Nephrology: What You May Have Missed in 2023

This article highlights a selection of important nephrology studies published in 2023 that have relevance for nonnephrologist physicians. Four studies examined progression of chronic kidney disease or cardiovascular disease with respect to finerenone use, magnesium supplementation, iron markers, and COVID-19. Two studies examined treatments to improve specific aspects of chronic kidney disease management, including daprodustat to address anemia and patiromer to address hyperphosphatemia. One study showed that acetazolamide added to loop diuretics increased diuresis in acute decompensated heart failure across a wide range of renal function. Another study found that once-daily hydrochlorothiazide did not prevent kidney stone recurrence. Finally, an antibiotic stewardship intervention safely reduced antibiotic prescribing for suspected urinary tract infection in frail older adults.

The Ethics of Cancer Screening Based on Race and Ethnicity

Racial and ethnic disparities in incidence and mortality are well documented for many types of cancer. As a result, there is understandable policy and clinical interest in race- and ethnicity-based clinical screening guidelines to address cancer health disparities. Despite the theoretical benefits, such proposals do not typically address associated ethical considerations. Using the examples of gastric cancer and esophageal adenocarcinoma, which have demonstrated disparities according to race and ethnicity, this article examines relevant ethical arguments in considering screening based on race and ethnicity. Race- and ethnicity-based clinical preventive care services have the potential to improve the balance of harms and benefits of screening. As a result, programs focused on high-risk racial or ethnic groups could offer a practical alternative to screening the general population, in which the screening yield may be too low to demonstrate sufficient effectiveness. However, designing screening according to socially based categorizations such as race or ethnicity is controversial and has the potential for intersectional stigma related to social identity or other structurally mediated environmental factors. Other ethical considerations include miscategorization, unintended negative effects on health disparities, disregard for underlying risk factors, and the psychological costs of being assigned higher risk. Given the ethical considerations, the practical application of race and ethnicity in cancer screening is most relevant in multicultural countries if and only if alternative proxies are not available. Even in those instances, policymakers and clinicians should carefully address the ethical considerations within the historical and cultural context of the intended population. Further research on alternative proxies, such as social determinants of health and culturally based characteristics, could provide more adequate factors for risk stratification.

Glucagon-Like Peptide-1 Receptor Agonists and Risk for Suicidal Ideation and Behaviors in U.S. Older Adults With Type 2 Diabetes: A Target Trial Emulation Study: Annals of Internal Medicine: Vol 177, No 8

Background: A major concern has recently emerged about a potential link between glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and increased risk for suicidal ideation and behaviors based on International Classification of Diseases codes. Objective: To investigate the association between GLP-1 RAs, compared with sodium–glucose cotransporter-2 inhibitors (SGLT2is) or dipeptidyl peptidase-4 inhibitors (DPP4is), and risk for suicidal ideation and behaviors in older adults with type 2 diabetes (T2D). Design: Two target trial emulation studies comparing propensity score (PS)–matched cohorts for GLP-1 RAs versus SGLT2is and GLP-1 RAs versus DPP4is. Setting: U.S. national Medicare administrative data from January 2017 to December 2020. Patients: Older adults (≥66 years) with T2D; no record of suicidal ideation or behaviors; and a first prescription for a GLP-1 RA, SGLT2i, or DPP4i. Measurements: The primary end point was a composite of suicidal ideation and behaviors. New GLP-1 RA users were matched 1:1 on PS to new users of an SGLT2i or DPP4i in each pairwise comparison. A Cox proportional hazards regression was used to estimate the hazard ratio (HR) and 95% CIs within matched groups. Results: This study included 21 807 pairs of patients treated with a GLP-1 RA versus an SGLT2i and 21 402 pairs of patients treated with a GLP-1 RA versus a DPP4i. The HR of suicidal ideation and behaviors associated with GLP-1 RAs relative to SGLT2is was 1.07 (95% CI, 0.80 to 1.45; rate difference, 0.16 [CI, −0.53 to 0.86] per 1000 person-years); the HR relative to DPP4is was 0.94 (CI, 0.71 to 1.24; rate difference, −0.18 [CI, −0.92 to 0.57] per 1000 person-years). Limitations: Low event rate; imprecise estimates; unmeasured confounders, such as body mass index; and potential misclassification of outcomes. Conclusion: Among Medicare beneficiaries with T2D, this study found no clear increased risk for suicidal ideation and behaviors with GLP-1 RAs, although estimates were imprecise and a modest adverse risk could not be ruled out. Primary Funding Source: American Foundation for Pharmaceutical Education, Pharmaceutical Research and Manufacturers of America Foundation, National Institute on Aging, and National Institute of Diabetes and Digestive and Kidney Diseases.

