Lower Risk Of Chronic Kidney Disease Research Articles

Adherence to a Healthful Plant-Based Diet and Risk of Chronic Kidney Disease Among Individuals with Diabetes

Objective Chronic kidney disease (CKD) is highly prevalent among people with diabetes. While identifying modifiable risk factors to prevent a decline in kidney function among those living with diabetes is pivotal, there is limited evidence on dietary risk factors for CKD. In this study, we examined the associations between healthy and less healthy plant-based diets (PBDs) and the risk of CKD among those with diabetes, and to identify potential underlying mechanisms. Methods We conducted a prospective analysis among 7,747 UK Biobank participants with prevalent diabetes. Multivariable Cox proportional hazard regression models were used to examine the associations between healthful and unhealthful PBDs and the risk of CKD. Causal mediation analyses were further employed to explore the underlying mechanisms of the observed associations. Results Among 7,747 study participants with diabetes, 1,030 developed incident CKD over 10.2 years of follow-up. Higher adherence to a healthy PBD was associated with a 24% lower CKD risk (HRQ4 versus Q1: 0.76 [95%CI: 0.63–0.92], p trend = 0.002), while higher adherence to an unhealthy PBD was associated with a 35% higher risk (HRQ4 versus Q1: 1.35 [95%CI: 1.11–1.65], p trend = 0.006). The observed associations were predominantly mediated by markers of body fatness (proportion mediated: 11–25%) and kidney function (23–89%). Conclusions In this prospective cohort study of middle-aged adults with diabetes, adherence to a healthy PBD was associated with lower CKD risk, whereas adherence to an unhealthy PBD was associated with a higher CKD risk. Associations were primarily mediated by markers of lower body fatness and improved kidney function.

Plant-based diets for kidney disease prevention and treatment.

Plant-based diets are associated with a lower risk of hypertension, diabetes, cardiovascular disease, and mortality. Using the most recent evidence, we critically appraised the role of plant-based diets in primary and secondary prevention of chronic kidney disease (CKD) with a focus on key nutritional factors (dietary acid load, phosphorus, potassium, sodium, and fiber). In healthy individuals, observational studies found that greater intake of plant protein and higher adherence to plant-based diets (overall, healthful, and provegetarian) was associated with a lower risk of CKD. In those with CKD, plant-based diets were associated with a lower risk of mortality, improved kidney function, and favorable metabolic profiles (fibroblast growth factor-23, uremic toxins, insulin sensitivity, inflammatory biomarkers). Only few studies reported nutrient content of plant-based diets. These studies found that plant-based diets had lower dietary acid load, lower or no significant difference in phosphorus and sodium, and higher potassium and fiber. One study reported that vegetarian diets were associated with severe vitamin D deficiency compared to nonvegetarian diets. Plant-based diets provide several benefits for prevention and management of CKD, with little risk for individuals with CKD. Incorporation of vitamin D rich foods in plant-based diets may be helpful.

Associations of accelerometer-measured physical activity and sedentary time with renal function and chronic kidney disease: a national population-based study.

There is limited information about the relationship between physical activity (PA) and sedentary behaviors in chronic kidney disease (CKD). Therefore, this study aims to explore the associations of accelerometer-measured PA and sedentary behaviors with CKD. A cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey in the 2003-2004 and 2005-2006 survey cycles. A uniaxial accelerometer measured physical activity (PA) and sedentary time (ST). The associations of PA and ST with estimated glomerular filtration rate (eGFR) and odds of CKD adopted the generalized linear regression, multivariable logistic regression, and isotemporal substitution models. A total of 5,990 adults with 605 CKD patients were included in this study. Compared with the individuals in the first quartile group, participants in the fourth quartile of low-intensity physical activity (LIPA), moderate to vigorous physical activity (MVPA), and ST were associated with 52% (35%, 65%) and 42% (14%, 62%) lower odds of CKD and 64% (17%, 131%) higher odds of CKD, respectively. Substituting 30 min/day of ST with equivalent LIPA/MVPA contributed to risk reduction in CKD. The findings suggest that increased LIPA and MVPA and reduced ST were associated with a lower risk of CKD and that replacing ST with LIPA may decrease the risk of CKD.

Female reproductive factors, exogenous hormone use, and incident chronic kidney disease and end-stage renal disease.

