Assessment of Urinary Uromodulin and the Corresponding Gene Expression as a Biomarker of Diabetic Nephropathy
Condition: Diabetic Nephropathy
MeSH terms: Kidney Diseases; Diabetic Nephropathies
Study type: Observational

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
    

Intervention name(s): ACR, fasting, postprandial blood glucose ,HbA1c, creatinine, cystatin-C, BUN, Na, K , lipid profile
Intervention type(s): Diagnostic Test
Intervention description(s): 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
Intervention MeSH terms: Cystatins
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
      
Biospecimen description: 
      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