Pharmacokinetics of oral micronized β-estradiol in postmenopausal women receiving maintenance hemodialysis

BACKGROUND: Although 11% of postmenopausal women with end-stage renal disease (ESRD) are prescribed hormone replacement therapy (HRT), the appropriate use remains poorly explored. Although there remains controversy surrounding the benefits of HRT, it may be of particular interest in this population, which has a high risk of bone loss and a fourfold increase in fracture risk compared to the general population. However, the appropriate dose of estrogen for use in postmenopausal women with ESRD is not known. The objective of this study was to evaluate the steady-state pharmacokinetics of oral micronized beta-estradiol in postmenopausal women with ESRD compared with postmenopausal women with normal renal function in order to determine equivalent dosing. METHODS: Six postmenopausal women with ESRD receiving maintenance hemodialysis and 6 healthy postmenopausal controls received 14 days of micronized beta-estradiol (1.0 mg for control, 0.5 mg for ESRD). Blood, urine, and dialysate samples were obtained during a dosage interval on day 14. Estradiol, estrone, albumin, and sex-hormone binding globulin (SHBG) concentrations were determined. Free estradiol concentrations were calculated using a previously described method. RESULTS: Women with ESRD had significantly lower serum albumin (610 +/- 31 micromol/L vs. 684 +/- 83 micromol/L) and SHBG (78 +/- 17 vs. 118 +/- 13 nmol/L) than control subjects. Total clearance of estradiol was not significantly different. Due to difference in binding, free estradiol concentrations were significant higher in ESRD women (53.2 +/- 17.7 pg/mL) than control women (43.5 +/- 8.7 pg/mL), despite receiving 50% of the dose. There was no significant difference in estrone concentrations. Clearance of both estradiol and estrone in the dialysate was minimal. CONCLUSION: Women with ESRD should receive approximately 50% of the dose typically prescribed to women without ESRD

Prevalence and Management of Anemia Among Patients with Chronic Kidney Disease in a Health Maintenance Organization

Background: Anemia often develops among patients with chronic kidney disease (CKD) and is an important cause of cardiovascular disease among patients with end-stage renal disease (ESRD). Objective: To evaluate the epidemiology and treatment of anemia among patients with CKD by undertaking an analysis of data from one Health Maintenance Organization. Methods: The CKD cohort was comprised of 1658 patients followed between 1 January 1994 and 1 December 1997 who had serum creatinine (SCr) levels above gender-specific norms. The prevalence of anemia and epoetin-alpha (recombinant human erythropoietin) use was determined, and the association with anemia and kidney function was assessed with multinomial logistic regression analysis. Results: 36% of patients with CKD had anemia, with at least two hematocrit (HCT) values (separated by >=30 days) lower than the gender-specific norm ( =33%, 6% had a lowest HCT value 30 to 32.9%, and 19% had a lowest HCT value =4.0, 3.0 to 3.9 and 2.0 to 2.9 mg/dl, respectively, compared with patients with SCr levelAnaemia, Antianaemics, Drug utilisation, Epoetin alfa, Pharmacoeconomics

