Chronic Kidney Disease Events Research Articles

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.

Gestational Exposure to Maternal Systemic Glucocorticoids and Childhood Risk of CKD

Background & ObjectivesThe potential effects of antenatal glucocorticoid exposure on the health of children are unclear. We examined the association of gestational exposure to maternal systemic glucocorticoids (SG) and the risk of developing chronic kidney disease (CKD) in childhood. Study designRetrospective cohort study. Setting & ParticipantsNewborns cared for at the largest healthcare delivery system in Taiwan between 2004 and 2018. ExposureMaternal prescriptions for SG between the last menstrual period and birth as a proxy for gestational exposure. OutcomeIncidence of childhood CKD, including congenital anomalies of the kidney and urinary tract (CAKUT) and other kidney diseases (non-CAKUT) over 10 years. Analytical ApproachCox proportional hazards models with stabilized inverse probability of treatment weighting and robust sandwich estimator were used to estimate the average association between SG and incident CKD after adjustment for offspring characteristics (aHR). ResultsAmong 23,363 singleton-born children, gestational SG exposure was significantly associated with a higher risk of childhood CKD (aHR, 1.69 [95% CI, 1.01–2.84]). Stratified analyses showed stronger associations between SG and childhood CKD within the strata of birth <37 weeks gestational age (aHR, 2.38 [95% CI, 1.19–4.78]), male sex (aHR, 1.89 [95% CI, 1.00–3.55]), gestational exposure in the second trimester (aHR, 6.70 [95% CI, 2.17–20.64]), and total dose >24 mg hydrocortisone equivalent (aHR, 1.91 [95% CI, 1.05–3.47). LimitationsStudy was limited to the Taiwan healthcare delivery system and childhood CKD events through age 10 years. ConclusionsThe findings of this study suggest that gestational exposure to systemic glucocorticoids is associated with the occurrence of kidney disease in childhood. If these findings are confirmed, they may inform clinicians who are considering prescribing SG during pregnancy.

Relationship Between Lipoprotein(a), Renal Function Indicators, and Chronic Kidney Disease: Evidence From a Large Prospective Cohort Study.

Chronic kidney disease (CKD) poses a significant global public health challenge. While lipoprotein(a) (Lp[a]) has been established as a significant factor in cardiovascular disease, its connection to CKD risk remains a topic of debate. Existing evidence indicates diverse risks of kidney disease among individuals with various renal function indicators, even when within the normal range. This study aims to investigate the joint associations between different renal function indicators and Lp(a) regarding the risks of incident CKD in the general population. The analysis involved a cohort of 329,415 participants without prior CKD who were enrolled in the UK Biobank between 2006 and 2010. The participants, with an average age of 56 (SD 8.1) years, included 154,298/329,415 (46.84%) males. At baseline, Lp(a) levels were measured using an immunoturbidimetric assay and classified into 2 groups: low (<75 nmol/L) and high (≥75 nmol/L). To assess participants' baseline renal function, we used the baseline urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR). The relationship between Lp(a), renal function indicators, and the risk of CKD was evaluated using multivariable Cox regression models. These models were adjusted for various factors, including sociodemographic variables, lifestyle factors, comorbidities, and laboratory measures. A total of 6003 incident CKD events were documented over a median follow-up period of 12.5 years. The association between elevated Lp(a) levels and CKD risk did not achieve statistical significance among all participants, with a hazard ratio (HR) of 1.05 and a 95% CI ranging from 0.98 to 1.13 (P=.16). However, a notable interaction was identified between Lp(a) and UACR in relation to CKD risk (P for interaction=.04), whereas no significant interaction was observed between Lp(a) and eGFR (P for interaction=.96). When compared with the reference group with low Lp(a) and low-normal UACR (<10 mg/g), the group with high Lp(a) and low-normal UACR exhibited a nonsignificant association with CKD risk (HR 0.98, 95% CI 0.90-1.08; P=.74). By contrast, both the low Lp(a) and high-normal UACR (≥10 mg/g) group (HR 1.16, 95% CI 1.08-1.24; P<.001) and the high Lp(a) and high-normal UACR group (HR 1.32, 95% CI 1.19-1.46; P<.001) demonstrated significant associations with increased CKD risks. In individuals with high-normal UACR, elevated Lp(a) was linked to a significant increase in CKD risk, with an HR of 1.14 and a 95% CI ranging from 1.03 to 1.26 (P=.01). Subgroup analyses and sensitivity analyses consistently produced results that were largely in line with the main findings. The analysis revealed a significant interaction between Lp(a) and UACR in relation to CKD risk. This implies that Lp(a) may act as a risk factor for CKD even when considering UACR. Our findings have the potential to provide valuable insights into the assessment and prevention of CKD, emphasizing the combined impact of Lp(a) and UACR from a public health perspective within the general population. This could contribute to enhancing public awareness regarding the management of Lp(a) for the prevention of CKD.

Increased Cardiovascular Risk in Young Patients with CKD and the Role of Lipid-Lowering Therapy.