Morbidity and Mortality of Hospital-Onset SARS-CoV-2 Infections Due to Omicron Versus Prior Variants: A Propensity-Matched Analysis: Annals of Internal Medicine: Vol 177, No 8

Background: Many hospitals have scaled back measures to prevent nosocomial SARS-CoV-2 infection given large decreases in the morbidity and mortality of SARS-CoV-2 infections for most people. Little is known, however, about the morbidity and mortality of nosocomial SARS-CoV-2 infections for hospitalized patients in the Omicron era. Objective: To estimate the effect of nosocomial SARS-CoV-2 infection on hospitalized patients’ outcomes during the pre-Omicron and Omicron periods. Design: Retrospective matched cohort study. Setting: 5 acute care hospitals in Massachusetts, December 2020 to April 2023. Patients: Adults testing positive for SARS-CoV-2 on or after hospital day 5, after negative SARS-CoV-2 test results on admission and on hospital day 3, were matched to control participants by hospital, service, time period, days since admission, and propensity scores that incorporated demographics, comorbid conditions, vaccination status, primary diagnosis category, vital signs, and laboratory test values. Measurements: Primary outcomes were hospital mortality and time to discharge. Secondary outcomes were intensive care unit (ICU) admission, need for advanced oxygen support, discharge destination, hospital-free days, and 30-day readmissions. Results: There were 274 cases of hospital-onset SARS-CoV-2 infection during the pre-Omicron period and 1037 cases during the Omicron period (0.17 vs. 0.49 cases per 100 admissions). Patients with hospital-onset SARS-CoV-2 infection were older and had more comorbid conditions than those without. During the pre-Omicron period, hospital-onset SARS-CoV-2 infection was associated with increased risk for ICU admission, increased need for high-flow oxygen, longer time to discharge (median difference, 4.7 days [95% CI, 2.9 to 6.6 days]), and higher mortality (risk ratio, 2.0 [CI, 1.1 to 3.8]) versus matched control participants. During the Omicron period, hospital-onset SARS-CoV-2 infection remained associated with increased risk for ICU admission and increased time to discharge (median difference, 4.2 days [CI, 3.6 to 5.0 days]). The association with increased hospital mortality was attenuated but still significant (risk ratio, 1.6 [CI, 1.2 to 2.3]). Limitation: Residual confounding may be present. Conclusion: Hospital-onset SARS-CoV-2 infection during the Omicron period remains associated with increased morbidity and mortality. Primary Funding Source: Harvard Medical School Department of Population Medicine.

Trends in Diet Quality Among U.S. Adults From 1999 to 2020 by Race, Ethnicity, and Socioeconomic Disadvantage

Background: Few data have assessed trends in diet quality among U.S. adults. Objective: To evaluate trends in diet quality by race, ethnicity, and socioeconomic disadvantage. Design: Repeated cross-sectional study. Setting: United States. Participants: Noninstitutionalized adults aged 20 years or older who responded to the 1999–2020 National Health and Nutrition Examination Survey (NHANES). Measurements: The proportion of participants meeting the targets of the validated American Heart Association (AHA) 2020 continuous diet score (based on higher intake of fruits, vegetables, whole grains, fish and shellfish, and nuts, seeds, and legumes and lower intake of sugar-sweetened beverages, processed meat, saturated fat, and sodium) and the Healthy Eating Index (HEI)-2015, and energy-adjusted consumption of their components and other individual food groups and nutrients. Poor diet was defined as less than 40% adherence to the AHA score, intermediate as 40% to 79.9% adherence, and ideal as at least 80% adherence. Results: A total of 51 703 adults were included. From 1999 to 2020, the proportion of U.S. adults with poor diet quality decreased from 48.8% to 37.4% (difference, −11.4 percentage points [95% CI, −16.8 to −5.96 percentage points]), the proportion with intermediate quality increased from 50.6% to 61.1% (difference, 10.5 percentage points [CI, 5.20 to 16.1 percentage points]), and the proportion with ideal quality increased from 0.66% to 1.58% (difference, 0.93 percentage points [CI, 0.35 to 1.51 percentage points]) (P for trend < 0.001 for each). Persistent or worsening disparities in diet quality were observed by age, sex, race and ethnicity, education, income, food security, Supplemental Nutrition Assistance Program participation, and health insurance coverage. For example, the proportion of adults with poor diet quality decreased from 47.9% to 33.0% among those with food security (P for trend < 0.001) but did not change (51.3% to 48.2%) among those experiencing food insecurity (P for trend = 0.140) (P for interaction = 0.001). Findings were similar for HEI-2015. Limitations: Self-reported diet; cross-sectional study design. Conclusion: Diet quality among U.S. adults improved modestly between 1999 and 2020, but the proportion with poor diet quality remains high, and dietary disparities persist or are worsening. Primary Funding Source: National Institutes of Health.

