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Background Vaccination against hepatitis B virus (HBV) is recommended for dialysis patients. Two reports comparing seroprotection (SP) rates following HepB and HepB-CpG in vaccine-naïve patients with chronic kidney disease enrolled few dialysis patients (n = 122 combined). SP rates in a subset of dialysis patients were not reported or not powered to detect statistically significant differences. SP rates in those requiring additional vaccine series or booster doses are not known. Methods A retrospective cohort analysis including dialysis patients completing HepB or HepB-CpG vaccination between January 2019 and December 2020. Vaccine-naïve patients received a series of HepB or HepB-CpG (Series 1). A repeat series was given to nonresponders (Series 2). A booster regimen consists of one dose of either vaccine. Primary outcome was achieving SP (anti-HBs >10 mIU/mL) at least 60 days after the last HBV vaccine dose for Series 1 and Series 2, and achieving SP at least 3 weeks post-booster. Results For Series 1 (n = 3509), SP after HepB vaccination was significantly higher (62.9% versus 50.1% for HepB-CpG; P Conclusions SP rates in hepatitis B vaccine-naïve dialysis patients administered a recommended four doses of HepB were higher than those recommended two doses of HepB-CpG. SP rates were higher and achieved sooner if HepB-CpG was utilized initially and, if needed, for Series 2. Optimal HepB-CpG dosing deserves further study.

BackgroundPatients receiving maintenance dialysis represent a high risk, immune-compromised population with 15-25% COVID mortality rate who were unrepresented in clinical trials evaluated for mRNA vaccines’ emergency use authorization.MethodAll patients receiving maintenance dialysis that received two doses of SARS-CoV-2 mRNA vaccines with antibody test results drawn ≥14 days after the second dose, as documented in the electronic health record through March 18, 2021 were included. We report seroresponse based on levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike antigen (seropositive ≥2) using FDA-approved semi-quantitative chemiluminescent assay (ADVIA Centaur® XP/XPT COV2G).ResultsAmong 186 dialysis patients from 32 clinics in 8 states tested 23±8 days after receiving 2 vaccine doses, mean age was 68±12 years, with 47% women, 21% Black, 26% residents in long-term care facilities and 97% undergoing in-center hemodialysis. Overall seropositive rate was 165/186 (88.7%) with 70% at maximum titer and with no significant difference in seropositivity between BNT162b2/Pfizer (N=148) and mRNA-1273/Moderna (N=18) vaccines (88.1% vs. 94.4%, p=0.42). Among patients with COVID-19 history, seropositive rate was 38/38 (100%) with 97% at maximum titer.ConclusionMost patients receiving maintenance dialysis were seropositive after two doses of BNT162b2/Pfizer or mRNA-1273/Moderna vaccine. Early evidence suggests that vaccinated dialysis patients with prior COVID-19 develop robust antibody response. These results support an equitable and aggressive vaccination strategy for eligible dialysis patients, regardless of age, sex, race, ethnicity, or disability, to prevent the extremely high morbidity and mortality associated with COVID-19 in this high risk population.SignificanceIn this retrospective observational evaluation of SARS-CoV-2 mRNA vaccine response defined by detectable levels of immunoglobulin-G against the receptor binding domain of the S1 subunit of SARS-CoV-2 spike antigen of ≥2 in serum of patients receiving maintenance dialysis, 165/186 (88.7%) were found to be seropositive (with 70% at maximum titer) at least 14 days after completing the second dose. No significant differences were observed by race or other subgroup or by vaccine manufacturer. Therefore, an equitable and aggressive vaccination strategy for all eligible maintenance dialysis patients, regardless of age, sex, race, ethnicity, or disability, is warranted to prevent the extremely high morbidity and mortality associated with COVID-19 in this high risk population.

Due to age and impaired kidney function, older adults with kidney disease are at increased risk of medication-related problems and related hospitalizations. One proa ctive approach to minimize this risk is deprescribing. Deprescribing refers to the systematic process of reducing or stopping a medication. Aside from preventing harm, deprescribing can potentially optimize patients’ quality of life by aligning medications with their goals of care. For some patients, deprescribing could involve less aggressive management of their diabetes and/or hypertension. In other instances, deprescribing targets may include potentially inappropriate medications that carry greater risk of harm than benefit in older adults, medications that have questionable efficacy, including medications that have varying efficacy by degree of kidney function, and that increase medication regimen complexity. We include a guide for clinicians to utilize in deprescribing, the List, Evaluate, Shared Decision-Making, Support (LESS) framework. The LESS framework provides key considerations at each step of the deprescribing process that can be tailored for the medications and context of individu al patients. Patient characteristics or clinical events that warrant consideration of deprescribing include limited life expectancy, cognitive impairment, and health status changes, such as dialysis initiation or recent hospitalization. We acknowledge patient-, clinician-, and system-level challenges to the depre scribing process. These include patient hesitancy and challenges to discussing goals of care, clinician time constraints and a lack of evidence-based guidelines, and system-level challenges of interoperable electronic health records and limited incentives for deprescribing. However, novel evidence-based tools designed to facilitate deprescribing and future evidence on effectiveness of deprescribing could help mitigate these barriers. This review provides foundational knowledge on deprescribing as an emerging component of clinical practice and research within nephrology.

Dialysis facilities voluntarily reported severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections in vaccinated dialysis patients detected between January 1, 2021, and August 31, 2021, to the Centers for Disease Control and Prevention. Among 4087 patients reported, most were symptomatic, a third required hospitalization, and 9% died within 30 days of diagnosis. Monitoring SARS-CoV-2 infections and outcomes among vaccinated people on dialysis provides valuable insight into this population.

Given the increased morbidity and mortality from COVID-19 among patients undergoing maintenance dialysis, we examined the seroresponse to an additional dose of SARS-CoV-2 mRNA vaccine, using a hypothesized protective anti-spike protein IgG antibody threshold of 7 based on prior work. Among 395 patients, 384 (97%) had seroresponse ≥7 following administration of the third dose. Among those with suboptimal (peak

SARS-CoV-2 vaccine effectiveness and immunogenicity threshold associated with protection against COVID-19 related hospitalization or death in the dialysis population is unknown.Retrospective, observational study.Adult patients receiving maintenance dialysis through a national dialysis provider without COVID-19 history treated between February 1, 2021 and December 18, 2021 with follow up through January 17, 2022.SARS-CoV-2 vaccination status.All SARS-CoV-2 infections, composite of hospitalization or death following COVID-19.Logistic regression was used to determine COVID-19 case rates and vaccine effectiveness.Of 16,213 patients receiving dialysis during the study period, 12,278 (76%) were fully vaccinated, 589 (4%) were partially vaccinated and 3,346 (21%) were unvaccinated by the end of follow-up. Of 1,225 COVID-19 cases identified, 550 (45%) occurred in unvaccinated patients, while 891 (73%) cases occurring during the Delta period. Between pre-Delta period and Delta periods vaccine effectiveness against a severe COVID-19 related event (hospitalization or death) was 84% and 70%, respectively. In the subset of 3,202 vaccinated patients with at least one anti-spike IgG assessment, lower anti-spike IgG levels were associated with higher case rates per 10,000 days and adjusted hazard ratios for both infection and COVID-related hospitalization or death.Observational design, residual biases and confounding may exist.Among maintenance dialysis patients, SARS-CoV-2 vaccination was associated with a lower risk of COVID-19 diagnosis and associated hospitalization or death. Among vaccinated patients, low anti-spike IgG level is associated with worse COVID-19 related outcomes.