Randomized Placebo-Controlled Trial of Reloxaliase in Enteric Hyperoxaluria

BACKGROUND Enteric hyperoxaluria is caused by increased intestinal oxalate absorption and can lead to kidney stones, chronic kidney disease, and kidney failure. Reloxaliase is an orally administered recombinant enzyme that degrades oxalate along the gastrointestinal tract, thereby preventing its absorption. METHODS We randomly assigned participants with enteric hyperoxaluria to reloxaliase or placebo, three to five times per day with food for 4 weeks. The primary end point was percent change from baseline in 24-hour urinary oxalate (UOx) excretion during weeks 1 to 4. Secondary end points included the proportion of participants with more than a 20% reduction in 24-hour UOx and an efficacy assessment in the bariatric surgery subgroup. RESULTS A total of 115 patients underwent randomization. The 24-hour UOx decreased from a baseline geometric mean of 83.2 to 67.4 mg/24 hr during weeks 1 to 4 in reloxaliase-treated participants. Corresponding data for placebo-treated participants were 84.2 to 78.1 mg/24 hr. Estimates from the mixed-effect model repeated-measures (MMRM) analysis showed a 22.6% reduction in geometric mean UOx during weeks 1 to 4 for reloxaliase and 9.7% for placebo, a difference of 14.3 percentage points (95% confidence interval [CI], 4.9 to 22.8; P=0.004). A 20% or greater reduction in 24-hour UOx was observed in 48.3% of reloxaliase-treated participants and 31.6% of placebo-treated participants (P=0.06). In the bariatric surgery subgroup, MMRM analysis showed a 21.2% reduction in geometric mean UOx for reloxaliase and a 6.0% reduction for placebo, for a difference of 16.2 percentage points (95% CI, 4.2% to 26.7%). Adverse events occurred in 69% of reloxaliase-treated participants versus 53% of individuals taking placebo and were most commonly gastrointestinal. All but one of the adverse events were grade 1 or 2 in severity; no reloxaliase-treated participants discontinued the study. CONCLUSIONS Reloxaliase treatment for 4 weeks reduced UOx excretion in patients with enteric hyperoxaluria; adverse events were relatively common, but not dose-limiting. These data establish the foundation for a clinical trial to determine the impact of reloxaliase on nephrolithiasis in patients with enteric hyperoxaluria. (Funded by Allena Pharmaceuticals; ClinicalTrials.gov number, NCT03456830.

The Study of Treatment for Renal Insufficiency: Data and Evaluation (STRIDE), a National Registry of Chronic Kidney Disease

Optimization of care in patients with chronic kidney disease (CKD) could be the key to improved clinical and economic outcomes, both during the phase of CKD as well as in patients with end-stage renal disease (ESRD). CKD is a major public health problem that has been insufficiently studied. There is little published information on outcomes among CKD patients, specifically, data on mortality, morbidity, and quality of life. Indeed, recent efforts by the National Kidney Foundation (NKF) have served to define the classification, evaluation, and approach to management of CKD in practice. The Study of Treatment for Renal Insufficiency: Data and Evaluation (STRIDE) registry is an initiative to study CKD patients in nephrology practices across the country. It is a prospective observational study whose objective is to profile demographic and clinical variables, practice patterns, comorbid conditions, quality of life, and outcomes in a nationally based sample of CKD patients. This article details the design, methodology, and process of enrollment into the registry.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73215/1/j.1525-139X.2002.00088.x.pd

Atherosclerotic renovascular disease in United States patients aged 67 years or older: Risk factors, revascularization, and prognosis

Atherosclerotic renovascular disease in United States patients aged 67 years or older: Risk factors, revascularization, and prognosis.BackgroundAlthough atherosclerotic renovascular disease is increasingly recognized in chronic kidney disease, few national level studies have examined its clinical epidemiology.MethodsClaims data from a 5% random sample of the United States Medicare population were used to select patients without atherosclerotic renovascular disease in the 2 years preceding December 31, 1999 (N = 1,085,250), followed until December 31, 2001.ResultsThe incidence of atherosclerotic renovascular disease was 3.7 per 1000 patient-years. Major antecedent associations [P < 0.05, with adjusted hazards ratios (HR) > 1.5] included chronic kidney disease (adjusted HR 2.54), hypertension (2.42), peripheral vascular disease (2.00), and atherosclerotic heart disease (1.70). Adverse event rates after incident atherosclerotic renovascular disease greatly exceeded those in the general population (P < 0.0001): atherosclerotic heart disease, 303.9 per 1000 patient-years (vs. 73.5 in the general population); peripheral vascular disease, 258.6 (vs. 52.2); congestive heart failure, 194.5 (vs. 56.3); cerebrovascular accident or transient ischemic attack, 175.5 (vs. 52.9); death, 166.3 (vs. 63.3); and renal replacement therapy, 28.8 (vs. 1.3). Among atherosclerotic renovascular disease patients, 16.2% underwent a renal revascularization procedure, percutaneously in 96%. Revascularization was not associated with renal replacement therapy, congestive heart failure, or death but was associated with atherosclerotic heart disease (adjusted HR 1.42) (P = 0.004) and peripheral vascular disease (adjusted HR 1.38) (P = 0.002).ConclusionAtherosclerotic renovascular disease is strongly associated with cardiovascular disease, both past and future. Absolute cardiovascular risk exceeds that of renal replacement therapy. Renal revascularization is used selectively and shows inconsistent associations with cardiovascular outcomes, renal replacement therapy, and death