Younger women have a slower progressive loss of kidney function than age-matched men and the sex advantage diminishes after menopause, suggesting a role for female hormones in the development of kidney diseases. To examine the relationships of numerous reproductive factors and exogenous hormone use with long-term risk of chronic kidney disease (CKD) and end-stage renal disease (ESRD) in women. A total of 260,108 women without prevalent CKD and ESRD were included. The relationships of various reproductive factors and exogenous hormone use with incident CKD and ESRD were assessed, with multivariable adjustment for potential confounders. During a median of ∼12.5 years of follow-up, 8,766 CKD and 554 ESRD cases were identified. Younger age at first live birth, hysterectomy or bilateral oophorectomy before 50 years old, menopausal before 45 years old, and menopausal hormone therapy (MHT) initiated before 50 years old was associated with a higher risk of CKD. The relationships of these factors with ESRD were generally consistent with those for CKD. Each 5-year increment in menopausal age was associated with an 11% lower risk of CKD (HR = 0.89; 95% CI: 0.87, 0.91) and a 13% lower risk of ESRD (HR = 0.87; 95% CI: 0.79, 0.95). Each 5-year delay in starting MHT was associated with a 13% lower risk of CKD (HR = 0.87; 95% CI: 0.84, 0.90) and a 15% lower risk of ESRD (HR = 0.85; 95% CI: 0.73, 0.99). Several reproductive characteristics reflecting shorter cumulative exposure to endogenous estrogen or premature exposure to exogenous hormones are associated with a greater risk of CKD and ESRD in women, supporting a potential role of female hormones in renal pathophysiology.

Blood metabolites and chronic kidney disease: a Mendelian randomization study

BackgroundHuman blood metabolites have demonstrated close associations with chronic kidney disease (CKD) in observational studies. Nonetheless, the causal relationship between metabolites and CKD is still unclear. This study aimed to assess the associations between metabolites and CKD risk.MethodsWe applied a two-sample Mendelian randomization (MR) analysis to evaluate relationships between 1400 blood metabolites and eight phenotypes (outcomes) (CKD, estimated glomerular filtration rate(eGFR), urine albumin to creatinine ratio, rapid progress to CKD, rapid decline of eGFR, membranous nephropathy, immunoglobulin A nephropathy, and diabetic nephropathy). The inverse variance weighted (IVW), MR-Egger, and weighted median were used to investigate the causal relationship. Sensitivity analyses were performed with Cochran’s Q, MR-Egger intercept, MR-PRESSO Global test, and leave-one-out analysis. Bonferroni correction was used to test the strength of the causal relationship.ResultsThrough the MR analysis of 1400 metabolites and eight clinical phenotypes, a total of 48 metabolites were found to be associated with various outcomes. Among them, N-acetylleucine (OR = 0.923, 95%CI: 0.89–0.957, PIVW = 1.450 × 10–5) has a strong causal relationship with lower risk of CKD after the Bonferroni-corrected test, whereas Glycine to alanine ratio has a strong causal relationship with higher risk of CKD (OR = 1.106, 95%CI: 1.063–1.151, PIVW = 5.850 × 10–7). No horizontal pleiotropy and heterogeneity were detected.ConclusionOur study offers groundbreaking insights into the integration of metabolomics and genomics to reveal the pathogenesis of and therapeutic strategies for CKD. It underscores 48 metabolites as potential causal candidates, meriting further investigation.

Possible sarcopenia and risk of chronic kidney disease: a four-year follow-up study and Mendelian randomization analysis

ABSTRACT Introduction Chronic kidney disease (CKD) is a common risk factor for sarcopenia. However, whether sarcopenia increases the risk of CKD remains unclear. To investigate the longitudinal and causal associations between possible sarcopenia and CKD, this study was performed. Methods Possible sarcopenia was defined according to the Asian Working Group for Sarcopenia in 2019. Participants aged ≥ 40 years were recruited from the baseline survey of the China Health and Retirement Longitudinal Study and followed up for four years. Binary logistic regression was used to evaluate the cross-sectional and longitudinal associations between possible sarcopenia, low muscle strength, low physical performance and CKD. Propensity score matching was used to balance the intergroup differences. Subgroup and interactive analyses were adopted to identify potential interactive effects. Mendelian Randomization analysis was used to assess the causal association between appendicular lean mass (ALM) and CKD. Results After data cleansing, a total of 7296 participants were included in the baseline survey. In the cross-sectional analyses, the odds ratios (ORs) of prevalent CKD were 1.50 (95% CI = 1.23–1.84, p < 0.001) for possible sarcopenia, 1.37 (95% CI = 1.10–1.70, p < 0.01) for low muscle strength and 1.42 (95% CI = 1.16–1.74, p < 0.001) for low physical performance in the full models. No significant interaction effects of covariates were detected (all P for interaction > 0.05). After four years of follow-up, an increased risk of incident CKD was also observed in participants with possible sarcopenia (OR = 1.66, 95% CI = 1.13–2.44, p = 0.010) and low physical performance (OR = 1.69, 95% CI = 1.16–2.45, p = 0.006), but not in participants with low muscle strength (OR = 1.19, 95% CI = 0.75–1.88, p = 0.469). In the Mendelian Randomization analysis, the inverse variance weighted estimator showed that a 1-standard deviation increase of genetically predicted ALM was associated with a lower risk of CKD (OR = 0.92, 95% CI = 0.85–0.99, p = 0.035). All the sensitivity analyses supported the main findings. Conclusions Possible sarcopenia is an independent risk factor for CKD and may serve as a predictor of CKD for early identification and intervention.

