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

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

Glycoprotein YKL-40 Is Elevated and Predicts Disease Severity in Puumala Hantavirus Infection

Most cases of hemorrhagic fever with renal syndrome (HFRS) in Europe are caused by the Puumala hantavirus (PUUV). Typical features of the disease are increased vascular permeability, acute kidney injury (AKI), and thrombocytopenia. YKL-40 is an inflammatory glycoprotein involved in various forms of acute and chronic inflammation. In the present study, we examined plasma YKL-40 levels and the associations of YKL-40 with disease severity in acute PUUV infection. A total of 79 patients treated in Tampere University Hospital during 2005–2014 were studied. Plasma YKL-40 was measured in the acute phase, the recovery phase, and one year after hospitalization. Plasma YKL-40 levels were higher during the acute phase compared to the recovery phase and one year after hospitalization (median YKL-40 142 ng/mL, range 11–3320, vs. 45 ng/mL, range 15–529, vs. 32 ng/mL, range 3–213, p < 0.001). YKL-40 level was correlated with the length of hospital stay (r = 0.229, p = 0.042), the levels of inflammatory markers—that is, blood leukocytes (r = 0.234, p = 0.040), plasma C-reactive protein (r = 0.332, p = 0.003), and interleukin-6 (r = 0.544, p < 0.001), and maximum plasma creatinine level (r = 0.370, p = 0.001). In conclusion, plasma YKL-40 levels were found to be elevated during acute PUUV infection and correlated with the overall severity of the disease, as well as with the degree of inflammation and the severity of AKI

Glycoprotein YKL-40 Is Elevated and Predicts Disease Severity in Puumala Hantavirus Infection

Most cases of hemorrhagic fever with renal syndrome (HFRS) in Europe are caused by the Puumala hantavirus (PUUV). Typical features of the disease are increased vascular permeability, acute kidney injury (AKI), and thrombocytopenia. YKL-40 is an inflammatory glycoprotein involved in various forms of acute and chronic inflammation. In the present study, we examined plasma YKL-40 levels and the associations of YKL-40 with disease severity in acute PUUV infection. A total of 79 patients treated in Tampere University Hospital during 2005–2014 were studied. Plasma YKL-40 was measured in the acute phase, the recovery phase, and one year after hospitalization. Plasma YKL-40 levels were higher during the acute phase compared to the recovery phase and one year after hospitalization (median YKL-40 142 ng/mL, range 11–3320, vs. 45 ng/mL, range 15–529, vs. 32 ng/mL, range 3–213, p < 0.001). YKL-40 level was correlated with the length of hospital stay (r = 0.229, p = 0.042), the levels of inflammatory markers—that is, blood leukocytes (r = 0.234, p = 0.040), plasma C-reactive protein (r = 0.332, p = 0.003), and interleukin-6 (r = 0.544, p < 0.001), and maximum plasma creatinine level (r = 0.370, p = 0.001). In conclusion, plasma YKL-40 levels were found to be elevated during acute PUUV infection and correlated with the overall severity of the disease, as well as with the degree of inflammation and the severity of AKI

