Clinical Course Of Nephropathia Epidemica Research Articles

Polyuria in Hantavirus Infection Reflects Disease Severity and Is Associated with Prolonged Hospital Stay: A Systematic Analysis of 335 Patients from Southern Germany

Background/Aims: Puumala virus (PUUV) infection leads to nephropathia epidemica (NE), especially in endemic areas in Central Europe. The clinical course of NE is characterized by acute kidney injury (AKI) with thrombocytopenia followed by polyuria to a different degree. The prevalence of polyuria and its associated risk factors have not been reported in a large cohort of NE patients. Methods: Clinical and laboratory data during the acute phase of the disease were obtained from the medical reports and files of 335 patients who received in-hospital treatment during acute hantavirus infection. Comprehensive statistical models were developed to estimate the probability of polyuria. Results: The median age at diagnosis was 47 years (interquartile range, IQR 40-59) and 48% of the patients developed polyuria with a urinary output of 5,100 ml/day (IQR 4,200-7,300). The hospital stay was significantly longer in the polyuric group compared to the nonpolyuric group [8 days (IQR 6-10) vs. 6 days (IQR 5-8); p = 0.04]. Using logistic regression analysis, male gender (odds ratio, OR = 1.6; 95% confidence interval, CI 1.05-2.58; p = 0.03), oliguria/anuria during NE (OR = 2.56; 95% CI 1.65-4.01; p < 0.001), severe AKI (OR = 1.87; 95% CI 1.22-2.9; p < 0.001), and hematuria (OR = 1.78; 95% CI 1.02-3.15; p = 0.04) were significantly associated with the development of polyuria. In a multivariate model, the probability of polyuria was 0.19 (SEM ± 0.05) in female patients presenting with mild/moderate AKI without anuria/oliguria. Conclusions: Almost 50% of hospitalized NE patients developed polyuria, which was associated with a prolonged hospital stay. The probability of the development of polyuria was lowest in female patients with mild/moderate, non-oliguric/anuric AKI.

Magnetic resonance renography findings and their clinical associations in nephropathia epidemica

To evaluate, with magnetic resonance renography (MRR), the dynamics of renal function in patients with nephropathia epidemica (NE) and to correlate the findings with the clinical course of NE. MRR was performed on 20 hospitalized NE patients during the acute phase of the disease. A repeat MRR study was done 5-8 months later. Primary and repeat MRR studies were compared and functional findings evaluated. The uptake slope of the contrast enhancement curve was abnormal in the primary study in 14 patients, maximum level of enhancement in 11, decreasing slope of contrast enhancement curve in 14, and signal drop at time in 10 patients when the primary and repeat studies were compared. The greater change in the uptake slope of contrast enhancement, maximum level of enhancement, decreasing slope of enhancement, and signal drop at time between primary and repeat MRR studies evinced a mild association with the severity of clinical renal insufficiency and fluid volume overload. Measurable functional MRR findings were recorded in 14/20 NE patients. The severity of the findings was mildly associated with the degree of clinical renal insufficiency and fluid volume overload.

Value of ultrasonography in acute renal failure: analysis of qualitative features in patients with nephropathia epidemica

To assess the value of renal ultrasonography (US) and the frequency of qualitative pathology in patients with nephropathia epidemica (NE) and to determine whether these features are related to the clinical course of NE. Renal US was undertaken in 23 hospital-treated NE cases during the acute phase of the disease (first study). A second US study was performed 3-6 months later. Captured US images were used in the analysis. From acute to control phase the overall rating of kidney status improved in 20 patients, parenchymal swelling decreased and corticomedullary border differentiation improved in 21, echogenicity decreased in 18, and patchy pattern in parenchymal echo-texture decreased in 15. The severity of findings in US evinced some association with fluid volume overload, high blood pressure level and blood leukocyte count, and severe clinical renal insufficiency. The degree of parenchymal swelling had more statistically significant associations with clinical course than other US features. Qualitative US features are as sensitive as quantitative US parameters in assessment of NE patients' clinical course and recovery, assuming that a comparative study is available. US using only qualitative features is fairly limited in evaluating NE patients' clinical situation.

