- Former clinician-researcher now working in the private sectoredit
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1. The correction of metabolic acidosis with sodium bicarbonate remains controversial. Experiments in vitro have suggested possible deleterious effects after alkalinization of the extracellular fluid. Disequilibrium of carbon dioxide and... more
1. The correction of metabolic acidosis with sodium bicarbonate remains controversial. Experiments in vitro have suggested possible deleterious effects after alkalinization of the extracellular fluid. Disequilibrium of carbon dioxide and bicarbonate across cell membranes after alkali administration, leading to the phenomenon of ‘paradoxical’ intracellular acidosis, has been held responsible for some of these adverse effects. 2. Changes in intracellular pH in suspensions of leucocytes from healthy volunteers were monitored using a fluorescent intracellular dye. The effect in vitro of increasing extracellular pH with sodium bicarbonate was studied at different sodium bicarbonate concentrations. Lactic acid and propionic acid were added to the extracellular buffer to mimic conditions of metabolic acidosis. 3. The addition of a large bolus of sodium bicarbonate caused intracellular acidification as has been observed previously. The extent of the intracellular acidosis was dependent on s...
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Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the... more
Before the introduction of erythropoiesis-stimulating agents (ESAs) in 1989, repeated transfusions given to patients with end-stage renal disease caused iron overload, and the need for supplemental iron was rare. However, with the widespread introduction of ESAs, it was recognized that supplemental iron was necessary to optimize hemoglobin response and allow reduction of the ESA dose for economic reasons and recent concerns about ESA safety. Iron supplementation was also found to be more efficacious via intravenous compared to oral administration, and the use of intravenous iron has escalated in recent years. The safety of various iron compounds has been of theoretical concern due to their potential to induce iron overload, oxidative stress, hypersensitivity reactions, and a permissive environment for infectious processes. Therefore, an expert group was convened to assess the benefits and risks of parenteral iron, and to provide strategies for its optimal use while mitigating the ri...
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Patients with chronic kidney disease (CKD) have significantly increased risks of cardiovascular (CV) morbidity and mortality. Dyslipidemia is a common disorder in CKD patients. CKD patients have a different lipid profile with increased... more
Patients with chronic kidney disease (CKD) have significantly increased risks of cardiovascular (CV) morbidity and mortality. Dyslipidemia is a common disorder in CKD patients. CKD patients have a different lipid profile with increased atherogenic lipid fractions, and serum low-density lipoprotein cholesterol (LDL-C) levels may underestimate the atherogenic effect of LDL-C in these patients. Dyslipidemia may contribute to the increased CV morbidity and mortality, and to the progression of kidney disease in CKD patients. Currently, statins are the pharmacologic intervention of first choice, if lifestyle changes fail adequately to lower LDL-C levels in the setting of normal or moderately elevated triglycerides. Statins have been extensively studied in a large variety of patient populations and have proven efficacy in the treatment of dyslipidemia, and in reducing CV mortality. Although much evidence supports the CV benefits of statins in patients with normal renal function, there are ...
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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... more
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...
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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... more
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 p...
Research Interests: Nephrology, Pediatrics, Kidney diseases, Adolescent, Medicine, and 14 morePopulation, Humans, Child, Blood Pressure, Infant, Clinical Sciences, Newborn Infant, Age Factors, Reproducibility of Results, Intensive Care Medicine, Reference Values, Ambulatory Blood Pressure, Child preschool, and white coat hypertension
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Summary A 56-year-old man who received a live-related renal transplant in 1988 was started in 1995 on the selective angiotensin II antagonist losartan (Dupont-Merke) to treat worsening hypertension. Two months later because of pulmonary... more
Summary A 56-year-old man who received a live-related renal transplant in 1988 was started in 1995 on the selective angiotensin II antagonist losartan (Dupont-Merke) to treat worsening hypertension. Two months later because of pulmonary oedema, loop diuretics were started. Within two weeks, serum creatinine had increased from 245 to 571 mumol/l, and the patient became oliguric. A systolic bruit was noted over the graft. Renal angiography showed a 90% stenosis of the transplant renal artery. Losartan was withdrawn, with prompt improvement in renal function. A successful percutaneous transluminal angioplasty performed a few days later resulted in further improvement in renal function accompanied by a significant diuresis.