BackgroundSARS-CoV-2 vaccine effectiveness during the Delta period and immunogenicity threshold associated with protection against COVID-19 related hospitalization or death in the dialysis population is unknown.MethodsA retrospective, observational study assessed SARS-CoV-2 vaccine effectiveness and immunogenicity threshold in all adult maintenance dialysis patients without COVID-19 history treated between February 1 and October 2, 2021. All COVID-19 infections, composite of hospitalization or death following COVID-19 and available SARS-CoV-2 anti-spike immunoglobulin (Ig) G values were extracted from electronic medical record. COVID-19 cases per 10,000 days at risk and vaccine effectiveness during pre-Delta and Delta periods were determined.ResultsOf 15,718 patients receiving dialysis during the study period, 11,191 (71%) were fully vaccinated, 733 (5%) were partially vaccinated and 3,794 (24%) were unvaccinated. 967 COVID-19 were cases identified: 511 (53%) occurred in unvaccinated patients and 579 (60%) occurred during the Delta period. COVID-19 related hospitalization or death was less likely among vaccinated versus unvaccinated patients for all vaccines (adjusted HR 0.19 [0.12, 0.30]) and for BNT162b2/Pfizer, mRNA-1273/Moderna, and Ad26.COV2.S/Janssen (adjusted HR=0.25 [0.16, 0.40], 0.14 [0.08, 0.22], and 0.34 [0.17, 0.68] respectively). Among those with anti-spike IgG levels, those with IgG level ≥ 7 had significantly lower risk of a COVID-19 diagnosis (HR=0.25 [0.15, 0.42]) and none experienced a COVID-related hospitalization or death.ConclusionsAmong maintenance dialysis patients, SARS-CoV-2 vaccination was associated with a lower risk of COVID-19 diagnosis and associated hospitalization or death. Among vaccinated patients, low anti-spike IgG level is associated with worse COVID-19 related outcomes.Significance StatementSARS-CoV-2 vaccine effectiveness and association between antibody levels and clinical outcomes in maintenance dialysis patients is not known. Between February 1 and October 2, 2021, vaccine effectiveness was 85% against COVID-19 infection and 81% against composite of COVID-related hospitalization or death. COVID-19 case rates and severe outcomes were higher during the Delta dominant period (June 27-October 2, 2021). Increasing time (weeks) since full vaccination status was associated with increased risk for COVID-19 related hospitalization or death. Anti-spike IgG level ≥ 7 had lower risk of a COVID-19 diagnosis and no COVID-related hospitalization or death. Our findings supports utilization of SARS-CoV-2 vaccination and suggests that monitoring SARS-CoV-2 antibody levels and administering additional vaccine doses to maintain adequate immunity will be beneficial.

Rationale & ObjectivesHigh dose influenza vaccine provides better protection against influenza infection in older adults than standard dose vaccine. We compared vaccine seroresponse among hemodialysis patients over 4 months after high dose inactivated (HD-IIV3), standard dose inactivated (SD-IIV4) or recombinant (RIV4) influenza vaccine.Study DesignProspective observational study.Setting & ParticipantsPatients at four hemodialysis clinics who received influenza vaccination. Hemagglutination inhibition titers were measured at baseline and at 1, 2, 3 and 4 months following vaccination with HD-IIV3, SD-IIV4 or RIV4 influenza vaccine.OutcomeThe primary outcome was seroprotection rates at ≥1:40 and ≥1:160 (which correspond to antibody levels providing protection from infection in about 50% and 95% immunocompetent individuals, respectively) at 1, 3 and 4 months after vaccination.Analytical approachWe determined GMT and seroprotection and seroconversion rates. Chi-square or Fisher exact tests were used for categorical data; continuous values were analyzed using Wilcoxon rank-sum tests. Generalized estimating equation was used to determine association between GMT and age.Results254 HD patients received HD-IIV3 (n=141), SD-IIV4 (n=36) or RIV4 (n=77) vaccine. A robust initial seroresponse to influenza A strains was observed after all 3 vaccines, with no difference in seroprotection rates at either the ≥1:40 or ≥1:160 titer at 1 and 2 months. Seroresponses to RIV4 and SD-IIV4 waned thereafter, such that by month 3 and 4, seroprotection by HD-IIV3 was significantly higher. Seroprotection rates were lower to the B strains across all three vaccines. Results trended similarly across patients aged below 65 years.LimitationsDue to use of observational data, bias by unmeasured confounders may exist. Some of the subgroups by age were low in number.ConclusionsHemodialysis patients achieved high seroprotection rates after all 3 vaccines. The seroresponse waned more slowly with HD-IIV3 as compared to SD-IIV4 or RIV4 vaccine.

Background and ObjectivesWhile most maintenance dialysis patients exhibit initial seroresponse to vaccination, concerns remain regarding the durability of this antibody response. This study evaluated immunity over time.Design, setting, participants, and measurementsThis retrospective cohort study included maintenance dialysis patients from a midsize national dialysis provider who received a complete SARS-CoV-2 vaccine series and had at least one antibody titer checked after full vaccination. Immunoglobulin G spike antibodies (SAb-IgG) titers were assessed monthly with routine labs beginning after full vaccination and followed over time; the semiquantitative SAb-IgG titer reported a range between 0 and ≥ 20 U/L. Descriptive analyses compared trends over time by prior history of COVID-19 and type of vaccine received. Time-to-event analyses were conducted for the outcome of loss of seroresponse (SAb-IgG < 1 U/L or development of COVID-19). Cox proportional hazards regression was used to adjust for additional clinical characteristics of interest.ResultsAmong 1898 maintenance dialysis patients, 1567 (84%) had no prior history of COVID-19. Patients without a history of COVID-19 had declining titers over time. Among 441 BNT162b2/Pfizer recipients, median [IQR] SAb-IgG titer declined from 20 [5.99-20] U/L in month 1 to 1.30 [0.15-3.59] U/L by month 6. Among 779 mRNA-1273/Moderna recipients, median [IQR] SAb-IgG titer declined from 20 [20-20] in month 1 to 6.20 [1.74-20] by month 6. The 347 Ad26.COV2.S/Janssen recipients had a lower titer response than mRNA vaccine recipients over all time periods. In time-to-event analyses, Ad26.COV2.S/Janssen and mRNA-1273/Moderna recipients had the shortest and longest time to loss of seroresponse, respectively. The maximum titer reached in the first two months after full vaccination was predictive of the durability of the SAb-IgG seroresponse; patients with SAb-IgG titer 1-19.99 U/L were more likely to have loss of seroresponse compared to patients with SAb-IgG titer ≥ 20 U/L (HR 23.9 [95% CI: 16.1-35.5]).ConclusionsVaccine-induced seroresponse wanes over time among maintenance dialysis patients across vaccine types. Early titers after full vaccination predict the durability of seroresponse.

