Severity Biomarkers in Puumala Hantavirus Infection

Annually, over 10,000 cases of hemorrhagic fever with renal syndrome (HFRS) are diagnosed in Europe. Puumala hantavirus (PUUV) causes most of the European HFRS cases. PUUV causes usually a relatively mild disease, which is rarely fatal. However, the severity of the infection varies greatly, and factors affecting the severity are mostly unrevealed. Host genes are known to have an effect. The typical clinical features in PUUV infection include acute kidney injury, thrombocytopenia, and increased vascular permeability. The primary target of hantavirus is the endothelium of the vessels of different organs. Although PUUV does not cause direct cytopathology of the endothelial cells, remarkable changes in both the barrier function of the endothelium and the function of the infected endothelial cells occur. Host immune or inflammatory mechanisms are probably important in the development of the capillary leakage. Several immunoinflammatory biomarkers have been studied in the context of assessing the severity of HFRS caused by PUUV. Most of them are not used in clinical practice, but the increasing knowledge about the biomarkers has elucidated the pathogenesis of PUUV infection.

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Hemorrhagic fever with renal syndrome with concurrent aortic dissection: a case report

10.21203/rs.3.rs-49633/v1 ◽

2020 ◽

Author(s):

Fengqi Qiu ◽

Congcong Li ◽

Jianya Zhou

Keyword(s):

Acute Kidney Injury ◽

Aortic Dissection ◽

Kidney Injury ◽

Hemorrhagic Fever ◽

Sudden Onset ◽

High Fever ◽

Hantaan Virus ◽

Hantavirus Infection ◽

Microvascular Damage ◽

Stanford B

Abstract Background Hemorrhagic fever with renal syndrome (HFRS) is caused by hantaviruses presenting with high fever, hemorrhage, acute kidney injury. Microvascular injury and hemorrhage in mucus was often observed in patients with hantavirus infection. Infection with bacterial and virus related aortic aneurysm or dissection occurs sporadically. We present a previously unreported case of hemorrhagic fever with concurrent Stanford B aortic dissection. Case presentation: A 56-year-old man complained of high fever, generalized body ache, with decreased platelet counts of 10 × 10^9/L and acute kidney injury. The ELISA test for Hantaan virus of IgM and IgG antibodies were both positive. During the convalescent period, he complained sudden onset acute chest pain radiating to the back and the CTA revealed an aortic dissection of the descending aorta extending to iliac artery. He was diagnosed with Hemorrhagic fever with renal syndrome and Stanford B aortic dissection. The patient recovered completely after surgery with other support treatments. Conclusion We present a case of HFRS complicated with aortic dissection,and no study has reported the association of HFRS with aortic disease. However, we suppose that hantavirus infection not only cause microvascular damage but may be risk factor for acute macrovascular detriment. A causal relationship has yet to be confirmed.

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ABO and Rhesus Blood Groups in Acute Puumala Hantavirus Infection

Viruses ◽

10.3390/v13112271 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2271

Author(s):

Johanna Tietäväinen ◽

Outi Laine ◽

Satu Mäkelä ◽

Heini Huhtala ◽

Ilkka Pörsti ◽

...

Keyword(s):

