American Board of Internal Medicine Nephrology Procedure Requirements for Initial Certification: Time for a Change and Pursuing Consensus in the Nephrology Community.

In 1988, the American Board of Internal Medicine (ABIM) defined essential procedural skills in nephrology, and candidates for ABIM certification were required to present evidence of possessing the skills necessary for placement of temporary dialysis vascular access, hemodialysis, peritoneal dialysis, and percutaneous renal biopsy. In 1996, continuous renal replacement therapy was added to the list of nephrology requirements. These procedure requirements have not been modified since 1996 while the practice of nephrology has changed dramatically. In March 2021, the ABIM Nephrology Board embarked on a policy journey to revise the procedure requirements for nephrology certification. With the guidance of nephrology diplomates, training program directors, professional and patient organizations, and other stakeholders, the ABIM Nephrology Board revised the procedure requirements to reflect current practice and national priorities. The approved changes include the Opportunity to Train standard for placement of temporary dialysis catheters, percutaneous kidney biopsies, and home hemodialysis which better reflects the current state of training in most training programs, and the new requirements for home dialysis therapies training will align with the national priority to address the underuse of home dialysis therapies. This perspective details the ABIM process for considering changes to the certification procedure requirements and how ABIM collaborated with the larger nephrology community in considering revisions and additions to these requirements.

Clinical Characteristics and Outcomes of Drug-Induced Acute Kidney Injury Cases.

Introduction: Drug-induced acute kidney injury (DI-AKI) is a frequent adverse event. The identification of DI-AKI is challenged by competing etiologies, clinical heterogeneity among patients, and a lack of accurate diagnostic tools. Our research aims to describe the clinical characteristics and predictive variables of DI-AKI. Methods: We analyzed data from the Drug-Induced Renal Injury Consortium (DIRECT) study (NCT02159209), an international, multicenter, observational cohort study of enriched clinically adjudicated DI-AKI cases. Cases met the primary inclusion criteria if the patient was exposed to at least 1 nephrotoxic drug for a minimum of 24 hours prior to AKI onset. Cases were clinically adjudicated, and inter-rater reliability (IRR) was measured using Krippendorff's alpha. Variables associated with DI-AKI were identified using L1 regularized multivariable logistic regression. Model performance was assessed using the area under the receiver operating characteristic curve (ROC AUC). Results: A total of 314 AKI cases met the eligibility criteria for this analysis, and 271 (86%) cases were adjudicated as DI-AKI. The majority of the AKI cases were recruited from the United States (68%). The most frequent causal nephrotoxic drugs were vancomycin (48.7%), nonsteroidal antiinflammatory drugs (18.2%), and piperacillin/tazobactam (17.8%). The IRR for DI-AKI adjudication was 0.309. The multivariable model identified age, vascular capacity, hyperglycemia, infections, pyuria, serum creatinine (SCr) trends, and contrast media as significant predictors of DI-AKI with good performance (ROC AUC 0.86). Conclusion: The identification of DI-AKI is challenging even with comprehensive adjudication by experienced nephrologists. Our analysis identified key clinical characteristics and outcomes of DI-AKI compared to other AKI etiologies.

Subtle Changes in Tacrolimus Levels Have an Impact on Early Donor-Specific Antibodies in Kidney Transplantation.

Introduction: The impact of each immunosuppressive agent on de novo donor-specific antibodies in kidney transplant recipients varies among extant literature. Project aims: Patterns in immunosuppression and the effects on incidence of de novo donor-specific antibodies were evaluated. Design: Adult kidney transplant recipients from 2017 to 2019 without preformed antibodies were sampled. Allograft function, de novo donor-specific antibodies, tacrolimus concentrations, duration of goal-dose antiproliferatives, and steroid doses were recorded. Outcomes included incidence of de novo donor-specific antibodies, and their relation to tacrolimus concentrations, time at goal-dose antiproliferatives, and steroid doses. Results: Recipients (N = 153) were followed for 1 year; all were crossmatch negative and received rabbit antithymocyte globulin induction. Sixteen (10%) recipients developed de novo donor-specific antibodies in a median of 31 days [interquartile range, IQR: 12-67 days], most were Class II antibodies (87.5%). Incidence of de novo donor-specific antibodies did not differ based on induction dosing. Tacrolimus levels in the first month were lower for patients with de novo donor-specific antibodies (8.8 ng/mL vs 10.4 ng/mL, P < .01). There was no difference in time on goal antiproliferative doses, but higher steroid doses (0.4 vs 0.3 mg/kg/d; P = .02) were noted in patients with antibodies. Steroid dosing was likely impacted by baseline risk factors. Conclusion: A significant association was found between lower tacrolimus concentrations early post-transplant and incidence of de novo donor-specific antibodies. This highlighted the importance of clinician attention to subtle changes in tacrolimus and the impact it can have on antibody risk in the early post-transplant period.

