The Effects of Atorvastatin on the Nitrogen Oxide-system in Patients With Type 2 Diabetes and Nephropathy

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Effect of Atorvastatin on the NO-system in Patients With Type 2 Diabetes and Nephropathy

Conditions
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Nephropathy, Cardiovascular Diseases, Diabetes Mellitus

Intervention / Treatment
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* Drug: Atorvastatin
* Drug: Unikalk


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Atorvastatin<br> | Drug: Atorvastatin<br>* Zarator, 80 mg pr day for 5 days<br>* Other names: Zarator;|
| Placebo Comparator: Placebo<br> | Drug: Unikalk<br>* 1 tablet Unikalk pr day for 5 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fractional excretion of sodium |  | 5 days treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systolic blood pressure |  | 5 days | 
| Plasma renin concentration |  | 5 days | 
| Arterial stiffness |  | 5 days | 
| Plasma angiotensin II concentration |  | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atorvastatin, L-NMMA, NO, Nephrology, Diabetes Mellitus