Risk Of Incident Chronic Kidney Disease Research Articles

Arterial stiffness and incident chronic kidney disease: a large population-based cohort study.

Evidence from large population-based cohorts as to the association of arterial stiffness and incident chronic kidney disease (CKD) is mixed. This large population-based study aimed to investigate whether arterial stiffness, assessed oscillometrically, was associated with incident CKD. The study population comprised 4838 participants from the Vitamin D Assessment (ViDA) Study without known CKD (mean ± SD age = 66 ± 8). Arterial stiffness was assessed from 5 April, 2011 to 6 November, 2012 by way of aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure. Incident CKD was determined by linkage to national hospital discharge registers. Cox proportional hazards regression was used to assess the risk of CKD in relation to chosen arterial stiffness measures over the continuum and quartiles of values. During a mean ± SD follow-up of 10.5 ± 0.4years, 376 participants developed incident CKD. Following adjustment for potential confounders, aortic pulse wave velocity (hazard ratio (HR) per SD increase 1.69, 95% CI 1.45-1.97), estimated carotid-femoral pulse wave velocity (HR per SD increase 1.84, 95% CI 1.54-2.19), and aortic pulse pressure (HR per SD increase 1.37, 95% CI 1.22-1.53) were associated with the incidence of CKD. The risk of incident CKD was, compared to the first quartile, higher in the fourth quartile of aortic pulse wave velocity (HR 4.72, 95% CI 2.69-8.27; Ptrend < 0.001), estimated carotid-femoral pulse wave velocity (HR 4.28, 95% CI 2.45-7.50; Ptrend < 0.001) and aortic pulse pressure (HR 2.71, 95% CI 1.88-3.91; Ptrend < 0.001). Arterial stiffness, as measured by aortic pulse wave velocity, estimated carotid-femoral pulse wave velocity, and aortic pulse pressure may be utilised in clinical practice to help identify people at risk of future CKD. www.anzctr.org.au identifier:ACTRN12611000402943.

#736 The short-term and long-term impact of COVID-19 on the kidney disorders: an observational and Mendelian randomization study

Abstract Background and Aims The impact of “long COVID-19” on “short-term” or “long-term” influence on kidney function change remains unknown. We aimed to investigate the causal association between COVID-19 and subsequent kidney outcomes. Method 10121 participants exposed to COVID-19 were matched up to 3 unexposed controls by age, sex, Townsend deprive index and severity of COVID-19 from UK Biobank. Using conditional and time-varying Cox proportional hazard regression, we first investigated the association between the SARS-CoV-2 infection and incidence of acute kidney disorder and chronic kidney disease (CKD). One-sample mendelian randomization (MR) using polygenetic risk score (PRS) of COVID-19 as instrumental variable was performed. Then, we extended the finding with two-sample MR analyses using GWAS summary statistics from UKB as outcomes, and GWAS of COVID-19 severity, hospitalization and susceptibility from the COVID-19 Host Genetics Initiative (r7) database as exposures. Results In observational study, we observed time-varying effects of COVID-19 on the risk of acute kidney disorder incidence, with the highest hazard effect in the second week (HR 12.77, 95% CI: 5.93-27.70) and disappearing in the fourth week (HR 2.28, 95% CI: 0.75-6.93). In subgroup analysis, this time-varying effects were only found in patients with moderate and severe COVID-19, but not mild COVID-19 patients. No association was observed between SARS-CoV-2 infection and the risk of incident CKD. Subsequent individual-level MR showed that COVID-19 severity, hospitalization and susceptibility were significantly associated with increased risk of acute kidney disorder, but not CKD. Two-sample MR indicated that none of the COVID-19 phenotypes were associated with these two diseases nor other kidney traits. Conclusion COVID-19 had “short-term” effects on the risk of subsequent acute kidney disorder incidence, and the hazard effects were only observed in moderate or severe but not mild COVID-19 patients.