Moving toward a contemporary classification of drug-induced kidney disease.

Drug-induced kidney disease (DIKD) accounts for about one-fourth of all cases of acute kidney injury (AKI) in hospitalized patients, especially in critically ill setting. There is no standard definition or classification system of DIKD. To address this, a phenotype definition of DIKD using expert consensus was introduced in 2015. Recently, a novel framework for DIKD classification was proposed that incorporated functional change and tissue damage biomarkers. Medications were stratified into four categories, including "dysfunction without damage," "damage without dysfunction," "both dysfunction and damage," and "neither dysfunction nor damage" using this novel framework along with predominant mechanism(s) of nephrotoxicity for drugs and drug classes. Here, we briefly describe mechanisms and provide examples of drugs/drug classes related to the categories in the proposed framework. In addition, the possible movement of a patient's kidney disease between certain categories in specific conditions is considered. Finally, opportunities and barriers to adoption of this framework for DIKD classification in real clinical practice are discussed. This new classification system allows congruencies for DIKD with the proposed categorization of AKI, offering clarity as well as consistency for clinicians and researchers.

Sirolimus Long-Term Tolerability and Impact on Kidney Function in Lung Transplantation: A Single-Center Experience.

BACKGROUND: After lung transplant, 2 common complications are calcineurin inhibitor (CNI) induced nephrotoxicity and bronchiolitis obliterans syndrome. The objective of this study was to investigate the long-term effects of sirolimus conversion after lung transplantation. METHODS: This was a retrospective cohort study of patients who had undergone lung transplantation at a single center from June 2003 to December 2016. We compared patients converted to a sirolimus-based regimen to those maintained on our standard tacrolimus-based regimen. Kidney function, pulmonary function, and immunosuppression concentrations were compared between the groups. Additionally, indications, toxicity monitoring parameters, and discontinuation rates for sirolimus were collected. RESULTS: During the study period, 176 of the 205 patients who underwent lung transplants were converted to a sirolimus-containing regimen (86%). The most common reason for sirolimus initiation was impairment of kidney function or CNI-associated neurotoxicity. Sirolimus was initiated at a median of 150 days post-transplantation and continued for a medium time of 5.02 (2.27-7.85) years. Of those patients converted to sirolimus, 39 (22%) had sirolimus subsequently discontinued secondary to an adverse event. No difference in pulmonary function was found between the groups at 1- and 3-years post-transplantation. In the sirolimus group, the median estimated glomerular filtration rate improved by 8.6 mL/min/1.73 m2 at 3 months post-conversion (P < .001), which was maintained at both 1 and 3 years (P = .014 and .025, respectively). CONCLUSION: Sirolimus is a viable immunosuppressant option after lung transplant, which successfully allows for the reduction or withdrawal of the CNI, resulting in sustained improvement in kidney function.

Digital health and acute kidney injury: consensus report of the 27th Acute Disease Quality Initiative workgroup.

Acute kidney injury (AKI), which is a common complication of acute illnesses, affects the health of individuals in community, acute care and post-acute care settings. Although the recognition, prevention and management of AKI has advanced over the past decades, its incidence and related morbidity, mortality and health care burden remain overwhelming. The rapid growth of digital technologies has provided a new platform to improve patient care, and reports show demonstrable benefits in care processes and, in some instances, in patient outcomes. However, despite great progress, the potential benefits of using digital technology to manage AKI has not yet been fully explored or implemented in clinical practice. Digital health studies in AKI have shown variable evidence of benefits, and the digital divide means that access to digital technologies is not equitable. Upstream research and development costs, limited stakeholder participation and acceptance, and poor scalability of digital health solutions have hindered their widespread implementation and use. Here, we provide recommendations from the Acute Disease Quality Initiative consensus meeting, which involved experts in adult and paediatric nephrology, critical care, pharmacy and data science, at which the use of digital health for risk prediction, prevention, identification and management of AKI and its consequences was discussed.

Drug-Induced Acute Kidney Injury Risk Prediction Models.

