1961Gryboski et al. [48]United States of Americacase report17 years oldmale30 mg of bismuth thioglycolate (Thio-Bismol) intramuscularly (1.3 mg/kg)Vomit, mild tenesmus, false urge to void, weight loss, mild periorbital oedema, and azotemia (for creatinine and urea). Later, skin rash was also observed.Diagnosis of renal damage due to bismuth was based on retention of waste products, low urinary output, inability to concentrate urine, and mild acidosis. Normal renal function was restored within a month.1963Chamberlain and Franks [49]United States of Americacase report19 years oldfemale3 g of bismuth thioglycolate (Thio-Bismol) intramuscularlyNausea, vomit, emesis, proteinuria, glycosuria, haematuria, pyuria, periorbital oedema, reduction in urinary outputDiagnosis of acute nephritis. After 9 days, the patient was discharged from the hospital.1964Czerwinski and Ginn [50]United States of Americacase report119 years oldfemale21 tablets of bismuth sodium trithioglycollamate (Bistrimate) equivalent to 1.5 g of elemental bismuthNausea, vomit, hand tingling and numbness, cramping of the legs and thighs, urine glucosuria, proteinuria and granular casts. Azotemia and urine output decrease was also reported. Later, skin rash was also observed.Renal damage suffered by the patient was due to sodium bismuth trithioglycollamate. After 35 days, the patient was discharged from the hospital.1968James [51]United States of Americacase report114 years oldfemale7 to 8 tablets of bismuth sodium triglycollamate (Bistrimate) equivalent to 525 to 600 mg of elemental bismuthVomit, prostration and lethargy, urine output decrease, azotaemia, mouth dryness, feet numbness, and weight loss. No bismuth was detected in a specimen of serum submitted two days after admission.There was no history of any pre-existing renal disease. After 10 days, the patient was discharged from the hospital.1989Hudson and Mowat [52]United Kingdomcase report127 years oldmale100 tablets of colloidal bismuth (De-Nol) a total of 12 g of the drugAnorexia, nausea, vomiting, general malaise, weakness of legs, blurring of vision, thirst, poor urinary output, dehydration, proximal leg muscle weakness with hyperreflexia and ankle clonus. An abdominal X-ray film showed opacification of the colon by ingested bismuth. Bismuth in blood was detected in a decreasing concentration up to 96 days after ingestion, measured by atomic absorption spectrophotometry (AAS).Renal failure and neurotoxicity induced by bismuth were diagnosed. Five days later, renal function had returned to normal and neurological signs resolved.1990Taylor and Klenerman [53]United Kingdomcase report176 years oldmale80 tablets of tripotassium dicitrato bismuthate (De-Nol)Vomit, oliguria, haematochezia, and mild epigastric tenderness in admission. Bismuth was detectable in the blood with a concentration of 1600 µg/L. X-ray showed opacification of the colon by ingested bismuth.Acute abdominal pain developed with absent bowel sounds but he was judged unfit for surgery and died 4 days later. Necropsy revealed a perforated duodenal ulcer and pale kidneys which proved to contain bismuth with a mass fraction of 16 mg/g.1990Playford et al. [54]United Kingdomcase report168 years oldmaleFor two months, a 10 mL daily dose of tripotassium dicitrato bismuthate (De-Nol) being 864 mg of bismuth per day, a total of 48 g of bismuth.Confusion, difficulty walking, urinary incontinence, hallucinations, and ataxia. Alterations on the electroencephalogram were consistent with a metabolic encephalopathy. Blood bismuth was 880 µg/L and urinary 230 µg/L detected by inductively coupled plasma source spectrometry (ICP-MS).This patient had a history of renal impairment. For the bismuth intoxication, a chelation therapy used 2-3 dimercapto-l-propane sulphonic acid and after discontinuation of the bismuth administration its blood concentration decreased and improvement in his cerebral function was observed.1991Treiber et al. [55]Germanyprospective18 patients: 7 with impaired renal function (creatinine clearance = 34 ± 19 mL/min), 7 with normal renal function, and 4 dialysed. All patients had positive Helicobacter pylori status and diagnosis of duodenal ulcers, gastric ulcers, or gastritis type B confirmed by endoscopy.53.9 ± 14.4 years old for impaired renal function, 44.9 ± 9.2 years old for normal renal function, and 49.0 ± 14.7 years old for dialysed9 