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

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

Glucosuria Predicts the Severity of Puumala Hantavirus Infection

Introduction: Puumala hantavirus (PUUV) causes a mild type of hemorrhagic fever with renal syndrome characterized by acute kidney injury (AKI), increased capillary leakage, and thrombocytopenia. Albuminuria and hematuria in dipstick urine test at hospital admission are known to predict the severity of upcoming AKI. Methods: We analyzed dipstick urine glucose in 195 patients with acute PUUV infection at hospital admission, and divided them into 2 categories according to the presence or absence of glucose in the dipstick urine test. Determinants of disease severity were analyzed in glucosuric and nonglucosuric patients. Results: Altogether, 24 of 195 patients (12%) had glucosuria. The patients with glucosuria had more severe AKI than patients without glucosuria (median maximum creatinine concentration 459 mmol/l, range 78-1041 mmol/l vs. 166 mmol/l, range 51-1499 mmol/l; P <0.001). The glucosuric patients had more severe thrombocytopenia (median minimum platelet count 41 x 10(9)/l, range 5-102 x 10(9)/l vs. 62 x 10(9)/l, range 3249 x 10(9)/l; P = 0.006), and more pronounced signs of increased capillary leakage (change in weight, maximum plasma hematocrit, minimum plasma albumin). The glucosuric patients were more often in clinical shock at admission (20.8% vs. 1.2%; P <0.001) and the length of hospital stay was longer (median 7.5 days, range 4-22 days vs. 6 days, range 2-30 days; P = 0.009). Conclusion: Glucosuria is relatively rare, but when present it predicts a more severe disease course in patients with acute PUUV infection.Peer reviewe

Role of Urinary Findings and Adipokines in Puumala Virus-induced Acute Kidney Injury

