Search

Rationale & Objective: Plasma proneurotensin/neuromedin N (pro-NT/NMN) is a precursor of neurotensin, a tridecapeptide linked with type 2 diabetes mellitus and other comorbid conditions associated with kidney disease. Whether pro-NT/NMN is directly associated with incident chronic kidney disease (CKD), and whether that association differs by race, is uncertain. We evaluated whether pro-NT/NMN levels were associated with increased risk of kidney outcomes. Study Design: Prospective cohort. Setting & Participants: Participants in Biomarker Mediators of Racial Disparities in Risk Factors, a nested cohort from the REasons for Geographic And Racial Differences in Stroke study, with available stored serum and urine samples from baseline and second visits for biomarker measurement. Exposure: Baseline log-transformed pro-NT/NMN. Outcomes: Incident CKD, progressive estimated glomerular filtration rate (eGFR) decline, incident albuminuria, and incident kidney failure within median follow-up time of 9.4 years. Analytical Approach: Logistic regression. Results: Among 3,914 participants, the mean ± SD age was 64 ± 8 (SD) years, 48% were women, and 51% were Black. Median baseline eGFR was 90 (IQR, 77-102) mL/min/1.73 m2. Each SD higher of pro-NT/NMN was associated with 9% higher odds of progressive eGFR decline (OR, 1.09; 95% CI, 1.00-1.20). There was no association observed with incident CKD (OR, 1.10; 95% CI, 0.96-1.27), incident albuminuria (OR, 1.08; 95% CI, 0.96-1.22), or incident kidney failure (OR, 1.10; 95% CI, 0.83-1.46). There were no differences in results by race or sex. Limitations: Single measurement of pro-NT/NMN and limited generalizability. Conclusions: Higher pro-NT/NMN was associated with progressive eGFR decline but no other manifestations of kidney disease incidence. Plain-Language Summary: Neurotensin is a peptide secreted by the small intestine in response to a meal. Higher levels of neurotensin and its stable precursor, proneurotensin/neuromedin N (pro-NT/NMN), have been associated with cardiovascular disease and type 2 diabetes mellitus, important risk factors for the development of kidney disease. Whether pro-NT/NMN is directly associated with kidney outcomes has been less studied and has been done so in largely homogenous cohorts of White participants. Using the REasons for Geographic And Racial Differences in Stroke study, we followed Black and White participants and evaluated the risk of developing kidney outcomes. We found that elevated levels of pro-NT/NMN were associated with kidney function decline. Pro-NT/NMN may help individuals who may benefit from closer monitoring of kidney function.

Background: Trimethylamine N-oxide (TMAO) is a gut microbial metabolite derived from dietary l-carnitine and choline. High plasma TMAO levels are associated with cardiovascular disease and overall mortality, but little is known about the associations of TMAO and related metabolites with the risk of kidney function decline among patients with chronic kidney disease (CKD)., Methods: We prospectively followed 152 nondialysis patients with CKD stages 3-5 and measured plasma TMAO and related metabolites (trimethylamine [TMA], choline, carnitine, and γ-butyrobetaine) via liquid chromatography‒mass spectrometry. An estimated glomerular filtration rate (eGFR) slope >3 ml/min/per 1.73 m 2 per year was defined as a rapid decline. We performed logistic regression to determine the probability of rapid or slow eGFR decline, with each metabolite as the main predictor. The gut microbiota was profiled via whole metagenomic sequencing., Results: The participants had a median age of 66 years, 41.4 % were women, 39.5 % had diabetes, and the median eGFR was 23 mL/min/1.73 m 2 . A rapid decrease in the eGFR occurred in 65 patients (42.8 %) over a median follow-up of 3.3 years. After adjustment for baseline eGFR, proteinuria, and clinical factors, plasma TMAO levels were independently associated with increased odds of rapid eGFR decline (odds ratio, 2.42; 95 % CI, 1.36-4.32), whereas plasma TMA, choline, carnitine, and γ-butyrobetaine levels were not. Patients who exhibited rapid eGFR decline had a distinct gut microbial composition characterized by increased α-diversity and an abundance of TMA-producing bacteria, including those of the genera Desulfovibrio and Collinsella tanakaei, as well as increased expression of the TMA-producing enzymes bbuA and cutC., Conclusion: Our findings suggest the relevance of plasma TMAO in the progression of kidney disease among patients with CKD., Competing Interests: Conflict of interest All the authors declared no competing interests., (Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Geographic variation in the prevalence of chronic kidney disease and incidence of end-stage renal disease has been previously reported. However, the geographic epidemiology of rapid estimated glomerular filtration rate (eGFR) decline has not been examined. Methods: We built a longitudinal cohort of 2,107,570 US veterans to characterize the spatial epidemiology of and examine the associations between US county characteristics and rapid eGFR decline. Results: There were 169,029 (8.02%) with