creatinine, cystatin-C, BUN, Na, K , lipid profile

diabetic patients with macrolbuminuria

Description:

Consisted of 25 type 2 diabetic patients with macroalbuminuria (levels \>300 mg/g creatinine)

Treatment:

Diagnostic Test: ACR, fasting, postprandial blood glucose ,HbA1c, creatinine, cystatin-C, BUN, Na, K , lipid profile