Biomedical subjects

Adrian Covic

Publications and source records attributed to Adrian Covic.

At least 37 records · Page 2Linked to original sources

PubMed2005

Systemic vasculitis: still a challenging disease.

The efficacy of current therapeutic regimens in patients with systemic vasculitis is high, at the expense of considerable treatment toxicity. Optimal therapy for patients with these potentially life-threatening diseases is still debated. Our increased understanding of the pathogenetic mechanisms of systemic vasculitis has led to the development of new therapeutic alternatives, with better potential specificity for both the inflammation and immunologic causes of vasculitis: new immunosuppressive drugs (mycophenolate), monoclonal antibody modulators of lymphocyte function (rituximab), and cytokine-directed therapies (infliximab and eternacept). The safety and efficacy of such agents increasingly are being investigated in patients with systemic vasculitis. Additionally, many randomized prospective clinical trials have been completed to determine the precise roles for more conventional treatments (cyclophosphamide, azathioprine, and plasma exchange), providing an expanding evidence base to guide therapy in these challenging diseases. There now is clear evidence that duration of cyclophosphamide therapy can be relatively short (3 months), long-term maintenance therapy is needed to avoid relapse (often azathioprine), and patients at relatively greater risk for relapse can be identified. We review the most recent data on the current management of systemic antineutrophil cytoplasmic antibody-associated vasculitis, with emphasis on strategies to improve long-term outcome and reduce treatment toxicity while minimizing the risk for relapse.

Aged↗

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

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

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

Hypertension and cardiovascular risk assessment in dialysis patients.

INTRODUCTION: Cardiovascular (CV) disease is the main cause of morbidity and mortality in dialysis patients. Hypertension in patients affected by chronic renal insufficiency (CRI) has been recognized as one of the major classical CV risk factors in CRI from the very beginning of the dialysis era. However, its treatment is still unsatisfactory. METHODS: A discussion is employed to achieve a consensus on key points relating to the epidemiological, pathophysiological and clinical characteristics of hypertension in renal patients, in the light of global CV risk assessment. RESULTS: CV disease is accelerated by CRI, in particular by uraemia-specific risk factors. This is reflected by the fact that general population-based equations for calculating CV risk underestimate the real CV risk in CRI and dialysis patients. Hypertension in dialysis patients is clearly a major CV risk factor. Isolated systolic hypertension with increased pulse pressure is the most prevalent blood pressure (BP) anomaly in dialysis patients, due to stiffening of the arterial tree. BP should be assessed by clinical measurements on a routine basis, leaving 24 h monitoring for selected cases. The targets of BP control should be those recommended by the present guidelines, i.e. <140/90 mmHg, or the lowest possible values that are well tolerated. The pathophysiological cornerstone of hypertension in dialysis patients is extra-cellular volume expansion, which is typically sodium-sensitive, given the loss of renal function. Therefore, the principles of hypertension treatment in dialysis are an achievement of dry body weight, proper dialysis prescription with respect to dialysis time and intra-dialytic sodium balance, and dietary sodium and water restriction. Pharmacological treatment should only be the second option, after the adequate and complete application of all other means. No comparative pharmacological trials have specifically addressed the issue of hypertension control in dialysis patients. Therefore, this workshop group had to rely largely on data obtained in the general population. Drugs interfering with the renin-angiotensin system were felt to be the first choice, as they have widely been shown to interfere significantly with CV remodelling. Despite long-standing concerns, beta-blockers are being used increasingly even in patients with congestive heart failure and ischaemic cardiomyopathy. Other drug classes may be used in association or as first-line agents according to clinical requirements. CONCLUSIONS: Hypertension in renal patients has to be given particular and continued attention, and it should be adequately treated in light of the increased CV risk of this patient population. Research into the mechanisms of uraemic cardiomyopathy and cardiovascular remodelling should provide a precious new insight and lead to more precisely targeted and more effective therapies than in the past.

Blood Pressure↗

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

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↗

PubMed2004

Optimal composition of the dialysate, with emphasis on its influence on blood pressure.