male and 9 female240 mg of tripotassium dicitrate bismuthate (Telen) twice a day before meals (corresponding to 216 mg bismuth) for four weeks except for the dialysis patients where a 120 mg dose was used.A rapid increase in the plasma concentration of bismuth was observed in all patients following the first dose when measured by AAS. This increase was dependent on renal function assessed by creatinine levels. All patients noted black stools. Two patients reported nausea and one patient sleep disturbance. One patient reported allergic reaction and another one osteoarthritic symptom.Monotherapy with tripotassium dicitrate bismuthate resulted in eradication of Helicobacter pylori in 28% of the patients. After stopping the therapeutic regimen, the plasma concentrations of bismuth returned to pre-study levels within two weeks (in normal renal function patients) or four weeks (impaired renal function patients). Plasma concentrations in the dialysed patients receiving half of the dose did not exceed those of all the other individuals.1992Huwez et al. [56]United Kingdomcase report121 years oldmale39 tablets of bismuth subcitrate (brand not stated) a total of 4.68 g of the drugEpigastric pain, reduced urinary output, and deteriorated renal function. Renal biopsy revealed moderate acute tubular necrosis with focally prominent regenerative atypia. Serum bismuth was above 100 µg/L on day 14 after ingestion detected by ICP-MS.Serum bismuth concentration reduced due to distribution. Patient was discharged well on day 120.1995Stevens et al. [46]United Kingdomcase report121 years oldmale50–60 De-Nol tabletsNausea, vomiting, diarrhoea, exhaustion, anuria, and azotaemia. Measured by AAS, blood bismuth concentration was 590 µg/L. An abdominal radiograph showed opacification of the colon with bismuth. Evidence for proximal tubular damage in the pathogenesis of the renal failure was shown by glycosuria and a β2-microglobulin excretion.150 mg of dimercaprol was administered intramuscularly and patient was transferred. Dialysis using a cellulose acetate kidney and a recirculating dialysis system for four hours was commenced one hour after intravenous sodium-(2,3)-dimercaptopropane-(l)-sulphonate administration. The patient began to pass urine again on day 8 and by day 13 was independent of dialysis.1996Akpolat et al. [47]Turkeycase report116 years oldfemale10–15 tablets of tripotassium dicitrato bismuthate (brand not stated)Nausea, vomiting, dizziness, and oliguria. Renal biopsy was performed. Hematoxylin-eosin sections revealed vacuolation, flattening, necrosis, and prominent regeneration in tubular epithelium (mainly proximal tubuli epithelium) with widening of lumens and localized cell detachment. Moderate mononuclear cell infiltration in the interstitium and edema, congestion, and narrowing of Bowman’s capsular space in the glomeruli was also observed.The final diagnosis was acute tubular necrosis. The patient was managed with haemodialysis via femoral vein catheter. Her urine volume gradually increased, and azotemia subsided. After 20 days, the patient was discharged from the hospital.2001İşlek et al. [57]Turkeycase report12 years oldmale28 tablets of colloidal bismuth subcitrate (De-Nol) a total of 8.4 g of the drugVomit and three tablets were observed in the gastric aspirate. X-ray showed opacification of the intestine and the colon by ingested bismuth. Still somnolent and lethargic days later. Reduced urine output, facial edema, and azotemia developed. No bowel movement during the first three days after admission was observed and the stool was black in color on day four.Acute poisoning due to colloidal bismuth subcitrate was diagnosed and the patient was given gastric lavage in the paediatric emergency service. Intraperitoneal swan-neck catheter was placed for automated peritoneal dialysis therapy for six days. Urine volume gradually increased. A control abdominal X-ray demonstrated no opacification on day six. After 20 days, the patient was discharged from the hospital.2002Sarikaya et al. [58]Turkeycase report117 years oldfemale25 tablets of bismuth subcitrate (brand not stated) a total of 7.5 g of the drugDecreasing urine output and anuric for the last three days. Pretibial and periorbital oedema were observed. Gastric pain, eosinophiluria, azotemia, and increased renal parenchymal echo. Renal biopsy was performed. Signs of