Risk Of Chronic Kidney Disease In Patients Research Articles

Association between waist triglyceride index, body mass index, dietary inflammatory index, and triglyceride- glucose index with chronic kidney disease: the 1999-2018 cohort study from NHANES

PurposeTo compare the dietary inflammatory index (DII), triglyceride glucose index (TyG), waist triglyceride index (WTI), and body mass index (BMI) in predicting the survival of chronic kidney disease (CKD).MethodologyInclusion of 23,099 participants from the NHANES database who met specific criteria. Baseline was established using quartiles of DII index. The relationship between DII index, WTI index, TyG index, and BMI index with mortality rate in CKD patients was evaluated using Kaplan-Meier curves. Univariate and multivariate COX regression risk models were used to study the relationship between DII index, WTI index, and TyG index with mortality risk in CKD patients. Stratification of eGFR by age and gender was conducted to investigate the association between DII index, WTI index, and TyG index with mortality risk in CKD patients. Restricted cubic spline analysis was used to study the correlation between DII index, WTI index, and TyG index with mortality risk in CKD patients.ResultsThe incidence of CKD increased with the increase of DII index, WTI index and TyG index. After multivariable adjustment, the fourth quartile of DII index, TyG index and WTI index showed the highest risk for CKD [DII: hazard ratio (HR) 1.36, 95% confidential interval (CI) (1.23–1.51); TyG: HR 1.21; 95% CI (1.07–1.37); WTI: HR 1.29; 95% CI (1.13–1.46)]. There was no difference in the risk of developing CKD between the obese group (BMI ≥24 kg/m2) and the normal weight group (P>0.05).ConclusionThis study has identified a significant association between elevated DII index, WTI index, and TyG index with the risk of CKD. Furthermore, the DII index demonstrated superior prognostic capability in predicting CKD compared to other indicators.

Large-Scale Proteomics Improve Prediction of Chronic Kidney Disease in People With Diabetes.

To develop and validate a protein risk score for predicting chronic kidney disease (CKD) in patients with diabetes and compare its predictive performance with a validated clinical risk model (CKD Prediction Consortium [CKD-PC]) and CKD polygenic risk score. This cohort study included 2,094 patients with diabetes who had proteomics and genetic information and no history of CKD at baseline from the UK Biobank Pharma Proteomics Project. Based on nearly 3,000 plasma proteins, a CKD protein risk score including 11 proteins was constructed in the training set (including 1,047 participants; 117 CKD events). The median follow-up duration was 12.1 years. In the test set (including 1,047 participants; 112 CKD events), the CKD protein risk score was positively associated with incident CKD (per SD increment; hazard ratio 1.78; 95% CI 1.44, 2.20). Compared with the basic model (age + sex + race, C-index, 0.627; 95% CI 0.578, 0.675), the CKD protein risk score (C-index increase 0.122; 95% CI 0.071, 0.177), and the CKD-PC risk factors (C-index increase 0.175; 95% CI 0.126, 0.217) significantly improved the prediction performance of incident CKD, but the CKD polygenic risk score (C-index increase 0.007; 95% CI -0.016, 0.025) had no significant improvement. Adding the CKD protein risk score into the CKD-PC risk factors had the largest C-index of 0.825 (C-index from 0.802 to 0.825; difference 0.023; 95% CI 0.006, 0.044), and significantly improved the continuous 10-year net reclassification (0.199; 95% CI 0.059, 0.299) and 10-year integrated discrimination index (0.041; 95% CI 0.007, 0.083). Adding the CKD protein risk score to a validated clinical risk model significantly improved the discrimination and reclassification of CKD risk in patients with diabetes.

Efficacy and Safety of Anti-Osteoporotic Agents across CKD Stages: A Meta-Analysis of Randomized Clinical Trials.

