Epidemiology of Diabetic Kidney Disease among US Veterans.

Rationale: With a large number of patients and high mortality, diabetic kidney disease (DKD) imposes a significant burden on US health care. Although diabetes is the leading cause of chronic kidney disease and complications, the epidemiology of DKD in the contemporary US veteran population is generally unknown. Objective: We aimed to estimate the rate of DKD progression and to measure the general epidemiology of DKD in the United States veteran population. Study Design: We performed a retrospective observational research using electronic health-care records and administrative databases. Setting: The DKD patient cohort was abstracted from the Veterans Health Administration health-record data from January 2016 to March 2022. Participants: We defined DKD patients using the laboratory test data based on Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines. Analytic Approach: Summary statistics include the five-year cumulative incidence of progression to an advanced stage from the DKD stage at the cohort entry date and prevalence at a series of single time points. Results: A total of 685,288 patients (male [96%], mean age 62 years, Caucasian [64%], non-Hispanic [87%]) met our eligibility criteria. The 5-year cumulative incidence of progression to an advanced DKD stage or all-cause death from DKD stages G1 A2/A3, G2 A2/A3, G3a, and G3b were 52.0%, 47.4%, 50.5%, and 60.9%, respectively. In sum, 594,082 patients were classified as moderate or high risk as per KDIGO guidelines in 2021, and stages G3a and G3b accounted for 51.2% and 25.3%, respectively, of cases. Conclusion: More than half of DKD patients underwent a stage progression or death within 5 years. A substantial number of DKD patients at an earlier stage might be left undetermined. The study findings warrant a revision of DKD patient identification and management in US veterans.

Building an Equity-Centered Ecosystem: University of Utah Health as a Microcosm.

Academic medicine, and medicine in general, are less diverse than the general patient population. Family Medicine, while still lagging behind the general population, has the most diversity in leadership and in the specialty in general, and continues to lead in this effort, with 16.7% of chairs identifying as underrepresented in medicine. Historical and current systematic marginalization of Black or African American, Latina/e/o/x, Hispanic or of Spanish Origin (LHS), American Indian/Alaska Native, Native Hawaiian/Pacific Islander, and Southeast Asian individuals has created severe underrepresentation within health sciences professions. Over the last 30 years, the percentage of faculty from these groups has increased from 7 to 9% in allopathic academic medicine, with similar increases in Osteopathic Medicine, Dentistry, and Pharmacy, but all lag behind age-adjusted population means. Traditionally, diversity efforts have focused on increasing pathway programs to address this widening disparity. While pathway programs are a good start, they are only a portion of what is needed to create lasting change in the diversity of the medical profession as well as the career trajectory and success of underrepresented in medicine (URiM) health professionals toward self-actualization and positions of leadership. This article elucidates all parts of an ecosystem necessary to ensure that equity, diversity, and inclusion outcomes can improve.

Education Standards for Pharmacists Providing Comprehensive Medication Management in Outpatient Nephrology Settings.

Chronic kidney disease is a public health problem that has generated renewed interest due to poor patient outcomes and high cost. The Advancing American Kidney Health initiative aimed to transform kidney care with goals of decreasing the incidence of kidney failure and increasing the number of patients receiving home dialysis or a kidney transplant. New value-based models of kidney care that specify inclusion of pharmacists as part of the kidney care team were developed to help achieve these goals. To support this Advancing American Kidney Health-catalyzed opportunity for pharmacist engagement, the pharmacy workforce must have a fundamental knowledge of the core principles needed to provide comprehensive medication management to address chronic kidney disease and the common comorbid conditions and secondary complications. The Advancing Kidney Health through Optimal Medication Management initiative was created by nephrology pharmacists with the vision that every person with kidney disease receives optimal medication management through team-based care that includes a pharmacist to ensure medications are safe, effective, and convenient. Here, we propose education standards for pharmacists providing care for individuals with kidney disease in the outpatient setting to complement proposed practice standards.

A Modeling Exercise to Identify Predictors of Student Readiness for Advanced Pharmacy Practice Experiences.

