Higher Risk Of Incident Chronic Kidney Disease Research Articles

Abstract P421: Smoking Timing, Healthy Diet, and Risk of Incident CKD Among Smokers: A Cohort Study in UK Biobank

Introduction: While smoking is a recognized risk factor for chronic kidney disease (CKD), the relationship between the smoking timing and CKD remains largely unstudied. Hypothesis: We assessed the hypothesis that there is an association between the smoking timing and the risk of CKD. Method: A total of 32,776 participants with complete data on the time from waking to the first cigarette and free of prevalent CKD from UK Biobank were included in this prospective study. The Cox proportional hazard model was used to investigate the associations between smoking timing and risk of CKD. The potential interactions of smoking timing with risk factors in relation to CKD risk were assessed on both multiplicative and additive scales. Results: During a median follow-up of 12 years, 940 incident CKD cases were reported. Shorter time from waking to the first cigarette was significantly associated with a higher risk of incident CKD ( P -trend=0.012). The adjusted hazard ratio (HR) associated with smoking timing was 1.28 (95% CI: 0.92-1.80) for 61-120 minutes, 1.48 (95% CI: 1.11-1.96) for 30-60 minutes, 1.36 (95% CI: 1.01-1.88) for 5-15 minutes, and 1.70 (95% CI: 1.22-2.37) for <5 minutes, respectively. Those who smoke within 5 minutes of waking had a 70% increased risk of CKD incident compared to those who delayed for over 120 minutes. Furthermore, there was a significant positive additive interaction between the timing of smoking and a healthy diet score ( P for additive interaction=0.01). Conclusion: Our findings indicate a significant association between the shorter time from waking to the first cigarette and a higher CKD risk; and the associations are exacerbated in the presence of an unhealthy diet.

Association of ketone bodies with incident CKD and death: A UK Biobank study

AimsAlthough cellular and animal models have suggested a protective effect of ketone bodies (KBs), clinical data are still lacking to support these findings. This study aimed to investigate the association of KB levels with incident chronic kidney disease (CKD) and death. MethodsThis was a prospective cohort study of 87,899 UK Biobank participants without baseline CKD who had plasma levels of β-hydroxybutyrate, acetoacetate, and acetone levels measured at the time of enrollment. The main predictor was plasma total KB, which was the sum of the aforementioned three KBs. The primary outcome was a composite of incident CKD, or all-cause mortality. Secondary outcomes included the individual components of the primary outcome. ResultsDuring a median follow-up of 11.9 years, a total of 8,145 primary outcome events occurred (incidence rate 8.0/1,000 person-years). In the multivariable Cox model, a 1-standard deviation increase in log total KB was associated with a 7 % [adjusted hazard ratio (aHR), 1.07; 95 % confidence interval (CI), 1.05–1.10] higher risk of the primary outcome. When stratified into quartiles, the aHR (95 % CI) for Q4 versus Q1 was 1.18 (1.11–1.27). This association was consistent for incident CKD (aHR, 1.04; 95 % CI, 1.01–1.07), and all-cause mortality (aHR, 1.10; 95 % CI, 1.07–1.13). Compared with Q1, Q4 was associated with a 12 % (aHR 1.12; 95 % CI 1.02–1.24) and 26 % (aHR 1.26; 95 % CI 1.15–1.37) higher risk of incident CKD and all-cause mortality, respectively. ConclusionsHigher KB levels were independently associated with higher risk of incident CKD and death.

Sweetened Beverage Intake and Incident Chronic Kidney Disease in the UK Biobank Study