Osteoporosis poses a significant health concern, especially for individuals with chronic kidney disease (CKD). CKD disrupts mineral and bone metabolism, heightening the risk of fractures and complicating the management of osteoporosis. While anti-osteoporotic interventions aim to address bone health in CKD patients, ongoing research is essential to understand the comparative efficacy and safety of these medications, particularly in different CKD stages, notably in stages 4 and 5. We searched PubMed/MEDLINE, EMBASE, and the Cochrane CENTRAL for randomized controlled trials assessing the efficacy and safety of osteoporosis interventions in CKD up to June 15, 2024. The analysis utilized the pooled odds ratio (OR) along with the corresponding 95% confidence interval (CI), employing Comprehensive Meta-Analysis software, version 3.0. To assess heterogeneity in the results of individual studies, we used Cochran's Q statistic and the I2 statistic. We analyzed 12 randomized controlled trials involving 31,027 participants, revealing a significantly lower risk of vertebral fractures with anti-osteoporotic agents (teriparatide, denosumab, romosozumab, raloxifene) compared to placebo (pooled OR, 0.28 [95% CI, 0.22-0.36]). Stratification by CKD stages showed a lower risk in Stages 1-3 but no significant reduction in stages 4 and 5. Teriparatide, denosumab, and romosozumab were effective in lowering fracture risk, whereas Raloxifene showed no significant effect. The lumbar spine, femoral neck, and total hip BMD showed no significant differences between anti-osteoporotic agents (denosumab, raloxifene, risedronate, alendronate, teriparatide) and placebo. However, romosozumab demonstrated a significantly greater BMD change in all kidney function categories. No reported side effects were observed in CKD stages 1-5 across the trials. Our meta-analysis highlights the effectiveness of anti-osteoporotic agents in lowering vertebral fracture risk in CKD patients, particularly in stages 1-3. However, this benefit is not apparent in stages 4 and 5, necessitating further research. Despite the absence of reported side effects in CKD patients, clinicians should carefully assess the suitability of these medications, considering individual risks and benefits.

Genetic association analyses highlight apolipoprotein B as a determinant of chronic kidney disease in patients with type 2 diabetes

BACKGROUNDBlood lipid levels were associated with chronic kidney disease (CKD) in patients with type 2 diabetes (T2D), but the genetic basis and causal nature remains unclear. OBJECTIVEThis study aimed to investigate the relationships of lipids and their fractions with CKD in patients with T2D. METHODSOur prospective analysis involved 8,607 White participants with T2D but no CKD at baseline from the UK Biobank. Five common lipid traits were included as exposures. Weighted genetic risk scores (GRSs) for these lipid traits were developed. The causal associations between lipid traits, as well as lipid fractions, and CKD were explored using linear or nonlinear Mendelian randomization (MR). The 10-year predicted probabilities of CKD were evaluated via integrating MR and Cox models. RESUTLSHigher GRS of apolipoprotein B (ApoB) was associated with an increased CKD risk (HR[95% CI]:1.07[1.02,1.13] per SD;P=0.008) after adjusting for potential confounders. Linear MR indicated a positive association between genetically predicted ApoB levels and CKD (HR[95% CI]:1.53[1.12,2.09];P=0.008), but no evidence of associations was found between other lipid traits and CKD in T2D. Regarding 12 ApoB-contained lipid fractions, a significant causal association was found between medium very-low-density lipoprotein particles and CKD (HR[95% CI]:1.16[1.02,1.32];P=0.020). Nonlinear MR did not support nonlinearity in these causal associations. The 10-year probability curve showed that ApoB levels was positively associated with the risk of CKD in patients with T2D. CONCLUSIONLower ApoB levels were causally associated with a reduced risk of CKD in patients with T2D, positioning ApoB as a potential therapeutic target for CKD prevention in this population.

