Ambulatory blood pressure monitoring: an essential tool for blood pressure assessment in uraemic patients.
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Blood Pressure↗
Biomedical subjects
Adrian Covic
Publications and source records attributed to Adrian Covic.
Haemodialysis increases QT(c) interval but not QT(c) dispersion in ESRD patients without manifest cardiac disease.
BACKGROUND: HD has been reported to determine an increase in QTc interval and QTc dispersion (QT(max)-QT(min))-risk factors that predispose to severe ventricular arrhythmias and sudden death. However, most studies have included end-stage renal disease (ESRD) patients with significant heart pathology. We therefore aimed to study the impact of a single HD session in subjects without manifest cardiac disease. METHODS: Sixty-eight stable, non-diabetic HD patients (47.1% males, age 40.2+/-12.7 years, HD duration 57+/-36 months and 37% hypertensive), with normal maximal ECG stress test and sub-endocardiac viability index and without ECG left ventricular hypertrophy were included. QT interval was calculated 10 min pre- and post-HD, as an average of three consecutive complexes, and corrected for heart rate using Bazett's formula (QTc=QT/(R-R)(1/2)). Na(+), K(+), Ca(2+), PO(4), pH and BP levels were also determined pre- and post-HD. RESULTS: The QTc interval increased significantly post-HD to 434+/-29 from 421+/-26 ms pre-HD (P=0.005); an abnormally prolonged QTc (>440 ms) was recorded in 34% cases pre-HD and in 46% post-HD, i.e. 1.5-2.3 times higher than in the high risk EURODIAB IDDM population. However, this effect was not homogeneous. Only 47 subjects had an increase in QTc duration after a dialysis session, while in 21 a decrease in QTc duration was recorded. The increase in QTc post-HD correlated with Ca(2+) homeostasis. Patients with greater increases in QTc after dialysis had higher baseline plasma calcium levels (r=0.47, P<0.001); also, a larger decrease in Ca(2+) post-HD correlated with higher increases in QTc interval (r=0.33, P<0.05). In contrast with QTc behaviour and with data from the literature, in this young HD population without manifest cardiac disease and with a low prevalence of HTA, post-HD QTc dispersion was similar to pre-HD values, increasing in only 39 patients. Furthermore, changes in QTc dispersion were not related to changes in electrolytes and BP following dialysis. However, changes in QTc dispersion and in QTc interval were directly correlated (r=0.37, P=0.42). There were no relationships between pre-HD measured echocardiographic variables, including: LV ejection fraction, internal diameters, wall thickness, mass and mass index and baseline or changes in QTc or QTc-d. CONCLUSIONS: Haemodialysis increases the QTc interval in ESRD patients, mainly related to rapid changes in electrolyte plasma concentrations. However, the impact on QTc dispersion is less important in the absence of significant coexisting cardiac disease.
Adult↗
How important and how treatable is vascular stiffness as a cardiovascular risk factor in renal failure?
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Cardiovascular Diseases↗
Ambulatory blood pressure monitoring in hemodialysis patients: a critique and literature review.
Ambulatory blood pressure (ABP) monitoring has been in use for nearly four decades. In that time, the advantages of using a more reproducible and accurate method to assess the true contribution of blood pressure to the cardiovascular risk profile of patients have steadily become more clearly established, balanced by the additional expense and expertise involved. In nephrology, and in particular in dialysis patients, there are significant difficulties in accurately registering truly representative blood pressure values and understanding the relationship between blood pressure, end-organ damage, and patient mortality. This arises because of the way in which hemodialysis acutely changes blood pressure values as well as the widespread abnormality of diurnal blood pressure rhythm seen in dialysis patients. Use of ABP monitoring can go some way to overcoming these obstacles. In this review we critically examine the use of ABP monitoring in the understanding of blood pressure control in dialysis patients.
Blood Pressure↗
The reproducibility of the circadian BP rhythm in treated hypertensive patients with polycystic kidney disease and mild chronic renal impairment--a prospective ABPM study.