An increasing body of evidence indicates an association between consuming sugar or its alternatives and cardiometabolic diseases. However, the effects of the consumption of sugar-sweetened beverages, artificially sweetened beverages, and natural juices on kidney health remain unclear. To investigate the association of the intake of sugar-sweetened beverages, artificially sweetened beverages, and natural juices with the risk of chronic kidney disease (CKD), and the effect of substituting these beverage types for one another on this association. This prospective, population-based cohort study analyzed data from the UK Biobank. Participants without a history of CKD who completed at least 1 dietary questionnaire were included. The follow-up period was from the date of the last dietary questionnaire until October 31, 2022, in England; July 31, 2021, in Scotland; and February 28, 2018, in Wales. Data were analyzed from May 1 to August 1, 2023. Consumption of sugar-sweetened beverages, artificially sweetened beverages, and natural juices. The primary outcome was incident CKD. Multivariable Cox proportional hazards models were used to estimate the associations between the 3 beverage types and incident CKD. A substitution analysis was used to evaluate the effect on the associations of substituting one beverage type for another. A total of 127 830 participants (mean [SD] age, 55.2 [8.0] years; 66 180 female [51.8%]) were included in the primary analysis. During a median (IQR) follow-up of 10.5 (10.4-11.2) years, 4459 (3.5%) cases of incident CKD occurred. The consumption of more than 1 serving per day of sugar-sweetened beverages was associated with higher risk of incident CKD (adjusted hazard ratio [AHR], 1.19 [95% CI, 1.05-1.34]) compared with not consuming sugar-sweetened beverages. The AHR for participants consuming more than 0 to 1 serving per day of artificially sweetened beverages was 1.10 (95% CI, 1.01-1.20) and for consuming more than 1 serving per day was 1.26 (95% CI, 1.12-1.43) compared with consuming no artificially sweetened beverages. By contrast, there was no significant association between natural juice intake and incident CKD (eg, for >1 serving per day: HR, 0.99 [95% CI, 0.87-1.11]; P = .10). Substituting sugar-sweetened beverages with artificially sweetened beverages did not show any significant difference in the risk of CKD (HR, 1.03 [95% CI, 0.96-1.10]). Conversely, replacing 1 serving per day of sugar-sweetened beverage with natural juice (HR, 0.93 [95% CI, 0.87-0.97]) or water (HR, 0.93 [95% CI, 0.88-0.99]) or replacing 1 serving per day of artificially sweetened beverage with natural juice (HR, 0.90 [95% CI, 0.84-0.96]) or water (HR, 0.91 [95% CI, 0.86-0.96]) was associated with a reduced risk of incident CKD. Findings from this cohort study suggest that lower consumption of sugar-sweetened beverages or artificially sweetened beverages may reduce the risk of developing CKD.

Risk of incident chronic kidney disease among patients with urolithiasis: a nationwide longitudinal cohort study.

Urolithiasis has been infrequently implicated to have a causal association with chronic kidney disease (CKD). Recently, several studies have demonstrated the relationship between urolithiasis and CKD. However, the generalizability of their results is limited. This study aimed to investigate the association between urolithiasis and the risk of incident CKD. This longitudinal cohort study used the National Health Insurance Service data, including 219570 Korean adults with incident urolithiasis requiring procedural interventions and without prior kidney disease and 219570 age- and sex-matched controls without urolithiasis between 1 January 2002 and 31 December 2020. Primary outcome was the development of CKD, defined by an estimated glomerular filtration rate <60ml/min/1.73m2 for at least two consecutive measurements at least 90days apart. The risk for incident CKD was further examined using the outcome defined by newly occurring diagnostic codes indicating CKD. Over a mean follow-up of 6years, 12338 (2.8%) primary outcome events of CKD were observed (incidence rate 4.6/1000 person-years). Per multivariable Cox analysis, urolithiasis was associated with a higher risk of incident CKD [adjusted hazard ratio 1.41 (95% confidence interval 1.36-1.46)]. This association remained consistent across all clinically relevant subgroups and when the CKD outcome was defined based on the diagnostic codes in the sensitivity analysis. In this large national cohort study, patients with urolithiasis were associated with a higher risk of incident CKD than those without urolithiasis. Further studies are warranted to establish the benefits of preventing urolithiasis in reducing CKD development.

Functional gastrointestinal disorders, mental health, genetic susceptibility, and incident chronic kidney disease.

Whether functional gastrointestinal disorders (FGIDs) are associated with the long-term risk of chronic kidney disease (CKD) remains unclear. We aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the association. About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were included. Participants with FGIDs (including irritable bowel syndrome [IBS], dyspepsia, and other functional intestinal disorders [FIDs; mainly composed of constipation]) were the exposure group, and non-FGID participants were the non-exposure group. The primary outcome was incident CKD, ascertained from hospital admission and death registry records. A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD, and the mediation analysis was performed to investigate the mediation proportions of mental health. At baseline, 33,156 (8.0%) participants were diagnosed with FGIDs, including 21,060 (5.1%), 8262 (2.0%), and 6437 (1.6%) cases of IBS, dyspepsia, and other FIDs, respectively. During a mean follow-up period of 12.1 years, 11,001 (2.6%) participants developed CKD. FGIDs were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.28-1.44). Similar results were observed for IBS (HR, 1.27; 95% CI, 1.17-1.38), dyspepsia (HR, 1.30; 95% CI, 1.17-1.44), and other FIDs (HR, 1.60; 95% CI, 1.43-1.79). Mediation analyses suggested that the mental health score significantly mediated 9.05% of the association of FGIDs with incident CKD and 5.63-13.97% of the associations of FGID subtypes with CKD. Specifically, the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of CKD. Participants with FGIDs had a higher risk of incident CKD, which was partly explained by mental health scores and was more pronounced in those with high genetic susceptibility to CKD.

