Browsing by Subject "Kidney Failure, Chronic"

Now showing 1 - 7 of 7
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    Assessment and management of hypertension in patients on dialysis
    (American Society of Nephrology, 2014-08) Agarwal, Rajiv; Flynn, Joseph; Pogue, Velvie; Rahman, Mahboob; Reisin, Efrain; Weir, Matthew R.; Department of Medicine, IU School of Medicine
    Hypertension is common, difficult to diagnose, and poorly controlled among patients with ESRD. However, controversy surrounds the diagnosis and treatment of hypertension. Here, we describe the diagnosis, epidemiology, and management of hypertension in dialysis patients, and examine the data sparking debate over appropriate methods for diagnosing and treating hypertension. Furthermore, we consider the issues uniquely related to hypertension in pediatric dialysis patients. Future clinical trials designed to clarify the controversial results discussed here should lead to the implementation of diagnostic and therapeutic techniques that improve long-term cardiovascular outcomes in patients with ESRD.
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    The Effects of Cinacalcet in Older and Younger Patients on Hemodialysis: The Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial
    (American Society of Nephrology, 2015-05-07) Parfrey, Patrick S.; Drüeke, Tilman B.; Block, Geoffrey A.; Correa-Rotter, Ricardo; Floege, Jürgen; Herzog, Charles A.; London, Gerard M.; Mahaffey, Kenneth W.; Moe, Sharon M.; Wheeler, David C.; Kubo, Yumi; Dehmel, Bastian; Goodman, William G.; Chertow, Glenn M.; Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators; Department of Medicine, IU School of Medicine
    BACKGROUND AND OBJECTIVES: The calcimimetic cinacalcet reduced the risk of death or cardiovascular (CV) events in older, but not younger, patients with moderate to severe secondary hyperparathyroidism (HPT) who were receiving hemodialysis. To determine whether the lower risk in younger patients might be due to lower baseline CV risk and more frequent use of cointerventions that reduce parathyroid hormone (kidney transplantation, parathyroidectomy, and commercial cinacalcet use), this study examined the effects of cinacalcet in older (≥65 years, n=1005) and younger (<65 years, n=2878) patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) was a global, multicenter, randomized placebo-controlled trial in 3883 prevalent patients on hemodialysis, whose outcomes included death, major CV events, and development of severe unremitting HPT. The age subgroup analysis was prespecified. RESULTS: Older patients had higher baseline prevalence of diabetes mellitus and CV comorbidity. Annualized rates of kidney transplantation and parathyroidectomy were >3-fold higher in younger relative to older patients and were more frequent in patients randomized to placebo. In older patients, the adjusted relative hazard (95% confidence interval) for the primary composite (CV) end point (cinacalcet versus placebo) was 0.70 (0.60 to 0.81); in younger patients, the relative hazard was 0.97 (0.86 to 1.09). Corresponding adjusted relative hazards for mortality were 0.68 (0.51 to 0.81) and 0.99 (0.86 to 1.13). Reduction in the risk of severe unremitting HPT was similar in both groups. CONCLUSIONS: In the EVOLVE trial, cinacalcet decreased the risk of death and of major CV events in older, but not younger, patients with moderate to severe HPT who were receiving hemodialysis. Effect modification by age may be partly explained by differences in underlying CV risk and differential application of cointerventions that reduce parathyroid hormone.
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    Effects of cinacalcet on atherosclerotic and nonatherosclerotic cardiovascular events in patients receiving hemodialysis: the EValuation Of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) trial
    (Ovid Technologies Wolters Kluwer -American Heart Association, 2014-12) Wheeler, David C.; London, Gerard M.; Parfrey, Patrick S.; Block, Geoffrey A.; Correa‐Rotter, Ricardo; Dehmel, Bastian; Drüeke, Tilman B.; Floege, Jürgen; Kubo, Yumi; Mahaffey, Kenneth W.; Goodman, William G.; Moe, Sharon M.; Trotman, Marie-Louise; Abdalla, Safa; Chertow, Glenn M.; Herzog, Charles A.; Department of Medicine, IU School of Medicine
    BACKGROUND: Premature cardiovascular disease limits the duration and quality of life on long-term hemodialysis. The objective of this study was to define the frequency of fatal and nonfatal cardiovascular events attributable to atherosclerotic and nonatherosclerotic mechanisms, risk factors for these events, and the effects of cinacalcet, using adjudicated data collected during the EValuation of Cinacalcet HCl Therapy to Lower CardioVascular Events (EVOLVE) Trial. METHODS AND RESULTS: EVOLVE was a randomized, double-blind, placebo-controlled clinical trial that randomized 3883 hemodialysis patients with moderate to severe secondary hyperparathyroidism to cinacalcet or matched placebo for up to 64 months. For this post hoc analysis, the outcome measure was fatal and nonfatal cardiovascular events reflecting atherosclerotic and nonatherosclerotic cardiovascular diseases. During the trial, 1518 patients experienced an adjudicated cardiovascular event, including 958 attributable to nonatherosclerotic disease. Of 1421 deaths during the trial, 768 (54%) were due to cardiovascular disease. Sudden death was the most frequent fatal cardiovascular event, accounting for 24.5% of overall mortality. Combining fatal and nonfatal cardiovascular events, randomization to cinacalcet reduced the rates of sudden death and heart failure. Patients randomized to cinacalcet experienced fewer nonatherosclerotic cardiovascular events (adjusted relative hazard 0.84, 95% CI 0.74 to 0.96), while the effect of cinacalcet on atherosclerotic events did not reach statistical significance. CONCLUSIONS: Accepting the limitations of post hoc analysis, any benefits of cinacalcet on cardiovascular disease in the context of hemodialysis may result from attenuation of nonatherosclerotic processes. CLINICAL TRIALS REGISTRATION: Unique identifier: NCT00345839. URL: ClinicalTrials.gov.
