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Biomedical subjects

David J A Goldsmith

Publications and source records attributed to David J A Goldsmith.

At least 19 recordsLinked to original sources
PubMed2006

Arterial wave reflections and mortality in haemodialysis patients--only relevant in elderly, cardiovascularly compromised?

BACKGROUND: Chronic kidney disease (CKD) patients have a 3-30-fold increased risk of death compared with the general population. This mortality difference is even more pronounced in younger subjects. Two markers of aortic stiffness--aortic pulse wave velocity (PWV) and augmentation index (AIx)--have been prospectively related to all-cause and cardiovascular (CV) mortality in end-stage renal disease (ESRD) populations. The aims of our study were first, to confirm the important deleterious effect of arterial stiffness in uraemia and second, to assess the impact on survival of increased AIx in a relatively young non-diabetic dialysis population, with minimal CV disease. METHODS: Ninety-two patients (mean age 42.6 +/- 11.2 years) were included in the study and followed for a period of 61 +/- 25 months. None of the patients had diabetes mellitus, and only 3.3% had prior history of CV disease. AIx was determined by applantation tonometry using a SphygmoCor device (AtCor, PWV Inc., Westmead, Sydney, Australia). RESULTS: Mean AIx in our study population was 19.9 +/- 13.7%; other significant haemodynamic parameters were: systolic blood pressure (SBP) 129 +/- 24 mmHg, pulse pressure 35.3 +/- 17.5 mmHg with 27.2% of the study population receiving angiotensin-converting enzyme inhibitors (ACE-I). On univariate analysis, in our group AIx correlated with: body weight (P < 0.001), radial SBP (P < 0.001) and haemoglobin levels (P < 0.05). There was no correlation between AIx and any of the echocardiographic parameters. In the stepwise multiple regression analysis, the only independent predictors for AIx were weight (P < 0.001), SBP (P < 0.001) and haemoglobin (P < 0.05) with the model explaining 33% of the AIx variability (adjusted R(2) = 0.33). During the follow-up period, 15 deaths were recorded. In the Cox analysis (P = 0.014; chi square 20.7 for the model) the only independent predictors for all-cause mortality were age (P = 0.001), left ventricular mass index (P = 0.032) and ACE-I therapy (P = 0.039) while AIx did not reach statistical significance. There was no difference in patients' survival when divided by AIx tertiles, assessed by the log rank test (P = 0.78). CONCLUSION: Our results fail to support the notion that an increased effect of wave reflections on central arteries is a strong and independent predictor of mortality in all ESRD patients on haemodialysis. The effect of arterial wave reflections might be in fact dependent on patient age and concurrent comorbidity status.

Adult↗
PubMed2006

Posttransplantation anemia in adult renal allograft recipients: prevalence and predictors.

BACKGROUND: Management of anemia is an important factor in the care of patients with chronic kidney disease as the anemic state can confer significant morbidity and mortality. Posttransplantation anemia (PTA) has received comparatively less attention in the literature, and the prevalence and predictors of PTA vary between different studies. The purpose of this study was to investigate a large posttransplant population from 3 centres in the UK to elucidate the point prevalence of PTA, its determinants and the use of erythropoiesis stimulating agents (ESA) in these patients. METHODS: All adult patients with functioning renal transplants and attending renal transplant outpatients at Guy's, King's College, or St. Helier Hospitals, London, as of 31/12/2004 who had a valid hemoglobin in the previous 3 months, and who were more than 3 months postengraftment, were identified. Patients' notes and electronic patient records were obtained and a detailed cross-sectional clinical and biochemical database was constructed. The data were analyzed for the point prevalence of PTA, the prevalence of ESA use and for determinants of hemoglobin. The WHO criteria were used to define anemia and all patients on treatment with an ESA was classified as anemic irrespective of hemoglobin. RESULTS: A total of 1,511 (947 male) patients were studied. Mean age was 48.1+/-13.7 years with no difference between the sexes. Mean time posttransplantation was 8.5+/-7.2 years and mean estimated MDRD GFR was 47.6+/-18.9 ml/min with a higher GFR in males (49.9+/-19.0 v 43.8+/-18.0 mL/min, P<0.0001). Mean hemoglobin in the studied population was 12.9+/-1.6 g/dl with a significantly higher level among males than females (mean 13.3+/-1.6 v 12.3+/-1.4 g/dl, P<0.0001). The prevalence of anemia was 45.6% with a prevalence of 44.1% among males and 48.1% amongst females. Severe anemia was present in 50 subjects (3.3% of the total cohort). One hundred and forty-five patients (9.6% of the entire cohort) were being treated with an ESA. Of these subjects, 41 did not meet WHO criteria for the definition of anemia. After multiple regression analyses, age, female sex, renal function and to a lesser extent serum ferritin and therapy with angiotensin converting enzyme inhibitors/angiotensin II receptor blockers (both negatively associated) were predictive of hemoglobin. CONCLUSIONS: The prevalence of anemia posttransplantation was high while comparatively few patients were being treated with erythropoiesis stimulating agents. The strongest predictors of hemoglobin in this cohort of patients were age, female sex and allograft function. Medical therapy with MMF and sirolimus was associated with a high prevalence of anemia but this was likely to be the result of poorer graft function in these subjects who mostly had chronic allograft nephropathy. A large interventional prospective study with valid control groups is now needed to assess the long-term contributions of clinical and biochemical factors of renal function and to elucidate the effects of therapy on outcome.

