Plasma Soluble Urokinase Plasminogen Activator Receptor in Children with Urinary Tract Infection

Objective In this prospective study we investigated the role of plasma levels of soluble urokinase plasminogen activator receptor (suPAR) in children with urinary tract infection. Material and Methods We measured the levels of plasma suPAR during admission in 42 children with suspected acute pyelonephritis and compared the results to acute DMSA scintigraphy. Results The mean level of plasma suPAR at admission was significantly elevated in children with renal involvement (7.3 ng/ml) assessed by the DMSA scintigraphy compared to children without renal involvement (4.4 ng/ml, P = 0.010). The positive predictive value of suPAR seems high, since all patients without renal involvement had low suPAR values. During treatment the mean level of plasma suPAR decreased. Conclusion We conclude that plasma suPAR could be of clinical use for the diagnosis of acute pyelonephritis and that high levels of plasma suPAR might reflect the level of renal involvement and could therefore be a new indicator for renal scarring

Genetics of the ceramide/sphingosine-1-phosphate rheostat in blood pressure regulation and hypertension

<p>Abstract</p> <p>Background</p> <p>Several attempts to decipher the genetics of hypertension of unknown causes have been made including large-scale genome-wide association analysis (GWA), but only a few genes have been identified. Unsolved heterogeneity of the regulation of blood pressure and the shortcomings of the prevailing monogenic approach to capture genetic effects in a polygenic condition are the main reasons for the modest results. The level of the blood pressure is the consequence of the genotypic state of the presumably vast network of genes involved in regulating the vascular tonus and hence the blood pressure. Recently it has been suggested that components of the sphingolipid metabolism pathways may be of importance in vascular physiology. The basic metabolic network of sphingolipids has been established, but the influence of genetic variations on the blood pressure is not known. In the approach presented here the impact of genetic variations in the sphingolipid metabolism is elucidated by a two-step procedure. First, the physiological heterogeneity of the blood pressure is resolved by a latent class/structural equation modelling to obtain homogenous subpopulations. Second, the genetic effects of the sphingolipid metabolism with focus on <it>de novo </it>synthesis of ceramide are analysed. The model does not assume a particular genetic model, but assumes that genes operate in networks.</p> <p>Results</p> <p>The stratification of the study population revealed that (at least) 14 distinct subpopulations are present with different propensity to develop hypertension. Main effects of genes in the <it>de novo </it>synthesis of ceramides were rare (0.14% of all possible). However, epistasis was highly significant and prevalent amounting to approximately 70% of all possible two-gene interactions. The phenotypic variance explained by the ceramide synthesis network were substantial in 4 of the subpopulations amounting to more than 50% in the subpopulation in which all subjects were hypertensive. Construction of the network using the epistatic values revealed that only 17% of the interactions detected were in the direct metabolic pathway, the remaining jumping one or more intermediates.</p> <p>Conclusions</p> <p>This study established the components of the ceramide/sphingosine-1-phosphate rheostat as central to blood pressure regulation. The results in addition confirm that epistasis is of paramount importance and is most conspicuous in the regulation of the rheostat network. Finally, it is shown that applying a simple case-control approach with single gene association analysis is bound to fail, short of identifying a few potential genes with small effects.</p

Association between routine laboratory tests and long-term mortality among acutely admitted older medical patients:a cohort study

BACKGROUND: Older people have the highest incidence of acute medical admissions. Old age and acute hospital admissions are associated with a high risk of adverse health outcomes after discharge, such as reduced physical performance, readmissions and mortality. Hospitalisations in this population are often by acute admission and through the emergency department. This, along with the rapidly increasing proportion of older people, warrants the need for clinically feasible tools that can systematically assess vulnerability in older medical patients upon acute hospital admission. These are essential for prioritising treatment during hospitalisation and after discharge. Here we explore whether an abbreviated form of the FI-Lab frailty index, calculated as the number of admission laboratory test results outside of the reference interval (FI-OutRef) was associated with long term mortality among acutely admitted older medical patients. Secondly, we investigate other markers of aging (age, total number of chronic diagnoses, new chronic diagnoses, and new acute admissions) and their associations with long-term mortality. METHODS: A cohort study of acutely admitted medical patients aged 65 or older. Survival time within a 3 years post-discharge follow up period was used as the outcome. The associations between the markers and survival time were investigated by Cox regression analyses. For analyses, all markers were grouped by quartiles. RESULTS: A total of 4,005 patients were included. Among the 3,172 patients without a cancer diagnosis, mortality within 3 years was 39.9%. Univariate and multiple regression analyses for each marker showed that all were significantly associated with post-discharge survival. The changes between the estimates for the FI-OutRef quartiles in the univariate- and the multiple analyses were negligible. Among all the markers investigated, FI-OutRef had the highest hazard ratio of the fourth quartile versus the first quartile: 3.45 (95% CI: 2.83-s4.22, P < 0.001). CONCLUSION: Among acutely admitted older medical patients, FI-OutRef was strongly associated with long-term mortality. This association was independent of age, sex, and number of chronic diagnoses, new chronic diagnoses, and new acute admissions. Hence FI-OutRef could be a biomarker of advancement of aging within the acute care setting. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12877-017-0434-3) contains supplementary material, which is available to authorized users

The plasma level of soluble urokinase receptor is elevated in patients with Streptococcus pneumoniae bacteraemia and predicts mortality

ABSTRACTThis multicentre prospective study was conducted to investigate whether the level of the soluble form of urokinase-type plasminogen activator receptor (suPAR) is elevated during pneumococcal bacteraemia and is of predictive value in the early stage of the disease. Plasma levels of suPAR were increased significantly (median 5.5; range 2.4–21.0 ng/mL) in 141 patients with pneumococcal bacteraemia, compared to 31 healthy controls (median 2.6, range 1.5–4.0 ng/mL, p 0.001). Furthermore, suPAR levels were elevated significantly in patients who died from the infection (n = 24) compared to survivors (n = 117; p < 0.001). No correlation was found between suPAR levels and C-reactive protein. In univariate logistic regression analysis, hypotension, renal failure, cerebral symptoms and high serum concentrations of protein YKL-40 and suPAR were associated significantly with mortality (p < 0.05). In multivariate analysis, only suPAR remained a significant predictor of death (mortality rate of 13 for suPAR levels of > 10 ng/mL; 95% CI: 1.1–158). The increase in suPAR levels may reflect increased expression by vascular or inflammatory cells in the setting of pneumococcal sepsis. This plasma protein may be used to identify patients who are severely ill with pneumococcal bacteraemia