Acute Kidney Injury Following Ingestion of Raw Fish Gallbladder of Indian Crap (Labeo Rohita): Thirty Case Series During 1975–2018

Introduction

In tropical countries like India, poisons and toxins are important contributing factors in the etiology of acute kidney injury (AKI) besides infections such as malaria, leptospira, and gastroenteritis. Fishes have been used as delicious food that is rich in protein, vitamins, fatty acids, and minerals. The Indian carp (Labeo rohita) is the most superior of all fresh water fishes, and its gallbladder has been used as Ayurvedic and traditional medical remedies in improving the brightness of eyes, night blindness, bronchial asthma, rheumatism, chronic ill health, dyspepsia, and improvement of general health.[1] [Figure 1] Besides fish poisoning (ichthyotoxicosis), ingestion of some selected parts of fish such as gallbladder, ovary, testes, and liver for homicidal and suicidal purpose have been described as fugu in Japan and fuguism in the Philippines.[2] The common carp fishes (Cyprinouscarpio) such as Indian carp (Labeo rohita), grass carp (Ctenopharyngodonidella), and silver carp (Hypophthalmichthysmolitrix) have been reported from Assam, Manipur, Maharashtra, and Odisha. Here we report 30 sporadic patients who developed AKI following ingestion of raw gallbladder of Indian carp fish during 1975–2018 (44 years).

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Figure 1

(a) Taxonomy of Indian carp (Labeorohita). Kingdom: Animalia, Phylum: Chordata, Class: Actinopterygii, Order: Cypriniformes, Family: Cyprinidae, Genus: Labeo, Species: rohita. (b) Digestive system of the fish (Labeorohita)

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Materials and Methods

All admitted AKI patients following a definite history of ingestion of raw fish gallbladder of Indian carp were admitted to two medical colleges and one superspeciality hospital. Detailed history of the mode of ingestion of raw fish gallbladder, indication for which ingested, and details of prescriber/advisor (Ayurvedic physicians, well-wishers, family members, friends, or quacks) were obtained. The time lag between ingestion and onset of symptom, clinical features, and management details were recorded. Laboratory investigations, including kidney function tests, liver function test, complete blood count, and urine analysis, were done. Electrocardiogram and echocardiography were done whenever required. Kidney biopsy was done in selected patients with Franklin’s modification of Vim–Silverman’s needle with or without ultrasound guidance. Kidney tissue was obtained in 14 patients and liver tissue in six patients. Only light microscopic study of biopsy specimen was done.

Results

Thirty patients were admitted to hospitals with AKI following definite history of ingestion of raw fish gallbladder of Indian carp. Associated comorbidities for which it was taken, number of ingestions of raw fish gallbladder, reason or diseases for which ingested, duration with the onset of symptom after ingestion, clinical features, and management details were recorded are highlighted in Table 1. All the individual cases details such as year, place, prescriber, number of fish consumed, liver toxicity, number of dialysis, and clinical outcome have been described. All 30 patients had taken one gallbladder each, except three patients who took two at a time. One patient gave the history of taking fish gallbladder at regular intervals of months and years on three to four occasions for improving health and vitality. The severity of the disease was dose related. The patient who took at the regular interval had AKI with less severity with normal urine output. The demography details, symptomatology, and investigations are detailed in Table 2. The symptoms appeared 2 to 12 hours after the ingestion of gallbladder. The gastrointestinal symptoms such as nausea, severe vomiting, abdominal cramps or pain, and loose motion were prominent in all (100%) of cases. Hepatic involvement was noted in 10 (33.3%) patients. Six patients had hypertension in addition to vomiting, diarrhea, and hypovolemia. The first organ affected was the gastrointestinal tract. Oliguria and anuria with jaundice were observed after 24 to 72 hours. Skin rashes appeared after the first week. Urine examination revealed hematuria, proteinuria along with red blood cells (RBCs), hyaline, granular, and hemoglobin casts. The mean levels of hemoglobin, urea, creatinine, sodium, potassium, bilirubin, and liver enzymes are shown in Table 2. Six patients had hyponatremia (113–126 mmol/L). Five patients had hyperkalemia (6.5–8.6 mmol/L). Kidney tissue obtained in 14 patients showed glomerulitis in three patients and acute tubular necrosis in all 14 cases. Distal tubular degeneration with hemoglobin casts was seen in two cases. There was interstitial edema with inflammatory cell infiltration in six cases. Liver biopsy tissue was obtained in six out of 10 cases with hepatic involvement. All of them showed features of acute toxic hepatic necrosis. Twenty-two of them required hemodialysis support, and the other eight patients were managed conservatively. There were six patients with multiorgan dysfunction with renal, hepatic, gastrointestinal, and cardiac involvement. They had a fulminating clinical course with catastrophic consequences. Two patients developed intravascular hemolysis with hemoglobinuria, and one of the two had glucose-6-phosphate dehydrogenase (G6PD) deficiency. Two of them had myocarditis, and one of the two expired. Thus, out of 30 patients, 25 cases (83.3%) recovered and five (16.7%) died due to septicemia, and myocarditis. Early and intensive hemodialysis resulted in a better prognosis.

