BackgroundNowadays, there is a considerable bulk of evidence showing that ATP has a prominent role in the regulation of human urinary bladder function and in the pathophysiology of detrusor overactivity. ATP mediates nonadrenergic-noncholinergic detrusor contractions in overactive bladders. In vitro studies have demonstrated that uroepithelial cells and cholinergic nerves from overactive human bladder samples (OAB) release more ATP than controls. Here, we compared the urinary ATP concentration in samples collected non-invasively from OAB women with detrusor overactivity and age-matched controls.MethodsPatients with neurologic diseases, history of malignancy, urinary tract infections or renal impairment (creatinine clearance <70 ml/min) were excluded. All patients completed a 3-day voiding diary, a 24 h urine collection and blood sampling to evaluate creatinine clearance. Urine samples collected during voluntary voids were immediately freeze-preserved for ATP determination by the luciferin-luciferase bioluminescence assay; for comparison purposes, samples were also tested for urinary nerve growth factor (NGF) by ELISA.ResultsThe urinary content of ATP, but not of NGF, normalized to patients’ urine creatinine levels (ATP/Cr) or urinary volume (ATP.Vol) were significantly (P<0.05) higher in OAB women with detrusor overactivity (n = 34) than in healthy controls (n = 30). Significant differences between the two groups were still observed by boosting urinary ATP/Cr content after water intake, but these were not detected for NGF/Cr. In OAB patients, urinary ATP/Cr levels correlated inversely with mean voided volumes determined in a 3-day voiding diary.ConclusionA high area under the receiver operator characteristics (ROC) curve (0.741; 95% CI 0.62–0.86; P<0.001) is consistent with urinary ATP/Cr being a highly sensitive dynamic biomarker for assessing detrusor overactivity in women with OAB syndrome.

Raynaud's phenomenon and digital ulcers (DUs) are frequent among systemic sclerosis (SSc) patients. Our aim was to investigate the diagnostic and predictive value for DU of endothelial dysfunction biomarkers (flow-mediated dilatation (FMD), serum levels of endothelin-1 (ET-1), and ADMA), angiogenic/angiostatic biomarkers (vascular endothelial growth factor (VEGF), endoglin, and endostatin), and nailfold videocapillaroscopy (NVC). We compared our results with a literature review. In a cohort study of 77 SSc patients, we followed two groups of patients: (i) naïve DU patients (39) and (ii) active DU at baseline (38 patients) for 3 years. Telangiectasia (p < 0.001) and diffuse disease subset (p = 0.001) were significantly more frequent in patients with active DU at enrolment. Additionally, NVC late scleroderma pattern (AUC 0.846, 95%CI 0.760-0.932), lower values of FMD (AUC 0.754, 95%CI 0.643-0.864), increased serum levels of ET-1 (AUC 0.758, 95%CI 0.649-0.866), ADMA (AUC 0.634, 95%CI 0.511-0.757), and endoglin as well as low VEGF serum levels (AUC 0.705, 95%CI 0.579-0.830) were significantly associated to new DU events in the 3-year follow-up. Cox regression analysis showed that FMD > 9.41 % (HR 0.37, 95%CI 0.14-0.99); ET-1 >11.85 pmol/L (HR 3.81, 95%CI 1.41-10.26) and late NVC pattern (HR 2.29, 95%CI 0.97-5.38) were independent predictors of DU recurrence. When estimating the probability of occurrence of first DU in naïve DU patients, only late NVC pattern (HR 12.66, 95%CI 2.06-77.89) was an independent predictor factor. In conclusion, late scleroderma patterns in NVC are the best independent predictors of SSc patients who are at risk of developing DU. Endothelial dysfunction assessed by FMD and ET-1 was also found to be an independent predictor of DU recurrence in a 3-year follow-up.

