RESUMO
Hantaviruses cause the acute zoonotic diseases hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Infected patients show strong systemic inflammation and immune cell activation. NK cells are highly activated in HFRS, suggesting that also other innate lymphoid cells (ILCs) might be responding to infection. Here, we characterized peripheral ILC responses, and measured plasma levels of soluble factors and plasma viral load, in 17 Puumala virus (PUUV)-infected HFRS patients. This revealed an increased frequency of ILC2 in patients, in particular the ILC2 lineage-committed c-Kitlo ILC2 subset. Patients' ILCs showed an activated profile with increased proliferation and displayed altered expression of several homing markers. How ILCs are activated during viral infection is largely unknown. When analyzing PUUV-mediated activation of ILCs in vitro we observed that this was dependent on type I interferons, suggesting a role for type I interferons-produced in response to virus infection-in the activation of ILCs. Further, stimulation of naïve ILC2s with IFN-ß affected ILC2 cytokine responses in vitro, causing decreased IL-5 and IL-13, and increased IL-10, CXCL10, and GM-CSF secretion. These results show that ILCs are activated in HFRS patients and suggest that the classical antiviral type I IFNs are involved in shaping ILC functions.
Assuntos
Febre Hemorrágica com Síndrome Renal , Imunidade Inata , Interferon Tipo I , Linfócitos , Febre Hemorrágica com Síndrome Renal/imunologia , Febre Hemorrágica com Síndrome Renal/virologia , Humanos , Interferon Tipo I/imunologia , Interferon Tipo I/metabolismo , Imunidade Inata/imunologia , Linfócitos/imunologia , Linfócitos/metabolismo , Virus Puumala/imunologia , Masculino , Orthohantavírus/imunologia , Feminino , Adulto , Pessoa de Meia-Idade , Citocinas/metabolismo , Citocinas/imunologiaRESUMO
In humans, orthohantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). An earlier study reported that acute Andes virus HPS caused a massive and transient elevation in the number of circulating plasmablasts with specificity towards both viral and host antigens suggestive of polyclonal B cell activation. Immunoglobulins (Igs), produced by different B cell populations, comprise heavy and light chains; however, a certain amount of free light chains (FLCs) is constantly present in serum. Upregulation of FLCs, especially clonal species, associates with renal pathogenesis by fibril or deposit formations affecting the glomeruli, induction of epithelial cell disorders, or cast formation in the tubular network. We report that acute orthohantavirus infection increases the level of Ig FLCs in serum of both HFRS and HPS patients, and that the increase correlates with the severity of acute kidney injury in HFRS. The fact that the kappa to lambda FLC ratio in the sera of HFRS and HPS patients remained within the normal range suggests polyclonal B cell activation rather than proliferation of a single B cell clone. HFRS patients demonstrated increased urinary excretion of FLCs, and we found plasma cell infiltration in archival patient kidney biopsies that we speculate to contribute to the observed FLC excreta. Analysis of hospitalized HFRS patients' peripheral blood mononuclear cells showed elevated plasmablast levels, a fraction of which stained positive for Puumala virus antigen. Furthermore, B cells isolated from healthy donors were susceptible to Puumala virus in vitro, and the virus infection induced increased production of Igs and FLCs. The findings propose that hantaviruses directly activate B cells, and that the ensuing intense production of polyclonal Igs and FLCs may contribute to acute hantavirus infection-associated pathological findings.
Assuntos
Injúria Renal Aguda/patologia , Linfócitos B/imunologia , Infecções por Hantavirus/imunologia , Cadeias Leves de Imunoglobulina/sangue , Ativação Linfocitária/imunologia , Orthohantavírus/imunologia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/etiologia , Infecções por Hantavirus/sangue , Infecções por Hantavirus/virologia , Humanos , Cadeias Leves de Imunoglobulina/imunologiaRESUMO
[This corrects the article DOI: 10.1371/journal.ppat.1009400.].
