Creatinine Clearance (creatinine + clearance)

Distribution by Scientific Domains
Distribution within Medical Sciences

Terms modified by Creatinine Clearance

  • creatinine clearance rate

  • Selected Abstracts


    Administration of enoxaparin by continuous infusion in a naturalistic setting: analysis of renal function and safety,

    JOURNAL OF CLINICAL PHARMACY & THERAPEUTICS, Issue 3 2005
    S. L. Kane-Gill Pharm D MSc
    Summary Study objective:, To describe the clinical use and safety of continuous infusion (CI) enoxaparin in a naturalistic setting and to evaluate the influence of renal function on enoxaparin elimination. Design:, Retrospective medical record review. Setting:, 1000-bed tertiary care teaching centre. Patients:, Hospitalized patients that received enoxaparin by CI during a 2-year period. Interventions:, None. Measurements:, Specific details of dosage and monitoring were collected. Adverse drug reactions (ADR) were recorded. Creatinine clearance (CrCl) was calculated using Cockroft and Gault and Brater equations. A population pharmacokinetic analysis was performed using the non-linear mixed effect model (NONMEM). For patients located in the intensive care unit (ICU) and ward, POSTHOC pharmacokinetic parameter estimates were evaluated using the Wilcoxon rank-sum. Pearson correlation coefficient was calculated to determine the association between renal function and anti-Xa clearance. Main results:, Sixty-seven patients received enoxaparin by CI of which 61·2% were in the ward and 38·8% in the ICU. The average initial rate and duration of infusion were 5·2 mg/h and 5·6 days, respectively. The number of anti-Xa concentration measurements averaged five per patient. Nine patients experienced an ADR. The most frequent ADR was gastrointestinal bleeding (n = 4). Among the 67 patients, 48 had available anti-Xa concentrations and were included in the NONMEM model. The anti-Xa CL and volume of distribution for ICU and ward patients averaged 0·64 ± 0·34 L/h, 10·6 ± 1·55 L and 1·01 ± 0·39 L/h, 9·08 ± 1·17 L, respectively. CrCl was not a significant covariate when included in the NONMEM model, and the association between CrCl and anti-Xa clearance was not significant (R2 = 0·0005; P = 0·8916). Conclusions:, This study is the first to report the use and safety of prolonged CI enoxaparin. Pharmacokinetic parameters of enoxaparin differ in ICU vs. ward patients. Overall, we found the safety of CI to be comparable to subcutaneous administration. Also, we found no effect of renal function on enoxaparin elimination. [source]


    The reliability of different formulae to predict creatinine clearance

    JOURNAL OF INTERNAL MEDICINE, Issue 5 2003
    J. C. Verhave
    Abstract., Verhave JC, Baljé-Volkers CP, Hillege HL, de Zeeuw D, de Jong PE (University Medical Center Groningen, Groningen University, Institute of Drug Exploration, Groningen, the Netherlands). The reliability of different formulae to predict creatinine clearance. J Intern Med 2003; 253: 563,573. Objectives., Creatinine clearance (CCR) is a commonly used tool to measure glomerular filtration rate (GFR) in clinical practice. This tool requires collection of 24-h urine, which is quite bothersome. Several different formulae have been used to estimate GFR using plasma creatinine and other easy formulae to obtain biometrical data. We examined 10 formulae and compared them with actually measured CCR in a large sample of the general population. Design., Cross-sectional cohort study. Setting., University hospital outpatient clinic, a population based study. Subjects., A total of 8592 inhabitants of the city of Groningen, 28,75 years of age. The cohort is enriched for microalbuminuria. Results., In general, the formulae did not give an accurate estimation of CCR, particularly not in male and in obese subjects. Six formulae, including the Cockcroft,Gault gave a fairly good estimation of CCR in the overall population and in subgroups of specific gender, body mass index and age. All formulae however, gave an underestimation of the measured CCR in higher ranges of CCR and an overestimation in the lower ranges. Moreover, the age-related decline of CCR is hard to approximate with a formula. Conclusions., We conclude that formulae to estimate CCR in the general population, although giving a fairly good estimate of mean CCR, do not offer reliable data on CCR in the upper and lower ranges and do not adequately estimate the age,related decline in CCR. [source]


    Effect of NSAID administration on creatinine clearance in healthy dogs undergoing anaesthesia and surgery

    JOURNAL OF SMALL ANIMAL PRACTICE, Issue 12 2000
    S. F. Forsyth
    Thirty healthy male dogs were randomly assigned to receive carprofen (4 mg/kg intravenously), ketoprofen (2 mg/kg intravenously) or saline (0.2 ml/kg intravenously) at induction of anaesthesia for castration surgery. A routine castration was undertaken and a buccal mucosal bleeding time was assessed at the completion of surgery. Twenty-four hours after surgery a 24,hour endogenous creatinine clearance study was undertaken. Buccal mucosal bleeding time was not significantly different between the three groups. Creatinine clearance was significantly lower (P , 0.01) in the two groups of dogs that received a non-steroidal anti-inflammatory drug compared with that in the dogs that received sterile saline. There was no significant difference between the carprofen and ketoprofen groups with respect to creatinine clearance. [source]


    The pharmacokinetics of idraparinux, a long-acting indirect factor Xa inhibitor: population pharmacokinetic analysis from Phase III clinical trials

    JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2009
    C. VEYRAT-FOLLET
    Summary.,Background: Idraparinux, a long-acting synthetic pentasaccharide, is a specific antithrombin-dependent inhibitor of activated factor X that has been investigated in the treatment and prevention of thromboembolic events. Objectives: To characterize the population pharmacokinetic profile of idraparinux in patients enrolled in van Gogh and Amadeus Phase III clinical trials. Patients and methods: Idraparinux was administered once-weekly subcutaneously at a dose of 2.5 mg, or 2.5 mg (first dose) and then 1.5 mg for patients with severe renal insufficiency (creatinine clearance <30 mL min,1). A population pharmacokinetic model was developed using data from 704 patients with acute deep-vein thrombosis or pulmonary embolism, 1310 patients suffering from atrial fibrillation, and 40 healthy subjects. Potential covariates analyzed included demographics (age, sex, weight and ethnicity), and serum creatinine and creatinine clearance determinations. Results: A three-compartment model best described idraparinux pharmacokinetics, with interindividual variability on clearance, central volume of distribution, and absorption rate constant; residual variability was low. Typical clearance, central volume of distribution, absorption rate constant and volume of distribution at steady-state were 0.0255 L h,1, 3.36 L, 1.37 h and 30.8 L, respectively. Peak concentration was reached at 2.5 h. The terminal half-life was 66.3 days and time to steady-state was 35 weeks. At steady-state, exposures were similar for patients without and with severe renal impairment receiving adjusted-dose. Creatinine clearance was the most important covariate affecting idraparinux clearance. The particular characteristics of idraparinux , rapid onset of action and long-acting anticoagulant effect , offer interesting clinical perspectives currently under investigation with idrabiotaparinux, the reversible biotinylated form of idraparinux. [source]


