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Star fruit: A neglected but serious fruit intoxicant in chronic renal failure

Article · January 2002

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 Hon-Jek Yap, MD; Yung-Chang Chen, MD;
Ji-Tseng Fang, MD; Chiu-Ching Huang, MD

Star Fruit: A Neglected but

Serious Fruit Intoxicant in
Chronic Renal Failure
Star fruit originated in Southeast Asia and is readily available in Taiwan. Star fruit causes
several symptoms in patients with chronic renal failure or end-stage renal disease. The
symptoms vary and include insomnia, intractable hiccups, agitation, muscle weakness, con-
fusion, consciousness disturbances of various degrees, seizures, and cardiorespiratory ar-
rest. The various star fruit subspecies contain different toxins, including a powerful
neurotoxin that is suspected to accumulate in blood, cross the blood-brain barrier in chron-
ic renal failure patients, and eventually cause irreversible damage.
This investigation reports on three patients who suffered from star fruit intoxication, each of
whom had different renal function status, clinical presentations and outcomes, and re-
sponses to different management. To our knowledge, this was the first case series study of
star fruit intoxication that utilized electroencephalography and that treated the patients with
plasma exchange. Nonetheless, star fruit intoxication cannot be treated effectively. Our case
series study suggests that plasma exchange is an effective treatment for status seizure, but
not for consciousness disturbances. This finding with regard to seizures, however, requires
further study of the effectiveness, timing, frequency, and dosage of plasma exchange in star
fruit intoxication in order to confirm this conclusion.
Star fruit intoxication is a neglected but serious fruit intoxication frequently observed in pa-
tients with chronic renal failure. Because no effective treatment is currently available, pa-
tients—especially those who are newly diagnosed with chronic renal failure or end-stage
renal disease—must be warned not to ingest star fruit, even in small amounts.

tar fruit, or carambola—which origi- es to different management. To our knowledge,

S nates in Southeast Asia and is readily
available in many tropical countries
such as Brazil, Thailand, and Taiwan—be-
longs to the oxalidaceae family, species Aver-
rhoa carambola. In the first description of the
star fruit’s neurotoxic activity, fruit extracts
were injected into the peritoneal cavities of
mice, which provoked convulsion.1 Many at-
tempts to isolate the substance that provokes
neurotoxicity failed. Since then, several inves-
The authors are with the tigators have reported star fruit intoxication in
Division of Critical Care patients with normal renal function, chronic
Nephrology, Section of renal failure, and end-stage renal disease.2-4
Nephrology, Department This investigation reports on three patients
of Medicine, Chang Gung
Memorial Hospital,
who suffered from star fruit intoxication. The
Chang Gung University, patients had various renal function status, clin-
Taoyuan, Taiwan. ical presentations and outcomes, and respons-
564 DIALYSIS & TRANSPLANTATION VOLUME 31, NUMBER 8 AUGUST 2002
this was the first case series study of star fruit
intoxication involving electroencephalography
and treatment with plasma exchange.
CASE REPORTS
Case 1
A 67-year-old male, who had been on he-
modialysis for 1 year, ate 2 pieces of star
fruit, which resulted in persistent hiccups,
nausea, agitation, and insomnia for 2 days.
Although he received a 4-hour session of he-
modialysis on the third day, the symptoms
persisted, but did not progress to a more se-
vere condition. He did not display any con-
fusion or other neurological signs.
On examination, blood pressure was
112/58 mmHg, and body temperature was
 STAR FRUIT INTOXICATION
37.2°C. The initial laboratory investi-
gation revealed the following values:
blood urea nitrogen 69 mg/dl, creati-
nine 12.6 mg/dl, sodium 136 mmol/L,
potassium 4.4 mmol/L, calcium 9.1
mg/dl, glucose 93 mg/dl, carbon diox-
ide 20.1 mEq/L, WBC 7600/mm3, and
hemoglobin 9.8 g/dl. The symptoms
spontaneously regressed 2 days after
dialysis, with no sequelae.
Case 2
A 64-year-old male diabetic patient
with chronic renal failure, hyperten-
sion, and gout was admitted to the
hospital due to multiple spinal
stenoses related to intervertebral disc
protrusion. One week after admis-
sion, he ate 2 fresh star fruits, and on
the following day he started to hiccup
and experience nausea and vomiting.