Research Interests: Acute kidney injury, Kidney transplantation, Medicine, Acute renal failure, Renal transplantation, and 15 moreHumans, Male, Serum Creatinine, Renal Function, Middle Aged, Losartan, Imidazoles, Angiotensin II, Diuresis, Percutaneous Transluminal Angioplasty, Renal artery stenosis, Creatinine, Tetrazoles, Antihypertensive agents, and Medical and Health Sciences
The proportion of patients with vasculitis and rapidly progressive nephritis aged 70 years or over has risen from about 10% in the 1980s to over 30% in series reported in the 1990s. This study was undertaken to examine the presentation... more
The proportion of patients with vasculitis and rapidly progressive nephritis aged 70 years or over has risen from about 10% in the 1980s to over 30% in series reported in the 1990s. This study was undertaken to examine the presentation and outcome of such older patients. Seventeen of 56 patients (30%) who presented at two renal units were aged 70 years or over. Mean creatinine level at presentation was 530 mumol/l, and five patients received dialysis at presentation. Outcome was dependent on three factors, namely comorbid pathology, response to immunosuppressive therapy, and the occurrence in three cases of temporary spontaneous partial remission. Overall patient survival at one and two years was 62.5% and 50%, respectively, and 90% and 100% of surviving patients were independent of dialysis at one and two years, respectively. Response to chemotherapy was excellent, with full rehabilitation in many cases and no deaths directly attributable to adverse effects of immunosuppressive the...
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Research Interests: Kidney transplantation, Medicine, Transplantation, Humans, Internal Medicine, and 14 moreBlood Pressure, Circadian Rhythm, Female, Male, Renal Function, Clinical Sciences, Aged, Middle Aged, Adult, Retrospective Studies, Kidney Disease, Renal Dialysis, Ambulatory Blood Pressure, and Glomerular Filtration Rate
... Original Article Urea kinetic modelling—are any of the 'bedside' Kt/V formulae reliable enough?Adrian Covic1, David JA Goldsmith2, Ken Hill3, Michael C. Venning3 and Peter Ackrill3 ... ASAIO... more
... Original Article Urea kinetic modelling—are any of the 'bedside' Kt/V formulae reliable enough?Adrian Covic1, David JA Goldsmith2, Ken Hill3, Michael C. Venning3 and Peter Ackrill3 ... ASAIO Trans 1987; G, Giacchino F. Single pool urea kinetic model (UKM) and 33: 286–288 ...
... Find all citations by this author (default). Or filter your current search. Covic A, Find all citations by this author (default). Or filter your current search. Goldsmith DJ, Find all citations by this author (default). Or filter your... more
... Find all citations by this author (default). Or filter your current search. Covic A, Find all citations by this author (default). Or filter your current search. Goldsmith DJ, Find all citations by this author (default). Or filter your current search. ...
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< i> Background and Aim:</i> Due to increasing evidence suggesting a link between hyperphosphatemia and cardiovascular disease (CVD), mediated through vascular calcification in patients on... more
< i> Background and Aim:</i> Due to increasing evidence suggesting a link between hyperphosphatemia and cardiovascular disease (CVD), mediated through vascular calcification in patients on dialysis, the following question arises: At what stage of chronic ...
Research Interests: Incidence Geometry, Kidney transplantation, Survival Analysis, Treatment Outcome, Adolescent, and 15 moreMedicine, Ischaemic heart disease, Humans, Survivors, Blood Pressure, Female, Disease, Male, Middle Aged, Adult, Left ventricular hypertrophy, Cardiovascular Diseases, Chronic Kidney Failure, Malignancy, and Medical and Health Sciences
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The case of a man with progressive breathlessness and pulmonary infiltration caused by AL amyloidosis associated with multiple myeloma is presented. There was a marked peripheral eosinophilia, which has not previously been described with... more
The case of a man with progressive breathlessness and pulmonary infiltration caused by AL amyloidosis associated with multiple myeloma is presented. There was a marked peripheral eosinophilia, which has not previously been described with amyloidosis. E osinophilia is a challenging disease with a wide differential diagnosis (see box 1). A broad variety of allergic, infectious, neoplastic, and idiopathic diseases are associated with increased blood and/or tissue eosinophilia and range in severity from self limited conditions to life threatening disorders. We report a patient who had marked peripheral eosinophilia associated with pulmonary symp-toms. He was diagnosed to have pulmonary amyloidosis. CASE REPORT
STUDY AIMS To survey bone mineral disturbances in the hemodialysis (HD) population in Europe and current clinical practice in Europe for the prevention, diagnosis and treatment of secondary hyperparathyroidism (SHPT) in HD patients.... more
STUDY AIMS To survey bone mineral disturbances in the hemodialysis (HD) population in Europe and current clinical practice in Europe for the prevention, diagnosis and treatment of secondary hyperparathyroidism (SHPT) in HD patients. PRIMARY OBJECTIVES First, to estimate the prevalence of Kidney Disease Outcomes Quality Initiative (K/DOQI) guideline achievement in a representative sample of European hemodialysis subjects. As part of this objective, we will investigate the prevalence of achievement by type of dialysis, type of center and time on dialysis (less than or greater than 1 year). Among new dialysis subjects (less than 1 year), we will evaluate prevalence of K/DOQI target achievement until the end of the study. The study will run for 3 years. Second, to estimate the association of bone mineral markers (parathyroid hormone [PTH], calcium [Ca], serum phosphorus [P] and calcium phosphate product [CaxP]) classified by achievement of K/DOQI targets with mortality and overall cardi...