    Partial depletion of macrophages by ED7 reduces renal injury in Adriamycin nephropathy

    NEPHROLOGY, Issue 5 2005
    YIPING WANG
    SUMMARY: Background: Because macrophages are considered to be possible effectors of disease in Adriamycin (ADR) nephrosis, we hypothesized that depletion of macrophages might protect against the initiation of renal injury. In the present study, a monoclonal antibody (ED7) directed against CD11b/CD18 integrin, which is expressed by macrophages, was used to investigate the pathogenetic effects of macrophages in ADR nephropathy. Methods: Male Wistar rats were treated with ED7 antibody, starting 1 day prior to ADR (7.5 mg/kg) treatment, or 7 days post-ADR when overt proteinuria was established. Results: Circulating ED7-positive cells were reduced by approximately 30% in rats with ADR nephrosis by the ED7 antibody, while the number of macrophages in the renal cortex of ADR rats was reduced by nearly 50% with the ED7 treatment, whether administered before or after ADR. Creatinine clearance was significantly ameliorated by ED7 when commenced pre-ADR (P < 0.05), but not when commenced post-ADR (P = NS) in comparison to untreated ADR rats. However, proteinuria was not alleviated by either ED7 treatment. Morphometric analysis showed less glomerular sclerosis when ED7 was commenced pre-ADR compared with ADR alone (P < 0.01), but not when commenced post-ADR (P = NS). Tubular atrophy was reduced by ED7 when it was commenced pre-ADR (tubular cell height and tubular diameter: P < 0.01 and P < 0.001, respectively), as was interstitial expansion (P < 0.01) compared with ADR alone. Cortical macrophage infiltration was reduced by 50% compared with ADR alone by the ED7 commenced before or after ADR. The number of cortical CD4+ T cells fell with ED7 starting pre-ADR, but not with the ED7 treatment commencing after ADR. Conclusion: Partial macrophage depletion starting before but not after ADR protected both renal function and structure in this model of chronic proteinuric renal disease. [source]


    Glomerular Size in Early Protocol Biopsies is Associated with Graft Outcome

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2005
    F. Azevedo
    Long-term consequences of glomerular enlargement after transplantation are not well understood. The aim is to evaluate the relationship between glomerular volume (Vg) estimated in protocol biopsies, graft function and graft survival. Vg and Banff chronic damage score were evaluated in protocol biopsies at 4 months. Creatinine clearance (CrCl) was estimated by the Cockroft-Gault formula. Vg estimated in 144 patients was 4.8 ± 2.0 × 106,3. It was associated with donor age (r = 0.23, p < 0.01), recipient body mass index (r = 0.17, p = 0.04), delayed graft function (Vg = 5.9 ± 2.3 vs. 4.6 ± 1.9 × 106,3, p < 0.01) and CrCl (r = 0.17, p = 0.04). The best cutoff of Vg, Banff chronic damage score and CrCl was determined by Cox regression analysis, being 5.0 × 106,3 for Vg (relative risk (RR): 2.4, 95% confidence interval (CI): 1.03,5.6), >2 for chronic damage score (RR: 3.4, 95% CI: 1.03,8.9) and 60 mL/min for CrCl (RR: 3.5, 95% CI: 1.04,11.9). These variables were independent predictors of death-censored graft survival. According to Vg and CrCl, four groups of patients were defined. Patients with small glomeruli and high CrCl had a 95% graft survival while patients with large glomeruli and low CrCl had a 45% graft survival at 15 years (p < 0.01). Large glomerular volume, high Banff chronic score and poor early renal function in stable grafts are independently associated with death-censored graft survival. [source]


    Outcome of Nonheart-Beating Donor Kidneys with Prolonged Delayed Graft Function after Transplantation

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2005
    Jeroen J. M. Renkens
    Nonheart-beating donor (NHBD) kidneys are frequently associated with delayed graft function (DGF), with a deleterious effect on kidney function and allograft survival. The influence and the duration of DGF on the outcome of NHBD kidneys are assessed. All recipients of an NHBD kidney in the period 1993,2003 were reviewed. Excluded from analysis were patients with primary nonfunction (PNF). One hundred and five patients with a functioning NHBD graft were reviewed: 23 (22%) had immediate function (group 1), 40 (38%) had DGF , 2 weeks (group 2), 31 (30%) had DGF 15 days to 4 weeks (group 3) and 11 (10%) had DGF for >4 weeks (group 4). Creatinine clearance at 3 months was higher in groups 1 and 2 versus group 4 (p = 0.015 and p = 0.006, respectively) and was higher in group 2 versus group 4, at 1 year (p = 0.01). Graft survival was 95%, 98%, 97% and 89%, respectively, at 1 year and 95%, 85%, 77% and 89%, respectively, at 5 years, which was not significantly different. The duration of DGF in NHB kidneys has a negative effect on creatinine clearance, but no effect on graft survival. [source]


    Monitoring of renal function in patients with spinal cord injury

    BJU INTERNATIONAL, Issue 9 2000
    S.A. Macdiarmid
    Objective To assess the sensitivity of serum creatinine level in detecting clinically important and early deterioration of renal function in patients with spinal cord injury (SCI), and to evaluate the optimal method of determining creatinine clearance in these patients. Patients and methods The serum creatinine level of 36 patients (25 paraplegics and 11 quadriplegics) was evaluated and compared with the corresponding measured creatinine clearance rate. Correlations were also assessed between the creatinine clearance measured by 24-h endogenous clearance, single-shot 99mTc-labelled diethylenetriamine pentaacetic acid (99mTc-DTPA) clearance technique, and the Cockcroft,Gault formula, to test their validity. Results Of the 36 patients 11 (31%) had a measured creatinine clearance of < 100 mL/min (mean 84.8) and a corresponding normal serum creatinine level. Creatinine clearance calculated by the Cockcroft,Gault formula did not correlate well with that measured by the 24-h endogenous clearance (r = 0.426) and 99mTc-DTPA clearance (r = 0.366), overestimating creatinine clearance in all but three patients. The mean (sd) difference between the creatinine clearance measured by the 24-h and DTPA clearance technique was 17.7 (16.5)% and the correlation between these techniques was good (r = 0.71). Conclusion Serum creatinine level is not sensitive in detecting early deterioration of renal function in patients with SCI. The Cockcroft,Gault formula generally significantly overestimates the true creatinine clearance and is not recommended. The 24-h endogenous creatinine clearance measured on appropriately collected urine samples is an acceptable accurate and practical method of determining glomerular filtration rate in patients with SCI. [source]