Chronic kidney disease (CKD) is associated with a significantly increased risk of cardiovascular disease (CVD). This review summarizes known risk factors, pathophysiological mechanisms, and current therapeutic possibilities, focusing on lipid-lowering therapy in CKD. Novel data on lipid-lowering therapy in CKD mainly stem from clinical trials and clinical studies. In addition to traditional CVD risk factors, patients with CKD often present with non-traditional risk factors that include, e.g., anemia, proteinuria, or calcium-phosphate imbalance. Dyslipidemia remains an important contributing CVD risk factor in CKD, although the mechanisms involved differ from the general population. While statins are the most commonly used lipid-lowering therapy in CKD patients, some statins may require dose reduction. Importantly, statins showed diminished beneficial effect on cardiovascular events in patients with severe CKD and hypercholesterolemia despite high CVD risk and effective reduction of LDL cholesterol. Ezetimibe enables the reduction of the dose of statins and their putative toxicity and, in combination with statins, reduces CVD endpoints in CKD patients. The use of novel drugs such as PCSK9 inhibitors is safe in CKD, but their potential to reduce cardiovascular events in CKD needs to be elucidated in future studies.

The role and mechanism of RIPK1 in vascular endothelial dysfunction in chronic kidney disease.

Endothelial dysfunction is common in patients with chronic kidney disease (CKD) and cardiovascular events, but the mechanism is unclear. In our study, we found elevated levels of RIPK1 in patients with CKD and cardiovascular events through bioinformation analysis. Elevated RIPK1 levels were found in serum samples of CKD patients and were associated with vascular endothelial dysfunction and renal function. We constructed the five of six nephrectomy of CKD mice model, finding that RIPK1 expressions were elevated in abdominal aorta endothelial cells. After RIPK1 inhibition and overexpression, it was found that RIPK1 could regulate the expression of endothelial nitric oxide synthase (eNOS) and cell adhesion molecule 1 (ICAM-1), and activation of inflammatory responses and endoplasmic reticulum (ER) stress. In addition, uremic toxin induced abnormal expression of RIPK1 invitro. We observed RIPK1-mediating endothelial dysfunction and inflammation responses by ER stress pathways through gain and loss of function. In order to explore the specific mechanism, we conducted co-immunoprecipitation and expression regulation of RIPK1 and IKK, finding that RIPK1 formed complex with IKK and regulated IKK expression. In conclusion, we demonstrated that RIPK1 levels were closely associated with vascular endothelial dysfunction in patients with CKD. With uremic toxins, RIPK1 expression was elevated, which led to the activation of inflammation through the ER stress pathway, resulting in vascular endothelial injury. Besides, activation of RIPK1-IKK-NF-κB axis was a key driver of endothelial dysfunction in CKD. Our study provides a new perspective for the study of cardiovascular events in CKD.

Effects of sodium-glucose co-transporter 2 inhibitors on heart failure events in chronic kidney disease: a systematic review and meta-analysis.

Sodium-glucose co-transporter 2 (SGLT-2) inhibitors significantly reduce the risk for hospitalizations for heart failure (HF) in patients with diabetes, and HF; findings in patients with chronic kidney disease (CKD) are not uniform. We aimed to perform a meta-analysis exploring the effect of SGLT-2 inhibitors on HF events in patients with CKD and across subgroups defined by baseline kidney function. A systematic search in major electronic databases was performed. Randomized controlled trials providing data on the effect of SGLT-2 inhibitors on the primary outcome, time to hospitalization or urgent visit for worsening HF in patients with prevalent CKD at baseline or across subgroups stratified by baseline estimated glomerular-filtration-rate (eGFR) were included. Twelve studies (n=89,191 participants) were included in the meta-analysis. In patients with CKD, treatment with SGLT-2 inhibitors reduced the risk for HF events by 32% compared to placebo (hazard ratio [HR] 0.68; 95%CI 0.63-0.73). Reduction in HF events with SGLT-2 inhibitors was more prominent in patients with eGFR<60 ml/min/1.73m2 (HR 0.68; 95%CI 0.62-0.74) than in those with eGFR≥60 ml/min/1.73m2 (HR 0.76; 95%CI 0.69-0.83). Subgroup analysis according to type of SGLT-2 inhibitor showed a consistent treatment effect across all studied agents (p-subgroup-analysis=0.44). Sensitivity analysis including data from studies including only diabetic patients showed an even more pronounced effect in eGFR subgroup<60 ml/min/1.73m2 (HR 0.62; 95%CI 0.54-0.70). Treatment with SGLT-2 inhibitors led to a significant reduction in HF events in patients with CKD. Such findings may change the landscape of prevention of HF events in patients with advanced CKD. PROSPERO Registration number: CRD42022382857.

Transcatheter left atrial appendage occlusion in patients with chronic kidney disease: a systematic review and meta-analysis.

