Mullan, Aidan F.

Significance Statement Glomerular size differs by cortex depth. Larger nephrons are prognostic of progressive kidney disease, but it is unknown whether this risk differs by cortex depth or by glomeruli versus proximal or distal tubule size. We studied the average minor axis diameter in oval proximal and distal tubules separately and by cortex depth in patients who had radical nephrectomy to remove a tumor from 2019 to 2020. In adjusted analyses, larger glomerular volume in the middle and deep cortex predicted progressive kidney disease. Wider proximal tubular diameter did not predict progressive kidney disease independent of glomerular volume. Wider distal tubular diameter showed a gradient of strength of prediction of progressive kidney disease in the more superficial cortex than in the deep cortex. Background Larger nephrons are prognostic of progressive kidney disease, but whether this risk differs by nephron segments or by depth in the cortex is unclear. Methods We studied patients who underwent radical nephrectomy for a tumor between 2000 and 2019. Large wedge kidney sections were scanned into digital images. We estimated the diameters of proximal and distal tubules by the minor axis of oval tubular profiles and estimated glomerular volume with the Weibel–Gomez stereological model. Analyses were performed separately in the superficial, middle, and deep cortex. Cox proportional hazard models assessed the risk of progressive CKD (dialysis, kidney transplantation, sustained eGFR <10 ml/min per 1.73 m 2 , or a sustained 40% decline from the postnephrectomy baseline eGFR) with glomerular volume or tubule diameters. At each cortical depth, models were unadjusted, adjusted for glomerular volume or tubular diameter, and further adjusted for clinical characteristics (age, sex, body mass index, hypertension, diabetes, postnephrectomy baseline eGFR, and proteinuria). Results Among 1367 patients were 62 progressive CKD events during a median follow-up of 4.5 years. Glomerular volume predicted CKD outcomes at all depths, but only in the middle and deep cortex after adjusted analyses. Proximal tubular diameter also predicted progressive CKD at any depth but not after adjusted analyses. Distal tubular diameter showed a gradient of more strongly predicting progressive CKD in the superficial than deep cortex, even in adjusted analysis. Conclusions Larger glomeruli are independent predictors of progressive CKD in the deeper cortex, whereas in the superficial cortex, wider distal tubular diameters are an independent predictor of progressive CKD.

Abstract Background Multiple anaphylaxis mediators have been demonstrated to provoke migraine‐like attacks following intravascular infusion, suggesting that anaphylaxis could cause headache; however, headache is rarely noted in anaphylaxis and is not included among diagnostic criteria. Objective Our study objectives were to estimate the frequency of headache among prospectively enrolled emergency department (ED) patients with anaphylaxis and assess the association of headache with patient and anaphylaxis characteristics. Methods A cross‐sectional study of ED patients aged ≥5 years who met anaphylaxis diagnostic criteria from January 8, 2020 to September 9, 2022 was conducted. The primary outcome of interest was headache frequency among patients who met at least one anaphylaxis criterion. We explored the association of headache with patient characteristics and anaphylaxis characteristics. Results We included 63 patients with anaphylaxis. In all, 17 (27%, 95% confidence interval [CI] 17%–40%) patients reported the presence of a headache. Female patients had more than a nine times increased odds of having headache (odds ratio [OR] 9.3, 95% CI 1.14–77.1, p = 0.016). Presentation with headache was associated with the presence of dyspnea (OR 5.5, 95% CI 1.56–19.7, p = 0.006). Conclusion Headache in anaphylaxis may be more common than previously recognized, especially in females. Larger prospective studies are needed to characterize headache as a marker of neurological involvement in anaphylaxis.

Abstract Purpose Twenty five percent of practicing physicians in the US are International Medical Graduates (IMGs) – physicians who completed their medical school training outside of the United States and Canada. There are multiple studies demonstrating higher socio-economic background is associated with medical school matriculation in the US. However, despite a substantial prevalence of IMGs in the American healthcare system, studies of the association between demographics, socio-economic background, and securing a residency position in the match are lacking. Methods We created a survey with questions on residency match-related data and information on personal socio-economic background. An invitation to participate in the study was sent to all IMGs that applied to the included residency programs after the conclusion of the 2022 residency match. We used multivariable logistic regression to compare survey responses to the odds of securing a residency match. Results The total number of survey respondents was 744 (response rate 15.1%). We found that younger age, higher United States Medical License Examination (USMLE) scores, higher-income country of origin (including the United States), fewer match attempts, applying to fewer specialties, having parents with college degree or higher, and coming from higher-than-average or lower-than-average family income were associated with increased odds of matching. Gender, personal income, and visa status did not demonstrate significant associations with residency match. Conclusions Residency match is a significant expense for IMGs, especially for those from lower-income countries. International applicants from higher socio-economic backgrounds might have advantages in securing medical residency positions in the United States when controlling for other variables.