    Immunosuppression with mycophenolate mofetil attenuates the development of hypertension and albuminuria in deoxycorticosterone acetate-salt hypertensive rats

    CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 10 2010
    Erika I Boesen
    Summary 1. The interplay between the immune and renin,angiotensin systems is emerging as a crucial factor in the development and progression of hypertension. The aim of the present study was to determine the involvement of immune cells in the hypertension and renal injury produced by a non-angiotensin II-dependent form of hypertension, namely deoxycorticosterone acetate (DOCA)-salt-induced hypertension, in rats. 2. Male Sprague-Dawley rats underwent uninephrectomy and received either a sustained-release pellet of DOCA s.c. and 0.9% NaCl (saline) to drink for 21 days or a placebo pellet and water to drink for 21 days. Additional groups of DOCA-salt- and placebo-treated rats were treated concurrently with the immune suppressant mycophenolate mofetil (MMF; 30 mg/kg per day). Rats were placed in metabolic cages for 24 h urine collection prior to and at weekly intervals during the 21 day experimental period. 3. Mycophenolate mofetil significantly attenuated the development of hypertension in DOCA-salt rats compared with untreated DOCA-salt hypertensive rats (mean arterial pressure by telemetry on Day 18 146 ± 7 vs 180 ± 3 mmHg, respectively; P < 0.001), as well as proteinuria (87 ± 27 vs 305 ± 63 mg/day, respectively, on Day 21) and albuminuria (51 ± 15 vs 247 ± 73 mg/day, respectively, on Day 21). Creatinine clearance was better preserved in MMF-treated DOCA-salt rats compared with untreated DOCA-salt rats (0.74 ± 0.07 vs 0.49 ± 0.09 mL/min, respectively; P < 0.05), but was still significantly reduced compared with that in the placebo group (1.15 ± 0.12 mL/min; P < 0.05). Finally, MMF treatment significantly attenuated the DOCA-salt-induced rise in renal cortical T-lymphocyte and macrophage infiltration (P < 0.05). 4. These data indicate that immune cells play a deleterious role in both the hypertension and renal injury associated with DOCA-salt hypertension. [source]


    MR determination of glomerular filtration rate in subjects with solitary kidneys in comparison to clinical standards of renal function: feasibility and preliminary report,

    CONTRAST MEDIA & MOLECULAR IMAGING, Issue 2 2009
    Richard W. Katzberg
    Abstract This study was conducted to demonstrate the feasibility of quantifying single kidney glomerular filtration rate (skGFR) by magnetic resonance (MR) by comparison to the clinical estimates of GFR in volunteer subjects with a single kidney. Seven IRB-approved subjects with a solitary kidney, stable serum creatinine (SCr) and a 24,h creatinine clearance (CrCl) volunteered to undergo an MR examination that determined renal extraction fraction (EF) with a breathhold inversion recovery echo planar pulse sequence and renal blood flow with a velocity encoded phase imaging sequence. The product of EF and blood flow determines GFR. These values were compared with the 24,h CrCl, estimated GFR by the modification of diet in renal disease (MDRD) regression analysis and the Cockroft,Gault (CG) determination of CrCl. The mean and standard deviation of differences between the MR GFR, MDRD and CG vs the 24,h CrCl were 12.3,±,35.7, ,8.9,±,18.5 and 1.2,±,19.6, respectively. The Student t -test showed that none of the mean differences were statistically significant between techniques. This clinical investigation shows that MR can be used for skGFR determination in human subjects with comparable values to those derived from clinically used serum-based GFR estimation techniques. Copyright © 2009 John Wiley & Sons, Ltd. [source]


    Prolonged exposure to inhaled nitric oxide transiently modifies tubular function in healthy piglets and promotes tubular apoptosis

    ACTA PHYSIOLOGICA, Issue 4 2009
    W. Go, dzik
    Abstract Aim:, Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator. We hypothesized that those piglets exposed to prolonged iNO react with a modified renal function. Methods:, Randomized, placebo-controlled exposure to 40 p.p.m. iNO (30 h) in piglets (n = 20). Plasma and urine were sampled during three periods (first and second 12 h periods, and finally a 6 h period). We measured urine volumes, plasma and urine electrolytes (UNa, UK, UCl), plasma creatinine and urea. We calculated creatinine clearance (Ccr), and fractional excretions of sodium and potassium (FENa, FEK) and urinary excretions of electrolytes (UENa, UEK, UECl). Haemodynamic data were recorded and renal tubular apoptosis detected. Results:, For the first 12 h, certain parameters significantly increased in the iNO group (mean ± SD): UNa (mmol L,1), 87.7 (±35.0) vs. 39.3 (±22.9), UCl (mmol L,1) 80.4 (±32.8) vs. 48.0 (±26.7), FENa (%) 2.1 (±0.8) vs. 0.7 (±0.5), FEK (%) 31.7 (±7.0) vs. 20.7 (±12.3), as well as UENa (mmol) 61.0 (±21.1) vs. 27.6 (±17.9) and UECl (mmol) 57.3 (24.5) vs. 37.6 (29.0). These changes were absent in the second and third periods of the study. Significant differences in percentage of apoptotic cell nuclei in the renal cortex and medulla were found after iNO exposure: 39% vs. 15%. Conclusion:, Exposure to 40 p.p.m. iNO in healthy anaesthetized piglets has a transient natriuretic effect that disappears after 12 h. We also found evidence of renal tubular apoptosis promotion after 30 h of iNO. [source]


    Myocardial perfusion imaging and cardiac events in a cohort of asymptomatic patients with diabetes living in southern France