BACKGROUND AND OBJECTIVES: Although most patients receiving maintenance dialysis exhibit initial seroresponse to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, concerns exist regarding the durability of this antibody response. This study evaluated seroresponse over time. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study included patients on maintenance dialysis, from a midsize national dialysis provider, who received a complete SARS-CoV-2 vaccine series and had at least one antibody titer checked after full vaccination. IgG spike antibodies (anti-spike IgG) titers were assessed monthly with routine laboratory tests after vaccination; the semiquantitative assay reported a range between zero and ≥20 Index. Descriptive analyses compared trends over time by history of coronavirus disease 2019 (COVID-19) and vaccine type. Time-to-event analyses examined the outcome of loss of seroresponse (anti-spike IgG

ImportanceVaccines against SARS-CoV-2 are highly effective in the general population; however, their efficacy may be diminished in maintenance dialysis patients, a population particularly vulnerable to COVID-19 infection and morbidity.ObjectiveWe assessed vaccine response in a national sample of maintenance dialysis patients and identified predictors of response.DesignRetrospective cohort studySetting130 Dialysis Clinic, Inc (DCI) facilitiesParticipantsMaintenance dialysis patients without known prior COVID-19 or a positive baseline antibody titerExposure(s)Vaccine type and clinical characteristicsMain Outcome(s)Using a semi-quantitative assay for antibodies against SARS-CoV-2 spike antigen, vaccine response was defined as at least one titer ≥1 U/L between 14 and 74 days after completion of a SARS-CoV-2 vaccine series. Regression analysis was used to identify characteristics associated with response.ResultsAmong 1528 patients, 437 received BNT162b2/Pfizer vaccine, 766 received mRNA-1273/Moderna, and 325 received Ad26.COV2.S/Janssen. Serologic response differed significantly by vaccine type: 381/437 (87%) among BNT162b2/Pfizer recipients, 736/766 (96%) among mRNA-1273/Moderna recipients, and 119/325 (37%) among Ad26.COV2.S/Janssen recipients. Vaccine type, older age, immune-modulating medication, history of transplantation, and lower serum albumin were associated with vaccine non-response.Conclusions and RelevanceSerologic response to mRNA vaccines is robust among maintenance dialysis patients. Future research should evaluate durability of this response, correlation between seroresponse and protection from COVID-19, and the role of the AD26.COV2.S/Janssen vaccine in this vulnerable population.

Medication-related problems are a leading cause of morbidity and mortality. Patients requiring dialysis are at a heightened risk of adverse drug reactions because of the prevalence of polypharmacy, multiple chronic conditions, and altered (but not well understood) medication pharmacokinetics and pharmacodynamics inherent to renal failure. To minimize preventable medication-related problems, healthcare providers need to prioritize medication safety for this population. The cornerstone of medication safety is medication reconciliation. Here, we present a case highlighting adverse outcomes when medication reconciliation is insufficient at care transitions. We review available literature on the prevalence of medication discrepancies worldwide. We also explain effective medication reconciliation and the practical considerations for implementation of effective medication reconciliation in dialysis units. In light of the addition of medication reconciliation requirements to the Centers for Medicare and Medicaid Services End-Stage Renal Disease (ESRD) Quality Incentive Program, this review also provides guidance to dialysis unit leadership for improving current medication reconciliation practices. Prioritization of medication reconciliation has the potential to positively impact rates of medication-related problems, as well as, medication adherence, healthcare costs, and quality of life.

Calciphylaxis is a rare but devastating disease with a mortality rate up to 50% in 1 year. It is characterized by profoundly painful ischemic skin lesions and vascular calcification that affects predominantly patients with end stage renal disease. The use of certain medications is an important modifiable risk factor in calciphylaxis and discontinuation of these is a mainstay of treatment.This review will provide an overview of calciphylaxis and will focus on how certain therapeutic agents can affect the risk of calcification and associated thrombosis, key processes involved in the development of calciphylaxis.Calciphylaxis treatment requires a multi-modal approach including prevention, risk factor management, wound care, reperfusion, and use of fibrinolytics and antioxidants. Patients with end stage renal disease represent the most affected population. This population often has multiple medications prescribed, some worth reconsidering before starting or continuing them. When possible, we recommend stopping all potentially contributing medications in patients with calciphylaxis, including warfarin, active vitamin D, calcium supplements, and iron.

Background and objectives High-dose influenza vaccine, which contains fourfold more antigen than standard dose, is associated with fewer cases of influenza and less influenza-related morbidity in the elderly general population. Whether the high-dose influenza vaccine benefits patients on dialysis, whose immune response to vaccination is less robust than that of healthy patients, is uncertain. Design, setting, participants, & measurements We compared hospitalizations and deaths during the 2015–2016 and 2016–2017 influenza seasons by vaccine type (standard trivalent, standard quadrivalent, and high-dose trivalent influenza vaccine) administered within a national dialysis organization. The association of vaccine type with outcomes was estimated using Cox proportional hazards regression with adjustment for patient factors and “center effect.” Analyses were stratified by age and dialysis modality. Results Between September 1 and December 31, 2015, standard dose trivalent, standard dose quadrivalent, and high-dose trivalent influenza vaccines were administered to 3057 (31%), 5981 (61%), and 805 (8%) patients, respectively. The adjusted rates of first hospitalizations by vaccine type during the influenza season were 8.43, 7.88, and 7.99 per 100 patient-months, respectively, and the adjusted rates of death were 1.00, 0.97, and 1.04, respectively. These differences were not significant. In 2016, 3614 (39%) received quadrivalent vaccine, and 5700 (61%) received high-dose trivalent vaccine. The adjusted rates of first hospitalization by vaccine type were 8.71 and 8.04 per 100 patient-months, respectively, and the adjusted rates of death were 0.98 and 1.02, respectively. Receipt of high dose was associated with a significant reduction in hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.86 to 1.00; P=0.04); there was no significant association with death. There was no significant heterogeneity of either association by age group or dialysis modality. Conclusions Receipt of high-dose compared with standard dose influenza vaccine in 2016–2017 was associated with lower rates of hospitalization in patients on dialysis, although that was not seen in 2015–2016.

Dialysis patients frequently experience medication-related problems. We studied the association of a multidisciplinary medication therapy management (MTM) with 30-day readmission rates.Retrospective cohort study.Maintenance dialysis patients discharged home from acute-care hospitals between May 2016 and April 2017 who returned to End-Stage Renal Disease Seamless Care Organization dialysis clinics after discharge were eligible. Patients who were readmitted within 3 days, died, or entered hospice within 30 days were excluded.MTM consisting of nurse medication reconciliation, pharmacist medication review, and nephrologist oversight was categorized into 3 levels of intensity: no MTM, partial MTM (defined as an incomplete MTM process), or full MTM (defined as a complete MTM process).The primary outcome was 30-day readmission.Time-varying Prentice, Williams, and Peterson total time hazards models explored associations between MTM and time to readmission after adjusting for age, race, sex, diabetes comorbidity, albumin level, vascular access type, kidney failure cause, dialysis vintage and modality, marital status, home medications, frequent prior hospitalizations, length of stay, discharge diagnoses, hierarchical condition category, and facility standardized hospitalization rates. Propensity score matching was performed to examine the robustness of the associations in a comparison between the full- and no-MTM exposure groups on time to readmission.Among 1,452 discharges, 586 received no MTM, 704 received partial MTM, and 162 received full MTM; 30-day readmission rates were 29%, 19%, and 11%, respectively (P 0.001). Compared with no MTM, discharges with full MTM had the lowest time-varying risk for readmission within 30 days (HR, 0.26; 95% CI, 0.15-0.45); discharges with partial MTM also had lower readmission risk (HR, 0.50; 95% CI, 0.37-0.68). In propensity score-matched sensitivity analysis, full MTM was associated with lower 30-day readmission risk (HR, 0.20; 95% CI, 0.06-0.69).Reliance on observational data. Residual bias and confounding.MTM services following hospital discharge were associated with fewer 30-day readmissions in dialysis patients. Randomized controlled studies evaluating different MTM delivery models and cost-effectiveness in dialysis populations are warranted.