#939 Association between alcohol consumption and the risk of incident chronic kidney disease in community-dwelling older adults

Abstract Background and Aims The relationship between alcohol consumption and kidney function decline is not well established, especially in older adults. This study aimed to investigate the effects of alcohol consumption on the risk of incident chronic kidney disease (CKD) in community-dwelling older adults. Method Adults aged ≥ 65 years with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 and without proteinuria between 2009 and 2010 were recruited and followed through December 2018 from a Korean national population-based cohort. Alcohol consumption was categorised into non-, mild, moderate, and heavy drinking groups based on self-administered questionnaires. New-onset CKD was defined as an eGFR &amp;lt;60 mL/min/1.73 m2. Results Of the total 122,319 subjects, the non-, mild, moderate, and heavy drinking groups were 99,091 (81.0%), 14,842 (12.1%), 4,257 (3.5%), and 4,139 (3.4%), respectively. During follow-up, 19,796 (20.0%), 4,636 (31.2%), 1,696 (39.8%), and 1,695 (41.0%) developed CKD in the non-, mild, moderate, and heavy drinking groups. Univariate Cox regression analyses showed a significantly increased risk of incident CKD in older adults in all drinking groups compared to non-drinkers (all P &amp;lt; 0.001). However, hazard ratios (HR) for developing CKD were 0.90 (95% confidence interval [CI] 0.87–0.94, P &amp;lt; 0.001) for mild, 0.89 (95% CI 0.84–0.95, P &amp;lt; 0.001) for moderate, and 0.93 (95% CI 0.88–0.99, P = 0.027) for heavy drinkers after fully adjusting for confounding variables. This inverse relationship between alcohol consumption and CKD risk was observed in males in all drinking groups, whereas in females it was found only in mild drinkers. Conclusion In the subgroup analysis, the beneficial effect of alcohol consumption on incident CKD was prominent among moderate drinkers aged 65–75 years, male mild drinkers aged ≥ 75 years, and female mild drinkers aged &amp;lt; 85 years. This study shows that alcohol consumption is inversely associated with the risk of incident CKD in older adults. Further studies are required to elucidate the effects of alcohol on kidney damage in older adults.

#208 Obesity is associated with incident chronic kidney disease in individuals with normal renal function

Abstract Background and Aims Obesity is a representative modifiable risk factor for chronic kidney disease (CKD). This study aimed to investigate whether both body mass index (BMI), waist-to-hip ratio (WHR) and changes of WHR during follow-up are risk factors for development of incident CKD. Method A total of 2 711 participants from a community-based cohort with normal renal function were prospectively analyzed. Among participants with obesity, we analyzed the change in WHR to evaluate the association of obesity reduction with CKD development. Results During a mean follow-up of 11.03 ± 4.22 years, incident CKD occurred in 190 (7.0%) participants. In the fully adjusted multivariable Cox proportional hazard models, the risk of incident CKD increased with higher BMI (hazard ratio, 1.06; 95% confidence interval, 1.00–1.11; p = 0.033) and higher WHR (hazard ratio, 1.33; 95% confidence interval, 1.07–1.66; p = 0.009). In the Kaplan–Meier analysis, cumulative adverse renal events were significantly more common in the maintained obesity group than in the reduced obesity group (p = 0.001). Conclusion Both higher BMI and WHR were associated with development of CKD, but the magnitude of the effect of WHR was higher than that of BMI. Moreover, reducing obesity would be beneficial for renal prognosis.