Adult↗
PubMed2006

The epidemics of cardiovascular disease in elderly patients with chronic kidney disease--two facets of the same problem.

There is increasing evidence that even mild renal dysfunction is a novel potent cardiovascular risk factor in the general elderly population. With more severe renal impairment, cardiovascular risk increases proportionately. This issue deserves attention, as chronic kidney disease (CKD) is predominantly a disease of the elderly, and the mean age of end-stage renal disease patients entering dialysis is growing constantly. In the dialysis population, when clinically significant cardiovascular disease (CVD) (particularly congestive heart failure) is present, survival is worse. Thus, every effort should be made to identify and treat cardiovascular risk factor in the early stages of CKD. However, elderly renal patients receive less proper cardiovascular therapy compared to non-renal subjects of the same age. This review deals briefly with the most significant data published in the last decade on CVD in elderly with CKD.

Age Factors↗
PubMed2005

Dynamics of the circadian blood pressure profiles after renal transplantation.

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+/-5.1 years; 11 males, on dialysis for 25.6 months) 1 month preRTx and repeated 1 month and >1 year (ABPM3) 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: SBP3 sleep-to-awake ratio is related with serum creatinine3 (r=0.58, P=0.001), creatinine clearance (r=-0.41, P=0.036) and SBP1 sleep-to-awake ratio (r=0.48, P=0.034); similarly DBP3 sleep-to-awake ratio is related with serum creatinine3 (r=0.63, P=0.001), creatinine clearance (r=-0.471, P=0.036) and SBP1 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.

Adult↗
PubMed2005

Increased arterial stiffness in children on haemodialysis.

BACKGROUND: Measures of aortic stiffness--aortic pulse wave velocity (PWV) and augmentation index (AIx)--have been shown to be powerful predictors of survival in adult haemodialysis (HD) patients. Very few data have been reported regarding arterial stiffness in paediatric renal populations. METHODS: PWV and aortic AIx were determined from contour analysis of arterial waveforms recorded by applanation tonometry using a SphygmoCor device in 14 children on HD (age = 14.1 years) and in 15 age, height matched children controls. RESULTS: Pre-HD AIx (29.7 +/- 15.4%) and PWV (6.6 +/- 1.0 m/s) were significantly higher compared with children controls (8.3 +/- 8.0% and 5.4 +/- 0.6 m/s, respectively, P < 0.0001). The only significant difference between normal and HD children was BP level: 103/61 vs 114/72 mmHg, P < 0.05. In children of HD patients, a multiple linear regression model including BP, age, height, weight, Ca and P levels as independent variables accounted for 57% of the variability in AIx. Dialysis had no impact on AIx (post-HD: 28.5 +/- 12.7%) or on PWV (post-HD: 6.7 +/- 0.8 m/s). CONCLUSIONS: We show, in this first-ever report of increased arterial stiffness in children on dialysis, that end-stage renal disease is associated with abnormalities in arterial wall elastic properties, comparable with adult levels, even in childhood. Most importantly, the absence of a discernible amelioration with dialysis implies that purely structural and not functional alterations lie behind the increased arterial stiffness.