BACKGROUND: Diurnal BP rhythm is known to be abnormal (reduced BP fall with sleep) in chronic renal failure, dialysis and renal transplantation patients. In subjects with primary hypertension and with reduced diurnal BP fall with sleep there is consistent evidence of increased target-organ damage. However, the few studies that have addressed the reproducibility of diurnal rhythm in normal or hypertensive subjects have concluded that the BP fall with sleep is poorly reproducible. It is not known whether the same is true for patients with renal disease. METHODS: In 30 subjects with autosomal polycystic kidney disease (ADPKD), mild chronic renal failure and normal office BP levels on standardised anti-hypertensive treatment, ambulatory blood pressure monitoring (ABPM) was done three times over a twelve month period to assess the reproducibility of blood pressure fall with sleep. RESULTS: When comparing ABPM 2 with the ABPM 1 recording (3 months difference between measurements) only 43.3% of the patients maintained the initial dipping category (defined by quartiles of the ABPM 1 diurnal BP distribution). The same proportion of subjects had a similar dipping category, when ABPM 3 was compared to ABPM 1 (9 months difference between measurements), but a large (24%) subset of patients had dramatic shifts in their amplitude in nocturnal BP fall, significantly greater than those recorded after a shorter inter-measurement interval. Equally important, our study reveals the fact that, with time, there is no tendency to decrease circadian variation: a similar proportion (a quarter to one third) of patients increased or decreased their amplitude in nocturnal BP fall, at 3 and 9 months. When several ABPM measurements are repeated for the same patients, the repeatability is even worse, since only 36.6% of our study population maintained the initial dipping category across all three ABPM determinations (ABPM 1 and ABPM 2 and ABPM 3). CONCLUSIONS: There is a widespread abnormality in diurnal BP rhythm in ADPKD patients with renal impairment, but the extent of this abnormality varies considerably over time. It is too simplistic to assume that, having arbitrarily categorised subjects into "dippers" or "non-dippers", these labels will always be valid. Thus, it would be unwise to extrapolate the impact of a single baseline circadian BP profile on organ target end points.
Antihypertensive Agents↗
The challenge of cardiovascular risk factors in end-stage renal disease.
Due to the impressive cardiovascular (CV) morbidity and mortality in uremic patients, assessment of CV risk factors in the dialysis population is a crucial challenge in nephrology. Cardiovascular risk factors in dialysis patients may have a different significance in ESRD patients compared to the general population. The Framingham risk equation seems not to be valid in chronic uremia. Furthermore, new powerful outcome predictors have emerged in recent years: pulse pressure, dipping status, pulse wave velocity, augmentation index. The concept of "U"-shaped association between blood pressure (as well as cholesterolemia) and mortality are extensively discussed. The authors are focusing on the value of office and ambulatory blood pressure measurements in the uremic population. An extensive evaluation of blood pressure and vascular compliance in dialysis patients is proposed. Efficient dialysis, ACE-inhibitors and beta-blockers, statins, antiplatelet treatment and adequate control of calcium-phosphorus metabolism should be the mainstay of therapy in the ESRD patients with several CV risk factors.
Adult↗
The influence of dialytic modality on arterial stiffness, pulse wave reflections, and vasomotor function.