CHRONIC KIDNEY DISEASE INCIDENCE AND CARDIORESPIRATORY FITNESS ASSOCIATION IN HYPERTENSIVE PATIENTS

Objective: Chronic hypertension (HTN) is considered a strong risk factor for developing chronic kidney disease (CKD). Increased cardiorespiratory fitness (CRF) is associated with lower CKD risk. However, the CRF-CKD association in patients with HTN has not been assessed. Thus, we examined the the association between CRF and the risk of developing CKD in hypertensive patients. Design and method: Hypertensive individuals (n=471,579; age 63.0+8.8 years) with normal kidney function prior to HTN and no evidence of ischemia indicated by a maximal standardized exercise treadmill test (ETT). The cohort was part of the ETHOS study (n=750,302). We established five CRF categories based on age-and-gender-adjusted peak metabolic equivalents (METs) achieved: Least-Fit (4.5±1.2 METs; n=106,955); Low-Fit Fit (6.9±1.1 METs; n=122,612); Moderate-Fit (8.3±1.2 METs; n=91,995); Fit (10.3±1.2 METs; n=111,472); and High-Fit (13.2±1.6 METs; n=38,545). CKD risk across CRF categories was assessed by multivariable Cox Regression analysis, adjusted for age, blood pressure, body mass index (BMI), alcohol abuse, traditional risk factors, and medications. Results: During 6,146,773.0 person-years of follow-up (median 12.9 years), 58,701 individuals developed CKD (9.6 events/1,000 person-years of observation). The CRF-CKD association was inverse, independent of comorbidities and graded. The risk of developing CKD was 9% lower for each 1-MET increase (Hazard Ratio [HR] 0.91; 95% confidence interval [CI] 0.90-0.93). When CKD risk was assessed across CRF categories using the Least-fit category as the referent, the risk was 20% lower (HR 0.80; CI 0.78-0.81, p&lt;0.001) for those in the Low-fit category (6.9±1.1 METs). The risk declined progressively with increased CRF and was 49% lower for those in the highest CRF category (HR 0.49; CI 0.47-0.51, p&lt;0.001). Similar findings were observed in the subgroup of hypertensive patients with diabetes mellitus (n=192,966). Conclusions: We noted an inverse and dose-response association between CRF and CKD incidence. The risk was attenuated significantly beyond a MET level of 6.9±1.1 METs, suggesting that moderate increases in exercise capacity lowers the risk of developing CKD in hypertensive patients.

Abstract 35: Association of SGLT2 Inhibitors and Other Second Line Therapies With Incident Chronic Kidney Disease in Patients With Type 2 Diabetes

Introduction: Type 2 diabetes (T2D) is a strong risk factor for chronic kidney disease (CKD). Clinical trials have shown that intensive glycemic control prevents the development of kidney failure and decreases in eGFR in patients with T2D and CKD. Furthermore, sodium-glucose cotransporter-2 inhibitors (SGLT2i) slow the progression of CKD compared to other glucose lowering medications. However, it’s unknown whether SGLT2 inhibitors reduce the risk of incident CKD. Using data from the US MarketScan administrative databases (2014-21), we assessed the association between use of SGLT2i vs. other 2 nd line therapies and risk of incident CKD among patients with T2D on metformin. Methods: We included 428,814 matched patients with T2D on metformin and a 2 nd line therapy. SGLT2i users were matched with up to 5 other 2 nd line therapy users by age, sex, date of enrollment, and date of 2 nd line therapy initiation. Other 2 nd line therapies included dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sulfonylureas, thiazolidinediones, and insulin. Incident CKD was defined using ICD codes. Those with prevalent CKD were excluded. Cox proportional hazards models were used. Results: Participants were on average age 53±10 years at baseline and 46% were female. Over a median follow-up of 2.0 years, 6,024 patients were diagnosed with CKD. After multivariable adjustments, SGLT2i users had a lower risk of incident CKD than those taking other 2 nd line therapies (Table; HR [95% CI]: 0.43 [0.39-0.47]). When compared to users of each 2 nd line therapy individually, SGLT2i users consistently had a lower risk of CKD. Conclusion: In this analysis using real-world data, among patients with T2D on metformin, SGLT2i use was associated with a lower risk of incident CKD than other 2 nd line diabetes therapies (when assessed as a group and individually). Results from this study may inform clinical guidelines regarding treatment options for those with diabetes at high-risk for CKD.