AbstractObjectivesPatients with limited English proficiency (LEP) have been shown to experience disparities in emergency department (ED) care. The objectives of this study were to examine the associations between LEP and irregular ED departures and return ED visits.MethodsWe conducted a multicenter cross‐sectional analysis of 18 EDs within an integrated health system in the upper Midwest from January 1, 2018, to December 31, 2021. ED visits of pediatric and adult patients who were discharged on the index visit were included for analysis. We analyzed the association of LEP with irregular departures, 72‐h and 7‐day return visits, and ED disposition at the time of that return visit. Multivariable model associations were calculated using generalized estimating equations and reported as odds ratios (OR) with 95% confidence intervals (CIs).ResultsA total of 745,464 total ED visits were analyzed, including 27,906 (3.7%) visits among patients with LEP. The most common preferred languages among patients with LEP were Spanish (12,759; 45.7%), Somali (4978; 17.8%), and Arabic (3185; 11.4%). After multivariable adjustment there were no differences in proportions of irregular departures (OR 1.09, 95% CI 0.99–1.21), 72‐h returns (OR 0.99, 95% CI 0.92–1.06), or 7‐day returns (OR 0.99, 95% CI 0.93–1.05) between patients with LEP or English proficiency. Patients with LEP returning within 72 h (OR 1.19, 95% CI 1.01–1.40) and 7 days (OR 1.15, 95% CI 1.01–1.33) were more likely to be admitted to the hospital.ConclusionsAfter multivariable adjustment, we did not find an increased frequency of irregular ED departures or 72‐h or 7‐day returns among patients with LEP compared with people proficient in English. However, we did find that higher proportions of patients with LEP were admitted to the hospital at the time of the return ED visit.

Significance Statement Nephrosclerosis (glomerulosclerosis, interstitial fibrosis, and tubular atrophy) is the defining pathology of both kidney aging and CKD. Optimal thresholds for nephrosclerosis that identify persons with a progressive disease are unknown. This study determined a young-age threshold (18–29 years) and age-based 95th percentile thresholds for nephrosclerosis on the basis of morphometry of kidney biopsy sections from normotensive living kidney donors. These thresholds were 7.1-fold to 36-fold higher in older (70 years or older) versus younger (aged 18–29 years) normotensive donors. Age-based thresholds, but not young-age threshold, were prognostic for determining risk of progressive CKD among patients who underwent a radical nephrectomy or a for-cause native kidney biopsy, suggesting that age-based thresholds are more useful than a single young-age threshold for identifying CKD on biopsy. Background Nephrosclerosis, defined by globally sclerotic glomeruli (GSG) and interstitial fibrosis and tubular atrophy (IFTA), is a pathology of both kidney aging and CKD. A comparison of risk of progressive CKD using aged-based thresholds for nephrosclerosis versus a single young-adult threshold is needed. Methods We conducted morphometric analyses of kidney biopsy images for %GSG, %IFTA, and IFTA foci density among 3020 living kidney donors, 1363 patients with kidney tumor, and 314 patients with native kidney disease. Using normotensive donors, we defined young-age thresholds (18–29 years) and age-based (roughly by decade) 95th percentile thresholds. We compared age-adjusted risk of progressive CKD (kidney failure or 40% decline in eGFR) between nephrosclerosis that was “normal compared with young,” “normal for age but abnormal compared with young,” and “abnormal for age” in patients with tumor and patients with kidney disease. Results The 95th percentiles in the youngest group (18–29 years) to the oldest group (70 years or older) ranged from 1.7% to 16% for %GSG, 0.18% to 6.5% for %IFTA, and 8.2 to 59.3 per cm 2 for IFTA foci density. Risk of progressive CKD did not differ between persons with nephrosclerosis “normal compared with young” versus “normal for age but abnormal compared with young.” Risk of progressive CKD was significantly higher with %GSG, %IFTA, or IFTA foci density that was abnormal versus normal for age in both cohorts. Conclusions Given that increased risk of progressive CKD occurs only when nephrosclerosis is abnormal for age, age-based thresholds for nephrosclerosis seem to be better than a single young-age threshold for identifying clinically relevant CKD.

