| | Quiz Page December 2008: Acute Kidney Injury, Hematuria, and Orange Skin PigmentationClinical Presentation  A 51-year-old man developed nausea, vomiting, diarrhea, abdominal pain, and dark red urine 2 hours after inhaling a noxious powder at an industrial galvanizing plant. Two days later, he presented for medical care, noting low urine output and a cough productive of bloody phlegm. On examination, he had striking orange pigmentation to his skin and sclerae, tenderness in the right upper abdomen and bilateral flanks, and edema. Blood pressure was 110/75 mm Hg on presentation and remained normal. Laboratory tests showed the following values: hemoglobin, 5.8 g/dL; platelet count, 171 × 103/μL; reticulocyte count, 1.3%; mean cell volume, 89.77 fL; serum creatinine, 6.8 mg/dL (518 μmol/L); total bilirubin, 1.9 mg/dL (33.1 μmol/L); indirect bilirubin, 1.1 mg/dL (19.5 μmol/L); and direct bilirubin, 0.8 mg/dL (13.6 μmol/L). The orange pigmentation to his skin gradually changed to a mixed color of orange and bronze. On day 7, mean cell volume reached 100.94 fL, reticulocyte count was 3.5%, total bilirubin level was 1.2 mg/dL (21.2 μmol/L), indirect bilirubin level was 0.7 mg/dL (12.5 μmol/L), direct bilirubin level was 0.5 mg/dL (8.7 μmol/L), serum aspartate aminotransferase level was 200 U/L, serum alanine aminotransferase level was 204 U/L, lactate dehydrogenase level was 1,448 U/L, and creatinine clearance was 3.33 mL/min (0.06 mL/s). Proteinuria was quantitated at protein of 1.06 g/24 h, with albuminuria of 400 mg of albumin. Urine sediment showed 0 to 3 red blood cells/high-power field without dysmorphic features. Abdominal ultrasound showed enlarged kidneys with hyperechoic kidney parenchyma, an enlarged liver, and sand-like echogenicities in the gallbladder. The patient was treated with dexamethasone, packed red blood cell transfusion, and hemodialysis and hemoperfusion on the day of admission. After failing to recover kidney function, a kidney biopsy was performed 10 days after presentation of symptoms. ■ Describe the light microscopy and electron microscopy findings on the kidney biopsy specimen (Fig 1). ■ What are the possible causes of acute kidney failure in this patient? ■ What is the clinical pathologic diagnosis? Discussion Describe the light microscopy and electron microscopy findings on the kidney biopsy specimen Light microscopy of the kidney biopsy specimen shows mild mesangial cell proliferation (Fig 1A), but severe tubular injury with albumin casts, dilated tubules with denuded tubular basement membrane, and severe vacuolar and granular degeneration of the tubular epithelial cells (Fig 1B). Histochemical examination shows hemoglobin-containing casts (Fig 1C) and tubular epithelial cells with hemosiderin deposits on hematoxylin and eosin staining (Fig 1D), confirmed by iron staining (Fig 1E). Electron microscopy shows normal glomeruli, but tubular epithelial cells with lysosomes and phagocytic vacuoles. Furthermore, cellular debris was seen in tubules, with detached brush border and uncharacterized dark granules in the cytoplasm (Fig 1F). What are the possible causes of acute kidney failure in this patient? The patient had acute kidney injury after a noxious inhalation at an industrial galvanizing plant. The history suggests kidney damage related to exposure to heavy metals or industrial toxins. The differential diagnosis includes acute kidney injury caused by exposure to various heavy metals, including lead, cadmium, mercury, and arsenic.1, 2, 3 Lead Occupational exposure to inorganic lead occurs in mines and smelting houses after welding of lead-painted metal and in battery plants. Symptoms of acute lead poisoning are headache, irritability, abdominal pain, acute psychosis, and reduced consciousness in severe cases. Acute lead exposure is known to cause proximal tubular damage. Chronic lead poisoning can cause anemia resulting from hemolysis and damage to the