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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.
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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
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.
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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
BACKGROUND: The incidence of cardiovascular complications may be higher in unilateral than in bilateral primary aldosteronism (PA). We compared non-invasive hemodynamics before and after targeted therapy of bilateral versus unilateral PA. METHODS: Adrenal vein sampling was performed, and cardiovascular variables were recorded using radial artery pulse wave analysis and whole-body impedance cardiography (n=114). In a subset of 40 patients (adrenalectomy n=20, spironolactone-based treatment n=20), hemodynamic recordings were again performed after 33 months of targeted PA treatment. RESULTS: In initial cross-sectional analysis, 51 patients had bilateral and 63 had unilateral PA. The mean ages were 50.6 and 54.3 years (p=0.081), and body mass indexes were 30.3 and 30.6 kg/m2 (p=0.724), respectively. Aortic blood pressure and cardiac output did not significantly differ between the groups, but evaluated left cardiac work was ~10% higher in unilateral PA (p=0.022). In the followup study, initial and final blood pressure levels in the aorta were not significantly different, while initial cardiac output (+13%, p=0.015) and left cardiac work (+17%, p=0.009) were higher in unilateral than in bilateral PA. After a median treatment time of 33 months, the differences in cardiac load were abolished, and extracellular water volume was reduced by 1.3 and 1.4 liters in bilateral versus unilateral PA, respectively (p=0.814). CONCLUSIONS: These results suggest that unilateral PA burdens the heart more than bilateral PA, providing a possible explanation for the higher incidence of cardiac complications in unilateral disease. A similar reduction in aldosterone-induced volume excess was obtained with targeted surgical and medical treatment of PA.
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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.
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PURPOSE: A German multicentre study BLOOMY was the first to use machine learning approach to develop mortality prediction scores for bloodstream infection (BSI) patients, but the scores have not been assessed in other cohorts. Our aim was to assess how the BLOOMY 14-day and 6-month scores estimate mortality in our cohort of 497 cases with BSI. METHODS: Clinical data, laboratory data, and patient outcome were gathered retrospectively from patient records. The scores were calculated as presented in the BLOOMY study with the exception in the day of the evaluation. RESULTS: In our cohort, BLOOMY 14-day score estimated death by day 14 with an area under curve (AUC) of 0.87 (95% Confidence Interval 0.80-0.94). Using ≥ 6 points as a cutoff, sensitivity was 68.8%, specificity 88.1%, positive predictive value (PPV) 39.3%, and negative predictive value (NPV) 96.2%. These results were similar in the original BLOOMY cohort and outweighed both quick Sepsis-Related Organ Failure Assessment (AUC 0.76) and Pitt Bacteraemia Score (AUC 0.79) in our cohort. BLOOMY 6-month score to estimate 6-month mortality had an AUC of 0.79 (0.73-0.85). Using ≥ 6 points as a cutoff, sensitivity was 98.3%, specificity 10.7%, PPV 25.7%, and NPV 95.2%. AUCs of 6-month score to estimate 1-year and 5-year mortality were 0.80 (0.74-0.85) and 0.77 (0.73-0.82), respectively. CONCLUSION: The BLOOMY 14-day and 6-month scores performed well in the estimations of mortality in our cohort and exceeded some established scores, but their adoption in clinical work remains to be seen.
