Severe Renal Impairment (severe + renal_impairment)

Distribution by Scientific Domains

Selected Abstracts

Gadolinium-based contrast agents and their potential role in the pathogenesis of nephrogenic systemic fibrosis: The role of excess ligand

Martin A. Sieber PhD
Abstract Purpose To investigate the role of excess ligand present in gadolinium (Gd) -based contrast agents in the development of nephrogenic systemic fibrosis (NSF). Using a dosing regimen to simulate the exposure seen in patients with severe renal impairment, we investigated the effect of excess ligand on Gd-deposition and the depletion of endogenous ions. Materials and Methods Gadodiamide and gadoversetamide were formulated with 0%, 5%, and 10% excess ligand. Forty-two, healthy, male Hannover Wistar rats received daily intravenous injections of each formulation over a period of 20 days. At the end of the study, histopathological analysis of the skin was performed and the concentrations of Gd, Zn, and Cu were measured in several tissues. The levels of Zn in the urine were also measured. Results The most severe skin lesions were observed after injection of formulations containing 0% free ligand and in those animals with the highest Gd concentrations in the skin. There were no significant reductions in the levels of Zn or Cu observed in the skin; however, the levels of Zn in the urine were elevated following administration of formulations with the highest amount of excess ligand. Conclusion Our findings suggest that there is an inverse correlation between the amount of excess ligand present in Gd-containing contrast agents and the amount of Gd in the tissue, and further underline the importance of the inherent stability of these agents in the development of NSF. J. Magn. Reson. Imaging 2008;27:955,962. 2008 Wiley-Liss, Inc. [source]

Frequency of renal impairment, advanced age, obesity and cancer in venous thromboembolism patients in clinical practice

Summary.,Background:,Low-molecular-weight heparin (LMWH) dosed by weight is recommended as first-line therapy for the initial treatment of venous thromboembolism (VTE) and as monotherapy for long-term treatment of cancer-related VTE. In ,special populations' such as those with renal impairment or the elderly, weight-based dosing may be excessive, and capping the dose in obese patients may lead to inadequate dosing. Objectives:,We determined the frequency of ,special population' characteristics (renal impairment, advanced age, obesity) and cancer among VTE patients in clinical practice, and assessed whether these characteristics appeared to influence the type and dose of anticoagulants prescribed. Methods:,During 2004,2005, among consecutive patients with VTE at two large Canadian hospitals, the proportions with the above characteristics were calculated and treatments prescribed were determined. Results:,Of 524 VTE patients, 31% were aged > 75 years. Moderate renal impairment [creatinine clearance (CrCl) 30,59 mL min,1] was present in 20% of patients, and severe renal impairment (CrCl < 30 mL min,1) in 5% of patients. LMWH was prescribed to 67% of patients with severe renal impairment and to 83% of patients with moderate renal impairment. Body weight was > 100 kg in 15% of patients. Underdosing of LMWH by > 10% was documented in 36% of such patients compared with 8% of patients < 100 kg (P < 0.001). Among 26% of patients with active cancer, only one-third were prescribed LMWH monotherapy. Conclusions:,In clinical practice, renal impairment, advanced age, obesity and cancer are frequently present in patients with VTE. A considerable proportion of these patients may not receive the optimal type or dose of medication to treat VTE. [source]

Review: The role of microRNAs in kidney disease

NEPHROLOGY, Issue 6 2010
ABSTRACT MicroRNAs (miRNAs) are short non-coding RNAs that modulate physiological and pathological processes by inhibiting target gene expression via blockade of protein translation or by inducing mRNA degradation. These miRNAs potentially regulate the expression of thousands of proteins. As a result, miRNAs have emerged rapidly as a major new area of biomedical research with relevance to kidney disease. MiRNA expression has been shown to differ between the kidney and other organs as well as between different kidney regions. Furthermore, miRNAs have been found to be functionally important in models of podocyte development, diabetic nephropathy and polycystic kidney disease. Of particular interest, podocyte-specific deletion of Dicer, a key enzyme in the biogenesis of miRNA, results in proteinuria and severe renal impairment in mice. One miRNA (miR-192) can also act as an effector of transforming growth factor-, activity in the high-glucose environment of diabetic nephropathy. Differential expression of miRNAs has been reported in kidney allograft rejection. It is anticipated that future studies involving miRNAs will generate new insights into the complex pathophysiology underlying various kidney diseases, generate diagnostic biomarkers and might be of value as therapeutic targets for progressive kidney diseases. The purpose of this review is to highlight key miRNA developments in kidney diseases and how this might influence the diagnosis and management of patients with kidney disease in the future. [source]

Gadolinium and nephrogenic systemic fibrosis: Association or causation (Review Article)

NEPHROLOGY, Issue 3 2008
SUMMARY: With widespread availability of magnetic resonance imaging (MRI), it has become standard practice for patients with severe renal impairment or previous severe reactions to iodine-containing contrast media to receive gadolinium-based MRI contrast agents instead of traditional radiographic contrast agents, particularly for magnetic resonance angiography. However, there is growing concern about the use of gadolinium contrast agents in the presence of severe renal insufficiency, because of increasing reports of nephrogenic fibrosing dermopathy (NFD)/nephrogenic systemic fibrosis (NSF), associated with the exposure to certain gadolinium-containing contrast agents. In this review we explore the causal link between gadolinium exposure and NSF, using an established system of epidemiological criteria proposed by Bradford Hill. Though the current evidence makes gadolinium a strong suspect as an aetiologic agent for NSF in the presence of severe renal failure, the die is not cast yet. At this stage there needs to be cautious approach to the use of gadolinium-containing contrast agents in the presence of severe renal failure (glomerular filtration rate <30 mL/min per 1.73 m2). [source]

Latest news and product developments

PRESCRIBER, Issue 10 2007
Article first published online: 13 SEP 200
Sitagliptin: novel drug for type 2 diabetes Sitagliptin (Januvia), the first dipeptidyl peptidase-4 (DPP-4) inhibitor, has been introduced for the treatment of type 2 diabetes in combination with metformin or a glitazone when either agent plus exercise and diet fail to control blood glucose. Inhibition of DPP-4 prevents the breakdown of incretin hormones that promote insulin release from pancreatic beta cells. In trials lasting up to 24 weeks, adding sitagliptin to established therapy reduced HbA1C by 0.67-0.90 per cent. It is contraindicated in patients with moderate or more severe renal impairment. At the recommended dose of 100mg per day, a month's treatment with sitagliptin costs 33.36. Guide to treating mentalillness in primary care A new guide from the Centre for Clinical and Academic Workforce Innovation aims to help health professionals and others treating people with mental illness. A Complete Guide to Primary Care Mental Health, a toolkit presented as a reference book and CD, covers aspects of treatment, the law and working with the voluntary sector and includes training materials compatible with evidence-based guidance. Copies are available from Follow-up improves statin adherence Patients may take long holidays from statin treatment but a visit to the doctor is among the most effective ways to improve adherence, a US study shows (Arch Intern Med 2007;167:847,52). Observation of 239 911 patients who began statin treatment during a seven-year period showed that 54 per cent stopped their treatment for at least 90 days. Of these, 48 per cent restarted within one year and 60 per cent within two years. Factors associated with restarting treatment were a visit to the doctor who prescribed the statin (odds ratio, OR, 6.1) or a visit to a different doctor (OR 2.9). A cholesterol test and hospital admission for a cardiovascular event were also significant factors. Pharmacist MUR does not reduce heart failure deaths Medication review by trained community pharmacists does not reduce admissions or deaths among patients with heart failure, according to a study from East Anglia (BMJ online: 23 April 2007; doi:10.1136/bmj.39164.568183.AE). Patients admitted as emergencies with heart failure were randomised to usual care or two home visits by a community pharmacist within two and eight weeks after discharge. Pharmacists reviewed medication and advised on self-management of symptoms and lifestyle. There were no significant differences in hospital admissions over the next six months (rate ratio 1.15 for pharmacist vs control) or deaths (rate ratio 1.18); quality of life scores were similar in the two groups. The authors speculate that the interventions may have been too brief or too late (lifestyle changes having been made already), or disadvantaged by not adjusting beta-blocker doses. A Cardiff study of pharmacist medication reviews for elderly patients (BMJ online: 20 April 2007; doi:10.1136/bmj.39171. 577106.55), found that their advice had the potential to undermine patients' ,confidence, integrity and self-governanc'. The study found that pharmacists gave advice unnecessarily and uninvited. CHD targets met early The national programme to tackle heart disease has made substantial progress towards it targets, the Department of Health says in a 10-year report, and a 40 per cent cut in mortality will be achieved ahead of the deadline of 2010. Coronary Heart Disease Ten Years On: Improving Heart Care, a report by Professor Roger Boyle, National Director for Heart Disease and Stroke, states that 7 per cent of the population is now taking statins, resulting in 9700 deaths avoided annually. The prevalence of untreated hypertension fell from 32 to 24 per cent between 1998 and 2003. The report also summarises changes in service delivery, nutrition and smoking cessation. HRT: ovarian cancer risk The MHRA has not altered its advice on the use of HRT following news that five years' use increases ovarian cancer risk in women over 50. The Million Women Study revealed an approximately 20 per cent increased risk of ovarian cancer or death among women still using HRT after five or more years. There was no difference in risk between oestrogen-only and combined formulations. The MHRA says HRT is still indicated for relieving symptoms of the menopause for short-term use; as an alternative for women over 50 who cannot take other treatments to prevent osteoporosis, or when such options fail; and in women under 50 who experience a premature menopause. Poor angina treatment Over half of patients with angina continue to experience attacks despite treatment, according to a survey by the British Cardiac Patients Association. The survey of 600 patients with angina also found that twot-hirds of respondents reported that angina had a moderate to severe impact on their lives. Half said that the adverse effects of their treatment negatively affected their work, two-thirds reported an adverse impact on sex, and almost three-quarters of patients taking beta-blockers reported fatigue. A second survey of 2000 adults revealed widespread ignorance about the prevalence and symptoms of angina. The surveys were sponsored by Servier Laboratories Limited and conducted in collaboration with Research Quorum. Cabergoline restriction Indications for the dopamine agonist cabergoline (Cabaser) are being restricted to match those of pergolide (Celance), the MHRA has announced. Pergolide was recently withdrawn in the United States and its use in the EU is limited because of the risk of cardiac valvular damage. Similar toxicity has been reported with cabergolide, which is now restricted to second-line use when a nonergot treatment for Parkinson's disease has failed. It is contraindicated in patients with valvular damage or a history of fibrotic disorders and requires patient monitoring. Sodium reduction cuts CV events Long-term reduction in dietary sodium may reduce cardiovascular events by 25 per cent, US epidemiologists say (BMJ online: 20 April 2007; doi:10.1136/bmj.39147.604896.55). Participants in the two Trials of Hypertension Prevention (TOHP I and II) reduced their sodium intake by 44 and 33mmol per 24hr. After 10,15 years' follow-up of 2415 participants, the adjusted relative risk of cardiovascular events was 0.75 compared with controls. There was a nonsignificant 20 per cent reduction in mortality. Copyright 2007 Wiley Interface Ltd [source]

