Nephropathia epidemica (NE) is a hemorrhagic fever with renal syndrome caused by Puumala hantavirus. Its long-term prognosis is considered favorable. There are, however, some reports about subsequent hypertension, glomerular hyperfiltration, and proteinuria after previous hantavirus infection. Therefore, we studied 36 patients 5 and 10 years after acute NE, with 29 seronegative controls. Office blood pressure, ambulatory 24-h blood pressure (ABP), glomerular filtration rate (GFR), and proteinuria were examined. Hypertensive subjects were defined as those patients having increased ambulatory or office blood pressure, or receiving antihypertensive therapy. Office blood pressure was used to define hypertension only if ABP was not determined. At 5 years, the prevalence of hypertension was higher among NE patients than in controls (50 vs 21%, P=0.020). At 10 years, the difference between the groups was no more significant (39 vs 17%, P=0.098). Five years after NE, patients showed higher GFR (121+/-19 vs 109+/-16 ml/min/1.73 m(2), P=0.012) and urinary protein excretion (0.19 g/day, range 0.12-0.38 vs 0.14 g/day, range 0.09-0.24, P=<0.001) than controls. At 10 years, there were no more differences in GFR or protein excretion between the groups (GFR: 113+/-20 vs 108+/-17 ml/min/1.73 m(2), P=0.370; proteinuria: 0.14 g/day, range 0.07-0.24 vs 0.13 g/day, range 0.06-0.31, P=0.610). In conclusion, the 10-year prognosis of NE is favorable, as glomerular hyperfiltration and slight proteinuria detected at 5 years disappeared during the longer follow-up. However, the possibility exists that NE may predispose some patients to the development of hypertension.

Purpose: Previous reports have described panhypopituitarism associated with severe cases of hemorrhagic fever with renal syndrome (HFRS), but the prevalence of hormonal deficiencies after nephropathia epidemica (NE), a milder form of HFRS, has not been studied. This study was conducted to determine the prevalence of hormonal defects in patients with acute NE and during long-term follow-up. Methods: Fifty-four patients with serologically confirmed acute NE were examined by serum hormonal measurements during the acute NE, after 3 months, and after 1 to 10 (median 5) years. Results: Thirty out of 54 (56%) patients had abnormalities of the gonadal and/or thyroid axis during the acute NE. After a median follow-up of 5 years, 9 (17%) patients were diagnosed with a chronic, overt hormonal deficit: hypopituitarism was found in 5 patients and primary hypothyroidism in 5. In addition, chronic subclinical testicular failure was found in 5 men. High creatinine levels and inflammatory markers during NE associated with the acute central hormone deficiencies, but not with the chronic ones. Conclusions: Hormonal defects are common during acute NE and surprisingly many patients develop chronic hormonal deficiencies after NE. The occurrence of long-term hormonal defects cannot be predicted by the severity of acute NE. According to the reviewer's advice, we have now added two new tables (Tables 3 and 4) to clarify the presentation of the observations. Table 3 shows the clinical diagnoses and serial plasma hormone levels in those 9 NE patients who presented with chronic, overt hormonal deficits. In Table 4, we show the acute-phase clinical and laboratory findings of the 9 patients, who developed chronic hormonal defects after NE, compared to those 45 patients, whose hormone levels remained normal during the follow-up. Since the clinical diagnoses of hormonal deficiencies are now shown in Table 3 (in the revised version), we have omitted the corresponding text from Results, Hormonal deficiencies: "Of these 9 patients, 2 were diagnosed with isolated central hypogonadism, 2 had multiple pituitary hormone deficiencies, 2 had primary hypothyroidism only, one had primary hypothyroidism and primary hypogonadism, one was diagnosed with isolated central hypogonadism and peripheral hypothyroidism, and one with primary hypothyroidism and a possible GH deficiency (undetectable GH level and IGF-1 6.5 nmol/l; reference range 10-29 nmol/l)." In order to further clarify the results, we have also referred to the patients described in Table 3 (e.g. "patient 1, table 3") in the revised text: Results, page 8, Hormonal deficiencies, lines 6 and 12, as well as in Results, Imaging studies, page 9, the first and the third line). We have omitted the following text from Results, Imaging studies: "Testo 11.6-10.8-8.1-7.4 nmol/l, LH 1.6-1.4-2.0-2.6 U/l, fT4 12.5-11.8-10.4-10.4 pmol/l, and TSH 1.2-1.1-1.0-0.9 mU/l, measured in the acute phase, and after 1 year, 5 and 9 years, respectively", since the same values are now shown in Table 3 (patient 2) o...

Background/Aims: We previously found increased urinary protein excretion, glomerular filtration rate (GFR) and blood pressure in a retrospective analysis of patients with previous nephropathia epidemica (NE). Here, we evaluated the long-term outcome after NE in a prospectively recruited patient group. Methods: Proteinuria, GFR and ambulatory 24-hour blood pressure were assessed 4–7 years (mean 6) after acute NE in 37 patients, and these values were compared to those from 38 seronegative controls. Results: Six years after NE, the prevalence of elevated urinary α₁-microglobulin excretion was higher in the patients than controls (9/35 vs. 1/38; p = 0.005). The patients also had higher urinary protein excretion (0.17 ± 0.05 vs. 0.14 ± 0.04 g/day; p = 0.006), GFR (119 ± 19 vs. 109 ± 14 ml/min/1.73 m²; p = 0.016) and mean systolic (123 ± 11 vs. 117 ± 9 mm Hg; p = 0.012), nighttime systolic (109 ± 11 vs. 100 ± 9 mm Hg; p = 0.001) and nighttime diastolic blood pressure (70 ± 7 vs. 66 ± 7 mm Hg; p = 0.035) than the controls. Conclusions: These results confirm our previous findings of a higher prevalence of tubular proteinuria and increased urinary protein excretion, GFR and systolic blood pressure 6 years after acute NE.

IL-18 had poor-to-moderate ability to predict AKI, RRT, or 90-day mortality in this large cohort of critically ill patients. Thus, it should be used with caution for diagnostic or predictive purposes in the critically ill.

Nephropathia epidemica induced by Puumala hantavirus typically causes acute reversible renal function impairment. A typical renal biopsy finding is acute tubulointerstitial nephritis with slight glomerular mesangial changes. We describe here 5 patients who developed the nephrotic syndrome during the convalescent phase of an otherwise typical acute febrile nephropathia epidemica. Renal biopsy of all patients disclosed type I mesangiocapillary glomerulonephritis (MCGN). A clinical remission of the nephrotic syndrome was observed in 4 patients during the follow-up period, and 1 entered into chronic renal failure. Three patients had microscopic hematuria and proteinuria and 2 elevated blood pressure at the latest assessment visit. No patient had clinical or laboratory findings compatible with chronic bacterial, parasitic or viral infections (hepatitis B or C), malignancies, or other disorders known to be associated with MCGN. In conclusion, Puumala hantavirus has to be added to the list of potential agents associated with type I MCGN. Further studies are necessary to establish the incidence of MCGN caused by various hantavirus infections.