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Bacteriemia , Humanos , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Bacteriemia/mortalidade , Bacteriemia/diagnóstico , Idoso de 80 Anos ou mais , Adulto , Sepse/mortalidade , Sepse/diagnóstico , Hospitalização/estatística & dados numéricos , Prognóstico , Sensibilidade e Especificidade , Alemanha/epidemiologiaRESUMO
INTRODUCTION: Hantaviruses cause two kinds of clinical syndromes. Hemorrhagic fever with renal syndrome is caused by Hantaan virus in Asia, Puumala virus (PUUV) and Dobrava virus in Europe, and Seoul virus worldwide. Hantavirus cardiopulmonary syndrome is caused by Sin Nombre virus in North America and Andes virus and related viruses in Latin America. All hantaviruses are carried by rodents and insectivores. Humans are infected via inhaled aerosols of rodent excreta. In the history, there are several epidemics of acute infectious diseases during many wars, which have been suggested or proven to be caused by various hantaviruses. MATERIALS AND METHODS: Literature review of 41 original publications and reviews published between 1943 and 2022 was performed. Among them, 23 publications handle hantavirus infections among military forces, and the rest 17 hantavirus infections themselves. RESULTS: A large epidemic during World War II in 1942 among German and Finnish soldiers in Northern Finland with more than 1,000 patients was most probably caused by PUUV. During Korean War in 1951-1954,â¼ 3,200 cases occurred among United Nations soldiers in an epidemic caused by Hantaan virus. During Balkan war from 1991 to 1995, numerous soldiers got ill because of hantavirus infection caused by PUUV and Dobrava virus. Several other reports of cases of various hantavirus infections especially among U.S. soldiers acting in South Korea, Germany, Bosnia, and Kosovo have been described in the literature. CONCLUSIONS: Military maneuvers usually include soil removal, spreading, digging with accompanied dust, and living in field and other harsh conditions, which easily expose soldiers to rodents and their excreta. Therefore, the risks of hantavirus infections in military context are obvious. All military infections have been caused by hantaviruses leading to hemorrhagic fever with renal syndrome.
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Infecções por Hantavirus , Febre Hemorrágica com Síndrome Renal , Militares , Orthohantavírus , Animais , Humanos , Febre Hemorrágica com Síndrome Renal/epidemiologia , Febre Hemorrágica com Síndrome Renal/complicações , Infecções por Hantavirus/epidemiologia , Infecções por Hantavirus/etiologia , RoedoresRESUMO
High resting heart rate is a cardiovascular risk factor, but limited data exist on the underlying hemodynamics and reproducibility of supine-to-upright increase in heart rate. We recorded noninvasive hemodynamics in 574 volunteers [age, 44.9 yr; body mass index (BMI), 26.4 kg/m2; 49% male] during passive head-up tilt (HUT) using whole body impedance cardiography and radial artery tonometry. Heart rate regulation was evaluated using heart rate variability (HRV) analyses. Comparisons were made between quartiles of supine-to-upright heart rate changes, in which heart rate at rest ranged 62.6-64.8 beats/min (P = 0.285). The average upright increases in heart rate in the quartiles 1-4 were 4.7, 9.9, 13.5, and 21.0 beats/min, respectively (P < 0.0001). No differences were observed in the low-frequency power of HRV, whether in the supine or upright position, or in the high-frequency power of HRV in the supine position. Upright high-frequency power of HRV was highest in quartile 1 with lowest upright heart rate and lowest in quartile 4 with highest upright heart rate. Mean systolic blood pressure before and during HUT (126 vs. 108 mmHg) and the increase in systemic vascular resistance during HUT (650 vs. 173 dyn·s/cm5/m2) were highest in quartile 1 and lowest in quartile 4. The increases in heart rate during HUT on three separate occasions several weeks apart were highly reproducible (r = 0.682) among 215 participants. To conclude, supine-to-upright increase in heart rate is a reproducible phenotype with underlying differences in the modulation of cardiac parasympathetic tone and systemic vascular resistance. As heart rate at rest influences prognosis, future research should elucidate the prognostic significance of these phenotypic differences.NEW & NOTEWORTHY Subjects with similar supine heart rates are characterized by variable increases in heart rate during upright posture. Individual heart rate increases in response to upright posture are highly reproducible as hemodynamic phenotypes and present underlying differences in the modulation of cardiac parasympathetic tone and systemic vascular resistance. These results indicate that resting heart rate obtained in the supine position alone is not an optimal means of classifying people into groups with differences in cardiovascular function.