Blood Group ◽

Blood Donors ◽

Kidney Injury ◽

Hemorrhagic Fever ◽

Blood Groups ◽

University Hospital ◽

Hantavirus Infection ◽

Capillary Leakage ◽

Lower Systolic Blood Pressure ◽

Rhesus Blood Group

Puumala hantavirus (PUUV) causes hemorrhagic fever with renal syndrome. We aimed to evaluate whether ABO and rhesus blood groups associate with the susceptibility or the severity of PUUV infection. We analyzed blood groups in 289 adult patients treated in Tampere University hospital due to PUUV infection during the years 1982–2017. Patients’ blood group distribution was compared to that of healthy, voluntary blood donors living in the Tampere University Hospital responsibility area (n = 21,833). The severity of PUUV infection, as judged by the severity of acute kidney injury (AKI), thrombocytopenia, inflammation, capillary leakage, and the length of hospital care, was analyzed across the groups. The ABO and rhesus blood group distributions did not differ between the patients and blood donors. Patients with non-O blood groups had lower systolic blood pressure compared to patients with blood group O, but there was no difference in other markers of capillary leakage or in the severity of AKI. Minor deviations in the number of platelets and leukocytes were detected between the O and non-O blood groups. To conclude, patients with blood group O may be less susceptible to hypotension, but otherwise blood groups have no major influences on disease susceptibility or severity during acute PUUV infection.

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Coagulopathy in Acute Puumala Hantavirus Infection

Viruses ◽

10.3390/v13081553 ◽

2021 ◽

Vol 13 (8) ◽

pp. 1553

Author(s):

Sirpa Koskela ◽

Satu Mäkelä ◽

Tomas Strandin ◽

Antti Vaheri ◽

Tuula Outinen ◽

...

Keyword(s):

Acute Kidney Injury ◽

Platelet Count ◽

Disseminated Intravascular Coagulation ◽

Inflammatory Mediators ◽

Kidney Injury ◽

Hemorrhagic Fever ◽

Endothelial Activation ◽

Hantavirus Infection ◽

Increased Risk ◽

Low Platelet Count

Puumala hantavirus (PUUV) causes a hemorrhagic fever with renal syndrome (HFRS), also called nephropathia epidemica (NE), which is mainly endemic in Europe and Russia. The clinical features include a low platelet count, altered coagulation, endothelial activation, and acute kidney injury (AKI). Multiple connections between coagulation pathways and inflammatory mediators, as well as complement and kallikrein–kinin systems, have been reported. The bleeding symptoms are usually mild. PUUV-infected patients also have an increased risk for disseminated intravascular coagulation (DIC) and thrombosis.

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A Case of Hantavirus Infection Detected During the COVID-19 Pandemic

Klimik Dergisi/Klimik Journal ◽

10.36519/kd.2021.3656 ◽

2021 ◽

Vol 34 (2) ◽

pp. 141-143

Author(s):

Sinan Çetin ◽

Ahmet Melih Şahin

Keyword(s):

Acute Kidney Injury ◽

Differential Diagnosis ◽

Kidney Injury ◽

Hemorrhagic Fever ◽

Acute Illness ◽

Hantavirus Infection ◽

Bunyaviridae Family ◽

Symptoms And Signs

Hantaviruses are viruses belonging to the Bunyaviridae family, and they cause two forms of acute illness in humans: hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). HFRS form seen in our country progresses with fever, acute kidney injury, thrombocytopenia and bleeding. Therefore, hantavirus infections should be kept in mind in the differential diagnosis of patients presenting with these symptoms and signs. This report presents a case followed up with the differential diagnosis of coronavirus disease-19 (COVID-19) during the pandemic and diagnosed with HFRS due to hantavirus.

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Factors Determining Nephrotoxicity and Mortality in Critical Care Patients Receiving Colistin

The Journal of Infection in Developing Countries ◽

10.3855/jidc.9443 ◽

2018 ◽

Vol 11 (12) ◽

pp. 912-917 ◽

Cited By ~ 1

Author(s):

Ali Ciftci ◽

Seval Izdes ◽

Neriman Defne Altintas

Keyword(s):