Association between monocyte-lymphocyte ratio and all-cause and cardiovascular mortality in patients with chronic kidney diseases: A data analysis from national health and nutrition examination survey (NHANES) 2003-2010

Background The relationship between monocyte-to-lymphocyte ratio (MLR) and prognosis in patients with chronic kidney disease (CKD) remains unclear. The aim of this study was to investigate the association between MLR and both all-cause mortality and cardiovascular disease (CVD) mortality in patients with CKD. Methods This study analyzed data from National Health and Nutrition Examination Survey 2003-2010. This study included 11262 eligible subjects, and 3015 of them were with CKD. We first compared the differences in clinical characteristics between individuals with and without CKD, and then grouped the CKD population based on quartiles of MLR. The partial correlation analysis was conducted to assess the relationships between MLR and some important clinical features. Cox proportional hazards models were used to investigate the associations between MLR and mortality from all-cause and cardiovascular disease. Restricted cubic spline (RCS) was used to investigate the dose-response relationship between MLR and mortality, the receiver operating characteristic (ROC) curves is used to compare the efficacy of MLR with different clinical biological indicators in assessing the risk of death. Results During a median follow-up of 10.3 years in CKD population, 1398 (43%) all-cause deaths and 526 (16%) CVD deaths occurred. It has been found that individuals with CKD have higher MLR level. The partial correlation analysis results showed that even after adjusting for age, sex, and race, MLR is still correlated with blood glucose, lipid levels, and kidney function indicators. The results of the cox proportional hazards regression model and Kaplan-Meier curve shown after adjusting for covariates, higher MLR was significantly associated with an increased risk of mortality. Consistent results were also observed when MLR was examined as categorical variable (quartiles). The RCS demonstrated a positive association between MLR and the risk of all-cause mortality and cardiovascular mortality. The ROC results indicate that the predictive efficacy of MLR for all-cause mortality risk is comparable to eGFR, higher than NLR and CRP. The predictive efficacy of MLR for cardiovascular mortality risk is higher than these three indicators. Conclusion Compared to non-CKD population, the CKD population has higher levels of MLR. In the CKD population, MLR is positively correlated with the risk of death. Furthermore, the predictive efficacy of MLR for mortality risk is higher than other clinical indicators. This suggests that MLR can serve as a simple and effective clinical indicator for predicting mortality risk in CKD patients.

Loneliness, social isolation and incident chronic kidney disease among patients with diabetes

BackgroundIndividuals with diabetes have a significantly higher risk of developing chronic kidney disease (CKD) and higher levels of social isolation and loneliness compared with those without diabetes. Recently, the American...

#435 Endothelial activation and inflammation in chronic kidney disease (CKD): role of neutrophil extracellular traps (NETs)

Abstract Background and Aims Advanced chronic kidney disease (CKD), especially in stages 4-5, amplifies cardiovascular disease (CVD) risk by around 50%. This heightened susceptibility is linked to a 1.5 to 3-fold increase in venous thromboembolism incidence, driven by coagulation dysregulation and heightened inflammation. During inflammation, neutrophils can release extracellular traps (NETs), that was described contribute to endothelial damage, through adhesion molecule elevation, and tissue factor (TF) secretion, exacerbating thrombosis. Additionally, NETs interact with von Willebrand Factor (vWF) and factor XII, further amplifying thrombus formation and the activation of the intrinsic coagulation pathway. The aim of this study was to observe whether NETs may contribute to increased CVD risk in CKD patients by inducing endothelial activation and thromboinflammatory responses to a larger extent compared to NETs from healthy donors. Method For that, neutrophils were isolated from healthy donors’ and CKD patients’ (stages 3-5 HD) peripheral blood, and NETs were collected by stimulating neutrophils with PMA for 3.5 hours. Human aortic endothelial cells (HAoECs) were subsequently exposed to NETs for 3 to 24 hours, followed by gene expression analysis with a focus on inflammation, endothelial activation, and prothrombotic markers. Additionally, protein analysis of the supernatant was conducted using ELISA. All experiments were performed under ethical protocol EK 225-21 from the University Hospital of Aachen. Results Exposure to both healthy NETs as well as the ones isolated from CKD patients resulted in a notable upregulation of endothelial activation (VCAM-1), prothrombotic (TF), and inflammatory (IL-6) gene expression within 3 hours, without difference between healthy and CKD conditions. On the other hand, when examining the cellular supernatant, a significantly higher increase in vWF secretion was observed upon treatment with CKD-NETs compared to healthy NETs. Furthermore, while secretion of the inflammatory cytokine IL-6 presented a comparable increase upon treatment with NETs derived from healthy and CKD neutrophils, IL-1β secretion was markedly enhanced after CKD-NET treatment in comparison to healthy NETs. Conclusion In summary, our findings suggest that NETs exert a significant influence on endothelial cells, contributing to increased thromboinflammatory activation. Notably, CKD-NETs evoked a more rapid impact on the endothelium, accompanied by increased secretion of IL-1β and vWF, and underlying mechanisms will be further investigated.

