Sophie Elizabeth Claudel

Background: Dietary sodium intake is a modifiable determinant of blood pressure, and impaired renal sodium handling is implicated in the pathogenesis of hypertension. Whether dietary sodium intake modulates renal tubular sodium transporter abundance among normotensive adults at risk for hypertension is unknown. Methods: Forty-six normotensive adults with normal kidney function at risk of developing hypertension were prospectively enrolled to complete a very low sodium (LS) diet followed by a high sodium (HS) diet. Urinary extracellular vesicle (uEV) proteins were quantified from a 24-hour urine collection at the end of each diet. We compared normalized uEV protein concentrations between diets and tested whether diet modified uEV protein associations with serum aldosterone, urinary aldosterone, and serum cortisol-cortisone ratio under either diet using Wilcoxon rank sums and linear mixed effects models, respectively. Results: Participants achieved median [IQR] urine sodium 13.2 [7.7-19.9] mEq/24h on the LS diet and 244.0 [197.1-297.0] mEq/24h on the HS diet. LS intake induced greater renin activity, greater plasma and urinary aldosterone, and lower urinary cortisol, when compared to HS intake. In parallel, NCC, ENaC, SGLT2, OXSR1, and Pendrin uEV concentrations were significantly higher during LS intake than HS intake ( p p in vivo renal sodium, water, and electrolyte handling.

Aims: The objective of this study was to estimate the prevalence and trends in prevalence of dysglycemia in the United States (U.S.). Methods: This is a repeat cross‐sectional analysis of adults age ≥ 20 years who participated in the National Health and Nutrition Examination Survey (NHANES) between 2013–2023. Age‐standardized pre‐diabetes, undiagnosed diabetes, diagnosed diabetes, and total diabetes prevalence were estimated for each of the 4 survey cycles, then stratified by sociodemographic and clinical characteristics. Linear trends were estimated using logistic regression. Prevalence calculations and trend analyses were repeated to assess the proportion of participants meeting glycemic, blood pressure, and lipid control targets. Results: Among 24 230 participants across all survey years, 6773 had pre‐diabetes, and 4784 had diabetes (3826 diagnosed/958 undiagnosed). The age‐adjusted prevalence of total diabetes was stable across the study period: 14.6% (95% CI 13.0%–16.2%) in 2013–2014 and 16.3% (14.6%–18.0%) in 2021–2023 (prevalence ratio (PR) 1.07 [95% CI 0.90–1.26], p ‐trend = 0.47). The age‐adjusted prevalence of pre‐diabetes increased significantly during the study period from 26.4% (23.7%–29.1%) in 2013–2014 to 30.7% (28.4%–33.0%) in 2021–2023 ( p ‐trend = 0.04, PR 1.12 [1.02–1.23]). Conclusion: While the prevalence of diabetes has stabilized over the last decade, the rise in pre‐diabetes signals a growing population at risk for future cardiometabolic and kidney disease.

Background: Measured urine albumin-to-creatinine ratio (ACR) is known to be variable between measurements from the same individual with chronic kidney disease (CKD) or diabetes, but the factors predisposing to increased variability remain unclear. Our objective was to quantify and identify predictors of short-term, within-person variability in albuminuria in a generalizable population. Methods: This is a cross-sectional analysis of 4,829 adults in the 2009-2010 United States National Health and Nutrition Examination Survey who provided two urine samples within 10 days. We calculated the absolute percentage change, within-person coefficient of variation, and 95% reference change values for the overall population and within clinically meaningful subgroups. We then performed linear regression modeling to assess for a priori selected predictors of variability. Results: The mean age was 47.8 (SD 16.5) years, the mean eGFR was 95.8 (SD 20.4) ml/min per 1.73m2, 11.3% had diabetes, and 51.5% of the participants were women. Factors associated with greater variability in temporally proximate repeat urine ACR samples included age, sex, and severity of initial urine ACR. Overall, albuminuria varied by approximately 28%, but there was heterogeneity within clinical subgroups. Reclassification into alternative albuminuria category following the second collection was low. Conclusion: Patients’ urine ACR can fluctuate roughly ±30% on average and confirmatory testing is wise in those with borderline values. Reviewing longitudinal trends in urine ACR or averaging several collections is likely more clinically meaningful than any single value.

