Impact of acute versus repetitive moderate intensity endurance exercise on kidney injury markers.

Exercise may lead to kidney injury through several mechanisms. Urinary Kidney Injury Molecule-1 (uKIM1) and Neutrophil Gelatinase-Associated Lipocalin (uNGAL) are known biomarkers for acute kidney injury, but their response to repetitive exercise remains unknown. We examined the effects of a single versus repetitive bouts of exercise on markers for kidney injury in a middle-aged population. Sixty subjects (aged 29-78 years, 50% male) were included and walked 30, 40 or 50 km for three consecutive days. At baseline and after exercise day 1 and 3, a urine sample was collected to determine uNGAL and uKIM1. Furthermore, urinary cystatin C, creatinine, and osmolality were used to correct for dehydration-related changes in urinary concentration. Baseline uNGAL was 9.2 (5.2-14.7) ng/mL and increased to 20.7 (11.0-37.2) ng/mL and 14.2(8.0-26.3) ng/mL after day 1 and day 3, respectively, (P ≤ 0.001). Baseline uKIM1 concentration was 2.6 (1.4-6.0) ng/mL and increased to 5.2 (2.4-9.1) ng/mL (P = 0.002) after day 1, whereas uKIM1 was not different from baseline at day 3 (2.9 [1.4-6.4] ng/mL (P = 0.52)). Furthermore, both uNGAL and uKIM1 levels were higher after day 1 compared to day 3 (P < 0.01). When corrected for urinary cystatin C, creatinine, and osmolality, uNGAL demonstrated a similar response compared to the uncorrected data, whereas differences in uKIM1 between baseline, day 1 and day 3 (Ptime = 0.63) were no longer observed for cystatin C and creatinine corrected data. A single bout of prolonged exercise significantly increased uNGAL concentration, whereas no changes in uKIM1 were found. Repetitive bouts of exercise show that there is no cumulative effect of kidney injury markers

Diagnostic and Prognostic Utility of Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Patients with Cardiovascular Diseases - Review

NGAL (neutrophil gelatinase-associated lipocalin) is an acute phase protein, participating in antibacterial immunity. NGAL forms a complex with metalloproteinase 9 (MMP-9), thereby increasing its activity and preventing its degradation. NGAL is freely filtered through the glomerular membrane and reabsorbed by endocytosis in the proximal tubule. NGAL detected in urine is produced mainly in the distal nephron. Elevated serum and urine NGAL allows diagnosis of acute kidney injury approximately 24 hours earlier than plasma creatinine concentration. Increased levels of NGAL were detected in patients with acute myocardial infarction, heart failure or stroke and were demonstrated to be strong predictors of adverse prognosis

Problems with Bazett QTc correction in paediatric screening of prolonged QTc interval

Background Bazett formula is frequently used in paediatric screening for the long QT syndrome (LQTS) and proposals exist that using standing rather than supine electrocardiograms (ECG) improves the sensitivity of LQTS diagnosis. Nevertheless, compared to adults, children have higher heart rates (especially during postural provocations) and Bazett correction is also known to lead to artificially prolonged QTc values at increased heart rates. This study assessed the incidence of erroneously increased QTc values in normal children without QT abnormalities. Methods Continuous 12-lead ECGs were recorded in 332 healthy children (166 girls) aged 10.7 ± 2.6 years while they performed postural manoeuvring consisting of episodes (in the following order) of supine, sitting, standing, supine, standing, sitting, and supine positions, each lasting 10 min. Detailed analyses of QT/RR profiles confirmed the absence of prolonged individually corrected QTc interval in each child. Heart rate and QT intervals were measured in 10-s ECG segments and in each segment, QTc intervals were obtained using Bazett, Fridericia, and Framingham formulas. In each child, the heart rates and QTc values obtained during supine, sitting and standing positions were averaged. QTc durations by the three formulas were classified to  480 ms. Results At supine position, averaged heart rate was 77.5 ± 10.5 beat per minute (bpm) and Bazett, Fridericia and Framingham QTc intervals were 425.3 ± 15.8, 407.8 ± 13.9, and 408.2 ± 13.1 ms, respectively. At sitting and standing, averaged heart rate increased to 90.9 ± 10.1 and 100.9 ± 10.5 bpm, respectively. While Fridericia and Framingham formulas showed only minimal QTc changes, Bazett correction led to QTc increases to 435 ± 15.1 and 444.9 ± 15.9 ms at sitting and standing, respectively. At sitting, Bazett correction identified 51, 4, and 0 children as having the QTc intervals 440–460, 460–480, and > 480 ms, respectively. At sitting, these numbers increased to 118, 11, and 1, while on standing these numbers were 151, 45, and 5, respectively. Irrespective of the postural position, Fridericia and Framingham formulas identified only a small number (< 7) of children with QT interval between 440 and 460 ms and no children with longer QTc. Conclusion During screening for LQTS in children, the use of Bazett formula leads to a high number of false positive cases especially if the heart rates are increased (e.g. by postural manoeuvring). The use of Fridericia formula can be recommended to replace the Bazett correction not only for adult but also for paediatric ECGs