UNLABELLED: Introduction. From the beginning of the dialysis era, the most appropriate composition of the dialysate has been one of the central topics in the delivery of dialysis treatment. METHODS: A discussion is employed to achieve a consensus on key points relating to the composition of the dialysate, focusing on the relationships with blood pressure behaviour. RESULTS: Sodium balance is the cornerstone of intra-dialysis cardiovascular stability and good inter-dialysis blood pressure control. Hypernatric dialysis carries the risk of positive sodium balance, with the consequent possibility of the worsening sense of thirst and hypertension. Conversely, hyponatric dialysis may lead to negative sodium balance, with the possibility of intra-dialysis cardiovascular instability and 'disequilibrium' symptoms including fatigue, muscle cramps and headache. The goal is to remove with dialysis the exact amount of sodium that has accumulated in the inter-dialysis interval. The conductivity kinetic model is applicable on-line at each dialysis session and has been proved to be able to improve intra-dialytic cardiovascular stability in hypotension-prone patients. Therefore, it should be regarded as a promising tool to be implemented in everyday clinical practice. Serum potassium concentration and variations during dialysis treatment certainly play a role in the genesis of cardiac arrhythmia. Potassium profiling, with a constant gradient between plasma and dialysate, should be implemented in clinical practice to minimize the arrhythmogenic potential of dialysis. Calcium plays a role both in myocardial contractility and in peripheral vascular resistance. Therefore, an increase in dialysate calcium concentration may be useful in cardiac compromised hypotension-prone patients. Acid-buffering by means of base supplementation is one of the major roles of dialysis. Bicarbonate concentration in the dialysate should be personalized in order to reach a midweek pre-dialysis serum bicarbonate concentration of 22 mmol/l. The role of convective dialysis techniques in cardiovascular stability is still under debate. It has been demonstrated that dialysate temperature and sodium balance play a role and this should be taken into account. Whether removal of vasoactive, middle-sized compounds by convection plays an independent role in improving cardiovascular stability is still uncertain. CONCLUSIONS: The prescription of dialysis fluid is moving from a pre-fixed, standard dialysate solution to individualization of electrolyte and buffer composition, not only during the dialysis session, but also within the same session (profiling) in order to provide patients with an optimal blood purification coupled with a high degree of tolerability.

Acid-Base Equilibrium↗

PubMed2004

Nephrology and renal replacement therapy in Romania--transition still continues (Cinderella story revisited).

UNLABELLED: INTRODUCTION. This report describes the current status of nephrology and renal replacement therapy (RRT) in Romania, a country with previously limited facilities, highlighting national changes in the European context. METHODS: Trends in RRT development were analysed in 2003, on a national basis, using the same questionnaires as in previous surveys (1991, 1995). Survival data and prognostic risk factors were calculated retrospectively from a large representative sample of 2284 patients starting RRT between January 1, 1995 and December 31, 2001 (44% of the total RRT population investigated). RESULTS: In 2003, RRT incidence [128 per million population (p.m.p.)] and prevalence (250 p.m.p.) were six and five times higher, respectively, than in 1995. The annual rate of increase in the stock of RRT patients (11%) was supported mainly by an exponential development of the continuous ambulatory peritoneal dialysis (CAPD) population (+600%), while the haemodialysis (HD) growth rate was stable (+33%) and renal transplantation made a marginal contribution. Renal care infrastructure followed the same trend: nephrology departments (+100%) and nephrologists (+205%). The characteristics of RRT incident patients changed accordingly to current European epidemiology (increasing age and prevalence of diabetes and nephroangiosclerosis). 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). Patients' survival was negatively influenced (Cox regression analysis) by age >65 years (P < 0.001), lack of pre-dialysis monitoring by a nephrologist [P = 0.01, hazards ratio (HR) = 0.8], severe anaemia, lack of erythropoetin treatment (P < 0.001, HR = 0.6), and co-morbidity, e.g. cardiovascular diseases (P < 0.001, HR = 1.8) and diabetes mellitus (P < 0.001, HR = 2.2). CONCLUSIONS: Although the rate of increase in RRT patient stock in 1996-2003 in Romania was the highest in Europe, the prevalence remained below the European mean. As CAPD had the greatest expansion, followed by HD, an effective transplantation programme must be set up to overcome the imbalance. The quality of RRT appears to be good and survival was similar to that in other registries. Further evolution implies strategies of prevention, based on national surveys, supported by the Romanian Renal Registry.

