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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 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Atorvastatin | Active Comparator |
| |
| Unikalk | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atorvastatin | Drug | Zarator, 80 mg pr. day for 5 days |
|
|
| Measure | Description | Time Frame |
|---|---|---|
| Fractional excretion of sodium (FeNa) | Fractional excretion of urinary sodium before, during and after L-NMMA infusion | 5 days treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Systolic blood pressure | 5 days | |
| Plasma renin concentration | 5 days | |
| Arterial stiffness (Pulse wave velocity) |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Medicinsk Forskning, Regionshospitalet Holstebro | Holstebro | 7500 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38018702 | Derived | Tunnicliffe DJ, Palmer SC, Cashmore BA, Saglimbene VM, Krishnasamy R, Lambert K, Johnson DW, Craig JC, Strippoli GF. HMG CoA reductase inhibitors (statins) for people with chronic kidney disease not requiring dialysis. Cochrane Database Syst Rev. 2023 Nov 29;11(11):CD007784. doi: 10.1002/14651858.CD007784.pub3. |
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| ID | Term |
|---|---|
| D007674 | Kidney Diseases |
| D002318 | Cardiovascular Diseases |
| ID | Term |
|---|---|
| D014570 | Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
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| ID | Term |
|---|---|
| D000069059 | Atorvastatin |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Unikalk | Drug | 1 tablet Unikalk pr day for 5. days |
|
| 5 days |
| Diastolic blood pressure | 5 day |
| Augmentation Index | 5 days |
| Urinary albumin excretion | 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 |
| plasma aldosterone concentration | 5 days |
| Urinary Aquaporin 2(u-AQP2) excretion | 5 days |
| atrial natriuretic peptide (ANP) concentration | 5 days |
| Brain natriuretic peptide concentration | 5 days |
| D052801 | Male Urogenital Diseases |
| D006538 |
| Heptanoic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |