Effect of Calcium Channel Blocker on the Serum Fibrobalst Growth Factor-23 (FGF-23) Levels in Type-2 Diabetic Patients With Proteinuria Purpose
Condition: We Searched for the Effects of Calcium Channel Blocker Amlodipine on the Clinical and Laboratory Parameters of Diabetic Patients With Proteinuria.
MeSH terms: Proteinuria
Study type: Interventional
Phase: Phase 4

Summary: 
      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.

      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 relationship between FGF-23
      levels and proteinuria in CKD patients.

      There is no data about the effects of calcium channel blocker on FGF23 levels in diabetic
      patients with proteinuria. The aim of this study was to find out whether the beneficial
      effects of calcium channel blocker in diabetic proteinuria has any relation with the
      alteration of FGF-23 levels. The investigators searched for the effects of calcium channel
      blocker amlodipine on the clinical and laboratory parameters of diabetic patients with
      proteinuria.

      The investigators registered the study 'The effect of renin angiotensin system Blockage
      (RAS), calcium channel blocker and combined drugs on TWEAK, PTX3 and FMD levels in Diabetic
      Proteinuric Patients with Hypertension' (ClinicalTrials.gov Identifier:NCT00921570). The
      investigators will use the samples of the some patients for this study. The investigators
      also registered the study 'FGF-23 and Endothelial Dysfunction in Diabetic Proteinuric
      Patients' (ClinicalTrials.gov Identifier: NCT01703234). The investigators will combine these
      two registered studies (NCT00921570 and NCT01703234) in one study.
    

Detailed description: 
      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 61 screened patients 32 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 calcium channel blocker on serum FGF-23 concentrations,
      patients with proteinuria were given an calcium channel blocker (Amlodipine 10 mg/day) for 12
      weeks. The effect of calcium channel blocker on insulin sensitivity and proteinuria was also
      investigated.

      After the intervention period, blood samples were obtained for assay of plasma PTX3
      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): Amlodipine
Intervention type(s): Drug
Intervention description(s): 10 mg/day for 12 weeks
Intervention MeSH terms: Amlodipine
Intervention model: Single Group Assignment
Masking: Single (Participant)
Primary purpose: Prevention