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Saudi Journal of Kidney Diseases and Transplantation
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REVIEW ARTICLE  
Year : 2017  |  Volume : 28  |  Issue : 4  |  Page : 709-715
Toxicity of star fruit (Averrhoa carambola) in renal patients: A systematic review of the literature


1 Clinical Epidemiology and Biostatistics Department, Pontificia Universidad Javeriana; Medical School, Pontificia Universidad Javeriana, Bogota, Colombia
2 Medical School, Pontificia Universidad Javeriana, Bogota, Colombia
3 Clinical Epidemiology and Biostatistics Department, Pontificia Universidad Javeriana, Bogota, Colombia

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Date of Web Publication21-Jul-2017
 

   Abstract 


Several reports have discussed the neurotoxic effects of star fruit (Averrhoa carambola) in patients with chronic kidney disease (CKD). There is also some evidence highlighting the potentially harmful effects on patients with apparently normal renal function, who after consuming this fruit, developed acute renal injury. We performed a systematic review of the literature in the two main global databases (PubMed and Embase) as well as in Lilacs, for Latin American publications. We also included case reports, case series, or review articles which presented individual patient data. Animal or in vitro studies were excluded. We initially screened 259 references, of which 42 were selected for full-text review and 26 were finally selected for data extraction. A total of 123 patients from eight countries were documented: Brazil, with 47 cases, had the highest reported incidence, followed by Taiwan (36), Bangladesh (20), China and France (8 each), Sri Lanka (2), and Thailand and Colombia (1 each); 28 (22%) of the patients died. Despite the relatively low frequency of star fruit consumption, it has become a global issue. Patients with already diagnosed CKD are the obvious target for preventive measures, but persons with undiagnosed kidney conditions could also be at risk.

How to cite this article:
Aranguren C, Vergara C, Rosselli D. Toxicity of star fruit (Averrhoa carambola) in renal patients: A systematic review of the literature. Saudi J Kidney Dis Transpl 2017;28:709-15

How to cite this URL:
Aranguren C, Vergara C, Rosselli D. Toxicity of star fruit (Averrhoa carambola) in renal patients: A systematic review of the literature. Saudi J Kidney Dis Transpl [serial online] 2017 [cited 2017 Nov 23];28:709-15. Available from: http://www.sjkdt.org/text.asp?2017/28/4/709/211347



   Introduction Top


Averrhoa carambola, better known as star fruit or carambolo, is of Asian origin, but is now grown in different regions of the world, in particular in Central and South America and also in the Southern United States and Australia.[1]

This fruit has been used as a natural remedy and as a beverage, and it has become increasingly popular in Europe and the US where it is marketed as an exotic fruit.[2]

There are several studies that have analyzed the nephrotoxic and neurotoxic effects of two components of this fruit: caramboxin acid and oxalic acid. These may cause kidney damage and stimulate the GABAergic system, the principal inhibitory system of the central nervous system.[3] This largely explains the clinical manifestations of patients suffering star fruit poisoning, which include hiccups, altered states of consciousness, vomiting, psychomotor agitation, epileptic seizures, coma, and death.

Several studies have described the toxic effects of star fruit and provide evidence to suggest a recommendation against the consumption of this fruit by patients with chronic kidney disease (CKD).[4] Given the increased availability of star fruit and its growing popularity worldwide, it is important to raise awareness of the harmful effects that its consumption can have on kidney function, not only in patients with impaired renal function but also in apparently healthy persons. The purpose of this study was to review the literature indexed in scientific databases, collecting case reports of star fruit toxicity in renal disease patients and in previously healthy participants.


   Methods Top


A systematic literature review was performed searching for articles related to renal toxicity associated with star fruit intake. Our search was carried out in PubMed, Lilacs, and Embase. The terms used in our search were: “star fruit” or “carambola” or “carambolo” or “star fruit” and “kidney disease” and “neurotoxicity,” with no restriction by date or language of publication.

We included case reports, case series, or review articles as long as they presented individual patient data. Exclusion criteria included systematic literature reviews, animal or in vitro studies, items related to biological characteristics of the plant, and articles related to other effects of star fruit.

Review lists, with title and abstract, were independently checked by two researchers to exclude irrelevant publications. Remaining articles were retrieved in full text for data extraction.


   Results Top


We initially considered 259 references, of which 42 were found to be duplicates and 175 were considered irrelevant. Out of the 42 fulltext articles that were selected for review, two were not found, and 14 had no relevant clinical information; thus, 26 articles were used in our analysis.

[Table 1] shows the 26 articles (21 case reports and 5 cases series) that were included and the 123 cases that were evaluated (34–85 years of age; 77 males, 62%). In 99 of the 123 cases (80%), star fruit intoxication was associated with CKD, and in the remaining 24 (20%), consumption was associated with acute nephropathy of whom three developed CKD and two became dialysis dependent; the other patients had a nondiagnosed IgA nephropathy.[24],[25],[26],[27],[28]
Table 1: Summary of the case reports in the literature, in chronological order.

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Patients came from eight countries in four continents: Bangladesh (20 cases), Brazil (47 cases), China (8 cases), Colombia (1 case), France (8 cases), Sri Lanka (2 cases), Thailand (1 case), and Taiwan (36 cases). The first publication was in 1998.[5] In the majority of cases, the first symptoms included hiccups, nausea, vomiting, and confusion. These appeared after a few hours of ingestion and worsened until they progressed to severe mental states and seizures; 11 patients were reported to have entered a comatose state and nine had status epilepticus.

The initial medical care provided was directed toward controlling gastrointestinal and neurological symptoms. Hemodialysis (HD) was then initiated either as a response to suspected intoxication, as a continuation of treatment for CKD, or as a way to control the acute renal failure.