Rationale & objective During the COVID-19 pandemic, patients receiving maintenance dialysis are a highly vulnerable population due to their comorbidities and circumstances that limit physical distancing during treatment. This study sought to characterize the risk factors for and outcomes following COVID-19 infection in this population. Study design Retrospective cohort study. Setting & participants Maintenance dialysis patients in clinics with at least one patient with a positive test for SARS-CoV-2 from February to June 2020, treated by a mid-size national dialysis provider. Predictors Demographics, dialysis characteristics, residence in a congregate setting, comorbid conditions, measures of frailty, and use of selected medications. Outcomes COVID-19 defined as having a positive SARS-CoV-2 test and all-cause mortality among those with COVID-19. Analytical approach Logistic regression analyses to identify clinical characteristics associated with COVID-19and risk factors associated with mortality among patients following COVID-19. Results 438/7948 (5.5%) maintenance dialysis patients developed COVID-19. Male sex, Black race, in-center dialysis (vs. home dialysis), treatment at an urban clinic, residence in a congregate setting, and greater comorbidity were associated with contracting COVID-19. Odds of COVID-19 was 17-fold higher for those residing in a congregate setting [OR = 17.10 (95% CI 13.51, 21.54)]. Of the 438 maintenance dialysis patients with COVID-19, 109 (24.9%) died. Older age, heart disease, and markers of frailty were associated with mortality. Limitations No distinction between symptomatic and asymptomatic SARS-CoV-2 positivity, with asymptomatic screening limited by testing capacity during this initial COVID-19 surge period. Conclusions COVID-19 is common among patients receiving maintenance dialysis, particularly those residing in congregate settings. Among maintenance dialysis patients with COVID-19, mortality is high, exceeding 20%.

The intent of this study was to evaluate the appropriateness of commonly used intravenous (iv) vancomycin dosing schemes in patients on automated peritoneal dialysis (APD) using population pharmacokinetic (PK) modelling and Monte Carlo simulation.Data from a single-dose PK study of 10 non-infected APD patients ≥18 years old were analysed. Patients received iv vancomycin (15 mg/kg) followed by three cycler-assisted APD dwells over 8 h, followed by two 8 h dwells. Serum and dialysate samples were collected over the entire 24 h. A three-compartment model was fitted to the data with BigNPAG. Monte Carlo simulation was used to determine the probability of achieving an AUC/MIC ratio of400 in both the serum and the peritoneal cavity for a variety of iv vancomycin dosing schemes (1-2 g every 24-48 h).In the probability of target attainment (PTA) analyses, only 2 g of iv vancomycin every 24 h conferred90% probability of achieving an AUC/MIC ratio of400 for MIC values2 mg/L in the serum. However, this dosing regimen resulted in average trough concentrations20 mg/L. In the peritoneal cavity, no regimen yielded PTA ≥90% for MIC values ≥0.5 mg/L.Although expert guidelines suggest iv vancomycin may be an acceptable empirical therapy for patients on APD with infection, these analyses indicate that iv vancomycin may not be effective for peritonitis but may be a viable option for non-peritoneal infections with MIC values ≤1 mg/L.

Patients with ESRD undergoing dialysis have highly complex medication regimens and disproportionately higher total cost of care compared with the general Medicare population. As shown by several studies, dialysis-dependent patients are at especially high risk for medication-related problems. Providing medication reconciliation and therapy management services is critically important to avoid costs associated with medication-related problems, such as adverse drug events and hospitalizations in the ESRD population. The Medicare Modernization Act of 2003 included an unfunded mandate stipulating that medication therapy management be offered to high-risk patients enrolled in Medicare Part D. Medication management services are distinct from the dispensing of medications and involve a complete medication review for all disease states. The dialysis facility is a logical coordination center for medication management services, like medication therapy management, and it is likely the first health care facility that a patient will present to after a care transition. A dedicated and adequately trained clinician, such as a pharmacist, is needed to provide consistent, high-quality medication management services. Medication reconciliation and medication management services that could consistently and systematically identify and resolve medication-related problems would be likely to improve ESRD patient outcomes and reduce total cost of care. Herein, this work provides a review of available evidence and recommendations for optimal delivery of medication management services to ESRD patients in a dialysis facility-centered model.

Medication regimen simplification may improve adherence in end-stage kidney disease. The effect of nocturnal home hemodialysis (NHHD) on medication burden is unknown. A retrospective pilot study of NHHD patients was conducted. Medication information was collected at baseline, NHHD start, and at 3, 6, 12, 18, and 24 months. SF-36 scores were collected at baseline, 6, 12, and 24 months. The number of medications, pill burden, and number of administrations per day were determined. Medication Regimen Complexity Index was used at each time point as a comparator. Medications for anemia, mineral and bone disorders (MBD), cardiovascular (CV) disease, infection, and vitamins were analyzed for number of medications and pill burden. Thirty-five patients were included. Patients used 10.5 ± 4.4 medications at baseline and 11.8 ± 4.7 at the end of the study (P=NS). Regarding the number of medications, anemia medications, anti-infectives, and vitamins increased; MBD and CV medications decreased by the end of the study. Total pill burden did not change over 24 months, nor did anemia pill burden. Mineral bone disorder and CV pill burden decreased, and vitamins and anti-infective pill burden increased. Daily medication administration times decreased significantly from 5.0 ± 1.5 to 3.6 ± 1.5 by 24 months. Switching to NHHD was associated with a significant increase in Medication Regimen Complexity Index at 24 months (P

Study Objective. To investigate the impact of a pharmaceutical care program managed by clinical pharmacists on drug use, drug costs, hospitalization rates, and drug-related problems (DRPs) in ambulatory patients undergoing hemodialysis. Design. Prospective, randomized, controlled, longitudinal, 2-year pilot study. Setting. Nonprofit university-affiliated dialysis clinic. Patients. One hundred four patients older than 18 years with end-stage renal disease (ESRD) who were undergoing a stable hemodialysis regimen for at least 3 months. Intervention. Patients were randomly assigned to receive either pharmaceutical care, consisting of one-on-one care, with in-depth drug therapy reviews conducted by a clinical pharmacist (57 patients), or standard of care, consisting of brief drug therapy reviews conducted by a nurse (47 patients). Measurements and Main Results. Baseline data on demographic and clinical characteristics were collected. Mean numbers of concomitant drugs, drug costs, hospitalization rates, and lengths of stay were compared between the groups. In the pharmaceutical care group, DRPs were identified and recorded. Baseline age, length of time receiving hemodialysis, and etiology of ESRD were not significantly different between the groups. Mean number of concomitant drugs at baseline was similar between the groups. At the end of the 2-year follow-up, pharmaceutical care was associated with a significant decrease of 14% fewer drugs compared with standard of care, as documented during each drug therapy review (p