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This paper reflects the position of the CKD-MBD workgroup, an official working group of ERA-EDTA and of the ERBP advisory board, the official guideline-producing body of ERA-EDTA, on the topic of the use of calcimimetics in patients with... more
This paper reflects the position of the CKD-MBD workgroup, an official working group of ERA-EDTA and of the ERBP advisory board, the official guideline-producing body of ERA-EDTA, on the topic of the use of calcimimetics in patients with CKD stage 5D, as based on two recent meta-analysis.
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Increased aortic stiffness markers - aortic pulse wave velocity (PWV) and augmentation index (AIx) - are powerful predictors of survival in ESRD patients - well-recognized for the high prevalence of coronary artery disease (CAD) and... more
Increased aortic stiffness markers - aortic pulse wave velocity (PWV) and augmentation index (AIx) - are powerful predictors of survival in ESRD patients - well-recognized for the high prevalence of coronary artery disease (CAD) and unusually high PWV and AIx. Recently, decreased aortic compliance has been shown to be predictive of primary coronary events in hypertensive patients with normal renal function. We aimed to explore relationships between arterial stiffness and CAD in cohorts of patients with chronic kidney disease (CKD). 46 patients with chronic kidney disease (33 males, aged 55.7+/- 13.2 years, 20 on dialysis, 18 post renal transplantation, and 8 with glomerular filtration rate (GFR) between 10 and 25 ml/min) underwent coronary angiography for the assessment of CAD. PWV and aortic AIx were determined from pulse waveform analysis of arterial waveforms recorded by applanation tonometry using a SphygmoCortm device. The atherosclerosis burden score was calculated by adding t...
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Rifampicin re-administration may cause immunologically mediated acute tubulo-interstitial injury. Retrospectively, 170 consecutive cases with acute renal failure (ARF) following re-treatment with rifampicin (71% males, 29% females, age 21... more
Rifampicin re-administration may cause immunologically mediated acute tubulo-interstitial injury. Retrospectively, 170 consecutive cases with acute renal failure (ARF) following re-treatment with rifampicin (71% males, 29% females, age 21 to 68 years) were analysed, which accounted for 12% of all ARF patients treated by two large dialysis referral centres in Romania, Timisoara and Iasi, between 1974-2001 and 1988-2001, respectively. The most frequent clinical features of rifampicin-induced ARF were: Anuria, gastro-intestinal (abdominal pain, nausea, vomiting and diarrhoea) and "flu-like" symptoms. Urine analysis revealed sterile leucocyturia in 54%, proteinuria in 31%, haematuria in 26% and haemoglobinuria in 7% of cases. Haemolytic anaemia was frequent, found in 66% of the patients; half of these had Hct values of < 30%, thrombocytopenia and also more severe renal damage (a longer anuric phase and a slower recovery of the renal function), thus suggesting a severe multi...
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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... more
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. 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. When comparing ABPM 2 with the ABPM 1 recording (3 months difference between measurements) only 43.3% of the patients maintained ...
Research Interests: Cardiology, Nephrology, Risk assessment, Medicine, Prospective studies, and 15 moreHumans, Internal Medicine, Hypertension, Blood Pressure, Circadian Rhythm, Female, Male, Clinical Sciences, Kidney Disease, Reproducibility of Results, Risk Assessment, Chronic Kidney Failure, Ambulatory Blood Pressure, Cohort Studies, and Antihypertensive agents
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Research Interests: Medicine, Multivariate Analysis, Humans, Internal Medicine, Kidney, and 15 moreEurope, Female, Male, Propensity Score, Propensity Score Matching, Clinical Sciences, Aged, Middle Aged, Phosphates, Cardiovascular Diseases, Biological markers, Chi Square Distribution, Chelating Agents, hyperphosphatemia, and Medical prescription
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It is increasingly acknowledged that mineral and bone disorders (MBDs) contribute to the excessively high cardiovascular (CV) disease morbidity and mortality observed in patients with chronic kidney disease (CKD). There is ongoing debate... more
It is increasingly acknowledged that mineral and bone disorders (MBDs) contribute to the excessively high cardiovascular (CV) disease morbidity and mortality observed in patients with chronic kidney disease (CKD). There is ongoing debate as to whether screening for CV calcification, one of the hallmarks of CKD-MBD, should be implemented in clinical practice in patients with CKD. Issues to be considered in this controversy relate to prevalence, severity, relevance, and last but not least, modifiability and reversibility of vascular and valvular calcifications in the setting of CKD. The recent expansion of the armamentarium to treat CKD-MBD (calcium-free phosphate binders and calcimimetics) creates new opportunities. Mounting experimental and clinical evidence indicates that progression of CV calcification may indeed be attenuated. Whether this will translate into better outcomes remains to be proven. We acknowledge that hard outcome data so far are limited and, overall, yielded incon...