    DIABETIC MEDICINE, Issue 4 2006
    A. Sultan
    Abstract Aims, To assess the association between abnormal stress myocardial perfusion imaging (MPI) and cardiac events (CE) in asymptomatic patients with diabetes and with , 1 additional risk factor. Predictors of abnormal stress MPI were also evaluated. Methods, Four hundred and forty-seven consecutive patients who underwent stress MPI were prospectively followed for 2.1 [0.5,4.1] years for the subsequent occurrence of hard CE (myocardial infarction and sudden or coronary death) and soft CE (unstable angina and ischaemic heart failure requiring hospitalization). Re-vascularization procedures performed as a result of the screening protocol were not included in the analysis. Results, Follow-up was successful in 419 of 447 patients (94%), of whom 71 had abnormal MPI at baseline. Medical therapy was intensified in all subjects and especially in those with abnormal MPI. Twenty-three patients with abnormal MPI underwent a re-vascularization procedure. CEs occurred in 14 patients, including six of 71 patients (8.5%) with abnormal MPI and eight of 348 patients (2.3%) with normal MPI (P < 0.005). Only two patients developed a hard CE and 12 a soft CE. In multivariate analysis, abnormal MPI was the strongest predictor for CEs [odds ratio (OR) (95% CI) = 5.6 (1.7,18.5)]. Low-density lipoprotein cholesterol , 3.35 mmol/l [OR (95% CI) = 7.3; 1.5,34.7] and age > median [OR (95% CI) = 6.0 (1.2,28.6)] were additional independent predictors for CE. The independent predictors for abnormal MPI were male gender, plasma triglycerides , 1.70 mmol/l, creatinine clearance < 60 ml/min and HbA1c > 8%, with male gender the strongest [OR (95% CI) = 4.0 (1.8,8.8)]. Conclusions, Asymptomatic patients with diabetes in this study had a very low hard cardiac event rate over an intermediate period. This could be explained by the effects of intervention or by the low event rate in the background population. Randomized studies of cardiac heart disease screening are required in asymptomatic subjects with diabetes to determine the effectiveness of this intervention. Diabet. Med. (2006) [source]


    Urinary L-FABP and anaemia: distinct roles of urinary markers in type 2 diabetes

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2 2010
    M. Von Eynatten
    Eur J Clin Invest 2010; 40 (2): 95,102 Abstract Background, Urinary liver-type fatty acid binding protein (L-FABP) and kidney injury molecule (KIM)-1, novel urinary biomarkers of renal tubulointerstitial function, have previously been associated with acute ischaemic kidney injury. We studied the clinical significance of urinary L-FABP, KIM-1 and N -acetyl-,-glucosaminidase (NAG) as potential markers of renal function and chronic ischaemic injury in patients with diabetic nephropathy. Material and methods, A total of 130 type 2 diabetes patients with early diabetic nephropathy and 40 healthy controls were studied. Urinary L-FABP, KIM-1, NAG, albumin excretion rate (AER) and creatinine clearance were obtained from 24-h urine samples, and correlated with measures of red blood cell count, renal function and metabolic control. Results, Urinary L-FABP was significantly increased in diabetes patients compared with healthy controls [8·1 (interquartile 0·6,11·6) vs. 2·4 (0·5,3·6) ,g/g creatinine, P < 0·001] and correlated with AER (r = 0·276, P = 0·002), creatinine clearance (r = ,0·189, P = 0·033) and haemoglobin levels (r = ,0·190, P = 0·030). In multivariable linear regression analysis, haemoglobin (, = ,0·247, P = 0·015) and AER (, = 0·198, P = 0·046) were significant predictors of urinary L-FABP. Prevalent anaemia was independently associated with a 6-fold risk for increased tubulointerstitial kidney damage (upper vs. lower two L-FABP tertiles: OR, 6·06; 95% CI: 1·65,22·23; P = 0·007). Urinary KIM-1 was not significantly associated with kidney function, AER, or measures of red blood cell count while urinary NAG was associated with parameters of glucose control and renal function. Conclusions, Different urinary biomarkers may reflect distinct pathophysiological mechanisms of tubulointerstitial damage in early diabetic nephropathy: Urinary L-FABP could be a novel biomarker for chronic intrarenal ischaemia. [source]


    Anaemia after renal transplantation

    EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 2005
    M. Lorenz
    Abstract Anaemia is a frequent complication among long-term renal transplant recipients. A prevalence of approximately 40% has been reported in several studies. If renal function declines to stage 5 kidney disease, the prevalence of anaemia in kidney transplants is even higher. A positive correlation between haemoglobin concentration and creatinine clearance has been reported, which is a function of endogenous erythropoietin production by the functioning graft. Inflammation related to a retained kidney graft may cause hypo-responsiveness to erythropoietic agents once kidney transplant recipients return to dialysis. Furthermore, the use of azathioprine, mycophenolate mofetil and sirolimus may be associated with post-transplant anaemia. Along with erythropoietin deficiency, depletion of iron stores is one of the major reasons for anaemia in the kidney transplant population. The proportion of hypochromic red blood cells appears to be a useful parameter to measure iron supply and utilization as well as to estimate mortality risks in kidney transplant recipients. While anaemia is an important cardiovascular risk-factor after transplantation, our data suggest that anaemia is not associated with mortality and graft loss. Nevertheless, inadequate attention is paid so far to the management of anaemia after renal transplantation. A promising future aspect for risk reduction of cardiovascular disease includes the effect of erythropoietic agents on endothelial progenitor cells. [source]


    Lenalidomide and dexamethasone for the treatment of refractory/relapsed multiple myeloma: dosing of lenalidomide according to renal function and effect on renal impairment

    EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 1 2010
    Meletios A. Dimopoulos
    Abstract Objectives:, Lenalidomide and dexamethasone (LenDex) is an active regimen for relapsed/refractory multiple myeloma (MM). However, there is limited data for the effect of LenDex on renal impairment (RI) and on renal reversibility. Patients & Methods:, Fifty consecutive patients with relapsed/refractory MM received LenDex in 28-d cycles. Median lines of previous therapies were 2 (range: 1,6). Lenalidomide was administered on days 1,21 according to creatinine clearance (CrCl), while dexamethasone was given at a dose of 40 mg on days 1,4 and 15,18 for the first four cycles and only on days 1,4 thereafter. Results:, Twelve patients (24%) had RI at baseline, defined as CrCl < 50 mL/min. Most patients were pretreated with either thalidomide or bortezomib and > 50% of them were refractory to both drugs. At least partial response was documented in 60.5% and 58% of patients with and without RI. Median progression-free survival (PFS) and overall survival (OS) for all patients was 9 and 16 months, respectively. RI was not associated with an inferior PFS or OS. There were no differences in the incidence of adverse events among patients with and without RI. Three of 12 patients with RI (25%) achieved complete renal response and two (16%) achieved minor renal response with LenDex. Conclusions:, We conclude that LenDex is an active treatment even in heavily pretreated MM. With dosing of lenalidomide according to renal function, LenDex can be administered to patients with RI (who may not have other treatment options) without excessive toxicity. Furthermore, LenDex may improve the renal function in approximately 40% of patients with RI. [source]