Akuutin munuaisvaurion (acute kidney injury, AKI) laukaisevia tekijöitä on useita ja se on yksi yleisimmistä sairaalapotilaiden komplikaatioista, joka johtaa hoidon tarpeen pitkittymiseen. Vaikka AKI:n laukaiseva tekijä on usein pääteltävissä, sen patogeneesi on tuntematon ja sen tiedetään liittyvän huonoon ennusteeseen monissa sairaustiloissa. Biomarkkereita, joilla vaikea AKI olisi ennustettavissa, ei juuri tunneta eikä akuuttiin munuaisten vajaatoimintaan ei ole spesifistä hoitoa. Puumala-viruksen aiheuttama myyräkuume on Suomessa yleinen AKI:n aiheuttaja. Infektion vaikeusaste vaihtelee lievästä, jopa oireettomasta, vakavaan tautimuotoon. Sairaalahoitoon joutuneista myyräkuumepotilaista valtaosalla todetaan AKI ja kolmasosalla se on vaikea-asteinen. Myyräkuumeeseen liittyvän AKI:n ennuste on kuitenkin hyvä ja munuaisilmentymien tiedetään korjaantuvan yleensä täydellisesti. Vaikka myyräkuumeen taudinkulku tunnetaan hyvin, sen patogeneesi tunnetaan vain osittain. Runsas, nopeasti ilmaantuva proteinuria on myyräkuumeessa tavallista. Albuminurian määrän yhteyttä taudin vaikeusasteeseen selvitettiin 205 myyräkuumepotilaalla. Mitä enemmän albuminuriaa sairaalaan tulovaiheessa todettiin virtsan liuskatestillä, sitä vaikeampi AKI kehittyi sairaalahoidon aikana. Albuminurian määrä korreloi myös muihin muuttujiin jotka kuvastavat taudin vaikeusastetta. Virtsan proteiinien erityksen huippu todettiin 4-5 päivää aiemmin kuin korkeimmat plasman kreatiniiniarvot. Myös sairaalaan tulovaiheen virtsan liuskatestin haematurian määrän todettiin näillä 205 potilaalla liittyvän vaikeampaan munuaisvaurioon sairaalahoidon aikana. Glukosuriaa havaittiin sairaalaan tullessa virtsan liuskatestissä 12 %:lla 195 myyräkuumepotilaasta. Sen ilmenemisellä todettiin olevan vahva yhteys kaikkiin taudin vaikeusastetta kuvaaviin muuttujiin, kuten munuaisvaurion vaikeusasteeseen, verihiutaleiden mataluuteen ja sokkioireisiin, jotka liittyvät myyräkuumeessa vaikeaan kapillaarisuonten läpäisevyyshäiriöön. Glukosuria ei selittynyt selvästi korkeilla veren sokeriarvoilla, vaan sen taustalla lienee ohimenevä tubulusfunktion häiriö. Albuminurian on todettu olevan ohimenevää myyräkuumeessa, mutta sen häviämisnopeudesta ei ole julkaistu tutkimustietoa. Albuminurian häviämisnopeutta ja siihen vaikuttavia tekijöitä tutkittiin 141 myyräkuumepotilaalla eri ajankohdissa, sekä akuutissa vaiheessa, että toipumisvaiheessa 6 kuukauden kuluessa infektiosta. Albuminuria todettiin hävinneeksi 2-3 viikon kuluessa kuumeen alusta eikä häviämisen nopeus riippunut sen määrästä tai AKI:n vaikeusasteesta taudin akuutissa vaiheessa. Puumala-virusinfektion aikana elimistössä todetaan voimakas immuunivasteen aktivoituminen. Adipokiinit, joita kutsutaan myös adiposytokiineiksi, osallistuvat inflammaatiovasteen säätelyyn. Plasman adipokiinien (resistiini, leptiini ja adiponektiini) pitoisuudet määritettiin 79 potilaalta taudin akuutissa ja toipumisvaiheessa, sekä vuoden kuluttua taudin sairastamisesta. Resistiinin todettiin olevan selvästi koholla taudin akuutissa vaiheessa verrattuna myöhempiin mittauksiin. Resistiinin nousu korreloi AKI:n vaikeuteen. Korkeampi resistiinitaso korreloi myös suurempaan albuminurian määrään sairaalaan tulovaiheen liuskatestissä. Muiden adipokiinien lievillä plasmapitoisuuksien muutoksilla ei ollut selvää yhteyttä myyräkuumeen vaikeusasteeseen. Yhteenvetona todetaan, että myyräkuumeessa voidaan arvioida vaikean munuaisvaurion kehittymisen riskiä laskemalla taudin varhaisessa vaiheessa otetun virtsan liuskatestin albuminurian, hematurian ja glukosurian määrät yhteen. Tällaista virtsalöydösten yhteyttä akuutin munuaisvaurion vaikeusasteeseen ei ole aiemmin raportoitu missään muissa AKI:n muodoissa. Glukosurian esiintyminen varoittaa myös suuremmasta riskistä henkeä uhkaavalle taudille, koska se liittyi kliinisen sokin esiintymiseen. On syytä huomioida, että virtsalöydösten muutokset ovat myyräkuumeessa nopeita, joten tulkinnassa täytyy ottaa huomioon viive kuumeen alusta näytteenottohetkeen. Joillakin inflammaatiovasteen markkereista on todettu olevan yhteyttä myyräkuumeen vaikeusasteeseen. Kohonnut plasman resistiini-taso liittyy sekä munuaisvaurion vaikeusasteeseen että albuminurian määrään sairaalahoitoa vaativassa myyräkuumeessa.Acute kidney injury (AKI) triggered by various factors is one of the common complications in hospital-treated patients, often leading to a prolonged need of hospital care. Although predisposing factors can be apparent, the pathogenesis of AKI remains unclear. AKI is considered as one of the factors related to worse prognosis in many disease states. Biomarkers to predict severe AKI are scarce and specific treatment for AKI does not exist. Hemorrhagic fever with renal syndrome (HFRS), caused by Puumala virus (PUUV), also called nephropathia epidemica, is a common cause of AKI in Finland. The clinical course of PUUV infection varies from mild, even asymptomatic, to severe. The majority of patients admitted to hospital due to acute PUUV infection have AKI, severe AKI in a third of them. However, AKI related to PUUV infection has a favourable prognosis and renal recovery is usually complete. While the clinical course of PUUV infection is well known, the pathogenesis of infection is only partly understood. A high amount of abruptly emerging proteinuria is a usual finding in acute PUUV infection. The association between the amount of albuminuria and disease severity was analysed in 205 patients with acute PUUV infection. Higher degree of albuminuria detected by urinary dipstick tests on hospital admission were associated with more severe upcoming AKI during hospital stay. The amount of albuminuria also correlated with other markers reflecting disease severity. Peak values of urinary protein excretion were detected 4-5 days earlier than the peak values of plasma creatinine. Higher degree of haematuria in urinary dipstick tests on hospital admission was associated with higher degree of dipstick-verified albuminuria and also with the severity of AKI during hospitalization. Glucosuria in urinary dipstick tests was detected in 12 % of 195 patients with acute PUUV infection on hospital admission. The presence of glucosuria was associated with all markers of disease severity including the severity of AKI, lower blood thrombocyte count and the presence of clinical shock, a sign of severe capillary leakage in acute PUUV infection. The presence of glucosuria was not explained solely by high blood glucose but maybe a transient change in tubular function. Albuminuria has been found to be transient in PUUV infection, although reports about the disappearance rate are missing. Urinary albumin excretion in various time-points during the acute and convalescent phase within six months after acute infection was studied in 141 patients to discover the rate of decrease. Albuminuria had disappeared within 2-3 weeks after fever onset. Disappearance rate was not affected by the amount of albuminuria, or the severity of AKI during the acute phase of the disease. In acute PUUV infection, a strong immune activation is detected. Adipokines, also called adipocytokines, are considered to have an immunomodulating effect. The levels of plasma adipokines (resistin, leptin and adiponectin) were determined in the acute phase, convalescent phase and after one year in 79 patients with acute PUUV infection. Resistin levels were clearly elevated during acute infection compared with levels determined later. Higher resistin levels correlated with the severity of AKI and also a higher degree of dipstick albuminuria on hospital admission. The slight changes in plasma levels of other adipokines did not have significant associations with the disease-severity markers. To conclude, the probability of severe AKI emerging in acute PUUV infection can be assessed by combining the plus-counts of urinary dipstick test results for albuminuria, haematuria and glucosuria detected in the early phase of the disease. Such correlation of urinary findings with AKI severity have not been reported previously in any form of AKI. The presence of glucosuria can be a warning sign of a severe life-threatening outcome as it was associated with clinical shock. Of note, the delay between urine testing and fever onset should be taken into account, as the alterations in urine findings are rapid and thus delays affect predictive capacity of these urine tests. Some of the markers of host inflammatory response are associated with disease severity in acute PUUV infection. The rise in plasma resistin level, correlates with the severity of AKI and higher degree of albuminuria in hospital-treated PUUV-infected patients