Adolescent↗
PubMed2005

Arterial stiffness in renal patients: an update.

According to recent data, arterial stiffness is a major independent risk factor for cardiovascular morbidity and mortality in both the general and renal populations. Because of several factors (vascular calcifications among them), large arteries are stiffer in patients with chronic kidney disease compared with the nonrenal population, contributing to the enormous cardiovascular mortality in renal patients. This review briefly analyzes methods for determination of arterial stiffness, focusing on 2 parameters, pulse wave velocity and the augmentation index, particularly useful in assessing arterial compliance in renal patients. Effects of different methods of renal replacement therapy on arterial wall properties also are discussed. Finally, the most promising novel and/or potential therapies regarding reduction of arterial stiffness in renal patients are reviewed.

Arteriosclerosis↗
PubMed2005

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

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.

Adult↗
PubMed2005

What we CAN do about chronic allograft nephropathy: role of immunosuppressive modulations.

Given the potency of modern immunosuppressive agents, kidney transplantation across alloantingen barriers is a routine phenomenon with excellent 1-year graft survival in most centers. However, the improvement in 1-year graft survival has not been matched by improvements in long-term graft function and chronic allograft nephropathy (CAN) remains the second commonest cause of graft attrition over time. Calcineurin inhibitors, namely cyclosporine A (CyA) and tacrolimus, have been implicated as causal agents in the development of the fibrotic processes that are the hallmarks of CAN. Many studies have, therefore, concentrated on the improvement of long term graft function through the modulation of immunosuppressive therapy. It is the purpose of this review to describe and appraise the available evidence for the prevention and management of CAN through modulation of immunosuppressive agents.

Chronic Disease↗
PubMed2005

Acute effect of CyA A (Neoral) on large artery hemodynamics in renal transplant patients.

BACKGROUND: CyA A (CyA) may induce intrarenal vasoconstriction, endothelial dysfunction, and hypertension. There are only two contradictory reports describing the acute effect of CyA on renal resistances measured by color Doppler flowmetry. Therefore, we studied the acute influence of oral CyA on arterial haemodynamics by assessing simultaneous changes in blood pressure, applanation tonometry-derived pulse wave analysis and duplex ultrasound-derived intrarenal resistance indices. METHODS: Augmentation index (AIx) (difference between the first and second systolic peak on the aortic pressure waveform divided by the pulse pressure = AIx) was determined from contour analysis of arterial waveforms recorded by applanation tonometry using the AtCor device in 18 live-related renal transplants (11 females/7 males, age = 32.0 +/- 8.1 years, transplantation duration = 17.5 +/- 16.1 months, and mean serum creatinine = 133 +/- 70 micromol/L). All studies were performed just before (C0), and 2 hours after (C2) the oral administration of CyA. At the same C0 and C2 moments the resistive index (RI) = (peak systolic frequency shift - minimum diastolic frequency shift)/peak systolic frequency shift, and pulsatility index (PI) = (peak systolic frequency shift - minimum diastolic frequency shift)/mean frequency shift were calculated from Doppler recorded waveforms. RESULTS: Blood pressure and heart rate did not differ significantly at C0 and at C2 serum levels: 134.3/82.9 vs. 128.1/80.0 mm Hg and 72.0 vs. 71.0 beats/min, respectively, despite a marked increase in whole blood concentration (CyA(C0)= 90.8 +/- 45.9 vs. CyA(C2)= 547.4 +/- 251.3 ng/mL) (P= 0.05). Mean AIx fell significantly from 17.2 +/- 13.8 to 12.9 +/- 14.2 (P < 0.0001). There was no correlation between the extent (expressed as absolute or relative change) of the measured alteration in AIx and total administered CyA dose, or increment in blood level between C0 and C2. In support, the intake of CyA did not induce a significant increase in Doppler resistance (RI(C0)= 0.68 +/- 0.08 vs. RI(C2)= 0.70 +/- 0.09) and pulsatility indices (PI(C0)= 1.32 +/- 0.31 vs. PI(C2)= 1.33 +/- 0.28). Finally, three patients were studied twice (>1 week): one under two levels of creatinine, one with no antihypertensives, and a third receiving verapamil initially. All these maintained a significant decrease in AIx at C2 from C0 supporting the reproducibility of the phenomenon. CONCLUSION: We demonstrate that Neoral CyA acutely improves large arterial compliance function and does not induce an acute rise in intrarenal resistance in stable renal transplant subjects with normal renal function. We speculate that there may be an effect of vitamin E, the diluent vehicle in which CyA is carried (1000 IU/100 mg CyA), shown to improve endothelial function.