BACKGROUND: Measurements of aortic stiffness [aortic pulse wave velocity (PWV) and augmentation index (Alx)] have been established as powerful predictors of survival on hemodialysis (HD). Abnormal endothelial-dependent and endothelial-independent vascular reactivity and increased arterial stiffness are commonly described in HD patients. There is, however, a lack of information on the comparative impact of different renal replacement therapies (RRTs) on PWV and Alx, and how these different methods might influence endothelial-dependent abnormal vasodilatation. OBJECTIVE: To describe in a cross-sectional design arterial compliance and distensibility in continuous ambulatory peritoneal dialysis (CAPD) versus HD versus renal transplant (RTx) patients, compared with age- and blood pressure-matched essential hypertensive controls. The PWV and aortic Alx were determined from contour analysis of arterial waveforms recorded by applanation tonometry in 40 CAPD, 41 HD, 20 RTx patients (with normal serum creatinine), and 20 controls with essential hypertension (all normotensive under treatment). Endothelial-dependent and endothelial-independent vascular reactivities were assessed by changes in Alx following challenges with inhaled salbutamol and sublingual nitroglycerin respectively. RESULTS: CAPD patients had significantly stiffer arteries than all other categories. The PWV was 8.29 +/- 1.09 m/ second in CAPD patients, significantly higher (p < 0.05) compared to HD subjects (7.19 +/- 1.87 m/s). Both dialysis subgroups had significantly higher PWV values compared to RTx patients (6.59 +/- 1.62 m/s) and essential hypertensive controls (6.34 +/- 1.32 m/s), p < 0.05. The Alx had a profile similar to PWV in different RRTs. All groups with the exception of CAPD subjects had a significant decrease in Alx following salbutamol. Moreover, the vasodilatation induced by either nitroglycerin or salbutamol was significantly blunted compared to HD. Overall, both dialysis categories had more abnormal responses compared to RTx patients and essential hypertensive controls. CONCLUSION: CAPD is associated with stiffer arteries and more profoundly abnormal endothelial-dependent vasomotor function, compared to matched HD subjects. These differences in arterial physical properties might explain differences seen in cardiac structure and function between the RRTs.
Adult↗
What is the role of ambulatory BP monitoring in pediatric nephrology?
Ambulatory blood pressure monitoring (ABPM) has been developed to overcome recognized deficiencies and inaccuracies of classic (office) BP measurements in the diagnosis and management of hypertension (HTN). Although in adults it has become a valuable tool for the diagnosis and ongoing management of HTN, and its use has been documented in over 50 studies in children, few pediatric nephrologists systematically use this approach for HTN assessment. Some of the reluctance to completely embrace the technique comes from the fact that none of the major hypertension trials has been based on ambulatory BP readings. The prognostic information from ABPM studies is slowly accumulating, but there is still relatively little information on the long-term prognostic value of ABPM-derived readings. For children there are particular problems in measuring representative BP values. It would be very helpful to know to what extent ABPM can help. However, there have been few comprehensive reviews in this particular population, which leaves the practicing nephrologist rather confused. The purpose of this review is to assess the present state of knowledge of ABPM usage in children, high-lighting important studies that help to delineate the place of ABPM in their medical management. We discuss: advantages and limitations of ABPM, the variability of blood pressure in children, clinical uses of ABPM in pre-dialysis renal failure, dialysis, renal transplantation, primary renal diseases, and diabetes, comparison with adult data. The relationship between casual BP (CBP) and ABPM is presented, specifically the prevalence and relevance of either white-coat hypertension or relative 'office' hypertension. We conclude that in 2004, the sole reliance on casual BP to diagnose and to treat hypertension in children brings with it many difficulties. ABPM offers some clear solutions to these problems and thus should be routinely used in appropriately defined clinical settings, but is not a panacea.
Adolescent↗
[Risk of sudden death in patients with chronic renal failure and hemodialysis].