Allele 2 of interleukin-1 receptor antagonist gene increases the risk of thyroid peroxidase antibodies in subacute thyroiditis

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Allele 2 of interleukin-1 receptor antagonist gene increases the risk of thyroid peroxidase antibodies in subacute thyroiditis

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High plasma resistin associates with severe acute kidney injury in Puumala hantavirus infection

Background Puumala hantavirus (PUUV) infected patients typically suffer from acute kidney injury (AKI). Adipokines have inflammation modulating functions in acute diseases including AKI. We examined plasma levels of three adipokines (resistin, leptin, and adiponectin) in acute PUUV infection and their associations with disease severity. Methods This study included 79 patients hospitalized due to acute PUUV infection. Plasma resistin, leptin, adiponectin, as well as IL-6 and CRP, were measured at the acute phase, recovery phase and one year after hospitalization. Results Plasma resistin levels were significantly higher in the acute phase compared to the recovery phase and one year after (median resistin 28 pg/mL (11-107) vs. 17 pg/mL (7-36) vs. 14 pg/mL (7-31), p= 353.6 mu mol/L) (OR 1.08, 95% CI 1.02-1.14). Neither plasma leptin nor adiponectin level had any correlation with creatinine concentration or the amount of albuminuria. Conclusions Plasma resistin independently associates with the severity of AKI in acute PUUV infection. The association of resistin with the amount of albuminuria suggests that the level of plasma resistin is not only influenced by renal clearance but could have some role in the pathogenesis of AKI during PUUV infection.Peer reviewe