Adult↗

PubMed2004

Cardiovascular disease in renal allograft recipients is associated with elevated sialic acid or markers of inflammation.

BACKGROUND: Cardiovascular disease (CVD) is more common in patients with renal failure, even after renal transplantation. We wished to examine the relationship between markers of inflammation and CVD in stable renal transplant patients. METHODS: Ninety stable renal transplant outpatients with no recent illnesses or rejection were invited for study. Blood was drawn for a variety of inflammatory markers including total plasma sialic acid (SA) levels. RESULTS: Patients with CVD were significantly older than patients without (54 +/- 12 vs. 42 +/- 14 yr, p < 0.01) and had significantly lower total cholesterol (4.5 +/- 1.6 vs. 5.1 +/- 1.0 mmol/L, p < 0.01). Time from transplantation, present creatinine and blood pressure, smoking history were similar in both groups. Patients with CVD had significantly higher levels of SA (89.2 +/- 22.3 vs. 77.4 +/- 13.9 mg/dL, p = 0.01); fibrinogen [4.6 (2.2-6.7) vs. 3.6(1.9-5.7) g/L; p = 0.05); and C-reactive protein (CRP) [2.2 (1.5-8.0) vs 1.5 (0.7-3.0) microg/dL] than those without CVD. A logistic multiple linear regression analysis of the data with CVD as the dependent variable, and all the other parameters as independent variables, showed significant associations (F = 16.9; p < 0.001) with diastolic blood pressure (beta = 5.6; p = 0.02) and CRP (beta = 4.4; p = 0.04). CONCLUSIONS: This study suggests that inflammation is associated with a higher prevalence of cardiovascular disease in patients with renal allografts. The measurement of sialic acid as a risk factor may be superior to that of CRP in this group as its concentration is independent of renal function.

Adult↗

PubMed2004

Coronary artery calcification and aortic pulse wave velocity in chronic kidney disease patients.

BACKGROUND: Patients with end-stage renal disease (ESRD) are at increased risk of cardiovascular mortality and morbidity. Many complications arise in ESRD patients as a result of the twin arterial pathologies of atherosclerosis and arteriosclerosis. Part of this latter process is calcification of the arterial media, which is thought significantly to increase vascular stiffness. The aim of our study was to explore the relationship between measures of arterial stiffness-pulse wave velocity (PWV)-and the extent of calcification in the coronary arteries (CAC). METHODS: Over a period of 2 years 82 patients from our renal unit were invited to participate in our study. Sixty-two patients agreed to undergo electron beam computerized tomography (EBCT), and in 55 (38 males and 17 females), PWV measurements were made. EBCT and PWV measurements were done according to previously described protocols. RESULTS: The mean age of the 55 patients was 56.4 years. The mean duration of dialysis was 65.4 months, and the mean CAC score was 2551. The mean PWV was 9.13 m/s. PWV strongly correlated with total CAC even after correction for age, dialysis duration, and time averaged C-reactive protein (CRP) (P= 0.0001). CAC scores were significantly different when compared according to PWV tertiles (P= 0.0001). CONCLUSION: We have demonstrated that PWV is strongly related to the degree of EBCT-derived coronary artery calcium score in chronic kidney disease patients.

Adult↗

PubMed2004

Vascular calcification: a stiff challenge for the nephrologist: does preventing bone disease cause arterial disease?