#1054 Dietary manganese intake and risk of chronic kidney disease: insights from the UK Biobank Study

Abstract Background and Aims Manganese, an essential trace element crucial for various physiological processes, has been linked to metabolic syndrome and cardiovascular health. Despite these associations, the relationship between dietary manganese intake and incident chronic kidney disease (CKD) remains unclear. In this study, the connection between dietary manganese consumption and the development of CKD in individuals with normal kidney function was investigated. Method A total of 135,577 participants enrolled in the UK Biobank were assessed. Dietary manganese intake was determined through a 24-hour dietary recall questionnaire and categorized into quartiles. Individuals with prevalent CKD or an estimated glomerular filtration rate (eGFR) &amp;lt;60 mL/min/1.73 m2 at baseline were excluded. The primary outcome was incident CKD diagnosed using ICD-10 and OPCS-4 codes. Incident CKD, defined as eGFR &amp;lt;60 mL/min/1.73 m2 or a urine albumin-to-creatinine ratio (UACR) ≥30 mg/g, was also evaluated in a sub-cohort that included eGFR and UACR follow-up data. Results During a follow-up period of 1,492,228 person-years (median, 11.2 years), incident CKD occurred in 4,900 (3.6%) participants. The incidence of CKD exhibited a progressive increase among individuals with low manganese intake (2.3, 3.0, 3.6, and 4.2 events per 1000 person-years in Q4–Q1, respectively). In a multivariate Cox proportional hazard model, the adjusted hazard ratios (95% confidence intervals) for the lowest, second, and third quartiles were 1.39 (1.26–1.54), 1.22 (1.11–1.34), and 1.12 (1.02–1.23), respectively, compared to the highest quartile. Similar findings were observed in relation to eGFR or UACR-defined CKD outcomes. Conclusion Lower dietary manganese consumption was found to be associated with an elevated risk of incident CKD in adults with normal kidney function. This implies that a deficiency in dietary manganese intake may contribute to an increased risk of CKD development.

#1215 Association between dietary magnesium intake and incident chronic kidney disease

Abstract Background and Aims Recent studies suggest a close association between low serum magnesium levels and kidney injury. However, whether dietary magnesium intake relates with kidney function is not well known. In this study, the relationship of dietary magnesium intake with the development of chronic kidney disease (CKD) was evaluated. Method This observational prospective study screened 210,965 European adults aged 40-70 who underwent dietary questionnaire from April 2009 to June 2012 in UK Biobank cohort. Participants with underlying CKD (baseline eGFR &amp;lt; 60 mL/min/1.73 m² or urine albumin-to-creatinine ratio &amp;gt;30 mg/g/Cr) or implausible energy intake (reported energy intake &amp;lt; 1.1 × basal metabolic rate [BMR] or 2.5 × BMR) were excluded. Dietary magnesium intake was assessed through online 24-hour recall dietary questionnaire and adjusted for energy intake using residual method. The participants were categorized into quartile according to energy-adjusted dietary magnesium intake. Primary outcome was incident CKD diagnosed through ICD-10 and OPCS-4 codes. Incident CKD defined as eGFR &amp;lt; 60 mL/min/1.73 m² was also assessed as an additional primary outcome in the sub-cohort with primary care creatinine follow-up data. Results A total of 114,916 participants was included in the final analysis. The median age was 57.0 (IQR, 50.0-63.0) years and 56.8% were female. Median magnesium intake amount per person was 345.6 (IQR, 296.8-402.5) mg/day. During a 1,095,128.6 person-year follow-up, CKD outcome occurred in 3,337 patients. Incidence of CKD was progressively lower in patients with higher magnesium intake (3.2%, 2.9%, 2.8%, and 2.7% in Q1-4, respectively). Cox regression analysis revealed that the hazard ratios (HRs) for incident CKD decreased in a stepwise manner towards higher magnesium intake quartiles (2Q: HR, 0.89; 95% CI, 0.81-0.98; 3Q: HR, 0.87; 95% CI, 0.0.79-0.95; 4Q: HR, 0.84; 95% CI, 0.76-0.92) relative to 1Q (P for trend &amp;lt; 0.001). This association was maintained even after adjustments were made for confounding factors. Similar results were observed with eGFR-defined CKD outcome (2Q: adjusted HR [AHR], 0.75; 95% CI, 0.64-0.89; 3Q: AHR, 0.73; 95% CI, 0.61-0.87; 4Q: AHR, 0.70; 95% CI, 0.58-0.85) relative to 1Q (P for trend &amp;lt; 0.001). Conclusion Higher intake of dietary magnesium may relate with lower risk of incident CKD in adults with normal kidney function.