Dietary vitamin intake and cancer risk in patients with chronic kidney disease: results from the National Health and Nutrition Examination Survey (2007-2018).

The relationship between vitamin intake and cancer risk in the chronic kidney disease (CKD) population is unknown. For this reason, we investigated the relationship between dietary vitamin intake and cancer risk in CKD patients and looked for effective vitamin dietary patterns. This study included 3518 CKD patients from 2007 to 2018 National Health and Nutrition Examination Survey database. All participants were categorized into four groups based on vitamin intake by K-mean clustering. The data were collected and analyzed from June 2023 to December 2023. A total of 3518 CKD patients with a mean age of (61.8 ± 16.3) years were included in the study. During a median follow-up of 7.3years, 137 participants died of cancer. In the multivariate adjusted cox proportional hazards model for single vitamin intake, vitamin E Q4 intake (reference Q1) reduced cancer mortality (HR (95% CI) = 0.45 (0.24-0.87), P = 0.018). Further plotting of the restricted cubic spline curve revealed a linearly decreasing relationship between vitamin E intake and cancer mortality (Poverall = 0.010 Pnon-linear = 0.163). In the multivariate adjusted cox proportional hazards model for multivitamin co-intake, the vitamin C/K intake group reduced cancer mortality compared to the low vitamin intake group (HR (95% CI) = 0.42 (0.20-0.88), P = 0.022). Increased vitamin C intake was independently associated with reduced cancer risk in CKD patients, and a vitamin dietary pattern with high vitamin C/K intake was also effective in reducing cancer risk.

Causal association of monocytes with chronic kidney disease and the mediation role of frailty: A study integrating large-scale two-sample Mendelian randomization and single-cell analysis

BackgroundRecent research reported that frailty was prevalent among adults with chronic kidney disease (CKD) in clinical trials, and monocytes illustrated a similar difference in these two diseases compared to the normal. However, the scientific evidence for a causal relationship between these two diseases was lacking, with further exploration into whether monocytes co-regulate them. MethodsWe aimed to integrate large-scale Mendelian randomization (MR) and single-cell transcriptome analysis to determine whether there was a causal relationship between frailty and CKD (Bidirectional two-sample Mendelian determined the causal direction), whether monocytes impacted them, and whether the two diseases shared genetic variation sites. Based on 441 Genome-wide association study datasets, this study utilized five MR methods, multiple sensitivity analysis, and corresponding single-cell transcriptome datasets as proof. ResultsThe association between frailty and CKD was significantly causal, and frailty increased the risk of CKD in patients (OR (95 %CI): 3.5597 (1.8369–6.8982), p = 0.000168909). The exposure monocyte can increase the risk of frailty and CKD in patients, especially with high expression of HLA genes in these cells. The existing two-sample MR results cannot reject the hypothesis that monocytes increase the risk of CKD by inducing frailty. rs9275271’ 1mb genetic location above and below had been proven to be an effective genetic space for both frailty and CKD. ConclusionWe conducted the largest MR to date on frailty, monocyte, and CKD, and found a significant causal association between frailty and CKD, with the single-cell analysis confirmed. The exposure monocytes increased the risk of frailty and CKD, particularly with high expression of HLA genes in these cells. We identified a potential common genetic variant space, rs9275271, associated with frailty and CKD, providing insights into the genetic basis of these conditions.