BACKGROUND: Acute kidney injury (AKI) risk prediction models can predict AKI with short lead times and excellent model performance. However, these prediction models have not ascertained the etiology of the AKI. Drugs are an important contributor to AKI, and it is difficult to distinguish drug causes from other etiologies. SUMMARY: Clinical adjudication of AKI etiology can reduce misclassification associated with temporal relationships, since expert adjudicators are trained to assess an outcome in a consistent manner using standardized definitions. Drug-induced acute kidney injury (DI-AKI) varies by drug and is heterogeneous in onset and mechanisms, limiting a universal approach to risk prediction and necessitating expert review. DI-AKI models should be constructed using a high-quality prospective dataset to maximize model performance, internal and external validity. Predictor selection and engineering requires careful attention to unique issues arising from interactions such as drug dose and concentrations. Various statistical methods, such as least absolute shrinkage and selection operator regression or advanced machine learning techniques, may be applied to perform feature selection and capture trends and interactions between predictors. Finally, the model should be carefully evaluated by internal and external validation. KEY MESSAGES: The development of DI-AKI risk prediction models is needed to identify high-risk patients, identify new risk factors, formulate, and apply preventative strategies. DI-AKI risk prediction models require a well-defined dataset of clinically adjudicated cases to improve model performance, validity, and reduce the risk of misclassification.

Impact of Medication Reconciliation by a Dialysis Pharmacist.

Integrating a pharmacist into a hemodialysis unit significantly reduced medication discrepancies and medication-related problems over time.Medication reconciliation for the Centers for Medicare and Medicaid Services End-Stage Renal Disease Quality Incentive Program can be optimally performed by a dialysis pharmacist.

A Clinician's Guide to Dosing Analgesics, Anticonvulsants, and Psychotropic Medications in Continuous Renal Replacement Therapy.

Acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) is a common complication in critical illness and has a significant impact on pharmacokinetic factors determining drug exposure, including absorption, distribution, transport, metabolism, and clearance. In this review, we provide a practical guide to drug dosing considerations in critically ill patients undergoing CRRT, focusing on the most commonly used analgesic, anticonvulsant, and psychotropic medications in the clinical care of critically ill patients. A literature search was conducted to identify articles in which drug dosing was evaluated in adult patients receiving CRRT between the years 1980 and 2020. We included articles with pharmacokinetic/pharmacodynamic analyses and those that described medication clearance via CRRT. A summary of the data focused on practical pharmacokinetic and pharmacodynamic principles is presented, with recommendations for drug dosing of analgesics, anticonvulsants, and psychotropic medications. Pharmacokinetic and pharmacodynamic studies to guide drug dosing of analgesics, anticonvulsants, and psychotropic medications in critically ill patients receiving CRRT are sparse. Considering the widespread use of these medications, narrow therapeutic index of these drug classes, and risks of over- and underdosing, additional studies in patients receiving CRRT are needed to inform drug dosing.

Transferring Key Success Factors from Ambulatory Care into the Community Pharmacy in the United States.

In the United States, pharmacists' scope of practice continues to expand, with increasing opportunities for pharmacists in all practice settings to enhance health in society. In ambulatory care, pharmacists remain integral members on the healthcare team and have demonstrated positive impacts on patient care. Sharing similar characteristics as pharmacists in the community setting, a deeper look into common elements of a successful ambulatory care practice that can be applied in the community pharmacy setting is warranted. Key success factors identified from ambulatory care include (1) maximizing a pharmacist's unique knowledge base and skill set, (2) forming collaborations with physicians and other providers, (3) demonstrating outcomes and value, and (4) maintaining sustainability. Opportunities exist for pharmacists in the community setting to utilize these success factors when developing, implementing, and/or expanding direct patient care services that improve accessibility to quality care and population health.

Pharmacokinetics of Intraperitoneal Vancomycin and Amikacin in Automated Peritoneal Dialysis Patients With Peritonitis.

Objective: The study aimed to evaluate the vancomycin and amikacin concentrations in serum and dialysate for automatic peritoneal dialysis (APD) patients. Methods: A total of 558 serum and dialysate samples of 12 episodes of gram-positive and 18 episodes of gram-negative peritonitis were included to investigate the relationship between vancomycin and amikacin concentrations in serum and dialysate on the first and third days of treatment. Samples were analysed 30, 120 min, and 48 h after intraperitoneal administration of vancomycin in peritonitis caused by gram-positive agents and 30, 120 min, and 24 h after intraperitoneal administration of amikacin in peritonitis caused by gram-negative agents. Vancomycin was administered every 72 h and amikacin once a day. The target therapeutic concentration of amikacin was 25-35 mg/l at the peak moment and 4-8 mg/l at the trough moment; and after 48 h for vancomycin, 15-20 mg/l at the trough moment. Results: For peritonitis caused by gram-negative agents, at the peak moment, therapeutic levels of amikacin were reached in dialysate in 80.7% of patients with evolution to cure and in 50% of patients evaluated as non-cure (p = 0.05). At the trough moment, only 38% were in therapeutic concentrations in the dialysate in the cure group and 42.8% in the non-cure group (p = 1). Peak plasma concentrations were subtherapeutic in 98.4% of the samples in the cure group and in 100% of the non-cure group. At the trough moment, therapeutic concentrations were present in 74.4% of the cure group and 71.4% of the non-cure group (p = 1). Regarding vancomycin and among gram-positive agents, therapeutic levels were reached at the peak moment in 94% of the cure group and 6% of the non-cure group (p = 0.007). After 48 h, 56.8% of the cure group had a therapeutic serum concentration whereas for the non-cure group it was only 33.3% (p = 0.39). Conclusion: Despite a small sample size, we demonstrated peak dialysate amikacin level and peak serum vancomycin level correlates well with Gram-negative and Gram positve peritonitis cure, respectively. It is suggested to study the antibiotics pharmacodynamics for a better understanding of therapeutic success in a larger sample.

