We Searched for the Effects of Calcium Channel Blocker Amlodipine on the Clinical and Laboratory Parameters of Diabetic Patients With Proteinuria. Clinical Trial
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.
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.
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Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention