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| Name | Class |
|---|---|
| Ain Shams University | OTHER |
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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.
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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Controlgroup | 25 healthy volunteer as a control |
| |
| diabetic patients with normoalbuminuria | Consisted of 25 type 2 diabetic patients with normoalbuminuria (levels <30 mg/g creatinine) |
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| diabetic patients with microalbuminuria | Consisted of 25 type 2 diabetic patients with microalbuminuria (between 30-300 mg/g creatinine). |
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| diabetic patients with macrolbuminuria | Consisted of 25 type 2 diabetic patients with macroalbuminuria (levels >300 mg/g creatinine) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ACR, fasting, postprandial blood glucose ,HbA1c, creatinine, cystatin-C, BUN, Na, K , lipid profile | Diagnostic Test | 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:prescence of non diabetic or obstructive kidney disease,
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Patients were selected from those admitted to the Internal Medicine Department and outpatients of Tanta University Hospital
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| Name | Affiliation | Role |
|---|---|---|
| Tarek M mohamed, prof | Faculty of science, tanta university | Study Director |
| Eman M Abd elAzeem, prof | faculty of science, Ain shams University | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Tanta university hospital, faculty of science, tanta university | Tanta | Al Gharbia | 31515 | Egypt |
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| Label | URL |
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| Related Info | View source |
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| ID | Term |
|---|---|
| D003928 | Diabetic Nephropathies |
| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
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| ID | Term |
|---|---|
| D001806 | Blood Urea Nitrogen |
| ID | Term |
|---|---|
| D001774 | Blood Chemical Analysis |
| D019963 | Clinical Chemistry Tests |
| D019411 | Clinical Laboratory Techniques |
| D019937 | Diagnostic Techniques and Procedures |
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Urine samples: first morning samples were collected 3ml for ACR 15ml was stored at -80 ℃ until the time of exosome isolation 6ml of peripheral venous blood were collected 2ml of venous blood was collected in an EDTA vacutainer tube for determination of HbA1c.
1ml of venous blood was drawn from each subject 2hrs after meal for postprandial
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| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D048909 | Diabetes Complications |
| D003920 | Diabetes Mellitus |
| D004700 | Endocrine System Diseases |
| D003933 | Diagnosis |
| D007677 | Kidney Function Tests |
| D003950 | Diagnostic Techniques, Urological |
| D008919 | Investigative Techniques |