Chronic kidney disease (CKD) is a risk factor for embolic stroke, and many nonvalvular atrial fibrillation (NVAF) patients have concomitant CKD. Anticoagulation therapy can be challenging in CKD due to increased bleeding risk, and left atrial appendage occlusion (LAAO) may be a promising alternative. This systematic review aimed to consolidate current evidence on the safety and effectiveness of transcatheter LAAO in patients with CKD and end-stage renal disease (ESRD). Medline, Cochrane, and Embase databases were searched from inception to September 2, 2022. We conducted a meta-analysis if an outcome was evaluated in at least two similar studies. We included 15 studies with 77,780 total patients. Of the 15 studies, 11 had a cohort design (five prospective and six retrospective), and four were case series. Patients with CKD were older and had a higher prevalence of comorbidities than non-CKD patients. The two groups did not differ in procedural failure rate, vascular complications, or pericardial tamponade. CKD patients exhibited higher odds of in-hospital acute kidney injury (AKI) and bleeding, longer-term bleeding, and mortality than those without CKD. The risk of in-hospital and longer-term cardioembolic events was similar between CKD and non-CKD populations (odds ratio = 1.01 [95% CI 0.70-1.15] and 1.05 [95% CI 0.55-2.00], respectively). Patients with ESRD had higher odds of in-hospital mortality and cardioembolic events than non-ESRD patients, with no differences in risk of pericardial tamponade. Based on observational studies, LAAO may be an effective option to prevent cardioembolic events in CKD. However, CKD patients may have higher odds of AKI and in-hospital and long-term bleeding and mortality. The adverse clinical outcomes observed in CKD patients may be attributed to this population's high burden of comorbidities, especially among those with ERSD, rather than the LAAO procedure itself. To ensure maximum clinical benefit, careful patient selection, management, and surveillance involving multidisciplinary teams are essential for CKD patients undergoing LAAO. Transcatheter Left Atrial Appendage Occlusion (laao) Can Prevent Cardioembolic Events In Chronic Kidney Disease (ckd) Patients. However, Ckd Patients, Particularly Those With End-stage Renal Disease/dialysis (esrd), May Face Increased Odds Of Acute Kidney Injury, In-hospital And Long-term Bleeding, And Mortality. Notably, These Adverse Outcomes In Ckd Patients May Be Linked To Their High Comorbidity Burden, Particularly In Those With Esrd, Rather Than The Laao Procedure Itself. Careful Patient Selection, Management, And Surveillance Involving Multidisciplinary Teams Are Essential For Ckd Patients Undergoing Laao To Ensure Maximum Clinical Benefit Transcatheter left atrial appendage occlusion (LAAO) can prevent cardioembolic events in chronic kidney disease (CKD) patients. However, CKD patients, particularly those with end-stage renal disease/dialysis (ESRD), may face increased odds of acute kidney injury, in-hospital and long-term bleeding, and mortality. Notably, these adverse outcomes in CKD patients may be linked to their high comorbidity burden, particularly in those with ESRD, rather than the LAAO procedure itself. Careful patient selection, management, and surveillance involving multidisciplinary teams are essential for CKD patients undergoing LAAO to ensure maximum clinical benefit.

Chronic kidney disease in patients with long-term type 1 diabetes mellitus

BACKGROUND: Patients with type 1 diabetes mellitus (T1D) have an earlier age of onset and a longer course of the disease, already by middle age they have the development of microand macrovascular diabetic complications that reduce the quality and duration of life.AIM: To evaluate the prevalence of chronic kidney disease (CKD) and other late complications of T1D depending on renal dysfunction in the population of patients with T1D with disease duration of 20 and more years, who underwent examination and treatment in Endocrinology Research Centre.MATERIALS AND METHODS: A one-stage single-center epidemiological non-randomised study was conducted using the database of Endocrinology Research Centre with the study of 500 patients’medical histories with long-term T1D (20 years and mores), without kidney damage and with CKD at different stages (CKD C1–C5, C5D, after transplantation), examined and treated from 2011 to 2023.RESULTS: Normal renal function was observed in 10.8% of patients (n=54). Terminal stage of CKD was reached in 28.0% (n=140), of which 12.4% were on renal replacement therapy with program hemodialysis (RRT-HD), and 12.0% after isolated kidney transplantation or combined kidney and pancreas transplantation, the rest were at different stages of CKD. Normoalbuminuria was observed in 15.4% (n=77) among 500 patients. The prevalence of late complications of DM among the examined patients was high and increasing with the progression of renal dysfunction: diabetic retinopathy was diagnosed in 96% of patients, distal symmetrical polyneuropathy — in 97% of patients, various forms of autonomic neuropathy — in more than half of patients. About 60% of patients had diagnosed arterial atherosclerosis in the legs, about one third — atherosclerosis of brachiocephalic arteries, 23% — confirmed coronary heart disease, and suffered cardiovascular events (myocardial infarction, acute cerebral circulation disorder) — 19% of patients, about half of whom had CKD of different severity. Factors for increased risk of cardiovascular disease: estimated glomerular filtration rate (eGFR)&lt;60 mL/min/1.73m2, OR=7.1; 95% CI 3.6–8.4; p&lt;0.001), eGFR &lt;30 mL/min/1.73m2 OR=8.7; 95% CI 2.8–8.4; p&lt;0.001), eGFR &lt;15 mL/min/1.73m2 OR=14; 95% CI 6.3–31.3; p&lt;0.001); albuminuria &gt; 30 mg/g OR=2.4; 95% CI 1.6–3.6; p&lt;0.001), dialysis OR=14.1; 95% CI 6.2–32.1; p&lt;0.001), kidney transplant OR=11.7; 95% CI 5.4–24.9; p&lt;0.001). Manifestation of T1D between 1996–2002 reduced the risk of developing CKD by 10.75; 95% CI 4.37; 27.03) vs manifestation of T1D earlier. Age of T1D debut 6–17 years increased the risk of reaching terminal CKD vs age of debut &gt;18 years: OR=2.4; 95% CI 1.22; 5.022; p=0.012).CONCLUSION: Despite a significant reduction in the risk of developing CKD in individuals with T1D debut between 1996 and 2002, renal dysfunction is a frequent complication in patients with a long disease course, combining with other late complications and contributing to a high risk of terminal stage of CKD and cardiovascular events. Early age of T1D debut increases the risk of terminal CKD.