RESUMO
Innate immune cells like monocytes patrol the vasculature and mucosal surfaces, recognize pathogens, rapidly redistribute to affected tissues and cause inflammation by secretion of cytokines. We previously showed that monocytes are reduced in blood but accumulate in the airways of patients with Puumala virus (PUUV) caused hemorrhagic fever with renal syndrome (HFRS). However, the dynamics of monocyte infiltration to the kidneys during HFRS, and its impact on disease severity are currently unknown. Here, we examined longitudinal peripheral blood samples and renal biopsies from HFRS patients and performed in vitro experiments to investigate the fate of monocytes during HFRS. During the early stages of HFRS, circulating CD14-CD16+ nonclassical monocytes (NCMs) that patrol the vasculature were reduced in most patients. Instead, CD14+CD16- classical (CMs) and CD14+CD16+ intermediate monocytes (IMs) were increased in blood, in particular in HFRS patients with more severe disease. Blood monocytes from patients with acute HFRS expressed higher levels of HLA-DR, the endothelial adhesion marker CD62L and the chemokine receptors CCR7 and CCR2, as compared to convalescence, suggesting monocyte activation and migration to peripheral tissues during acute HFRS. Supporting this hypothesis, increased numbers of HLA-DR+, CD14+, CD16+ and CD68+ cells were observed in the renal tissues of acute HFRS patients compared to controls. In vitro, blood CD16+ monocytes upregulated CD62L after direct exposure to PUUV whereas CD16- monocytes upregulated CCR7 after contact with PUUV-infected endothelial cells, suggesting differential mechanisms of activation and response between monocyte subsets. Together, our findings suggest that NCMs are reduced in blood, potentially via CD62L-mediated attachment to endothelial cells and monocytes are recruited to the kidneys during HFRS. Monocyte mobilization, activation and functional impairment together may influence the severity of disease in acute PUUV-HFRS.
Assuntos
Febre Hemorrágica com Síndrome Renal/sangue , Febre Hemorrágica com Síndrome Renal/imunologia , Monócitos/imunologia , Adulto , Idoso , Feminino , Humanos , Rim/imunologia , Masculino , Pessoa de Meia-Idade , Virus PuumalaRESUMO
BACKGROUND: An increased risk of kidney disease in patients with celiac disease has been reported, but the association has remained obscure. Only few studies have investigated the association between renal comorbidities and dermatitis herpetiformis, a cutaneous manifestation of celiac disease. OBJECTIVES: We investigated whether patients with different phenotypes of celiac disease are at higher risk of kidney diseases than age- and sex-matched references. METHODS: The diagnoses of glomerulonephritis, diabetic nephropathy, interstitial nephritis, and end-stage renal disease obtained from the National Hospital Discharge Register between 1970 and 2015 were identified in celiac disease (Marsh III, n = 1072) and dermatitis herpetiformis (n = 368) patients diagnosed at Tampere University Hospital catchment region and in 4296 reference subjects. Using the Cox proportional hazards model, we compared the risk of kidney diseases between patients and references. The study protocol was approved by the Regional Ethics Committee of Tampere University Hospital (R16090). As the study was register based, no consent from patients was required. RESULTS: Even after adjusting for type 1 diabetes, celiac disease was associated with an elevated risk of kidney disease (hazard ratio [HR] 1.85, 95% confidence interval [CI] 1.12-3.03), glomerulonephritis (HR 3.37, 95% CI 1.64-6.95), and IgA nephropathy (IgAN) (HR 18.98, 95% CI 2.29-157.63). No similarly elevated risk was found among dermatitis herpetiformis patients (HR 1.50, 95% CI 0.63-3.55; HR 2.21, 95% CI 0.77-6.38; and HR 5.87, 95% CI 0.53-64.79, respectively). CONCLUSION: Celiac disease patients were at increased risk of kidney diseases, notably IgAN. The risk was dependent on the celiac disease phenotype and was not seen in patients with dermatitis herpetiformis. Awareness of possible renal manifestations is recommended when treating celiac disease patients.