Population pharmacokinetic analysis of varenicline in adult smokers

Patanjali Ravva
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT? , Several clinical pharmacology studies have characterized the pharmacokinetics of varenicline in young adult and elderly smokers and subjects with impaired renal function. , Varenicline pharmacokinetics is linear over the recommended dose range. , Varenicline total clearance is linearly related to its renal clearance. , Both are progressively reduced as renal function declines, which results in a progressive increase in varenicline systemic exposure and prolonged half-life. WHAT THIS STUDY ADDS? , This work provides an integrated model-based analysis of varenicline pharmacokinetics across multiple studies in the target patient population. , The model describes the impact of patient-specific covariates, such as renal function, and provides a rationale for dose adjustment. , The resulting model also provides a means to predict individual-specific drug exposures to clinical responses in subsequent analyses. AIMS To characterize the population pharmacokinetics of varenicline and identify factors leading to its exposure variability in adult smokers. METHODS Data were pooled from nine clinical studies consisting of 1878 subjects. Models were developed to describe concentration,time profiles across individuals. Covariates were assessed using a full model approach; parameters and bootstrap 95% confidence intervals (CI) were estimated using nonlinear mixed effects modelling. RESULTS A two-compartment model with first-order absorption and elimination best described varenicline pharmacokinetics. The final population parameter estimates (95% CI) were: CL/F, 10.4 l h,1 (10.2, 10.6); V2/F, 337 l (309, 364); V3/F, 78.1 l (61.9, 98.9); Q/F, 2.08 l h,1 (1.39, 3.79); Ka, 1.69 h,1 (1.27, 2.00); and Alag, 0.43 h (0.37, 0.46). Random interindividual variances were estimated for Ka[70% coefficient of variation (CV)], CL/F (25% CV), and V2/F (50% CV) using a block covariance matrix. Fixed effect parameters were precisely estimated [most with % relative standard error < 10 and all with % relative standard error < 25], and a visual predictive check indicated adequate model performance. CL/F decreased from 10.4 l h,1 for a typical subject with normal renal function (CLcr = 100 ml min,1) to 4.4 l h,1 for a typical subject with severe renal impairment (CLcr = 20 ml min,1), which corresponds to a 2.4-fold increase in daily steady-state exposure. Bodyweight was the primary predictor of variability in volume of distribution. After accounting for renal function, there was no apparent effect of age, gender or race on varenicline pharmacokinetics. CONCLUSIONS Renal function is the clinically important factor leading to interindividual variability in varenicline exposure. A dose reduction to 1 mg day,1, which is half the recommended dose, is indicated for subjects with severe renal impairment. [source]

Effect of severe renal impairment on the pharmacokinetics of azimilide following single dose oral administration

Alfred E. Corey
Aims To assess the influence of severe renal impairment on azimilide pharmacokinetics. Methods A single oral dose of 125 mg azimilide dihydrochloride was administered to subjects with normal and severely impaired renal function. Blood and urine samples were collected for 22,28 and 10 days, respectively. Results Azimilide renal clearance decreased in subjects with renal impairment (mean 14 vs 4.8 ml h,1 kg,1, 95% confidence interval on the ratio 0.23, 0.50). However, no change in any other pharmacokinetic parameter including oral clearance (mean 109 vs 104 ml h,1 kg,1, 95% confidence interval on the ratio 0.67, 1.36) was observed. Conclusions Since azimilide blood concentrations are essentially unaffected by renal function, an a priori dosage regimen adjustment is not required in patients with renal impairment. [source]