Cardiovascular Event Predictors in Hospitalized Chronic Kidney Disease (CKD) Patients: A Nationwide Inpatient Sample Analysis.

This study seeks to confirm the risk factors linked to cardiovascular (CV) events in chronic kidney disease (CKD), which have been identified as CKD-related. We aim to achieve this using a larger, more diverse, and nationally representative dataset, contrasting with previous research conducted on smaller patient cohorts. The study utilized the nationwide inpatient sample database to identify adult hospitalizations for CKD from 2016 to 2020, employing validated ICD-10-CM/PCS codes. A comprehensive literature review was conducted to identify both traditional and CKD-specific risk factors associated with CV events. Risk factors and CV events were defined using a combination of ICD-10-CM/PCS codes and statistical commands. Only risk factors with specific ICD-10 codes and hospitalizations with complete data were included in the study. CV events of interest included cardiac arrhythmias, sudden cardiac death, acute heart failure, and acute coronary syndromes. Univariate and multivariate regression models were employed to evaluate the association between CKD-specific risk factors and CV events while adjusting for the impact of traditional CV risk factors such as old age, hypertension, diabetes, hypercholesterolemia, inactivity, and smoking. A total of 690,375 hospitalizations for CKD were included in the analysis. The study population was predominantly male (375,564, 54.4%) and mostly hospitalized at urban teaching hospitals (512,258, 74.2%). The mean age of the study population was 61 years (SD 0.1), and 86.7% (598,555) had a Charlson comorbidity index (CCI) of 3 or more. At least one traditional risk factor for CV events was present in 84.1% of all CKD hospitalizations (580,605), while 65.4% (451,505) included at least one CKD-specific risk factor for CV events. The incidence of CV events in the study was as follows: acute coronary syndromes (41,422; 6%), sudden cardiac death (13,807; 2%), heart failure (404,560; 58.6%), and cardiac arrhythmias (124,267; 18%). A total of 91.7% (113,912) of all cardiac arrhythmias were atrial fibrillations. Significant odds of CV events on multivariate analyses included: malnutrition (aOR: 1.09; 95% CI: 1.06-1.13; p<0.001), post-dialytic hypotension (aOR: 1.34; 95% CI: 1.26-1.42; p<0.001), thrombophilia (aOR: 1.46; 95% CI: 1.29-1.65; p<0.001), sleep disorder (aOR: 1.17; 95% CI: 1.09-1.25; p<0.001), and post-renal transplant immunosuppressive therapy (aOR: 1.39; 95% CI: 1.26-1.53; p<0.001). The study confirmed the predictive reliability of malnutrition, post-dialytic hypotension, thrombophilia, sleep disorders, and post-renal transplant immunosuppressive therapy, highlighting their association with increased risk for CV events in CKD patients. No significant association was observed between uremic syndrome, hyperhomocysteinemia, hyperuricemia, hypertriglyceridemia, leptin levels, carnitine deficiency, anemia, and the odds of experiencing CV events.

Long-term air pollution exposure, habitual physical activity, and incident chronic kidney disease

Both air pollution and physical inactivity contribute to the increased risk of incident chronic kidney disease (CKD). However, the detrimental effects of air pollution exposure could be augmented by an elevated intake of air pollutants during exercise. In the present study, we analyzed 367,978 participants who were CKD-free at baseline (2006–2010) based on the UK Biobank. Air pollutants included fine particulate matter (PM2.5 and PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOX). Physical activity (PA) was obtained by the self-reported questionnaire. Using Cox proportional hazards models, hazard ratios (HRs) for incident CKD related to air pollution, PA, and incident CKD were evaluated. During a median of 12.4 years of follow-up, 14,191 incident CKD events were documented. High PM2.5, PM10, NO2, and NOX increased CKD risks by 11 %, 15 %, 14 %, and 12 %, respectively, while moderate and high PA reduced CKD risks by 18 % and 22 %, respectively. Participants with high PA and low air pollution exposure had 29 %, 31 %, 30 %, and 30 % risks of incident CKD than those with low PA and high air pollution exposure for the four air pollutants, with multivariable-adjusted HRs of 0.71 (95 % confidence intervals [CI]: 0.65–0.76) for PM2.5, 0.69 (95 % CI: 0.64–0.75) for PM10, 0.70 (95 % CI: 0.64–0.75) for NO2, and 0.70 (95 % CI: 0.64–0.75) for NOX. No clear interactions were observed between each air pollutant exposure and PA (all P for interaction > 0.05). The findings that reducing air pollution exposure and increasing PA were both independently correlated with a diminished risk of incident CKD suggest that PA could be targeted to prevent CKD generally regardless of air pollution levels. Further research is needed in areas polluted moderately and severely to examine our findings.