Census Tract Rurality, Predominant Race and Ethnicity, and Distance to Lung Cancer Screening Facilities: An Ecological Study: Annals of Internal Medicine: Vol 178, No 2

Background: The U.S. Preventive Services Task Force recommends annual lung cancer screening (LCS) for adults who meet specific age and smoking history criteria. Objective: To evaluate race-, ethnicity-, and rurality-based differences in distance to the nearest LCS facility. Design: Cross-sectional ecological study. Setting: U.S. census tracts. Participants: 71 691 census tracts. Measurements: The outcome variable was road network distance in miles between a census tract and the nearest LCS facility. Distance was log-transformed, and geometric means are reported. Census tracts were classified as majority (>50%) American Indian/Alaska Native (AI/AN), Asian, Black, non-Hispanic White (NHW), no single race, or Hispanic. Rurality was defined using the rural-urban commuting area codes. Ordinary least-squares regression examined the associations between distance and census tract race, ethnicity, and rurality. Results: Geometric mean distance to the nearest LCS facility was 6.5 miles. Compared with NHW-majority census tracts, distance to the nearest LCS facility was 5.26 times (426%) longer in AI/AN-majority census tracts and 7% to 39% shorter in Asian-, Black-, and Hispanic-majority census tracts. Adjustment for rurality reduced the mean distance in AI/AN-majority census tracts, but the mean distance was still 3.16 times the distance in NHW-majority census tracts. Adjustment for rurality reduced the observed advantage in Asian- and Black-majority census tracts and changed the direction of associations in Hispanic-majority census tracts. Limitation: Analyses did not account for travel time or cost. Conclusion: Differences exist in distance to LCS facilities by race and ethnicity that can only be partially explained by rurality. Primary Funding Source: Lung Ambition Alliance and the Center for Lung Research in Honor of Wayne Gittinger.

Association Between False-Positive Results and Return to Screening Mammography in the Breast Cancer Surveillance Consortium Cohort

Background: False-positive results on screening mammography may affect women’s willingness to return for future screening. Objective: To evaluate the association between screening mammography results and the probability of subsequent screening. Design: Cohort study. Setting: 177 facilities participating in the Breast Cancer Surveillance Consortium (BCSC). Patients: 3 529 825 screening mammograms (3 184 482 true negatives and 345 343 false positives) performed from 2005 to 2017 among 1 053 672 women aged 40 to 73 years without a breast cancer diagnosis. Measurements: Mammography results (true-negative result or false-positive recall with a recommendation for immediate additional imaging only, short-interval follow-up, or biopsy) from 1 or 2 screening mammograms. Absolute differences in the probability of returning for screening within 9 to 30 months of false-positive versus true-negative screening results were estimated, adjusting for race, ethnicity, age, time since last mammogram, BCSC registry, and clustering within women and facilities. Results: Women were more likely to return after a true-negative result (76.9% [95% CI, 75.1% to 78.6%]) than after a false-positive recall for additional imaging only (adjusted absolute difference, −1.9 percentage points [CI, −3.1 to −0.7 percentage points]), short-interval follow-up (−15.9 percentage points [CI, −19.7 to −12.0 percentage points]), or biopsy (−10.0 percentage points [CI, −14.2 to −5.9 percentage points]). Asian and Hispanic/Latinx women had the largest decreases in the probability of returning after a false positive with a recommendation for short-interval follow-up (−20 to −25 percentage points) or biopsy (−13 to −14 percentage points) versus a true negative. Among women with 2 screening mammograms within 5 years, a false-positive result on the second was associated with a decreased probability of returning for a third regardless of the first screening result. Limitation: Women could receive care at non-BCSC facilities. Conclusion: Women were less likely to return to screening after false-positive mammography results, especially with recommendations for short-interval follow-up or biopsy, raising concerns about continued participation in routine screening among these women at increased breast cancer risk. Primary Funding Source: National Cancer Institute.