Abstract P416: Higher Household Income is Protective Against Chronic Kidney Disease Among White but Not Black Adults: An Analysis of 2017-2020 NHANES

Introduction: Chronic kidney disease (CKD) disproportionately affects Black adults in the U.S. Prior work suggests that lower income is a risk factor for CKD among Black but not White adults; however, this has not been examined in a nationally representative population, using the updated, race-free kidney function equation. Objective: To examine the relationship between household income and CKD between Black and White adults. Methods: We used data from the 2017-2020 NHANES. CKD was defined as an estimated glomerular filtration rate (eGFR) &lt; 60 mL/min/1.73m 2 based on the race-free CKD-EPI equation and/or a urine albumin-creatinine ratio &gt;30 mg/g. The poverty income ratio (PIR) (ranging from 0 to ≥5) was reported in NHANES (calculated as a multiple of interviewees self-reported income in dollars as compared to the federal poverty line). We examined the association between PIR and CKD using survey-weighted Poisson regression models, adjusted for age, sex, education, marital status, and medical comorbidities. We also examined how this association differed between Black and White adults aged ≥18 years old in separate subgroup analyses via interaction terms. Results: The weighted sample was 51.7% female, 15.5% Black, and 84.5% White with mean age (±SE) of 47.5±0.3 years. In the total sample, and among White adults, higher household income was associated with a lower prevalence of CKD ( Table ). A one-unit higher PIR was associated with a 11% (95% CI: 5%, 16%) lower prevalence of CKD in the total sample and a 12% (95% CI: 6%, 18%) lower prevalence of CKD among White adults. However, this association was not significant for Black adults. The interaction term for race and income was significant ( P = 0.001). Conclusion: Higher income was associated with a lower risk of CKD among White, but not Black adults. Further work is needed to characterize the complex relationship between socioeconomic status and race to address disparities in CKD.

Serum Metabolomic Markers of Protein-Rich Foods and Incident CKD: Results From the Atherosclerosis Risk in Communities Study

Rationale & ObjectiveWhile urine excretion of nitrogen estimates total protein intake, biomarkers of specific dietary protein sources have been sparsely studied. Using untargeted metabolomics, this study aimed to identify serum metabolomic markers of six protein-rich foods and to examine whether dietary protein-related metabolites are associated with incident chronic kidney disease (CKD). Study DesignProspective cohort study. Setting & Participants3,726 participants from the Atherosclerosis Risk in Communities (ARIC) study without CKD at baseline. ExposureDietary intake of six protein-rich foods (fish, nuts, legumes, red and processed meat, eggs, poultry), serum metabolites. OutcomesIncident CKD [eGFR <60 mL/min/1.73 m2 with ≥25% eGFR decline relative to visit 1, hospitalization or death related to CKD, or end-stage kidney disease. Analytical ApproachMultivariable linear regression models estimated cross-sectional associations between protein-rich foods and serum metabolites. C-statistics assessed the metabolites’ ability to improve discrimination of highest versus lower three quartiles of intake of protein-rich foods beyond covariates (demographics, clinical factors, health behaviors, and intake of nonprotein food groups). Cox regression models identified prospective associations between protein-related metabolites and incident chronic kidney disease (CKD). ResultsThirty significant associations were identified between protein-rich foods and serum metabolites (fish, n=8; nuts, n=5; legumes, n=0; red and processed meat, n=5; eggs, n=3; poultry, n=9). Metabolites collectively significantly improved discrimination of high intake of protein-rich foods compared to covariates alone (difference in C-statistics=0.033, 0.051, 0.003, 0.024, and 0.025 for fish, nuts, red and processed meat, eggs, and poultry-related metabolites, respectively; p<1.00 x 10-16 for all). Dietary intake of fish was positively associated with 1-docosahexaenoylglycerophosphocholine (22:6n3), which was inversely associated with incident CKD (HR 0.82, 95% CI 0.75-0.89, p=7.81×10-6). LimitationsResidual confounding and sample storage duration. ConclusionsWe identified candidate biomarkers of fish, nuts, red and processed meat, eggs, and poultry. A fish-related metabolite, 1-docosahexaenoylglycerophosphocholine (22:6n3), was associated with lower risk of CKD.

Association between questionnaire-based and accelerometer-based physical activity and the incidence of chronic kidney disease using data from UK Biobank: a prospective cohort study