Risk Factors ◽

Acute Kidney Injury ◽

Demographic Data ◽

Kidney Injury ◽

Apache Ii ◽

Factors Affecting ◽

Acute Kidney Injury Group ◽

Injury Group ◽

Independent Risk Factors ◽

Critical Patients

Introduction: We aimed to determine risk factors for nephrotoxicity and factors affecting mortality in patients who received colistin. Methodology: Critical patients who received colistin were enrolled. Pregnancy, age < 18 years, basal creatinine level > 2 mg/dL, colistin use for < 48 hours, and previous renal replacement therapy were exclusion criteria. KDIGO stages were determined according to creatinine levels. Patients were grouped as those with no acute kidney injury (Group N0) and those with acute kidney injury (Group N). Their demographic data, APACHE II and SOFA scores, treatments, and laboratory results were recorded. Results: A total of 91 patients were included: 27 in Group N0 and 64 in Group N. Demographic data were similar between groups; however, higher admission APACHE-II scores (OR:1.179, 95% CI:1.033-1.346, p = 0.015) and need for vasopressors (OR:5.486, 95% CI:1.522–19.769, p = 0.009) were found to be independent risk factors for nephrotoxicity. Higher APACHE II scores (OR:1.253, %95 CI:1.093-1.437, p = 0.001), presence of coronary artery disease (OR:7.720, % 95 CI: 1.613-36.956, p = 0.011), need for vasopressors (OR: 4.587, % 95 CI: 1.224 – 17.241, p = 0.024), hypoalbuminemia (OR: 4.721, % 95 CI: 1.088 – 20.469, p = 0.038), and higher direct bilirubin levels (OR: 1.806, % 95 CI: 1.055 – 3.092, p = 0.031) were independent risk factors for mortality. Conclusion: When use of colistin is considered in ICU patients, presence of modifiable risk factors for nephrotoxicity such as hypoalbuminemia, nephrotoxic drug administration, and presence of shock should be determined and managed to prevent nephrotoxicity.

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TRPV4-mediated Ca2+ influx is essential to glomerular endothelial inflammation in sepsis associated acute kidney injury

10.21203/rs.3.rs-1031344/v1 ◽

2021 ◽

Author(s):

Xia Wang ◽

Yinhua Wang ◽

Guo Zhou ◽

Yi Li ◽

Huanhuan Huo ◽

...

Keyword(s):

Acute Kidney Injury ◽

Endothelial Cells ◽

Cell Injury ◽

Cecal Ligation ◽

Kidney Injury ◽

Blood Perfusion ◽

High Morbidity ◽

Endothelial Inflammation ◽

Glomerular Endothelial Cells

Abstract Background Sepsis-associated acute kidney injury (S-AKI) is a frequent complication of critical patients and is associated with high morbidity and mortality. The glomerular endothelial cell injury is the main characteristics during S-AKI. Ca2+ influx is a key step in the establishment of endothelial injury. Transient receptor vanilloid subtype 4 (TRPV4) ion channels are permeable to Ca2+ and are widely expressed in endothelial cells. However, the role of TRPV4 on glomerular endothelial inflammation in S-AKI has remained elusive. Methods Mouse glomerular endothelial cells (MRGEC) were used to test the molecular mechanism of TRPV4 on LPS-induced glomerular endothelial inflammation. The cecal-ligation-and-puncture (CLP) model was established by ligation of cecum with 4-0 suture and punctured with a 21-gauge needle. Then 0.2mL faeces was extruded from the puncture site to trigger peritoneal inflammation. Results In the present study, we found that blocking TRPV4 diminishes LPS-induced cytosolic Ca2+-elevations, which are essential for glomerular endothelial inflammation and barrier function. Furthermore, TRPV4 regulated LPS-induced phosphorylation and translocation of NF-κB and IRF-3 in mouse glomerular endothelial cells (MRGEC). Clamping intracellular Ca2+ mimics the LPS-induce response seen in the absence of TRPV4. In vivo, pharmacological blockade or knock down of TRPV4 reduced the inflammatory response of glomerular endothelial cells, inhibited translocation of NF-κB and IRF-3, increased survival rate and improved renal function in CLP-induced sepsis but without altering renal cortical blood perfusion. Conclusions Taken together, these results suggested that inhibition of TRPV4 ameliorates glomerular endothelial inflammation, kidney dysfunction, and increased mortality via mediating Ca2+ overload and NF-κB/IRF-3 activation. These discoveries may provide novel pharmacological strategies for the treatment of glomerular endothelial dysfunction and kidney injury during endotoxemia, sepsis, and other inflammatory diseases.