There has been an explosion of interest in vascular calcification in the last 5 years. Four key "germinal" findings have fallen onto very fertile soil. First, on the background of an increasing cardiovascular disease burden it has been found that at least cross-sectionally, and in a limited fashion prospectively, achieved dialysis plasma phosphate levels are linked to all-cause and cardiovascular mortality. Second, there are increasing reports of calcific uremic arteriolopathy in Australia and the United States. Third, we know know that the mechanical properties of the carotid artery, and the aorta, have a profound influence on survival for dialysis patients. Vascular calcification itself (as assessed by x-ray films and ultrasound) has been linked to aortic stiffness. Fourth, increasing numbers of studies are showing extremely extensive coronary artery calcification (CAC) in dialysis patients, even at a young age. From these apparently unlinked observations the following assertion has been posited-that in the widespread (over) use of calcium-containing oral phosphate binders (OPB) to prevent uremic osteodystrophy in our dialysis population we have unwittingly accelerated widespread uremic vasculopathy and thereby contributed to premature cardiovascular mortality. It is the purpose of this article to discuss vascular calcification (and particularly CAC) in dialysis patients as we understand it today. We will review the published series, with special reference to the Sevelamer Treat to Goal trial and also discuss the new Kidney Disease Outcome Quality Initiative (K-DOQI) guidelines on the use of phosphate binders in chronic kidney disease.

Bone Diseases↗

PubMed2003

Ambulatory blood pressure monitoring in renal transplantation: should ABPM be routinely performed in renal transplant patients?

In renal transplant recipients, hypertension is common and associated with increased cardiovascular and allograft rejection risks. Ambulatory blood pressure monitoring is required for its accurate diagnosis and adequate treatment, as it clearly offers several advantages over office or casual blood pressure measurements. First, it correlates better with target-organ damage and with cardiovascular mortality. Second, ambulatory blood pressure monitoring can eliminate "white coat" hypertension. Most important is the identification of nocturnal hypertension, an independent cardiovascular risk factor. A circadian nondipping pattern is often found in renal transplant recipients, most probably resulting from cyclosporine A and persistent fluid overload in the early posttransplant phase (approximately 70% prevalence), but reflecting an underlying renal (parenchymal or vascular) allograft disease when persistent (approximately 25% prevalence) beyond the first year posttransplant.

Blood Pressure↗

PubMed2003

Successful use of Molecular Absorbent Regenerating System (MARS) dialysis for the treatment of fulminant hepatic failure in children accidentally poisoned by toxic mushroom ingestion.

BACKGROUND: Acute liver failure (ALF) as a result of mushroom poisoning is associated with a high mortality (particularly in children), despite optimal medical therapy (OMT), including charcoal haemoperfusion and haemodiafiltration. MARS is a new, cell-free, extracorporeal liver assistance method utilizing an albumin dialysate for the removal of albumin-bound toxins. METHODS: We describe the first series in the literature (also first MARS treatments in Romania) with ALF because of mushroom poisoning in children (M/F=2/4, age=7-16 years). Liver function was evaluated pre-MARS and 15-min post-MARS, 24 h following each treatment and 30 days post-MARS. FINDINGS: All patients had severe hepatic dysfunction: hepatic encephalopathy (HE; four grade II, one grade III, one grade IV), ALT=4082 (3400-5600) IU/L, bilirubin=6.3 (2-10) mg/dL, prothrombin time (PT)=52.5 (23-141) s. MARS was uneventful and well-tolerated. Two 6-h sessions per patient were performed with a similar immediate impact on liver tests: mean drop in ALT of -33 and -35%, respectively, and in bilirubin of -39 and -36%, respectively. ALT levels 24 h following MARS-1, remained unchanged but continued to drop by a further -28% following MARS-2. By contrast, all patients had a significant rebound in bilirubin (+39%) 24 h following MARS-1; however, following MARS-2 a rebound was seen only in two cases (+220%). PT improved by 37% after MARS-1 and normalized in four patients after MARS-2. OUTCOME: Four patients survived and completely recovered the hepatic function. Negative prognostic markers: lack of complete correction of PT, continuous rebound and increase in bilirubin, and lack of improvement in HE post-MARS-1. Survival in six well-matched cases, treated by OMT=0/6 (P<0.05). CONCLUSIONS: MARS is a safe and highly effective depurative therapy in children with ALF. Survival is predicted only by the impact/results of the initial MARS sessions and not by any of the baseline parameters.

Adolescent↗

PubMed2003

A retrospective 5-year study in Moldova of acute renal failure due to leptospirosis: 58 cases and a review of the literature.