Drug dosing considerations in continuous renal replacement therapy.

Acute kidney injury (AKI) is a common complication in critically ill patients, which is associated with increased in-hospital mortality. Delivering effective antibiotics to treat patients with sepsis receiving continuous renal replacement therapy (RRT) is complicated by variability in pharmacokinetics, dialysis delivery, lack of primary literature, and therapeutic drug monitoring. Pharmacokinetic alterations include changes in absorption, distribution, protein binding (PB), metabolism, and renal elimination. Drug absorption may be significantly changed due to alterations in gastric pH, perfusion, gastrointestinal motility, and intestinal atrophy. Volume of distribution for hydrophilic drugs may be increased due to volume overload. Estimation of renal clearance is challenged by the effective delivery of RRT. Drug characteristics such as PB, volume of distribution, and molecular weight impact removal of the drug by RRT. The totality of these alterations leads to reduced exposure. Despite our best knowledge, therapeutic drug monitoring of patients receiving continuous RRT demonstrates wide variability in antimicrobial concentrations, highlighting the need for expanded monitoring of all drugs. This review article will focus on changes in drug pharmacokinetics in AKI and dosing considerations to attain antibiotic pharmacodynamic targets in critically ill patients receiving continuous RRT.

Urinary Exosomes Identify Inflammatory Pathways in Vancomycin Associated Acute Kidney Injury.

BACKGROUND: Vancomycin is commonly used as a first line therapy for gram positive organisms such as methicillin resistant Staphylococcusaureus. Vancomycin-induced acute kidney injury (V-AKI) has been reported in up to 43% of patients, especially in those with higher targeted trough concentrations. The precise mechanism of injury in humans remains elusive, with recent evidence directed towards proximal tubule cell apoptosis. In this study, we investigated the protein contents of urinary exosomes in patients with V-AKI to further elucidate biomarkers of mechanisms of injury and potential responses. METHODS: Urine samples from patients with V-AKI who were enrolled in the DIRECT study and matched healthy controls from the UAB-UCSD O'Brien Center Biorepository were included in the analysis. Exosomes were extracted using solvent exclusion principle and polyethylene glycol induced precipitation. Protein identity and quantification was determined by label-free liquid chromatography mass spectrometry (LC/MS). The mean peak serum creatinine was 3.7 ± 1.4 mg/dL and time to kidney injury was 4.0 ± 3.0 days. At discharge, 90% of patients demonstrated partial recovery; 33% experienced full recovery by day 28. Proteomic analyses on five V-AKI and 7 control samples revealed 2009 proteins in all samples and 251 proteins significantly associated with V-AKI (Pi-score > 1). The top discriminatory proteins were complement C3, complement C4, galectin-3-binding protein, fibrinogen, alpha-2 macroglobulin, immunoglobulin heavy constant mu and serotransferrin. CONCLUSION: Urinary exosomes reveal up-regulation of inflammatory proteins after nephrotoxic injury in V-AKI. Further studies are necessary in a large patient sample to confirm these findings for elucidation of pathophysiologic mechanisms and validation of potential injury biomarkers.

Pharmacy students' readiness to use the electronic health record: A tale of two institutions.

