Nephropathia epidemica (NE), a mild type of hemorrhagic fever of renal syndrome (HFRS), is caused by Puumala hantavirus (PUUV). A sudden onset of high fever, headache, nausea and back and abdominal pain are the most typical symptoms. Renal involvement comprises oliguria followed by polyuria together with proteinuria and hematuria. Renal histopathology reveals acute tubulointerstitial nephritis. A complete recovery is the usual outcome.

The long-term prognosis of NE has previously been assessed in a retrospective study of 46 patients with previous NE (Mäkelä et al. 2000). Three to seven years after serologically confirmed PUUV infection, patients evinced a higher glomerular filtration rate (GFR), more proteinuria and higher ambulatory blood pressure (ABP) than healthy, seronegative controls (Mäkelä et al. 2000). This cohort of NE patients and controls were re-examined a median of 10 years after acute NE. Thirty-six patients and 29 controls took part. There were no longer significant differences in GFR and ABP or in the amount of proteinuria between patients and controls. There was nevertheless a slight predominance of hypertensive subjects in the patient group.

In the present series, the renal outcome and blood pressure of patients with previous NE were further studied in a prospectively collected group of 37 patients. Six years after acute NE, the patients had higher GFR, more proteinuria and higher ABP compared with 38 seronegative controls. The clinical severity of the acute phase of NE did not influence the long-term findings. Serum hormonal levels were studied in 54 patients during acute NE, after 3 months, and after 1 and 5 years. All levels were analyzed retrospectively. During acute NE, 56 % of the patients evinced hormonal abnormalities. Chronic, overt hormonal deficits were detected in 17 % of the patients after a median follow-up of 5 years: 5 had hypopituitarism and 5 had primary hypothyroidism. Furthermore, in 5 males chronic subclinical testicular failure was diagnosed. The acute-phase central hormonal deficiencies correlated with the severity of the acute renal failure and inflammatory markers. In contrast, the severity of acute NE was not associated with the development of chronic hormonal deficiencies.

The clinical courses of seven patients with nephrotic-range proteinuria concomitant with hematuria emerging 1 to 12 weeks after acute NE have been described. In five cases a renal biopsy specimen showed membranoproliferative glomerulonephritis (MPGN), while membranous glomerulonephritis (MGN) and mesangial glomerulonephritis (MesGN) were detected each in one. All patients achieved remission in a median of 0.6 years, indicating a good prognosis. In conclusion, the present series confirms the favorable long-term outcome of acute NE. However, the possibility remains that NE may predispose patients to hypertension. Hormonal alterations are common during and after acute NE. Furthermore, as a rare phenomenon, the convalescent phase of acute NE may be complicated by glomerulonephritis.