acute tubular necrosis were encountered in the proximal tubule epithelium. Epithelial flattening, lumen widening, and atrophic changes were seen in the convoluted tubules and mononuclear cell infiltration and edema in the interstitium.The patient was managed with hemodialysis via a subclavian vein catheter. Urine volume gradually increased. Urinary examination did not show any protein, erythrocytes, or leukocytes. After 21 days, the patient was discharged from the hospital.2002Hruz et al. [59]Switzerlandcase report122 years oldfemale5.4 g of colloidal bismuth subcitrate (brand not stated)Drowsiness, pain over both renal flanks, oliguric, azotemia, proximal tubular dysfunction (Fanconi’s syndrome: hypophosphatemia, hypouricemia, metabolic acidosis, and renal glucosuria despite normal plasma glucose concentration), proteinuria. Measured by AAS, serum bismuth concentration reached 640 µg/L on day three. Ultrasonography showed enlargement of both kidneys. Magnetic resonance imaging showed enlarged and edematous kidneys with thinning of the cortical area. On day 8, the patient showed ulcerations of both tonsils and stomatitis.Intravenous treatment with the chelating agent sodium- 2,3-dimercapto-1-propanesulfonate was started. Because of persistent renal failure and with the aim to eliminate bismuth, hemodialysis was started. Diuresis resumed 10 days after admission. Signs of Fanconi’s syndrome with tubular proteinuria and the ulcerations on both tonsils disappeared. After 19 days, the patient was discharged from the hospital.2005Cengiz et al. [60]Turkeycase report116 years oldfemale60 tablets of colloidal bismuth subcitrate (De-Nol) a total of 18 g of the drugNausea, vomiting, facial paraesthesia, and periorbital and pretibial edema. Ultrasonography demonstrated slightly increased kidney size bilaterally and slightly increased echogenicity in the renal parenchyma. Measured by AAS, serum bismuth concentration was 495 µg/L after 12 days of ingestion.Hemodialysis therapy was started and oral treatment with a metal chelating agent (penicillamine 20 mg/kg per day) was also prescribed. Azotemia subsided after a month. After 16 days, the patient was discharged from the hospital.2013Erden et al. [61]Turkeycase report121 years oldfemale20 tablets of colloidal bismuth subcitrate (brand not stated). Each tablet included 300 mg of drug, which is equivalent to 120 mg of bismuth oxide.Abdominal ultrasonography demonstrated slightly increased echogenicity in the renal parenchyma. Oliguria followed by anuria was observed. Blood chemistry and urine sediment showed signs of proximal tubular dysfunction (Fanconi’s syndrome) and azotemia.Oral treatment with the chelating agent sodium-2,3-dimercapto-1-propanesulfonate was initiated. Hemodialysis was performed because of anuria and severe metabolic acidosis. Afterwards, the patient’s urine output progressively increased. After 15 days, the patient was discharged from the hospital. Azotemia did not subside, and the patient needed hemodialysis for approximately one year after due to the chronic renal failure caused by the bismuth ingestion.2014Kratochwil et al. [62]Germanycohort8 patients: 7 with progressive advanced neuroendocrine liver metastases refractory to treatment and 1 with bone marrow carcinosisnot given4 male and 4 female213Bi-DOTATOC receptor-targeted alpha-radionuclide therapy was administered in increasing activities in cycles every 2 months. To minimize renal toxicity, 1000 mL of a nephroprotective solution containing 30 g lysine and 30 g arginine and 500 mL of gelofusine was administered simultaneously, followed by 1000 mL of saline.Acute haematological toxicity was low. One patient with a previous history of grade IV thrombopenia with 90Y-DOTATOC therapy developed grade II thrombopenia with 213Bi-DOTATOC. During the long-term follow-up, three patients developed chronic anaemia. Erythropoietin levels in lower normal range were found in two patients. Graves’ disease (toxic diffuse goiter) was diagnosed one year after the last treatment cycle and must be considered therapy-associated because thyroid cells can also express somatostatin receptors.Anemia was interpreted as a side effect of endocrine kidney function rather than bone marrow function. Acute hematological and chronic kidney toxicity are most relevant in peptide receptor radiation therapy. During the follow-up of two years, none