Machine learning models for predicting the onset of chronic kidney disease after surgery in patients with renal cell carcinoma

BackgroundPatients with renal cell carcinoma (RCC) have an elevated risk of chronic kidney disease (CKD) following nephrectomy. Therefore, continuous monitoring and subsequent interventions are necessary. It is recommended to evaluate renal function postoperatively. Therefore, a tool to predict CKD onset is essential for postoperative follow-up and management.MethodsWe constructed a cohort using data from eight tertiary hospitals from the Korean Renal Cell Carcinoma (KORCC) database. A dataset of 4389 patients with RCC was constructed for analysis from the collected data. Nine machine learning (ML) models were used to classify the occurrence and nonoccurrence of CKD after surgery. The final model was selected based on the area under the receiver operating characteristic (AUROC), and the importance of the variables constituting the model was confirmed using the shapley additive explanation (SHAP) value and Kaplan-Meier survival analyses.ResultsThe gradient boost algorithm was the most effective among the various ML models tested. The gradient boost model demonstrated superior performance with an AUROC of 0.826. The SHAP value confirmed that preoperative eGFR, albumin level, and tumor size had a significant impact on the occurrence of CKD after surgery.ConclusionsWe developed a model to predict CKD onset after surgery in patients with RCC. This predictive model is a quantitative approach to evaluate post-surgical CKD risk in patients with RCC, facilitating improved prognosis through personalized postoperative care.

Severity and Remission of Metabolic Dysfunction-Associated Fatty/Steatotic Liver Disease With Chronic Kidney Disease Occurrence.

The association of the severity of hepatic steatosis in metabolic dysfunction-associated fatty liver disease (MAFLD)/metabolic dysfunction-associated steatotic liver disease (MASLD) and the remission of MAFLD/MASLD with CKD occurrence is unclear. The study enrolled 79 540 participants from the Kailuan cohort. Hepatic steatosis was diagnosed by ultrasound. MAFLD/MASLD was defined as hepatic steatosis combined with metabolic dysfunction and MASLD further excluded alcohol or other causes of liver disease. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate<60 mL/min per 1.73 m2 or positive proteinuria (≥1+). Hazard ratio (HR) was calculated by Cox regression models. After a median follow-up of 12.9 years, CKD occurred in 20 465 participants. After adjusting for potential confounders, MAFLD was associated with a higher risk of CKD compared with non-MAFLD (HR, 1.12 [95% CI, 1.09-1.16]), and this risk increased with increasing severity of hepatic steatosis (P-trend<0.001). Consistent findings were observed when MASLD was used as the exposure. Compared with persistent non-MAFLD, no statistical difference was found in the risk of CKD in MAFLD remission (HR, 1.04 [95% CI, 0.95-1.15]); however, MASLD remission still had a higher risk of CKD compared with persistent non-MASLD (HR, 1.15 [95% CI, 1.03-1.27]). When grouped according to the prior severity of hepatic steatosis, there was no statistically significant difference in risk of CKD in mild-MAFLD/MASLD remission compared with persistent non-MAFLD/MASLD, but moderated/severe-MAFLD/MASLD remission still had a higher risk. The risk of CKD in patients with MAFLD/MASLD increased with the severity of hepatic steatosis. Even after remission of the disease, patients with MAFLD/MASLD with prior moderate to severe hepatic steatosis still had a higher risk of CKD.

Chronic kidney disease and risk of kidney or urothelial malignancy: systematic review and meta-analysis.