#986 Sarcopenia and chronic kidney disease among adults over 45 years old: findings from CHARLS

Abstract Background and Aims Little is known about the association between sarcopenia and chronic kidney disease (CKD) among Chinese adults older than 45. The present study sought to investigate the relationship between sarcopenia and CKD based on a large, nationally representative survey. Method The China Health and Retirement Longitudinal Study (CHARLS) provided data for the study in four waves in 2011, 2013, 2015, and 2018. Based on the Asia Working Group for Sarcopenia 2019 (AWGS 2019) criteria, sarcopenia and possible sarcopenia were defined. CKD was defined as eGFR less than 60 mL/min/1.73 m2, calculated according to the CKD Epidemiology Collaboration (CKD-EPI) equation, or self-reported CKD. Logistic regression models were conducted to analyze the cross-sectional relationship between sarcopenia and CKD. Cox proportional hazards regression models were used to examine the effect of sarcopenia on CKD. Stratified analyses were used to assess the association between sarcopenia status and CKD in various subgroups. Results Totally, 12323 participants over 45 years old (48.2% males; mean age 59.3 ± 9.5 years) were enrolled in a cross-sectional study in 2011, and further 10445 individuals were followed up in 2013, 2015 and 2018. The prevalence of CKD was 8.4% (1040/12323) in general populations, 7.2% (556/7703) in individuals without sarcopenia, 10.1% (380/3760) in adults with possible sarcopenia, and 12.1% (104/860) in individuals with sarcopenia, respectively. In cross-sectional study, possible sarcopenia [OR (95% CI): 1.236 (1.069-1.430)] was significantly associated with CKD (P &amp;lt; 0.01). While sarcopenia was not significantly associated with CKD. 783 cases (7.5%) with incident CKD events were identified during the 7 years of follow-up. In subgroup analyses, the incidence of CKD was 1.855 (95% CI 1.176-2.928) in the sarcopenia group compared with non-sarcopenia group among the female participants. The sarcopenia group (HR: 1.639, 95% CI 1.099-2.443) was independently associated with a higher incidence of CKD among non-smokers. Low muscle mass alone was not significantly associated with an increased risk of incident CKD (P &amp;gt; 0.05). Conclusion In our cross-sectional analysis, possible sarcopenia determined by AWGS2019 criteria was associated with a higher prevalence of CKD. In our longitudinal study, sarcopenia assessed using AWGS2019 criteria was associated with a higher risk of CKD in Chinese women over 45 years old or non-smokers.

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.

The association between circadian syndrome and chronic kidney disease in an aging population: a 4-year follow-up study.

Circadian syndrome (CircS) is proposed as a novel risk cluster based on reduced sleep duration, abdominal obesity, depression, hypertension, dyslipidemia and hyperglycemia. However, the association between CircS and chronic kidney disease (CKD) remains unclear. To investigate the cross-sectional and longitudinal association between CircS and CKD, this study was performed. A national prospective cohort (China Health and Retirement Longitudinal Study, CHARLS) was used in this study. To define CKD, the estimated glomerular filtration rate (eGFR) was calculated based on the 2012 CKD-EPI creatinine-cystatin C equation. Participants with eGFR <60 mL.min-1/1.73/m2 were diagnosed with CKD. Multivariate binary logistic regression was used to assess the cross-sectional association between CircS and CKD. Subgroup and interactive analyses were performed to determine the interactive effects of covariates. In the sensitivity analysis, the obese population was excluded and another method for calculating the eGFR was used to verify the robustness of previous findings. In addition, participants without CKD at baseline were followed up for four years to investigate the longitudinal relationship between CircS and CKD. A total of 6355 participants were included in this study. In the full model, CircS was positively associated with CKD (OR = 1.28, 95% CI = 1.04-1.59, P < 0.05). As per one increase of CircS components, there was a 1.11-fold (95% CI = 1.04-1.18, P < 0.05) risk of prevalent CKD in the full model. A significant interactive effect of hyperuricemia in the CircS-CKD association (P for interaction < 0.01) was observed. Sensitivity analyses excluding the obese population and using the 2009 CKD-EPI creatinine equation to diagnose CKD supported the positive correlation between CircS and CKD. In the 2011-2015 follow-up cohort, the CircS group had a 2.18-fold risk of incident CKD (95% CI= 1.33-3.58, P < 0.01) in the full model. The OR was 1.29 (95% CI = 1.10-1.51, P < 0.001) with per one increase of CircS components. CircS is a risk factor for CKD and may serve as a predictor of CKD for early identification and intervention.