Background/Aim: The determinants of baseline fast solute transport are still unclear. We prospectively investigated the relationship of peritoneal solute transport with markers of inflammation, angiogenesis, and membrane status, with a focus on fast transporters. Methods: Seventy-one incident peritoneal dialysis patients were assessed with baseline and annual peritoneal equilibration tests, using a 3.86% glucose dialysis solution. Residual renal function and markers of inflammation, including systemic and intraperitoneal interleukin-6 (IL-6), effluent cancer antigen 125 (CA-125), and vascular endothelial growth factor (VEGF) appearance rates (ARs), were investigated. The time course of the dialysate-to-plasma ratio of creatinine (D/P creatinine ratio) and its relationship with the biomarkers were investigated by a mixed linear model. Results: Incident fast/fast average transporters had a similar age, diabetes prevalence, and serum and effluent IL-6 levels, but significantly higher levels of CA-125 and VEGF ARs than the slow/slow average group; the D/P creatinine ratio was not correlated with systemic IL-6, but was correlated with effluent CA-125 AR (r = 0.45, p < 0.0001) and VEGF AR (r = 0.52, p < 0.0001). The D/P creatinine ratio decreased with a U-shaped profile (p = 0.02). Intraperitoneal IL-6 was the significant and positive determinant of the time course of the D/P creatinine ratio (p < 0.0001). Effluent CA-125 decreased with time on peritoneal dialysis (p = 0.013). Conclusions: Baseline peritoneal fast transport was not associated with systemic inflammation, but was related to peritoneal locally produced substances able to mediate transitory hyperpermeability. The D/P creatinine ratio changed during the follow-up period with a U-shaped profile. This was associated with effluent IL-6 and partly with VEGF. CA-125 decreased throughout the follow-up period.

Urinary neutrophil gelatinase-associated lipocalin (uNGAL) has been suggested as potential early marker of delayed graft function (DGF) following kidney transplantation (KTx). We conducted a prospective study in 40 consecutive KTx recipients to evaluate serial changes of uNGAL within the first week after KTx and assess its performance in predicting DGF (dialysis requirement during initial posttransplant week) and graft function throughout first year. Urine samples were collected on post-KTx days 0, 1, 2, 4, and 7. Linear mixed and multivariable regression models, receiver-operating characteristic (ROC), and areas under ROC curves were used. At all-time points, mean uNGAL levels were significantly higher in patients developing DGF (n = 18). Shortly after KTx (3–6 h), uNGAL values were higher in DGF recipients (on average +242 ng/mL, considering mean dialysis time of 4.1 years) and rose further in following days, contrasting with prompt function recipients. Day-1 uNGAL levels accurately predicted DGF (AUC-ROC = 0.93), with a performance higher than serum creatinine (AUC-ROC = 0.76), and similar to cystatin C (AUC-ROC = 0.95). Multivariable analyses revealed that uNGAL levels at days 4 and 7 were strongly associated with one-year serum creatinine. Urinary NGAL is an early marker of graft injury and is independently associated with dialysis requirement within one week after KTx and one-year graft function.

The total leucocyte count in the synovial fluid offers great negative predictive value in the diagnosis of PJI and the addition of more specific markers such as CRP and ADA improves the positive predictive value. Thus the addition of simple and inexpensive markers to the measurement of the leucocyte count in the synovial fluid may reduce the number of equivocal results which demand more expensive investigation. Cite this article: 2017;99-B:351-7.

To identify a new marker of expression of disease, independent of HFE genotype in patients with hereditary haemochromatosis (HHC), the total peripheral blood lymphocyte counts were analysed according to iron status in two groups of subjects with HFE mutations. The groups consisted of 38 homozygotes for C282Y, and 107 heterozygotes for the C282Y or compound heterozygotes for C282Y and H63D. For control purposes, totallymphocyte counts and iron status were also examined in 20 index patients with African dietary iron overload, a condition not associated with HFE mutations, and in 144 members of their families and communities. Mean lymphocyte numbers were lower in C282Y homozygous HHC index subjects with cirrhosis and higher iron stores than in those without cirrhosis and with lower iron burdens [(1.65 +/-0.43) x 10(6)/mL vs. (2.27 +/-0.49) x 10(6)/mL; p = 0.008]. Similarly, mean lymphocyte counts were significantly lower in C282Y heterozygotes and C282Y/H63D compound heterozygotes with iron overload and increased serum ferritin concentrations compared to those with normal serum ferritin concentrations (p < 0.05). Statistically significant negative correlations were found, in males, between lymphocyte counts and the total body iron stores, either in C282Y homozygous HHC patients (p = 0.031 in a multiple regression model dependent on age) and in C282Y heterozygotes or C282Y/H63D compound heterozygotes with iron overload (p = 0.029 in a simple linear model). In contrast, lymphocyte counts increased with increasing serum ferritin concentrations among the index subjects with African iron overload (r = 0.324, not statistically significant) and among the members of their families and communities (r = 0.170, p = 0.042). These results suggest that a lower peripheral blood lymphocyte count is associated with a greater degree ofiron loading in HFE haemochromatosis but not in African iron overload, and they support the notion that the lymphocyte count may serve as a marker of a non-HFE gene that influences the clinical expression of HFE haemochromatosis.