Objective. To model the relationship of common pharmacy education assessment data including student demographics, pre-pharmacy performance, core didactic performance, and external testing measures to identify predictors of student readiness for advanced pharmacy practice experiences (APPEs). Methods. The associations between 23 predictive covariates from 226 graduating students from 2015-2018 (5786 observations) and APPE readiness as measured by midpoint core APPE scores were modeled. Multiple linear and Poisson regression models with backward selection were used. A selection criterion of p >.10 was used for covariate elimination from the model. Three models were evaluated: average of all midpoint core APPE rotation scores; average of midpoint acute care pharmacy practice and ambulatory care APPE rotation scores; and number of midpoint core clerkship failing scores. Results. The average age of the population at admission was 25.4±4.5 years, 47% were female, and 75.2% had prior degrees. Across the three prediction models, knowledge-retention covariates were the strongest predictors. Total score on the Pharmacy Curriculum Outcomes Assessment was a modest yet consistent predictor across the models. All other significant predictors were unique to the various models. Conclusion. This four-year, population-based modeling study of the relationship of common pharmacy education assessment data to APPE midpoint scores shows a modest correlation with knowledge-based measures. There is a need for greater innovation in this area of research.

Reducing Diabetic Ketoacidosis Intensive Care Unit Admissions Through an Electronic Health Record-Driven, Standardized Care Pathway.

Diabetic ketoacidosis (DKA) is a common condition, with wide variation in admission location and clinical practice. We aimed to decrease intensive care unit (ICU) admission for DKA by implementing a standardized, electronic health record-driven clinical care pathway that used subcutaneous insulin, rather than a continuous insulin infusion, for patients with nonsevere DKA. This is a retrospective, observational preintervention to postintervention study of 214 hospital admissions for DKA that evaluated the effect of our intervention on clinical, safety, and cost outcomes. The primary outcome was ICU admission, which decreased from 67.0% to 41.7% (p < .001). Diabetes nurse educator consultation increased from 45.3% to 63.9% (p = .006), and 30-day Emergency Department (ED) return visit decreased from 12.3% to 2.8% (p = .008). Time to initiation of basal insulin increased from 18.19 ± 1.25 hours to 22.47 ± 1.76 hours (p = .05) and reopening of the anion gap increased from 4.7% to 13.9% (p = .02). No changes in ED length of stay (LOS), hospital LOS, hypoglycemia, treatment-induced hypokalemia, 30-day hospital readmission, or inpatient mortality were observed. The implementation of a standardized DKA care pathway using subcutaneous insulin for nonsevere DKA resulted in decreased ICU use and increased diabetes education, without affecting patient safety.

Health Care Costs in a Cohort of HIV-Infected U.S. Veterans Receiving Regimens Containing Tenofovir Disoproxil Fumarate/Emtricitabine.

BACKGROUND: Tenofovir disoproxil fumarate (TDF), a key component in many human immunodeficiency virus (HIV) treatment regimens, is associated with increased renal and bone toxicities. The contributions of such toxicities to treatment costs, as well as the relative differences in treatment costs for various TDF/emtricitabine (FTC) regimens, remains unexplored. OBJECTIVE: To estimate and compare mean overall and renal- and bone-specific costs, including total, inpatient, outpatient, and pharmacy costs in patients treated with TDF/FTC+efavirenz (EFV) compared with several non-EFV-containing TDF/FTC regimens. METHODS: We conducted a national cohort study of treatment-naive HIV-infected U.S. veterans who initiated treatment from 2003 to 2015 with TDF/FTC in combination with EFV, elvitegravir/cobicistat, rilpivirine, or ritonavir-boosted protease inhibitors (atazanavir, darunavir, or lopinavir). Outcomes of interest were quarterly total, inpatient, outpatient, and pharmacy costs using data from the Veterans Health Administration (VHA) electronic medical record and Managerial Cost Accounting System (an activity-based accounting system that allocates VHA expenditures to patient encounters). We controlled for measured confounders using inverse probability of treatment (IPT) weights and assessed differences using standardized mean differences (SMDs). For comparisons where SMDs exceeded 0.1 after IPT weighting, we used the more conservative matching weights in sensitivity analyses. For hypothesis testing, we compared IPT-adjusted differences in quarterly costs between treatment groups using Mann-Whitney U-tests and generalized estimating equation (GEE) regression models. RESULTS: Of 33,048 HIV-positive veterans, 7,222 met eligibility criteria, including 4,172 TDF/FTC + EFV recipients; mean (SD) age of the cohort was 50.0 (10.0) years; 96.7% were male; 60.1% were black; and 30.1% were white. Quarterly periods of exposure to EFV-containing regimens were 22,499 and of exposure to non-EFV-containing regimens were 11,633. After IPT weighting, absolute SMDs were < 0.1 except for a few covariates in the rilpivirine comparison. The per-patient adjusted mean total quarterly costs were $7,145 for EFV versus $8,726 for non-EFV (P < 0.001; Mann-Whitney U-test) and the per-patient adjusted mean difference in total quarterly costs was $1,419 lower for EFV versus all non-EFV combined (P < 0.001; GEE model). Corresponding values for outpatient costs ($2,656 vs. $2,942; P < 0.001; difference, -$254; P = 0.001), inpatient costs ($2,009 vs. $2,614; P < 0.001), radiology costs ($213 vs. $276; P < 0.001), and pharmacy costs ($2,480 vs. $3,170; P < 0.001; difference, -$600; P < 0.001) were all lower for EFV versus all non-EFV combined. Findings based on matching weights were qualitatively similar. Contributions of renal and bone costs to the total costs of treatment were very small, ranging between $52 and $94 per patient per quarter for renal outcomes and between $6 and $114 for bone outcomes. CONCLUSIONS: Among 7,222 HIV-treated veterans over an average follow-up of 1.2 years per patient, those patients receiving TDF/FTC + EFV had lower overall health care costs compared with those receiving non-EFV regimens. DISCLOSURES: This study was funded by Bristol-Myers Squibb. Nelson, Ma, Crook, Knippenberg, Nyman, and LaFleur are employees of the University of Utah, which received a grant from Bristol-Myers Squibb to conduct this study. Nyman also discloses honoraria for consulting from Otsuka and for writing a book chapter from Fresenius. La Fleur reports advisory board and consulting fees from Bristol-Myers Squibb outside of this study. Paul and Esker are employees of, and own stock in, Bristol-Myers Squibb.