    Dialysate concentration and pharmacokinetics of 2F-Ara-A in a patient with acute renal failure

    EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2005
    Jan T. Kielstein
    Abstract:, Fludarabine is frequently used for treatment of B-cell chronic lymphocytic leukemia and in conditioning regimes for hematopoietic cell transplantations. The total body clearance of the principal metabolite 2-fluoro-ara-A (2F-Ara-A) correlates with the creatinine clearance. We report data on total dialysate concentration as well as pharmacokinetics of 2F-Ara-A in a patient with anuric acute renal failure. On three consecutive days the patient received a daily dose of 80 mg (40 mg/m2) fludarabine and underwent three consecutive extended (daily) dialysis (ED) sessions. ED removed a considerable amount of the drug. The average dialysis clearance was 33.85 ml/min which is about 25% of the clearance in patients without renal failure. No toxic side effects of the treatment were observed. This case suggests that fludarabine treatment can be considered in patients requiring dialysis if dose reduction and adequate removal of the drug by hemodialysis is provided. [source]


    Population pharmacokinetics of imipenem in burn patients

    FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 6 2003
    Eric Dailly
    Abstract The interindividual variability of imipenem pharmacokinetic parameters in burn patients suggest that these parameters have to be estimated with a large number of patients. The aim of this study is (i) to estimate these parameters with a population pharmacokinetic approach, and (ii) to test the influence of factors on pharmacokinetics parameters. Data are provided by therapeutic drug monitoring (n = 47, 118 samples) and analysed by a nonlinear mixed effect modelling method. Among the tested covariates (age, gender, body weight, height, size of burn and creatinine plasma level) creatinine plasma level affects imipenem pharmacokinetic parameters substantially. The best fit is obtained with a two-compartment model integrating a linear,inverse relationship between imipenem clearance and creatinine plasma level. The estimates of imipenem clearance (16.37 ± 0.204 L/h) and of the distribution volume of the central compartment (0.376 ± 0.039 L/kg) are higher in the population of burn patients than the estimates in healthy subjects. This result is connected with high values of glomerule filtration rate and confirms the interest of therapeutic drug monitoring of imipenem in burn patients and particularly for patients with extreme values of creatinine clearance. [source]


    Application of pharmacokinetic modelling to the routine therapeutic drug monitoring of anticancer drugs

    FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 4 2002
    Annick Rousseau
    Abstract Over the last 10 years, proofs of the clinical interest of therapeutic drug monitoring (TDM) of certain anticancer drugs have been established. Numerous studies have shown that TDM is an efficient tool for controlling the toxicity of therapeutic drugs, and a few trials have even demonstrated that it can improve their efficacy. This article critically reviews TDM tools based on pharmacokinetic modelling of anticancer drugs. The administered dose of anticancer drugs is sometimes adjusted individually using either a priori or a posteriori methods. The most frequent clinical application of a priori formulae concerns carboplatin and allows the computation of the first dose based on biometrical and biological data such as weight, age, gender, creatinine clearance and glomerular filtration rate. A posteriori methods use drug plasma concentrations to adjust the subsequent dose(s). Thus, nomograms allowing dose adjustment on the basis of blood concentration are routinely used for 5-fluorouracil given as long continuous infusions. Multilinear regression models have been developed, for example for etoposide, doxorubicin, carboplatin, cyclophosphamide and irinotecan, to predict a single exposure variable [such as area under concentration,time curve (AUC)] from a small number of plasma concentrations obtained at predetermined times after a standard dose. These models can only be applied by using the same dose and schedule as the original study. Bayesian estimation offers more flexibility in blood sampling times and, owing to its precision and to the amount of information provided, is the method of choice for ensuring that a given patient benefits from the desired systemic exposure. Unlike the other a posteriori methods, Bayesian estimation is based on population pharmacokinetic studies and can take into account the effects of different individual factors on the pharmacokinetics of the drug. Bayesian estimators have been used to determine maximum tolerated systemic exposure thresholds (e.g. for topotecan or teniposide) as well as for the routine monitoring of drugs characterized by a very high interindividual pharmacokinetic variability such as methotrexate or carboplatin. The development of these methods has contributed to improving cancer chemotherapy in terms of patient outcome and survival and should be pursued. [source]


    Survival to discharge among patients treated with CRRT

    HEMODIALYSIS INTERNATIONAL, Issue 1 2005
    R. Wald
    Continuous renal replacement therapy (CRRT) is widely used in critically ill patients with acute renal failure (ARF). The survival of patients who require CRRT and the factors predicting their outcomes are not well defined. We sought to identify clinical features to predict survival in patients treated with CRRT. We reviewed the charts of all patients who received CRRT at the Toronto General Hospital during the year 2002. Our cohort (n = 85) represented 97% of patients treated with this modality in 3 critical care units. We identified demographic variables, underlying diagnoses, transplantation status, location (medical-surgical, coronary or cardiovascular surgery intensive care units), CRRT duration, baseline creatinine clearance (CrCl), and presence of oliguria (<400 ml/d) on the day of CRRT initiation. The principal outcome was survival to hospital discharge. Among those alive at discharge, we assessed whether there was an ongoing need for renal replacement therapy. Greater than one-third (38%, 32/85) of patients survived to hospital discharge. Three (9%) of the survivors remained dialysis-dependent at the time of discharge. Survivors were younger than non-survivors (mean age 56 vs 60 y.), were on CRRT for a shorter duration (7 vs 13 d.), and had a higher baseline CrCl (79 vs 68 ml/min). Patient survival varied among different critical care units (medical surgical 33%, coronary 38%, and cardiovascular surgery 45%). Multivariable logistic regression revealed that shorter duration of CRRT, non-oliguria, and baseline CrCl > 60 ml/min were independently associated with survival to hospital discharge (p < 0.05). Critically ill patients with ARF who require CRRT continue to have high in-hospital mortality. A shorter period of CRRT dependence, non-oliguria, and higher baseline renal function may predict a more favorable prognosis. The majority of CRRT patients who survive their critical illness are independent from dialysis at the time of hospital discharge. [source]


    Invasive bladder carcinoma: A pilot study of conservative treatment with accelerated radiotherapy and concomitant cisplatin,