Adiponectin-to-leptin ratio and incident chronic kidney disease: Sex and body composition-dependent association.

The association between the adiponectin-to-leptin ratio (A/L ratio) and the risk of incident chronic kidney disease (CKD) is poorly understood. This study aimed to investigate the association between A/L ratio and the risk of incident CKD and to examine whether such a relationship varied according to sex and body composition. In this prospective community-based cohort, participants with normal kidney function were analysed (N=5192). The association between the A/L ratio at baseline and the risk of incident CKD, defined as two or more occasions with an estimated glomerular filtration rate of <60mL/min/m2 or proteinuria of ≥1+ on a dipstick test during the follow-up period, was evaluated using multivariable Cox proportional hazards analyses. Subgroup analyses were conducted based on sex, body mass index (BMI) and the presence of sarcopenia. The participants' mean age was 57.2±8.3years, and 53.2% were women. The A/L ratio was higher in men compared with women (1.5 [0.8-3.2] and 0.5 [0.3-0.9] μg/ng, P<0.001). During a median follow-up of 9.8 [9.5-10.0] years, 417 incident CKD events occurred (8.7 per 1000 person-years). Men in the highest quartile of A/L ratio had a lower risk of incident CKD (adjusted hazard ratio [aHR], 0.57; 95% confidence interval [CI], 0.33-0.99) than those in the lowest quartile. Additionally, a 1.0 increase in A/L ratio was associated with a 12% decreased risk of incident CKD in men (aHR, 0.88; 95% CI, 0.80-0.97). However, no significant association was observed in women. In subgroup analysis stratified by BMI and the presence of sarcopenia, the association between a high A/L ratio and a reduced risk of incident CKD was consistent in men with a BMI<23.0kg/m2 and those with sarcopenia. However, no significant association was observed between men with a BMI≥23.0kg/m2 and those without sarcopenia. A high A/L ratio is an independent marker of a reduced risk of incident CKD in men, especially in those with a BMI<23.0kg/m2 and sarcopenia.

Association between dyslipidemia and the risk of incident chronic kidney disease affected by genetic susceptibility: Polygenic risk score analysis.

The effect of dyslipidemia on kidney disease outcomes has been inconclusive, and it requires further clarification. Therefore, we aimed to investigate the effects of genetic factors on the association between dyslipidemia and the risk of chronic kidney disease (CKD) using polygenic risk score (PRS). We analyzed data from 373,523 participants from the UK Biobank aged 40-69 years with no history of CKD. Baseline data included plasma levels of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride, as well as genome-wide genotype data for PRS. Our primary outcome, incident CKD, was defined as a composite of estimated glomerular filtration rate < 60 ml/min/1.73 m2 and CKD diagnosis according to International Classification of Disease-10 codes. The effects of the association between lipid levels and PRS on incident CKD were assessed using the Cox proportional hazards model. To investigate the effect of this association, we introduced multiplicative interaction terms into a multivariate analysis model and performed subgroup analysis stratified by PRS tertiles. In total, 4,424 participants developed CKD. In the multivariable analysis, PRS was significantly predictive of the risk of incident CKD as both a continuous variable and a categorized variable. In addition, lower total cholesterol, LDL-C, HDL-C, and higher triglyceride levels were significantly associated with the risk of incident CKD. There were interactions between triglycerides and intermediate and high PRS, and the interactions were inversely associated with the risk of incident CKD. This study showed that PRS presented significant predictive power for incident CKD and individuals in the low-PRS group had a higher risk of triglyceride-related incident CKD.