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Identification of hantavirus infection by Western blot assay and TaqMan PCR in patients hospitalized with acute kidney injury

Diagnostic Microbiology and Infectious Disease ◽

10.1016/j.diagmicrobio.2014.01.032 ◽

2014 ◽

Vol 79 (2) ◽

pp. 166-170 ◽

Cited By ~ 4

Author(s):

Miklós Oldal ◽

Viktória Németh ◽

Mónika Madai ◽

Gábor Kemenesi ◽

Bianka Dallos ◽

...

Keyword(s):

Acute Kidney Injury ◽

Western Blot ◽

Kidney Injury ◽

Hantavirus Infection ◽

Western Blot Assay ◽

Taqman Pcr

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Effects on renal outcome of concomitant acute pyelonephritis, acute kidney injury and obstruction duration in obstructive uropathy by urolithiasis: a retrospective cohort study

BMJ Open ◽

10.1136/bmjopen-2019-030438 ◽

2019 ◽

Vol 9 (11) ◽

pp. e030438

Author(s):

Eung Hyun Lee ◽

Su-Hyun Kim ◽

Jung-ho Shin ◽

Sung Bin Park ◽

Byung Hoon Chi ◽

...

Keyword(s):

Acute Kidney Injury ◽

Renal Function ◽

Cohort Study ◽

Retrospective Cohort Study ◽

Acute Pyelonephritis ◽

Retrospective Cohort ◽

Obstructive Uropathy ◽

Kidney Injury ◽

Renal Outcome ◽

Factors Affecting

ObjectiveObstruction release from urolithiasis can be delayed with a lack of suggested time for preventing the deterioration of renal function. The objective of this study was to investigate the effect of obstruction duration, concomitant acute kidney injury (AKI) or acute pyelonephritis (APN) during the obstruction on the prognosis of renal function.DesignRetrospective cohort study.Setting and participants1607 patients from a urolithiasis-related obstructive uropathy cohort, between January 2005 and December 2015.Outcome measuresEstimated glomerular filtration rate (eGFR) decrease ≥30% and/or end-stage renal disease (ESRD), and eGFR decrease ≥50% and/or ESRD, according to obstruction duration, AKI and APN accompanied by obstructive uropathy.ResultsWhen the prognosis was divided by obstruction duration quartile, the longer the obstruction duration the higher the probability of eGFR reduction >50% (p=0.02). In patients with concomitant APN or severe AKI during hospitalisation with obstructive uropathy, an eGFR decrease of >30% and >50% occurred more frequently, compared with others (p<0.001). When we adjusted for sex, age, hypertension, diabetes mellitus, APN, AKI grades and obstruction release >7 days for multivariate analysis, we found that concomitant APN (HR 3.495, 95% CI 1.942 to 6.289, p<0.001), concomitant AKI (HR 3.284, 95% CI 1.354 to 7.965, p=0.009 for AKI stage II; HR 6.425, 95% CI 2.599 to 15.881, p<0.001 for AKI stage III) and an obstruction duration >7 days (HR 1.854, 95% CI 1.095 to 3.140, p=0.001) were independently associated with an eGFR decrease >50%. Tree analysis also showed that AKI grade 3, APN and an obstruction duration >7 days were the most important factors affecting renal outcome.ConclusionsIn patients with urolithiasis-related obstructive uropathy, concomitant APN was strongly associated with deterioration of renal function after obstruction release. The elapsed time to release the obstruction also affected renal function.

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Flash-Like Albuminuria in Acute Kidney Injury Caused by Puumala Hantavirus Infection

Pathogens ◽

10.3390/pathogens9080615 ◽

2020 ◽

Vol 9 (8) ◽

pp. 615

Author(s):

Paula Mantula ◽

Johanna Tietäväinen ◽

Jan Clement ◽

Onni Niemelä ◽

Ilkka Pörsti ◽

...