Low-density-lipoprotein cholesterol (LDL-c) guides lipid-lowering therapy, although other lipid parameters could better reflect cardiovascular disease (CVD) risk. Discordance between these parameters and LDL-c has not been evaluated in metabolic syndrome (MetS) patients. We characterized a comprehensive lipid profile in 177 MetS patients. The 2016 ESC/EAS Guidelines for the Management of Dyslipidemias were used to define LDL-c targets. The atherogenic lipoprotein profile was compared in patients with LDL-c within and above the target. Only 34.4% (61) of patients had mean LDL-c levels within the guidelines and patients with LDL-c above target presented significantly elevated levels of Apolipoprotein B (ApoB), non-high-density lipoprotein cholesterol (non-HDL-c) and oxidized LDL-c. In patients with LDL-c within target, 25%, 31% and 49% presented levels above the recommended range for ApoB, non-HDL-c and oxidized LDL-c, respectively. Patients presented a strong association of LDL-c and non-HDL-c (r = 0.796), ApoB (r = 0.749) and oxidized LDL-c (r = 0.452). Similarly, non-HDL-c was strongly correlated with ApoB (r = 0.857) and oxidized-LDL-c (r = 0.555). The logistic regression model evidenced higher triglycerides and HDL-c and lower ApoB as predictors of having LDL-c within target. Reliance solely on LDL-c could result in missed opportunities for CVD risk reduction. ApoB, oxidized LDL-c, and particularly non-HDL-c, could be valuable parameters to estimate the CVD risk of MetS patients and have the potential to be targeted therapeutically.

Background and objectives Insulin resistance has been associated with cardiovascular disease in peritoneal dialysis patients. Few studies have addressed the impact of fast transport status or dialysis prescription on insulin resistance. The aim of this study was to test whether insulin resistance is associated with obesity parameters, peritoneal transport rate, and glucose absorption.Design, setting, participants, & measurements Insulin resistance was evaluated with homeostasis model assessment method (HOMA-IR), additionally corrected by adiponectin (HOMA-AD). Enrolled patients were prevalent nondiabetics attending at Santo António Hospital Peritoneal Dialysis Unit, who were free of hospitalization or infectious events in the previous 3 months (51 patients aged 50.4615.9 years, 59% women). Leptin, adiponectin, insulin-like growth factor-binding protein 1 (IGFBP-1), and daily glucose absorption were also measured. Lean tissue index, fat tissue index (FTI), and relative fat mass (rel.FM) were assessed using multifrequency bioimpedance. Patients were categorized according to dialysate to plasma creatinine ratio at 4 hours, 3.86% peritoneal equilibration test, and obesity parameters.Results Obesity was present in 49% of patients according to rel.FM. HOMA-IR correlated better with FTI than with body mass index. Significant correlations were found in obese, but not in nonobese patients, between HOMA-IR and leptin, leptin/adiponectin ratio (LAR), and IGFBP-1. HOMA-IR correlated with HOMA-AD, but did not correlate with glucose absorption or transport rate. There were no significant differences in insulin resistance indices, glucose absorption, and body composition parameters between fast and nonfast transporters. A total of 18 patients (35.3%) who had insulin resistance presented with higher LAR and rel. FM (7.3 [12.3, interquartile range] versus 0.7 [1.4, interquartile range], P,0.001, and 39.4610.1% versus 27.2611.5%, P=0.002, respectively), lower IGFBP-1 (8.267.2 versus 21.0616.3 ng/ml, P=0.002), but similar glucose absorption and small-solute transport compared with patients without insulin resistance. FTI and LAR were independent correlates of HOMA-IR in multivariate analysis adjusted for glucose absorption and small-solute transport (r=0.82, P,0.001).Conclusions Insulin resistance in nondiabetic peritoneal dialysis patients is associated with obesity and LAR independent of glucose absorption and small-solute transport status. Fast transport status was not associated with higher likelihood of obesity or insulin resistance.