Association between the High-Sensitivity C-Reactive Protein/Albumin Ratio and New-Onset Chronic Kidney Disease in Chinese Individuals

Introduction: Inflammation is associated with development of chronic kidney disease (CKD). However, the association of the high-sensitivity C-reactive protein (hs-CRP)/albumin ratio (CAR) on the risk of CKD in the general population is unknown. This study explored the relationship between the CAR and CKD and the ability of this ratio to predict CKD in the general population. Methods: A total of 47,472 participants in the Kailuan study who met the inclusion criteria in 2010 were selected and grouped using the quartile method. A Cox proportional hazard regression model was used to evaluate the association of the CAR on the risk of CKD. The C-index, net reclassification index (NRI), and overall identification index (IDI) were calculated to evaluate the ability of the CAR to predict CKD. Results: During a follow-up of 378,383 person-years, CKD events occurred in 6,249 study participants (13.16%). The Cox proportional hazard regression model showed that the hazard ratio (95% confidence interval) for CKD events was 1.18 (1.10–1.28) in the Q3 group and 1.42 (1.32–1.53) in the Q4 group when compared with the Q1 group. Compared with the single index, the C-index, NRI, and IDI values were significantly improved when the CAR was added for prediction of risk of CKD. Conclusions: A higher CAR was an independent risk factor for CKD. The ability of the CAR to predict CKD was better than that of hs-CRP or albumin. The CAR provides an important reference index for predicting the risk of CKD.

Depressive symptoms and sleep duration in relation to chronic kidney disease: Evidence from the China health and retirement longitudinal study

ObjectiveNowadays, the joint effects of depressive symptoms and sleep duration on the risk of chronic kidney disease (CKD) are still unclear. We aimed to prospectively assess the combined effect of depressive symptoms and sleep duration on the incidence of CKD in middle-aged and elderly Chinese population. MethodsA total of 10,953 participants from the China Health and Retirement Longitudinal Study (CHARLS) were included. Depressive symptoms were measured using the 10-item Center for Epidemiological Studies Depression scale (CESD-10). Sleep duration was evaluated by self-reported. CKD events were based on self-reported physicians' diagnosis or personal estimate glomerular filtration rate level (eGFR <60 mL/min/1.73 m2). Cox regression models were established to analyze the correlation between depressive symptoms, sleep duration and the risk of CKD. ResultsOver a mean follow-up time was 6.76 ± 0.98 years, 851 (7.8%) participants had reported CKD events during the follow-up. Elevated depressive symptoms (HR = 1.65, 95% CI = 1.43–1.90) and short sleep duration (HR = 1.48, 95% CI = 1.27–1.72) were independently associated with an increased CKD risk after adjusting for potential confounding factors. Participants with short sleep duration (< 6 h)/elevated depressive symptoms (HR = 2.24, 95% CI = 1.89–2.65) were associated with the highest risk of CKD than those with normal sleep duration/low depressive symptoms. ConclusionsElevated depressive symptoms and short sleep duration were independent risk factors for CKD. There was a combined effect between depressive symptoms and sleep duration in increasing the risk of CKD.

Contrast-associated acute kidney injury and cardiovascular events: a secondary analysis of the PRESERVE cohort.

Contrast-associated acute kidney injury (CA-AKI) has been associated with a higher risk of cardiovascular (CV) events. We studied the risk of CV events in chronic kidney disease (CKD) patients undergoing angiography and whether biomarkers can predict such events. We also explored whether CA-AKI mediates the association of pre-angiography estimated glomerular filtration rate (eGFR) on CV events. We analysed participants from the Prevention of Serious Adverse Events following the Angiography (PRESERVE) trial. Urinary tissue inhibitor of matrix metalloproteinase [TIMP]-2 and insulin growth factor binding protein [IGFBP]-7, plasma brain-type natriuretic peptide (BNP), high sensitivity C-reactive protein (hs-CRP), and serum cardiac troponin-I (Tn-I) were assayed before and after angiography. We assessed the composite risk of CV events by day 90. Of the 922 participants, 119 (12.9%) developed CV events, and 73 (7.9%) developed CA-AKI. Most cases of CA-AKI (90%) were stage 1. There were no differences in urinary [TIMP-2]•[IGFBP7] concentrations or the proportion of patients with CA-AKI among those with and without CV events. Higher BNP, Tn-I, and hs-CRP were associated with CV events, but their discriminatory capacity was modest (AUROC <0.7). CA-AKI did not mediate the association of the pre-angiography eGFR on CV events. Most episodes of CA-AKI are stage 1 AKI and are not associated with CV events. Less severe CA-AKI episodes also did not mediate the risk of pre-angiography eGFR on CV events. Our findings suggest that most CV events after contrast procedures are due to underlying CKD and CV risk factors rather than less severe CA-AKI episodes and should help enhance the utilization of clinically indicated contrast procedures among high-risk patients with CKD. Further research is required to examine whether moderate-to-severe CA-AKI episodes are associated with CV events.

Absolute and Relative Risks of Kidney and Urological Complications in Patients With Inflammatory Bowel Disease.