Objective: To evaluate chronic kidney disease (CKD)–associated anemia management challenges and limitations and discuss strategies to improve treatment rates and patient response to therapy, monitoring of patient response to therapy, and education of prescribing providers and patients. Data Sources: Multiple MEDLINE searches were performed using a comprehensive search term list to identify studies for inclusion, including, but not limited to, anemia, erythropoiesis-stimulating agent (ESA), epoetin, darbepoetin, CERA, hemoglobin, CKD, dialysis, end-stage renal disease, quality of life, and pharmacist. Annual data reports and clinical practice guidelines published by the National Kidney Foundation and US Renal Data System were included. Information provided within product package inserts for recombinant human erythropoietin (epoetin alfa; Epogen, Procrit) and darbepoetin alfa (Aranesp) were also included. Study Selection and Data Extraction: Only articles that were published in English and were relevant for this review were included. Data Synthesis: Anemia is a common complication of CKD, with significant impact on patients' quality of life. Anemia of CKD represents a significant burden on the healthcare system, with ESA use resulting in substantial financial costs. As new therapies, formularies, and dosing regimens evolve, the collaborative role of the clinical pharmacist is integral to a multidisciplinary treatment strategy, both in the inpatient and outpatient settings, such as hospitals or dialysis centers, respectively. This review focuses on initial and target hemoglobin (Hb) concentrations, as well as patient characteristics, treatment preferences, and dosing schedules, which are important considerations in managing CKD-associated anemia. To ensure effective therapeutic strategies, a patient-centered approach is required. Pharmacists are ideally positioned to help select ESA therapy, influence formulary use, educate healthcare professionals and patients, develop and implement dosing and monitoring protocols, and possibly promote quality improvement. Conclusions: An approach to CKD-associated anemia management that involves collaboration with pharmacists is essential to achieve patient-specific, cost-effective ESA therapy.

End-stage renal disease and initiation of hemodialysis (HD) adversely affect health-related quality of life (HRQOL). There are currently no data evaluating the effect of pharmaceutical care (PC) on HRQOL in HD patients. HD patients were randomized to receive PC; one-on-one, in-depth medication reviews conducted by a clinical pharmacist or Standard of Care (SOC); and brief medication reviews conducted by dialysis nurses. The renal quality of life profile (RQLP) was administered at baseline and then at 1 and 2 years after study initiation. The RQLP is a 43-item questionnaire that has 5 dimensions: Eating/Drinking, Physical Activities, Leisure Time, Psychosocial Activities, and Impact of Treatment, where increasing scores reflect worsening of HRQOL. A total of 107 patients were enrolled (SOC: n=46; PC: n=61). Besides gender, there were no differences in the demographics or the baseline total RQLP scores. The mean+/-SD total RQLP scores at Year 1 were significantly worse in SOC compared with PC (88+/-31 vs. 71+/-34, respectively; P=0.03). Significant worsening of Eating and Drinking (5.9+/-3.3 vs. 4.4+/-3.1, respectively; P=0.04), Physical Activities (37+/-13.6 vs. 30+/-16.3, respectively; P=0.04), and Leisure Time scores (8.3+/-3.4 vs. 5.9+/-3.6, respectively; P=0.03) was also observed in the SOC group. After 2 years, only the SOC patients had worsening of Leisure Time (7.5+/-3.0 vs. 5.2+/-3.9, respectively; P=0.04). No other parameters were different between the groups after 2 years. These data indicate that patients who have clinical care provided by pharmacists do not have worsened HRQOL after 1 year and are able to maintain HRQOL for an additional year.

Purpose The data describing the compatibility of tobramycin and ceftazidime in icodextrin-based peritoneal dialysis (PD) solution is limited. The objective of this study was to assess the chemical stability of tobramycin and ceftazidime in icodextrin PD solution in polyvinyl chloride containers. Methods Commercially available 2-L bags of icodextrin 7.5% PD solution were used for each sample. Nine tobramycin study samples were prepared by adding 80 mg tobramycin HCl to each bag. Nine ceftazidime samples were prepared by adding 1000 mg ceftazidime to each bag. Three bags of tobramycin–icodextrin solution were stored under each of the following conditions: refrigeration (4°C), room temperature (25°C), and body temperature (37°C). Three bags of ceftazidime–icodextrin solution were also stored at each of the respective temperatures. Samples were withdrawn from each bag immediately after preparation and at predetermined intervals (1, 2, 4, 6, 8, 12, 24, 48, 72, 96, 120, 168, and 336 hours after preparation). Solutions were visually inspected for precipitation, cloudiness, and discoloration at each sampling interval. All samples were immediately frozen (–80°C) after collection and stored prior to assay. Total concentrations of tobramycin and ceftazidime in dialysate fluid were determined by high-performance liquid chromatography. The last time point when tobramycin or ceftazidime concentration was >90% from baseline was used to denote stability. Results All solutions were clear in appearance and no color change or precipitation was observed during the study. For tobramycin, under refrigeration, a mean of 94.6% ± 2.3% of the initial concentration remained at 336 hours (14 days); at room temperature, 90.5% ± 4.3% remained at 168 hours (7 days); at body temperature, 90.0% ± 8.1% remained at 24 hours. For ceftazidime, under refrigeration, a mean of 98.0% ± 0.3% of the initial concentration remained at 168 hours (7 days); at room temperature, 91.6% ± 2.0% remained at 48 hours; at body temperature, 93.9% ± 1.1% remained at 8 hours. Stability was not assessed beyond these respective time points. Conclusion Premixed tobramycin–icodextrin PD solution remains stable for 336 hours (14 days) when refrigerated (4°C) and for 168 hours (7 days) at room temperature (25°C). Ceftazidime–icodextrin PD solution is stable for 168 hours and 48 hours, respectively, when stored at 4°C and 25°C. It is recommended that the bags be kept refrigerated whenever possible. Tobramycin–icodextrin solution stored at body temperature was stable up to 24 hours, and ceftazidime–icodextrin solutions up to 8 hours, permitting the practice of pre-warming solutions prior to administration.

Screening processes to identify patients who have chronic kidney disease (CKD) early in the disease allow time to manage its comorbidities and complications effectively and aggressively. The Kidney Early Evaluation Program (KEEP), sponsored by the National Kidney Foundation (NKF), is a free screening program that targets people who have diabetes, hypertension, and parents, grandparents, or siblings with diabetes, hypertension, or CKD.To (1) introduce KEEP and its objectives and (2) review population data and progress with goals to date.The KEEP goals are to raise awareness of CKD, especially in high-risk patients, provide free testing, and encourage dialogue between patients and their physicians, leading to a treatment plan. Of the 55,000 patients who have been screened through KEEP, approximately 13,000 (29%), or nearly 1 in 3 patients, have been identified as having CKD. Once a patient has been diagnosed with CKD, clinicians must address risk factors such as diabetes, hypertension, and kidney-specific diseases (e.g., glomerular diseases) that contribute to the process of renal decline. The NKF through the Kidney Disease Outcomes Quality Initiative has assembled a series of guidelines addressing dialysis adequacy, vascular access, anemia, nutrition, CKD, bone and mineral metabolism, dyslipidemia, hypertension, cardiovascular disease, and diabetes.CKD is quite common but often unrecognized and undertreated, even though rigorous guidelines for diagnosis and care have been developed. Ten areas have been identified as important for optimal care of the CKD patient. Each of these areas should be addressed and closely monitored in this population: hypertension, anemia, glucose control, lipid control, smoking cessation, aspirin prophylaxis and use of a beta-blocker post-myocardial infarction, use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, diet, exercise, and weight control.

