FISH BILE INDUCED ACUTE KIDNEY INJURY -- ANALYSIS OF CLINICAL VARIABLES AND OUTCOMES

Fish gall bladder is considered a traditional medicine to treat rheumatism, decreased visual acuity, and urticaria and to increase sexual vitality. [1] However it can lead to acute renal failure and acute liver injury as reported in cases of fish poisoning from India, [2] Japan [3] and Hong Kong. [4] The ichthyotoxic effects of fish gall bladder is attributed to the presence of a toxin, sodium cyprinol sulfate which is a C27 bile acid. [5] The toxin is heat stable and insoluble in alcohol as cases are reported even after consumption of cooked bile.

Fish is a staple food item in the eastern part of India. Ingestion of raw gall bladder of grass carp, a commonly available fresh water fish is presumed to be a treatment of diabetes in this part of world. Ingestion of fish bile seems to cause Acute Kidney Injury (AKI) in such cases.

This retrospective observational study was carried out in patients of fish bile induced AKI admitted between January 2013 to January 2015 in the Department of Nephrology and Transplantation , Rabindranath Tagore International Institute Of Cardiac Sciences, RTIICS, KOLKATA, INDIA. This is a tertiary care centre in eastern India with an active Clinical Nephrology, Dialysis and Transplantation program.

INCLUSION CRITERIA:

1. Definitive history of fish bile intake.

2. AKI as diagnosed by RIFLE criteria (ADQI 2004).

EXCLUSION CRITERIA:

1. History of bile intake not present

2. Patient not meeting clinical criteria of RIFLE

3. Other tropical causes of AKI

STUDY DESIGN:

Total number of ten cases, both male and females were selected from the study period, based on the above mentioned inclusion and exclusion criteria. The creatinine at the time of admission and discharge, number of days of hospital stay, requirement of haemodialysis and cost of treatment incurred to the patient were calculated for the fish bile induced AKI.

ANALYSIS OF DATA: 

The data thus obtained from the fish bile induced AKI cohort were then tabulated and compared with our regular cohort of cases of tropical causes of AKI.

Commonest presenting symptom, which eventually leads to hospital admission, was invariably gastrointestinal (80%) and the mean duration of appearance of symptoms post ingestion was 65.2 ± 10.8 hours.

At presentation the mean urine output was 570 ± 285 ml/24 hours (non oliguric in all cases).

8 out of 10 patients (80%) required hemodialysis, with a mean of 5±2.6 sessions of hemodialysis.

There was no mortality in all these cases with mean hospital stay of 13±6.8 days. One patient had hepatic dysfunction and renal biopsy which was done in 4 cases revealed Acute Interstitial Nephritis without any glomerular or vascular damage.

Mean Creatinine on admission and discharge were 6.5±3.2 mg/dl and 1.2±0.28 mg/dl respectively.

Results in comparisons to other causes of renal failure in the same hospital and during the same time span are shown in table 1.

Fish belonging to the family Cyprinidae are commonly reported for their toxicity. The family includes grass carp (C idellus), common carp (Cyprinuscarpio), silver carp (Hypophthalmichthysmolitrix), Mylopharyngodonpiceus, Labeorohita and Aristichthys nobilis. [7] Amongst these, fish of the grass carp variety has been commonly reported for its toxicity but Xuan et al. also reported toxicity secondary to ingestion of shark (minnow) fish (M chrysophekadion) and the bony-lipped barb fish (O melanopi).[8] 

        Even though fish gall bladder can cause severe systemic complications, toxicity does not occur in all cases. In rural Vietnam, gall bladder from smaller fish are consumed regularly without evident toxicity. Thus it can be said that toxicity is directly proportional to the size and quantity of gall bladder or bile consumed. [8]

        Following ingestion almost all patients develop gastrointestinal symptoms within a few hours as reported by Xuan et al.[8] in his series of 17 cases from Vietnam. Deng et al.[9] has also reported extra-renal manifestations of the toxin with deleterious effects on the heart and liver with eventual multi-organ dysfunction syndrome.

         However patients usually seek therapy for renal failure which has an incidence of 55-100%. Renal failure is mostly secondary to acute tubular necrosis which may be a direct effect of the toxin. Kidney biopsy has shown the presence of proximal tubular cell damage with focal destruction of epithelial cells on light microscopy. [8],[9] The toxin is believed to damage lysosomes and inhibit cytochrome oxidase thus blocking cellular metabolism, leading to cell necrosis. This in addition to loss of fluid can lead to decreased effective circulating blood volume and eventually renal failure. However the exact mechanism of systemic injury especially renal failure is not known and needs further study.

       Most of the reported cases till date have undergone hemodialysis in view of renal failure Pandey et al.[10] in their case have also given Niaoduqing, a traditional Chinese medicine, to protect renal function.

        Most of our patient had predominant gastrointestinal symptoms. They usually responded to good supportive care and hemodialysis with complete recovery. These cases exemplify the practice of traditional folk medicine in rural India. Good awareness programs can aid diagnosis and prevent death from such a dangerous preventable cause of acute kidney injury which is the aim of International Society of Nephrology "0 by 25 Initiative".