rapid eGFR decline (defined as eGFR slope < –5 ml/min per 1.73 m2/year). The prevalence of rapid eGFR decline adjusted for age, race, gender, diabetes, and hypertension varied by county from 4.10%–6.72% in the lowest prevalence quintile to 8.41%–22.04% in the highest prevalence quintile (P for heterogeneity < 0.001). Examination of adjusted prevalence showed substantial geographic variation in those with and without diabetes and those with and without hypertension (P for heterogeneity < 0.001). Cohort participants had higher odds of rapid eGFR decline when living in counties with unfavorable characteristics in domains including health outcomes (odds ratio [OR] = 1.15; confidence interval [CI] = 1.09–1.22), health behaviors (OR = 1.08; CI = 1.03–1.13), clinical care (OR = 1.11; CI = 1.06–1.16), socioeconomic conditions (OR = 1.15; CI = 1.09–1.22), and physical environment (OR = 1.15; CI = 1.01–1.20); living in counties with high percentage of minorities and immigrants was associated with rapid eGFR decline (OR = 1.25; CI = 1.20–1.31). Spatial analyses suggest the presence of cluster of counties with high prevalence of rapid eGFR decline. Discussion: Our findings show substantial geographic variation in rapid eGFR decline among US veterans; the variation persists in analyses stratified by diabetes and hypertension status; results show associations between US county characteristics in domains capturing health, socioeconomic, environmental, and diversity conditions, and rapid eGFR decline.

Introduction: Low serum bicarbonate at a single point in time is associated with accelerated kidney decline in patients with chronic kidney disease (CKD). We modeled how changes in serum bicarbonate over time affect incidence of adverse kidney outcomes., Methods: We analyzed data from Optum's deidentified Integrated Claims-Clinical data set of US patients (2007-2019) with ≥1 year of prior medical record data, CKD stages G3 to G5, and metabolic acidosis (i.e., index serum bicarbonate 12 to <22 mmol/l). The primary predictor of interest was the change in serum bicarbonate, evaluated at each postindex outpatient serum bicarbonate test as a time-dependent continuous variable. The primary outcome was a composite of either a ≥40% decline in estimated glomerular filtration rate (eGFR) from index or evidence of dialysis or transplantation, evaluated using Cox proportional hazards models., Results: A total of 24,384 patients were included in the cohort with median follow-up of 3.7 years. A within-patient increase in serum bicarbonate over time was associated with a lower risk of the composite kidney outcome. The unadjusted hazard ratio (HR) per 1-mmol/l increase in serum bicarbonate was 0.911 (95% confidence interval [CI]: 0.905-0.917; P  < 0.001). After adjustment for baseline eGFR and serum bicarbonate, the time-adjusted effect of baseline eGFR and other covariates, the HR per 1-mmol/l increase in serum bicarbonate was largely unchanged (0.916 [95% CI: 0.910-0.922; P  < 0.001])., Conclusion: In a real-world population of US patients with CKD and metabolic acidosis, a within-patient increase in serum bicarbonate over time independent of changes in eGFR, was associated with a lower risk of CKD progression., (© 2023 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Secretion of solutes by the proximal tubules represents an intrinsic kidney function not directly reflected by the glomerular filtration rate (GFR). The early loss of secretory clearance may reflect unrecognized kidney dysfunction, portending future disease progression., Methods: We designed a nested case-control study within the Jackson Heart Study (JHS), a prospective study of African American adults in Mississippi, to associate baseline differences in proximal tubular secretion of 5 endogenously produced solutes with future estimated glomerular rate (eGFR) decline. We matched 127 pairs by creatinine-eGFR, age, diabetes, and sex among the patients who provided a 24-hour urine collection; cases had a ≥25% decline in eGFR compared to <10% in controls over 10 years of follow-up. We measured baseline plasma and urine concentrations of secretory solutes using liquid chromatography-mass spectrometry to determine the odds ratio of kidney disease progression., Results: Mean age was 60 years; 76% were women; 30% had diabetes; mean baseline eGFR was 94±20 ml/min per 1.73 m 2 . The eGFR decline over 10 years was 38±13% in cases and 0±10% in controls. After adjustment for the matching variables plus albuminuria, systolic blood pressure, body mass index, and smoking, each 50% lower kidney clearance of isovalerylglycine, kynurenic acid, and xanthosine were associated with 1.4 to 2.2 greater odds of eGFR decline. Kynurenic acid exhibited the strongest association; each 50% lower clearance of this secretory solute was associated with 2.20-fold higher odds of eGFR decline (95% confidence interval [CI] 1.32-3.67)., Conclusion: We found that in this community-based study of adults without significant kidney disease, lower proximal tubular secretory solute clearance is associated with future eGFR decline., (© 2022 International Society of Nephrology. Published by Elsevier Inc.)