Human Leukocyte Antigens B8-DRB1*03 in Pediatric Patients With Nephropathia Epidemica Caused by Puumala Hantavirus

In adults, HLA haplotype B8-DRB1*03 is clearly associated with a severe clinical course of nephropathia epidemica caused by Puumala hantavirus. We investigated whether the same applies in pediatric patients. This HLA haplotype was found in 20 of 39 (51%) of the patients, a significantly higher figure than in the Finnish population (19%). There were, however, no significant differences in the clinical picture between patients with and without HLA B8-DRB1*03.

Medical imaging in nephropathia epidemica and their clinical correlations

Background This study was designed to evaluate radiological findings in chest and sinus radiographs and renal ultrasound (US) in patients with nephropathia epidemica (NE) and to determine whether changes in these medical images are related to each other or to the clinical course of NE. Methods Radiological findings and clinical course were studied in 380 hospital-treated NE patients during the years 1982–1998. Results In 35% of the patients there were clear changes in chest radiographs. Pleural effusion, atelectasis, and interstitial infiltration were the most common X-ray findings. Forty-seven percent had changes in renal US, with increased cortical echoicity and cortical swelling being the most common findings. Thirty-three percent of the patients with clinical symptoms of sinusitis had changes in sinus radiographs. Abnormal findings on chest radiographs were clearly associated with fluid volume overload, high blood pressure level, leukocytosis, degree of clinical renal insufficiency, and thrombocytopenia. Abnormal findings in renal US were associated to some extent with fluid volume overload and degree of clinical renal insufficiency. Conclusions Some 35% of patients had clear changes in chest radiographs and 47% showed changes in renal US. Abnormal findings in chest radiographs were clearly associated, and abnormal findings in renal US were associated to some extent, with the severity of the clinical course of NE.

Renal MRI findings and their clinical associations in nephropathia epidemica: analysis of quantitative findings.

Morphologic renal magnetic resonance imaging (MRI) findings in patients with nephropathia epidemica (NE) were evaluated, and these findings were correlated with the clinical course of NE. Renal MRI was performed in 20 hospitalized NE patients during the acute phase of their disease. A repeat MRI study was made 5-8 months later. Renal parenchymal volume, renal length and parenchymal thickness were decreased in all patients in the repeat study. Edema/fluid collections were found bilaterally in 16 patients in the primary MRI study. Greater change in parenchymal volume, renal length and parenchymal thickness between the primary and the repeat MRI study as well as the presence of edema/fluid collections in the primary study evinced mild association with clinical fluid volume overload, high blood pressure level, inflammation, thrombocytopenia and severe clinical renal insufficiency. Change in parenchymal volume was associated with a severe clinical course more markedly than the other MRI findings. Measurable renal MRI changes occurred in every NE patient. The severity of the findings in MRI evinced mild association with clinical fluid volume overload, high blood pressure level, inflammation, thrombocytopenia and severe clinical renal insufficiency. Based on this study and our previous ultrasound (US) findings, we prefer US as the primary examination mode in NE patients.

Renal ultrasound findings and their clinical associations in Nephropathia epidemica. Analysis of quantitative parameters

Purpose: To evaluate renal US findings in patients with nephropathia epidemica (NE) and to determine whether changes in these findings are related to the clinical course of NE. Material and Methods: Renal US was undertaken in 23 hospital-treated NE patients during the acute phase of their disease (first study). The second US study was performed 3–6 months later. Results: The resistive index (RI) was abnormal in 12 patients and fluid collections (perirenal, pleural, pericardial, ascites) were found in 13 patients in the first study. Renal length decreased in every patient, cortical parenchymal thickness in 19 patients and RI in 18 patients from the first to the second studies. The mean change was significant in all parameters. Increased RI and presence of fluid collections in the first study as well as a greater change in length and RI between the first and the second studies were associated with high maximum daily urine excretion, substantial change in body weight between the anuric and polyuric phases, high maximum serum creatinine and urea concentration, high blood leukocyte count and low hematocrit value. Conclusion: Renal US changes occurred in every patient with NE. The severity of the findings was associated with fluid volume overload and degree of clinical renal insufficiency.