Discussion

The fish gallbladder ingestion-associated toxic AKI case series consists of 30 patients admitted in three different tertiary hospitals of Odisha. There have been many case reports of AKI and acute hepatic toxicities after ingestion of Indian carp (Labeorohita), grass carp (Ctenopharyngodonidella), silver carp (Hypophthalmichthysmolitrix), and carps (Cyprinous carpio) seen all across the country.[3] The severity of the disease is dose dependent. The volume of bile ingested depends on the size of the gallbladder and the fish. The larger the size of the ingested fish and gallbladder, the higher is the risk of intoxication.[3]

Fish bile, like mammalian bile, contains a similar composition of bile salts, cholesterols, phospholipids, bile pigments, organic anions, glycoproteins, and inorganic ions.[4] The bile of rohu and mrigal contains mainly taurine derivatives of lithocholic acid. In Cyprinids (carp fishes), bile alcohol sulfate is the principal bile salt.[5] The main toxin of fish gallbladder poisoning in carp fishes is believed to be water-soluble sodium cyprinol sulfate.[6] Besides the kidney, it can also damage the heart, liver, and gastrointestinal tract leading to multiple organ dysfunction.[7] The toxin in the fish gallbladder can directly damage the mucous membrane of the gastrointestinal tract. It also produces toxic hepatitis and toxic myocarditis.[6] In the present report, we noticed AKI and gastrointestinal tract involvement in all cases. Ten patients had hepatic involvement, and three had myocarditis. Vomiting and diarrhea resulting in hypovolemia may be a contributing factor in the pathogenesis of AKI. The toxin, sodium cyprinol sulfate, produces direct toxic damage to the lysosome and targets the kidney, liver, heart, and gastrointestinal tract, resulting in multiorgan dysfunction.[7] The cyanide and histamine inhibit cytochrome oxidase, thereby blocking the cellular energy metabolism causing necrosis of tubular epithelial cells in the proximal tubule.[8] Xuan BHN et al.[7] reported 11 patients with multiple organ dysfunction after ingestion of raw gallbladder of grass carp in south China. Other reports are from Japan,[9] Taiwan,[10] Formosa,[11] Korea, Vietnam,[8] Maryland, Pennsylvania, USA,[12] and India. Multiple organ dysfunction following ingestion of raw fish gallbladder of Indian carp has also been reported from Assam,[13] Maharashtra,[3] Bihar,[14] and Odisha.[15,16] Other sporadic case reports have also been published in the recent literature.[17,18] Recently, a large case series has been published with the similar presentations of AKI with consumption of raw gallbladder of Indian carp fish.[19] The species of fishes belonging to the order Cypriniformes common carp (Cyprinouscarpio), grass carp (Ctenopharyngodonidella), Indian carp (Labeorohita), and silver carp (Hypophthalmichthysmolitrix) have been associated with hepatorenal syndrome.[14] The bile components responsible for this syndrome have not been characterized fully. The bile in the gallbladder of Cyprinid fishes (carp fishes) contains principal bile salt, the sodium cyprinol sulfate that is responsible for toxicity. It was reported that the toxic effect of 5a-cyprinol sulfate on kidney function was more harmful than that of 5a-bile-induced hepatitis and renal failure. Xuan BHN et al. and Hwang DF et al.[5] have described the light microscopy, which showed hydropic bubbles and fatty degeneration of damaged epithelial cells in the proximal tubule.[7,20] Furthermore, in all said studies, histopathology of kidney and liver tissue specimen demonstrated acute tubular necrosis of the proximal tubule and hepatic necrosis in the liver. Electron microscopy examination showed vacuolar degeneration of mitochondria in the tubular epithelial cell, swelling of tubular endothelial cells, partial fusion of foot processes of glomeruli, deformation, and narrowing of Bowman’s capsule. We performed only light microscopy in all 14 patients, which showed toxic glomerulitis in three cases, acute tubular necrosis in all, and RBC cast in three cases. Two cases had intravascular hemolysis and hemoglobinuria where distal tubular degeneration with hemoglobin casts was seen; one of them had G6PD deficiency. There was interstitial edema with inflammatory cell infiltration in the interstitial with mononuclear and polymorphonuclear cells in six patients. Six out of 10 patients with hepatic involvement, where liver biopsy was available, showed evidence of acute toxic hepatic necrosis of liver tissue as in the previous reports of toxic hepatitis.

Conclusion

This largest and longest four-decade case series highlights that indiscriminate ingestion of raw fish gallbladder by unqualified prescription results in AKI with multiple organ dysfunction and death. This very uncommon cause of AKI is a lesson to physicians and nephrologists to keep in mind for the future while probing the etiology of AKI. Public health workers need to educate the rural mass where such practices are seen and to prevent them from such poisoning.