Cardiovascular mortality in uremic patients treated by hemodialysis overrates ten times cardiovascular mortality in general population. Approximatively 40% of patients on iterative hemodialysis die from cardiac diseases, half of cases by sudden death. Several risk factors for sudden death are well known: QTc interval prolongation, decrease of RR interval <750 msec, decrease of heart rate variability, presence of late ventricular potentials (LVP), presence of high risk ventricular extrasystoles, decrease of ejection fraction (EF) <40 %, presence of left ventricular hypertrophy. Our study evaluated the above-mentioned risk factors for sudden death in patients with chronic renal failure on hemodialysis. We studied 37 patients, 22 males and 15 females, with mean age of 42 years old, without diabetes, heart failure and arrhythmias, without myocardial ischemia on ECG, being on hemodialysis (HD) programme for minimum 1 year (HD parameters are: 4 h x 3/week, qB = 300 ml/min, buffer = bicarbonate, Ca dialysate = 1.75 mmol/l, K dialysate = 2.1 mmol/l, conductivity = 135 mS). The patients were evaluated by echocardiography, standard and Holter ECG. Statistics evaluation was performed in SPSS v.9.0. Program. The results proved that 80% of patients on HD have risk factors for sudden death, which are closely related with age and hyperhydration. Statistics proved that presence of high-risk arrhythmias is connected with heart rate variability and prolongation of QTc interval (favored by HD). 50% of our patients have 2 to 4 risk factors for sudden death, which increase incidence of sudden death in patients on HD.
Adult↗
New immunosuppressive therapies in renal transplantation: monoclonal antibodies.
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.
Antibodies, Monoclonal↗
The success story of peritoneal dialysis in Romania: analysis of differences in mortality by dialysis modality and influence of risk factors in a national cohort.
BACKGROUND: This report describes the status of renal replacement therapy (RRT), particularly continuous ambulatory peritoneal dialysis (CAPD), in Romania (a country with previously limited facilities), outlines the fast development rate of CAPD, and presents national changes in a European context. METHODS: Trends in the development of RRT were analyzed in 2003 on a national basis using annual center questionnaires from 1995 to 2003. Survival data and prognostic risk factors were calculated retrospectively from a representative sample of 2284 patients starting RRT between 1 January 1995 and 31 December 2001 (44% of the total RRT population investigated). RESULTS: The annual rate of increase in the number of RRT patients (11%) was supported mainly by an exponential development of the CAPD population (+600%); the hemodialysis (HD) growth rate was stable (+33%) and renal transplantation had a marginal contribution. The characteristics of both HD and PD incident patients changed according to current European epidemiology (increasing age and prevalence of diabetes and nephroangiosclerosis). There were significant differences between PD and HD incident populations, PD patients being significantly older and having a higher prevalence of diabetic nephropathy and baseline comorbidities, probably reflecting different inclusion policies. The estimated overall survival of RRT patients in Romania was 90.6% at 1 year [confidence interval (CI) 89.4 - 91.8] and 62.2% at 5 years (CI 59.4 - 65.0). The initial treatment modality did not significantly influence patients' survival. There was no difference in unadjusted technique survival during the first 2 years; afterwards, there was a clear advantage for HD, with more patients being transferred from PD to HD. Several factors seemed to significantly and negatively influence PD patients' survival (Cox regression analysis): male gender, lack of predialysis erythropoietin treatment, and initial comorbidities. Stratified analysis to discover the influence of these factors on patients' survival revealed that HD was associated with an increased risk of death in the younger nondiabetic end-stage renal disease population, regardless of other coexisting comorbid conditions. However, in older patients (>65 years) and in diabetics, regardless of the presence or absence of associated comorbid conditions, there was no significant difference in death rates between HD and PD patients. CONCLUSIONS: We report an impressive quantitative and qualitative development of CAPD in one of the rapidly growing Central and Eastern Europe countries. CAPD should be the method of choice for young nondiabetic end-stage renal disease patients. Improvement in predialysis nephrologic care and in transplantation rates is required to further ensure the ultimate success of the Romanian PD program.
Adolescent↗
Serial echocardiographic changes in patients on hemodialysis: an evaluation of guideline implementation.