Assuntos
Doença Celíaca , Dermatite Herpetiforme , Glomerulonefrite por IGA , Glomerulonefrite , Doença Celíaca/complicações , Doença Celíaca/epidemiologia , Dermatite Herpetiforme/complicações , Dermatite Herpetiforme/epidemiologia , Glomerulonefrite/complicações , Glomerulonefrite/epidemiologia , Glomerulonefrite por IGA/complicações , Glomerulonefrite por IGA/epidemiologia , Humanos , Fenótipo , Estudos RetrospectivosRESUMO
BACKGROUND: Gastrointestinal (GI) symptoms are common in end-stage kidney disease. Mounting evidence indicates that the intestine plays an important role in the pathogenesis of IgA nephropathy (IgAN). However, no studies have addressed the obvious question; do IgAN patients suffer from GI symptoms? METHODS: Presence of GI symptoms and health-related quality of life were evaluated using the validated Gastrointestinal Symptom Rating Scale (GSRS) and Psychological General Well-Being (PGWB) questionnaires in 104 patients with kidney biopsy-verified IgAN and in 147 healthy controls. A person was regarded to experience 'increased GI symptoms' if the GSRS score exceeded plus 1 standard deviation of the mean of the corresponding score in the healthy controls. RESULTS: According to the GSRS total score, the IgAN patients had more GI symptoms than the healthy controls (2.0 vs. 1.7, p < 0.001). Female IgAN patients had higher GSRS total score than male patients (2.2 vs. 1.7, p = 0.001). More IgAN patients with preserved kidney function (eGFR > 60ml/min/1.73m2) suffered from increased symptoms of diarrhoea (76 vs. 25%, p = 0.028), constipation (81 vs. 19%, p = 0.046) and reflux (85 vs. 15%, p = 0.004) than did IgAN patients with reduced kidney function (eGFR < 60ml/min/1.73m2). CONCLUSIONS: IgAN patients and especially female IgAN patients experienced more GI symptoms than healthy controls. More prevalent GI symptoms were already observed before kidney function was clearly reduced. Systematic enquiry of GI symptoms might increase the standard of care among IgAN patients. Moreover, GI symptoms may provide clues for future studies that examine the pathophysiology of IgAN.
Assuntos
Bem-Estar Psicológico , Qualidade de Vida , Humanos , Feminino , Masculino , Estudos TransversaisRESUMO
Hard ticks (Acari: Ixodidae) act as important vectors of zoonotic pathogens. For instance, Borrelia burgdorferi s.l. spirochetes pose a severe health risk as aetiological agents of Lyme borreliosis. Commonly, to study the abundance of questing (host-seeking) ticks, a 1 m2 piece of cloth is dragged over vegetation for a determined distance. Here, we designed a tick-sampling study to estimate the sampling efficiency of this standard method. We established 10 m dragging transects in a hemiboreal mixed forest patch in SW Finland for a 5-day monitoring period. Five of the transects were cloth-dragged 3× a day, whereas another five transects were dragged 6× a day in a manner that after each morning, midday and afternoon dragging, a second dragging was conducted on the same transect immediately. Captured Ixodes ricinus ticks were subsequently analysed for tick-borne pathogens. The initial population size of nymphal ticks on a transect was approximated by the accumulated nymph catch from the dragging sessions. The sampling efficiency of the cloth dragging was low, as a single dragging in a previously untouched vegetation strip always caught less than 12% (mean 6%) of the estimated population of active nymphs that were assumed to be questing during the study. Clear results were not found for daily activity rhythm, as ticks were caught in all daily dragging sessions. Approximately every third nymph and every second adult carried a pathogen, but nothing indicated that the occurrence of a pathogen affected the likelihood of the tick being caught by cloth dragging. Our results suggest that only a minority of active ticks can be caught by a single cloth dragging. The abundance estimates in many tick investigations might thus be downward biased.
