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High Single-dose Vancomycin Loading Is Not Associated With Increased Nephrotoxicity in Emergency Department Sepsis Patients.
Rosini, JM, Davis, JJ, Muenzer, J, Levine, BJ, Papas, MA, Comer, D, Arnold, R
Academic emergency medicine : official journal of the Society for Academic Emergency Medicine. 2016;(6):744-6
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OBJECTIVE Vancomycin loading doses are recommended; however, the risk of nephrotoxicity with these doses is unknown. The primary objective of this study was to compare nephrotoxicity in emergency department (ED) sepsis patients who received vancomycin at high doses (>20 mg/kg) versus lower doses (≤20 mg/kg). METHODS A retrospective cohort study was performed in three academic EDs. Inclusion criteria were age ≥ 18 years, intravenous vancomycin order, and hospital admission. Exclusion criteria were no documented weight, hemodialysis-dependent, and inadequate serum creatinine (SCr) values for the measured outcome. Analyses compared the incidence of nephrotoxicity for patients who received vancomycin at high dose (>20 mg/kg) versus low dose (≤20 mg/kg). RESULTS A total of 2,131 consecutive patients prescribed vancomycin over 6 months were identified. Of these, 1,330 patients had three SCr values assessed for the primary outcome. High-dose initial vancomycin was associated with a significantly lower rate of nephrotoxicity (5.8% vs. 11.1%). After age, sex, and initial SCr were adjusted for, the risk of high-dose vancomycin compared to low-dose was decreased for the development of nephrotoxicity (relative risk = 0.60; 95% confidence interval = 0.44 to 0.82). CONCLUSION Initial dosing of vancomycin > 20 mg/kg was not associated with an increased rate of nephrotoxicity compared with lower doses. Findings from this study support compliance with initial weight-based vancomycin loading doses.
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Cystatin C: A Marker for Inflammation and Renal Function Among HIV-infected Children and Adolescents.
Deyà-Martínez, À, Fortuny, C, Soler-Palacín, P, Neth, O, Sánchez, E, Martín-Nalda, A, Falcón-Neyra, L, Vila, A, Valls, A, Noguera-Julian, A
The Pediatric infectious disease journal. 2016;(2):196-200
Abstract
BACKGROUND Renal disease is a leading cause of morbidity in HIV-infected adults in the highly active antiretroviral therapy (HAART) era. Cystatin C has been proposed as a more sensitive marker of renal function, but it may be affected by ongoing inflammation. We aimed to study the cystatin C levels in a cohort of HIV-infected pediatric patients at 3 Spanish centers. METHODS This is a multicenter cross-sectional observational study. Renal function was assessed by means of first morning urine protein/creatinine and albumin/creatinine ratios and creatinine-estimated glomerular filtration rates (GFRs), together with the following inflammation markers: cystatin C, reactive C protein, β-2-microglobulin and 25(OH)-vitamin D levels. A control group of healthy children and adolescents was used. RESULTS Eighty-three patients (51 females, median age: 13.3 years; 32 males, median age: 13.6 years) and 44 controls (24 females, median age: 12.2 years; 20 males, median age: 10.9 years) were included. Among the former, mean CD4 cell count was 860/mm, 29(35%) patients had a previous AIDS diagnosis, 73(88%) were on HAART and HIV viremia was undetectable in 61(73%). No differences in cystatin C levels were observed between the 2 groups. In HIV-infected patients, cystatin C levels correlated with GFR (r = -0.27; P = 0.01), age at first HAART (r = -0.21; P = 0.05), and β-2-microglobulin (r = 0.569; P < 0.01). In multivariate analysis, lower GFR (P = 0.014) and higher β-2-microglobulin levels (P = 0.001) remained as independent risk factors for higher cystatin C values. CONCLUSIONS Cystatin C values were associated with GFR and β-2-microglobulin. Cystatin C may be useful as a marker of renal function in HIV-infected pediatric patients, independently of ongoing inflammation or viremia.
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Pharmacokinetics of eribulin mesylate in cancer patients with normal and impaired renal function.