BACKGROUND: Few studies have addressed the description of serial changes in left ventricular mass (LVM) and relevant risk factors. All these studies were initiated before the implementation of EBPG or K/DOQI guidelines. The aims of our study were to prospectively describe trends in left ventricular (LV) structure and function, evaluate risk factors for progression of LVM derived from serial echocardiographic measurements starting January 2003, 6 months after full implementation of EBPG in our unit. METHODS: One hundred seventy-six patients were enrolled at baseline, between 1 January 2003 and 1 October 2004; 33 patients were excluded from analysis due to poor echocardiographic window, 14 patients died and 26 were transplanted or transferred during the follow-up period of minimum 12 months. One hundred and three patients were included in the final analysis (mean age 51 years, mean follow-up 24.1 +/- 14.4 months). Echocardiography was performed at inclusion and at the end of study. Biochemical, blood pressure (BP) and medication data were collected and the means of monthly values were used. RESULTS: At baseline, 86.4% of the patients had left ventricular hypertrophy (LVH) (56.3% concentric hypertrophy, 30.1% eccentric hypertrophy, 6.8% concentric remodeling and only 6.8% normal LV geometry), 25.6% had systolic dy-sfunction and 50.5% had abnormal LV volume index (LVVI). Similar data were recorded at follow-up (82.5%, 44.7%, 37.9%, 7.7%, 9.7%, and 19.5%, respectively). Baseline left ventricular mass index (LVMI) significantly correlated with hemoglobin (Hb) and total protein level. LVMI at follow-up correlated to Hb, SBP, PP, mean level of serum phosphate, calcium x phosphate product and cholesterol. Independent predictors for LVMI (multiple regressions) were anemia and mineral metabolism markers. In our population, 62.1% of the patients had a regression of LVMI, with a mean decrease in LVMI of 12 g/m 2 (1.7 +/- 11.7 g/m 2 /month) over more than 12 months of guideline implementation. Regressors had a significant improvement of anemia, serum phosphate level and calcium x phosphate product (p<0.05). CONCLUSION: Our study suggests that a holistic interventional approach, targeting various pathogenic mechanisms, as per guidelines, can elicit at least a partial regression in LV structural and functional abnormalities in hemodialysis patients.
Echocardiography↗
Analysis of safety and efficacy of pegylated-interferon alpha-2a in hepatitis C virus positive hemodialysis patients: results from a large, multicenter audit.
BACKGROUND: Hepatitis C virus (HCV) infection rates are still high in hemodialysis (HD) centers in developing countries. Standard interferon (IFN) monotherapy is associated with good results in HCV-positive patients (more than 30% rate of sustained virological response) but with poor tolerance. Pegylated interferon (PEG-IFN) is better tolerated and has a more sustained antiviral effect in the general population. There have been no large trials to date with PEG-IFN in hemodialysis populations. METHODS: We report the largest series to date of HCV+ HD patients (n=78) treated with PEG-IFN alfa -2a 135 microg s.c. weekly monotherapy. The primary outcomes were (a) efficacy - assessed by the viral response at 12, 48 weeks and 6 months after completion of therapy, and (b) rate of serious adverse events. RESULTS: In 48/78 (61.5%) patients an early (12 weeks) viral response was obtained. Viral end-of-treatment response (ETR) was evaluated in the 21 patients (26.9%) who reached week 48 on therapy: only 15 subjects (19.2% of the initial population) had undetectable HCV-RNA levels. In these 15 patients, a sustained viral response (SVR) was recorded in 11 - i.e. 14.1% of the initial intention-to-treat (ITT) population. A high prevalence of noncompliance (32%) and of adverse events (83%) was recorded; minor adverse effects (flu-like syndrome, mild-to-moderate thrombocytopenia, leukopenia and anemia) responded to symptomatic therapy or dose reduction, but often caused lack of compliance. The incidence rate of serious adverse events was 0.19/patient-year (median time to event 20.5 weeks), and incidence of deaths was 0.11/patient-year. CONCLUSIONS: In dialysis patients, PEG-IFN alfa -2a is poorly tolerated and associated with a high number of serious adverse events, causing a significant lack of compliance/discontinuation of therapy. In this largest HCV-positive hemodialysis population survey, we report a low sustained viral response in an ITT analysis, compared with previously published historical data using non-PEG-IFN, a low compliance rate and an unsatisfactory overall safety profile, not supporting the superiority of PEG-IFN monotherapy.
Adolescent↗