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Hemodinâmica , Postura , Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Feminino , Frequência Cardíaca/fisiologia , Reprodutibilidade dos Testes , Postura/fisiologia , Hemodinâmica/fisiologia , Pressão Sanguínea/fisiologiaRESUMO
High haemoglobin level has been associated with metabolic syndrome, elevated blood pressure (BP), and increased mortality risk. In this cross-sectional study, we investigated the association of blood haemoglobin with haemodynamics in 743 subjects, using whole-body impedance cardiography and pulse wave analysis. The participants were allocated to sex-stratified haemoglobin tertiles with mean values 135, 144, and 154 g/L, respectively. The mean age was similar in all tertiles, while body mass index was higher in the highest versus the lowest haemoglobin tertile. The highest haemoglobin tertile had the highest erythrocyte and leukocyte counts, plasma C-reactive protein, uric acid, renin activity, and aldosterone. The lipid profile was less favourable and insulin sensitivity lower in the highest versus the lowest haemoglobin tertile. Aortic BP, cardiac output, and systemic vascular resistance were similar in all tertiles, while the pulse wave velocity (PWV) was higher in the highest versus the lowest haemoglobin tertile. In linear regression analysis, age (Beta 0.478), mean aortic BP (Beta 0.178), uric acid (Beta 0.150), heart rate (Beta 0.148), and aldosterone-to-renin ratio (Beta 0.123) had the strongest associations with PWV (p < 0.001 for all). Additionally, haemoglobin concentration was an explanatory factory for PWV (Beta 0.070, p = 0.028). To conclude, blood haemoglobin concentration had a small direct and independent association with a measure of large artery stiffness.
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OBJECTIVE: To compare blood pressure (BP) in tonometric radial artery recordings during passive head-up tilt with ambulatory recordings and evaluate possible laboratory cutoff values for hypertension. METHODS: Laboratory BP and ambulatory BP were recorded in normotensive (nâ =â 69), unmedicated hypertensive (nâ =â 190), and medicated hypertensive (nâ =â 151) subjects. RESULTS: Mean age was 50.2 years, BMI 27.7â kg/m 2 , ambulatory daytime BP 139/87â mmHg, and 276 were male (65%). As supine-to-upright changes in SBP ranged from -52 to +30â mmHg, and in DBP from -21 to +32â mmHg, the mean values of BP supine and upright measurements were compared with ambulatory BP. The mean(supine+upright) systolic laboratory BP was corresponding to ambulatory level (difference +1â mmHg), while mean(supine+upright) DBP was 4â mmHg lower ( P â <â 0.05) than ambulatory value. Correlograms indicated that laboratory 136/82â mmHg corresponded to ambulatory 135/85â mmHg. When compared with ambulatory 135/85â mmHg, the sensitivity and specificity of laboratory 136/82â mmHg to define hypertension were 71.5% and 77.3% for SBP, and 71.7% and 72.8%, for DBP, respectively. The laboratory cutoff 136/82â mmHg classified 311/410 subjects similarly to ambulatory BP as normotensive or hypertensive, 68 were hypertensive only in ambulatory, while 31 were hypertensive only in laboratory measurements. CONCLUSION: BP responses to upright posture were variable. When compared with ambulatory BP, mean(supine+upright) laboratory cutoff 136/82â mmHg classified 76% of subjects similarly as normotensive or hypertensive. In the remaining 24% the discordant results may be attributed to white-coat or masked hypertension, or higher physical activity during out-of-office recordings.
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Hipertensão , Hipertensão Mascarada , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Pressão Sanguínea , Hipertensão/diagnóstico , Determinação da Pressão Arterial/métodos , Monitorização Ambulatorial da Pressão Arterial , PosturaRESUMO
BACKGROUND: Obesity-related hypertension and the associated metabolic abnormalities are considered as a distinct hypertensive phenotype. Here we examined how abdominal fat content, as judged by waist:height ratio, influenced blood pressure and hemodynamic profile in normotensive subjects and never-treated hypertensive patients. METHODS: The 541 participants (20-72 years) underwent physical examination and laboratory analyses and were divided into age and sex-adjusted quartiles of waist:height ratio. Supine hemodynamics were recorded using whole-body impedance cardiography, combined with analyses of radial tonometric pulse wave form and heart rate variability. RESULTS: Mean waist:height ratios in the quartiles were 0.46, 0.51, 0.55 and 0.62. Radial and aortic blood pressure, systemic vascular resistance, pulse wave velocity, markers of glucose and lipid metabolism, leptin levels and C-reactive protein were higher in quartile 4 when compared with quartiles 1 and 2 (p < 0.05 for all). Cardiac index was lower in quartile 4 versus quartile 1, while no differences were seen in heart rate variability, augmentation index, plasma renin activity, and aldosterone concentration between the quartiles. Linear regression analyses showed independent associations of abdominal obesity with higher aortic systolic and diastolic blood pressure, systemic vascular resistance, and pulse wave velocity (p < 0.05 for waist:height ratio in all regression models). CONCLUSION: Higher waist:height ratio was associated with elevated blood pressure, systemic vascular resistance, and arterial stiffness, but not with alterations in cardiac sympathovagal modulation or activation of the circulating renin-angiotensin-aldosterone system. Although obesity-related elevation of blood pressure has distinct phenotypic features, these results suggest that its main characteristics correspond those of primary hypertension. TRIAL REGISTRATION: ClinicalTrails.gov NCT01742702 (date of registration 5th December 2012).