Chronic kidney disease (CKD) is highly prevalent, affecting approximately 11% of US adults. Multiple studies have evaluated a potential association between CKD and urinary tract malignancies. Summary estimates of urinary tract malignancy risk in CKD patients with and without common co-existing conditions may guide clinical practice recommendations. Four electronic databases were searched for original cohort studies evaluating the association between CKD and urinary tract cancers (kidney cancer and urothelial carcinoma) through 25 May 2023, in persons with at least moderate CKD and no dialysis or kidney transplantation. Quality assessment was performed for studies meeting inclusion criteria using the Newcastle-Ottawa Scale. Meta-analysis with a random-effects model was performed for unadjusted incidence rate ratios (IRR) as well as adjusted hazard ratios (aHR) for confounding conditions (diabetes, hypertension and/or tobacco use), shown to have association with kidney cancer and urothelial carcinoma. Sub-analysis was conducted for estimates associated with CKD stages separately. Six cohort studies with 8617563 persons were included. Overall, the methodological quality of the studies was good. CKD was associated with both higher unadjusted incidence and adjusted hazard of kidney cancer (IRR 3.36, 95% confidence interval (CI) 2.32-4.88; aHR 2.04, 95% CI 1.77-2.36) and urothelial cancer (IRR 3.96, 95% CI 2.44-6.40; aHR 1.35, 95% CI 1.22-1.50) compared with persons without CKD. Examining incident urinary tract cancers by CKD severity, risks were elevated in stage 3 CKD (kidney aHR 1.89, 95% CI 1.56-2.30; urothelial carcinoma aHR 1.35, 95% CI 1.20-1.52) as well as in stages 4/5 CKD (kidney cancer aHR 2.30, 95% CI 2.00-2.66; urothelial carcinoma aHR 1.24, 95% CI 1.04-1.49). Even moderate CKD is associated with elevated risk of kidney cancer and urothelial carcinoma. Providers should consider these elevated risks when managing individuals with CKD, particularly when considering evaluation for the presence and etiology of hematuria.

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

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

Gut dysbiosis and the role of probiotics in chronic kidney disease

Chronic inflammatory condition in chronic kidney disease (CKD) patients is associated with increased risk of cardiovascular morbidity and mortality. Gut dysbiosis is assumed as one of leading factors to the chronic inflammatory condition. The relationship between the kidney and the gastrointestinal, knowns as the gut-kidney axis, has a role in production and accumulation of uremic toxins derived from gut microbial fermentation of protein, and translocation of endotoxins and microbial from gut lumen into bloodstream due to alterations of intestinal epithelial barrier in CKD patients. Probiotics supplementation is one of the optional theraphy to restore the gut dysbiosis in CKD patients. Recent studies found that probiotics supplementation in CKD patients decreased uremic toxins and pro-inflammatory cytokines production, and delayed CKD progression. The improvement of this chronic inflammatory condition is expected to decrease cardiovascular disease risk in CKD patients. This review aims to describe the importance of gut-kidney axis in CKD patients, particularly in gut dysbiosis, and the role of probiotics in progression of CKD.

Chronic kidney disease and non-alcoholic fatty liver disease - new pathogenetic links

This article discusses the association between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). There is ample evidence of an increased risk of CKD in patients with NAFLD. Most researchers attribute to the common risk factors for these two conditions. Currently, in addition to traditional factors associated with CKD and NAFLD, such as components of the metabolic syndrome, the influence of new pathogenetic factors, i. e. endothelial dysfunction, metabolic disorders of fibroblast growth factor-21, pathological activation of the renin-angiotensin system and influence of adiponectin level change are considered. Further examination of these mechanisms will open up new therapeutic options for the treatment of CKD and NAFLD.

