When AKI Strikes in Wilson Disease

Introduction: Wilson’s disease (WD) is a rare genetic disorder due to mutation in copper-transporting ATPase, ATP7B gene resulting in elevated plasma copper level and subsequent deposition in various organs with predominantly hepatic and neurologic disturbances. Renal involvement is rare and can be attributed to multiple pathophysiologic processes. Case Description: A 23 yo female presented to the ED with weakness, dark urine and yellowish discoloration of skin for 1 week. She had no prior medical or surgical history. She was on over the counter vitamin A and denied acetaminophen use. Her family history revealed a recent diagnosis of WD in her sister. Vital signs were normal. On physical examination, she had scleral icterus, yellowish skin discoloration without abdominal distention, tenderness or peripheral edema. Laboratory evaluation revealed total bilirubin 8.5 mg/dl, direct bilirubin 4.26 mg/dl, AST 213 U/L, ALT 70U/L, ALP 53 U/L. Her electrolytes and renal function were normal with a creatinine of 0.6 mg/dl. Cell counts were normal. Urinalysis showed 1+ bilirubin, no RBCs, 2+ protein, 6-10 WBC/ hpf. Abdominal ultrasound and CT were unremarkable. Hepatitis panel, HIV, EBV, syphilis, antismooth muscle and antimitochondrial antibody were negative. After transfer to our hospital, Ceruloplasmin level, 24-hour urine copper and genetic testing were ordered. She had a drop in hemoglobin to 6.3 mg/dl, associated with a rise in total bilirubin to 30 mg/dl. Kayser-Fleischer ring was suspected on ophthalmologic evaluation. LFTs worsened and she subsequently developed metabolic acidosis with acute kidney injury. Urine sediment showed acute tubular necrosis, and she required renal replacement with CVVHD. She received a liver transplant and intraoperative liver biopsy showed end stage liver with bridging fibrosis and copper accumulation. Renal function improved post transplantation. Discussion: A variety of mechanisms have been proposed for acute kidney injury in the setting of WD which include direct tubular toxicity from copper deposition resulting in electrolyte and acid base disorders with Fanconi’s syndrome, hepatorenal syndrome, acute tubular necrosis from intratubular cast formation, and cholemic nephropathy. Being aware that patients with Wilson’s disease are at risk of severe renal injury during the disease course and being proactive with volume resuscitation and blood product transfusion can prevent long term sequela.