Prior studies on the relationship between chronic kidney disease (CKD) and physical activity (PA) mainly relied on subjective PA data and rarely considered the genetic risk. This study aims to thoroughly investigate this relationship by utilizing both accelerometer-measured and questionnaire-measured PA data. This prospective cohort study encompasses two cohorts from the UK Biobank. The questionnaire-based cohort involves 448,444 CKD-free participants who completed an International Physical Activity Questionnaire between 2006 and 2010 and had genetic data. PA was categorized into distinct activities: leisure, housework, job-related, and transportation. The accelerometer-based cohort involves 89,296 CKD-free participants who provided a full week of accelerometer-based physical activity data between 2013 and 2015 and had genetic data. PA was classified as light-intensity, moderate-intensity, vigorous-intensity, moderate to vigorous-intensity PA (LPA, MPA, VPA, MVPA), and total PA. Incident CKD was ascertained from linked hospital inpatient and death records. Genetic risk was assessed using polygenic risk scores. Cox proportional hazard models with restricted cubic splines were used for the analysis. In the questionnaire-based cohort, 18,184 (4.05%) participants developed CKD during 13.6 years of follow-up. Engaging in strenuous sports, other exercises, walking for pleasure, stair climbing, and heavy DIY were associated with a reduced risk of CKD. In the accelerometer-based cohort, 2297 (2.57%) participants developed CKD during 7.9 years of follow-up. Higher levels [highest quartile vs lowest quartile] of MPA (HR 0.639, 95% CI 0.554-0.737), VPA (HR 0.639, 95% CI 0.549-0.745), MVPA (HR 0.630, 95% CI 0.545-0.729), and total PA (HR 0.649, 95% CI 0.563-0.750) were associated with a lower CKD risk. There were significant interactions between MPA and genetic risk on the risk of CKD incidence (P for interaction=0.025). A linear dose-response relationship was observed between MPA, total PA, and the risk of CKD incidence with no minimal or maximal threshold. These associations are robust in different subgroups and a series of sensitivity analyses. Engaging in multiple types of PA and higher levels of total PA, MPA, VPA, and MVPA may be associated with a lower risk of developing CKD, regardless of genetic risk. This finding holds substantial implications for clinical approaches to CKD prevention and provides evidence to inform future PA guideline development. Medical Science Advancement Program of Wuhan University, and the National Science Foundation of China.

Association between Fiber Intake and Risk of Incident Chronic Kidney Disease: The UK Biobank Study.

Dietary fiber intake is associated with a lower risk of diabetes, cardiovascular disease, and cancer. However, it is unknown whether dietary fiber has a beneficial effect on preventing the development of chronic kidney disease (CKD). Using the UK Biobank prospective cohort, 110,412 participants who completed at least one dietary questionnaire and had an estimated glomerular filtration rate ≥60 mL/min/1.73 m2, urinary albumin-to-creatinine ratio <30 mg/g, and no history of CKD were included. The primary exposure was total dietary fiber density, calculated by dividing the absolute amount of daily total fiber intake by total energy intake (g/1,000 kcal). We separately examined soluble and insoluble fiber densities as additional predictors. The primary outcome was incident CKD based on diagnosis codes. A total of 3,507 (3.2%) participants developed incident CKD during a median follow-up of 9.9 years. In a multivariable cause-specific model, the adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for incident CKD were 0.85 (0.77-0.94), 0.78 (0.70-0.86), and 0.76 (0.68-0.86), respectively, for the second, third, and highest quartiles of dietary fiber density (reference: lowest quartile). In a continuous model, the aHR for each +∆1.0g/1,000 kcal increase in dietary fiber density was 0.97 (95% CI, 0.95-0.99). This pattern of associations was similar for both soluble and insoluble fiber densities and did not differ across subgroups of sex, age, body mass index, hypertension, diabetes, smoking, and inflammation. Increased fiber intake was associated with a lower risk of CKD in this large well-characterized cohort.

Adherence to healthy lifestyle was associated with an attenuation of the risk of chronic kidney disease from metabolic dysfunction–associated fatty liver disease: Results from two prospective cohorts

AimsNon-alcoholic fatty liver disease (NAFLD) and metabolic dysfunction–associated fatty liver disease (MAFLD) are important risk factors of chronic kidney disease (CKD). Whether adherence to a healthy lifestyle can modify these effects remain unknown. This study aimed to evaluate the modification effects of healthy lifestyle on the associations among NAFLD, MAFLD, and the risk of CKD, with taking into the effect of genetic risk. MethodsThe Tianjin Chronic Low-grade Systemic Inflammation and Health Cohort Study (TCLSIH), the UK Biobank Study (UKB). The outcome was incident CKD. The exposures including NAFLD, MAFLD, healthy lifestyle, and a genetic risk score (GRS) for CKD. ResultsAfter 1,135,334 person–year follow-up, we documented 2975 incident CKD cases in the two cohorts. MAFLD and NAFLD were associated with a higher risk of CKD, particularly in patients with MAFLD. In the TCLSIH and UKB, the hazard ratios (95% confidence intervals) of incident CKD for MAFLD were 1.47 (1.30, 1.66) and 1.73 (1.57, 1.91), respectively. Adherence to a healthier lifestyle decreased the risk of CKD from MAFLD with significant interaction effects (TCLSIH: Pinteraction = 0.02; UKB: Pinteraction = 0.04). Participants with a lower CKD–GRS experienced a higher risk of CKD from MAFLD, but achieved two healthy lifestyles can significantly decreased the risk of CKD in patients with MAFLD. ConclusionsMAFLD and NAFLD are associated with a higher CKD risk, particularly MAFLD. Adherence to a healthier lifestyle was associated with a lower risk of CKD from MAFLD. These results highlight the important role of following a healthy lifestyle to prevent CKD.

