Ewa Wieczorek-Surdacka

Effect of a hemodialysis session on plasma levels of endothelin-1 in hypertensive and normotensive subjects with end-stage renal failure.

Background: Elevated plasma endothelin-1 (ET-1) was found in end-stage renal failure (ESRF). However, there are discordant reports on the influence of hypertension on plasma ET-1 in ESRF and on the effect of hemodialysis on ET-1 concentrations. Aim: To compare the time course of plasma ET-1 during hemodialysis in hypertensive (HT) and normotensive (NT) ESRF patients. Methods: Plasma ET-1 and mean blood pressure (MP) were measured in 12 HT patients and 11 matched NT patients on maintenance hemodialysis at baseline (B), after a 2.5–3.5 h hemodialysis with ultrafiltration (P1) and after a subsequent 1 h isovolumic dialysis (P2). Results: In HT patients, plasma ET-1 increased at P1 with no further change after P2 (B vs. P1 and P2, p < 0.05). In NT patients, ET-1 levels were similar at B, P1 and P2. In HT, but not in NT subjects, volume loss correlated with change of ET-1 at P1. In HT patients, MP fell during P1 and tended to return towards baseline at P2. In NT patients, MP dropped after P1 and remained lower also at P2. Conclusion: Hypertensive ESRF subjects exhibit potentiated ET-1 release on hemodialysis, possibly stimulated by volume depletion with sympathetic activation, which may attenuate hypotensive hemodialysis effects thus contributing to hypertension in ESRF.

Effects of Atorvastatin Dose and Concomitant Use of Angiotensin-Converting Enzyme Inhibitors on Renal Function Changes over Time in Patients with Stable Coronary Artery Disease: A Prospective Observational Study

Angiotensin-converting enzyme inhibitors (ACEI) and statins are widely used in patients with coronary artery disease (CAD). Our aim was to compare changes in glomerular filtration rate (GFR) over time in subjects with stable CAD according to atorvastatin dose and concomitant use of ACEI. We studied 78 men with stable CAD referred for an elective coronary angiography who attained the then-current guideline-recommended target level of low-density lipoproteins (LDL) cholesterol below 2.5 mmol/L in a routine fasting lipid panel on admission and were receiving atorvastatin at a daily dose of 10–40 mg for ≥3 months preceding the index hospitalization. Due to an observational study design, atorvastatin dosage was not intentionally modified for other reasons. GFR was estimated during index hospitalization and at about one year after discharge from our center. Irrespective of ACEI use, a prevention of kidney function loss was observed only in those treated with the highest atorvastatin dose. In 38 subjects on ACEI, both of the higher atorvastatin doses were associated with increasing beneficial effects on GFR changes (mean ± SEM: −4.2 ± 2.4, 1.1 ± 1.6, 5.2 ± 2.4 mL/min per 1.73 m2 for the 10-mg, 20-mg and 40-mg atorvastatin group, respectively, p = 0.02 by ANOVA; Spearman’s rho = 0.50, p = 0.001 for trend). In sharp contrast, in 40 patients without ACEI, no significant trend effect was observed across increasing atorvastatin dosage (respective GFR changes: −1.3 ± 1.0, −4.7 ± 2.1, 4.8 ± 3.6 mL/min per 1.73 m2, p = 0.02 by ANOVA; rho = 0.08, p = 0.6 for trend). The results were substantially unchanged after adjustment for baseline GFR or time-dependent variations of LDL cholesterol. Thus, concomitant ACEI use appears to facilitate the ability of increasing atorvastatin doses to beneficially modulate time-dependent changes in GFR in men with stable CAD.

Clinical Correlates and Prognostic Value of Plasma Galectin-3 Levels in Degenerative Aortic Stenosis: A Single-Center Prospective Study of Patients Referred for Invasive Treatment