Tenofovir-Associated Bone Adverse Outcomes among a US National Historical Cohort of HIV-Infected Veterans: Risk Modification by Concomitant Antiretrovirals.

INTRODUCTION: Tenofovir disoproxil fumarate (TDF) has been associated with greater incidences of bone complications, which might be modified by some concomitantly administered antiretrovirals, possibly by their effect on tenofovir concentrations. We compared bone adverse outcomes among treatment-naïve HIV-infected US veterans initiating efavirenz (EFV)-containing TDF/emtricitabine (FTC) regimens versus those initiating non-EFV-containing TDF/FTC regimens. METHODS: Using national Veterans Health Administration clinical and administrative data sets, we identified a cohort of treatment-naïve HIV-infected veterans without bone disease who initiated therapy with TDF/FTC plus EFV, rilpivirine, elvitegravir/cobicistat, or ritonavir-boosted protease inhibitors in 2003-2015. The primary composite adverse bone outcome was the unadjusted incidence rate (IR) of osteoporosis, osteopenia, or fragility fracture (any hip, wrist, or spine fracture). To account for selection bias and confounding, we used inverse probability of treatment-weighted Cox proportional hazards regression models to calculate adjusted hazard ratios (HRs) for each outcome associated with EFV + TDF/FTC versus each non-EFV-containing TDF/FTC regimen. RESULTS: Of 33,048 HIV-positive veterans, 7161 initiated a TDF/FTC-containing regimen (mean age, 50 years; baseline CD4 < 200 cells/mm3, 33.3%; HIV-1 RNA > 100,000 copies/ml, 22.3%; mean follow-up, 13.0 months). Of these, 4137 initiated EFV- and 3024 non-EFV-containing regimens. Veterans initiating EFV- versus non-EFV-containing TDF/FTC regimens had a lower IR of the composite bone outcome (29.3 vs. 41.4 per 1000 patient-years), with significant risk reductions for this outcome [HR, 0.69; 95% confidence interval (CI), 0.58-0.83] and fragility fracture (HR, 0.59; 95% CI, 0.44-0.78). CONCLUSION: EFV + TDF/FTC is associated with a lower risk of adverse bone outcomes compared with other TDF-containing regimens in the VHA. FUNDING: Bristol-Myers Squibb.

Removal of vancomycin administered during dialysis by a high-flux dialyzer.