Urine Biomarkers of Kidney Tubule Health and Risk of Incident CKD in Persons Without Diabetes: The ARIC, MESA, and REGARDS Studies

Rationale & ObjectiveTubulointerstitial damage is a feature of early chronic kidney disease (CKD), but current clinical tests capture it poorly. Urine biomarkers of tubulointerstitial health may identify risk of CKD. Study DesignProspective cohort (ARIC) and case-cohort (MESA and REGARDS). Setting & ParticipantsAdults with eGFR ≥60 mL/min/1.73m2 and without diabetes in the ARIC, REGARDS, and MESA studies. ExposureBaseline urine monocyte chemoattractant protein-1 (MCP-1), alpha-1-microglobulin (α1m), kidney injury molecule-1 (KIM-1), epidermal growth factor (EGF), and chitinase-3-like protein 1 (YKL-40). OutcomeIncident CKD or ESKD (end-stage kidney disease). Analytical ApproachMultivariable Cox proportional hazards regression for each cohort; meta-analysis of results from all three cohorts. Results872 ARIC participants (444 cases of incident CKD), 636 MESA participants (158 cases), and 924 REGARDS participants (488 cases) were sampled. Across cohorts, mean age ranged from 60±10 to 63±8 years and baseline eGFR ranged from 88±13 to 91±14 mL/min/1.73m2. In ARIC, higher concentrations of urine MCP-1, α1m, and KIM-1 were associated with incident CKD. In MESA, higher concentration of urine MCP-1 and lower concentration of EGF was each associated with incident CKD. In REGARDS, none of the biomarkers were associated with incident CKD. In meta-analysis of all three cohorts, each two-fold higher α1m concentration was associated with incident CKD (HR=1.19 [1.08, 1.31]). LimitationsObservational design susceptible to confounding; competing risks during long follow-up period; meta-analysis limited to three cohorts. ConclusionsIn three combined cohorts of adults without prevalent CKD or diabetes, higher urine α1m was independently associated with incident CKD. Four biomarkers were associated with incident CKD in at least one of the cohorts when analyzed individually. Kidney tubule health markers might inform CKD risk independent of eGFR and albuminuria.

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 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 &lt;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.

Abstract MP16: Degree of Joint Risk Factor Control and Incident Chronic Kidney Disease Among Obese Individuals

Introduction: Individuals who are obese are at a higher risk for chronic kidney disease (CKD) than the non-obese population. Hypothesis: We assessed the hypothesis that controlling joint risk factors might reduce the increased risk of CKD observed in participants with obesity. Methods: We included a total of 97,538 participants who were obese at baseline and matched 97,538 normal weight control participants from the UK Biobank in the analysis. The degree of joint risk factor control was assessed based on 6 major CKD risk factors, including blood pressure, hemoglobin A1c, low-density lipoprotein cholesterol, albuminuria, smoking, and physical activity. The Cox proportional hazards models were used to estimate associations between the degree of risk factor control and risk of CKD. Results: Among obese participants, joint risk factor control showed an association with a stepwise reduction of incident CKD risk. Each additional risk factor control corresponded to an 11% (HR: 0.89, 95%CI: 0.86-0.91) reduced risk of CKD among obese participants; with the optimal controlling of all six risk factors associated with a 49% (HR: 0.51, 95% CI: 0.43-0.61) decrease in risk of CKD. Furthermore, in obese individuals who jointly controlled all six risk factors, the excess risk of CKD associated with obesity was effectively neutralized compared to normal weight control subjects. Notably, the protective correlations between the degree of joint risk factor control and the incidence of CKD were more pronounced in men compared to women, in individuals with a lower healthy food score versus a higher score, and among diabetes medication users as opposed to nonusers ( P for interaction=0.017, 0.033, 0.014 respectively). Conclusion: The joint risk factor control is associated with an inverse association of CKD risk in an accumulative manner among obese people. Achieving ideal control over risk factors may effectively counterbalance the excessive risk of CKD typically associated with obesity.

