Woman with congenital HIV infection and medication-induced Fanconi syndrome

A 19-year-old woman with congenital HIV infection was admitted to the hospital after experiencing nausea, vomiting, diarrhea, and fatigue for 1 week. Her CD4 count was 27. She had undergone percutaneous endoscopic placement of a gastrostomy tube for feeding 5 months earlier. In addition, she had extensive genitoanal ulceration due to infection with herpes simplex virus complicated by secondary bacterial infection. Her home medications included tenofovir disoproxil fumarate, sulfamethoxazole and trimethoprim, lamivudine, lopinavir/ritonavir, duloxetine hydrochloride, Nystatin, azithromycin, hydromorphone, and lorazepam. An electrocardiogram 11 months earlier had been normal except for sinus tachycardia, but in addition to sinus tachycardia the electrocardiogram recorded soon after the current admission showed changes suggestive of severe hypokalemia (Figure ​(Figure11): sagging ST segments, low T waves, and prominent U waves (which because of the tachycardia fuse with the subsequent P waves). Serum electrolyte concentrations in mEq/L were potassium, 1.4; sodium, 139; chloride, 119; and bicarbonate, 14. Her serum calcium concentration was 7.8 mg/dL, and the creatinine and urea nitrogen concentrations were 1.9 mg/dL and 6 mg/dL, respectively. Urinalysis at that time showed a glucose concentration of >1000 mg/dL while her serum glucose was only 90 mg/dL. Her serum uric acid concentration was 0.8 mg/dL, and serum phosphorus was 1.4. The hypercholemic, hypokalemic, metabolic acidosis was thought to be due to therapy with tenofovir. In addition to this, her metabolic acidosis was certainly exacerbated by recent diarrhea. The tenofovir was discontinued because of the suspected Fanconi syndrome. Figure 1 Electrocardiogram recorded soon after admission. See text for explication. After 5 days of aggressive fluid therapy and electrolyte replacement, her serum potassium concentration increased to 4.4 mEq/KL, and the tenofovir was restarted because of her serious HIV infection. After 5 weeks in the hospital, the patient had improved; her electrocardiogram was normal except for sinus tachycardia (Figure ​(Figure22), and she was discharged to inpatient hospice care on numerous medications, including electrolyte replacement. Figure 2 Electrocardiogram recorded shortly before discharge. See text for explication. Six days after discharge, the patient was readmitted with confusion and profound weakness. The admission electrocardiogram, seen in Figure ​Figure33, showed sinus tachycardia at a rate of 153 beats/minute, right axis deviation, and an intraventricular conduction defect (QRS duration, 0.20 seconds) that suggested hyperkalemia. Serum electrolyte concentrations in mEq/L at this time were potassium, 10.5; sodium, 135; chloride, 120; and bicarbonate, 12. The serum calcium level was 14.5 mg/dL despite a serum albumin level of only 2.2 gm/dL, the highest albumin level recorded during either admission. Her serum creatinine and urea nitrogen concentrations were 2.5 mg/dL and 41 mg/dL, respectively. As the hyperkalemia was treated with oral sodium polystyrene sulfonate, insulin, 50% dextrose solution, and emergent hemodialysis, the QRS duration shortened to 0.12 seconds, and T waves became more peaked and “typical” of hyperkalemia (Figure ​(Figure44). In addition, the QT interval was noticeably short considering the intraventricular conduction defect (QT interval, 0.25 seconds; QT interval corrected for heart rate, 0.40 seconds), a feature consistent with hypercalcemia. Figure 3 Electrocardiogram recorded on the second admission. See text for explication. Figure 4 Electrocardiogram recorded an hour after the electrocardiogram in Figure ​Figure3.3. See text for explication. One of the patient's discharge medications on her previous admission was potassium chloride, 60 mEq three times per day by mouth, and that dosage in the presence of her renal dysfunction undoubtedly caused the hyperkalemia that occasioned the second admission. She improved, but never sufficiently to leave the hospital. Her stay was complicated by multiple nosocomial infections, pressure sores, and worsened debilitation, and she eventually developed gram-negative sepsis and died 6 weeks after admission.