INTRODUCTION: Hemodialysis patients frequently receive vancomycin for treatment of gram-positive bacterial infections. This drug is most conveniently administered in outpatient dialysis units during the hemodialysis treatment. However, there is a paucity of data on the removal of vancomycin by high-flux polyamide dialyzers. METHODS: This is a prospective crossover study in which seven uninfected chronic hemodialysis patients at three dialysis units received vancomycin 1 gram intravenously over one hour immediately after the dialysis treatment (Phase 1), and vancomycin 1.5 grams during the last hour of dialysis treatment using a polyarylethersulfone, polyvinylpyrrolidone, polyamide high-flux (Polyflux 24R) dialyzer (Phase 2). There was a three-week washout period between phases. Serial serum vancomycin concentrations were used to determine the removal of vancomycin when administered during dialysis. FINDINGS: Dialysis removed 35 ± 15% (range 18-56%) of the vancomycin dose when administered during the last hour of dialysis. The calculated area under the curve (AUC) of vancomycin levels for 0-44.5 hours from the start of infusion were similar between the two phases (AUCPhase 1 884 ± 124 mg-hr/L, mean ± SD; AUCPhase 2 856 ± 208 mg-hr/L; P=0.72). Serum vancomycin concentrations immediately prior to the next dialysis treatment following vancomycin administration were also similar between the two phases (13.1 ± 2.7 mg/L in Phase 1 and 12.3 ± 3.3 mg/L in Phase 2; P=0.55). DISCUSSION: When using a polyarylethersulfone, polyvinylpyrrolidone, and polyamide high-flux HD membrane with a 24R Polyflux dialyzer, vancomycin can be administered during the last hour of dialysis if the dose that is prescribed for intra-dialysis dosing is empirically increased to account for intra-dialytic drug removal.

Brief Report: Tenofovir-Associated Nephrotoxicity Among a US National Historical Cohort of HIV-Infected Veterans: Risk Modification by Concomitant Antiretrovirals.

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been associated with renal complications. The third agent in TDF-containing antiretroviral regimens may modify that risk. We compared renal adverse outcomes among treatment-naive HIV-infected patients initiating TDF-containing regimens including efavirenz (EFV) or other agents. SETTING: This population-based historical cohort study used national Veterans Health Administration (VHA) clinical and administrative data sets to identify treatment-naive HIV-infected veterans initiating antiretroviral therapy with TDF/emtricitabine (FTC) + EFV, rilpivirine (RPV), elvitegravir/cobicistat (EVG/c), or ritonavir (RTV)-boosted protease inhibitors (PIs) from 2003 to 2015. METHODS: Unadjusted incidence rates (IRs) for each regimen and covariate-adjusted hazard ratios [ using Cox proportional hazards models and inverse probability of treatment weighting] for between-regimen comparisons were calculated for renal outcomes including confirmed proteinuria, defined as 2 consecutive protein-to-creatinine ratios >150 mg/g or albumin-to-creatinine ratios >30 mg/g occurring ≥90 days apart; chronic kidney disease (CKD), defined as 2 consecutive estimated glomerular filtration rate measurements <60 mL·min·1.73 m occurring ≥90 days apart; and kidney dialysis. RESULTS: Of 33,048 HIV-positive veterans, 4172 received EFV + TDF/FTC, 234 EVG/c/TDF/FTC, 173 RPV/TDF/FTC, and 2651 RTV-boosted PIs + TDF/FTC. Confirmed proteinuria and CKD IRs were numerically lower with EFV + TDF/FTC versus non-EFV + TDF/FTC (dialysis IRs were rare and comparable). After inverse probability of treatment weighting adjustment, EFV + TDF/FTC was associated with lower CKD risk versus non-EFV + TDF/FTC (hazard ratio, 0.62; 95% confidence interval, 0.53 to 0.72), EVG/c/TDF/FTC (0.75; 0.59 to 0.95), RPV/TDF/FTC (0.20; 0.17 to 0.24), and RTV-boosted PIs + TDF/FTC (0.62; 0.53 to 0.72). CONCLUSIONS: EFV + TDF/FTC was associated with significantly lower risk of CKD versus other TDF-containing regimens in the Veterans Health Administration.

Bone disease in patients with kidney disease: A tricky interplay.

Managing bone disease in patients with kidney disease involves frequent lab testing and careful evaluation of therapeutic options. This review provides guidance.

Erratum.

The article incorrectly stated: "Elevations of both fibroblast growth factor 23 (FGF23) and parathyroid hormone (PTH) lead to hyperphosphatemia and hypocalcemia because of decreased urinary excretion of phosphorus." In fact, FGF23 normally acts to lower blood phosphate levels. Furthermore, an elevated phosphorus level causes an increase in serum calcium levels and not hypocalcemia. This information has been corrected in the online version of the article.