INTRODUCTION: Despite widespread implementation of the electronic health record (EHR) in practice, the EHR curriculum in pharmacy schools is slow to emerge. This study used a single assessment tool to evaluate pharmacy students' perceived readiness to use an EHR after completion of two different curricula. METHODS: Pharmacy students at the University of Nebraska Medical Center (UNMC) and the University of California San Diego (UCSD) pharmacy schools voluntarily participated. A 14-item survey was administered asking students to rate their comfort on several different EHR skills. Baseline data on non-academic EHR exposure was also collected. RESULTS: Seventy students at UNMC and 69 students at UCSD participated in the survey (27.2% and 28.5% response rate, respectively). Gender and academic year were similar between institutions. Overall, students were more comfortable finding information compared to entering new information in the EHR. Students were most comfortable reviewing laboratory information, progress notes, and medication lists and less comfortable performing medication reconciliation and identifying clinical errors. There were no differences between institutions for overall comfort. Students with at least one month of extracurricular EHR experience rated themselves as more comfortable, but not all of those differences were statistically significant. CONCLUSIONS: This study demonstrated that two different EHR curricula in two different pharmacy schools can result in similar student confidence. The information and assessment tool from this study can be a helpful starting point for other schools to determine student preparedness to work with the EHR as well as provide information to inform EHR curricula design and assessment.

Identification of Novel Biomarkers for Predicting Kidney Injury Due to Drugs Using "Omic" Strategies.

Drug-induced kidney injury accounts for 20% of community- and hospital-acquired cases of acute kidney injury (AKI). The incidence is higher among older individuals, who often have co-existing morbidities and are exposed to more diagnostic procedures and therapies. While demographic and clinical components have been identified as risk factors, the proposed cellular mechanisms of drug-induced kidney injury are numerous and complicated. There are also limitations recognized in the use of traditional biomarkers, such as serum creatinine and blood urea nitrogen, to provide high sensitivity, specificity, and timeliness to identification of drug-induced kidney injury. Therefore, novel biomarkers are currently being investigated, identified, developed, and validated for their performance over the traditional biomarkers. This review will provide an overview of drug-induced kidney injury and will discuss what is known regarding "omic" (proteomic, genomic, transcriptomic, and metabolomic) biomarker strategies for drugs known to induce nephrotoxicity.

Self-Perceptions of Readiness to Use Electronic Health Records Among Medical Students: Survey Study.

BACKGROUND: Although several national organizations have declared the ability to work with electronic health records (EHRs) as a core competency of medical education, EHR education and use among medical students vary widely. Previous studies have reported EHR tasks performed by medical students, but students' self-perceived readiness and comfort with EHRs are relatively unknown. OBJECTIVE: This study aimed to better understand medical students' self-perceived readiness to use EHRs to identify potential curricular gaps and inform future training efforts based on students' perspectives. METHODS: The authors deployed a survey investigating self-perceived comfort with EHRs at 2 institutions in the United States in May 2019. Descriptive statistics were generated regarding demographics, comfort level with various EHR-related tasks, and cross-institutional comparisons. We also assessed the impact of extracurricular EHR experience on comfort level. RESULTS: In total, 147 medical students responded, of which 80 (54.4%) were female, with equal distribution across all 4 years of training. Overall confidence was generally higher for students with longer extracurricular EHR experience, even when adjusted for age, gender, year of training, and institution. Students were most comfortable with tasks related to looking up information in the EHR and felt less comfortable with tasks related to entering new information and managing medications. Fourth-year students at both schools reported similar levels of comfort with EHR use, despite differences in preclinical EHR training. Open-ended comments emphasized the value of experiential training over didactic formats. CONCLUSIONS: Information entry and medication management in the EHR represent areas for future curricular development. Experiential training via extracurricular activities and early clinical exposure may be high-yield approaches to help medical students achieve critical EHR competencies.

Relationship between 2-Hour Tacrolimus Concentrations and Clinical Outcomes in Long Term Kidney Transplantation.

Background: Tacrolimus is routinely monitored using trough concentrations, however, recent data have suggested that area under the curve (AUC) provides better correlation with toxicity and efficacy. Area under the curve is cumbersome to measure, but studies have demonstrated that surrogate time points such as 2-hour concentrations are well correlated with AUC. Methods: This is a single center, retrospective study of adult kidney transplant recipients with 2-hour tacrolimus concentrations measured over three years post-transplant. The primary outcome was to determine the difference in serum creatinine (Scr) in those with 2-hour tacrolimus concentrations greater than 20 ng/mL versus those less than or equal to 20 ng/mL. Results: A total of 150 kidney transplant recipients were included. The mean Scr and glomerular filtration rate were 1.49 ± 1.01 mg/dL and 59 ± 23.2 ml/min/1.73 m2, respectively, for the entire cohort. The rate of donor specific antibody formation was 2% and 8% experienced biopsy-proven rejection. The rate of cytomegalovirus viremia was 2% and BK viremia was 13%. There was no significant difference in kidney function over 36 months for the groups specified a priori. Conclusions: Long-term outcomes of maintaining tacrolimus 2-hour concentrations over 20 ng/mL is favorable with minimal opportunistic infections.