Treatment with fluvastatin rapidly modulates, via different pathways, and in dependence on the baseline level, inflammation in hemodialysis patients.
BACKGROUND
Hemodialysis (HD) patients are frequently in an elevated inflammatory state which is correlated to the atherosclerosis-related and overall morbidity and mortality in this population. Statins, beyond their antilipidemic effects, are also considered to have anti-inflammatory, immunomodulating and antioxidant properties. The individual response of HD patients to a short course of fluvastatin, the mechanisms involved in the immunomodulating and anti-inflammatory effects of this drug and the time interval to the appearance of these effects are investigated in this longitudinal study.


METHODS
In a group of 51 HD patients, fluvastatin 40 mg/day was administered for 4 weeks. Serial measurements of the lipid profile, C-reactive protein (CRP), interleukin-6 (IL-6), soluble IL-6 receptor (sIL-6R), interleukin-10 (IL-10), and serum oxidized LDL (ox-LDL), were performed before, during, and after the treatment period.


RESULTS
Total cholesterol was significantly reduced after 14 days of treatment with fluvastatin (from mean +/- SD 216.7 +/- 34.3 to 179.2 +/- 42.3 mg/dl, p < 0.001). IL-6 and ox-LDL were reduced on day 28 (p < 0.001 and p < 0.01, respectively) and IL-10 was increased on day 14 (p = 0.05); CRP did not change significantly during the treatment period while sIL-6R was increased on day 28 of fluvastatin administration (p < 0.05). In a subgroup of patients with CRP, IL-6, sIL-6R, and ox-LDL baseline serum values > or = the median and IL-10 < or = the median, CRP was reduced on day 28 of fluvastatin treatment (p < 0.01), IL-6 and ox-LDL were reduced earlier, on day 14 (p = 0.05 and p < 0.05, respectively) while sIL-6R did not change significantly during the treatment period.


CONCLUSIONS
Treatment with fluvastatin rapidly modulates inflammation in HD patients. Enhancement of anti-inflammatory mechanisms and attenuation of the inflammatory and oxidative state contribute to this modulation. Patients in an elevated baseline inflammatory state respond more rapidly and effectively to the treatment. This immediate and multi-potent action of the statins could be clinically useful in acute atherosclerosis complications or in the treatment of chronic inflammation in HD patients.
Tsirpanlis
George
G
Department of Nephrology, General Hospital of Athens, Athens, Greece. tsipg@hellasnet.gr
Boufidou
Fotini
F
Manganas
Stamatios
S
Chantzis
Konstantinos
K
Bleta
Aliki
A
Stamatelou
Kyriaki
K
Psimenou
Erasmia
E
Nicolaou
Chrysoula
C
D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D005229:Fatty Acids, Monounsaturated / Q000627:therapeutic use*; D005260:Female; D000077340:Fluvastatin; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy*; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D007676:Kidney Failure, Chronic / Q000178:diet therapy*; D008055:Lipids / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D019947:Receptors, Interleukin-6 / Q000097:blood; D006435:Renal Dialysis; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D015850:Interleukin-6; D008055:Lipids; D008077:Lipoproteins, LDL; D019947:Receptors, Interleukin-6; C099252:oxidized low density lipoprotein; D016753:Interleukin-10; D000077340:Fluvastatin; D002097:C-Reactive Protein