He later experienced depressed con-
sciousness and agitation.
On examination, his blood pressure
was 130/80 mmHg, and body temper-
ature was 37.3°C. The initial laborato-
Table I. Summary of three cases of star fruit intoxication.
Age (years)
Sex
Creatinine level on admission
(mg/dl)
Underlying disease
Symptoms and signs
Treatment
Outcome
HD = hemodialysis; ESRD = end-stage renal disease; CRF = chronic renal failure
ry investigation revealed the following
values: blood urea nitrogen 31 mg/dl,
creatinine 4.4 mg/dl, sodium 141
mmol/L, potassium 3.89 mmol/L, cal-
cium 7.9 mg/dl, ammonia 14 µmol/L,
glucose 219 mg/dl, magnesium 2.0
mg/dl, WBC 6800/mm3, hemoglobin
10.4 g/dl, pH 7.464, PaCO2 30.8
mmHg, PaO2 144 mmHg, HCO3 22.3
mmol/L, cortisol 19.11 µg/dl, free T4
1.2 ng/dl, and TSH 0.89 µIU/ml. A
computed tomography scan of the
brain was normal.
A fever rising to 38.5°C devel-
oped a few hours later. The septic
work-up included a CSF study, uri-
nalysis and culture, blood culture,
chest x-ray, abdominal echogram,
and echocardiogram, all of which
were within normal limits. An MRI
of the brain was administered, but no
specific abnormality found. Elec-
troencephalography revealed diffuse
cortical dysfunction, which suggest-
ed metabolic encephalopathy.
One week of antibiotic and sup-
Case 1 Case 2
67 64
Male Male
12.6 4.4
ESRD (maintenance HD Diabetic, with CRF
for 1 year)
Persistent hiccups, Hiccups, nausea,
nausea, agitation, vomiting; followed by
insomnia for 2 days depressed consciousness,
agitation, fever
Supportive HD
Spontaneous recovery Recovery after HD
AUGUST 2002 DIALYSIS & TRANSPLANTATION
portive treatment did not improve the
condition or degree of consciousness.
One 2-hour session of hemodialysis
was arranged because of deteriorating
renal function, with blood urea nitro-
gen raised from 32 to 76 mg/dl, and
creatinine elevated from 4.3 to 6.2
mg/dl. Consciousness improved pro-
gressively after dialysis. He recovered
from mental and consciousness dis-
turbance 2 days after the dialysis,
without neurological sequelae.
Case 3
A 64-year-old female—whose chronic
renal failure had been diagnosed 6
months prior, and who was under reg-
ular follow-up at another hospital—
was admitted 1 day after ingesting 2
pieces of star fruit. Initial symptoms
were agitation, persistent hiccups, nau-
sea, and vomiting, which progressed to
loss of consciousness and status
seizure on the day of admission.
On examination, her blood pressure
was 152/94 mmHg, and body temper-
Case 3
64
Female
9.1
CRF
Agitation, persistent
hiccups, nausea, vomiting;
progressing to loss of
consciousness, status
seizure, fever on the
subsequent day
HD & plasma exchange
Status seizure subsided
after plasma exchange;
died 26 days later due to
pneumonia
565
 STAR FRUIT INTOXICATION
ature was 36.7°C. The patient was co-
matose, with status seizure. The initial
laboratory investigation revealed:
blood urea nitrogen 105 mg/dl, creati-
nine 9.1 mg/dl, sodium 141 mmol/L,
potassium 3.6 mmol/L, calcium 8.6
mg/dl, WBC 6800/mm3, hemoglobin
9.8 g/dl, pH 7.365, PaCO2 29.4 mmHg,
PaO2 112 mmHg, HCO3 16.4 mmol/L.
A computed tomography scan of the
brain was normal.
A fever rising to 38.4°C developed
on the second day. The septic work-up
included urinalysis and culture, blood
culture, and chest x-ray, all of which
were normal. The patient suffered sta-
tus seizure despite being under mida-
zolam and phenytoin medication and
undergoing emergent hemodialysis.
