Acute nephrotoxicity and neurotoxicity associated with concentrated star fruit juice consumption

Abstract

Star fruit toxicity has been hugely described in patients with chronic kidney disease, either on conservative or renal replacement therapy. This is a case report of a man, without prior kidney or neurological dysfunction, who appeared to develop nephrotoxicity and neurotoxicity less than 12 hours after drinking concentrated star fruit juice (approximately 20 units of the fruit). He received timely renal replacement therapy and renal function fully recovered after discharge.

Background

Star fruit (Averrhoa carambola) is a member of the Oxalidaceae family, introduced from tropical America more than 150 years ago. Its culture is now widely spread, and the fruit is generally consumed in natura or in juices, either natural or industrialised.¹ Transversal cuts through its five or six sides have a star shape. There are many subspecies of fruit, and it is noticed that the sourer the fruit, the larger the concentration of oxalic acid.^2–4

The ingestion of huge amounts of star fruit can induce nephrotoxicity and/or neurotoxicity. Many outbreaks of intoxication have been associated with variable neurological signs, especially affecting patients with chronic kidney disease (CKD).^5–7 Star fruit toxicity was initially described in 1980 by Muir and Lan.⁸ The group showed that seizures were induced by intraperitoneal injections of star fruit extract exceeding 8 g/kg. The toxic effects in humans are related to the amount of oxalic acid and also to a neurotoxin (‘caramboxin’) extracted from the star fruit, which is capable of inducing seizures and acute neurotoxicity.^{9 10}

The following report suggests that careful attention is necessary when investigating patients who ingested large amounts of star fruit, even in the absence of previous comorbidities, and that adequate treatment must be promptly initiated.

Case presentation

The patient was a 43-year-old Caucasian man, who was admitted to the intensive care unit (ICU), complaining about hiccups, nausea, vomiting, malaise and headache. He was agitated, and his blood test result showed high levels of urea (80 mg/dL) and creatinine (5 mg/dL). The patient mentioned that the symptoms appeared 6 days prior as unstoppable hiccups after the ingestion of the natural juice of 20 medium units of star fruit, diluted in 2 L of water. The hiccups started less than 12 hours after ingestion and worsened with time. At the first medical evaluation, the patient was awake, conscious, haemodynamically stable and oriented in time and space but showed intense psychomotor agitation. His pupils were isochoric; the patient was breathing normally, was well hydrated and showed no oedema of the ankles. He had no history of psychiatric, neurological or cardiovascular disturbances and denied substance abuse of any kind. He related the elimination of a renal calculus 8 months before this admission. He had underwent routine laboratory tests 2 months prior, and kidney function was normal.

His physical examination showed a blood pressure of 140/90 mm Hg and heart rate of 88 bpm. The Oxigen Saturation (SO₂) was 98%. The neurological evaluation was also normal, besides agitation.

The initial and follow-up blood test results are summarised in tables 1 and 2. The abdominal CT scan, as well as total abdominal ultrasound, showed no anatomical changes or signs of kidney stones.

Table 1.

Renal function according to the evaluation time

Time (days)	Serum creatinine (mg/dL)	Serum urea (mg/dL)
−60	0.8	29.0
1*	5.0	80.0
5	2.2	38.0
12	1.3	30.3
30	0.8	28.2

*First evaluation day.

Table 2.

Laboratory tests results

White cell count	Results	Red blood cell count	Results
Leucocytes/mL	8600	Red blood cells (million)	4.47
Neutrophils/mL	4644	Haemoglobin (g/dL)	14.0
Segment-nucleated neutrophils/mL	86	Hematocrit (%)	41.0
Eosinophils/mL	172	Mean globular volume (fL)	91.72
Linfocytes/mL	3440	Mean globular haemoglobin (pg)	31.32
Monocytes/mL	344
Platelets (mm3)	393 000
Sodium (mEq/L)	142	Magnesium (mg/mL)	2.0
Potassium (mEq/L)	4.4	Phosphorus (mg/mL)	2.5
Total calcium (mg/dL)	9.3	Uric acid (mg/mL)	3.6
GTR(UI/L)	51.0
AST (U/L)	45.0
ALT (U/L)	81.0
Urinalysis		Urinaysis (microscopy)
Colour	Light yellow	Epithelial cells	Few
Density	1020	Leucocytes/high power field	03
pH	6.5	Red cells/high power field	10
Ascorbic acid	Absent	Cilinders	Absent
Proteins	Absent	Crystals	Absent
Glucose	Absent	Granulations	Absent
Ketones	Absent	Mucus	Present
Nitrites	Absent
Urobilins	Absent
Urine culture	No bacterial growth in 48 hours

ALT, Alanine aminotransferase; AST, Aspartate Aminotransferase; GTR, Glutamate Transferase Rate.