Purpose of review: Chronic kidney disease of uncertain etiology (CKDu) has devastating impacts on individuals and communities in affected regions, but it remains an ill-defined diagnosis of exclusion despite decades of environmental and epidemiologic research. The purpose of this review is to synthesize recent literature describing the global burden of disease and potential causal factors. Recent findings: A large, international prevalence study quantitatively identified Uddanam, India, Northwest Nicaragua, and Anuradhapura, Sri Lanka as prominent CKDu hotspots. Stronger evidence for the role of heat stress in exacerbating kidney function decline among individuals with CKDu now includes validated measurements of core body temperature. Additionally, recent studies use urine metabolomics to support environmental exposure evaluation and generate hypotheses for future pathway analysis. While longitudinal studies remain infrequent, three key longitudinal studies provide greater insight into trajectories of kidney function decline in CKDu. Summary: The cause(s) of CKDu remain uncertain, but greater integration of genetic, translational, biopsy, and longitudinal epidemiologic data hold promise for elucidating mechanistic pathways. Increased standardization of kidney biopsy protocols, epidemiologic definitions, and population surveillance methodologies would strengthen ongoing efforts to identify, treat, and prevent CKDu.

Hyperuricemia has been associated with chronic kidney disease (CKD) and its progression in several observational studies.^1–3 However, randomized controlled trials have not demonstrated that urate-lowering therapies reduce the risk of CKD progression.^4,5 While the effects of a hyperuricemic environment on the kidneys are not fully understood, some studies suggest it may influence podocytes by promoting oxidative stress and inflammatory responses.^6,7 In this study, we explored the associations between serum uric acid levels, histopathologic lesions, and podocyte injury, as evidenced by foot process effacement, in a cohort of patients with biopsy-confirmed kidney disease. Serum uric acid levels were measured in 519 individuals enrolled into the Boston Kidney Biopsy Cohort (BKBC), a prospective cohort study of individuals with pathologist-adjudicated, semi-quantitative assessment of histopathology. Foot process effacement severity was evaluated using semi-quantitative scores derived from pathologists' descriptions of foot process effacement severity in electron microscopy (EM) reports ( Supplemental Methods).⁸ We assessed the correlation between serum uric acid levels, the estimated glomerular filtration rate (eGFR), and albuminuria using Spearman correlation coefficients. Multivariable linear regression models tested the associations of serum uric acid levels with histopathologic lesion severity and foot process effacement ( Supplemental Methods).

Background: Chronic diseases may injure the pancreas and result in a reduction in pancreas volume (PV), which may adversely impact its critical role in endocrine and exocrine function. Less is known about whether individuals with smaller PV face higher risks of adverse clinical outcomes. Methods: We estimated baseline age‐adjusted predicted PV (pPV) from abdominal magnetic resonance imaging in 36 592 UK Biobank participants. Since the initial magnetic resonance imaging occurred 9.0 (interquartile range, 7.5–10.1) years after baseline, we fit a linear regression equation that included age for the outcome of PV slope in 451 participants with repeat magnetic resonance imaging 2.8 (interquartile range, 2.2–4.8) years after the initial scan. Using these data, we calculated baseline age‐adjusted pPV slope by adding or subtracting the annual change to the initial PV measurement assuming linear change in PV over time. Multivariable‐adjusted proportional hazards models tested associations of pPV with incident chronic kidney disease, cardiovascular disease (CVD; myocardial infarction, heart failure, or stroke), and death. Results: Participants (52.2% women) were 55±8 years old and had a pPV of 63.3±15.3 mL. During median follow‐up of 13.9 years, there were 757 incident chronic kidney disease, 1392 CVD, and 702 death events. In final adjusted models, participants in the first pPV quartile had a 1.67‐fold (95% CI, 1.34–2.07) and 1.28‐fold (95% CI, 1.10–1.49) increased risk of incident CVD and death compared with the fourth quartile, respectively. pPV had nonlinear associations with incident CVD and death (each P <0.001). pPV was not associated with incident chronic kidney disease. Conclusions: Lower pPV is associated with increased risk of incident CVD and death but not incident chronic kidney disease. Future studies should investigate the pathophysiologic mechanisms driving these associations.