The burden of kidney and urological complications in patients with inflammatory bowel disease (IBD) remains poorly characterized. We analyzed association between developing IBD (as a time-varying exposure) and relative risks of receiving diagnoses of chronic kidney disease (CKD), acute kidney injury (AKI), or kidney stones, and experiencing a clinically-relevant decline in estimated glomerular filtration rate (eGFR) (CKD progression; composite of kidney failure or an eGFR decline ≥30%) in 1,682,795 individuals seeking healthcare in Stockholm, Sweden, during 2006-2018. We quantified 5- and 10-year absolute risks of these complications in a parallel matched cohort of IBD cases and random controls matched (1:5) on sex, age, and eGFR. During median 9 years, 10,117 participants developed IBD. Incident IBD was associated with higher risks of kidney-related complications compared with non-IBD periods: hazard ratio (HR) (95% confidence interval) was 1.24 (1.10-1.40) for receiving a CKD diagnosis and 1.11 (1.00-1.24) for CKD progression. For absolute risks, 11.8% IBD cases had a CKD event within 10-year. Of these, 6.4% received a CKD diagnosis, and 7.9% reached CKD progression. The risks of AKI (HR 1.97 [1.70-2.29]; 10-year absolute risk 3.6%) and kidney stones (HR 1.69 [1.48-1.93]; 10-year absolute risk 5.6%) were also elevated. Risks were similar in Crohn's disease and ulcerative colitis. More than 10% of patients with IBD developed CKD within 10-year from diagnosis, with many not being identified through diagnostic codes. This, together with their elevated AKI and kidney stone risks, highlights the need of established protocols for kidney function monitoring and referral to nephrological/urological care for patients with IBD.

Warfarin treatment quality and outcomes in patients with non-valvular atrial fibrillation and CKD G3-G5D

IntroductionWarfarin treatment quality is calculated as time in therapeutic range (TTR). TTR ≥ 70 % is considered reducing the risk of adverse events for patients with atrial fibrillation (AF). The association of TTR and adverse events in chronic kidney disease (CKD) is however poorly investigated. The aim is to explore this further. Materials and methodsSwedish cohort study based on national healthcare registers between 2009 and 2018, including Swedish Renal Registry, Swedish Stroke Register and AuriculA - the Swedish national quality register for AF and anticoagulation. Investigating the effect of individual TTR (iTTR) and iTTR ≥ 70 % versus <70 % on the risk of ischemic stroke, major bleeding and death for patients with CKD GFR category 3–5 (G3-G5) including patients on dialysis (G5D) and non-valvular AF (NVAF). ResultsOf 2379 included patients 21.9 % had G3, 47.5 % G4, 10.8 % G5 and 19.8 % G5D. TTR in G3 was 75.6 %, G4 72.2 %, G5 67.6 % and G5D 62.0 %. Increase by 10 percentage points iTTR conferred lower risk of major bleeding, ischemic stroke and death for all patients (hazard ratio 0.91 (95 % Confidence interval 0.87–0.94), 0.92 (0.85–0.99) and 0.88 (0.85–0.90)). iTTR≥ 70 % versus <70 % was associated with lower risk of bleeding and death in all patients (0.63 (0.51–0.77) and (0.51 (0.43–0.61)), and a non-significant tendency towards lower stroke risk (0.67 (0.43–1.06)). ConclusionsWarfarin treatment quality worsens with decreasing GFR. Higher iTTR confers lower risk of bleeding, ischemic stroke and death in patients with NVAF and G3-G5D. iTTR ≥ 70 % was associated with better safety profile. Close monitoring of patients with CKD on warfarin is recommended.

Association between dietary vitamin E intake and chronic kidney disease events in US adults: a cross-sectional study from NHANES 2009-2016.

The relationship between vitamin E supplementation and the prevalence of chronic kidney disease (CKD) is unclear. We discussed the relationship between vitamin E intake and CKD prevalence and further investigated the effect on different CKD risk strata. We ultimately included 20295 participants from the National Health and Nutrition Examination Survey (NHANES) database from 2009 to 2016. Multiple logistic regression and restricted cubic splines (RCS) were applied to explore the relationship between vitamin E intake and CKD prevalence and risk stratification. Subgroup analysis was applied to assess the stability of the association between vitamin E intake and CKD. In the CKD prevalence study, we found a negative association between high vitamin E intake and CKD prevalence through an adjusted multiple logistic regression model, the odds ratio (OR) was 0.86 [95% confidence interval (CI) 0.74-1.00; P for trend=.041] and RCS showed a nonlinear negative correlation (P-nonlinear=.0002, <.05). In the CKD risk stratification study, we found that in very high-risk patients, the OR was 0.51 (95% CI 0.32-0.84; P for trend=.006) and the RCS also showed a nonlinear negative correlation (P-nonlinear <.0001, <.05). Subgroup analysis demonstrated that the correlations were stable across populations (P-values >.01 for all interactions). Dietary vitamin E intake was negatively associated with the prevalence of CKD in US adults. Increased vitamin E intake was a protective factor across CKD risk strata, and as vitamin E intake increased, there was a non-linear downward trend in the proportion progressing to very high-risk CKD.

Non-invasive chronic kidney disease risk stratification tool derived from retina-based deep learning and clinical factors

Despite the importance of preventing chronic kidney disease (CKD), predicting high-risk patients who require active intervention is challenging, especially in people with preserved kidney function. In this study, a predictive risk score for CKD (Reti-CKD score) was derived from a deep learning algorithm using retinal photographs. The performance of the Reti-CKD score was verified using two longitudinal cohorts of the UK Biobank and Korean Diabetic Cohort. Validation was done in people with preserved kidney function, excluding individuals with eGFR <90 mL/min/1.73 m2 or proteinuria at baseline. In the UK Biobank, 720/30,477 (2.4%) participants had CKD events during the 10.8-year follow-up period. In the Korean Diabetic Cohort, 206/5014 (4.1%) had CKD events during the 6.1-year follow-up period. When the validation cohorts were divided into quartiles of Reti-CKD score, the hazard ratios for CKD development were 3.68 (95% Confidence Interval [CI], 2.88–4.41) in the UK Biobank and 9.36 (5.26–16.67) in the Korean Diabetic Cohort in the highest quartile compared to the lowest. The Reti-CKD score, compared to eGFR based methods, showed a superior concordance index for predicting CKD incidence, with a delta of 0.020 (95% CI, 0.011–0.029) in the UK Biobank and 0.024 (95% CI, 0.002–0.046) in the Korean Diabetic Cohort. In people with preserved kidney function, the Reti-CKD score effectively stratifies future CKD risk with greater performance than conventional eGFR-based methods.

