Acute Sin Nombre Hantavirus Infection Complicated by Renal Failure Requiring Hemodialysis

Abstract

To the Editor: The hantavirus pulmonary syndrome (HPS), a zoonotic viral infection transmitted by rodents, is an unusual cause of acute respiratory failure and is rarely associated with renal insufficiency. We report a case of infection with Sin Nombre hantavirus complicated by acute respiratory failure and renal failure requiring hemodialysis. Report of a Case. A 57-year-old man was transferred to Saint Marys Hospital in Rochester, Minn, because of respiratory insufficiency and altered mental status. He described a flulike illness beginning in late October and progressing over 1 week. Symptoms included headache, fever, chills, and difficulty thinking clearly. He had cleaned his garage several days before the onset of illness. He had no recent history of trauma, travel, or exposure to illness. He had donated his left kidney to his brother earlier in the year. A review of systems was otherwise unremarkable. His shortness of breath worsened, and he required supplemental oxygen. On physical examination, the patient's heart rate was 127 beats/min, and supine blood pressure was 100/63 mm Hg. His skin showed signs of dehydration without rash. Crackles were noted bilaterally on chest auscultation. Findings on abdominal examination were normal. Laboratory evaluation revealed a white blood cell count of 10.3 × 109/L with 85% neutrophils, a platelet count of 67 × 109/L, and a normal hemoglobin concentration. The serum creatinine level was 1.9 mg/dL. Urinalysis showed an elevated protein-osmolality ratio of 0.65 (normal, 0.12). Chest radiography revealed diffuse pulmonary infiltrates. Arterial blood gas studies yielded a PaO2 of 65 mm Hg while the patient received 5 L of oxygen via nasal cannula. Computed tomography of the head showed normal findings, but computed tomography of the chest, abdomen, and pelvis revealed bilateral perihilar infiltrates in the mid and upper lung fields with stranding in the retroperitoneum bilaterally. Blood was withdrawn for cultures. Lumbar puncture revealed a cerebrospinal fluid protein level of 58 mg/dL and a glucose concentration of 80 mg/dL. Antibiotic therapy was initiated with levofloxacin, cefepime, metronidazole, and doxycycline. Two days later, the patient's increased oxygen requirements and hypotension led to transfer to the medical intensive care unit (MICU), where he underwent endotracheal intubation and mechanical ventilation with 100% oxygen. Intravenous fluids and infusions of vasopressin and phenylephrine were administered. Echocardiography showed a left ventricular ejection fraction of 65% to 70% with mild hypokinesia of the basal to inferolateral portions of the left ventricular wall. Bronchoalveolar lavage fluid obtained on arrival at the MICU showed no growth on cultures. Because of persistent hypotension, a pulmonary artery catheter was inserted. The cardiac index was 2.03 L/min per m2, the pulmonary artery occlusion pressure was 22 mm Hg, and the systemic vascular resistance index was 2125 dyne · s · cm−5 · m−2. The serum creatinine concentration increased to 3.5 mg/dL, and the serum bicarbonate level was 12 mEq/L. The calculated urinary fractional excretion of sodium was 0.11. Continuous venovenous hemodialysis was initiated after nephrology consultation. Five days after MICU admission, vasopressors were tapered and discontinued. Multiple fungal, viral, and bacterial serologies yielded normal findings. Blood culture results remained negative, and antibiotics were discontinued. On day 12 of the MICU stay, the patient was extubated successfully, and continuous dialysis was replaced with intermittent hemodialysis. Two days later, viral serologies sent to the Centers for Disease Control and Prevention were reported to be positive for Sin Nombre virus, with an IgM titer of 1:6400 and an IgG titer of 1:1600, both consistent with acute hantavirus infection. Supportive therapy was continued, and the patient remained in the MICU for 5 more days. He returned home 3 weeks later. At the time of discharge, his renal function had not fully recovered, but he did not require hemodialysis. Two months later, his renal function had returned to baseline. Discussion. Hantavirus pulmonary syndrome was first recognized after an outbreak of