Kinetics of Biomarkers of Oxidative Stress in Septic Shock: A Pilot Study

Septic shock is a major cause of mortality in ICU patients, its pathophysiology is complex and not properly understood. Oxidative stress seems to be one of the most important mechanisms of shock progression to multiple organ failure. In the present pilot study, we have analysed eight oxidative-stress-related biomarkers in seven consecutive time points (i.e., the first seven days) in 21 septic shock patients admitted to the ICU. Our objective was to describe the kinetics of four biomarkers related to pro-oxidative processes (nitrite/nitrate, malondialdehyde, 8-oxo-2′-deoxyguanosine, soluble endoglin) compared to four biomarkers of antioxidant processes (the ferric reducing ability of plasma, superoxide dismutase, asymmetric dimethylarginine, mid-regional pro-adrenomedullin) and four inflammatory biomarkers (CRP, IL-6, IL-10 and neopterin). Furthermore, we analysed each biomarker’s ability to predict mortality at the time of admission and 12 h after admission. Although a small number of study subjects were recruited, we have identified four promising molecules for further investigation: soluble endoglin, superoxide dismutase, asymmetric dimethylarginine and neopterin

Kinetics of Biomarkers of Oxidative Stress in Septic Shock: A Pilot Study

Septic shock is a major cause of mortality in ICU patients, its pathophysiology is complex and not properly understood. Oxidative stress seems to be one of the most important mechanisms of shock progression to multiple organ failure. In the present pilot study, we have analysed eight oxidative-stress-related biomarkers in seven consecutive time points (i.e., the first seven days) in 21 septic shock patients admitted to the ICU. Our objective was to describe the kinetics of four biomarkers related to pro-oxidative processes (nitrite/nitrate, malondialdehyde, 8-oxo-2&prime;-deoxyguanosine, soluble endoglin) compared to four biomarkers of antioxidant processes (the ferric reducing ability of plasma, superoxide dismutase, asymmetric dimethylarginine, mid-regional pro-adrenomedullin) and four inflammatory biomarkers (CRP, IL-6, IL-10 and neopterin). Furthermore, we analysed each biomarker&rsquo;s ability to predict mortality at the time of admission and 12 h after admission. Although a small number of study subjects were recruited, we have identified four promising molecules for further investigation: soluble endoglin, superoxide dismutase, asymmetric dimethylarginine and neopterin

Infectious Complications and Immune/Inflammatory Response in Cardiogenic Shock Patients: A Prospective Observational Study.

IntroductionPatients with cardiogenic shock (CS) are at a high risk of developing infectious complications; however, their early detection is difficult, mainly due to a frequently occurring noninfectious inflammatory response, which accompanies an extensive myocardial infarction (MI) or a postcardiac arrest syndrome. The goal of our prospective study was to describe infectious complications in CS and the immune/inflammatory response based on a serial measurement of several blood-based inflammatory biomarkers.MethodsEighty patients with CS were evaluated and their infections were monitored. Inflammatory markers (C-reactive protein, procalcitonin, pentraxin 3, presepsin) were measured seven times per week. The control groups consisted of 11 patients with ST segment elevation myocardial infarction without CS and without infection, and 22 patients in septic shock.ResultsInfection was diagnosed in 46.3% of patients with CS; 16 patients developed an infection within 48 h. Respiratory infection was most common, occurring in 33 out of 37 patients. Infection was a significant or even the main reason of death only in 3.8% of all patients with CS, and we did not find statistically significant difference in 3-month mortality between group of patients with CS with and without infection. There was no statistically significant prolongation of the duration of mechanical ventilation associated with infection. Strong inflammatory response is often in patients with CS due to MI, but we found no significant difference in the course of the inflammatory response expressed by evaluated biomarkers in patients with CS with and without infection. We found a strong relationship between the elevated inflammatory markers (sampled at 12 h) and the 3-month mortality: the area under the curve of receiver operating characteristic ranged between 0.683 and 0.875.ConclusionThe prevalence of infection in patients with CS was 46.3%, and respiratory tract infections were the most common type. Infections did not prolong statistically significantly the duration of mechanical ventilation and did not increase the prevalence of hospital mortality in this high-risk CS population. CS due to acute myocardial infarction was accompanied by a strong and highly variable inflammatory response, but it did not reach the intensity of the inflammatory response observed in patients with septic shock. An extensive immune/inflammatory response in patients with CS is linked to a poor prognosis