Fluvastatin and low-density lipoprotein oxidation in hypercholesterolemic renal transplant patients.
BACKGROUND
Hyperlipidemia contributes to the development and progression of vascular disease in organ transplant patients. Oxidative modification of low-density lipoproteins (LDLs) has been suggested as a key event in early atherogenesis.


METHODS
We conducted a pilot study in renal transplanted patients with persistent hypercholesterolemia above 6.5 mmol/liter. We studied the LDL oxidation before and after one year of fluvastatin treatment. Twenty patients (12 males and 8 females, 46 +/- 10 years old) who received a kidney transplant 24 +/- 18 months before the study were treated with fluvastatin (20 mg/day for 12 weeks). Patients with a total cholesterol under 6.3 mmol/liter continued to receive 20 mg/day for another 40 weeks (group I, N = 10). Nine patients with a total cholesterol above 6.3 mmol/liter received 40 mg/day for a further 40 weeks (group II).


RESULTS
Cyclosporine levels did not experience a significant variation. Total and LDL cholesterol decreased significantly in both groups (21.7 and 27.9% in group I, 18.3 and 27.2% in group II, respectively). The lag-phase time, which was significantly enlarged before fluvastatin treatment in the patients with respect to the controls (N = 18, 82 +/- 45 vs. 50 +/- 8 min) was shortened after one year of fluvastatin treatment (64 +/- 24 vs. 50 +/- 8 min, P = 0.04). Fluvastatin was stopped in only one patient because of nausea and vomiting. Transaminases and creatin-phospho-kinase were not altered. All of the patients maintained a functioning graft during the study period.


CONCLUSIONS
Fluvastatin significantly reduced total and LDL cholesterol, without interferences with cyclosporine A through levels. Fluvastatin has not demonstrated an antioxidant effect in our renal hypercholesterolemic transplant patients.
Department of Nephrology, Hospital Princeps d'Espanya, Spain.
A
A
Martínez-Castelao
J M
JM
Grinyó
C
C
Fiol
M J
MJ
Castiñeiras
I
I
Hurtado
S
S
Gil-Vernet
D
D
Serón
I
I
Porta
A
A
Miñarro
A
A
Villarroya
J
J
Alsina
D000328:Adult; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001056:Apolipoproteins C / Q000097:blood / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood / Q000627:therapeutic use; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D005500:Follow-Up Studies; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007211:Indoles / Q000627:therapeutic use*; D016030:Kidney Transplantation; D008077:Lipoproteins, LDL / Q000097:blood / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D010865:Pilot Projects; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D000924:Anticholesteremic Agents; D001056:Apolipoproteins C; D008078:Cholesterol, LDL; D005229:Fatty Acids, Monounsaturated; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007166:Immunosuppressive Agents; D007211:Indoles; D008077:Lipoproteins, LDL; D014280:Triglycerides; D000077340:Fluvastatin; D016572:Cyclosporine; D002784:Cholesterol; D003404:Creatinine