Tan, AR, Sarantopoulos, J, Lee, L, Reyderman, L, He, Y, Olivo, M, Goel, S
Cancer chemotherapy and pharmacology. 2015;(5):1051-61
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PURPOSE To evaluate the effect of renal impairment on eribulin mesylate pharmacokinetics following a single dose in adults with advanced solid tumors. METHODS Patients were grouped by renal function: moderate impairment (creatinine clearance [CrCl] 30-50 mL/min), severe impairment (CrCl 15-29 mL/min), or normal (CrCl ≥80 mL/min). During each 21-day cycle, eribulin mesylate doses (days 1 and 8) were administered intravenously: moderate, 1.1 mg/m(2) (except cycle 1 day 1, 1.4 mg/m(2)); severe, 0.7 mg/m(2); normal, 1.4 mg/m(2). RESULTS Nineteen patients were enrolled (normal, n = 6; moderate, n = 7; severe, n = 6). Renal impairment was associated with an increased mean dose-normalized area under the concentration-time curve (ratios for moderate/normal and severe/normal: 1.49; 90 % confidence interval [CI] 0.9, 2.45). CrCl and renal function correlated positively, with a numerically small slope (0.0184; 90 % CI -0.00254, 0.0394). A simulated dose reduction to eribulin 1.1 mg/m(2) in patients with moderate or severe renal impairment achieved the same exposure as 1.4 mg/m(2) in those with normal renal function. All groups had similar toxicity profiles, with no unexpected adverse events. CONCLUSIONS Renal impairment decreased eribulin clearance and increased exposure. Pharmacokinetic evaluation supports an eribulin dose reduction to 1.1 mg/m(2) in patients with moderate or severe renal impairment. CLINICALTRIALS. GOV IDENTIFIER NCT01418677.
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Association between cardiovascular vs. non-cardiovascular co-morbidities and outcomes in heart failure with preserved ejection fraction.
Lund, LH, Donal, E, Oger, E, Hage, C, Persson, H, Haugen-Löfman, I, Ennezat, PV, Sportouch-Dukhan, C, Drouet, E, Daubert, JC, et al
European journal of heart failure. 2014;(9):992-1001
Abstract
AIMS: The prevalence of cardiovascular and non-cardiovascular co-morbidities and their relative importance for outcomes in heart failure with preserved ejection fraction (HFPEF) remain poorly characterized. This study aimed to investigate this. METHODS AND RESULTS The Karolinska-Rennes (KaRen) Study was a multinational prospective observational study designed to characterize HFPEF. Inclusion required acute HF, defined by the Framingham criteria, LVEF ≥ 45%, and NT-pro-BNP ≥ 300 ng/L or BNP ≥ 100 ng/L. Detailed clinical data were collected at baseline and patients were followed prospectively for 18 months. Predictors of the primary (HF hospitalization or all-cause mortality) and secondary (all-cause mortality) outcomes were assessed with multivariable Cox regression. A total of 539 patients [56% women; median (interquartile range) age 79 (72-84) years; NT-pro-BNP/BNP 2448 (1290-4790)/429 (229-805) ng/L] were included. Known history of HF was present in 40%. Co-morbidities included hypertension (78%), atrial fibrillation/flutter (65%), anaemia (51%), renal dysfunction (46%), CAD (33%), diabetes (30%), lung disease (25%), and cancer (16%). The primary outcome occurred in 268 patients [50%; 106 deaths (20%) and 162 HF hospitalizations (30%)]. Important independent predictors of the primary and/or secondary outcomes were age, history of non-cardiovascular syncope, valve disease, anaemia, lower sodium, and higher potassium, but no cardiovascular co-morbidities. Renin-angiotensin system antagonist and mineralocorticoid receptor antagonist use predicted improved prognosis. CONCLUSION HFPEF was associated with higher age, female gender, hypertension, atrial fibrillation/flutter, and numerous non-cardiovascular co-morbidities. Prognosis was determined by non-cardiovascular co-morbidities, but use of conventional heart failure medications may still be associated with improved outcomes.
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The effect of high-flux hemodialysis on hemoglobin concentrations in patients with CKD: results of the MINOXIS study.