    INTERNATIONAL JOURNAL OF CANCER, Issue 6 2001
    Abderrahim Zouhair M.D.
    Abstract From November 1992 to December 1997, 25 patients (inoperable or refusing cystectomy) were included in a prospective study to assess the feasibility, tolerance, and curative potential of accelerated radiotherapy (RT) and concomitant cisplatin. Median age was 74 years (range 49,86). Stage distribution was as follows: 1 T1, 10 T2, 8 T3, and 6 T4. Two patients had clinically positive pelvic nodes. The goal was to deliver a total dose of 40 Gy to the whole pelvis and bladder in 4 weeks using a concomitant boost of 20 Gy to the tumor or to the whole bladder during the third and fourth weeks (total dose 60 Gy), with daily cisplatin (6 mg/m2) before RT for patients with creatinine clearance > 50 ml/min. All but one patient completed the RT protocol. Daily cisplatin was sucessfully delivered in 18 patients. One patient presented with grade III ototoxicity. Diarrhea was scored grade III in two and grade IV in two patients. Acute urinary toxicity was scored grade III in one patient. Posttreatment late effects included bladder grade II and grade III in two patients and one patient, respectively; large bowel grade III in one; urethral grade III in one; and femoral head radionecrosis in one. Four-year overall and disease-specific survival rates were 23% and 35%, respectively. The latter was 60% for patients with T2 tumors. The 4-year actuarial locoregional control rate for all patients was 61%. In summary, accelerated RT and concomitant cisplatin is feasible with acceptable tolerance even in relatively old patients. Although outcome was better for patients with low-stage tumors, local control and survival rates appeared similar to those of standard RT schedules for a similar patient population. © 2001 Wiley-Liss, Inc. [source]


    Assessment of renal function with color Doppler ultrasound in autosomal dominant polycystic kidney disease

    INTERNATIONAL JOURNAL OF UROLOGY, Issue 3 2001
    Akira Kondo
    Abstract Background: Measurement of renal blood flow by color Doppler ultrasound is useful for assessment of renal function in a variety of renal disorders. In autosomal dominant polycystic kidney disease (ADPKD), however, it might be difficult to visualize interlobar arteries because of deformity of renal structure. To evaluate the usefulness of color Doppler in ADPKD, parameters determined by blood flow examination were compared with the results of ordinal renal function tests. Methods: Twenty-one patients with ADPKD were examined by color Doppler ultrasound measurement. In each patient, 10 interlobar arteries in both kidneys were investigated. Minimum blood flow velocity (Vmin), maximum blood flow velocity (Vmax), mean blood flow velocity (Vmean), acceleration, resistive index and pulsatility index were measured in relation to the results of creatinine clearance, serum creatinine, blood urea nitrogen and 15 and 120 min values of the phenolsulfonphthalein test. Results: In all patients, interlobar arteries were able to be visualized and blood-flow profile was measured. Although variations of Vmin, Vmax, Vmean and acceleration were relatively large, the resistive index and pulsatility index varied little in each kidney. Mean values of Vmin (P < 0.005), Vmean (P < 0.05), resistive index (P < 0.005) and pulsatility index (P < 0.005) were well correlated to creatinine clearance with statistical significance. Conclusions: In ADPKD, color Doppler ultrasound measurement is a useful method for assessment of renal function and could be used for monitoring the dynamic state of renal blood flow as a non-invasive technique. [source]


    Once-Daily Cefepime Versus Ceftriaxone for Nursing Home,Acquired Pneumonia

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 5 2007
    Joseph A. Paladino PharmD
    OBJECTIVES: To compare once-daily intramuscular cefepime with ceftriaxone controls. DESIGN: Double-blind study. SETTING: Six skilled nursing facilities. PARTICIPANTS: Residents aged 60 and older with nursing home,acquired pneumonia. INTERVENTION: Cultures were obtained, and patients were randomized to cefepime or ceftriaxone 1 g intramuscularly every 24 hours. MEASUREMENTS: Clinical success: cure or improvement. Cure was defined as complete resolution of all symptoms and signs of pneumonia or a return to the patient's baseline state. Improvement was defined as clear improvement but incomplete resolution of all pretherapy symptoms or signs or incomplete return to the patient's usual baseline status. Safety and pharmacoeconomics were also assessed. RESULTS: Sixty-nine patients were randomized; 61 were evaluable: (32 to cefepime, 29 ceftriaxone). Patients were predominately female (76%). They had a mean age±standard deviation of 85±6, with a mean 5.8±1.9 comorbidities; they had age-appropriate renal dysfunction, with a mean estimated creatinine clearance of 35±7 mL/min. Clinical success occurred in 78% of cefepime- and 66% of ceftriaxone-treated patients (P=.39). Fifty-seven patients (93%) were switched to oral antibiotics after 3 days. Antibiotic-related adverse events occurred in 5% of patients. Seven patients (11.5%) were hospitalized. The overall mortality rate was 8%. Mean antibiotic costs were $117±40 for cefepime- and $215±68 for ceftriaxone-treated patients (P<.001). Cost-effectiveness analysis of total costs showed that cefepime would cost $597 and ceftriaxone $1,709 per expected successfully treated patient. One- and two-way sensitivity analyses using a generic price for ceftriaxone and improving its comparative efficacy revealed that the results were robust. CONCLUSIONS: Once-daily cefepime was a cost-effective alternative to ceftriaxone for the treatment of elderly nursing home residents who developed pneumonia and did not require hospitalization. [source]


    Estimation of Glomerular Filtration Rate in Older Patients with Chronic Renal Insufficiency: Is the Modification of Diet in Renal Disease Formula an Improvement?