Adult↗
PubMed2004

Coronary artery calcification is related to coronary atherosclerosis in chronic renal disease patients: a study comparing EBCT-generated coronary artery calcium scores and coronary angiography.

BACKGROUND: Coronary artery calcification (CAC) measured by electron beam computed tomography (EBCT) correlates with plaque burden, vessel stenosis and is predictive of future cardiac events in the general population. Extensive CAC has been described recently in dialysis cohorts. For the first time we studied the relationship between CAC and coronary angiographic findings in patients with chronic renal failure, on dialysis and after renal transplantation. METHODS: We studied 46 patients who all had an EBCT-derived Agatston coronary calcium score and a diagnostic coronary angiogram within a 12-month period. The mean age was 55.7+/-13.2 (SD) years (range 29-80). The mean duration of dialysis was 54.4 months (range 1-372). RESULTS: The mean CAC was 2370+/-352.8. The mean CAC in patients with an abnormal coronary angiogram (n = 35) was 2869.6+/-417.9, while that in patients with a normal coronary angiogram (n = 11) was 559.4+/-255.1 (P = 0.001 for the inter-mean comparison). Total CAC correlated with the number of diseased vessels (P = 0.0001) and with severity of atherosclerosis in all the vessels (P = 0.0001). The individual coronary artery calcification score correlated well with the severity of atherosclerotic coronary disease (P<0.0001 for all) in the left anterior descending, right coronary and circumflex arteries. Running a multivariate regression analysis for atherosclerosis burden, we found that the only predictor was CAC (r = 0.34, P = 0.0001). CONCLUSION: CAC is common and more severe in patients with chronic kidney disease. Although in chronic kidney disease patients CAC can occur in the absence of occlusive coronary atherosclerosis, our data suggest that, as in the general population, CAC in chronic kidney disease patients is associated with obstructive atherosclerosis and may therefore be associated with a worse outcome.

Adult↗
PubMed2004

Illness representations and quality of life scores in haemodialysis patients.

BACKGROUND: Health-related quality of life (QoL) in haemodialysis (HD) patients is a significant predictor of mortality and hospitalization. Patients' adaptation to a chronic disease is determined by their beliefs about illness and treatment. In this cross-sectional study we examined the impact of illness representations on QoL of HD patients and the influence of HD duration on this relationship. METHODS: Eighty-two clinically stable HD patients completed the Short Form-36 Health Survey (mean age 47.9+/-12.1, mean treatment duration 72+/-50.6, 53.6% males). Illness representations were assessed by a structured interview containing questions derived from The Revised Illness Perception Questionnaire. RESULTS: Our results indicate a relatively low QoL of HD patients, with an important proportion of patients scoring less than 43 for the physical component summary (65.9%) and less than 51 for the mental component summary (58.5%). HD patients consider their illness as having a chronic course, which they understand and control quite well. A higher personal control is associated with a lower emotional response and a better understanding of the disease. However, the perceived negative consequences of the disease upon patients' personal lives are considerable, as is their emotional response. Four of the six components of illness representations were strongly related to QoL parameters. On multiple regression analysis, between 15 and 31% in the variance of the physical and mental component of QoL was explained by three dimensions of illness representations: the perceived course of the disease, personal control and emotional response. Only the emotional response dimension of the illness representations is related to treatment duration (r = -0.48, P<0.01). CONCLUSION: Our study demonstrates important relationships between illness representations and QoL in end-stage renal disease patients treated by HD. Future research will have to plan for interventions that could alter illness representations in order to confirm the real impact of illness representations upon patients' QoL.