Polymorphism of the cytokine genes in hospitalized patients with Puumala hantavirus infection.

Nephropathia epidemica (NE) is a mild type of haemorrhagic fever with renal syndrome caused by Puumala (PUU) hantavirus. The clinical course of NE varies from asymptomatic to fatal. The aim of this study was to establish whether polymorphisms in the cytokine genes are associated with susceptibility to and outcome of NE. The genotypes of the genes of tumour necrosis factor alpha (TNFalpha), interleukin-1alpha (IL-1alpha), IL-1beta and IL-1 receptor antagonist (IL-1RA) were analysed by polymerase chain reaction in 87 subjects, all hospital-treated for serologically confirmed acute NE. The control group comprised 400 healthy blood donors. Nineteen out of these 400 (5%) controls were PUU virus-seropositive. IL-1RA allele 2 and IL-1beta (base exchange polymorphism at position -511) allele 2 were strongly associated with each other in both groups. NE patients were more often IL-1RA-2 negative/IL-1beta-2 negative than PUU-seronegative blood donors (38 vs 27%, odds ratio 1.65, 95% confidence interval 1.0-2.7). However, there were no differences in the clinical severity of NE between the IL-1RA-2 negative/IL-1beta-2 negative and the other patients. The other allele frequencies studied evinced no statistically significant differences between the groups. Thirty-three out of 87 (38%) patients and 121 out of 381 (32%) seronegative controls were carriers of the high-producer genotype TNF2 allele. Several parameters showed the clinical course of NE to be more severe in TNF2 carriers than in non-carriers. These data suggest that non-carriage of the IL-1RA allele 2 and IL-1beta (-511) allele 2 may contribute to susceptibility to NE. Furthermore, TNFalpha polymorphism seems to be associated with the outcome of NE.

Clinical aspects of nephropathia epidemica (Puumala virus infection) in Europe: a review.

Nephropathia epidemica (NE) is a prevalent zoonosis throughout Europe and is caused by the Puumala type of hantavirus. The incidence of NE varies in a cyclic fashion, with peaks occurring every 3rd to 4th year, coinciding with peaks in vole populations. The clinical course of NE is generally milder than haemorrhagic fever with renal syndrome caused by hantaviruses in other parts of the world. Typically, NE has a sudden onset with fever, headache, backpain and gastrointestinal symptoms. However, severe complications, e.g. gastrointestinal haemorrhage, occur and fatal cases have been reported. Renal involvement is prominent and manifests as initial oliguria and later as marked polyuria. Tests of renal function show pronounced glomerular and tubular involvement. Vaccine against Puumala virus infection as well as specific treatment for NE are still lacking.

Association of HLA B27 with benign clinical course of nephropathia epidemica caused by Puumala hantavirus.

Both the severe course of nephropathia epidemica (NE) caused by Puumala hantavirus, and the fast progression of human immunodeficiency virus (HIV) disease, are associated with the HLA B8 DRB1*0301 haplotype. As HLA B27, on the contrary, is associated with the slow progression of HIV disease, we wanted to test whether the same is true for NE. Only six (8%) NE patients, half the figure expected, had the HLA B27 allele in 74 randomly selected hospital-treated patients. All six had a benign overall clinical course of NE; none had any severe complications, the severity of renal failure was also mild, and the treatment time at the hospital was half that needed for HLA B27- patients (P = 0.004). Patients who were HLA B27 had maximal blood leucocyte count > 10.000 x 10(9)/L (P = 0.020) more often, probably reflecting differences in immune response. Thus, similar HLA associations can be found in both HIV infection and NE caused by Puumala virus.