Nuclear Magnetic Resonance–Based Metabolomics and Risk of CKD

Chronic kidney disease (CKD) leads to lipid and metabolic abnormalities, but a comprehensive investigation of lipids, lipoprotein particles, and circulating metabolites associated with the risk of CKD has been lacking. We examined the associations of nuclear magnetic resonance (NMR)-based metabolomics data with CKD risk in the UK Biobank study. Observational cohort study. A total of 91,532 participants in the UK Biobank Study without CKD and not receiving lipid-lowering therapy. Levels of metabolites including lipid concentration and composition within 14 lipoprotein subclasses, as well as other metabolic biomarkers were quantified via NMR spectroscopy. Incident CKD identified using ICD codes in any primary care data, hospital admission records, or death register records. Cox proportional hazards regression models were used to estimate hazard ratios and 95% confidence intervals. We identified 2,269 CKD cases over a median follow-up period of 13.1 years via linkage with the electronic health records. After adjusting for covariates and correcting for multiple testing, 90 of 142 biomarkers were significantly associated with incident CKD. In general, higher concentrations of very-low-density lipoprotein (VLDL) particles were associated with a higher risk of CKD whereas higher concentrations of high-density lipoprotein (HDL) particles were associated with a lower risk of CKD. Higher concentrations of cholesterol, phospholipids, and total lipids within VLDL were associated with a higher risk of CKD, whereas within HDL they were associated with a lower risk of CKD. Further, higher triglyceride levels within all lipoprotein subclasses, including all HDL particles, were associated with greater risk of CKD. We also identified that several amino acids, fatty acids, and inflammatory biomarkers were associated with risk of CKD. Potential underreporting of CKD cases because of case identification via electronic health records. Our findings highlight multiple known and novel pathways linking circulating metabolites to the risk of CKD. The relationship between individual lipoprotein particle subclasses and lipid-related traits and risk of chronic kidney disease (CKD) in general population is unclear. Using data from 91,532 participants in the UK Biobank, we evaluated the associations of metabolites measured using nuclear magnetic resonance testing with the risk of CKD. We identified that 90 out of 142 lipid biomarkers were significantly associated with incident CKD. We found that very-low-density lipoproteins, high-density lipoproteins, the lipid concentration and composition within these lipoproteins, triglycerides within all the lipoprotein subclasses, fatty acids, amino acids, and inflammation biomarkers were associated with CKD risk. These findings advance our knowledge about mechanistic pathways that may contribute to the development of CKD.

Association of mitochondrial DNA copy number with chronic kidney disease in older adults

BackgroundMitochondrial dysfunction in kidney cells has been implicated in the pathogenesis of chronic kidney disease (CKD). Estimation of mitochondrial DNA copy number (mtDNA-CN) is considered a convenient method for representing mitochondrial function in large samples. However, no study has investigated the association between mtDNA-CN and CKD in older adults with the highest prevalence. The objective is to examine cross-sectional and prospective associations between mtDNA-CN values and CKD risk in older adults to determine whether mtDNA-CN represents a novel potential biomarker for the recognition of CKD risk.Patients and methodsIn a Chinese community-based cohort of over 65-year-olds, we included 14,467 participants (52.6% females). CKD was defined by eGFR < 60 mL/min/1.73 m2 or ICD-10 codes (patients = 3831 (26.5%)). Participants had peripheral blood levels of mtDNA-CN calculated from probe intensities of the Axiom CAS Array.ResultsThe risk of CKD prevalence decreased with mtDNA-CN per 1-SD increment, independent of established risk factors for older CKD (odds ratio [OR] per SD 0.90, 95% confidence interval [CI] 0.86, 0.93, P < 0.001), and has comparable strength of association with these established risk factors. Furthermore, the progression of kidney function was stratified according to the worsening of eGFR categories. The risk of kidney function progression to a more severe stage gradually decreased as the mtDNA-CN increased (P trend < 0.001). Non-CKD participants in the highest quartile of mtDNA-CN had a lower risk of developing CKD compared to the lowest quartile within 2 years of follow-up, reducing the risk of CKD by 36% (95% CI 0.42, 0.97; P = 0.037).ConclusionsBased on the analysis of the largest sample to date investigating the association between mtDNA-CN and CKD in older adults, higher levels of mtDNA-CN were found to be associated with a lower risk of CKD, suggesting that a reduced level of mtDNA-CN is a potential risk factor for CKD.