Adult↗
PubMed2004

Insights from ambulatory blood pressure monitoring: diagnosis of hypertension and diurnal blood pressure in renal transplant recipients.

BACKGROUND: Accurate diagnosis of hypertension is essential in chronic kidney disease patients, as it is linked to increased left ventricular mass, stroke, cardiovascular mortality and morbidity, and progression to end-stage renal disease. Elevated blood pressure (BP) detected by ambulatory BP monitoring (ABPM) has been shown to be predictive of worse outcome in chronic kidney disease patients. Another predictor of worse outcome is diurnal BP variation, measured also by ABPM. In this study, the authors examined the relationship (concordance or discordance) between blood pressure measured by ABPM compared with daytime office BP, and also explored the predictors of diurnal variation in renal transplant recipients. METHODS: All the patients who underwent renal transplantation and follow-up at the authors' institution from January 1998 to January 2003 were involved in this study (n=177) in addition to another randomly selected 64 patients that underwent transplantation before 1998. All patients had their ABPM performed according to previously described protocols at least 2 weeks after discharge from the hospital, dialysis-independent and with a functioning renal allograft. RESULTS: The authors found a positive correlation between systolic BP (SBP) diurnal variation and age (r =0.263, P <0.0001), glomerular filtration rate (GFR) (r =-0.229, P <0.0001), cyclosporine trough (r =0.171, P =0.047), and ABPM-to-transplant interval (r =-0.133, P =0.039). After fitting a regression model, the authors found that only GFR (P <0.0001) and age (P =0.001) were independent predictors of SBP diurnal variation (r =0.357). Concordance rate between casual BP and ABPM was 80%, and by using casual BP, only 15% of hypertensive renal transplant patients would be erroneously diagnosed as normotensive. CONCLUSIONS: The authors found that SBP diurnal variation is predicted independently by age and GFR, although it does correlate with cyclosporine trough and ABPM-to-transplant interval. In addition, the authors showed that ABPM is a more sensitive method for diagnosing hypertension than is sole reliance on office BP in renal transplant recipients.

Blood Pressure Monitoring, Ambulatory↗
PubMed2004

Sirolimus-induced pneumonitis: three cases and a review of the literature.

Interstitial pneumonitis is a rare disease that is seen in the context of some infections (e.g. PCP and CMV pneumonia), as side-effects of drugs (e.g. beta-blockers, amiodarone) and rarely in the context of renal transplantation. It manifests itself usually as a pneumonic illness; with symptoms of dyspnea, cough, fatigue and sometimes fever. Characteristic radiological changes are bilateral lower zone haziness. Interstitial pneumonitis is now emerging in solid organ transplant patients secondary to sirolimus). We describe three cases of sirolimus-induced pneumonitis in two patients who started sirolimus to permit cyclosporin withdrawal and in one patient initially started on sirolimus. The presentations in these cases ranged from insidious to fulminant; there was a rapid response to sirolimus withdrawal. This is an important syndrome, with an unknown frequency.

Aged↗
PubMed2004

Systolic blood pressure diurnal variation is not a predictor of renal target organ damage in kidney transplant recipients.

Elevated blood pressure and diurnal blood pressure variation detected by ambulatory blood pressure monitoring has been shown to be predictive of worse outcome in end-stage renal disease patients in small studies. What has been lacking is a large study to determine whether these ambulatory blood pressure monitoring (ABPM)-derived variables are predictors of worse outcome in renal transplant recipients. All the patients that underwent renal transplantation and follow up at this institution from January 1998 till October 2002 were involved in this study (n=177). All patients were followed up for at least 48 weeks. Last creatinine correlated positively with duration of dialysis (p=0.035, r=0.158), kidney-donor age (p<0.0001, r=0.377), early kidney function (p<0.0001, r=0.610, r=0.683), 24-h systolic blood pressure (SBP) load (p=0.002, r=0.228), and ABPM-derived pulse pressure (p<0.0001, r=0.269). However neither office blood pressure nor SBP diurnal variation were predictors of kidney outcome. Regression analysis showed that early kidney function was the only independent predictor of transplant outcome (p<0.0001). Systolic blood pressure diurnal variation, though an important predictor of target organ damage in chronic kidney disease patients, was not a predictor of renal transplant function in renal transplant recipients. Only early kidney function was an independent predictor of later serum creatinine.

