Cardiovascular Diseases, Diabetes Mellitus, Nephropathy
Conditions
Keywords
Atorvastatin, L-NMMA, NO, Nephrology, Diabetes Mellitus
Brief summary
It has been documented that statin reduce mortality and morbidity in patients with cardiovascular disease. This effect can partly be related to a reduction in cholesterol levels in blood. Nitric oxide (NO) production is reduced in several chronic diseases such as nephropathy, diabetes and hypertension. The purpose of this study is to investigate the effect of Atorvastatin treatment on the NO-system measuring renal and cardiovascular variables in patients with type 2 diabetes with nephropathy.
Detailed description
Subjects will be examined on two examination days. 4 days prior to each examination day subjects are treated with either atorvastatin or placebo. During treatment periods subject are given a standardized diet. On the examination days subject are given L-NMMA(L-NG-monomethyl Arginine citrate), a NO inhibitor, 6 mg bolus infusion followed by continuous 4 mg/kg/hr infusion for 1 hour. Renal function, central hemodynamic and vasoactive hormones are evaluated prior, during and after L-NMMA infusion. Renal function is measured by renal clearance of 51Cr-EDTA and urinary sodium, potassium and albumin concentration. Urinary excretion of protein from sodium channels such as the NaCl cotransporter (NCC), the Na-K-Cl cotransporter (NKCC) and the epithelial sodium channel (ENaC) will be measured to evaluate channel activity in the nephron. Central blood pressure, pulse wave analysis, and augmentation index are measured using SphygmoCor® from Atcor.
Interventions
DRUGAtorvastatin
Zarator, 80 mg pr day for 5 days
DRUGUnikalk
1 tablet Unikalk pr day for 5 days
Sponsors
Erling Bjerregaard Pedersen
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men and women * minimum 40 years * Chronic Kidney disease * Estimated GFR (eGFR) between 30 and 90 ml/min * Diabetes Mellitus type II
Exclusion criteria
* Nephrotic Syndrome * Anamnestic or clinical signs of significant heart, lung, lever, kidney and brain disease * Neoplastic disease * Alcohol abuse, * Drug abuse * Pregnancy or nursing * Blood donation within a month before examination * Hgb \< 6,0
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Fractional excretion of sodium | 5 days treatment |
Secondary
| Measure | Time frame |
|---|---|
| Plasma renin concentration | 5 days |
| Arterial stiffness | 5 days |
| Systolic blood pressure | 5 days |
| Urinary excretion of protein from sodium channels such as the NaCl cotransporter (NCC), the Na-K-Cl cotransporter (NKCC) and the epithelial sodium channel (ENaC) | 5 days |
| Augmentations index | 5 days |
| Plasma angiotensin II concentration | 5 days |
Countries
Denmark
Outcome results
None listed