Atorvastatin treatment in the short term: does it induce renoprotection or vasculoprotection in renal transplantation?
BACKGROUND
Proteinuria and dyslipidemia are nonimmune risk factors implicated in the deterioration of kidney function and associated with an increased risk of accelerated atherogenesis. Statin therapy, used for cholesterol reduction, has shown a renoprotective effect in animal models, particularly in cases of proteinuria. This may occur through lipid-independent mechanisms, such as improved endothelial dysfunction/vascular biology, reduced inflammatory cytokine production (transforming growth factor-beta 1 [TGF-beta1]), and regulation of fibrogenic responses. We studied mechanisms of action of agents, such as statins, to change proteinuria, inflammatory parameters, and TGF-beta1 plasma levels in relation to vascular tone.


METHODS
Fifty-six kidney transplant recipients (30 men and 26 women of overall mean age 54 +/- 13 years) were treated posttransplantation with atorvastatin (10 mg/d) for 12 weeks without renin-angiotensin-system blockade drugs. Inflammatory variables, biochemical parameters, lipid profile, renal function, and TGF-beta1 levels were determined at baseline and at 3 months. Vascular stiffness was evaluated using pulse wave velocity (PWV).


RESULTS
Baseline TGF-beta1 plasma levels were higher among transplant recipients than healthy controls, namely 8.12 ng/mL (range, 5.82-13.12) to 2.55 (range, 1.78- 4.35) (P < .01). Furthermore, the levels remained higher after the treatment with atorvastatin, namely, 7.59 (range, 4.97-12.35) to 2.55 (range, 1.78-4.35) ng/mL (P < .01). Atorvastatin treatment significantly decreased total cholesterol as well as low-density lipoprotein cholesterol plasma levels, but did not modify mean blood pressure (MBP), proteinuria, creatinine clearance, or inflammatory factors. Reduction in TGF-beta1 plasma levels was statistically significant among patients with PWV >9.75 (m/s) (pathology reference value) namely, from 10.7 ng/mL (range, 7.02-13.98) to 6.7 (range, 3.96-11.94) (P = .038). Among older patients, atorvastatin significantly decrease TGF-beta1 plasma levels: from 9.5 ng/mL (range, 6.45-14.44) to 5.65 (range, 3.63-9.48; P < .05). The decreased TGF-beta1 was not related to changes in lipid profiles.


CONCLUSIONS
Atorvastatin (10 mg/d) improved the lipid profile and moreover among older patients with worse PWV (>9.75 m/s), TGF-beta1 levels were significantly reduced. Our results suggested that statins displayed potent actions distinct from their hypolipidemic effects.
Navarro-Muñoz
M
M
Department of Nephrology, Hospital Universitari Germans Trias i Pujol, Universidad Autónoma de Barcelona, Badalona, Spain. maribelnavarro.igtp@gmail.com
Bonet
J
J
Bayés
B
B
Lauzurica
R
R
Blanco
S
S
Romero
R
R
D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D001794:Blood Pressure / Q000187:drug effects; D015331:Cohort Studies; D050171:Dyslipidemias / Q000453:epidemiology / Q000517:prevention & control; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006538:Heptanoic Acids; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000009:adverse effects / Q000276:immunology / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology / Q000517:prevention & control; D011507:Proteinuria / Q000453:epidemiology / Q000517:prevention & control; D011758:Pyrroles; D016212:Transforming Growth Factor beta / Q000097:blood
D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D011758:Pyrroles; D016212:Transforming Growth Factor beta; D000069059:Atorvastatin