Of the 99 patients with previously diagnosed CKD, 75 (76%) underwent HD (57 of them survived and 18 died) and 13 patients (13%) received peritoneal dialysis (11 survived and 2 died). Three patients underwent hemofiltration (all survived) and one patient underwent hemodiafiltration and survived; seven patients died before receiving any treatment. On the other hand, of the 24 patients with previously normal renal function, one died, 19 recovered without dialysis, and four needed HD for acute renal failure (3 of them developed CKD).

Neurological symptoms were more severe in patients with CKD; 36 of the 99 cases presented with confusion or incoherent speech, 29 had seizures, 22 had altered consciousness, and 11 had coma. Of the 24 patients with previously normal renal function, two presented with insomnia and one each had confusion, seizures, and altered consciousness.

Diabetes was mentioned as comorbidity in 50 patients (48%) and hypertension in 42 (34%). Out of the 123 cases, 28 deaths were reported (22%); the cause of death was pneumonia associated with septic shock and multiorgan failure in four of these cases.


   Discussion Top


Star fruit intoxication, despite being relatively rare, is now a global phenomenon. While the majority of cases apparently occur in Asian countries, where production and consumption are higher, sporadic cases are described worldwide. The fruit is frequently used for medicinal purposes, in the treatment of diseases such as diabetes, due to its alleged hypoglycemic effects, a fact that increases the number of cases in Asian countries.[7],[27] The high price of this exotic fruit in European and American markets might limit its access, but this could probably change in the near future. Intoxication most frequently occurs in patients with CKD, and in those with a history of diabetes or hypertension, all of which have a growing worldwide prevalence. Despite the response to HD, it is still potentially fatal or can induce long-term sequelae.[15],[23] The biological mechanisms by which intoxication occurs have been studied in different in vivo and in vitro models,[3] and the main mechanism for renal toxicity could be the accumulation of calcium oxalate crystals, which causes tubular obstruction and the subsequent apoptosis of renal tubular epithelial cells.[29] It has also been shown that star fruit has a high content of oxalates that can cause acute oxalate nephropathy in rats.[19] Neurotoxic effects are due to caramboxin, a nonproteinogenic amino acid, which has an agonist effect on NMDA glutamate receptors and that normally does not cross the blood-brain barrier.[3] Symptoms such as hiccups, altered states of consciousness, seizures, and coma are due to the inability of the kidney to excrete these toxic components of star fruit. Patients with already diagnosed kidney failure should be told to avoid star fruit. More problematic is to address the risk of acute renal failure, which has been described in a few participants with previously normal renal function.[7],[19]

Given the growing popularity of star fruit, it is vital to increase awareness among patients and physicians about the risks of its consumption. Patients with compromised renal function, those at risk of developing it, or those undergoing procedures such as HD are the target population for these recommendations. People with normal renal function should also avoid or at least limit the intake of star fruit since they may also be affected.[7],[27] One in every five patients described, had a previous normal renal function, and developed the symptoms after consuming different amounts of fruit (from 300 mL to 3 L). Having an empty stomach or being dehydrated appear to be risk factors to develop acute renal injury. [7],[19],[26],[27]

Physicians, nutritionists, and professionals in the culinary or hospitality industry should also be educated about the risks of star fruit intoxication. We also suggest that surveillance and reporting mechanisms are established to improve the understanding of this phenomenon. Future studies may also benefit from considering social, demographic and biological, and/or genetic attributes of patients to see if there are any particularly high-risk groups.

Conflict of interest: None declared.



 
   References Top

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Garcia-Cairasco N, Moyses-Neto M, Del Vecchio F, et al. Elucidating the neurotoxicity of the star fruit. Angew Chem Int Ed Engl 2013;52:13067-70.  Back to cited text no. 3
    
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Tse KC, Yip PS, Lam MF, et al. Star fruit into xication in uraemic patients: Case series and review of the literature. Intern Med J 2003;33: 314-6.  Back to cited text no. 4
    
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19.
Neto MM, Silva GE, Costa RS, et al. Star fruit: Simultaneous neurotoxic and nephrotoxic effects in people with previously normal renal function. NDT Plus 2009;2:485-8.  Back to cited text no. 19
    
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Auxiliadora-Martins M, Alkmin Teixeira GC, da Silva GS, et al. Severe encephalopathy after ingestion of star fruit juice in a patient with chronic renal failure admitted to the Intensive Care Unit. Heart Lung 2010;39:448-52.  Back to cited text no. 21
    
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Chen SH, Tsai MH, Tseng YL, Tseng YL, Lui CC, Chuang YC. Star fruit intoxication in a patient with moderate renal insufficiency presents as a posterior reversible encephalopathy syndrome. Acta Neurol Taiwan 2010;19: 287-91.  Back to cited text no. 22
    
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24.
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27.
Abeysekera RA, Wijetunge S, Nanayakkara N, et al. Star fruit toxicity: A cause of both acute kidney injury and chronic kidney disease: A report of two cases. BMC Res Notes 2015; 8:796.  Back to cited text no. 27
    
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29.
Carolino RO, Beleboni RO, Pizzo AB, et al. Convulsant activity and neurochemical altera-tions induced by a fraction obtained from fruit Averrhoa carambola (Oxalidaceae: Geraniales). Neurochem Int 2005;46:523-31.  Back to cited text no. 29
    

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Correspondence Address:
Diego Rosselli
Department of Clinical Epidemiology and Biostatistics, Medical School, Pontificia Universidad Javeriana, Bogota
Colombia
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