Hantavirus infection is a relatively rare cause of a possibly life-threatening disease with acute renal failure (haemorrhagic fever with renal syndrome (HFRS) and pulmonary involvement (hantavirus pulmonary syndrome (HPS)). It is a zoonotic infection caused by single-stranded RNA viruses of the hantavirus genus in the family of Bunyaviridae. There are 23 known species within the genus [
1]. The most commonly found species in Western-Europe is Puumala virus [
2], which is carried by the bank vole (
Myodes glareolus). Clinical cases of Puumala virus infection usually present as a mild form of HFRS, called nephropathia epidemica (NE). NE normally presents with an influenza-like illness, followed by acute renal failure, with massive proteinuria. Infection occurs by inhalation of aerosols of dried up excretions of the bank vole, containing the virus.
In case of hantavirus infection there is no specific treatment. Generally the treatment is supportive and renal function recovers completely within a few days in most cases. Haemodialysis, oxygen therapy and shock therapy are sometimes needed.
We encountered a case in which the delay in serological results and an unusual laboratory finding lead to a diagnostic dilemma in the first days of admission.
Case presentation
We present a case of an 18-year-old man with acute renal failure that was admitted to the hospital. The patient, who worked as a chef and reported himself as a smoker,had no known past medical history. He presented with abdominal pain, vomiting and diarrhoea. At presentation he had a tachycardia of 98 beats/min, with a blood pressure of 139/72 mmHg, a body temperature of 36.9 °C and normal urine output. Routine blood analysis showed leucocytosis (40,5 × 109/l (87% neutrophils)) and a serum creatinine of 233 μmol/l, resulting in an estimated glomerular filtration rate of 32 ml/min/1,73 m2, C-reactive protein was 44 mg/l, ALT 32 IU/l, AST 78 IU/l, GGT 25 IU/l, Alkaline Phosphatase 73 IU/l, bilirubin < 17 μmol/l and albumin 24 g/l. Post renal obstruction was excluded using ultrasound sonography. Urine analysis showed erythrocyturia, without casts, and massive proteinuria (protein/creatinine ratio 842.7 mg/mmol creatinine with urine creatinine of 15.7 mmol/l). It was considered as an acute glomerulonephritis, most likely caused by an infectious cause, e.g., leptospirosis or hantavirus infection, or an autoimmune disease, e.g., AAV or anti-GBM glomerulonephritis, considering age, history and physical examination. No specific history indicating hantavirus infection was recorded, e.g., cleaning up dusty sheds, contact with rodents.
ANCA was negative. Anti-GBM was 9.7 kIU/l, which is within equivocal range (7–10 kIU/l).
The detectable anti-GBM antibodies, with hantavirus serology still in progress, lead to a diagnostic and therapeutic dilemma, even though it was still in equivocal range. Treatment of anti-GBM glomerulonephritis consists of plasmapheresis in combination with immunosuppressants, which may be disadvantageous in case of a viral infection and has possible adverse effects. Late initiation of therapy in case of an anti-GBM glomerulonephritis, however, would increase the risk of developing end-stage renal failure [
3].
Because of the equivocal anti-GBM antibodies, a slight improvement of renal function on day 2 and no other signs or symptoms of anti-GBM glomerulonephritis, like elevated C-reactive protein or pulmonary involvement, there was a considerable doubt about anti-GBM glomerulonephritis being the correct diagnosis. Therefore no renal biopsy was done and plasmapheresis and immunosuppressants were not administered.
Four days after admission a second anti-GBM measurement showed an increase in anti-GBM antibodies and was undeniably positive (16.0 kIU/l), with further renal and clinical improvement.
Only supportive care was initiated. Dialysis was not needed. The patient’s kidney function improved without further intervention and after 5 days of admission he was discharged from the hospital.
On day seven serum was found positive for anti-Puumala hantavirus IgG as well as IgM antibodies, suggesting acute viral infection.
The spontaneous improvement of renal function is consisting with the natural course of NE and hantavirus infection became the most likely diagnosis. No renal biopsy was done to exclude other causes.
Twelve weeks after admission, renal functions were completely restored and anti-GBM antibodies were no longer detectable. A second serum sample showed a persisting highly.
positive result for anti-Puumala IgG (Ratio 5.2), and a disappearance 118 of IgM antibodies.
119 (Ratio 0.03; < 1.0 is regarded negative) consistent with a completed seroconversion of anti-Puumala hantavirus antibodies, confirming the diagnosis of acute hantavirus infection (Table
1).
Table 1
Overview of laboratory test results including renal function, immunology testing and hantavirus serology
Creatinine (μmol/l) | 305 | 204 | | 72 |
eGFR (ml/min/1,73 m2) | 23 | 37 | | > 90 |
ANCA | Negative | – | | – |
Anti-MPO (kIU/l) | < 3.5 | – | | – |
Anti-Pr3 (kIU/l) | < 2.0 | – | | – |
Anti-GBM (kIU/l) | 9.7 | 16.0 | | < 0.8 |
Anti-Puumala IgG | | | Positive | Positive |
Anti-Puumala IgM | | | Positive | Negative |