Bezafibrates cause moderate, reversible impairment in renal function in patients without prior renal disease.
OBJECTIVE
To determine whether bezafibrates have adverse effects on renal function.


METHODS
(1) A 3-year retrospective survey of 526 patients who were on bezafibrate for a while and 614 controls following fluctuations of serum creatinine levels. (2) A prospective study on 33 patients with previous evidence of bezafibrate-induced elevation in serum creatinine. The patients were examined after 3 months on bezafibrate 400 mg/day and then after 3 months without bezafibrate. Eight patients repeated the tests after 3 months on bezafibrate 200 mg/day.


RESULTS
Retrospective: 295 bezafibrate-treated patients (56%) and 67 controls (11%) demonstrated fluctuations > or = 0.2 mg/dl in serum creatinine levels (p < 0.001); 113 patients (21%) and 16 controls (3%) showed fluctuations > or = 0.3 mg/dl (p < 0.001). Prospective: bezafibrate 400 mg/dl increased serum creatinine from 1.16 +/- 0.19 to 1.42 +/- 0.2 mg/dl (p < 0.001) and urea from 37 +/- 8 to 44 +/- 8 mg/dl (p < 0.001); creatinine clearance (Ccr) decreased from 104 +/- 23 to 82 +/- 27 ml/min (p < 0.001). CPK increased from 82 +/- 32 to 130 +/-58 mg/dl (p < 0.0001) and urinary myoglobin increased from 95.4 +/- 21 to 199 +/- 99 mg/dl (p < 0.0001). The 8 patients given bezafibrate 200 mg/dl experienced similar dose-dependent changes.


CONCLUSIONS
Bezafibrate causes quiet common, dose-dependent and reversible changes in serum creatinine in patients with normal renal function, associated with a significant increase in serum CPK and urine myoglobin, suggestive of drug-induced mild subclinical skeletal muscle injury compromising renal function.
Charach
Gideon
G
Department of Internal Medicine, Tel Aviv University, Tel Aviv, Israel. drcharach@012.net.il
Grosskopf
Itamar
I
Rotmensch
Heschi H
HH
Kitzis
Ilan
I
Weintraub
Moshe
M
D000328:Adult; D000368:Aged; D001629:Bezafibrate / Q000009:adverse effects*; D003402:Creatine Kinase / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects; D009212:Myoglobinuria / Q000175:diagnosis; D011446:Prospective Studies; D012189:Retrospective Studies
D003404:Creatinine; D003402:Creatine Kinase; D001629:Bezafibrate