#4296 EFFECTS OF FERRIC CITRATE HYDRATE ON FIBROBLAST GROWTH FACTOR 23 AND PLATELET COUNT IN CKD AND NON-CKD PATIENTS WITH IRON DEFICIENCY ANAEMIA

Abstract Background and Aims Iron deficiency increases the transcription and cleavage of the peptide hormone, fibroblast growth factor 23(FGF23). Elevated FGF23 has been associated with increased risk of cardiovascular events and mortality. Iron deficiency also increases platelet count (PLT) in part, and higher levels PLT are associated with arterial thrombosis in the brain. Ferric citrate hydrate (FC, Riona®, Torii Pharmaceutical Co., Ltd. Tokyo, Japan) is an oral iron-based phosphate binder for patients with chronic kidney disease (CKD) and also an iron preparation approved for treatment of iron deficiency anaemia (IDA) in Japan. A phase 3 study was conducted to investigate the efficacy and safety of FC in CKD and non-CKD patients with IDA. This study aimed to evaluate the effects of FC on intact FGF23 and c-terminal FGF23 levels, and the proportion of patients with high PLT (exceeding upper limit: &amp;gt;35.2 × 104/µL). Method A randomized, open-label, multicentre, uncontrolled, 24-week study was conducted at 31 centres in Japan from July 2018 to December 2019 (JapicCTI-184000) in CKD and non-CKD patients with IDA (Hb: ≥8.0 g/dL and &amp;lt;11.0 g/dL, serum ferritin &amp;lt;50 ng/mL in CKD (eGFRcre &amp;lt;60 mL/min/1.73 m2) and &amp;lt;12 ng/mL in non-CKD). CKD patients scheduled to initiate maintenance dialysis were excluded. Dynamic allocation was used to randomise subjects (CKD and non-CKD with Hb at baseline) to the FC-low group (500 mg [approximately 120 mg elemental iron]/day) or FC-high group (1000 mg [approximately 240 mg elemental iron]/day) (1:1). Notably, if investigators determined that sufficient iron replacement had been achieved from week 8 onwards, the study treatment was completed. For this reason, changes from baseline to week 8 were evaluated. Results Of 73 patients (CKD n = 42, non-CKD n = 31), 36 were allocated to the FC-low group (CKD n = 21, non-CKD n = 15) and 37 to the FC-high group (CKD n = 21, non-CKD n = 16). Baseline levels of serum ferritin, transferrin saturation (TSAT), c-terminal FGF23, intact FGF23, and PLT are shown in Table 1. Regardless of CKD status, serum ferritin and TSAT increased. After FC-low treatment, mean changes from baseline to week 8 (95% CI) in serum ferritin and TSAT were 18.8 (13.3, 24.2) ng/mL and 8.1 (4.4, 11.8) % in CKD, 17.5 (13.8, 21.3) ng/mL and 13.8 (8.7, 18.9) % in non-CKD;, they were 28.1 (13.4, 42.7) ng/mL and 8.8 (5.4, 12.1) % in CKD, 15.9 (12.1, 19.8) ng/mL and 19.9 (9.8, 30.1) % in non-CKD. After administration of FC, in both groups, intact FGF23 levels did not change, whereas c-terminal FGF23 levels decreased. Median changes (interquartile range) from baseline to week 8 of c-terminal FGF23 were -58.00 (-227.50, -12.25) RU/mL in CKD and -725.00 (-1124.00, -168.50) RU/mL in non-CKD, and -66.00 (-265.70, -27.00) RU/mL in CKD and -649.50 (-1127.00, -326.65) RU/mL in non-CKD. Serum phosphate did not change regardless of CKD status. At baseline, high PLT was observed in the FC-low group in 1 CKD case (5.0%) and 8 non-CKD cases (53.3%), and in the FC-high group in 3 CKD cases (15.8%) and 8 non-CKD cases (50.0%). In all these patients, PLT reduction to below 35.2 × 104/µL was observed until week 8. Conclusion In patients with IDA, administration of FC increased serum ferritin and TSAT, decreased c-terminal FGF23, and normalized PLT in patients with high PLT at baseline regardless of CKD status. FC may decrease the potential risk of cardiovascular events in CKD or non-CKD patients with IDA.