BACKGROUND: Renal involvement [as acute renal failure (ARF)] is a prominent feature of both mild and severe leptospirosis-a re-emerging infectious disease. Few large series describe in detail clinical and laboratory features of cases with ARF and their outcome. METHODS: We performed a retrospective analysis (1997-2001) of all consecutive, serological confirmed leptospirosis cases with ARF (n=58, 53 male, age 44+/-13 years, rural residents=31%, animal contact=88%. RESULTS: Clinical manifestations (>50% prevalence): oliguria 95%, fever and jaundice 93%, nausea and vomiting 83%, haemorrhagic diathesis 80%, headache, hepatomegaly 76%, myalgias, abdominal pain 70%, hypotension 62%, disturbed consciousness 50%. A pattern of multiple organ failure (MOF) was frequent: ARF together with hepatic failure in 72%, respiratory failure in 38%, circulatory failure in 33%, pancreatitis in 25% and rhabdomyolysis in 5% of cases. Renal dysfunction: 35% of cases had a renal K(+)-wasting defect and 43% a FE(Na)(+)>1% and low-osmolarity urine despite volume depletion. Haematuria was encountered in 12 and mild proteinuria in 10 subjects. OUTCOME: 26% deaths, 64% normal hepatic and renal function at 90 days from presentation (however 29% maintained the initial tubular defect), 10% persistent mild renal failure. All deceased patients had, beside ARF, at least two other organ failures, affected consciousness, and haemorrhagic diathesis vs a prevalence for the above features of only 34, 33, and 72%, respectively, in the survivors group (P<0.05). CONCLUSIONS: Leptospirosis presenting with ARF is a severe disease, frequently leading to MOF and to death in one-third of the patients. In particular, the haemorrhagic diathesis and cerebral involvement are markers for unfavourable patient and renal outcomes.

Acute Kidney Injury↗

PubMed2003

Recent insights from studies using ambulatory blood pressure monitoring in patients with renal disease.

PURPOSE OF REVIEW: To identify and evaluate recent (2000-2003) published studies employing ambulatory blood pressure monitoring in patients with chronic renal failure, on dialysis, and after renal transplantation. RECENT FINDINGS: We discuss several studies that have employed ambulatory blood pressure monitoring to refine the analysis of the link between blood pressure levels, and diurnal alterations, and end-organ damage or patient survival. There is now some evidence that an abnormal diurnal blood pressure profile, although intrinsically not a very reproducible label, has predictive value for patient survival, and that the non-dipping phenomenon is linked to a high incidence of cardiovascular disease and autonomic dysfunction. SUMMARY: Ambulatory blood pressure monitoring remains an important adjunct to the comprehensive cardiovascular evaluation of patients with chronic, end-stage renal failure or after renal transplantation.

Blood Pressure Monitoring, Ambulatory↗

PubMed2002

Ambulatory blood pressure measurement in the renal patient.

Ambulatory blood pressure monitoring has been steadily growing in popularity as equipment becomes more accurate, affordable, and patient-friendly. In addition, software packages are more powerful and physician-customizable, and more physicians are accepting of ambulatory blood pressure monitoring's advantages. Summarizing the studies that deal mainly with hemodialysis patients, there are clear advantages to using more than isolated pre- and posthemodialysis blood pressure readings. If enough predialysis blood pressure readings are taken and averaged, this is a reasonable guide to end-organ damage (ie, left ventricular hypertrophy). Home and ambulatory blood pressure-derived values are complementary, and only this approach can discern any further contribution from diurnal blood pressure elevation. The cross-sectional association between blood pressure and end-organ damage is very weak in end-stage renal disease patients if the blood pressure values are "casual," but the relationship is much stronger when ambulatory blood pressure monitoring-derived measurements are used. One prospective study clearly linked the sustained loss of diurnal blood pressure fall with sleep with progressive left ventricular dilatation. Loss of circadian variation in blood pressure is associated with an increased mortality rate for dialysis patients and for diabetic patients, regardless of diabetes type. The combination of nondipping in renal impairment leads to a high mortality rate. Much more work is needed to dissect out the causes for abnormal diurnal blood pressure rhythm and attempt to modulate this parameter. Obstructive sleep apnea may be a promising target for intervention.

Blood Pressure↗