Serum Urate and Risk of Chronic Kidney Disease: A Mendelian Randomization Study Using Taiwan Biobank

ObjectiveTo evaluate the association between serum urate and risk of incident chronic kidney disease (CKD) and to assess whether serum urate plays a causal role in CKD. Patients and MethodsWe conducted a prospective cohort study and Mendelian randomization analysis that analyzed longitudinal data from the Taiwan Biobank between January 1, 2012, and December 31, 2021. ResultsA total of 34,831 individuals met the inclusion criteria, of which 4697 (13.5%) had hyperuricemia. After a median (interquartile range) follow-up of 4.1 (3.1-4.9) years, 429 participants developed CKD. After adjustment for age, sex, and comorbid conditions, each mg/dL increase in serum urate was associated with a 15% higher risk of incident CKD (HR, 1.15; 95% CI, 1.08 to 1.24; P<.001). The genetic risk score and seven Mendelian randomization methods revealed no significant association between serum urate levels and the risk of incident CKD (HR, 1.03; 95% CI, 0.72 to 1.46; P=0.89; all P>.05 for 7 Mendelian randomization methods). ConclusionThis prospective, population-based cohort study showed that elevated serum urate is a significant risk factor for incident CKD; however, Mendelian randomization analyses failed to provide evidence that serum urate had a causal effect on CKD in the East Asian population.

Abstract P536: The Association Between Arterial Stiffness and Incident Chronic Kidney Disease in a Large Community Cohort: The Atherosclerosis in Communities (ARIC) Study

Background: Arterial stiffness was cross-sectionally associated with the prevalence of chronic kidney disease (CKD). Whether arterial stiffness was prospectively associated with incident CKD is not well characterized. Methods: Among 3,777 participants (mean age 75 years old, 42.7% female, 21.3% Blacks) without prevalent CKD in ARIC study at visit 5 (2011 to 2013), we examined the association of six measures for arterial stiffness measurements, carotid-femoral pulse wave velocity (cfPWV), heart-ankle PWV (haPWV), brachial-ankle PWV (baPWV), heart-femoral PWV (hfPWV), femoral-ankle PWV (faPWV), heart-carotid PWV (hcPWV) with the risk of incident CKD (defined by &gt;25% decline to estimated glomerular filtration rate &lt;60 ml/min/1.73m 2 or hospitalization with CKD diagnosis) using Cox regression models to estimate hazard ratios (HRs). Each arterial stiffness parameter was stratified by quartiles. Results: During follow-up (median 6.6 years) through 2019, 590 had incident CKD (incidence rate 23.2 per 1000 person-years). In the demographically adjusted model, the highest quartile (Q4) of cfPWV, haPWV, baPWV, and hfPWV were significantly associated with an increased risk of incident CKD compared to the lowest (Q1) (HR, 1.70 [95%CI 1.31 to 2.22], 1.29 [95% CI 1.01 to 1.64], 1.51 [95% CI 1.16 to 1.97], and 1.36 [95% CI 1.05 to 1.76], respectively). Once the model was further adjusted for major clinical risk factors for CKD, the associations were modestly attenuated but remained significant for cfPWV and haPWV (HR in Q4 vs. Q1, 1.34 [95% CI 1.02 to 1.76] and 1.38 [95% CI 1.04 to 1.82]), but not for baPWV and hfPWV. Subgroup analyses showed the associations were consistent in subgroups by gender, race, age, hypertension, and diabetes. Conclusion: Arterial stiffness as measured by PWV was associated with a higher risk of incident CKD in older adults, especially cfPWV and haPWV. Our findings support the temporal relationship of subclinical arterial stiffness predating incident CKD in older adults.