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The patient with chronic kidney disease (CKD) represents an extreme model for arteriosclerosis, vascular calcification, and bone disorders, all of which are also associated with ageing in the general population. These pathological... more
The patient with chronic kidney disease (CKD) represents an extreme model for arteriosclerosis, vascular calcification, and bone disorders, all of which are also associated with ageing in the general population. These pathological features are also relevant to other common chronic health disorders such as diabetes, and chronic inflammatory and cardiovascular diseases. Although management and interventions for these major risk factors are now incorporated into most public health guidelines (eg, smoking cessation and control of bodyweight and blood pressure, as well as glucose and cholesterol concentrations), some residual cardiovascular risk is not reduced by implementation of these interventions. CKD should be regarded as an atypical disease in which both traditional and novel cardiovascular risk factors have effects on outcomes. But CKD can also be viewed conceptually as an accelerator of traditional cardiovascular risk factors. Findings from research into mineral bone disorder ass...
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Research Interests: Acute kidney injury, Medicine, Multivariate Analysis, Humans, Internal Medicine, and 15 moreRenin Angiotensin Aldosterone System, Female, Male, Propensity Score, Clinical Sciences, Aged, Cardiac Catheterization, Middle Aged, Percutaneous Coronary Intervention, Coronary Angiography, Cross Sectional Studies, Angiotensin Converting Enzyme Inhibitors, Contrast Media, Creatinine, and Angiotensin Receptor Antagonists
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BackgroundMeasurements of aortic stiffness [aortic pulse wave velocity (PWV) and augmentation index (AIx)] have been established as powerful predictors of survival on hemodialysis (HD). Abnormal endothelial-dependent and... more
BackgroundMeasurements of aortic stiffness [aortic pulse wave velocity (PWV) and augmentation index (AIx)] 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 AIx, and how these different methods might influence endothelial-dependent abnormal vasodilatation.ObjectiveTo 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 AIx were determined from contour analysis of arterial waveforms recorded by applanation tonometry in 40 CAPD, 41 HD, 20 RTx patients (with normal s...
Research Interests: Renal transplantation, Humans, Nitric oxide, Female, Hemodialysis, and 15 moreMale, Arterial stiffness, Clinical Sciences, Adult, Peritoneal Dialysis, Cross Sectional Studies, Chronic Kidney Failure, Blood Flow Velocity, Pulse Wave Velocity, Renal Replacement Therapy, Pulsatile Flow, Augmentation Index, Femoral Artery, PWV, and Carotid Arteries
The impact of body mass index (BMI) and body weight on hospitalization rates in haemodialysis patients is unknown. This study hypothesizes that being either underweight or obese is associated with a higher hospitalization rate.... more
The impact of body mass index (BMI) and body weight on hospitalization rates in haemodialysis patients is unknown. This study hypothesizes that being either underweight or obese is associated with a higher hospitalization rate. Observational study of 6296 European haemodialysis patients with prospective data collection and follow-up every six months for three years (COSMOS study). The risk of being hospitalized was estimated by a time-dependent Cox regression model and the annual risk (incidence rate ratios, IRR) by Poisson regression. We considered weight loss, weight gain and stable weight. Weight change analyses were also performed after patient stratification according to their baseline BMI. A total of 3096 patients were hospitalized at least once with 9731 hospitalizations in total. The hospitalization incidence (fully adjusted IRR 1.28, 95% CI [1.18-1.39]) was higher among underweight patients (BMI <20kg/m) than patients of normal weight (BMI 20-25kg/m), while the incidence...
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Arterial wall calcification, once considered an incidental finding, is now known to be a consistent and strong predictor of cardiovascular events in patients with chronic renal insufficiency. It is also commonly encountered in radiologic... more
Arterial wall calcification, once considered an incidental finding, is now known to be a consistent and strong predictor of cardiovascular events in patients with chronic renal insufficiency. It is also commonly encountered in radiologic examinations as an incidental finding. Forthcoming bench, translational, and clinical data seek to establish this and pre-calcification changes as surrogate imaging biomarkers for noninvasive prognostication and treatment follow-up. Emerging paradigms seek to establish vascular calcification as a surrogate marker of disease. Imaging of pre-calcification and decalcification events may prove more important than imaging of the calcification itself. Data-driven approaches to screening will be necessary to limit radiation exposure and prevent over-utilization of expensive imaging techniques.