Schneider, A, Drechsler, C, Krane, V, Krieter, DH, Scharnagl, H, Schneider, MP, Wanner, C, ,
Clinical journal of the American Society of Nephrology : CJASN. 2012;(1):52-9
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BACKGROUND AND OBJECTIVES Hemodialysis treatment induces markers of inflammation and oxidative stress, which could affect hemoglobin levels and the response to erythropoietin use. This study sought to determine whether high-flux dialysis would help improve markers of renal anemia, inflammation, and oxidative stress compared with low-flux dialysis. DESIGN, SETTINGS, PARTICIPANTS, & MEASUREMENTS In a prospective, controlled study, 221 patients undergoing maintenance hemodialysis and receiving darbepoetin-alfa treatment (mean age, 66 years; 55% male) from 19 centers were screened in a 20-week run-in period of low-flux hemodialysis with a synthetic dialysis membrane. Thereafter, 166 patients were enrolled and randomly assigned to receive a synthetic high-flux membrane or to continue on low-flux dialysis for 52 weeks. Data on myeloperoxidase, oxidized LDL, high-sensitivity C-reactive protein, and the Malnutrition Inflammation Score were collected at baseline and after 52 weeks; routine laboratory data, such as hemoglobin, ferritin, and albumin, and the use of darbepoetin-alfa, were also measured in the run-in period. Results After 52 weeks, the low-flux and the high-flux groups did not differ with respect to hemoglobin (mean ± SD, 11.7±0.9 g/dl versus 11.7±1.1 g/dl; P=0.62) or use of darbepoetin-alfa (mean dosage ± SD, 29.8±24.8 μg/wk versus 26.0±31.1 μg/wk; P=0.85). Markers of inflammation, oxidative stress, or nutritional status also did not differ between groups. CONCLUSION Over 1 year, high-flux dialysis had no superior effects on hemoglobin levels or markers of inflammation, oxidative stress, and nutritional status. These data do not support the hypothesis that enhanced convective toxin removal would improve patient outcome.
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Vitamin D therapy and cardiac structure and function in patients with chronic kidney disease: the PRIMO randomized controlled trial.
Thadhani, R, Appelbaum, E, Pritchett, Y, Chang, Y, Wenger, J, Tamez, H, Bhan, I, Agarwal, R, Zoccali, C, Wanner, C, et al
JAMA. 2012;(7):674-84
Abstract
CONTEXT Vitamin D is associated with decreased cardiovascular-related morbidity and mortality, possibly by modifying cardiac structure and function, yet firm evidence for either remains lacking. OBJECTIVE To determine the effects of an active vitamin D compound, paricalcitol, on left ventricular mass over 48 weeks in patients with an estimated glomerular filtration rate of 15 to 60 mL/min/1.73 m(2). DESIGN, SETTING, AND PARTICIPANTS Multinational, double-blind, randomized placebo-controlled trial among 227 patients with chronic kidney disease, mild to moderate left ventricular hypertrophy, and preserved left ventricular ejection fraction, conducted in 11 countries from July 2008 through September 2010. INTERVENTION Participants were randomly assigned to receive oral paricalcitol, 2 μg/d (n =115), or matching placebo (n = 112). MAIN OUTCOME MEASURES Change in left ventricular mass index over 48 weeks by cardiovascular magnetic resonance imaging. Secondary end points included echocardiographic changes in left ventricular diastolic function. RESULTS Treatment with paricalcitol reduced parathyroid hormone levels within 4 weeks and maintained levels within the normal range throughout the study duration. At 48 weeks, the change in left ventricular mass index did not differ between treatment groups (paricalcitol group, 0.34 g/m(2.7) [95% CI, -0.14 to 0.83 g/m(2.7)] vs placebo group, -0.07 g/m(2.7) [95% CI, -0.55 to 0.42 g/m(2.7)]). Doppler measures of diastolic function including peak early diastolic lateral mitral annular tissue velocity (paricalcitol group, -0.01 cm/s [95% CI, -0.63 to 0.60 cm/s] vs placebo group, -0.30 cm/s [95% CI, -0.93 to 0.34 cm/s]) also did not differ. Episodes of hypercalcemia were more frequent in the paricalcitol group compared with the placebo group. CONCLUSION Forty-eight week therapy with paricalcitol did not alter left ventricular mass index or improve certain measures of diastolic dysfunction in patients with chronic kidney disease. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00497146.