Rationale & Aims: Healthy dietary patterns have been associated with a lower risk of chronic kidney disease (CKD). We aimed to investigate the association of a fully food-based diet quality score assessed by the Lifelines Diet Score (LLDS) with either incident CKD or eGFR decline in the general population., Methods: For this study, data from a prospective general population-based Lifelines cohort in the Northern Netherlands was used. Diet was assessed with a 110-item food frequency questionnaire at baseline. The LLDS, based on international evidence for diet-disease relations at the food group level, was calculated to assess diet quality. For the analysis, the score was divided into tertiles. Logistic regression was performed to evaluate the association of the LLDS at baseline with either incident CKD (eGFR <60 mL/min/1.73 m 2 ) or a ≥20% eGFR decline at the second study visit, adjusted for relevant confounders., Results: A total of 78 346 participants free of CKD at baseline were included. During a mean (SD) follow-up of 3.6 ± 0.9 years, 2071 (2.6%) participants developed CKD and 7611 (9.7%) had a ≥20% eGFR decline. Participants in the highest tertile of LLDS had a lower risk of incident CKD (fully adjusted OR 0.83, [95% CI: 0.72-0.96]) and ≥20% eGFR decline (fully adjusted OR 0.80, [95% CI: 0.75-0.86]), compared with those in the lowest tertile. Similar dose-response associations were observed in continuous LLDS., Conclusions: Higher adherence to a high-quality diet was associated with a lower risk of incident CKD or ≥20% eGFR decline in the general population., Competing Interests: Conflict of interest The authors of this manuscript have no conflicts of interest., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Geographic variation in the prevalence of chronic kidney disease and incidence of end-stage renal disease has been previously reported. However, the geographic epidemiology of rapid estimated glomerular filtration rate (eGFR) decline has not been examined., Methods: We built a longitudinal cohort of 2,107,570 US veterans to characterize the spatial epidemiology of and examine the associations between US county characteristics and rapid eGFR decline., Results: There were 169,029 (8.02%) with rapid eGFR decline (defined as eGFR slope < -5 ml/min per 1.73 m 2 /year). The prevalence of rapid eGFR decline adjusted for age, race, gender, diabetes, and hypertension varied by county from 4.10%-6.72% in the lowest prevalence quintile to 8.41%-22.04% in the highest prevalence quintile ( P for heterogeneity < 0.001). Examination of adjusted prevalence showed substantial geographic variation in those with and without diabetes and those with and without hypertension ( P for heterogeneity < 0.001). Cohort participants had higher odds of rapid eGFR decline when living in counties with unfavorable characteristics in domains including health outcomes (odds ratio [OR] = 1.15; confidence interval [CI] = 1.09-1.22), health behaviors (OR = 1.08; CI = 1.03-1.13), clinical care (OR = 1.11; CI = 1.06-1.16), socioeconomic conditions (OR = 1.15; CI = 1.09-1.22), and physical environment (OR = 1.15; CI = 1.01-1.20); living in counties with high percentage of minorities and immigrants was associated with rapid eGFR decline (OR = 1.25; CI = 1.20-1.31). Spatial analyses suggest the presence of cluster of counties with high prevalence of rapid eGFR decline., Discussion: Our findings show substantial geographic variation in rapid eGFR decline among US veterans; the variation persists in analyses stratified by diabetes and hypertension status; results show associations between US county characteristics in domains capturing health, socioeconomic, environmental, and diversity conditions, and rapid eGFR decline.