Assuntos
Borrelia burgdorferi , Ixodes , Doença de Lyme , Animais , Finlândia , NinfaAssuntos
Hipersensibilidade a Drogas , Hipersensibilidade , Penicilinas , Humanos , Antibacterianos/efeitos adversos , Hipersensibilidade a Drogas/diagnóstico , Hipersensibilidade a Drogas/etiologia , Hipersensibilidade a Drogas/tratamento farmacológico , Hipersensibilidade/tratamento farmacológico , Penicilinas/efeitos adversos , Diálise Renal/efeitos adversosAssuntos
Doença Celíaca , Doença Celíaca/complicações , Doença Celíaca/epidemiologia , Comorbidade , Humanos , Rim , FenótipoRESUMO
Hantaviruses are zoonotic viruses that show various degrees of vasculopathy in humans. In this study, we analyzed the regulation of 2 fibrinolytic parameters, tissue plasminogen activator (tPA) and its physiological inhibitor, plasminogen activator inhibitor 1 (PAI-1), in Puumala hantavirus (PUUV)-infected patients and in human microvascular endothelial cells. We detected strong upregulation of tPA in the acute phase of illness and in PUUV-infected macaques and found the tPA level to positively correlate with disease severity. The median levels of PAI-1 during the acute stage did not differ from those during the recovery phase. In concordance, hantaviruses induced tPA but not PAI-1 in microvascular endothelial cells, and the induction was demonstrated to be dependent on type I interferon. Importantly, type I and II interferons directly upregulated tPA through signal transducer and activator of transcription 1 (STAT1), which regulated tPA gene expression via a STAT1-responsive enhancer element. These results suggest that tPA may be a general factor in the immunological response to viruses.
Assuntos
Febre Hemorrágica com Síndrome Renal/virologia , Interferon Tipo I/metabolismo , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Virus Puumala/patogenicidade , Fator de Transcrição STAT1/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Animais , Chlorocebus aethiops , Estudos de Coortes , Células Endoteliais/metabolismo , Regulação Viral da Expressão Gênica , Febre Hemorrágica com Síndrome Renal/metabolismo , Humanos , Interferon Tipo I/genética , Macaca fascicularis , Inibidor 1 de Ativador de Plasminogênio/genética , Fator de Transcrição STAT1/genética , Transdução de Sinais , Ativador de Plasminogênio Tecidual/genética , Regulação para Cima , Células Vero , Fatores de VirulênciaRESUMO
While the majority of kidney transplantations in Finland have been traditionally performed from deceased donors, the frequency of living donors should be increased. Kidney donation is a safe procedure for a carefully examined donor, and for the recipient living donation enables elective surgery and preemptive transplantation. Potential risks for the donor must be minimized, but according to current recommendations, mild hypertension or obesity are not absolute contraindications for donation. Guidelines for donor selection and examination have been updated to simplify the process for all parties. Legislation in Finland requires changes to optimize the use of all potential living donors.
Assuntos
Transplante de Rim , Doadores Vivos , Finlândia , Humanos , Doadores Vivos/legislação & jurisprudência , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Previous studies indicate that smoking affects the outcome of some infections and is a risk factor for Puumala virus (PUUV) infection. The aim of this study was to assess the effect of smoking on the clinical severity of PUUV infection and the prevalence of smoking in patients with PUUV infection. METHODS: A questionnaire on smoking habits was sent to 494 patients in 2012, who had been treated in Tampere University Hospital, Finland, for serologically confirmed PUUV infection during years 1982-2012. RESULTS: Of all patients, 357 (72%) participated. Maximum plasma creatinine level measured during acute illness was significantly higher in current smokers than in non-smokers (median: 273 versus 184 µmol/L, P < 0.001). Current smokers had a higher maximum blood leucocyte count than non-smokers (median: 10.8 versus 8.9 × 10(9)/L, P < 0.001) and they were younger than non-smokers (38 versus 45 years, P < 0.001). There were no differences between current smokers and non-smokers in the other variables reflecting the severity of PUUV infection. Altogether 51% were current smokers at the time of onset of the illness, 57% of males and 36% of females. During these years in Finland, smoking among males in the same aged population has decreased from 33 to 22% and among females, smoking has varied between 14 and 20%. CONCLUSIONS: Smoking is common in patients with PUUV infection. Current smokers suffer from more severe acute kidney injury (AKI) and they have higher leucocyte count than non-smokers in PUUV infection. Smoking cessation decreases the risk of severe AKI to the same level as observed in never-smokers.