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Hipertensão , Obesidade Abdominal , Humanos , Pressão Sanguínea , Estudos Transversais , Hipertensão Essencial , Hemodinâmica , Hipertensão/epidemiologia , Obesidade/complicações , Obesidade/diagnóstico , Obesidade Abdominal/diagnóstico , Análise de Onda de Pulso , Rigidez VascularRESUMO
The clinical outcome of Puumala hantavirus (PUUV) infection shows extensive variation, ranging from inapparent subclinical infection (70-80%) to severe hemorrhagic fever with renal syndrome (HFRS), with about 0.1% of cases being fatal. Most hospitalized patients experience acute kidney injury (AKI), histologically known as acute hemorrhagic tubulointerstitial nephritis. Why this variation? There is no evidence that there would be more virulent and less virulent variants infecting humans, although this has not been extensively studied. Individuals with the human leukocyte antigen (HLA) alleles B*08 and DRB1*0301 are likely to have a severe form of the PUUV infection, and those with B*27 are likely to have a benign clinical course. Other genetic factors, related to the tumor necrosis factor (TNF) gene and the C4A component of the complement system, may be involved. Various autoimmune phenomena and Epstein-Barr virus infection are associated with PUUV infection, but hantavirus-neutralizing antibodies are not associated with lower disease severity in PUUV HFRS. Wide individual differences occur in ocular and central nervous system (CNS) manifestations and in the long-term consequences of nephropathia epidemica (NE). Numerous biomarkers have been detected, and some are clinically used to assess and predict the severity of PUUV infection. A new addition is the plasma glucose concentration associated with the severity of both capillary leakage, thrombocytopenia, inflammation, and AKI in PUUV infection. Our question, "Why this variation?" remains largely unanswered.
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Injúria Renal Aguda , Infecções por Vírus Epstein-Barr , Infecções por Hantavirus , Febre Hemorrágica com Síndrome Renal , Virus Puumala , Humanos , Infecções por Vírus Epstein-Barr/complicações , Herpesvirus Humano 4 , Infecções por Hantavirus/complicaçõesRESUMO
PURPOSE: High sodium intake is an accepted risk factor for hypertension, while low Na+ intake has also been associated with increased risk of cardiovascular events. In this cross-sectional study, we examined the association of 24-h urinary Na+ excretion with haemodynamics and volume status. MATERIALS AND METHODS: Haemodynamics were recorded in 510 normotensive and never-treated hypertensive subjects using whole-body impedance cardiography and tonometric radial artery pulse wave analysis. The results were examined in sex-specific tertiles of 24-h Na+ excretion, and comparisons between normotensive and hypertensive participants were also performed. Regression analysis was used to investigate factors associated with volume status. The findings were additionally compared to 28 patients with primary aldosteronism. RESULTS: The mean values of 24-h urinary Na+ excretion in tertiles of the 510 participants were 94, 148 and 218 mmol, respectively. Average tertile age (43.4-44.7 years), office blood pressure and pulse wave velocity were corresponding in the tertiles. Plasma electrolytes, lipids, vitamin D metabolites, parathyroid hormone, renin activity, aldosterone, creatinine and insulin sensitivity did not differ in the tertiles. In supine laboratory recordings, there were no differences in aortic systolic and diastolic blood pressure, heart rate, cardiac output and systemic vascular resistance. Extracellular water volume was higher in the highest versus lowest tertile of Na+ excretion. In regression analysis, body surface area and 24-h Na+ excretion were independent explanatory variables for extracellular water volume. No differences in urine Na+ excretion and extracellular water volume were found between normotensive and hypertensive participants. When compared with the 510 participants, patients with primary aldosteronism had 6.0% excess in extracellular water (p = .003), and 24-h Na+ excretion was not related with extracellular water volume. CONCLUSION: In the absence of mineralocorticoid excess, Na+ intake, as evaluated from 24-h Na+ excretion, predominantly influences extracellular water volume without a clear effect on blood pressure.
