Showing papers by "Adrian Covic published in 2005"

Aortic pulse wave velocity and arterial wave reflections predict the extent and severity of coronary artery disease in chronic kidney disease patients.

Abstract: BACKGROUND Increased aortic stiffness markers - aortic pulse wave velocity (PWV) and augmentation index (AIx) - are powerful predictors of survival in ESRD patients - well-recognized for the high prevalence of coronary artery disease (CAD) and unusually high PWV and AIx. Recently, decreased aortic compliance has been shown to be predictive of primary coronary events in hypertensive patients with normal renal function. We aimed to explore relationships between arterial stiffness and CAD in cohorts of patients with chronic kidney disease (CKD). METHODS AND RESULTS 46 patients with chronic kidney disease (33 males, aged 55.7+/- 13.2 years, 20 on dialysis, 18 post renal transplantation, and 8 with glomerular filtration rate (GFR) between 10 and 25 ml/min) underwent coronary angiography for the assessment of CAD. PWV and aortic AIx were determined from pulse waveform analysis of arterial waveforms recorded by applanation tonometry using a SphygmoCortm device. The atherosclerosis burden score was calculated by adding the percentage luminal reduction of the most severe lesion in each artery. Patients with normal angiograms had significantly less arterial stiffness (as reflected by both a lower PWV=8.42+/-1.53 m/s and a lower AIx=17.9+/-5.55 %) compared with the 35 subjects with evidence of obstructive coronary disease at angiography (PWV=9.21+/-1.15 m/s and AIx=23.4+/-5.4 %, P<0.05 for both). Moreover, as more coronary vessels were affected, PWV and AIx increased proportionally. Based on receiver operating characteristics (ROC) curve analysis mean PWV levels showed an optimal cut-off point at 8.35 m/s (sensitivity=0.77; specificity=0.60), while mean AIx levels showed an optimal cut-off point at 17% (sensitivity=0.87; specificity=0.70). There was a statistically significant linear relationship between the atherosclerosis burden and both measures of arterial stiffness: PWV (r=0.31, p=0.007) and AIx (r=0.46, p=0.003). Independent predictors for the arterial stiffness parameters in this CKD population (multiple stepwise regression analysis) were age (r=0.69 for PWV and r=0.62 for AIx), and mean arterial pressure (MAP) (for AIx, p<0.0001). CONCLUSION This study provides the first direct evidence in a cross-sectional investigation that PWV and AIx are related to the extent of coronary obstruction in CKD patients.

New immunosuppressive therapies in renal transplantation: monoclonal antibodies.

Abstract: Remarkable advances in understanding the mechanisms of immune recognition and allograft rejection have been made in the past few years, leading to the development of innovative immunosuppressive strategies in the field of renal transplantation. Monoclonal antibodies (mAbs) have emerged as a new class of immunosuppressive agents, which appear to be effective (in both the treatment and the prevention of acute rejection) and well-tolerated in renal transplant recipients. The highly specific effects of these drugs make them less toxic than the oral long-term maintenance agents such as corticosteroids and the calcineurin inhibitors. Some of these mAbs have already confirmed their efficacy in preventing acute rejection in clinical phase III studies, and are now part of the well-established immunosuppressive regimens; these are the anti-CD25 mAbs (basiliximab and daclizumab). Other recently developed mAbs, like anti-CD52 (Campath-1H), anti-CD20 (rituximab), anti-LFA-1, anti-ICAM-1 and anti-tumour necrosis factor (TNF)-alpha (infliximab), are currently being tested, and show encouraging immunosuppressive potential. Blocking either the binding of cell-surface molecules or intracellular signal transduction, these mAbs could become an effective method to promote the holy grail of solid-organ transplantation, antigen-specific tolerance.

Dynamics of the circadian blood pressure profiles after renal transplantation.