Assuntos
Injúria Renal Aguda/etiologia , Febre Hemorrágica com Síndrome Renal/complicações , Virus Puumala/patogenicidade , Índice de Gravidade de Doença , Fumar/efeitos adversos , Adulto , Feminino , Finlândia , Febre Hemorrágica com Síndrome Renal/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Adenine phosphoribosyltransferase deficiency is a rare autosomal recessive disorder manifesting as urolithiasis or crystalline nephropathy. It leads to the generation of large amounts of poorly soluble 2,8-dihydroxyadenine excreted in urine, yielding kidney injury and in some patients, kidney failure. Early recognition of the disease, institution of xanthine analog therapy to block the formation of 2,8-dihydroxyadenine, high fluid intake, and low purine diet prevent CKD. Because of symptom variability and lack of awareness, however, the diagnosis is sometimes extremely deferred. We describe a patient with adenine phosphoribosyltransferase deficiency who was diagnosed during evaluation of a poorly functioning second kidney allograft. This report highlights the risk of renal allograft loss in patients with undiagnosed adenine phosphoribosyltransferase deficiency and the need for improved early detection of this disease.
Assuntos
Adenina Fosforribosiltransferase/deficiência , Cálculos Renais/cirurgia , Transplante de Rim/efeitos adversos , Erros Inatos do Metabolismo/complicações , Urolitíase/complicações , Adenina/análogos & derivados , Adenina/metabolismo , Aloenxertos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
Hantaviruses are zoonotic viruses that cause life-threatening diseases when transmitted to humans. Severe hantavirus infection is manifested by impairment of renal function, pulmonary oedema and capillary leakage. Both innate and adaptive immune responses contribute to the pathogenesis, but the underlying mechanisms are not fully understood. Here, we showed that galectin-3-binding protein (Gal-3BP) was upregulated as a result of hantavirus infection both in vitro and in vivo. Gal-3BP is a secreted glycoprotein found in human serum, and increased Gal-3BP levels have been reported in chronic viral infections and in several types of cancer. Our in vitro experiments showed that, whilst Vero E6 cells (an African green monkey kidney cell line) constitutively expressed and secreted Gal-3BP, this protein was detected in primary human cells only as a result of hantavirus infection. Analysis of Gal-3BP levels in serum samples of cynomolgus macaques infected experimentally with hantavirus indicated that hantavirus infection induced Gal-3BP also in vivo. Finally, analysis of plasma samples collected from patients hospitalized because of acute hantavirus infection showed higher Gal-3BP levels during the acute than the convalescent phase. Furthermore, the Gal-3BP levels in patients with haemorrhagic fever with renal syndrome correlated with increased complement activation and with clinical variables reflecting the severity of acute hantavirus infection.
Assuntos
Antígenos de Neoplasias/biossíntese , Biomarcadores Tumorais/biossíntese , Proteínas de Transporte/biossíntese , Galectina 3/metabolismo , Glicoproteínas/biossíntese , Infecções por Hantavirus/metabolismo , Doença Aguda , Animais , Antígenos de Neoplasias/sangue , Antígenos Virais/metabolismo , Biomarcadores Tumorais/sangue , Proteínas de Transporte/sangue , Chlorocebus aethiops , Ativação do Complemento , Feminino , Glicoproteínas/sangue , Infecções por Hantavirus/imunologia , Infecções por Hantavirus/virologia , Febre Hemorrágica com Síndrome Renal/imunologia , Febre Hemorrágica com Síndrome Renal/metabolismo , Febre Hemorrágica com Síndrome Renal/virologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Macaca fascicularis , Masculino , Virus Puumala , Distribuição Tecidual , Células VeroRESUMO
The pathogenesis of thrombocytopenia in Puumala hantavirus (PUUV) infection is probably multifactorial. We aimed to evaluate the possible spleen enlargement during acute PUUV infection, and to determine its association with thrombocytopenia and disease severity. Magnetic resonance imaging (MRI) of the spleen was performed in 20 patients with acute PUUV infection. MRI was repeated 5-8 months later. The change in spleen length was compared with markers describing the severity of the disease. In all patients, the spleen length was increased in the acute phase compared with the control phase (median 129 mm vs 111 mm, p < 0.001). The change correlated with maximum C-reactive protein value (r = 0.513, p = 0.021) and inversely with maximum leukocyte count (r = -0.471, p = 0.036), but not with maximum serum creatinine level or minimum platelet count. Enlarged spleen, evaluated by MRI, was shown to be a common finding during acute PUUV infection. However, it does not associate with thrombocytopenia and acute kidney injury.
