Faculty Bibliography

In people of African ancestry, apolipoprotein L1 gene (APOL1) variants have been identified as causing increased risk of progressive chronic kidney disease (CKD). In April of 2024, Kidney Disease: Improving Global Outcomes (KDIGO) convened a Controversies Conference on APOL1 Kidney Disease in Accra, Ghana. The goals of the conference were to review and discuss current evidence and controversies on APOL1 kidney disease, including naming, epidemiology, pathophysiology, APOL1 testing, treatment, and future research needs. Participants considered various terminologies for diseases related to APOL1 risk variants (such as APOL1-mediated or -induced kidney disease) and had highest support for using APOL1 kidney disease to describe kidney pathologies associated with the APOL1 G1 and G2 risk variants. Clinically, the term APOL1 kidney disease can be used on its own or as an overall category of kidney disease, with further specification added as needed (for example, APOL1 kidney disease, focal segmental glomerulosclerosis). Given that there currently are no established treatments for APOL1 kidney disease, and APOL1 genotype results are not by themselves actionable, there is insufficient evidence to guide recommendations for APOL1 population screening or routine testing. However, genotyping can be an important clinical consideration for individuals to inform risk stratification, frequency of follow-up, living kidney donation, as well as clinical trial eligibility. Key areas of need and strategies for future research were delineated and are reported here.

To date, the primary focus of chronic kidney disease (CKD) care has been on managing disease progression, complications, and kidney failure. In contrast, maintaining kidney health and preventing CKD have received limited attention, despite their potential to save millions of lives, reduce health care costs, and lessen environmental burdens. The cardiovascular-kidney-metabolic (CKM) concept frames CKD as part of a complex, high-risk syndrome requiring global risk assessment and multifactorial intervention. CKD incidence along with CKM risk factors may be reduced by a healthy diet, physical activity, and a supportive environment. However, risk for CKD does extend beyond the cardiovascular-metabolic component, and residual risk persists despite healthy lifestyles and treatment of risk factors. Post hoc analyses of clinical trials suggest pharmacological interventions, such as sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, may help to prevent or regress CKD in individuals with type 2 diabetes or obesity. Clinical trials are needed to validate these findings in broader high-risk populations. Personalized strategies to improve kidney health should include CKD risk prediction via targeted testing, genetic or biomarker assessments, shared decision-making, cost considerations, selection of therapeutics, and the potential for adverse effects. The overall goals of CKD prevention should prioritize a lifespan approach to risk evaluation along with safe, efficacious, and accessible interventions to maintain kidney health.

OBJECTIVE:The objective of this study is to examine real-world dose titration patterns of semaglutide for weight management (Wegovy, Novo Nordisk A/S) in US adults and identify characteristics associated with early discontinuation. METHODS:We identified 15,811 commercially insured adults who started semaglutide for weight management (administrated through single-dose prefilled pens) between June 2021 and December 2023. We depicted dose-titration patterns over 5 months and identified factors associated with discontinuation using multivariable Cox regression. Sensitivity analyses examined patterns after supply shortage resolution (after October 2023). RESULTS:Most semaglutide users deviated from the recommended monthly dose-escalation schedule within the first 5 months. By the fifth month, nearly one-half (46%) had discontinued the treatment, with similar rates (48%) among those initiating after supply stabilization. Discontinuation was strongly associated with copayment amount, with rates increased from 41% in the lowest quintile ($1-$54 per month) to 51% in the highest quintile ($161-$1460 per month). Higher discontinuation rates were also associated with lower household income and education level. CONCLUSIONS:The deviations from the recommended dose-escalation schedule and high discontinuation rate among real-world semaglutide users indicate important challenges in the delivery of evidence-based care. Policy interventions that reduce financial barriers to the persistence of semaglutide are needed.

OBJECTIVES/UNASSIGNED:To review the different analgesic modalities and benefits of non-opioid pain management options as well as their evidence-based, established superiority, compared to opioid medications. MATERIALS/UNASSIGNED:We review the updated literature about pain management of renal colic, a prevalent and painful urologic condition. Prescribers must know the efficacy, safety and possible ramifications of analgesic selections. RESULTS/UNASSIGNED:Commonly prescribed medications in the United States (US) include non-steroidal anti-inflammatory drugs (NSAIDs), acetaminophen, and opioids. In the context of the current epidemic of death from overdoses of opioids in the US, the frequency of opioid prescribing for renal colic is likely excessive, problematic and potentially remediable. We also present analgesic modalities revolving around interventions with peri-procedural pain management for ureteroscopy and percutaneous nephrolithotomy. After touching on the implications of misguided opioid use, especially in the context of kidney stone disease, and despite the evidence and consensus guidelines supporting NSAIDs in renal colic, current evidence has shown that many clinicians continue to prescribe opioids as first-line treatment. Finally, we highlight current efforts targeted at the reduction of opioid use and prescription in the setting of provider education and decision aids in curbing misguided opioid use in renal colic. CONCLUSIONS/UNASSIGNED:While the evidence against treating kidney stones with opioids is clear, more work is needed to shift current practices to reflect that renal colic is a non-opioid-requiring condition.