Adherence to Life’s Essential 8 and incident chronic kidney disease: a prospective study of 147,988 UK Biobank participants

BackgroundThe American Heart Association recently updated Life’s Essential 8 (LE8) score. This amalgamation of health factors, recognized for their individual associations with chronic kidney disease (CKD) risk, provides a robust tool to assess overall cardiovascular health (CVH), which could potentially be extrapolated to predict CKD risk. ObjectivesThis study aimed to investigate the association between levels of CVH, as measured by the LE8 score, and risk of CKD in the UK Biobank. MethodsA total of 147,988 participants free of CKD and cardiovascular disease from the UK Biobank were included in this prospective study. CVH levels were categorized as low (0–49), moderate (50–79), and high (80–100) using LE8 score. An adjusted Cox proportional hazard model was used to investigate the association between LE8 and CKD. The population attributable-risk (PAR) was also calculated. ResultsDuring a median follow-up of 10 y, 1936 CKD cases were documented. A higher LE8 score was associated with a significant lower risk of CKD (P < 0.001), and a linear dose–response relationship was observed. Similar patterns were also found in the associations of the LE8 behavior and biological subscale scores with CKD. Compared with participants with a low CVH category, participants with a moderate CVH were associated with a 39% lower risk of developing CKD (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.52, 0.72); and those with a high CVH had a 57% lower risk of CKD incidence (HR: 0.43; 95% CI: 0.35, 0.53) after adjustment for covariates. Among 8 distinct metrics of LE8 score, the BMI metric had the highest PAR (24.6%; 95% CI: 18.8, 30.2). Of the total CKD risk, 3.2% (95% CI: 1.4, 5.0) was attributable to inadequate or excessive sleep duration. ConclusionsHigh CVH, defined by LE8, is significantly associated with a lower risk of CKD. These results suggest that promoting optimal cardiovascular health may lower the burden of CKD.

Life’s Essential 8 and Mortality in US Adults with Chronic Kidney Disease

Introduction: The current prevalence of chronic kidney disease (CKD) is substantial, and CKD individuals face a heightened risk of mortality, encompassing both all-cause and cause-specific outcomes. The current study aims to investigate the potential impact of adhering to Life’s Essential 8 (LE8) on reducing mortality among CKD individuals. Methods: Using the National Health and Nutrition Survey (NHANES) data from 2005 to 2018, we analyzed 22,420 US adults (≥20 years old). CKD is defined by urinary albumin-to-creatinine ratio (≥30 mg/g or 3 mg/mmol) and estimated glomerular filtration rate (<60 mL/min/1.73 m²). The components of LE8, including diet, physical activity (PA), nicotine exposure, sleep, body mass index, blood lipids, blood glucose, and blood pressure (BP), were measured and given a score of 0–100. The total LE8 score was the unweighted average of all components and was divided into low cardiovascular health (CVH) (0–49), moderate CVH (50–79), and high CVH (80–100). A Cox proportional hazards regression model was used to explore the associations of LE8 with all-cause, cardiovascular disease (CVD), and cancer mortality, which were followed prospectively by the National Center for Health Statistics until December 31, 2019. Results: In the overall population, individuals with moderate CVH had a 47% lower risk of CKD, while high CVH was linked to a 55% lower risk compared to low CVH. During a median follow-up of 7.58 years, CKD individuals had a 93% higher all-cause mortality rate and a 149% higher CVD mortality rate compared to those without CKD. Among the CKD individuals, every 10-point increase in the LE8 score was associated with reduced risks of 17% for all-cause mortality (especially PA, nicotine exposure, blood glucose, and BP), 18% for CVD mortality (especially PA), and 12% for cancer mortality (especially PA and sleep health). In additional and sensitivity analysis, the results remained significant after further consideration of potential confounding of renal function. Additionally, LE8 demonstrated superior risk stratification for CVD mortality among CKD patients compared with LS7. Interaction was observed between LE8 and age, education level, marital status, and drinking status. Conclusion: The current study demonstrates that adherence to higher LE8 levels within CKD individuals is associated with a reduced risk of both all-cause and cause-specific mortality.