Assuntos
Febre Hemorrágica com Síndrome Renal/diagnóstico , Febre Hemorrágica com Síndrome Renal/patologia , Virus Puumala/isolamento & purificação , Esplenomegalia/etiologia , Esplenomegalia/patologia , Trombocitopenia/etiologia , Adolescente , Adulto , Idoso , Proteína C-Reativa/análise , Creatinina/sangue , Feminino , Humanos , Contagem de Leucócitos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Radiografia , Baço/diagnóstico por imagem , Baço/patologia , Adulto JovemRESUMO
INTRODUCTION: Presence of subclinical intestinal inflammation has repeatedly been shown in IgA nephropathy (IgAN) and the degree of histological inflammation has correlated with abnormal urinary findings. There is lack of noninvasive biomarkers evaluating the presence of subclinical intestinal damage in IgAN. We conducted this study hypothesizing that selected biomarkers regarded as indirect markers of intestinal damage could be elevated in IgAN. METHODS: Eighty-five primary IgAN patients (median age 55 years, 54% men) participated in this single-center study in Tampere, Finland. None had end-stage kidney disease or previously diagnosed enteropathies. Celiac disease was excluded with serum transglutaminase 2 antibody (TG2Ab) and endomysial antibody tests and inflammatory bowel disease with fecal calprotectin. Intestinal damage was evaluated from sera with analyses of intestinal fatty-acid binding protein (I-FABP), soluble cluster of differentiation molecule 14 (sCD14), and lipopolysaccharide binding protein. Fourteen people suffering from dyspepsia and 15 healthy people served as controls. RESULTS: I-FABP levels among IgAN patients were higher than in the healthy controls (median 830 pg/mL vs. 289 pg/mL, p < 0.001). Also, sCD14 was increased in IgAN patients compared to dyspepsia controls. Although TG2Ab levels were within the normal range among IgAN patients, they were higher than in the healthy controls (median 1.3 U/mL vs. 0.6 U/mL, p < 0.001). CONCLUSIONS: Elevated serum levels of I-FABP were present in primary IgAN patients without known enteropathies. Serum I-FABP may indicate the presence of subclinical intestinal damage. These findings encourage further investigation into the role of the intestine in the pathophysiology of IgAN.
RESUMO
Puumala orthohantavirus-caused hemorrhagic fever with renal syndrome (PUUV-HFRS) is characterized by strong neutrophil activation. Neutrophils are the most abundant immune cell type in the circulation and are specially equipped to rapidly respond to infections. They are more heterogenous than previously appreciated, with specific neutrophil subsets recently implicated in inflammation and immunosuppression. Furthermore, neutrophils can be divided based on their density to either low-density granulocytes (LDGs) or "normal density" polymorphonuclear cell (PMN) fractions. In the current study we aimed to identify and characterize the different neutrophil subsets in the circulation of PUUV-HFRS patients. PMNs exhibited an activation of antiviral pathways, while circulating LDGs were increased in frequency following acute PUUV-HFRS. Furthermore, cell surface marker expression analysis revealed that PUUV-associated LDGs are primarily immature and most likely reflect an increased neutrophil production from the bone marrow. Interestingly, both the frequency of LDGs and the presence of a "left shift" in blood associated with the extent of thrombocytopenia, one of the hallmarks of severe HFRS, suggesting that maturing neutrophils could play a role in disease pathogenesis. These results imply that elevated circulating LDGs might be a general finding in acute viral infections. However, in contrast to the COVID-19 associated LDGs described previously, the secretome of PUUV LDGs did not show significant immunosuppressive ability, which suggests inherent biological differences in the LDG responses that can be dependent on the causative virus or differing infection kinetics.