The Fatty Liver Index's Association with Incident Chronic Kidney Disease in Korean Middle-Aged Adults: A Community-Based Cohort Study.

(1) Background: The relationship between nonalcoholic fatty liver disease (NAFLD) and incident chronic kidney disease (CKD) is unclear, and long-term follow-up data are limited. Therefore, this study aimed to evaluate whether NAFLD, as assessed by the fatty liver index (FLI), could predict the development of CKD in a community-based Korean cohort over 16 years. (2) Methods: Among the 10,030 total participants, 7778 patients without CKD were selected from the Korean Genome and Epidemiology Study (KoGES). The FLI grade ranged from 0 to 100 and was divided into three groups: low (FLI, <30), intermediate (FLI, 30-59), and high (FLI, ≥60). An estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 or the development of proteinuria was considered to indicate incident CKD. (3) Results: During the 16-year follow-up period, 919 individuals (11.8%) developed CKD. The HRs of incident CKD in the intermediate FLI group (30-59) and high FLI group (≥60) increased compared with the reference low FLI group (<30) after adjusting for potentially confounding variables. NAFLD, as assessed by the FLI, was an independent risk factor for CKD. (4) Conclusions: Our findings suggest that the FLI, a simple surrogate biomarker of fatty liver disease, may be used to identify people at high risk of incident CKD in clinical practice.

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.

Associations of long-term exposure to ambient sulfur dioxide, carbon monoxide, ozone, and benzene with risk of incident chronic kidney disease in the UK

Limited studies have examined associations of gaseous air pollutants exposure with chronic kidney disease (CKD) in Europe. This study aimed to calculate the relationships between long-term exposure to ambient sulfur dioxide (SO2), carbon monoxide (CO), ozone (O3), and benzene and CKD in the UK. We included 502 369 participants from the UK biobank cohort. Associations of SO2, CO, O3, and benzene with CKD were estimated using Cox proportional hazards model. The shape of the exposure-response association between each air pollutant and CKD was then depicted using the shape constrained health impact function. We finally estimated the incidence of CKD attributable to each air pollutant by linking the constructed exposure-response association to the 2019 Global Burden of Disease data. Our results suggested SO2, high O3 days (daily max 8 hr O3 concentration > 120 µg m−3), CO, and benzene were positively associated with the risk of incident CKD. The hazard ratios (HRs) of CKD for SO2, CO, and benzene were 1.058 (95% CI: 1.039–1.078), 1.003 (95% CI: 1.001–1.005), and 1.619 (1.433–1.829) for every 1 μg m−3 increase in the concentration, respectively. For high O3 days, the HR of CKD was 1.044 (95% CI: 1.032–1.056) for every 1 d increase, but correlation to O3 concentration did not reach the statistical significance in the time-varying model. The risk of CKD increased non-linearly with increasing SO2, high O3 days, and CO, and linearly with increasing benzene. We estimated that 7.9%, 16.0%, 8.0% of incident CKD cases in the UK in 2021 could be attributed to exposure to SO2, O3, and benzene, respectively. We concluded that exposure to SO2, CO, O3, and benzene were all positively associated with increased CKD risk. Our findings highlight the importance of considering air pollution while making strategies targeting on CKD management.