Hypertension and diabetes mellitus are the two leading causes of chronic kidney disease (CKD). The purpose of this paper is to provide an overview of the present pharmacologic and adverse events involved in the treatment of hypertension and diabetes mellitus in patients with CKD. Proper management of hypertension and diabetes mellitus, a common co-morbidity associated with CKD, would slow the progression of kidney disease and reduce healthcare expenditures. Awareness of potential side effects due to the medications or renal insufficiency could prevent unnecessary harm to the patient and provide cost-containment. Active involvement of all healthcare team members can reduce progression of CKD and improve quality of life outcomes in CKD patients.

Background Little information is available on the disposition of vancomycin during chronic peritoneal dialysis (PD) in children. The primary objective of this study was to investigate the disposition of vancomycin following intraperitoneal (IP) administration in children receiving short-dwell [ e.g., automated PD (APD)] and long-dwell [ e.g., continuous ambulatory PD (CAPD)] PD. Methods A 6-hour exchange containing vancomycin 500 mg/L, using an exchange volume of 1100 mL/m2 body surface area (BSA), was followed by 4-, 6-, and 8-hour antibiotic-free exchanges. The 8-hour exchange was followed by three to four 90-minute antibiotic-free exchanges. Serial blood and dialysis effluent samples were obtained and analyzed for vancomycin concentration by high-pressure liquid chromatography. Pharmacokinetic parameters were computed using noncompartmental methods. Results The bioavailability of vancomycin during a 6-hour IP exchange was 70% ± 5%, resulting in a delivered dose of 12.0 ± 1.8 mg/kg, and a 6-hour serum vancomycin concentration of 23.3 ± 7.2 μg/mL. Total body vancomycin clearance measured 10.72 ± 4.52 mL/minute/1.73 m2 BSA, while clearance attributable to PD measured 2.78 ± 1.08 mL/min/1.73 m2 BSA and accounted for 29% ± 11% of total vancomycin clearance. Dialysis clearance during long-dwell (CAPD) and short-dwell (APD) regimens was similar, measuring 2.46 ± 1.04 and 3.09 ± 1.28 mL/min/1.73 m2 BSA, accounting for 25% ± 13% and 32% ± 12% of total body clearance respectively. Conclusions Intraperitoneal absorption and dialysis clearance of vancomycin in children receiving PD are similar to those reported in adult dialysis patients. In contrast, total body clearance of vancomycin appears to be increased and the elimination half-life decreased in children, due to increased elimination by non-renal nondialysis routes. For intermittent IP vancomycin therapy in children with peritonitis, an IP load containing vancomycin 1000 mg/L (or 30 mg/kg), followed a single full-fill (1100 mL/m2 BSA) daily exchange, containing vancomycin 250 mg/L (or 7.5 mg/kg), from day 2 until the end of treatment will maintain a vancomycin dialysate concentration of >4 μg/mL.

Background Intravenous iron is typically administered during the hemodialysis (HD) procedure. The extent of VIT 45, a novel intravenous iron formulation, removal by high-flux (HF) or high-efficiency (HE) dialysis membranes at various ultrafiltration rates (UFR) is unknown. Methods An in vitro HD system was constructed to determine the dialyzabiltiy of iron from a normal saline compartment (NSC) containing 1000 mg iron of VIT 45. The in vitro system utilized a 6-L closed-loop SBS system that was subject to 4 different HD conditions conducted over 4 hours: HE membrane + 0 ml/h UFR; HE membrane + 500 ml/h UFR; HF membrane + 0 ml/h UFR; HF membrane + 500 ml/h UFR. Blood flow and dialysate flow rates were 500 ml/min and 800 ml/min, respectively. The dialysate compartment was a 6-L closed-loop system. A volumetric HD machine controlled all blood, dialysate, and ultrafiltration rates. NSC and dialysate compartment samples were taken at various time points and iron elimination rate (khd) and HD clearance (Clhd) was determined. Iron removal from the NSC > 15% was considered clinically significant. Results The percent removal of iron from the NSC was < 0.5% at all time points in the study. Dialysate recovery of iron was negligible: 1.7–5.1 mg. VIT 45 removal elimination rates from NSC were less than -0.001 h −1 (range -0.0002 ± 0.0001 to -0.0001 ± 0.0002 h −1) for all study conditions. Dialyzer type or UFR did not effect iron removal. Conclusion HF or HE dialysis membranes do not remove clinically significant amounts of VIT 45 over a 4-hour in vitro HD session. This effect remained constant even controlling for UFR up to 500 ml/hour. VIT 45 is not dialyzed by HE or HF dialysis membranes irrespective of UFR. (Int J Artif Organs 2006; 29: 1062–6)

Background: Medication-related problems are common in hemodialysis (HD) patients. These patients often require 12 medications to treat 5 to 6 comorbid conditions. Medication-related problem research reports cannot be generalized to the entire HD population because data are obtained from single centers and limited numbers of patients. We conducted a pooled analysis to gain additional insight into the frequency, type, and severity of medication-related problems and extrapolated the data to the entire US HD population. Methods: Articles were identified through a MEDLINE search (1962 to March 2004). Seven studies were included in the analysis. Medication-related problems were categorized into the following 9 categories: indication without drug therapy, drug without indication, improper drug selection, subtherapeutic dosage, overdosage, adverse drug reaction, drug interaction, failure to receive drug, and inappropriate laboratory monitoring. A medication-related problem appearance rate was determined. Results: We identified 1,593 medication-related problems in 395 patients (51.2% men; age, 52.4 ± 8.2 years; 42.7% with diabetes). The most common medication-related problems found were inappropriate laboratory monitoring (23.5%) and indication without drug therapy (16.9%). Dosing errors accounted for 20.4% of medication-related problems (subtherapeutic dosage, 11.2%; overdosage, 9.2%). The medication-related problem appearance rate was 5.75e−0.37x, where x equals number of months of follow-up (P = 0.02). Conclusion: HD patients experience ongoing medication-related problems. Reduction in medication-related problems in dialysis patients may improve quality of life and result in decreased morbidity and mortality. Pharmacists are uniquely trained to detect and manage medication-related problems. Pharmacists should be an integral member of the dialysis health care team.

Objective: To evaluate and summarize the data on erythropoietin (EPO) use to prevent anemia in intensive care unit (ICU) patients. Data Sources: A literature search was performed using MEDLINE (1966–December 2003) using the key words erythropoietin, intensive care unit, anemia, and critically ill. Data Synthesis: Attempts to decrease the complications associated with anemia in ICU patients have recently focused on EPO use. Two comprehensive studies found that EPO significantly reduced the cumulative number of blood transfusions as compared to that of placebo. The assessing outcomes found no difference between the groups with respect to mortality rates, ventilation days, or length of stay. Conclusions: Available trials demonstrate reduced blood transfusions in ICU patients when EPO is administered. However, this result has not carried over as a defined clinical benefit. EPO use should be reserved for patients with longer hospital stays who are at risk for frequent blood transfusions as a comprehensive blood conservation strategy in the ICU.