Abstract: Background. Abnormalities of diurnal blood pressure (BP) rhythm (nondipping) are well-described in dialysis patients, and have prognostic importance. It is controversial whether successful renal transplantation (RTx) improves diurnal BP rhythm. To date, no study has attempted to define and model the evolution of diurnal BP rhythm profiles from dialysis to engraftment, focusing on the immediate (4-6 weeks) and medium-term (>1 year) postengraftment periods. Methods. To test if kidney transplantation normalizes the BP profile, ambulatory blood pressure monitoring (ABPM) was performed in 20 living related transplants (age, 30.3 + 5, years; 11 males, on dialysis for 25.6 months) 1 month preRTx and repeated 1 month and >1 year (ABPM 3 ) after successful RTx. Dipping was defined as a sleep-to-awake ratio >0.92 (for systolic BP) and >0.90 (for diastolic BP). Results. PreRTx only 15% patients were dippers. At 1 month postRTx (creatinine clearance, 65.8 ml/min), all patients were complete nondippers. However, after >1 year postRTx (creatinine clearance, 70.4 ml/min), 40% were now dippers. Most importantly, overall, 30% of the patients improved significantly their circadian rhythm (35.3% of the initial preRTx nondippers). Despite successful renal transplantation, 55% patients maintained unchanged their nondipping profile throughout all three ABPM recordings. The only determinants of long-term postRTx circadian rhythm are the contemporary level of the renal function and the baseline, dialysis dipping profile: SBP 3 sleep-to-awake ratio is related with serum creatinine 3 (r=0.58, P=0.001), creatinine clearance (r = -0.41, P=0.036) and SBP, sleep-to-awake ratio (r=0.48, P=0.034); similarly DBP 3 sleep-to-awake ratio is related with serum creatinine 3 (r=0.63, P=0.001), creatinine clearance (r = -0.471, P=0.036) and SBP 1 sleep-to-awake ratio (r=0.53, P=0.016). In all, 57% of the variance in dipping status can be attributed and explained by the contribution of renal function and initial circadian variability. Conclusions. Half of the nondipper dialysis patients maintain a permanently abnormal circadian rhythm, despite successful RTx. In the short term, RTx is associated with a highly abnormal diurnal profile, exclusively related to ciclosporin dose and levels. However, in the longer term, renal transplantation leads to a significant improvement of the circadian blood pressure profile, influenced by the renal function level and by the pretransplantation dipping profile.

Intradialytic changes in reflective properties of the arterial system during a single hemodialysis session.

Abstract: Increased aortic stiffness-measured as aortic augmentation index (AIx), a global stiffness marker-has emerged as a powerful predictor of survival in hemodialysis (HD). A single HD session is known to produce considerable improvement in aortic stiffness. We set out, for the first time, to examine the relative contributions to the post-HD drastic improvement in aortic stiffness of ultrafiltration rate and volume, or blood pressure (BP) changes. Aortic AIx (difference between the first and the second systolic peak of the aortic pressure waveform divided by pulse wave height) was determined hourly and recorded by applanation tonometry using a SphygmoCor device in 20 chronic HD patients (9 males, age 55.1 years). The other parameters recorded were: weight pre- and post-HD, ultrafiltration volume (UFV), hemoglobin, albumin, creatinine, urea reduction rate (URR), calcium and PTH, and BP. The dialysis significantly decreased AIx from 24.2+/-11.27% to 15.57+/-12.58% (p<0.05). In a univariate analysis, the intradialytic decrease in AIx (AIx 0-4) did not correlate with UFV, URR or with any of the biochemical markers. Significant correlations for AIx 0-4 were age (p=0.018), systolic blood pressure (SBP) at the beginning of HD (p=0.049), the intradialytic decrease in the SBP (p=0.001), and in pulse pressure (PP) (p=0.009). Multivariate stepwise regression showed that the decrease in SBP, PP, and intradialytic percentage reduction in weight explained 64.9% of the total variation in AIx 0-4. The decrease in SBP was the most important factor influencing the AIx variation (b=1.54, p=0.007). The most significant reduction in AIx was from the beginning of HD to the third hour (p=0.039), and correlated with the reduction in SBP (p=0.006) and PP (p=0.025) between the same moments. A single HD session produces a drastic improvement in aortic stiffness. The effect is not explained by the UFV depletion but is highly correlated with the decrease in SBP and PP. Further work is now needed to explore a potential role for endothelin and nitric oxide metabolism.

Cardiac troponins in renal failure - time for an optimistic consensus?

Abstract: Elevated cardiac troponin concentrations are now accepted as the gold standard biochemical markers for the diagnosis of myocardial damage in patients with unstable coronary syndromes, having also a demonstrated value in early risk stratification and in adopting different therapeutic strategies. The specificity and sensitivity of cardiac troponins for diagnosis of acute coronary diseases in renal failure have been a point of confusion over the past decade, mainly because of moderate elevations of these cardiac biomarkers, commonly observed in patients with chronic renal dysfunction and without any significant myocardial damage. This review discusses the cardiac troponins, their biochemistry, their currently accepted cut-off values and their real significance in chronic renal failure (CRF), concluding that troponins maintain their diagnostic and prognostic values in patients with CRF, being predictive not only of cardiovascular mortality but also of general mortality in this patient group.

[Descriptive epidemiologic study of nosocomial infections in "C.I. Parhon" hospital of Iaşi].

Abstract: Nosocomial infections (NI) represent a major public health problem. The descriptive study was carried out during one year, based on a lot of 12,731 in-patients from "C.I. Parhon" hospital. The objectives of the study were assessment of NI incidence and risk factors as well as monitoring resistance to antimicrobial drugs of bacterial pathogens from the hospital. The results of the study show lower NI incidence rates: 0.27%, most of them (91.5%) being urinary tract infections in the age group 65 y and over. 42.8% of cases were associated with risk factor of diabetes mellitus, neoplasm, skin or cardiovascular chronic conditions. The main etiological agent found for the NI was pseudomonas pyocyanea resistant to antibiotics. The antibiotic sensitivity analysis for the other gram negative rods illustrates gradually acquired resistance to the third or fourth generation of cephalosporins.