INTRODUCTION/UNASSIGNED:The prognostic value of the discrepancy between the estimated glomerular filtration rate (eGFR) using cystatin C (eGFRcys) and creatinine (eGFRcr) in recently hospitalized adults remains poorly understood. METHODS/UNASSIGNED:We characterized the difference between eGFRcys and eGFRcr, at 3 months after discharge, in 1534 hospitalized adults; 767 (50%) with acute kidney injury (AKI) matched 1:1 with patients who did not develop AKI. We used survival analysis to determine the associations between having lower eGFRcys than eGFRcr with risk of end-stage kidney disease (ESKD), major atherosclerotic cardiac events (MACE), heart failure hospitalization, and death after a a median follow-up of 4.7 years. RESULTS/UNASSIGNED:for interaction with AKI all > 0.1). CONCLUSION/UNASSIGNED:Our findings suggest that the eGFRcys-eGFRcr discrepancy may serve as a valuable prognostic marker in recently hospitalized patients, informing risk stratification and potential interventions.

RATIONALE & OBJECTIVE/OBJECTIVE:Despite national efforts, the uptake of home dialysis (peritoneal dialysis or home hemodialysis) remains low. Characteristics of the built environment may differentially impact home dialysis use. STUDY DESIGN/METHODS:Retrospective cohort study (2010-2019). SETTING & PARTICIPANTS/METHODS:1,103,695 adults (aged≥18 years) initiating dialysis in the US Renal Data System. EXPOSURE/METHODS:We examined 3 built environment domains based on residential ZIP code: (1) medically underserved areas (MUAs), defined as neighborhoods with limited primary care access; (2) distance to the nearest dialysis facility; and (3) distribution of housing characteristics (structure and overcrowding). OUTCOME/RESULTS:Uptake of home dialysis modalities at dialysis initiation. ANALYTICAL APPROACH/METHODS:We quantified associations between built environment characteristics and home dialysis initiation using multilevel logistic regression stratified by urbanicity type (urban, suburban, small-town, and rural). RESULTS:Among adults initiating dialysis, 40.8% lived in MUAs. Across ZIP codes, the mean percentage of overcrowded housing was 4.2% (SD, 4.7%), and the percentage of detached housing was 61.1% (SD, 21.1%); mean distance to the nearest dialysis facility was 5.5km (SD, 9.1km). Living in MUAs was associated with reduced home dialysis use only in urban (OR, 0.94; 95% CI, 0.91-0.96) and suburban (OR, 0.92; 95% CI, 0.89-0.94) areas. Similarly, housing overcrowding was associated with decreased home dialysis use only in urban (OR, 0.88; 95% CI, 0.86-0.89) and suburban (OR, 0.91; 95% CI, 0.90-0.93) areas. Longer distance to a dialysis facility was the most salient neighborhood factor associated with increased home dialysis use in small towns (OR, 1.14; 95% CI, 1.12-1.16) and rural areas (OR, 1.17; 95% CI, 1.15-1.19). LIMITATIONS/CONCLUSIONS:Housing characteristics were measured at the ZIP code level. CONCLUSIONS:Built environment characteristics associated with home dialysis uptake vary by urbanicity. Policies should address built environment barriers that are specific to urbanicity level. For example, increasing the frequency of dialysate delivery schedules could address housing space constraints in urban and suburban areas, and promoting home dialysis might be more effective for patients living far from dialysis centers in small-town and rural areas.

AIMS/OBJECTIVE:To characterize trends in obesity and prescriptions for glucagon-like peptide-1 receptor agonists (GLP-1RAs) across body mass index (BMI) categories among US youth and adults with type 1 diabetes (T1D) from 2008 to 2023. MATERIALS AND METHODS/METHODS:Patients with T1D were identified using a validated algorithm using de-identified electronic health record (EHRs) data from 33 US health systems. BMI categories were based on age- and sex-specific percentiles for youth (2-19 years) and World Health Organization cut points for adults (≥20 years). Trends in obesity and GLP1-RA prescriptions were characterized by BMI categories among youth and adults with T1D from 2008-2011 to 2020-2023. RESULTS:From 2008-2011 to 2020-2023, the prevalence of obesity among youth with T1D increased from 18.1% (95% confidence interval [CI], 17.3%-18.9%) to 26.0% (25.2%-26.8%) (p-for-trend < 0.001). Among adults with T1D, the prevalence of obesity rose from 30.5% (30.0%-31.0%) in 2008-2011 to 38.1% (37.8%-38.5%) in 2020-2023 (p-for-trend < 0.001). Obesity was highest in Black and Hispanic youth and adults, and racial and ethnic disparities persisted over time. Over the last 15-year period, GLP-1RA prescriptions significantly increased across all BMI categories in a dose-response manner among both youth and adults with T1D (all p-for-trend < 0.001). CONCLUSIONS:Over the last 15-year period, obesity has reached epidemic levels in US youth and adults with T1D, with significant disparities among racial and ethnic minoritized populations. These findings, coupled with the increase in GLP-1RA prescriptions, underscore the urgent need for data on GLP-1RAs' safety and effectiveness and guidance for obesity management in T1D.