Renal dosing in high-risk populations.

In patients with diminished kidney function, the pharmacokinetics of many medications are altered. Alterations in absorption, distribution, and metabolism are observed in addition to altered elimination through the kidney. Classes of intravenous medications in which dose modifications are frequently required for patients with diminished kidney function include antibiotics, some anticoagulants, and chemotherapy agents. Failure to follow renal dose adjustment recommendations can lead to an increased risk of toxicity. Equations frequently used to estimate kidney function for the purpose of making renal dose adjustments include the Cockcroft-Gault, Modification of Diet in Renal Disease (MDRD), and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations.

Assessing and treating hepatic encephalopathy in the older patient.

Altered mental status (AMS) and confusion are common reasons older patients may be admitted to a hospital. Hepatic encephalopathy (HE) is associated with confusion and AMS. The following case describes an older male presenting with confusion. The patient is treated for both a urinary tract infection and HE. The differential diagnosis for AMS is important for pharmacists to understand and evaluate to ensure appropriate treatment as well as rule out other medication-related causes of AMS. Managing patient compliance for the pharmacotherapy necessary to treat and prevent HE is particularly important to avoid future hospital admissions and complicated placements to an extended-care facility.

Comparative evaluation of the Cockcroft-Gault Equation and the Modification of Diet in Renal Disease (MDRD) study equation for drug dosing: an opinion of the Nephrology Practice and Research Network of the American College of Clinical Pharmacy.

Accurate assessment of kidney function is an important component of determining appropriate drug dosing regimens. Nearly all manufacturer-recommended dosage adjustments are based on creatinine clearance ranges derived from clinical pharmacokinetic studies performed during the drug development process. The Cockcroft-Gault (CG) equation provides an estimate of creatinine clearance and is the equation most commonly used to determine drug dosages in patients with impaired kidney function. The Modification of Diet in Renal Disease (MDRD) study equation has also been proposed for this purpose. Published studies report that drug dosages determined by the two equations do not agree in 10-40% of cases. However, interpretation and comparison of these studies are complicated by the variable creatinine methods used for calculating CG and MDRD estimates, the patient populations studied, and a lack of outcomes data demonstrating the clinical significance of dosing discrepancies. Moreover, the impact of reporting standardized serum creatinine values on the accuracy of the CG equation and corresponding drug dosing regimens have been questioned. Currently, no prospective pharmacokinetic studies have been conducted with use of the MDRD equation to generate dosing recommendations, and limited data are available to support its use in some patient populations representing demographic extremes. Collectively, these issues have resulted in considerable confusion among clinicians and have fueled a healthy debate on whether or not to use the MDRD equation to determine drug dosages. Each of these issues is reviewed, and a proposed algorithm for using creatinine-based kidney function assessments in drug dosing is provided. Knowledge of the advantages, limitations, and clinical role of each equation will facilitate their safe and effective use in drug dosing.

Use of estimated glomerular filtration rate for drug dosing in the chronic kidney disease patient.

PURPOSE OF REVIEW: Assessment of kidney function is necessary to stage chronic kidney disease (CKD) and appropriately dose medications. The Cockcroft-Gault equation provides an estimate of creatinine clearance (eClCr) and is the method commonly referenced in pharmacokinetic studies. The Modification of Diet in Renal Disease (MDRD) and CKD-Epidemiology Collaboration (EPI) equations provide an estimate of glomerular filtration rate (eGFR), with the MDRD eGFR now automatically reported by most clinical laboratories. This review describes the differences in the Cockcroft-Gault, MDRD, and CKD-EPI equations and considerations when applying estimates from these equations for drug dosing. RECENT FINDINGS: Studies evaluating drug-dosing regimens using eClCr and eGFR differ in their results depending on the population in which the equation is applied, the adjustment factors used to account for body size, and the number of dosing levels for a particular medication. The largest study to evaluate drug regimen design by method concluded that either the eGFR or Cockcroft-Gault estimates could be used for drug dosing. Differences in methodology among studies are a key factor in evaluating these results and will be highlighted in this review. SUMMARY: The Cockcroft-Gault, MDRD, and CKD-EPI equations provide reasonable estimates of kidney function; however, clinicians must understand the limitations when using these estimates for drug regimen design.