Galectin-3 (Gal-3), a β-galactoside-binding lectin, has been implicated in myocardial fibrosis, development of left ventricular (LV) dysfunction and transition from compensated LV hypertrophy to overt heart failure (HF), being a novel prognostic marker in HF. Risk stratification is crucial for the choice of the optimal therapy in degenerative aortic stenosis (AS), affecting elderly subjects with coexistent diseases. Our aim was to assess correlates and prognostic value of circulating Gal-3 in real-world patients with degenerative AS referred for invasive treatment. Gal-3 levels were measured at admission in 80 consecutive patients with symptomatic degenerative AS (mean age: 79 ± 8 years; aortic valve area (AVA) index: 0.4 ± 0.1 cm2/m2). The therapeutic strategy was chosen following a dedicated multidisciplinary team-oriented approach, including surgical valve replacement (n = 11), transcatheter valve implantation (n = 19), balloon aortic valvuloplasty (BAV) (n = 25) and optimal medical therapy (n = 25). Besides routine echocardiographic indices, valvulo-arterial impedance (Zva), an index of global LV afterload, was computed. There were 22 deaths over a median follow-up of 523 days. Baseline Gal-3 correlated negatively with estimated glomerular filtration rate (eGFR) (r = −0.61, p < 0.001) and was unrelated to age, symptomatic status, AVA index, LV ejection fraction, LV mass index or Zva. For the study group as a whole, Gal-3 tended to predict mortality (Gal-3 >17.8 vs. Gal-3 <17.8 ng/mL; hazard ratio (HR): 2.03 (95% confidence interval, 0.88–4.69), p = 0.09), which was abolished upon adjustment for eGFR (HR: 1.70 (0.61–4.73), p = 0.3). However, in post-BAV patients multivariate-adjusted pre-procedural Gal-3 was associated with worse survival (HR: 7.41 (1.52–36.1), p = 0.01) regardless of eGFR. In conclusion, the inverse eGFR–Gal-3 relationship underlies a weak association between Gal-3 and adverse outcome in patients with degenerative AS referred for invasive therapy irrespective of type of treatment employed. In contrast, pre-procedural Gal-3 appears an independent mortality predictor in high-risk AS patients undergoing BAV.

Serum uromodulin concentrations correlate with glomerular filtration rate in patients with chronic kidney disease

INTRODUCTION Urinary uromodulin excretion has been associated with kidney diseases. However, serum uromodulin concentrations have not been extensively studied in patients with chronic kidney disease (CKD), and the results of published studies are inconsistent. OBJECTIVES The aims of the study were to evaluate serum uromodulin concentrations in patients with CKD and to assess the utility of serum uromodulin measurements for diagnosing CKD stages. PATIENTS AND METHODS This observational study included 170 patients with CKD stages 1 to 5, not treated by renal replacement therapy, and 30 healthy individuals. The serum levels of creatinine, cystatin C, and uromodulin were measured, and estimated glomerular filtration rate (eGFR) was calculated according to the 2012 CKD Epidemiology Collaboration cystatin‑creatinine equation. RESULTS Among patients with CKD, serum uromodulin concentrations were significantly lower than in controls, and were strongly negatively correlated with renal retention markers (ie, serum creatinine and cystatin C) and strongly positively correlated with eGFR. An inverse, hyperbolic relationship between serum creatinine and uromodulin levels was analogous to the well‑known association between serum creatinine concentrations and eGFR. A receiver‑operating characteristic curve analysis showed a high diagnostic accuracy of the measurement of serum uromodulin concentrations in the assessment of CKD stages. CONCLUSIONS Serum uromodulin concentrations are closely correlated with eGFR, which is the recommended measure of renal function. As uromodulin is produced exclusively by renal tubular cells, the assessment of uromodulin levels in patients with CKD may be an alternative method for evaluating the number of functioning nephrons.

No Association of Proton Pump Inhibitor Use with Fasting or Postload Glycaemia in Patients with Cardiovascular Disease: A Cross-Sectional Retrospective Study

Background: Proton pump inhibitor (PPI) use was reportedly associated with an excess of adverse cardiovascular (CV) events, thus making their systemic effects relevant to public health. PPIs reduce gastric acid secretion, causing increased gastrin release. Gastrin stimulates β-cell neogenesis and enhances insulin release, exerting an incretin-like effect. Our aim was to assess, if PPI usage is associated with altered glycaemia in patients with CV disease. Methods: We retrospectively analyzed medical records of 102 subjects (80 with ischemic heart disease) who underwent a routine oral glucose tolerance test while hospitalized in a cardiology department. Fasting and 2-h postload glucose levels were compared according to PPI use for ≥1 month prior to admission. Results: Compared to 51 subjects without PPIs, those on a PPI were older, more frequently male, had a lower body-mass index and a tendency to a worse renal function. PPI users and non-users exhibited similar glucose levels at baseline (5.6 ± 0.9 vs. 5.5 ± 1.1 mmol/l, P = 0.5) and 2-hrs post glucose intake (9.8 ± 3.0 vs. 9.9 ± 3.4 mmol/l, P = 0.9). This was consistent across subgroups stratified by gender or diabetes status. The results were substantially unchanged after adjustment for different characteristics of subjects with and without PPIs. Conclusions: PPI use does not appear associated with altered glycaemia in subjects with CV disease. Unchanged glucose tolerance despite PPI usage may result from simultaneous activation of pathways that counteract the putative PPI-induced incretin-like effect.

