FGF-23 and Endothelial Dysfunction in Diabetic Proteinuric Patients
Condition: Proteinuria; Diabetic Nephropathy; Chronic Kidney Disease
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Diabetic Nephropathies; Proteinuria
Study type: Interventional
Phase: Phase 4

Summary: 
      There is no data about the effects of Renin angiotensin system blockage (RAS) on FGF23 and
      ADMA levels in diabetic patients with proteinuria. The aim of this study was to find out
      whether the beneficial effects of RAS blockage in diabetic proteinuria has any relation with
      the alteration of ADMA and FGF-23 levels. We searched for the effects of ACE inhibitor
      ramipril on the clinical and laboratory parameters of diabetic patients with proteinuria.
    

Detailed description: 
      In recent years, diabetic nephropathy, which may lead to dialysis treatment, is the most
      prevalent underlying disease of people in developed countries. A wide range of studies have
      been carried out, from various points of view, to understand the progress of renal
      dysfunction in diabetic nephropathy. The endogenous nitric oxide synthase (NOS) inhibitor
      asymmetric dimethylarginine (ADMA) is elevated in patients with chronic kidney disease (CKD)
      and may have a role in the cardiovascular mortality and morbidity of these patients. In
      diabetic nephropathy, high ADMA levels were related to progression of diabetic nephropathy.

      Fibroblast growth factor 23 (FGF-23) is a primary regulator of renal phosphate excretion.
      FGF23 is inversely associated with the GFR, a relationship underlying a fundamental mechanism
      for maintaining serum phosphate constancy during CKD progression. Such an adaptation may have
      deleterious trade-offs because, independently of serum phosphate, high FGF23 signals a high
      risk of death in ESRD patients. Some studies showed that there is a relationship between
      FGF-23 levels and proteinuria in CKD patients.

      There is no data about the effects of Renin angiotensin system blockage (RAS) on FGF23 and
      ADMA levels in diabetic patients with proteinuria. The aim of this study was to find out
      whether the beneficial effects of RAS blockage in diabetic proteinuria has any relation with
      the alteration of ADMA and FGF-23 levels. We searched for the effects of ACE inhibitor
      ramipril on the clinical and laboratory parameters of diabetic patients with proteinuria.

      The study 'Effect of Renin Angiotensin System Blockade on the Fas Antigen (CD95) and
      Asymmetric Dimethylarginine (ADMA) Levels in Type-2 Diabetic Patients With Proteinuria' has
      been previously registered to ClinicalTrials.gov (Identifier:NCT00893425). The serum samples
      of the above study will be used in order to measure the FGF23 levels in this study. Therefore
      the eligibility criteria and the study design is similar to the previous study
      (Identifier:NCT00893425).

      The patients who were non-obese (BMI<30kg/m2), non dyslipidemic (total cholesterol <200mg/dl,
      Triglyceride<150mg/dl), and free of cardiovascular events (negative medical history, negative
      ECG findings) were investigated for enrollment. CKD stage 1 patients older than 18 years of
      age and willing to participate to the study were screened. From the 231 patients with
      established type 2 diabetes mellitus, 126 had proteinuria and/or hypertension (24 h protein
      excretion 1-2 g/day, systolic blood pressures ≥140mmHg and/or diastolic blood pressures ≥ 90
      mmHg, respectively). All cases were first referrals and at the time of the study all were off
      treatment. Patients with history of coronary artery disease, smokers and those taking statins
      or renin-angiotensin blockers were excluded because of the effect of these factors on
      endothelial dysfunction. Of 126 screened patients 78 met the study criteria and were included
      in this study. The duration of proteinuria and diabetic nephropathy after initial diagnosis
      was not known.

      The exclusion criteria were as follows: A)Nephrotic syndrome, B)coronary heart disease
      (patients with ischemic ST-T alterations and voltage criteria for LVH on electrocardiogram,
      and with history of revascularization or myocardial infarction), C) elevated liver enzymes
      (AST or ALT levels ≥ 40U/L) and D) renal failure (serum creatinine levels > 1.3 mg/dl). In
      order to evaluate the effect of RAS blockade on FGF 23 concentrations, patients with
      proteinuria were given an ACE inhibitor (ramipril 10 mg/day) for 12 weeks. The effect of RAS
      blockade on insulin sensitivity and proteinuria was also investigated.

      After the intervention period, blood samples were obtained for assay of FGF-23
      concentrations, HbA1c , and insulin resistance scores (HOMA-IR).

      Urine samples were also collected over a 24-hour period to determine the degree of
      proteinuria.
    

Intervention name(s): Ramipril
Intervention type(s): Drug
Intervention description(s): ramipril 10 mg/day during 3 months
Intervention MeSH terms: Ramipril
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: FGF-23 , ramipril, endothelial dysfunction