Assuntos
Febre Hemorrágica com Síndrome Renal , Neutrófilos , Virus Puumala , Trombocitopenia , Febre Hemorrágica com Síndrome Renal/imunologia , Febre Hemorrágica com Síndrome Renal/virologia , Neutrófilos/imunologia , Humanos , Trombocitopenia/imunologia , Trombocitopenia/virologia , Virus Puumala/imunologia , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Ativação de Neutrófilo , IdosoRESUMO
A patient with severe capillary leakage syndrome caused by a Puumala hantavirus infection was treated with a single dose of icatibant, a bradykinin receptor antagonist, with a dramatic positive response. We suggest that this drug should be tested in a larger number of patients with severe hantavirus infection.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Bradicinina/análogos & derivados , Infecções por Hantavirus/tratamento farmacológico , Adulto , Bradicinina/uso terapêutico , Antagonistas dos Receptores da Bradicinina , Síndrome de Vazamento Capilar/tratamento farmacológico , Síndrome de Vazamento Capilar/virologia , Humanos , MasculinoRESUMO
The annual number of kidney transplantations in Finland is 150 to 200. Successful kidney transplantation improves the patient's quality of life and prognosis and is cost-effective as compared with dialytic therapy. Only a few per cent of transplantations are made from a living donor. Waiting times for kidney transplantations have become longer in the last few years. Whereas attempts should be made to better identify potential brain-dead organ donors in order to increase kidney transplantations, transplantations from living donors could also reduce the disproportion between the availability and the need of organs.
Assuntos
Transplante de Rim/estatística & dados numéricos , Doadores Vivos , Morte Encefálica , Análise Custo-Benefício , Finlândia , Humanos , Transplante de Rim/economia , Prognóstico , Qualidade de Vida , Diálise Renal/economia , Obtenção de Tecidos e Órgãos/organização & administração , Listas de EsperaRESUMO
BACKGROUND: Higher than normal estimated glomerular filtration rate (eGFR), i.e. renal hyperfiltration (RHF), has been associated with mortality. METHODS: A population-based screening program in Finland identified 1747 apparently healthy middle-aged cardiovascular risk subjects in 2005-2007. GFR was estimated with the creatinine-based Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation indexed for 1.73 m2 and for the actual body surface area (BSA) of the subjects. This individually corrected eGFR was calculated as eGFR (ml/min/BSA m2) = eGFR (ml/min/1.73 m2) x (BSA/1.73). BSA was calculated by the Mosteller formula. RHF was defined as eGFR of more than 1.96 SD above the mean eGFR of healthy individuals. All-cause mortality was obtained from the national registry. RESULTS: The higher the eGFR, the greater was the discrepancy between the two GFR estimating equations. During the 14 years of follow-up, 230 subjects died. There were no differences in mortality rates between the categories of individually corrected eGFR (p = 0.86) when adjusted for age, sex, body mass index, systolic BP, total cholesterol, new diabetes, current smoking, and alcohol use. The highest eGFR category was associated with increased standardized mortality rate (SMR) when CKD-EPI formula indexed for 1.73 m2 was used, but SMR was at the population level when individually corrected eGFR was applied. CONCLUSIONS: Higher than normal eGFR calculated by the creatinine-based CKD-EPI equation is associated with all-cause mortality when indexed to 1.73 m2, but not when indexed to actual BSA of a person. This challenges the current perception of the harmfulness of RHF in apparently healthy individuals.