Risk Factors for Incident CKD in Black and White Americans: The REGARDS Study

Little information exists on the incidence of and risk factors for chronic kidney disease (CKD) in contemporary US cohorts and whether risk factors differ by race, sex, or region in the United States. Observational cohort study. 4,198 Black and 7,799White participants aged at least 45years, recruited from 2003 through 2007across the continental United States,with baseline estimated glomerular filtration rate (eGFR)>60mL/min/1.73m2 and eGFRassessed again approximately 9 years later. Age, sex, race (Black or White), region ("stroke belt" or other), education, income, systolic blood pressure, body mass index, diabetes, coronary heart disease, hyperlipidemia, smoking, and albuminuria. (1) eGFR change and (2) incident CKD defined as eGFR<60mL/min/1.73m2 and≥40% decrease from baseline or kidney failure. Linear regression and modified Poisson regression were used to determine the association of risk factors with eGFR change and incident CKD overall and stratified by race, sex, and region. Mean age of participants was 63±8 (SD) years, 54% were female, and 35% were Black. After 9.4±1.0 years of follow-up, CKD developed in 9%. In an age-, sex-, and race-adjusted model, Black race (β=-0.13; P<0.001) was associated with higher risk of eGFR change, but this was attenuated in the fully adjusted model (β=0.02; P=0.5). Stroke belt residence was independently associated with eGFR change (β=-0.10; P<0.001) and incident CKD (relative risk, 1.14 [95% CI, 1.01-1.30]). Albuminuria was more strongly associated with eGFR change (β of-0.26 vs-0.17; P=0.01 for interaction) in Black compared with White participants. Results were similar for incident CKD. Persons of Hispanic ethnicity were excluded; unknown duration and/or severity of risk factors. Established CKD risk factors accounted for higher risk of incident CKD in Black versus White individuals. Albuminuria was a stronger risk factor for eGFR decrease and incident CKD in Black compared with White individuals. Living in the US stroke belt is a novel risk factor for CKD.

Abstract 13248: The Association of Serial Measures of Plasma Trimethylamine N-Oxide With Incident Chronic Kidney Disease and Renal Function Decline Among Older Adults: The Cardiovascular Health Study

Introduction: Trimethylamine N-oxide (TMAO) is a gut microbiota-derived metabolite of dietary phosphatidylcholine and carnitine. Experimentally, TMAO causes renal tubulointerstitial fibrosis and kidney injury. Yet, little is known about prospective associations between TMAO and renal outcomes. Hypothesis: Higher plasma TMAO levels are prospectively associated with higher risk of incident chronic kidney disease (CKD) and greater renal function decline. Methods: We included 4,131 US adults from the Cardiovascular Health Study, a community-based cohort, with normal baseline renal function (estimated glomerular filtration rate [eGFR] ≥ 60 mL/min/1.73m 2 ). TMAO was measured using liquid chromatography-mass spectrometry at baseline and year 7. Creatinine and Cystatin C were measured 4 times during serial follow-up and used to compute eGFR. Incident CKD was defined by eGFR (decline ≥ 30% plus eGFR&lt;60 at a follow-up visit) or presence of CKD hospitalization ICD codes. Time-varying Cox models assessed how serial TMAO measures related to incident CKD, adjusting for sociodemographic, lifestyle, diet, and CVD risk factors. Linear regression models assessed how baseline TMAO related to annualized eGFR change in 3,997 participants with at least one follow-up eGFR measure. Results: During a median follow-up of 14 years, 1,136 participants developed CKD. There was a non-linear dose-response relationship of TMAO with CKD incidence: higher TMAO levels were associated with higher risk of incident CKD with a plateauing of risk above the ~75 th percentile of TMAO levels (top Figure ). Higher baseline TMAO levels were also associated with greater annualized eGFR decline (P-linearity=0.004. bottom Figure ) after adjusting for baseline eGFR and other covariates. Conclusions: In this community-based cohort of older US adults, higher serial measures of plasma TMAO were associated with a higher risk of incident CKD and a greater rate of annualized renal function decline.

Nonalcoholic Fatty Liver Disease and Chronic Kidney Disease: Epidemiology, Pathogenesis, and Clinical and Research Implications.

Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease worldwide, affecting up to ~30% of adult populations. NAFLD defines a spectrum of progressive liver conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma, which often occur in close and bidirectional associations with metabolic disorders. Chronic kidney disease (CKD) is characterized by anatomic and/or functional renal damage, ultimately resulting in a reduced glomerular filtration rate. The physiological axis linking the liver and kidneys often passes unnoticed until clinically significant portal hypertension, as a major complication of cirrhosis, becomes apparent in the form of ascites, refractory ascites, or hepatorenal syndrome. However, the extensive evidence accumulated since 2008 indicates that noncirrhotic NAFLD is associated with a higher risk of incident CKD, independent of obesity, type 2 diabetes, and other common renal risk factors. In addition, subclinical portal hypertension has been demonstrated to occur in noncirrhotic NAFLD, with a potential adverse impact on renal vasoregulation. However, the mechanisms underlying this association remain unexplored to a substantial extent. With this background, in this review we discuss the current evidence showing a strong association between NAFLD and the risk of CKD, and the putative biological mechanisms underpinning this association. We also discuss in depth the potential pathogenic role of the hepatorenal reflex, which may be triggered by subclinical portal hypertension and is a poorly investigated but promising research topic. Finally, we address emerging pharmacotherapies for NAFLD that may also beneficially affect the risk of developing CKD in individuals with NAFLD.