Plasma exchange was arranged (2
plasma volumes) because there was no
improvement in the patient’s seizures or
consciousness disturbance. Status
seizures subsided after 1 session of
plasma exchange, but her conscious-
ness level did not improve. Another ses-
sion of plasma exchange with 2 plasma
volumes was therefore arranged in the
following days, but the patient’s con-
sciousness still did not improve. Elec-
troencephalography revealed diffuse
cortical dysfunction, suggesting meta-
bolic encephalopathy, and occasional
focal regional cortical epileptic activi-
ties were discovered on the right side.
She then received regular hemodialysis
and supportive treatment. The condition
and consciousness level, however, did
not improve, and she died 26 days later
due to pneumonia accompanied by sep-
tic shock and multi-organ failure.
DISCUSSION
In each of the above cases, the patients
ate 2 pieces of star fruit, which caused
varied symptoms. The severity of in-
toxication does not appear to depend on
the degree of renal function present, be-
cause the more severe symptoms devel-
oped in those patients with chronic
renal failure as opposed to those with
end-stage renal disease (Table I).
As in other reports,3,4 hiccups and
566 DIALYSIS & TRANSPLANTATION AUGUST 2002
agitation were the most frequent
symptoms. Consciousness distur-
bance was identified in the 2 cases
with chronic renal failure, 1 of which
was associated with status seizure.
Fever exceeding 38°C was also found
in the 2 cases associated with con-
sciousness disturbance—a symptom
not mentioned in other reports3,4—
yet, all culture studies were negative.
The brain scans (an MRI and a CT
scan) performed in our 2 cases with con-
sciousness disturbance were both nor-
mal, as others have reported. However,
these 2 cases also underwent electroen-
cephalography, which had not been per-
formed in earlier reports. This
investigation revealed diffuse cortical
dysfunction, which implies metabolic
encephalopathy and suggests that a neu-
rotoxin may, in fact, exist in star fruit, al-
though it has not yet been isolated.
Symptomatology
Martin et al.2 first described an
outbreak of intractable hiccups in pa-
tients undergoing regular hemo- dial-
ysis after ingesting star fruit.
Following this outbreak, star fruit was
found to cause several other symp-
toms in patients with chronic renal
failure or end-stage renal disease. The
symptoms vary and include insomnia,
intractable hiccups, agitation, muscle
weakness, confusion, consciousness
disturbance of various degrees,
seizures, and cardiorespiratory
arrest.3,4 Intractable hiccups is the
most common symptom observed in
most patients, and it does not respond
to medication such as haloperidol,
metoclopramide, or diazepam. Star
fruit can also cause acute renal failure
after being ingested in large amounts,
with typical changes of acute oxalate
nephropathy found.5
Neto et al.3 described 6 uremic pa-
tients under maintenance dialysis suf-
fering from star fruit intoxication, who
presented with various symptoms. The
researchers suspected that there were
different toxins in the different star fruit
subspecies, as well as a powerful neu-
rotoxin that can accumulate in blood
and cross the blood-brain barrier in
chronic renal failure patients, eventual-
ly causing irreversible damage. But, at-
tempts thus far to isolate the definite
neurotoxin have failed.
Anecdotal reports state that star fruit
is rich in potassium. Chang et al.4
demonstrated that fresh star fruit does,
in fact, contain a relatively high concen-
tration of potassium; their study found
about 34.4 mEq/L. However, in their
study severe hyperkalemia was discov-
ered in only 3 of 20 patients (a potassi-
um of 6.2, 6.4, and 7.1 mEq/L,
respectively), and hyperkalemia did not
cause the deaths of those patients.4 Our
3 cases revealed no hyperkalemia.
Patients with mild symptoms, such
as insomnia, intractable hiccups, agita-
tion, and even mild mental confusion,
recover spontaneously under supportive
care. All renal patients who have died
after ingesting star fruit suffered altered
consciousness. Clinical manifestations
of the survivors resembled those who
died except for consciousness distur-
bance and seizure, and in most reports,
including our cases, surviving patients
recovered without sequelae.3,4 Eight pa-
tients died in the Chang et al.4 case se-
ries, and altered consciousness was a
common feature in those cases. All pa-
tients who subsequently died were
found to have eaten 1 to 2 fresh fruits,
and death occurred within 5 days.