We evaluated sodium intake in 510 subjects by measuring their 24-h sodium excretion to the urine and examined whether sodium intake was related with alterations in cardiovascular function and fluid balance. All participants were without blood pressure lowering medications.Blood pressure was recorded by a device that senses the radial artery pulsations form the wrist. The amount of blood pumped by the heart, the transfer of pressure waves following cardiac contractions and body fluid status were evaluated using bioimpedance, a method recording changes in body electrical resistance.For the analyses, the participants were divided into tertiles according to their 24-h sodium excretions. We also compared results between normotensive and hypertensive subjects.The 24-h sodium excretion in the tertiles corresponded to about 6 g, 9 g and 13 g of salt intake per day, respectively. There were no differences between the tertiles in age, routine laboratory analyses, blood pressure, large arterial stiffness, amount blood pumped by the heart and resistance to blood flow in the arteries. However, there was more extracellular fluid in the highest versus the lowest tertile of sodium excretion. Further statistics indicated that extracellular fluid volume in the body was mainly determined by body size, but it was also moderately influenced by sodium intake.No differences in 24-h sodium excretion and extracellular water volume were found between normotensive and hypertensive participants.In subjects not using blood pressure lowering medications, sodium intake predominantly influences the amount of extracellular fluid without a clear effect on blood pressure.
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Hiperaldosteronismo , Hipertensão , Masculino , Feminino , Humanos , Adulto , Pressão Sanguínea/fisiologia , Água , Estudos Transversais , Análise de Onda de Pulso , Sódio/urinaRESUMO
Uric acid has promoted renal fibrosis and inflammation in experimental studies, but some studies have shown nephroprotective effects due to alleviated oxidative stress. We studied the influence of experimental hyperuricaemia in surgically 5/6 nephrectomized rats. Three weeks after subtotal nephrectomy or sham operation, the rats were allocated to control diet or 2.0% oxonic acid (uricase inhibitor) diet for 9 weeks. Then blood, urine and tissue samples were taken, and renal morphology and oxidative stress were examined. Inflammation and fibrosis were evaluated using immunohistochemistry and real-time PCR (RT-PCR). Remnant kidney rats ingesting normal or oxonic acid diet presented with ~60% reduction of creatinine clearance and suppressed plasma renin activity. Oxonic acid diet increased plasma uric acid levels by >80 µmol/L. In remnant kidney rats, moderate hyperuricaemia decreased glomerulosclerosis, tubulointerstitial damage and kidney mast cell count, without influencing the fibrosis marker collagen I messenger RNA (mRNA) content. In both sham-operated and 5/6 nephrectomized rats, the mast cell product 11-epi-prostaglandin-F2α excretion to the urine and kidney tissue cyclooxygenase-2 (COX-2) levels were decreased. To conclude, hyperuricaemic remnant kidney rats displayed improved kidney morphology and reduced markers of oxidative stress and inflammation. Thus, moderately elevated plasma uric acid had beneficial effects on the kidney in this low-renin model of experimental renal insufficiency.
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Hiperuricemia , Nefropatias , Insuficiência Renal , Animais , Ratos , Fibrose , Hiperuricemia/patologia , Inflamação/patologia , Rim , Nefrectomia , Ácido Oxônico/farmacologia , Insuficiência Renal/patologia , Renina/genética , Ácido ÚricoRESUMO
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.