Keyword(s):

Acute Kidney Injury ◽

Acute Phase ◽

Kidney Injury ◽

University Hospital ◽

Hantavirus Infection ◽

Puumala Virus ◽

Disappearance Rate ◽

Time Points ◽

Albumin Excretion ◽

Fever Onset

Transient proteinuria and acute kidney injury (AKI) are characteristics of Puumala virus (PUUV) infection. Albuminuria peaks around the fifth day and associates with AKI severity. To evaluate albuminuria disappearance rate, we quantified albumin excretion at different time points after the fever onset. The study included 141 consecutive patients hospitalized due to acute PUUV infection in Tampere University Hospital, Finland. Timed overnight albumin excretion (cU-Alb) was measured during the acute phase in 133 patients, once or twice during the convalescent phase within three months in 94 patients, and at six months in 36 patients. During hospitalization, 30% of the patients had moderately increased albuminuria (cU-Alb 20–200 μg/min), while 57% presented with severely increased albuminuria (cU-Alb >200 μg/min). Median cU-Alb was 311 μg/min (range 2.2–6460) ≤7 days after fever onset, 235 μg/min (range 6.8–5479) at 8–13 days and 2.8 μg/min (range 0.5–18.2) at 14–20 days. After that, only one of the measurements showed albuminuria (35.4 μg/min at day 44). At six months, the median cU-Alb was 2.0 μg/min (range 0.6–14.5). Albuminuria makes a flash-like appearance in PUUV infection and returns rapidly to normal levels within 2–3 weeks after fever onset. In the case of AKI, this is a unique phenomenon.

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Renal tubular injury exacerbated by vasohibin-1 deficiency in a murine cisplatin-induced acute kidney injury model

AJP Renal Physiology ◽

10.1152/ajprenal.00045.2019 ◽

2019 ◽

Vol 317 (2) ◽

pp. F264-F274 ◽

Cited By ~ 6

Author(s):

Satoshi Tanimura ◽

Katsuyuki Tanabe ◽

Hiromasa Miyake ◽

Kana Masuda ◽

Keigo Tsushida ◽

...

Keyword(s):

Acute Kidney Injury ◽

Endothelial Cells ◽

Kidney Injury ◽

Protective Effects ◽

Tubular Injury ◽

Injury Model ◽

Peritubular Capillaries ◽

Renal Tubular ◽

And Function ◽

Hospital Acquired

Acute kidney injury (AKI) is frequently encountered in clinical practice, particularly secondarily to cardiovascular surgery and administration of nephrotoxic agents, and is increasingly recognized for initiating a transition to chronic kidney disease. Clarifying the pathogenesis of AKI could facilitate the development of novel preventive strategies, because the occurrence of hospital-acquired AKI is often anticipated. Vasohibin-1 (VASH1) was initially identified as an antiangiogenic factor derived from endothelial cells. VASH1 expression in endothelial cells has subsequently been reported to enhance cellular stress tolerance. Considering the importance of maintaining peritubular capillaries in preventing the progression of AKI, the present study aimed to examine whether VASH1 deletion is involved in the pathogenesis of cisplatin-induced AKI. For this, we injected male C57BL/6J wild-type (WT) and VASH1 heterozygous knockout (VASH1+/−) mice intraperitoneally with either 20 mg/kg cisplatin or vehicle solution. Seventy-two hours after cisplatin injection, increased serum creatinine concentrations and renal tubular injury accompanied by apoptosis and oxidative stress were more prominent in VASH1+/− mice than in WT mice. Cisplatin-induced peritubular capillary loss was also accelerated by VASH1 deficiency. Moreover, the increased expression of ICAM-1 in the peritubular capillaries of cisplatin-treated VASH1+/− mice was associated with a more marked infiltration of macrophages into the kidney. Taken together, VASH1 expression could have protective effects on cisplatin-induced AKI probably by maintaining the number and function of peritubular capillaries.

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