Renin: Measurements, Correlates, and Associations With Long-Term Adverse Kidney Outcomes.

The association of renin with adverse kidney outcomes is largely unknown, and renin measurement strategies vary. We aimed to measure the clinical correlates of different renin measurements and the association between renin and incident chronic kidney disease (CKD), end-stage kidney disease (ESKD), and mortality. We performed a prospective cohort analysis of 9,420 participants in the Atherosclerosis Risk in Communities study followed from 1996 to 1998 through 2019. We estimated longitudinal associations of renin measured using SomaScan modified nucleotide aptamer assay with incident CKD, ESKD, and death using Cox proportional hazards models. Using samples from a subsequent study visit, we compared SomaScan renin with plasma renin activity (PRA) and renin level from Olink, and estimated associations with covariates using univariate and multivariable regression. Higher SomaScan renin levels were associated with a higher risk of incident CKD (hazard ratio per two-fold higher [HR], 1.14; 95% confidence interval [CI], 1.09 to 1.20), ESKD (HR, 1.20; 95% CI, 1.03 to 1.41), and mortality (HR, 1.08; 95% CI, 1.04 to 1.13) in analyses adjusted for demographic, clinical, and socioeconomic covariates. SomaScan renin was moderately correlated with PRA (r = 0.61) and highly correlated with Olink renin (r = 0.94). SomaScan renin and PRA had similar clinical correlates except for divergent associations with age and beta-blocker use, both of which correlated positively with SomaScan renin but negatively with PRA. SomaScan aptamer-based renin level was associated with a higher risk of CKD, ESKD, and mortality. It was moderately correlated with PRA, sharing generally similar clinical covariate associations.

Multi-pollutant air pollution and renal health in Asian children and adolescents: An 18-year longitudinal study

BackgroundFew studies have examined the effects of multi-pollutant air pollution on renal health, especially in children and adolescents. This study investigated the association between long-term ambient air pollution exposure and renal health in Asian children and adolescents. MethodsThis study included 10,942 children and adolescents from Taiwan and Hong Kong between 2000 and 2017. PM2.5, NO2 and O3 concentrations were estimated using satellite-based spatiotemporal regression models. Two-year average concentrations, those of the year of visit and the preceding year, were used. Linear mixed models were used to examine the association between air pollution and yearly changes in estimated glomerular filtration rate (eGFR). Cox regression models with time-dependent covariates were used to examine the association between air pollution and the development of chronic kidney disease (CKD). ResultsMedian age of the participants was 19 years (range: 2–25). The overall average concentration of PM2.5, NO2 and O3 was 26.7 μg/m3, 44.1 μg/m3 and 51.1 μg/m3, respectively. The mean yearly change in eGFR was 0.37 μL/min/1.73 m2 and the incidence rate of CKD was 6.8 per 1,000 person-years. In single-pollutant models, each 10 μg/m3 increase in PM2.5 was associated with a 0.45 μL/min/1.73 m2 [95% confidence interval (CI): 0.28–0.63] reduction in the yearly increase in eGFR and 53% [hazard ratio (HR): 1.53 (95%CI: 1.07–2.2)] greater risk of incident CKD. Each 10 μg/m3 increase in NO2 was associated with a 7% [HR (95%CI): 1.07 (1.00–1.15)] higher risk of incident CKD, while an equivalent increase in O3 was associated with a 19% [HR (95%CI): 0.81 (0.67–0.98)] lower risk. ConclusionsLong-term exposure to ambient PM2.5 and NO2 was associated with a slower growth of eGFR and a higher risk of incident CKD in children and adolescents. Our findings suggest that air pollution control in early life is imperative to improve lifelong renal health and alleviate the CKD burden.

Association Between Ultraprocessed Food Consumption and Risk of Incident CKD: A Prospective Cohort Study