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Bem-Estar Psicológico , Qualidade de Vida , Humanos , Feminino , Masculino , Estudos TransversaisAssuntos
Doença Celíaca , Doença Celíaca/complicações , Doença Celíaca/epidemiologia , Comorbidade , Humanos , Rim , FenótipoRESUMO
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.
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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
Eight decades ago, a report on "a swamp fever-like disease in German troups in Lapland" was published in this journal. The disease outbreak had occurred in 1942 and affected more than 1000 soldiers at the Finish front. The published, precise analysis of the clinical picture was obviously the first description of hantavirus disease in the German language area. Nowadays, hantavirus disease - in Central and Northern Europe also known as Nephropathia epidemica - is one of the most frequent notifiable virus diseases in Germany and Finland.
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Doenças Transmissíveis , Infecções por Hantavirus , Febre Hemorrágica com Síndrome Renal , Orthohantavírus , Humanos , Idioma , II Guerra Mundial , Febre Hemorrágica com Síndrome Renal/epidemiologia , Surtos de Doenças , Infecções por Hantavirus/diagnóstico , Infecções por Hantavirus/epidemiologiaRESUMO
Background Resting heart rate (HR) and its variability (HRV) reflects the cardiac sympathovagal balance that is stimulated by head-up tilting. HRV is influenced by the level of HR, but how much HRV offers additional information about cardiac autonomic tone than HR alone remains unresolved. We examined the relation of resting HR with HRV during head-up tilt. Methods. Hemodynamics of 569 subjects without known cardiovascular diseases and medications with direct cardiovascular effects were recorded using whole-body impedance cardiography, radial pulse wave analysis, and electrocardiography-based HRV analysis during passive head-up tilt. Results. Higher low frequency to the high-frequency ratio (LF/HF) of HRV (reflecting sympathovagal balance) was associated with higher HR in supine (p < .05, both linear regression analysis and variance analysis comparing HR tertiles) and upright postures (p < .001, linear regression analysis). The association of HR with HRV during tilt-testing remained significant when the HR dependence of HRV was mathematically weakened by dividing the HRV power spectra with the fourth power of the average RR-interval. Conclusion. Higher resting HR is related to higher LF/HF both supine and upright, reflecting elevated sympathetic influence on cardiac autonomic modulation. Lower resting HR is associated with lower resting LF/HF, while the differences in LF/HF between the HR tertiles were minor during head-up tilt, suggesting a greater change in cardiac sympathovagal balance in response to upright posture in those with lowest resting HR. Altogether, resting HR well predicts HRV levels during head-up tilt.Trial registration: Clinicaltrialsregister.eu 2006-002065-39, first registered 5 May 2006. ClinicalTrials.gov NCT01742702, first registered 5 December 2012.
Assuntos
Doenças Cardiovasculares , Sistema Nervoso Autônomo , Pressão Sanguínea/fisiologia , Coração , Frequência Cardíaca , HumanosRESUMO
Nephropathia epidemica (NE), a mild form of haemorrhagic fever with renal syndrome (HFRS), is an acute febrile illness caused by Puumala orthohantavirus (PUUV). NE manifests typically with acute kidney injury (AKI), with a case fatality rate of about 0.1%. The treatment and management of hantavirus infections are mainly supportive, although neutralizing monoclonal antibodies and immune sera therapeutics are under investigation. In order to assess the potential use of antibody therapeutics in NE, we sought to determine the relationship between circulating PUUV neutralizing antibodies, PUUV nucleocapsid protein (N) IgG antibodies, and viral loads with markers of disease severity. The study included serum samples of extensively characterized patient cohorts (n = 116) from Tampere University Hospital, Finland. The results showed that upon hospitalization, most patients already had considerable neutralizing and anti-PUUV-N IgG antibody levels. However, contrary to expectations, neutralizing antibody titers from the first day of hospitalization did not appear to protect from AKI or correlate with more favorable disease outcomes. This indicates that further studies are needed to investigate the applicability of neutralizing antibodies as a therapy for hospitalized NE patients.