Background. End-stage renal disease (ESRD) patients are prescribed numerous medications. The United States Renal Data System (USRDS) reported on medication prescribing patterns in 1998. Since then, several new medications, treatment guidelines and recommendations have been introduced. The objective was to analyse and compare haemodialysis (HD) patient medication prescribing patterns between the Dialysis Clinic, Inc. (DCI) database and the USRDS report. Methods. Point-prevalent (01/01/03) medication use data from the DCI national database was obtained. Data collected included patient demographics, reason for and duration of ESRD, and medication listed on profile. All medications were classified similar to the USRDS and by where taken (clinic vs home). Medication prescribing patterns were compared between DCI and USRDS databases. Comparisons between age groups (

Objective: To determine whether adherence to suggested monitoring parameters improved as a result of the development and implementation of an amiodarone protocol and management clinic. Adverse effects from amiodarone therapy were also evaluated to ascertain whether the Amiodarone Management Clinic (AMC) better identified adverse events as a result of improved monitoring. Methods: A retrospective review of charts of patients with an active amiodarone prescription was conducted. Patients were identified as enrolled in the AMC (intervention) or as receiving standard medical care (control) by nonpharmacist practitioners. Compliance with recommended monitoring parameters, including the presence of interacting medications and associated drug concentration or international normalized ratio (INR), was assessed for all patients and then compared between groups. Type and frequency of adverse effects were determined for both groups. Results: Two hundred twenty-five charts were reviewed; 154 and 71 patients were assigned to the intervention and control groups, respectively. One hundred one (66%) patients in the intervention group were considered compliant with thyroid function monitoring compared with 26 patients (37%) in the control group (p < 0.0001). One hundred six (69%) and 27 (38%) patients in the intervention and control groups, respectively, were deemed compliant with liver function monitoring (p < 0.0001). Intervention patients taking warfarin were more likely to have blood drawn for INR assessment; however, there was no difference in values between groups. Seventy-six patients had a documented adverse effect from amiodarone, 68 of whom were from the intervention group (p < 0.0001). Conclusions: Many patients receiving amiodarone are not managed according to published guidelines. Implementation of a pharmacist-managed protocol and clinic significantly improved compliance with 2 of the 3 parameters needing continuous monitoring. Although more adverse effects were documented for intervention patients, it is unclear whether the AMC actually improved the event detection rate.

ObjectiveTo determine the impact of dialysate flow rate (DFR) on cefazolin pharmacokinetics (PK) in peritoneal dialysis (PD) patients.MethodsA meta-analysis of published reports, identified by MEDLINE search (1966-2002) and other sources, containing information on cefazolin PK data in PD patients was conducted. Data were analyzed based upon low DFR (≤ 5.50 mL/minute) or high DFR (> 5.50 mL/minute). Data available were from North American (NA) ( n = 45) and Singaporean ( n = 10) patients. Complete data sets were available for 33 patients (CDS patients). Data were analyzed with respect to data origin and data set completeness: all patients (ALL), NA, and CDS. Analysis of log-transformed cefazolin PK data was performed to determine coefficient of determination ( r2) between DFR and cefazolin elimination rate constant (kel), clearance total (ClT), and clearance peritoneal (ClPD). Clearance total data were extrapolated to DFR observed in continuous flow PD.ResultsPublished literature provided data on 55 PD patients (12 high DFR, 43 low DFR). Regardless of data origin (ALL, NA, or CDS), a prominent coefficient of determination ( p < 0.0001) existed between DFR and all cefazolin PK data except ClPD. The p value for DFR correlation to ClPDwas 0.953, 0.011, and 0.036 for ALL, NA, and CDS patients, respectively. Cefazolin ClTand ClPDincreased at higher DFRs.ConclusionThese findings demonstrate that an increased DFR leads to an increased rate of cefazolin clearance in NA PD patients. The impact of Asian descent on cefazolin ClPDwarrants further investigation. Clinicians dosing cefazolin in PD patients using a higher DFR than that used to determine cefazolin PK should use increased doses or prescribe lower/comparable DFRs. Data are not yet available for patients prescribed very high DFRs ( e.g., continuous flow PD); extrapolation of our results demonstrates significant influences on clearance and risk for underdosing.

Clinicians treating peritoneal dialysis (PD)-associated peritonitis should be aware that continuous ambulatory PD (CAPD) and automated PD (APD) have different effects on the pharmacokinetics of antibiotics. Results from various APD and comparative CAPD pharmacokinetic studies are reviewed. In APD patients, antibiotic half-lives were shorter during the cycler exchanges. Antibiotic peritoneal clearance was greater in patients treated with APD than those treated with CAPD regimens. Antibiotic clearance depends upon residual renal function and dialysate flow rate. To ensure that maximal antibiotic bioavailability occurs with intermittent intraperitoneal (IP) dosing, it is recommended that the antibiotic-containing dialysate must dwell at least 4 hours to ensure an adequate antibiotic depot in the body. Knowledge of antibiotic disposition in PD patients will assist clinicians in appropriate IP antibiotic dose selection and prevention of dose-related adverse effects.

Anemia is a chronic condition that affects many patients with chronic kidney disease (CKD). These patients often require recombinant human erythropoietin (rHuEPO) to stimulate bone marrow to produce red blood cells. The agent often has to be administered 2-3 times/week for maximum efficacy A new product, darbepoetin-alpha, is a hyperglycosylated erythropoiesis-stimulating protein that has a longer terminal half-life than rHuEPO (25.3 vs 8.5 hrs), which allows for less frequent dosing. At an equivalent dosage as rHuEPO, darbepoetin-alpha maintains hemoglobin values within target range and has a similar adverse effect profile. It is safe and effective for treatment of anemia of CKD. Pharmacoeconomic and quality-of-life studies are warranted to determine the compound's overall benefit.

Background Empiric vancomycin treatment is frequently used in hemodialysis (HD) patients because of ease of administration when methicillin-resistant Staphylococcus aureus (MRSA) infection is suspected. Differing rates of MRSA indicate that empiric antibiotic treatment should be based on a center-specific antibiogram. Objective To develop a center-specific antibiogram, evaluate antibiotic prescribing patterns, and determine areas of improvement in infection treatment. Methods The antibiogram was constructed from culture and susceptibility (C&S) data from January through December 1999. Evaluation of prescribing habits was based on 3 criteria: (1) Hospital Infection Control Practices Advisory Committee and Centers for Disease Control and Prevention guidelines; (2) vancomycin for 1 dose followed by appropriate antibiotic based on C&S results; and (3) C&S obtained with more than 1 dose of antibiotic. Results HD was provided to 161 patients during the study period. Antibiotics were empirically prescribed 104 times in 62 different patients. Cultures were obtained 122 times, and 67 different isolates were identified. Gram-positive organisms and gram-negative organisms accounted for 77.6% and 22.4% of isolates, respectively. Gram-positive organisms were identified as Staphylococcus spp. (53.8%); 17.9% of the staphylococcal isolates were MRSA strains. No isolates of vancomycin-resistant enterococcus were identified. Based on the antibiogram, empiric antibiotic therapy within our center should be 1 dose each of vancomycin and an aminoglycoside. Empiric vancomycin was used 71 times. When criterion I is used, 12 prescriptions (16.9%) were considered appropriate. When criterion II and adjustment for MRSA reported for our center were used, 46 (64.8%) vancomycin prescriptions were considered appropriate. Forty-one patients had more than 1 dose of antibiotic therapy, and 18 (43.9%) of those patients did not have C&S data obtained as prescribed by criterion III. Areas of prescribing improvement include obtaining a C&S in all suspected infections prior to empiric therapy and a more aggressive antibiotic switch based on C&S results. Conclusions Antibiograms can be used to determine appropriate empric antibiotic therapy and identify areas of improvement.