Ultraprocessed foods have become readily available in the global food supply in the past few decades. Several adverse health outcomes have been linked with higher consumption of ultraprocessed foods. However, the impact of ultraprocessed foods on chronic kidney disease (CKD) risk remains unknown. Prospective cohort study. 14,679 middle-aged adults without CKD at baseline in the Atherosclerosis Risk in Communities (ARIC) study. Ultraprocessed foods consumption (servings per day) calculated using dietary data collected via a food frequency questionnaire at visit 1 and visit3. Incident CKD defined as estimated glomerular filtration rate (eGFR)< 60 mL/min/1.73 m2 accompanied by≥25% eGFR decline, CKD-related hospitalization or death, or kidney failure with kidney replacement therapy. Multivariable-adjusted Cox proportional hazards models were used to assess the association between ultraprocessed foods consumption and CKD. Restricted cubic splines were used to examine the shape of the association. During a median follow-up period of 24 years, there were 4,859 cases of incident CKD. The incidence rate for the highest quartile of ultraprocessed foods consumption was 16.5 (95% CI, 15.6-17.4) per 1,000 person-years and 14.7 (95% CI, 13.9-15.5) per 1,000 person-years for the lowest quartile of consumption. After adjusting for a range of confounders including lifestyle factors, demographic characteristics, and health behaviors, participants in the highest quartile of ultraprocessed foods consumption had a 24% higher risk (HR, 1.24 [95% CI, 1.15-1.35]) of developing CKD compared with those in the lowest quartile. There was an approximately linear relationship observed between ultraprocessed food intake and risk of CKD. By substituting 1 serving of ultraprocessed foods with minimally processed foods, there was a 6% lower risk of CKD observed (HR, 0.94 [95% CI, 0.93-0.96]; P< 0.001). Self-reported data and residual confounding. Higher ultraprocessed foods consumption was independently associated with a higher risk of incident CKD in a general population.

Genetic Risk Score for Plasma Uric Acid Levels Is Associated With Early Rapid Kidney Function Decline in Type 2 Diabetes.

Observational studies have shown that elevated uric acid (UA) is associated with chronic kidney disease (CKD). However, whether the relationship is causal remains unclear. To determine the association of plasma UA and incident CKD and the causal relationship between plasma UA and rapid decline in kidney function (RDKF) in patients with type 2 diabetes (T2D). Multivariable Cox regression was conducted to evaluate the hazard ratio (HR) between plasma UA and incident CKD among 1300 normoalbuminuric patients in 2 T2D study cohorts (DN, n = 402; SMART2D, n = 898). A weighted genetic risk score (wGRS) was calculated based on 10 single nucleotide polymorphism (SNPs) identified in genome-wide association studies of UA in East Asians. Mendelian randomization (MR) analysis was performed among 1146 Chinese T2D patients without CKD (estimated glomerular filtration rate [eGFR] > 60 mL/min/1.73m2) at baseline (DN, 478; SMART2D, 668). The wGRS and individual SNPs were used as genetic instruments and RDKF was defined as eGFR decline of 5 mL/min/1.73m2/year or greater. During mean follow-up of 5.2 and 5.4 years, 81 (9%) and 46 (11%) participants in SMART2D and DN developed CKD, respectively. A 1-SD increment in plasma UA conferred higher risk of incident CKD (DN, adjusted-HR = 1.40 [95% CI, 1.02-1.91], P = 0.036; SMART2D, adjusted-HR = 1.31 [95% CI, 1.04-1.64], P = 0.018). Higher wGRS was associated with increased odds for RDKF (meta-adjusted odds ratio = 1.12 [95% CI, 1.01-1.24], P = 0.030, Phet = 0.606). Elevated plasma UA is an independent risk factor for incident CKD. Furthermore, plasma UA potentially has a causal role in early eGFR loss in T2D patients.

The Association Between Visceral Adiposity Index and Worsening Renal Function in the Elderly.

BackgroundVisceral adiposity index (VAI) is an indicator of visceral fat accumulation and dysfunction. However, little is known about whether VAI is associated with worsening renal function (WRF) in the elderly. Therefore, our study aimed to explore the association between VAI and WRF among the elderly population.MethodsIn total, 5,583 elderly participants (aged ≥ 65 years) who participated in the annual health checkups at least twice between January 2017 and July 2021 were enrolled and divided into four groups according to the VAI quartiles. The primary endpoint was incident chronic kidney disease (CKD), defined as incident estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2. The secondary endpoint was rapid kidney function decline (RKFD), defined as decline in eGFR of 40%. To evaluate the association between VAI and WRF, three Cox regression models were conducted, where VAI was treated as a continuous variable and a categorical variable (Q1 as reference), respectively. Subgroup analysis in participants with different baseline characteristics was also performed.ResultsDuring a median of 2.46 year follow-up, 931 (16.68%) participants developed CKD. After fully adjusting for confounding factors, VAI was significantly associated with incident CKD (HR, 1.052; 95% CI: 1.029–1.076, p < 0.001), and RKFD (HR, 1.077; 95% CI: 1.041–1.114, p < 0.001). Moreover, compared to those with the lowest VAI quartiles, subjects with the highest quartiles had a higher risk of incident CKD (HR, 1.286; 95% CI: 1.033–1.601, p = 0.024), and RKFD (HR, 1.895; 95% CI: 1.086–3.307, p = 0.025). The risk of incident CKD also tended to increase with elevated VAI quartiles (all p-values for trend <0.05). This positive association remained consistent among participants with different genders, baseline weights, or kidney functions.ConclusionIn our study, elevated VAI was associated with increased risk of incident CKD and RKFD in the elderly population.