Significance Statement Nephron number currently can be estimated only from glomerular density on a kidney biopsy combined with cortical volume from kidney imaging. Because of measurement biases, refinement of this approach and validation across different patient populations have been needed. The prognostic importance of nephron number also has been unclear. The authors present an improved method of estimating nephron number that corrects for several biases, resulting in a 27% higher nephron number estimate for donor kidneys compared with a prior method. After accounting for comorbidities, the new nephron number estimate does not differ between kidney donors and kidney patients with tumor and shows consistent associations with clinical characteristics across these two populations. The findings also indicate that low nephron number predicts CKD independent of biopsy and clinical characteristics in both populations. Background Nephron number can be estimated from glomerular density and cortical volume. However, because of measurement biases, this approach needs refinement, comparison between disparate populations, and evaluation as a predictor of CKD outcomes. Methods We studied 3020 living kidney donors and 1354 patients who underwent radical nephrectomy for tumor. We determined cortex volume of the retained kidney from presurgical imaging and glomerular density by morphometric analysis of needle core biopsy of the donated kidney and wedge sections of the removed kidney. Glomerular density was corrected for missing glomerular tufts, absence of the kidney capsule, and then tissue shrinkage on the basis of analysis of 30 autopsy kidneys. We used logistic regression (in donors) and Cox proportional hazard models (in patients with tumor) to assess the risk of CKD outcomes associated with nephron number. Results Donors had 1.17 million nephrons per kidney; patients with tumor had 0.99 million nephrons per kidney. A lower nephron number was associated with older age, female sex, shorter height, hypertension, family history of ESKD, lower GFR, and proteinuria. After adjusting for these characteristics, nephron number did not differ between donors and patients with tumor. Low nephron number (defined by <5th or <10th percentile by age and sex in a healthy subset) in both populations predicted future risk of CKD outcomes independent of biopsy and clinical characteristics. Conclusions Compared with an older method for estimating nephron number, a new method that addresses several sources of bias results in nephron number estimates that are 27% higher in donors and 1% higher in patients with tumor and shows consistency between two populations. Low nephron number independently predicts CKD in both populations. Podcast This article contains a podcast at https://dts.podtrac.com/redirect.mp3/www.asn-online.org/media/podcast/JASN/2023_06_22_JASN0000000000000124.mp3

Introduction: Healthcare workers, particularly those in the emergency department (ED), experience high rates of injuries caused by workplace violence (WPV). Objective: Our goal was to establish the incidence of WPV among multidisciplinary ED staff within a regional health system and assess its impact on staff victims. Methods: We conducted a survey study of all multidisciplinary ED staff at 18 Midwestern EDs encompassing a larger health system between November 18–December 31, 2020. We solicited the incidence of verbal abuse and physical assault experienced and witnessed by respondents over the prior six months, as well as its impact on staff. Results: We included responses from 814 staff (24.5% response rate) for final analysis with 585 (71.9%) indicating some form of violence experienced in the preceding six months. A total of 582 (71.5%) respondents indicated experiencing verbal abuse, and 251 (30.8%) indicated experiencing some form of physical assault. All disciplines experienced some type of verbal abuse and nearly all experienced some type of physical assault. One hundred thirty-five (21.9%) respondents indicated that being the victim of WPV has affected their ability to perform their job, and nearly half (47.6%) indicated it has changed the way they interact with or perceive patients. Additionally, 132 (21.3%) indicated experiencing symptoms of post-traumatic stress, and 18.5% reported they have considered leaving their position due to an incident. Conclusion: Emergency department staff suffer violence at a high rate, and there is no discipline that is spared. As health systems seek to prioritize staff safety in violence-prone areas such as the ED, it is imperative to recognize that the entire multidisciplinary team is impacted and requires targeted efforts for improvement in safety.