severe respiratory illness in the southwestern United States in May 1993 that was traced to the Sin Nombre virus.1Duchin JS Koster FT Peters CJ Hantavirus Study Group et al.Hantavirus pulmonary syndrome: a clinical description of 17 patients with a newly recognized disease.N Engl J Med. 1994; 330: 949-955Crossref PubMed Scopus (572) Google Scholar Subsequently, other strains of hantaviruses were isolated in the United States, Canada, and South America. In the United States, the deer mouse (Peromyscus maniculatus) is the rodent host for Sin Nombre virus. Outside the United States, a common presentation of hantavirus infection is hemorrhagic fever with renal syndrome (HFRS), a group of similar illnesses that include Korean hemorrhagic fever, epidemic hemorrhagic fever, and nephropathia epidemica.2Peters CJ Khan AS Hantavirus pulmonary syndrome: the new American hemorrhagic fever.Clin Infect Dis. 2002; 34: 1224-1231Crossref PubMed Scopus (139) Google Scholar, 3Smadel JE Epidemic hemorrhagic fever.Am J Public Health. 1953; 43: 1327-1330Crossref Google Scholar Although hantavirus infection can occur without severe pulmonary symptoms, most patients with HPS experience pulmonary and hemodynamic compromise and require ICU admission and mechanical ventilation.4Hallin GW Simpson SQ Crowell RE et al.Cardiopulmonary manifestations of hantavirus pulmonary syndrome.Crit Care Med. 1996; 24: 252-258Crossref PubMed Scopus (171) Google Scholar In contrast to patients with septic shock, those with HPS reportedly have high vascular resistance and low cardiac output. Laboratory findings commonly include thrombocytopenia, leukocytosis with myeloid precursors, increased hematocrit level, and coagulopathy. Typically, renal function is only mildly impaired. Only 20% of patients with HPS have serum creatinine values higher than 2.0 mg/dL.5Peters CJ Simpson GL Levy H Spectrum of hantavirus infection: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome.Annu Rev Med. 1999; 50: 531-545Crossref PubMed Scopus (213) Google Scholar However, renal failure requiring dialysis has been described in patients infected with hantavirus strains other than Sin Nombre in the United States, and elsewhere renal impairment is a prominent feature of HFRS and HPS.5Peters CJ Simpson GL Levy H Spectrum of hantavirus infection: hemorrhagic fever with renal syndrome and hantavirus pulmonary syndrome.Annu Rev Med. 1999; 50: 531-545Crossref PubMed Scopus (213) Google Scholar, 6Castillo C Naranjo J Sepulveda A Ossa G Levy H Hantavirus pulmonary syndrome due to Andes virus in Temuco, Chile: clinical experience with 16 adults.Chest. 2001; 120: 548-554Crossref PubMed Scopus (60) Google Scholar To our knowledge, this is the first report of an acute Sin Nombre infection complicated by renal failure requiring hemodialysis occurring in the United States. The presence of a solitary kidney due to organ donation 10 months previously likely played a role, although living kidney donors are not typically considered at increased risk for renal dysfunction. The pathophysiology of viral injury includes inflammation and increased vascular permeability, typically involving the pulmonary bed in HPS and the retroperitoneum in HFRS. The treatment of HPS is directed primarily toward management of hemodynamic and respiratory complications. Ribavirin is effective in treating patients with HFRS, but in an open-label study in patients with HPS, the drug had no appreciable effect.7Chapman LE Mertz GJ Peters CJ Ribavirin Study Group et al.Intravenous ribavirin for hantavirus pulmonary syndrome: safety and tolerance during 1 year of open-label experience.Antivir Ther. 1999; 4: 211-219PubMed Google Scholar Limited case series of critically ill patients with HPS have shown increased survival with use of extracorporeal membrane oxygenation.8Crowley MR Katz RW Kessler R et al.Successful treatment of adults with severe Hantavirus pulmonary syndrome with extracorporeal membrane oxygenation [published correction appears in Crit Care Med. 1998;26:806].Crit Care Med. 1998; 26: 409-414Crossref PubMed Scopus (80) Google Scholar Conclusion. Hantavirus pulmonary syndrome due to Sin Nombre virus may be associated with renal insufficiency requiring dialysis. The presence of renal failure in the setting of other symptoms of HPS should not exclude this diagnosis.