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Paricalcitol versus cinacalcet plus low-dose vitamin D for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: study design and baseline characteristics of the IMPACT SHPT study.
Ketteler, M, Martin, KJ, Cozzolino, M, Goldsmith, D, Sharma, A, Khan, S, Dumas, E, Amdahl, M, Marx, S, Audhya, P
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2012;(5):1942-9
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BACKGROUND Paricalcitol and cinacalcet are common therapies for patients on haemodialysis with secondary hyperparathyroidism (SHPT). We conducted a multi-centre study in 12 countries to compare the safety and efficacy of paricalcitol and cinacalcet for the treatment of SHPT. METHODS Patients aged ≥18 years with Stage 5 chronic kidney disease receiving maintenance haemodialysis and with intact parathyroid hormone (iPTH) 300-800 pg/mL, calcium 8.4-10.0 mg/dL (2.09-2.49 mmol/L) and phosphorus ≤6.5 mg/dL (2.09 mmol/L) were randomized within two strata defined by the mode of paricalcitol administration to treatment with paricalcitol- (intra-venous, US and Russian sites, IV stratum; oral, non-US and non-Russian sites, oral stratum) or cinacalcet-centred therapy. The primary endpoint is the proportion of patients in each treatment group who achieve a mean iPTH value of 150-300 pg/mL during Weeks 21-28 of treatment. Assuming efficacy response rates of 36 and 66% for cinacalcet and paricalcitol, respectively, and a 20% discontinuation rate, 124 subjects in each stratum were estimated to provide 81% power to detect a 30% absolute difference in the primary endpoint. RESULTS Of 746 patients screened, 272 (mean age, 63 years; mean iPTH, 509 pg/mL) were randomized. Mean duration of haemodialysis at baseline was 3.7 years. Comorbidities included hypertension (90.4%), Type 2 diabetes (40.4%), congestive heart failure (17.3%), coronary artery disease (34.6%) and gastrointestinal disorders (75%). CONCLUSIONS The study participants are representative of a multinational cohort of patients on haemodialysis with elevated iPTH. The study results will provide valuable information on the best available treatment of SHPT in patients on haemodialysis.
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Monthly administration of a continuous erythropoietin receptor activator provides efficient haemoglobin control in non-dialysis patients during routine clinical practice: results from the non-interventional, single-cohort, multicentre, SUPRA study.
Heidenreich, S, Leistikow, F, Zinn, S, Baumann, J, Atzeni, A, Bajeski, V, Dietzmann, J, Dragoun, GP, ,
Clinical drug investigation. 2012;(2):99-110
Abstract
BACKGROUND The continuous erythropoietin receptor activator (C.E.R.A.) has a long half-life, a relatively low binding affinity for the erythropoiesis receptor and low systemic clearance. These characteristics permit once-monthly dosing, which could reduce staffing requirements and be advantageous for patients. However, outcomes observed during controlled trials of C.E.R.A. have not been assessed under everyday clinical conditions in which physicians make all therapeutic decisions based on their own experience, rather than according to a pre-defined protocol. OBJECTIVE This study aimed to assess whether the efficacy and safety of C.E.R.A. reported during controlled trials are reproducible under routine clinical conditions. METHODS This was a non-interventional, single-cohort, multicentre study carried out in 92 specialist nephrology clinics and private practices in Germany. The study included patients with non-dialysis chronic kidney disease and anaemia, with or without current erythropoiesis stimulating agent (ESA) therapy. C.E.R.A. initiation and dosing was at the discretion of the physician. The primary efficacy variable was the proportion of patients for whom all measured haemoglobin (Hb) values during months 7-9 were within the range 11-12 g/dL ('responders'). RESULTS 335 patients received ≥1 dose of C.E.R.A.; 150 had previously received ESA therapy. The mean number of doses was 7.6 per patient over a mean follow-up of 7.9 months. Mean ± SD Hb was 10.7 ± 1.1 g/dL at baseline and 11.3 ± 1.1 g/dL at the final visit (efficacy population, n = 205). The primary endpoint, all measured Hb values during months 7-9 within the range 11-12 g/dL, was achieved by 19.0% (39/205) of patients, increasing to 41.5% for Hb 11-13 g/dL, 42.0% for 10-12 g/dL and 76.6% for Hb ≥10 g/dL. Hb fluctuation during months 7-9 was ≤1 g/dL in 185/205 patients (90.2%). C.E.R.A. was well tolerated without novel safety concerns. CONCLUSION Hb levels remained stable during routine use of C.E.R.A. in an unselected population of non-dialysis chronic kidney disease patients with anaemia. C.E.R.A. was administered approximately monthly compared with 3-7 doses per month on previous ESA therapy.
