Vol 43 # 3 September 2011 - Kma.org.kw

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Fenofibrate-Induced Rhabdomyolisis in a Dialysis Patient with Subclinical ...
September 2011
aspartate aminotransferase (AST) 960 U/l (normal
range: 5.0-45), alanine aminotransferase (ALT) 490 U/
l (normal range: 5.0 - 45) and lactate dehydrogenase
(LDH) 1912 U/l (normal range: 100 - 210). His thyroid
stimulating hormone (TSH) serum concentration was
10.26 μIU/ml (normal range: 0.34-5.6), free T3 3.61
pg/ml (normal range: 2.5 - 3.9), free T4 0.74 ng/dl
(normal range: 0.54 - 1.12). Fenofibrate was stopped
and tiroxin dosage was increased. He was hospitalized
for five days and hemodialysis was performed four
times. During the follow-up period, serum CK level
decreased to 160 U/l at the end of one week.
DISCUSSION
Hypertriglyceridemia is a common metabolic
disorder in patients with chronic renal failure.
Fenofibrate is a drug of the fibrate class that reduces
triglycerides, very low density lipoprotein (VLDL),
low density lipoprotein (LDL), and total cholesterol
and increases high density lipoprotein (HDL).
Fibrate derivatives are often used for lipid lowering
in patients with chronic renal failure with adjusted
dosage. However, fibrate-related adverse reaction still
occasionally occurs. The most important side effect of
fenofibrate is rhabdomyolysis [4-6] . Our case had endstage
renal disease and underwent peritoneal dialysis
regularly, taking a reduced dosage of fenofibrate
(200 mg/d) for refractory hypertriglyceridemia. He
did not take any statins, cyclosporine, monoamine
oxidase inhibitors, or warfarin concurrently.
Rhabdomyolysis is a biochemical and clinical
syndrome resulting from skeletal muscle injury
and the release of muscle cell components into
the extracellular compartments. In our patient,
the presenting clinical features were myalgias,
myoglobinuria and an elevated serum creatine
kinase. Fulminant rhabdomyolysis may be associated
with tubular necrosis, acute renal failure, excessive
hyperkalemia and hypocalcemia which may induce
further life-thratening complications. Therefore, early
diagnosis of rhabdomyolysis is most important for
prevention of its potentially life-threatening sequelae
like acute renal failure, electrolyte imbalance and
shock.
Therapy of drug-induced rhabdomyolysis consists
of supportive and specific measures. Withdrawal of the
incriminated drug or detoxification in drug overdose
should be followed by supportive measures including
infusion therapy and correction of dehydration and
electrolyte imbalance. Forced diuresis with sodium
bicarbonate may protect the kidney function from
acidosis and precipitation of myoglobin in tubules.
Especially in patients with acute renal failure,
hemodialysis is necessary. Fenofibrate treatment
was discountinued immediately, hemodialysis was
performed four times and serum CK level was decreased
to normal range at the end of one week in our patient.
Rhabdomyolysis results from inherited muscle
enzyme deficiencies, toxins such as alcohol abuse
and cocaine, trauma, drugs such as statins, muscle
overexertion, infections, and other disorders [3] .
Drug-induced rhabdomyolysis occurs rarely. The
development of rhabdomyolysis is rare with only
simple fibrate treatment and has been reported in
only a few cases. In nearly all of the presented cases,
there was a predisposing factor for rhabdomyolysis
such as diabetes, older age, renal insufficiency, and
hypothyroidism [4-6] . Older age, hypothyroidism,
diabetes, taking any drug and renal insufficiency may
be a risk factor for rhabdomyolysis associated with
fibrates. Fenofibrate is renally metabolized and (80%)
is mainly excreted in urine. The tolerability of this
drug seems generally good over the short and long
term with a normal renal function. Since blood levels
of fibric acid derivates and fenofibrate are increased
in patients with renal failure, it is recommended to
adjust dosage in patients with mild to moderate renal
impairment. Rhabdomyolysis was precipitated by
micronized fenofibrate which was prescribed at a
dosage higher than recommended for renal failure.
Hypothyroidism is a rare cause of rhabdomyolysis.
In addition, hypothyroidism is a predisposing factor
for fenofibrate-induced rhabdomyolysis [7-9] . The
precise pathophysiology remains unclear. Myolysis
in hypothyroidism is caused by changes in muscle
fibres from fast twitching type II to slow twitching
type I fibres, deposition of glucosaminoglicans,
poor contractility of actin-myosin units, low myosin
ATPase activity and low ATP turnover in skeletal
muscle. In hypothyroidism, there is an inhibition of
mitochondrial activity in muscle cells as well as many
metabolic pathways such as Krebs cycle, fatty acid
catabolism and glycolytic energy production [7,8] . It
seems that these underlying metabolic anomalies may
sensitize the patient to the muscular adverse effects of
fenofibrate. Although there have been a few reports
that fenofibrate-induced rhabdomyolysis occurs in
patients with hypothyroidism [7-9] , there are no data in
the literature that this occurs in patients with subclinical
hypothyroidism. Our patient had subclinical
hypothyroidism and end-stage renal failure and was
on chronic renal replacement therapy while taking
fenofibrate prescribed for his dyslipidemia. This led
to the development of rhabdomyolysis.
CONCLUSION
Physicians should be aware of potentially lethal
adverse effects including rhabdomyolysis after
fenofibrate therapy in a patient with end-stage
renal failure on chronic renal replacement therapy.
Furthermore, they should carefully follow-up renal,
hepatic, thyroid functions, and muscle enzymes in all