Retinol intake is associated with the risk of chronic kidney disease in individuals with type 2 diabetes mellitus: results from NHANES

The aim of this study was to investigate the potential association between retinol intake and the risk of chronic kidney disease (CKD) in individuals with type 2 diabetes mellitus (T2DM). The study included individuals diagnosed with T2DM between 2009 and 2018 from the NHANES database. Demographic and laboratory test data were collected for these individuals, as well as information on CKD diagnosis. Logistic regression models were utilized to estimate the relationship between different retinol intakes and the risk of CKD in patients with T2DM. A total of 3988 patients were included in the study. The mean prevalence of CKD in the T2DM population in the United States from 2009 to 2018 was 36.98 (0.02)%. Multivariate logistic regression analysis revealed a 26% decrease in the incidence of CKD in individuals with higher retinol intake compared to those with lower retinol intake in T2DM (OR = 0.74; 95% CI 0.56–0.98). Furthermore, an increase in retinol intake per 1-standard deviation (SD) was associated with a 16% decreased risk of the incidence of CKD (OR = 0.84; 95% CI 0.72–0.97). Lower retinol intake is an independent risk factor for the onset of CKD in patients with T2DM, and augmenting moderate quantities of retinol confers potential nephroprotective advantages.

Modified Nutrition Risk in Critically Ill (m-NUTRIC) score to assess nutritional status and outcome in patients of chronic kidney disease: 2-year cross-sectional study

Introduction: Chronic kidney disease (CKD) is a major health concern in India and has high prevalence, morbidity, and mortality due to significant percentages of subjects with poor socioeconomic status as well as poor management of health resources. Many apparatuses are available to assess nutrition status among patients of CKD. This study was conducted to identify nutritional risk in CKD patients using a modified Nutrition Risk in Critically ill (m-NUTRIC) score without using interleukin-6 values. Method: This prospective observational study was conducted at a tertiary care teaching hospital for a time period of 2 years from 2020 to 2022. The modification of diet in renal disease approach was used for the staging of the CKD. m-NUTRIC scores were calculated and scores ≥5 were graded in high-risk categories and were associated with adverse outcomes, whereas scores &lt;5 were categorized as low risk. Result: Among 250 patients with CKD enrolled, 65 patients were in the age group 18 to 40 years having a mean m-NUTRIC score of 4.46 ± 1.76; in the age group 40 to 60 years 5.18 ± 1.67; and in the age group older than 60 years 5.88 ± 1.77. The mean (standard deviation [SD]) m-NUTRIC score in hemodialysis group was 5.69 ± 1.63 and in nonhemodialysis group was 4.15 ± 1.66. At m-NUTRIC cutoff of 5, predicted hemodialysis is having 66% specificity and 77% sensitivity. It predicts mortality with a sensitivity of 93% and a specificity of 89% at a cutoff of m-NUTRIC of 6. Conclusion: This study showed that m-NUTRIC score may be an important tool that determines requirement of hemodialysis and mortality in CKD patients. Moreover, these scores were higher in stages 4 and 5 of CKD.

456-P: Ceramide- and Phosphatidylcholine-Based Coronary Event Risk Tests 1 and 2 (CERT1, CERT2) Predict Both Type 2 Diabetes and Chronic Kidney Disease

The ceramide- and phosphatidylcholine-based scores CERT1 and CERT2 are predictors for cardiovascular events. The presence of chronic kidney disease (CKD) indicates a high risk of cardiovascular events, particularly in patients who also have type 2 diabetes (T2DM). However, little is known about the associations between T2DM, CKD and CERT1 or CERT2. Therefore, we determined CKD status (eGFR &amp;lt;60 ml/min. 1,73 m2 or albuminuria with an albumin/creatinine ratio &amp;gt;30 mg/g) and analyzed CERT1/2 in 945 high-risk patients, of whom 259 had T2DM. T2DM was diagnosed using ADA criteria. Both CERT1 and CERT2 were significantly higher in patients with T2DM than in nondiabetic subjects (4.5±3.4 vs. 3.5±2.9;p&amp;lt;0.001 and 5.9±2.6 vs. 5.2±2.3; p&amp;lt;0.001, respectively). Further, CERT1 and CERT2 predicted T2DM after adjusting for age, sex, smoking, BMI, LDL-C, HDL-C, with ORs of 1.10 [1.05-1.15]; p&amp;lt;0.001 and 1.10 [1.03-1.17]; p=0.004, respectively. CKD was present in 52.5% of our patients with T2DM and in 30.3% of nondiabetic subjects (p&amp;lt;0.001). CERT1 predicted the risk of CKD in patients with T2DM as well as in patients who did not have T2DM (with ORs of 1.11 [1.03-1.20]; p=0.005 and 1.10 [1.04-1.17]; p=0.001; respectively), as did CERT2 (ORs 1.16 [1.05-1.29]; p=0.005 and 1.14 [1.06-1.24]; p&amp;lt;0.001; respectively). We conclude that CERT1 and CERT2 are strong and significant predictors of T2DM as well as of CKD. Disclosure T. Plattner: None. C.H. Saely: None. A. Muendlein: None. A. Vonbank: None. A. Mader: None. L. Sprenger: None. M. Maechler: None. B. Larcher: None. H. Drexel: None. A. Leiherer: None.