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 7 2003
    Edmund J. Lamb PhD
    OBJECTIVES: To evaluate a new formula for glomerular filtration rate (GFR), derived from the Modification of Diet in Renal Disease (MDRD) study in older people. DESIGN: An observational study of the performance of the MDRD formula compared with other formulae and creatinine clearance (ClCr) as measures of the GFR. SETTING: Volunteers were recruited via outpatient clinics. PARTICIPANTS: Fifty-two patients (27 men, 25 women: mean age 80, range 69,92) with a variety of medical diagnoses. Mean GFR was 53.3 mL/min/1.73 m2 (range 15.9,100.2). Exclusion criteria included renal replacement therapy/renal transplantation and cognitive impairment. MEASUREMENTS:51Chromium ethylenediaminetetraacetic acid (51Cr EDTA) was used as the reference method against which the formulaic estimates of GFR were compared using bias plot and regression analyses. RESULTS: The MDRD and Cockcroft and Gault formulae (both coefficient of determination (R2) = 0.84) gave the best fit with GFR, followed by the Jelliffe formula (R2 = 0.81), ClCr (R2 = 0.73) and the Baracskay formula (R2 = 0.56). ClCr (,1.2%) demonstrated minimal bias compared with the MDRD (8.0%) and Cockcroft and Gault (,10.4%) formulae. However, imprecision compared with 51Cr EDTA was lowest for the Cockcroft and Gault formula, with 50% of estimates lying between ,9.5 and ,0.5 mL/min/1.73 m2 of measured 51Cr EDTA clearance. This compares with ,6.7 and 10.1 mL/min/1.73 m2 for ClCr and 0.0 and 12.7 mL/min/1.73 m2 for the MDRD formula. CONCLUSION: Calculated estimates of GFR are an improvement over ClCr estimation. On balance, the MDRD formula does not improve the estimate of GFR compared with the Cockcroft and Gault formula in older Caucasian patients with chronic renal insufficiency. [source]


    Predictors of Health Resource Use by Disabled Older Female Medicare Beneficiaries Living in the Community

    JOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 3 2003
    Michael Weiner MD
    OBJECTIVES: To identify specific clinical factors that could best predict resource use by disabled older women. DESIGN: Cross-sectional. SETTING: Urban community in Baltimore, Maryland. PARTICIPANTS: One thousand two community-dwelling, moderately to severely disabled, female Medicare beneficiaries aged 65 and older, from the Women's Health and Aging Study I (WHAS). MEASUREMENTS: WHAS data were merged with participants' 1992,1994 Medicare claims data for the year after baseline evaluation, reflecting inpatient, outpatient, home-based, and skilled-nursing services. The independent contributions of factors hypothesized to predict health expenditures were assessed, using chi-square and regression analyses, with the logarithm of Medicare expenditures as the primary outcome. RESULTS: Demographic factors were not associated with Medicare expenditures. Factors associated with expenditures in bivariate analyses included heart disease (1.4x), chronic obstructive pulmonary disease (1.3x), diabetes mellitus (1.1x), smoking, comorbidity, and severity of disability, as well as low creatinine clearance, serum albumin, caloric expenditure, or skinfold thickness. Heart disease, diabetes mellitus, and low skinfold thickness remained significant after adjustment for other factors. CONCLUSION: Heart disease, diabetes mellitus, and low skinfold thickness are important independent predictors of 1-year Medicare expenditures by disabled older women. Many other variables that reflect disease, disability, nutrition, or personal habits have less predictive ability. Most demographic factors are not predictors of expenditures in this population. Focusing on the best predictors may facilitate more-effective risk adjustment and creation of related health policies. [source]


    Low-dose vasopressin increases glomerular filtration rate, but impairs renal oxygenation in post-cardiac surgery patients

    ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 8 2009
    G. BRAGADOTTIR
    Background: The beneficial effects of vasopressin on diuresis and creatinine clearance have been demonstrated when used as an additional/alternative therapy in catecholamine-dependent vasodilatory shock. A detailed analysis of the effects of vasopressin on renal perfusion, glomerular filtration, excretory function and oxygenation in man is, however, lacking. The objective of this pharmacodynamic study was to evaluate the effects of low to moderate doses of vasopressin on renal blood flow (RBF), glomerular filtration rate (GFR), renal oxygen consumption (RVO2) and renal oxygen extraction (RO2Ex) in post-cardiac surgery patients. Methods: Twelve patients were studied during sedation and mechanical ventilation after cardiac surgery. Vasopressin was sequentially infused at 1.2, 2.4 and 4.8 U/h. At each infusion rate, systemic haemodynamics were evaluated by a pulmonary artery catheter, and RBF and GFR were measured by the renal vein thermodilution technique and by renal extraction of 51chromium,ethylenediaminetetraacetic acid, respectively. RVO2 and RO2Ex were calculated by arterial and renal vein blood samples. Results: The mean arterial pressure was not affected by vasopressin while cardiac output and heart rate decreased. RBF decreased and GFR, filtration fraction, sodium reabsorption, RVO2, RO2Ex and renal vascular resistance increased dose-dependently with vasopressin. Vasopressin exerted direct antidiuretic and antinatriuretic effects. Conclusions: Short-term infusion of low to moderate, non-hypertensive doses of vasopressin induced a post-glomerular renal vasoconstriction with a decrease in RBF and an increase in GFR in post-cardiac surgery patients. This was accompanied by an increase in RVO2, as a consequence of the increases in the filtered tubular load of sodium. Finally, vasopressin impaired the renal oxygen demand/supply relationship. [source]


    Clinical value of urinary kidney biomarkers for estimation of renal impairment in elderly Chinese with essential hypertension

    JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 1 2008
    XunHui Xu
    Abstract The purpose of this work was to observe the excretion of specific types of urinary proteins and urinary enzymes in elderly essential hypertension patients, for early detection and targeted treatment of hypertensive nephropathy in the elderly. A total of 120 elderly essential hypertensive patients and 38 healthy elderly volunteers were involved. The urinary excretion rate of retinal-binding protein (RBP), transferrin (Tf), albumin (Alb), and urinary enzyme N-acetyl-beta-D-glucosaminidase (NAG) activity were determined. Patients were divided into two groups according to their creatinine clearance (Cockroft-Gault formula). There were 88 patients in group A, whose glomerular filtration rate (GFR) was ,80,mL/min, and 32 patients in group B with a GFR <80,mL/min. Among the essential hypertensive patients, urinary excretion rates of RBP, Alb, Tf, and NAG were increased in both groups compared with the healthy controls. But the amount of urinary protein differed between group A and group B. The excretion rate of specific urinary protein and urinary enzyme had a positive relationship with the duration of course of hypertension. We believe that specific types of urinary proteins and urinary enzymes may be useful markers for early diagnosis of hypertensive nephropathy; they can also be regarded as a clinical indicator of the progression of hypertensive nephropathy, serving in the assessment of therapeutic effects. J. Clin. Lab. Anal. 22:86,90, 2008. © 2008 Wiley-Liss, Inc. [source]


