The Effects of Atorvastatin on the Nitric Oxide-system in Patients With Non-diabetic Nephropathy (STAN)

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 witk chronic kidney disease.

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 51Chromium-EDTA and urinary sodium, potassium and albumin concentration. Urinary excretion of protein from NCC, NKCC and 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.

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)

Inclusion Criteria: Men and women minimum 20 years Chronic Kidney disease Estimated GFR (eGFR) between 30 and 90 ml/min Exclusion Criteria: Nephrotic Syndrome Diabetes mellitus Anamnestic or clinical signs of significant heart, lung, lever, kidney, thyroid and brain disease Neoplastic disease Alcohol abuse, Drug abuse Pregnancy or nursing Blood donation within a month before examination Hgb < 6,0