Apabetalone Downregulates Fibrotic, Inflammatory and Calcific Processes in Renal Mesangial Cells and Patients with Renal Impairment.

Epigenetic mechanisms are implicated in transcriptional programs driving chronic kidney disease (CKD). Apabetalone is an orally available inhibitor of bromodomain and extraterminal (BET) proteins, which are epigenetic readers that modulate gene expression. In the phase 3 BETonMACE trial, apabetalone reduced risk of major adverse cardiac events (MACE) by 50% in the CKD subpopulation, indicating favorable effects along the kidney-heart axis. Activation of human renal mesangial cells (HRMCs) to a contractile phenotype that overproduces extracellular matrix (ECM) and inflammatory cytokines, and promotes calcification, frequently accompanies CKD to drive pathology. Here, we show apabetalone downregulated HRMC activation with TGF-β1 stimulation by suppressing TGF-β1-induced α-smooth muscle actin (α-SMA) expression, α-SMA assembly into stress fibers, enhanced contraction, collagen overproduction, and expression of key drivers of fibrosis, inflammation, or calcification including thrombospondin, fibronectin, periostin, SPARC, interleukin 6, and alkaline phosphatase. Lipopolysaccharide-stimulated expression of inflammatory genes IL6, IL1B, and PTGS2 was also suppressed. Transcriptomics confirmed apabetalone affected gene sets of ECM remodeling and integrins. Clinical translation of in vitro results was indicated in CKD patients where a single dose of apabetalone reduced plasma levels of key pro-fibrotic and inflammatory markers, and indicated inhibition of TGF-β1 signaling. While plasma proteins cannot be traced to the kidney alone, anti-fibrotic and anti-inflammatory effects of apabetalone identified in this study are consistent with the observed decrease in cardiovascular risk in CKD patients.

Calprotectin and CRP as biomarkers of cardiovascular disease risk in patients with chronic kidney disease: a follow-up study at 5 and 10 years

Chronic kidney disease (CKD) and low-grade inflammation are associated with increased risk of cardiovascular disease (CVD). Calprotectin, a protein mainly secreted by activated neutrophils during inflammatory conditions, has been linked to CVD risk in general populations. The aim of this study was to evaluate the association of calprotectin with CVD risk in CKD patients, relative to C-reactive protein (CRP). One hundred and fifty-three patients with moderate CKD were prospectively followed up at 5 and 10 years. We used Cox regression modelling with stepwise adjustments for other relevant covariates (age, sex, cystatin C, previous CVD, systolic blood pressure, HDL cholesterol and HbA1c) to assess the association of baseline calprotectin and CRP with the risk of fatal or non-fatal CVD events. Twenty-nine and 44 patients experienced a CVD event during median follow-up of 4.8 and 10.9 years, respectively. Higher calprotectin was associated with increased CVD risk at both time points, which remained statistically significant after multivariable adjustments, including adjustment for CRP. For CRP, the associations did not remain statistically significant after final multivariable adjustments. In conclusion, we have shown that in patients with CKD, calprotectin was independently associated with the risk of future CVD events, suggesting that calprotectin may provide prognostic information of CVD risk.