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Efficacy of IV iron compared to oral iron for increment of haemoglobin level in anemic chronic kidney disease patients on erythropoietin therapy.
Adhikary, L, Acharya, S
JNMA; journal of the Nepal Medical Association. 2011;(183):133-6
Abstract
INTRODUCTION Anemia is the most common finding in chronic kidney disease patients. Iron supplements are commonly prescribed for these patients with or without erythropoietin therapy by means of oral and intravenous iron. Both oral and intravenous irons have their own advantage and disadvantage, and the efficacy is also different. The objective of the study is to analyze the efficacy of oral and intravenous iron in chronic kidney disease patients on erythropoietin therapy, an erythropoiesis stimulating agents for increment of haemoglobin. METHODS This is a prospective study comparing intravenous iron to oral iron in chronic kidney disease patients who underwent maintenance hemodialysis at different centers and visited Kathmandu Medical College Teaching Hospital from April 2010 to April 2011. Patients having a haemoglobin level of < 11 g/dl, transferrin saturation (TSAT) < 25%, ferritin < 300ng/ml and who were on erythropoietin therapy were allocated alternately into two groups to receive oral iron (iron fumarate) or IV iron (iv sucrose). Haemoglobin was measured after 30 days of therapy. RESULTS A significant increase in haemoglobin levels was observed in both groups. But the mean haemoglobin increment was more in the IV iron group than in the oral iron group. Sixty percent 60% of patients in the IV iron group had an increase in the haemoglobin level of more than 1gm/dl while only 20% of the oral iron group had this increase. CONCLUSIONS Intravenous iron therapy is more effective in raising the hemoglobin level in hemodialysis dependent chronic kidney disease patients.
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Efficacy and safety of aliskiren in Japanese hypertensive patients with renal dysfunction.
Ito, S, Nakura, N, Le Breton, S, Keefe, D
Hypertension research : official journal of the Japanese Society of Hypertension. 2010;(1):62-6
Abstract
This 12-week, multicenter, open-label study assessed the efficacy, pharmacokinetics and safety of a once-daily aliskiren in Japanese hypertensive patients with renal dysfunction. Patients (n=40, aged 20-80 years) with mean sitting diastolic blood pressure (msDBP) >or=95 and <110 mm Hg and serum creatinine between >or=1.3 and <3.0 mg per 100 ml in males or between >or=1.2 and <3.0 mg per 100 ml in females were eligible. Patients began therapy with a once-daily morning oral dose of 75 mg of aliskiren. In patients with inadequate blood pressure control (msDBP >or=90 or mean sitting systolic blood pressure [msSBP] >or=140 mm Hg) and without safety concerns (serum potassium >5.5 mEq l(-1) or an increase in serum creatinine >or=20%), the aliskiren dose was increased to 150 mg and then to 300 mg in sequential steps starting from Week 2. Efficacy was assessed as change in msSBP/msDBP from baseline to the Week 8 endpoint (with the last observation carried forward). The mean reduction from baseline to Week 8 endpoint was 13.9+/-16.6 and 11.6+/-9.7 mm Hg for msSBP and msDBP, respectively. At the Week 8 endpoint, 65% patients had achieved blood pressure response (msDBP <90 or a 10 mm Hg decrease or msSBP <140 or a 20 mm Hg decrease) and 30% had achieved blood pressure control (msSBP <140 mm Hg and msDBP <90 mm Hg). Aliskiren was well tolerated with no new safety concerns in Japanese hypertensive patients with renal dysfunction.