Shifting Trends in the Indication of Glucagon-like Peptide-1 Receptor Agonist Prescriptions: A Nationwide Analysis

Epidemiology of Homebound Population Among Beneficiaries of a Large National Medicare Advantage Plan

Background: Interest in home-based care is increasing among Medicare Advantage (MA) plans. The epidemiology of homebound MA beneficiaries is unknown. Objective: To determine the prevalence, characteristics, predictors, health service use, and mortality outcomes of homebound beneficiaries of a large national MA plan. Design: Cross-sectional. Setting: National MA plan. Participants: Humana MA beneficiaries in 2022 (n = 2 435 519). Measurements: Homebound status was assessed via in-home assessment using previously defined categories: homebound (never or rarely left home in the past month), semihomebound (left home with assistance, had difficulty, or needed help leaving home), and not homebound. Demographic, clinical, health service use, and mortality outcomes were compared by homebound status. Results: In 2022, the overall prevalence of homebound beneficiaries was 22.0% (8.4% of beneficiaries were homebound, and 13.6% were semihomebound). In adjusted models, female sex (odds ratio [OR], 1.36 [95% CI, 1.35 to 1.37), low-income status or dual eligibility for Medicare and Medicaid (OR, 1.56 [CI, 1.55 to 1.57]), dementia (OR, 2.36 [CI, 2.33 to 2.39]), and moderate to severe frailty (OR, 4.32 [CI, 4.19 to 4.45]) were predictive of homebound status. In multivariable logistic regression, homebound status was associated with increased odds of any emergency department visit (OR, 1.14 [ CI, 1.14 to 1.15]), any inpatient hospital admission (OR, 1.44 [CI, 1.42 to 1.46]), any skilled-nursing facility admission (OR, 2.18 [CI, 2.13 to 2.23]), and death (OR, 2.55 [CI, 2.52 to 2.58]). Limitation: The study period overlapped the tail end of the COVID-19 pandemic, and data were derived from a single national MA plan, which limits generalizability. Conclusion: Overall homebound prevalence in a national MA plan was 22.0% and was independently associated with increased health service use and mortality. Study findings can inform strategic initiatives to identify and manage care for homebound beneficiaries. Primary Funding Source: Humana, under a collaborative research agreement with Johns Hopkins University.

Trends and Disparities in Ambulatory Follow-Up After Cardiovascular Hospitalizations: A Retrospective Cohort Study: Annals of Internal Medicine: Vol 177, No 9

Background: Timely follow-up after cardiovascular hospitalization is recommended to monitor recovery, titrate medications, and coordinate care. Objective: To describe trends and disparities in follow-up after acute myocardial infarction (AMI) and heart failure (HF) hospitalizations. Design: Retrospective cohort study. Setting: Medicare. Participants: Medicare fee-for-service beneficiaries hospitalized between 2010 and 2019. Measurements: Receipt of a cardiology visit within 30 days of discharge. Multivariable logistic regression models were used to estimate changes over time overall and across 5 sociodemographic characteristics on the basis of known disparities in cardiovascular outcomes. Results: The cohort included 1 678 088 AMI and 4 245 665 HF hospitalizations. Between 2010 and 2019, the rate of cardiology follow-up increased from 48.3% to 61.4% for AMI hospitalizations and from 35.2% to 48.3% for HF hospitalizations. For both conditions, follow-up rates increased for all subgroups, yet disparities worsened for Hispanic patients with AMI and patients with HF who were Asian, Black, Hispanic, Medicaid dual eligible, and residents of counties with higher levels of social deprivation. By 2019, the largest disparities were between Black and White patients (AMI, 51.9% vs. 59.8%, difference, 7.9 percentage points [pp] [95% CI, 6.8 to 9.0 pp]; HF, 39.8% vs. 48.7%, difference, 8.9 pp [CI, 8.2 to 9.7 pp]) and Medicaid dual-eligible and non–dual-eligible patients (AMI, 52.8% vs. 60.4%, difference, 7.6 pp [CI, 6.9 to 8.4 pp]; HF, 39.7% vs. 49.4%, difference, 9.6 pp [CI, 9.2 to 10.1 pp]). Differences between hospitals explained 7.3 pp [CI, 6.7 to 7.9 pp] of the variation in follow-up for AMI and 7.7 pp [CI, 7.2 to 8.1 pp]) for HF. Limitation: Generalizability to other payers. Conclusion: Equity-informed policy and health system strategies are needed to further reduce gaps in follow-up care for patients with AMI and patients with HF. Primary Funding Source: National Institute on Aging.