Adult↗
PubMed2004

Cardiac calcification in renal patients: what we do and don't know.

Cardiovascular (CV) disease is one of the major causes of mortality in patients with renal diseases, with an increased odds ratio of mortality with risk factors as diverse as blood pressure (high or low), cholesterol level (high or low), left ventricular hypertrophy, vascular stiffness, chronic inflammation, and hyperhomocysteinemia. Mainly cross-sectional studies of renal patients showed excess CV calcification (CVC) compared with the general population, but a clear link between calcification and subsequent mortality is tenuous to date. Several factors have been incriminated to explain the increase in CVC in this particular population. Increased duration of dialysis therapy, dyslipidemia, altered calcium-phosphorus metabolism, and chronic inflammation have all been associated with increased CVC. However, with the shortage of large, observational, population-based, prospective studies tracking these potential risk factors and the pathogenesis of CVC in renal patients not yet sufficiently understood, it is difficult with the present state of knowledge to make robust recommendations about care strategies. The purpose of this review is to examine the 10 available studies of renal patients that have used modern CVC imaging and quantification techniques for clues to likely targets for future interventional studies.

Adult↗
PubMed2004

Haemodialysis acutely improves endothelium-independent vasomotor function without significantly influencing the endothelium-mediated abnormal response to a beta 2-agonist.

BACKGROUND: Increased aortic stiffness markers--aortic pulse wave velocity (PWV) and augmentation index (AIx)--have emerged as powerful predictors of survival in haemodialysis (HD). Various and often contradictory abnormalities of endothelium-dependent (ED) and endothelium-independent (EID) vasomotor function, have been described in dialysis subjects, pre- and post-dialysis, using methods that are difficult to export to the clinical setting or to large prospective trials assessing their relevance. Therefore, we determined the influence of a HD session on PWV and the ED and EID vascular reactivity, employing pulse wave analysis (PWA) of the aortic waveforms, combined with provocative pharmacological stimuli known to reduce wave reflection. METHODS: PWV and aortic AIx (difference between the first and second systolic peak on the aortic pressure waveform divided by the pulse wave height) were determined from PWA of arterial waveforms recorded by applanation tonometry using a SphygmoCor device in 41 HD (20 males, age 41.8 years) and in 20 controls with essential hypertension (10 males, age 43.6 years). ED and EID vascular reactivity were assessed by changes in AIx following inhaled salbutamol and sublingual nitroglycerin (GTN), respectively, pre- and post-dialysis session. Echocardiography was performed in all patients, pre-HD and before the PWV recordings. RESULTS: Pre-HD AIx (27.9+/-11.9%) was significantly higher compared with hypertensive patients with normal renal function (16.5+/-17%, P<0.05). Dialysis significantly reduced AIx to 18.2+/-18.3% (P<0.05 compared with pre-HD AIx), a level comparable with non-renal subjects (P = NS). Overall, PWV increased following HD to 7.89+/-2.09 m/s (P = 0.004 vs pre-HD, 6.34+/-1.32 m/s in essential hypertensive patients, P<0.05); however, a 19.1% increase was seen in 29 subjects and a 9.1% decrease in the remaining 12 subjects, both P<0.05. In HD patients, either pre- or post-HD, the EID vascular reactivity is significantly greater than the ED vasodilatation elicited by a beta 2-agonist. Moreover, when compared with hypertensive patients with normal renal function, the dialysis session only improved the EID abnormality (post-HD GTN AIx(HD) = -20.8+/-22.9% vs post-GTN AIx(hypertensive) = -14.2+/-5.7%, P = NS), while it had a non-additive effect on the ED response. A smaller response to a GTN challenge was associated with a greater left ventricular mass: r =-0.42, P = 0.007. In contrast, a diminished response to a beta 2-agonist did not represent a marker for cardiac abnormalities. CONCLUSIONS: The HD session acutely restores EID but not ED vasomotor function comparable with essential hypertensive patients. Pulse-wave analysis methodology, combined with provocative pharmacological testing may be used to unveil subsets of patients with more severe cardiac structural abnormalities.

Adrenergic beta-Agonists↗