Although the unknown toxic sub-
stance was first thought to be remov-
able by hemodialysis,3 recent reports
have found that death occurs despite
emergent hemodialysis and intensive
medical care.4 In our 2 cases involving
consciousness disturbances, 1 patient
recovered after 1 session of 2-hour he-
modialysis, but the other patient with
consciousness disturbance and status
seizure did not.
Neto et al. revealed that seizure was
associated with cardiorespiratory ar-
rest and mortality,3 and this was exhib-
ited in our third case, who presented
with consciousness disturbance and
status seizure that did not respond to
 STAR FRUIT INTOXICATION
midazolam, phenytoin medication, or
emergent hemodialysis.
Plasma Exchange
Eliminating specific toxins by remov-
ing all plasma constituents is an ac-
cepted approach in toxicology. The
many recent examples include treating
severe preeclampsia, extensive rhab-
domyolysis, and life-threatening
bleeding in a hemophiliac with in-
hibitors to clotting factors.6
Despite the fact that the use of plas-
ma exchange in star fruit intoxication
has not been previously reported, we
arranged 1 session of plasma ex-
change, using about 2 plasma volumes,
in 1 patient whose status seizure exhib-
ited poor response to medication. Al-
though the status seizure subsided, the
patient did not recover consciousness,
even after another session of plasma
exchange. This patient died after 26
days due to pneumonia and septic
shock, an outcome that differed from
the findings of Chang et al., who re-
ported that most of their patients who
subsequently died did so within 5 days
due to cardiovascular collapse.4 From
this case, plasma exchange appears to
be an effective treatment for status
seizure resulting from star fruit intoxi-
cation, although a larger number of
cases would be required before defini-
tive conclusions can be drawn.
CONCLUSION
In conclusion, star fruit intoxication
should be suspected in patients with
chronic renal failure or end-stage renal
disease when they complain of hiccups,
agitation, insomnia, mental confusion,
consciousness disturbances, or seizures.
No effective treatment is available for
the hiccups or agitation, but the condi-
tions improve spontaneously after sev-
eral days. Consciousness disturbances
and seizures are symptoms associated
with high mortality due to the risk of
cardiorespiratory arrest.
Although hemodialysis was first
thought to be capable of removing
the suspected neurotoxin, recent re-
View publication stats
ports and our own experiences find
that death can occur despite emer-
gent hemodialysis and intensive
medical care, especially for patients
with seizures. Our case demonstrated
that plasma exchange is an effective
treatment for status seizure, but not
for consciousness disturbance. This
finding suggests the need for further
study of the effectiveness, timing,
frequency, and dosage of plasma ex-
change in star fruit intoxication in or-
der to attain a definite conclusion.
Star fruit is an often ignored, yet
serious, fruit intoxication frequently
observed in patients with chronic re-
nal failure. Because no effective treat-
ment is available, patients, especially
those who are newly diagnosed with
chronic renal failure or end-stage re-
nal disease, must be warned not to eat
star fruit, even in small amounts.
References
1. Muir CK, Lam CK. Depressant action of
Averrhoa carambola. Med J Malaysia 1980;
34:279-280.
2. Martin LC, Caramori JST, Barreti P, Soares
A. Intractable hiccups induced by carambola
(Averrhoa carambola) ingestion in patient with
end stage renal failure. J Bras Nefrol 1993;
15:92-94.
3. Neto MM, Robl F, Netto JC. Intoxication by star
fruit (Averrhoa carambola) in six dialysis patients?
Nephrol Dial Transplant 1998; 13:570-572.
4. Chang JM, Hwang SJ, Juo HT, et al. Fatal out-
come after ingestion of star fruit (Averrhoa
carambola) in uremic patients. Am J Kidney Dis
2000; 35:189-193.
5. Chen CL, Fang HC, Chou KJ, Wang JS,
Chung HM. Acute oxalate nephropathy after in-
gestion of star fruit. Am J Kidney Dis 2001;
37:418-422.
6. Jones JS, Dougherty J. Current status of
plasmapheresis in toxicology. Annals Emerg
Med 1986; 15:474-482. D&T
AUGUST 2002 DIALYSIS & TRANSPLANTATION 567