    Relationship between renal anemia and prognostic stages of IgA nephropathy

    JOURNAL OF CLINICAL LABORATORY ANALYSIS, Issue 2 2005
    Seiki Aruga
    Abstract In 2002, the Joint Committee of the Special Study Group on Progressive Glomerular Diseases, Ministry of Health, Labor and Welfare of Japan newly revised the clinical guidelines for IgA nephropathy (Sakai et al.: Jpn J Nephrol 37:417,421, 1995; Tomino and Sakai: Clin Exp Nephrol, 7, 93,97, 2003). The prognostic stages were classified into four groups: the good prognosis group (Group I), relatively good prognosis group (Group II), relatively poor prognosis group (Group III), and poor prognosis group (Group IV). The relationship between the levels of Hb, Ht, and RBC in peripheral blood and the renal prognostic stages was determined in 62 patients with IgA nephropathy in the present study. The mean levels of Hb, Ht, and RBC were significantly lower in Group IV than in Group I (P<0.05). However, there were no significant changes in the levels of serum creatinine (s-Cr) or creatinine clearance (CCr) among these four groups. It appears that the levels of Hb, Ht, and RBC in peripheral blood may be important clinical parameters for the evaluation of prognostic stages in patients with IgA nephropathy. J. Clin. Lab. Anal. 19:80,83, 2005. © 2005 Wiley-Liss, Inc. [source]


    Changes in renal artery resistance after meal-induced splanchnic vasodilatation in cirrhotic patients

    JOURNAL OF CLINICAL ULTRASOUND, Issue 9 2001
    Pascal Perney MD
    Abstract Purpose A relationship between vasomotor tone changes in mesenteric and renal vessels in cirrhotic patients has been suspected but remains controversial. The aim of this study was to assess by duplex Doppler sonography the changes in the circulatory resistance of the renal arteries and superior mesenteric artery (SMA) following meal-induced splanchnic vasodilatation. Methods Twenty-seven cirrhotic patients and 15 healthy volunteers with no hepatic or renal dysfunction were prospectively included in the study. The resistance index (RI) of the SMA and of the right and left renal arteries was measured by duplex Doppler sonography before and 30 minutes after ingestion of a standard 400-kcal balanced liquid meal. Values in controls and patients and values before and after the meal were compared, and correlations between RIs, Child-Pugh class (liver function), and creatinine clearance were assessed in cirrhotic patients. Results The fasting renal artery RI was greater in cirrhotic patients than in controls (p < 0.0001), but there was no difference in fasting SMA RIs. After the meal, there was a significant decrease in the SMA RI in controls (0.85 ± 0.04 before versus 0.74 ± 0.03 after meal, p = 0.0001) and in cirrhotic patients (0.85 ± 0.04 before versus 0.77 ± 0.04 after, p = 0.0001) and a significant increase in the renal artery RI (0.57 ± 0.06 before versus 0.62 ± 0.05 after in controls, p = 0.001; 0.68 ± 0.07 before versus 0.70 ± 0.07 after in cirrhotic patients, p = 0.001). No correlation was found in cirrhotic patients between the changes in renal artery RI and the postprandial SMA RI decrease, the Child-Pugh class, or the creatinine clearance. Conclusions Meal-induced SMA vasodilatation (RI decrease) is associated with a marked increase in the renal artery RI, worsening the renal vasoconstriction in cirrhotic patients. © 2001 John Wiley & Sons, Inc. J Clin Ultrasound 29:506,512, 2001. [source]


    Pharmacokinetics of roxatidine acetate in patients with chronic liver disease

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8 2001
    Mikihiro Tsutsumi
    Abstract Background and Aim: Patients with liver disease are prone to develop peptic ulceration and often receive H2 -receptor antagonists. Therefore, it is important to clarify whether the pharmacokinetics of H2 -receptor antagonists is affected by hepatic function. However, pharmacokinetics of a new H2 -receptor antagonist, roxatidine acetate, in chronic liver disease has not been well known. In this study, we analyzed the pharmacokinetics of roxatidine in patients with liver disease. Methods: Blood samples were obtained from 11 patients with chronic hepatitis, 11 patients with cirrhosis and six healthy subjects. Under fasting conditions, 75 mg of roxatidine acetate was administered orally, and plasma roxatidine levels were determined sequentially from 3 to 12 h. Relationships between pharmacokinetic variables and each parameter related to hepatic functions were also investigated. Results: There was no difference in the pharmacokinetic variables and serum levels of roxatidine between chronic hepatitis and healthy controls. In contrast, in cirrhosis, serum roxatidine levels were significantly higher than those in chronic hepatitis and normal control. Half-life, the area under the plasma concentration,time curve and clearance in cirrhosis were also significantly longer, bigger and smaller than those in chronic hepatitis and healthy controls, respectively. The half-life became longer and the clearance became smaller in parallel with the progression of liver disease. Serum levels of hyaluronate and ,-glutamyl transpeptidase showed a good correlation with half-life, clearance and elimination rate. A good correlation between creatinine clearance and elimination rate was found. Conclusion: Pharmacokinetics of roxatidine acetate is affected by hepatic function, and the dosage of roxatidine acetate for patients with liver disease, especially cirrhosis, should be modified. [source]


    The association between metabolic syndrome, microalbuminuria and impaired renal function in the general population: impact on cardiovascular disease and mortality

    JOURNAL OF INTERNAL MEDICINE, Issue 4 2007
    K. P. Klausen
    Abstract. Objective:, Microalbuminuria and metabolic syndrome are both associated with cardiovascular disease (CVD). The aim of this study was to determine the potential association between numbers of components in the metabolic syndrome, different levels of microalbuminuria and renal function. We also aimed to determine the risk of death and CVD at different levels of microalbuminuria and renal function and numbers of components in the metabolic syndrome. Design:, Population-based observational follow-up study Setting:, Epidemiological research unit (Copenhagen City Heart Study). Subjects:, A total of 2696 men and women, 30,70 years of age. Baseline measures:, Urinary albumin excretion (UAE), creatinine clearance and metabolic risk factors were measured in 1992,1994. Main outcome measurements:, The participants were followed prospectively by registers until 1999,2000 with respect to CVD, and until 2004 with respect to death. Results:, We found a strong association between microalbuminuria and the metabolic syndrome: 2% with none and 18% with five metabolic risk factors had microalbuminuria (P < 0.001). No association between impaired renal function defined as creatinine clearance <60 mL min,1 and the metabolic syndrome was found. Microalbuminuria was associated with increased risk of death and CVD to a similar extend as the metabolic syndrome, irrespective of concomitant presence of metabolic syndrome (RR,2; P < 0.001). Impaired renal function was not associated with increased risk of death and CVD in subjects with the metabolic syndrome. Conclusions:, Microalbuminuria (UAE >5 ,g min,1) confers increased risk of death and CVD to a similar extent as the metabolic syndrome. [source]