#3256 LONGITUDINAL ASSOCIATION BETWEEN IRON STORES BIOMARKERS AND MAJOR ADVERSE CARDIOVASCULAR EVENTS IN CHRONIC KIDNEY DISEASE

Abstract Background and Aims Iron deficiency is a frequent condition in moderate to severe chronic kidney disease (CKD), often left under-screened, and infrequently supplemented. Iron deficiency is a major contributor to anemia, which is known to negatively impact outcomes and quality of life in CKD. However, evidence of an anemia-independent effect of iron deficiency on cardiovascular morbidity and all-cause mortality has emerged. Current challenges of studying the association between iron deficiency and the risk of events in CKD are the definition of critical thresholds for these biomarkers, the potential interaction between them, and their evolution over time. Previous observational cohort studies have only focused on baseline values of transferrin saturation and ferritin, the two traditional biomarkers of iron deficiency. Our aim was to study the longitudinal association between iron stores biomarkers and cardiovascular risk in CKD by evaluating the total effect of these biomarkers on major adverse cardiovascular events (MACE). Method We used data from the CKD-REIN cohort, which included 3033 patients with moderate to severe CKD from 40 nationally representative nephrology clinics in France between 2013 and 2016. All patients with at least one measurement of TSAT and ferritin were included in the present study. Our primary endpoint was MACE, defined as the first event among cardiovascular death, myocardial infarction, stroke or hospitalization for acute heart failure. Repeated measures of TSAT and ferritin were included as time-dependent variables in cause-specific Cox proportional hazard models for risk of MACE, with initiation of kidney replacement therapy (KRT) and death as competitive events. Models were adjusted for time-varying estimated glomerular filtration rate (eGFR), white cells and baseline age, sex, iron supplementation, and erythropoietin stimulating agents. Analyses were not adjusted for hemoglobin level because the aim of the study was to investigate the total effect of iron deficiency on MACE. Non-linear effects of TSAT and ferritin and their interaction were modeled using natural splines functions. Results A total of 2670 patients were included in the analysis: 65% were men, median age was 68 years (interquartile range IQR 60-76). Median baseline eGFR was 34 ml/min/1.73 m2 (IQR 25-44), TSAT was 24% (IQR 18-30) and ferritin was 127 ng/ml (IQR 72-230). Over a median follow-up period of 4.4 years, participants had a median of 5 (IQR 2-8) and 4 (IQR 2-6) measurements of ferritin and TSAT, respectively; 396 MACE before KRT were recorded. The negative nonlinear association of iron deficiency with MACE was essentially captured by TSAT, and the interaction terms between TSAT and ferritin were not statistically significant (p = 0.94). Compared with patients with TSAT of 20% and ferritin of 100 ng/ml, those with TSAT values &amp;lt; 20% had a higher adjusted hazard of MACE independently of ferritin values (See Figure 1); for example, for TSAT = 10% and ferritin = 100 ng/ml, the hazard ratio (HR) was 1.96, 95% CI (1.60-2.39). Conclusion In CKD patients under nephrology care, current value of TSAT below 20% was associated with higher risk of MACE regardless of ferritin current value. Before investigating strategies of treatment in clinical trials as PIVOTAL in dialysis patients, further studies clarifying critical thresholds of TSAT and ferritin in non-dialysis CKD patients, in presence or absence of anemia and among specific CKD subpopulations are highly desirable.

#5619 THE ASSOCIATION BETWEEN THE LEVELS OF URIC ACID AND RENAL OUTCOMES IN EARLY CKD PATIENTS: A MULTI-CENTER REAL-WORLD DATA ANALYSIS

Abstract Background and Aims It is well known that serum uric acid (SUA) plays an important role both in patients with and without chronic kidney disease (CKD). However, the effect of SUA on renal outcomes of CKD patients, especially with asymptomatic hyperuricemia, remains controversial. Therefore, our study explores the relationship between SUA and adverse events in early CKD (stage 1-3) patients in a real-world setting. Method This multi-center real-world study analyzed the data from Chinese Renal Data System (CRDS). Eligible CKD patients (eGFR) (estimated glomerular filtration rate≥30 mL/min/1.73 m2) were enrolled. The primary endpoint is the decline of renal function defined as at least 40% decrease in eGFR. The secondary endpoints include onset of composite cardiovascular events and all-cause mortality. A multivariable cox regression model were used and the associations between levels of mean SUA and all endpoints were evaluated on a continuous scale with restricted cubic spline (RCS) curves based on Cox proportional hazards models. Kaplan-Meier survival curves were used to illustrate the ability of SUA to predict the end points. Results 25,202 adults (mean [SD] age, 52.59 [17.90] years, 8,212 male [46.1%], 9,604 female [53.9%]) were included in this study. During a median follow-up period of 2.61 years, 3,451 (15.9%) at least 40% decreased in eGFR. After adjustment for confounders, higher uric acid concentrations were independently associated with the higher risk for the decline of renal function [Per SD increment adjusted hazard ratio [aHR]: 1.41, 95%CI 1.36-1.47]; composite cardiovascular events [Per SD increment [aHR]: 1.04, 95%CI 1.01-1.07], all-cause mortality [Per SD increment [aHR]:1.32, 95%CI 1.14-1.54]. RCS curves showed that HRs for renal function progression, all-cause mortality and composite cardiovascular events increased significantly with the increase of SUA concentration in CKD patients. Results were consistent in stratified analyses. The KM curves suggested that patients with asymptomatic hyperuricemia had a substantially worse survival rate for renal function. Conclusion SUA is an independent risk factor for the decline of renal function, cardiovascular events and all-cause mortality in early CKD patients (stage 1-3). Treatment of asymptomatic hyperuricemia may be a potential avenue to improve outcomes in CKD patients.