hematopoietic system.1 Cadmium Inhalation of cadmium particles can be life-threatening because of acute pulmonary effects. A large amount of ingested cadmium may cause acute liver necrosis. The first sign of kidney damage is usually tubular dysfunction, and cadmium-induced tubular damage is irreversible.1 Mercury A major use of mercury in industry is in the electrochemical process of manufacturing chlorine. Acute mercury exposure typically presents with lung damage, but also may cause reversible kidney damage. Organic mercury poisoning has a latency of 1 month or longer after exposure, and the main symptoms relate to nervous system damage, such as paresthesias and numbness in the hands and feet, coordination difficulties, and concentric constriction of the visual field.1, 2 Arsenic Arsine gas (AsH3) is the most acutely toxic form of arsenic, with hemolytic toxic action that can be fatal. Exposure to AsH3 can occur from processing arsenic-contaminated substances, such as wastes from mines and manufacturing plants. Symptoms may appear after a few hours of arsine exposure. Exposure to AsH3 is reportedly fatal in up to 25% of human cases, typically from acute kidney injury. Symptoms are headache, weakness, dizziness, malaise, dyspnea, abdominal pain, nausea, and vomiting, followed by the appearance of dark red urine and jaundice or orange skin pigmentation. Acute oliguric kidney injury may occur as the result of massive tubular damage induced principally by the intratubular precipitation of hemoglobin and/or the direct toxic effect of arsine on kidney tissue, and the dark red urine and orange skin pigmentation may be caused by hemolysis.1, 3 What is the clinical pathologic diagnosis? The main clinical feature of this patient is acute kidney injury with dark red urine and orange skin pigmentation, which is most consistent with arsine poisoning. Urinary arsenic detected by means of the silver diethyl-dithiocarbamate method showed a level of 4.61 mg/L compared with the normal level of less than 2 mg/L. The main effect of arsine is rapid hemolysis with kidney tubular damage. Pathologically, there are necrotic changes in epithelial cells, hemoglobin cast and focal tubular hemosiderin deposition, and acute tubular necrosis. The dark granules seen in the cytoplasm on electron microscopy might be hemolytic product containing AsH3 metabolite. This is the first report of kidney biopsy findings in a patient with acute arsine poisoning. In our patient, after 7 hemodialysis and 4 hemoperfusion treatments, the patient's kidney function improved, with complete recovery after 1 year. Early diagnosis and treatment with both hemodialysis and hemoperfusion are essential and undoubtedly life-saving. Final Diagnosis Acute kidney injury caused by arsine poisoning. References 1. 1Jarup L. Hazards of heavy metal contamination. Br Med Bull. 2003;68:167–182. MEDLINE |
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2. 2Bernard A. Renal dysfunction induced by cadmium: Biomarkers of critical effects. Biometals. 2004;17:519–523. MEDLINE |
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3. 3Tanaka A. Toxicity of indium arsenide, gallium arsenide, and aluminium gallium arsenide. Toxicol Appl Pharmacol. 2004;198:405–411.
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Case provided and authored by Lihong Zhang, MD,1 Yanling Zhang, MD, PhD,1 Qiongzhen Lin, MD,1 Wanzhong Zou, MD,2 Wenyun Zhang, MD,3 Maodong Liu, MD,1 Haiying Lin, MD,1 Ying Li, MD,1 1Department of Nephrology, Third Hospital, Hebei Medical University, Shijiazhuang; 2Department of Pathology, Peking University, Beijing; and 3Department of Ultrasound, Third Hospital, Hebei Medical University, Shijiazhuang, China. Financial Disclosure: None. PII: S0272-6386(08)01105-0 doi:10.1053/j.ajkd.2008.05.036 © 2008 National Kidney Foundation, Inc. Published by Elsevier Inc All rights reserved. | 
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