Advanced liver fibrosis measured by transient elastography predicts chronic kidney disease development in individuals with non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are progressive chronic conditions that share important cardiometabolic risk factors and pathogenic mechanisms. We investigated the association between liver fibrosis measured by transient elastography (TE) and the risk of incident CKD in individuals with NAFLD. A total of 5983 participants with NAFLD (defined as controlled attenuation parameter >222dB/m) but without CKD who underwent TE between March 2012 and August 2018 were selected. The primary outcome was incident CKD, defined as the occurrence of eGFR <60mlmin-1 [1.73m]-2 or proteinuria (≥1+ on dipstick test) on two consecutive measurements during follow-up. The secondary outcome was a 25% decline in eGFR measured on two consecutive visits. The mean age was 51.8years and 3756 (62.8%) participants were male. During 17,801 person-years of follow-up (mean follow-up of 3.0years), 62 participants (1.0%) developed incident CKD. When stratified into TE-defined fibrosis stages (F0-F4), multivariable Cox models revealed that risk of incident CKD was 5.40-fold (95% CI 2.46, 11.84; p < 0.001) higher in the F3/F4 group (≥9.5kPa) than in the F0 group (<5.5kPa). During 17,577 person-years of follow-up (mean follow-up of 3.0years), 201 participants (3.4%) experienced the secondary outcome, for which the F3/F4 group had a 3.22-fold higher risk (95% CI 1.96, 5.28; p < 0.001) than the F0 group. In this large cohort of individuals with NAFLD but without baseline CKD, advanced liver fibrosis measured by TE was significantly associated with a higher risk of incident CKD.

Abstract 10683: Association Between Triglycerides and Incident Chronic Kidney Disease in Diabetics Across Stages of Albuminuria

Background: Hypertriglyceridemia, a component of the metabolic syndrome, is a known independent predictor of albuminuria and chronic kidney disease (CKD) in the general population. Urine albumin to creatinine ratio (UACR) and albuminuria are critical components in CKD staging as well as a hallmark of diabetic kidney disease. We sought to evaluate the relationship of triglycerides (TG) with incident CKD in diabetic non-CKD patients, stratified by level of albuminuria, which has been less studied thus far. Methods: This study comprised of 99,705 diabetic non-CKD veterans with data on TG and MetS components. The incident CKD outcome was defined as multiple eGFR measurements of &lt;60 mL/min/1.73m 2 at least 90 days apart. Using Cox proportional hazards models, we evaluated the association of TG with incident CKD, adjusted for case-mix characteristics, laboratory values including hemoglobin A1c, and stratified by baseline albuminuria categories. Results: The mean±SD age was 63±10, with a median [IQR] for TG of 147[99, 222] mg/dL, and UACR &lt;30 mg/g for 76% of patients. We observed a slight linear association between TG and incident CKD after adjustment for case-mix and laboratory variables among patients with Alb A1 and A2 stages (&lt;30 and 30-300 mg/g) (ref: TG 120-&lt;160 mg/dL) (Figure). While low TG were associated with a lower risk of incident CKD, elevated TG ≥240 mg/dL trended towards a higher risk of event. Among Alb A3 patients (&gt;300 mg/g), we observed an inverse U shape, where elevated TG ≥240 mg/dL trended towards a lower risk of incident CKD after adjustment. Conclusion: Elevated TG were associated with a higher risk of incident CKD in diabetic non-CKD patients with normal microalbuminuria. Patients with higher levels of albuminuria trended towards a lower relationship. Additional study is warranted to investigate the mechanism behind diabetic kidney disease risk with consideration for levels of albuminuria.

Serum uric acid and risk of incident chronic kidney disease: a national cohort study and updated meta-analysis

BackgroundWe prospectively examined the association between serum uric acid (SUA) levels and chronic kidney disease (CKD) in China and updated the evidence through a comprehensive meta-analysis of prospective studies worldwide.MethodsOur original analyses were based on data from the China Health and Retirement Longitudinal Study. The primary exposure of interest was SUA at baseline, and the main outcome was incident CKD. Logistic regression models were used to examine the association between SUA levels and incident CKD. A meta-analysis was performed to pool our effect estimate and those from other cohort studies.ResultsDuring a 4-year follow-up, 180 participants developed incident CKD. Participants in the highest SUA quartile were 2.73 times as likely to develop incident CKD compared to those in the lowest quartile (multivariable-adjusted OR, 2.73; 95% CI, 1.65–4.50). Each 1 mg/dL increment in the SUA levels was associated with a 49% increased risk of incident CKD (multivariable-adjusted OR, 1.49; 95% CI, 1.28–1.74). In the meta-analysis of 30 cohort studies (including the current study), pooled relative risks (95% CIs) of incident CKD were 1.15 (1.10–1.21) for SUA each 1 mg/dL increment, 1.22 (1.14–1.30) for the highest versus lowest SUA group, and 1.17 (1.12–1.23) for hyperuricemia versus no hyperuricemia.ConclusionsBaseline SUA levels were associated with higher risk of incident CKD in middle-aged and elderly Chinese adults, and this positive association was confirmed in the meta-analysis of multiple cohort studies. Our findings may imply that SUA levels need to be routinely monitored for future CKD risk.