Differential diagnosis

The main hypothesis, acute star fruit intoxication due to accumulation of oxalic acid, was confirmed by the lab tests (Urinary oxalate 110 mg/day on a 24-hour urine collection). The differential diagnosis was acute renal injury due to nephrolithiasis due to the medical history of the patient (although the patient did not complain about pain) or pyelonephritis, despite the absence of fever and toxaemia.

Treatment

The hypothesis of nephrotoxic acute kidney injury and acute neurotoxicity due to the ingestion of star fruit was considered, and therapeutic measures were taken. Abundant hydration with 30 mL/kg/day of saline 0.9% and sustained low efficiency dialysis (SLED) were initiated. Four sessions of SLED, with the duration of 6 hours each, were performed. Psychomotor agitation worsened on the first 2 days of dialysis, but after that, the patient showed progressive clinical improvement and was discharged from the ICU on the fifth day after admission. He then developed polyuria and went through full recovery of renal function, being discharged from the hospital on the 12th day of admission, with a serum creatinine level of 1.3 md/dL. He was kept on clinical follow-up and showed no further renal or neurological disturbances.

Outcome and follow-up

The patient was followed up for 30 days after his outpatient discharge. Laboratory tests were performed showing the recovery of renal function (table 1). The patient no longer had previous complaints.

Discussion

There have been lots of warnings to patients with CKD about the potential toxicity of star fruit, especially in late stages of the disease. This report, however, emphasises the fact that consumption of large quantities of star fruit juice (20 units, weighting 70–100 g) even in individuals with no previous kidney or neurological disease can result in acute injury. There is a correlation between the amount of fruit ingested, varying from small pieces to bigger amounts in a determined time period, and the signs manifested.¹¹ Neto et al¹¹ organised the toxic effects of star fruit in three levels:

1. Light intoxication: hiccups, vomiting and insomnia.

2. Moderate intoxication: psychomotor agitation, tingling, paraesthesias, loss of limb force, and lightheadedness.

3. Severe intoxication: severe psychic agitation, mental confusion, numbness and coma, seizures evolving to status epilepticus, haemodynamic instability, hypotension and shock.

However, all these data where obtained from patients on chronic haemodialysis. Cases of severe neurotoxicity due to star fruit consumption in patients with previous kidney dysfunction may be resolved by haemodialysis,^{10 12} but some authors believe that oxalic acid and its by-products, which are of low molecular weight and thermostable (caramboxin), may be involved in the mechanisms of nephrotoxicity and neurotoxicity of star fruit. It is believed that seizures are due to a specific action of caramboxin on GABA (Gamma-aminobutyric Acid) and glutamaergic receptors, altering the link of GABA to these receptors.^{13 14}

Very few cases regarding the association of acute renal damage to the ingestion of huge amounts off star fruit-derived products have been described. Fasting and dehydration seem to increase the risk of toxicity and the development of symptoms.^{11 15} The diagnosis is generally firmed on clinical basis, since kidney biopsies are not recommended as a routine diagnostic procedure in acute kidney injury,¹⁶ and the patients generally recover quickly when therapy is timely started in star fruit intoxication.^{7 15} In the present case, the average time between the initiation of symptoms and ingestion of star fruit juice was 12 hours, and the amount of juice ingested was approximately 2 L (20 units of fruit). Although even a small amount of fruit may induce severe neurological complications that can lead to the death of patients with CKD, the levels of intoxication may vary, and many factors, including the genetic profile and ethnicity, may be involved.¹

The presumption of acute star fruit intoxication demands an early start of haemodialysis, which is the most efficient form of treatment, especially in moderate to severe cases, such as the present one described. Peritoneal dialysis must not be used as its efficiency has not been confirmed. Continuous renal replacement therapy methods may be even more efficient in the most severe cases, when haemodynamic instability and/or status epilepticus may intensify as a result of a rebound effect in shorter and faster forms of dialysis.¹¹ If conventional haemodialysis is proposed, it must be offered on a daily basis, with an extended duration of 6–8 hours, to avoid this rebound effect. Seizures are always related to a poorer prognosis. Fatal outcomes are generally observed in patients who were belatedly dialysed or received no dialysis at all.

Learning points.

• Patients with impaired kidney function, even in the early stages, should be strongly advised to avoid the ingestion of star fruit.

• This educational role must be played by nephrologists, nutritionists and dietitians but also by every person involved in kidney care.

• Although the reports of intoxication are more frequent in patients under renal replacement therapy, it can also happen to individuals with normal kidney function.

• For instance, star fruit toxicity must be considered in the differential diagnosis of cases of numbness and alterations in mental status after large consumption of this fruit.

• Intensive care must be promptly initiated in every symptomatic patient to avoid further complications ant potential lethality.