End-stage renal disease (ESRD) patients are medically complex, require multiple medications for treatments of their various comorbidities, and cost the healthcare system billions of dollars each year. These patients are at risk of drug-related problems (DRPs) that may lead to increased morbidity, mortality, and cost to the healthcare system. Review of the literature demonstrates that pharmaceutical care provided by pharmacists improves ESRD patient care. Pharmacist review of ESRD patients' medication profiles and medical records has shown to be beneficial in identifying and resolving DRPs. Economic analysis suggests that for every $1 spent on pharmaceutical care, the healthcare system saves an estimated $3.98. Provision of pharmaceutical care by pharmacists should be consdiered for all ESRD patients.

Over the last 10 years, the main advances in RCN have come in our ability to predict outcomes for an individual patient. Treatment trials have been almost all uniformly disappointing. Recent positive trials with acetylcysteine and PGE1 will require confirmation in larger trials that are adequately powered for meaningful end points in the PCI population. In the meantime, adequate prehydration and maintenance of post-PCI urine flow rates of > 150 mL/min remain the most prudent measures. As the population ages, breakthroughs with respect to new contrast agents or effective prevention measures will be needed to offer PCI to the spectrum of patients at risk for renal injury.

The pharmacokinetics of intravenous (IV) vancomycin was studied in automated peritoneal dialysis (APD) patients who received a single IV dose of vancomycin (15 mg/kg total body weight). Dialysate samples were collected at the beginning, middle, and end of dwells 1 – 3 (on-cycler), and at the end of dwells 4 and 5 (off-cycler), for a 24-hour period. Blood samples were collected at the beginning, middle, and end of dwells 1 – 3 (on-cycler), and at the end of dwell 5 (off-cycler) for a 24-hr period. Pharmacokinetics parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and vancomycin clearance (Cl) values were normalized to 1.73 m2. Ten patients [4 males, 6 females; 47.4 ± 9.9 years of age (mean ± SD)] who had received PD for a median 3.5 months (range 2 – 66 months) were studied. Dwell times were 2.3 ± 0.1 hours on cycler and 7.3 ± 0.1 hours off cycler. Vancomycin half-life was significantly different on-cycler than off-cycler (11.6 ± 5.2 hr vs 62.8 ± 33.0 hr; p < 0.001). Vancomycin total Cl (ClT) was 7.4 ± 2.0 mL/min. Renal Cl (ClR) and PD Cl (ClPD) accounted for 23.6% and 28.0% of ClT, respectively. ClRcorrelated with GFR (ClR= 0.90 GFR – 1.01; r2= 0.79; p = 0.008). Mean vancomycin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (5 mg/mL) for the first cycler and the second ambulatory exchanges only.The results of this study suggest that, to provide adequate concentrations for susceptible organisms over a 24-hour period, current intermittent vancomycin dosing recommendations for PD-related peritonitis need to be changed to 35 mg/kg intraperitoneally on day 1, then 15 mg/kg IP thereafter ( i.e., once daily) in APD patients.

Cefazolin dialytic clearance has not been determined in patients undergoing hemodialysis with high-efficiency or high-flux dialyzers. The objective of this study is to determine the pharmacokinetics and dialytic clearance of cefazolin and develop dosing strategies in these patients. Twenty-five uninfected subjects undergoing chronic thrice-weekly hemodialysis were administered a single dose of intravenous cefazolin (15 mg/kg) after their standard hemodialysis session. Fifteen subjects underwent hemodialysis with high-efficiency hemodialyzers, and 10 subjects underwent hemodialysis with high-flux hemodialyzers. Blood and urine samples were collected serially over the interdialytic period, during the next intradialytic period, and immediately after the next hemodialysis session. Serum and urine concentrations of cefazolin were determined by high-performance liquid chromatography. Differential equations describing a two-compartment model were fit to the cefazolin serum concentration-time data over the study period, and pharmacokinetic parameters were determined. Mean dialytic clearance values for cefazolin were significantly greater in the high-flux group compared with the high-efficiency group (30.9 +/- 6.52 versus 18.0 +/- 6.26 mL/min, respectively; P: < 0.05). Cefazolin reduction ratios were significantly greater (0.62 +/- 0.08 versus 0.50 +/- 0.07; P: < 0.005) in the high-flux group compared with the high-efficiency group and correlated well with equilibrated urea reduction. The pharmacokinetic model developed from patient data was used to simulate cefazolin serum concentration data for high-efficiency and high-flux dialyzers. Cefazolin doses of 15 or 20 mg/kg after each hemodialysis session maintained adequate serum concentrations throughout a 2- or 3-day interdialytic period regardless of hemodialyzer type.

Recent findings on the use of beta-adrenergic blockers in patients with congestive heart failure (CHF) are reviewed. CHF is a progressive, debilitating disease that afflicts 4.6 million patients in the United States. Treatment has traditionally consisted of a diuretic, an angiotensin-converting-enzyme (ACE) inhibitor, and digoxin. Despite advances in ACE-inhibitor therapy, the five-year mortality rate remains nearly 50%. Overstimulation of the sympathetic nervous system is believed to contribute to mortality. Beta-blockers have recently been added to the standard of care for patients with New York Heart Association functional class II or III heart failure. Four randomized, double-blind, placebo-controlled clinical trials were recently completed that addressed the benefits of beta-blockers in CHF. The overall mortality rate was reduced 65% by carvedilol, 34% by metoprolol, and 33% by bisoprolol; all these reductions were significant compared with placebo, and the trials were ended early. Bucindolol, however, did not have a significant effect on mortality. These drugs are hepatically metabolized and may require dosage adjustment in hepatically impaired patients. Decompensation of heart failure is another consideration; a beta-blocker should be added only for patients with stable CHF. Dosages must be slowly adjusted to targeted levels. Adverse effects do not differ significantly among beta-blockers. In addition to their effect on mortality, beta-blockers reduce CHF-related morbidity, such as all-cause hospitalization. Carvedilol, metoprolol, and bisoprolol decrease the mortality and morbidity associated with CHF and can be used with limited adverse effects. The choice among these agents does not affect clinical outcomes; bucindolol, however, has proven ineffective.

Objective To identify correlations between the pharmacokinetic variables that describe drug disposition in peritoneal dialysis (PD) patients and the measures used to assess dialysis adequacy. Design and Methods This retrospective study re-evaluated data collected during previous pharmacokinetic studies for intraperitoneally administered cefazolin, ceftazidime, and gentamicin in continuous ambulatory peritoneal dialysis (CAPD) patients, and intravenous cefazolin and tobramycin in automated PD patients. Pharmacokinetic variables were compared to creatinine clearance (CCr), Kt/V, and peritoneal equilibration test data using the Pearson product correlation coefficient ( r). Results Prominent correlations were found between renal CCr and renal Kt/V, with renal clearances of CAPD cefazolin and ceftazidime, and automated PD tobramycin and cefazolin ( r values ranged from 0.698 to 0.986; p < 0.05). Conclusion These findings support current peritonitis treatment recommendations that patients with residual renal function may require higher doses or more frequent drug administration.