#4318 ASSOCIATION OF PLANT PROTEIN INTAKE AND RISK OF INCIDENT CHRONIC KIDNEY DISEASE: THE UK BIOBANK STUDY

Abstract Background and Aims Dietary intake from various protein sources can affect health differently. However, the association between plant protein intake and incident chronic kidney disease (CKD) is uncertain. Method Using the UK Biobank prospective cohort, we included 117,809 participants who completed more than one dietary questionnaire and had an estimated glomerular filtration rate (eGFR) ≥60 ml/min/1.73 m2, urinary albumin-to-creatinine ratio (UACR) &amp;lt;30 mg/g, and no prior history of CKD. The main predictor was the daily plant protein intake, assessed with a web-based 24-hour recall questionnaire. The primary outcome was incident CKD, based on the International Classification of Diseases, 10th Revision (ICD-10) or Office of Population Censuses and Surveys Classification of Interventions and Procedures, version 4 (OPCS-4) codes. We additionally analyzed this association in 37,955 participants with primary care-linked data for eGFR and UACR. We used strictly defined CKD based on ICD-10 and OPCS-4 codes or two consecutive measures of eGFR &amp;lt;60 ml/min/1.73 m2 or UACR &amp;gt;30 mg/g. Results During the median follow-up of 9.9 years, incident CKD occurred in 3745 (3.2%) participants (incidence rate, 3.2 per 1,000 person-years). In a multivariable cause-specific model, the adjusted hazard ratios (aHRs; 95% confidence intervals [CIs]) for the second, third, and highest quartiles were 0.91 (0.83-0.99), 0.79 (0.71-0.87), and 0.75 (0.64-0.85), respectively, compared with the lowest quartile. In a continuous model, the aHR (95% CIs) per 0.1 g/kg/day increase in plant protein intake was 0.91 (0.88-0.94). This beneficial association was also consistent in the secondary analysis with strictly defined CKD and various sensitivity analyses. Conclusion This large prospective cohort study showed that increased dietary plant protein intake was associated with a lower risk of CKD.

Environmental exposure to perchlorate, nitrate, and thiocyanate in relation to chronic kidney disease in the general US population, NHANES 2005-2016.

Few studies have explored the impact of perchlorate, nitrate, and thiocyanate (PNT) on kidney function. This study aimed to evaluate the association of urinary levels of PNT with renal function as well as the prevalence of chronic kidney disease (CKD) among the general population in the United States. This analysis included data from 13,373 adults (≥20 years) from the National Health and Nutrition Examination Survey 2005 to 2016. We used multivariable linear and logistic regression, to explore the associations of urinary PNT with kidney function. Restricted cubic splines were used to assess the potentially non-linear relationships between PNT exposure and outcomes. After traditional creatinine adjustment, perchlorate (P-traditional) was positively associated with estimated glomerular filtration rate (eGFR) (adjusted β: 2.75; 95% confidence interval [CI]: 2.25 to 3.26; P < 0.001), and negatively associated with urinary albumin-to-creatinine ratio (ACR) (adjusted β: -0.05; 95% CI: -0.07 to -0.02; P = 0.001) in adjusted models. After both traditional and covariate-adjusted creatinine adjustment, urinary nitrate and thiocyanate were positively associated with eGFR (all P values <0.05), and negatively associated with ACR (all P values <0.05); higher nitrate or thiocyanate was associated with a lower risk of CKD (all P values <0.001). Moreover, there were L-shaped non-linear associations between nitrate, thiocyanate, and outcomes. In the adjusted models, for quartiles of PNT, statistically significant dose-response associations were observed in most relationships. Most results were consistent in the stratified and sensitivity analyses. Exposures to PNT might be associated with kidney function, indicating a potential beneficial effect of environmental PNT exposure (especially nitrate and thiocyanate) on the human kidney.

Vegan Diet Is Associated with a Lower Risk of Chronic Kidney Disease in Patients with Hyperuricemia

Hyperuricemia is a well-known risk factor for chronic kidney disease (CKD). Little is known about whether a vegetarian diet is associated with a lower risk of CKD in patients with hyperuricemia. From 5 September 2005, to 31 December 2016, we retrospectively included clinically stable patients with hyperuricemia who received health check-ups at Taipei Tzu Chi Hospital. All participants completed a dietary habits questionnaire to determine whether they were omnivorous, lacto-ovo vegetarian, or vegan. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2 or the presence of proteinuria. A total of 3618 patients with hyperuricemia were recruited for this cross-sectional study, consisting of 225 vegans, 509 lacto-ovo vegetarians, and 2884 omnivores. After adjusting for age and sex, vegans had a significantly lower odds ratio (OR) of CKD than omnivores (OR, 0.62; p = 0.006). The OR of CKD remained significantly lower in vegans after adjusting for additional confounders (OR, 0.69; p = 0.04). Additionally, age (per year OR, 1.06; p < 0.001), diabetes mellitus (OR, 2.12; p < 0.001), hypertension (OR, 1.73; p < 0.001), obesity (OR, 1.24; p = 0.02), smoking (OR, 2.05; p < 0.001), and very high uric acid levels (OR, 2.08; p < 0.001) were independent risk factors for CKD in patients with hyperuricemia. Moreover, structural equation modeling revealed that a vegan diet was associated with a lower OR of CKD (OR, 0.69; p < 0.05). A vegan diet is associated with a 31% lower risk of CKD in patients with hyperuricemia. A vegan diet may be beneficial in reducing the occurrence of CKD in patients with hyperuricemia.