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    Effects of Cinacalcet on Fracture Events in Patients Receiving Hemodialysis: The EVOLVE Trial
    (American Society of Nephrology (ASN), 2015-06) Moe, Sharon M.; Abdalla, Safa; Chertow, Glenn M.; Parfrey, Patrick S.; Block, Geoffrey A.; Correa-Rotter, Ricardo; Floege, Jürgen; Herzog, Charles A.; London, Gerard M.; Mahaffey, Kenneth W.; Wheeler, David C.; Dehmel, Bastian; Goodman, William G.; Drüeke, Tilman B.; Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) Trial Investigators; Department of Medicine, IU School of Medicine
    Fractures are frequent in patients receiving hemodialysis. We tested the hypothesis that cinacalcet would reduce the rate of clinical fractures in patients receiving hemodialysis using data from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events trial, a placebo-controlled trial that randomized 3883 hemodialysis patients with secondary hyperparathyroidism to receive cinacalcet or placebo for ≤64 months. This study was a prespecified secondary analysis of the trial whose primary end point was all-cause mortality and non-fatal cardiovascular events, and one of the secondary end points was first clinical fracture event. Clinical fractures were observed in 255 of 1935 (13.2%) patients randomized to placebo and 238 of 1948 (12.2%) patients randomized to cinacalcet. In an unadjusted intention-to-treat analysis, the relative hazard for fracture (cinacalcet versus placebo) was 0.89 (95% confidence interval [95% CI], 0.75 to 1.07). After adjustment for baseline characteristics and multiple fractures, the relative hazard was 0.83 (95% CI, 0.72 to 0.98). Using a prespecified lag-censoring analysis (a measure of actual drug exposure), the relative hazard for fracture was 0.72 (95% CI, 0.58 to 0.90). When participants were censored at the time of cointerventions (parathyroidectomy, transplant, or provision of commercial cinacalcet), the relative hazard was 0.71 (95% CI, 0.58 to 0.87). Fracture rates were higher in older compared with younger patients and the effect of cinacalcet appeared more pronounced in older patients. In conclusion, using an unadjusted intention-to-treat analysis, cinacalcet did not reduce the rate of clinical fracture. However, when accounting for differences in baseline characteristics, multiple fractures, and/or events prompting discontinuation of study drug, cinacalcet reduced the rate of clinical fracture by 16%-29%.
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    Gentamicin pharmacokinetics and pharmacodynamics during short-daily hemodialysis
    (S. Karger AG, 2012) Decker, Brian S.; Mohamed, Ahmed N.; Chambers, Mary; Kraus, Michael A.; Moe, Sharon M.; Sowinski, Kevin M.; Department of Medicine, IU School of Medicine
    BACKGROUND/AIMS: Gentamicin pharmacokinetics have not been described in patients undergoing short-daily hemodialysis (SDHD). The aim of this study is to describe gentamicin pharmacokinetics and dialytic clearance (Cl(dial)) in SDHD patients and simulate gentamicin exposure after six dosing regimens to help guide future dosing. METHODS: Six anuric patients undergoing SDHD were enrolled. Patients received intravenous infusion of 2 mg/kg gentamicin on day 1 after the first HD session followed by HD sessions on days 2, 3, and 4. Blood samples for determination of gentamicin concentrations were serially collected. Gentamicin pharmacokinetic parameters and Cl(dial) and interindividual variability terms (IIV) were estimated using NONMEM VII. Influence of patient weight on systemic clearance (Cl(s)) and central volume of distribution (V(c)) and influence of urea removal estimates on Cl(dial) were assessed. The model was used to simulate gentamicin concentrations after six dosing regimens including pre- and postdialysis as well as daily and every-other-day dosing. RESULTS: A two-compartment model with first-order elimination from central compartment described gentamicin pharmacokinetics. Population estimates for Cl(s) and Cl(dial) were 7.6 and 134 ml/min, respectively. Patient weight was statistically significantly associated with Cl(s) and V(c). Predialysis every-other-day regimens were as effective (C(max) ≥8 mg/l and AUC(48 h) ≥140 mg·h/l) and less toxic (C(min) <2 mg/l and AUC(48 h) <240 mg·h/l) than postdialysis regimens. CONCLUSIONS: Estimated gentamicin Cl(dial) is higher than previous estimates with thrice-weekly regimens. Predialysis every-other-day dosing may be recommended during SDHD.
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    Phosphate Binders and Non-Phosphate Effects in the Gastrointestinal Tract
    (Elsevier, 2020-01) Biruete, Annabel; Hill Gallant, Kathleen M.; Lindemann, Stephen R.; Wiese, Gretchen; Chen, Neal; Moe, Sharon; Medicine, School of Medicine
    Phosphate binders are commonly prescribed in patients with end-stage kidney disease to prevent and treat hyperphosphatemia. These binders are usually associated with gastrointestinal distress, may bind molecules other than phosphate, and may alter the gut microbiota, altogether having systemic effects unrelated to phosphate control. Sevelamer is the most studied of the available binders for nonphosphate-related effects including binding to bile acids, endotoxins, gut microbiota-derived metabolites, and advanced glycation end products. Other binders (calcium- and noncalcium-based binders) may bind vitamins, such as vitamin K and folic acid. Moreover, the relatively new iron-based phosphate binders may alter the gut microbiota, as some of the iron or organic ligands may be used by the gastrointestinal bacteria. The objective of this narrative review is to provide the current evidence for the nonphosphate effects of phosphate binders on gastrointestinal function, nutrient and molecule binding, and the gut microbiome.
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