of the patients developed severe kidney failure requiring dialysis.2015Akinci et al. [63]Turkeycase report116 years oldfemale19 grams of bismuth subcitrate potassium (De-Nol) Opacity in the upright abdominal X-ray. On the 3rd day of admission, the patient developed acute renal failure, metabolic acidosis, and oliguria. The patient had sore throat from the 3rd day and bilateral tonsillar ulceration was observed. The patient became anuric on the 5th day. On the 15th day of admission the patient developed altered mental state. Neurological examination revealed confusion, somnolence, and cortical blindness, as well as bilateral pyramidal findings followed by frequent seizure attacks. Magnetic resonance imaging showed hyper-intense signal alterations at the levels of bilateral parietal vertices of both cerebellar hemispheres. Gastric lavage was performed. The patient underwent hemodialysis following catheterization through the jugular vein. Following dialysis performed on alternate days, urination resumed on the 10th day. On the 13th day, the patient became polyuric. Toxic metabolic encephalopathy was associated with the images. The laboratory parameters of the patient began to normalize on the 20th day of admission. After 24 days, the patient was discharged from the hospital.2017Disel et al. [64]Turkeycase report134 years oldfemale8 tablets of bismuth subcitrate (De-Nol) a total of 2400 mg of the drugNausea, vomit, apathy, proteinuria, glucosuria, and hemoglobinuria. A blue-black discoloration in the teeth and gum was observed. Ultrasonography revealed bilateral perirenal free fluid and grade 1–2 renal parenchymal changes. The patient became anuric and acidotic.The previous medical history described continuous bismuth therapy for peptic ulcer. Gastric lavage was performed. A diagnosis of acute renal failure due to bismuth toxicity was concluded. The patient underwent hemodialysis and one session of plasmapheresis. Apathy improved and the discoloration of the teeth and gum recovered. After 24 days, the patient was discharged from the hospital.2019Çelebi-Tayfur et al. [65]Turkeycase report1 pregnant patient16 years oldfemale20 tablets of colloidal bismuth subcitrate (De-Nol). Each tablet included 300 mg of drug, which is equivalent to 120 mg of bismuth oxideNausea, vomit, and anxiety. Beta human chorionic gonadotropin level in the blood was 150.07 mIU/mL. Ultrasonography demonstrated severely increased echogenicity on both renal parenchyma. Transvaginal ultrasonography detected an early pregnancy at 5 weeks and 4 days. Proteinuria, hematuria with red blood cells of normal morphology, and pyuria were also observed. The patient rapidly became oliguric, and azotemia was detected. Decontamination of bismuth was performed by gastric lavage and fluid therapy. A chelation therapy with parenteral dimercaprol was started. Continuous venovenous hemodiafiltration was performed for three days. The patient’s urine output progressively increased and renal function tests comprising arterial blood gas analysis gradually improved. After 21 days, the patient was discharged from the hospital. The council recommended termination of the pregnancy due to potential risks, but the patient preferred continuation of the pregnancy. The patient gave birth to a term healthy baby boy with vaginal delivery. 2020Halani and Wu [66]Canadacase report179 years oldmale1 to 2 bottles of bismuth subsalicylate (Pepto-Bismol) daily for 6 months, equivalent of 8.3 to 16.6 g of bismuth subsalicylate per dayConfusion, inattention, impaired hearing, and ataxia. His medical history included chronic kidney disease secondary to diabetic nephropathy.Acute kidney injury was diagnosed, and Pepto-Bismol was discontinued. Isotonic intravenous fluids were administered to facilitate renal excretion of the salicylate. The mental status, hearing, and gait improved.2021Aga et al. [67]Canadacase report168 years oldmaleSelf-treated with over-the-counter bismuth subsalicylate in a dose of <150 mg/kg (brand not stated)The patient was minimally responsive (Glasgow Coma Score 7). Nausea, vomit, metabolic acidosis, and increased colostomy outputs were observed. A prerenal acute kidney injury from emesis and high colostomy outputs was present.The acute salicylate toxicity after bismuth subsalicylate ingestion successfully managed with hemodialysis with complete neurological recovery.