How does preclinical laboratory training impact physical examination skills during the first clinical year? A retrospective analysis of routinely collected objective structured clinical examination scores among the first two matriculating classes of a reformed curriculum in one Polish medical school

Objective As a result of a curriculum reform launched in 2012 at our institution, preclinical training was shortened to 2 years instead of the traditional 3 years, creating additional incentives to optimise teaching methods. In accordance with the new curriculum, a semester-long preclinical module of clinical skills (CS) laboratory training takes place in the second year of study, while an introductory clinical course (ie, brief introductory clerkships) is scheduled for the Fall semester of the third year. Objective structured clinical examinations (OSCEs) are carried out at the conclusion of both the preclinical module and the introductory clinical course. Our aim was to compare the scores at physical examination stations between the first and second matriculating classes of a newly reformed curriculum on preclinical second-year OSCEs and early clinical third-year OSCEs. Design Analysis of routinely collected data. Setting One Polish medical school. Participants Complete OSCE records for 462 second-year students and 445 third-year students. Outcome measures OSCE scores by matriculation year. Results In comparison to the first class of the newly reformed curriculum, significantly higher (ie, better) OSCE scores were observed for those students who matriculated in 2013, a year after implementing the reformed curriculum. This finding was consistent for both second-year and third-year cohorts. Additionally, the magnitude of the improvement in median third-year OSCE scores was proportional to the corresponding advancement in preceding second-year preclinical OSCE scores for each of two different sets of physical examination tasks. In contrast, no significant difference was noted between the academic years in the ability to interpret laboratory data or ECG — tasks which had not been included in the second-year preclinical training. Conclusion Our results suggest the importance of preclinical training in a CS laboratory to improve students’ competence in physical examination at the completion of introductory clinical clerkships during the first clinical year.

Letter by Kruszelnicka et al regarding article, "evidence that links loss of cyclooxygenase-2 with increased asymmetric dimethylarginine: novel explanation of cardiovascular side effects associated with anti-inflammatory drugs".

Ahmetaj-Shala et al1 elegantly demonstrated that cyclooxygenase-2 deletion affected pathways governing the metabolism of the endogenous nitric oxide synthase inhibitor asymmetrical dimethylarginine (ADMA). This mechanism was proposed as an explanation for ≈20% ADMA rises in healthy volunteers taking the selective cyclooxygenase-2 antagonist celecoxib or the nonselective nonsteroidal anti-inflammatory drug (NSAID) naproxen,1 whose magnitude was similar to ADMA elevations in rheumatoid arthritis, first …

Endothelial and red blood cell turnover rate—factors possibly affecting circulating ADMA levels?

Sir, The interesting reports by Desai and co-workers [1] and Billecke and associates [2] have attracted our great attention. First, in endothelial cells supraphysiological concentrations of recombinant human erythropoietin (EPO) dosedependently decreased asymmetric dimethyl-L-arginine (ADMA) generation and stimulated the expression of dimethylarginine dimethylaminohydrolase type II (DDAHII), an enzyme decomposing ADMA, but not symmetric dimethyl-L-arginine (SDMA) [1]. This clearly contrasts with the opposite results by Scalera et al. [3] who had described EPO-mediated ADMA elevations and lowering of DDAH-II activity under similar conditions. Second, as acknowledged by Desai et al. [1], their shortterm (24-h) EPO effects are difficult to reconcile with serum ADMA elevations by 46% with unchanged SDMA despite concomitant upregulation of DDAH-I, the predominant DDAH isoform in the kidney and the liver, after EPO administration for 10 weeks in mice. Due to a simultaneous rise in haematocrit by 45%, red cell proteins with incorporated ADMA residues were proposed as a potential source of the EPO-induced ADMA accumulation [1]. However, this mechanism is unable to explain increased plasma ADMA in renal patients 7 days after initiation of EPO therapy, i.e. before a rise in erythrocyte counts [3]. Therefore, we would like to suggest that the recently reported EPO-induced acceleration of progenitor cellmediated endothelial turnover [4] might contribute to EPOdependent ADMA elevations as free ADMA is liberated during proteolysis, including that accompanying apoptosis. Importantly, the whole-body protein turnover rate determined ADMA levels in ageing and obesity [5]. Additionally, a similar mechanism might occur at accelerated erythropoiesis, usually associated with potentiated erythrocyte destruction. Furthermore, the importance of erythrocytes as a reservoir of protein-bound ADMA was suggested by Billecke et al. [2] who observed a positive correlation between proteolysis rate and gradual ADMA accumulation during 5-h incubations of lysed whole blood supernatants at 37◦C.