Increased Risk of Chronic Kidney Disease Associated With Weight Gain in Healthy Adults: Insight From Metabolic Profiles and Body Composition.

Objective: Obesity is an established risk factor for kidney damage. In this study, we explored the long-term association of changes in body mass index (BMI) over time with incident chronic kidney disease (CKD).Methods: For this analysis, 5,393 middle-aged adults without comorbidities in the Korean Genome and Epidemiology Study (KoGES) were included. Group-based trajectory modeling was used to determine the patterns of BMI change (decreasing, stable, and increasing BMI) between baseline and year 4. The primary outcome was the subsequent development of CKD from year 4. A multivariable Cox proportional hazards model was constructed to determine the risk of incident CKD according to BMI trajectories.Results: During 55,327 person-years, incident CKD occurred in 354 (6.5%) participants; 6.0, 6.1, and 7.8 per 1,000 person-years across the trajectories, respectively (P = 0.005). In the multivariable-adjusted Cox proportional hazards model, the increasing BMI trajectory was associated with a 1.4-fold [hazard ratio (HR), 1.41; 95% CI, 1.06–1.87] a higher risk of incident CKD compared with stable BMI trajectory. This association was stronger for overweight and obese individuals. The HRs for CKD development in these two groups were 1.6 (95% CI, 1.06–1.87) and 2.2 (95% CI, 1.40–3.48), respectively. While the increasing BMI group was gaining weight, there were concomitant increases in blood pressure, insulin resistance, serum concentrations of total cholesterol, triglyceride, and high-sensitivity C-reactive protein (hs-CRP), and fat mass, but high-density lipoprotein (HDL)-cholesterol level and muscle-to-fat (MF) ratio decreased.Conclusion: Weight gain is associated with an increased risk of incident CKD in healthy adults. This association is attributed to worsening metabolic profiles and increasing fat mass.

Metabolomics of Dietary Acid Load and Incident Chronic Kidney Disease

Blood biomarkers of dietary intake are more objective than self-reported dietary intake. Metabolites associated with dietary acid load were previously identified in 2 chronic kidney disease (CKD) populations. We aimed to extend these findings to a general population, replicating their association with dietary acid load, and investigating whether the individual biomarkers were prospectively associated with incident CKD. Among 15,792 participants in the Atherosclerosis Risk in Communities cohort followed up from 1987 to 1989 (baseline) to 2019, we evaluated 3,844 black and white men and women with dietary and metabolomic data in cross-sectional and prospective analyses. We hypothesized that a higher dietary acid load (using equations for potential renal acid load and net endogenous acid production) was associated with lower serum levels of 12 previously identified metabolites: indolepropionylglycine, indolepropionate, N-methylproline, N-δ-acetylornithine, threonate, oxalate, chiro-inositol, methyl glucopyranoside, stachydrine, catechol sulfate, hippurate, and tartronate. In addition, we hypothesized that lower serum levels of these 12 metabolites were associated with higher risk of incident CKD. Eleven out of 12 metabolites were significantly inversely associated with dietary acid load, after adjusting for demographics, socioeconomic status, health behaviors, health status, and estimated glomerular filtration rate: indolepropionylglycine, indolepropionate, N-methylproline, threonate, oxalate, chiro-inositol, catechol sulfate, hippurate, methyl glucopyranoside (α+β), stachydrine, and tartronate. N-methylproline was inversely associated with incident CKD (hazard ratio: 0.95, 95% confidence interval: 0.91, 0.99, P=.01). The metabolomic biomarkers of dietary acid load significantly improved prediction of elevated dietary acid load estimated using dietary data, beyond covariates (difference in C statistics: 0.021-0.077, P≤1.08×10-3). Inverse associations between candidate biomarkers of dietary acid load were replicated in a general population. N-methylproline, representative of citrus fruit consumption, is a promising marker of dietary acid load and could represent an important pathway between dietary acid load and CKD.