Prevention Of Chronic Kidney Disease Research Articles

#1427 Comparison of METS-IR and HOMA-IR for predicting new-onset CKD in middle-aged and older adults

Abstract Background and Aims Chronic kidney disease (CKD) has emerged as a mounting public health issue worldwide; therefore, prompt identification and prevention are imperative in mitigating CKD-associated complications and mortality rate. We aimed to compare the predictive powers of the homeostatic model assessment for insulin resistance (HOMA-IR) and the metabolic score for insulin resistance (METS-IR) for CKD incidence in middle-aged and older adults. Method This study used longitudinal prospective cohort data from the Korean Genome and Epidemiology Study. A total of 10,030 participants, aged 40–69 years, residing in the Ansung or Ansan regions of the Republic of Korea, were recruited between 2001 and 2002 through a two-stage cluster sampling method. We compared the predictive powers of METS-IR and HOMA-IR for CKD prevalence and incidence, respectively. CKD prevalence was measured by the area under the receiver operating characteristic (ROC) curve (AUC), and the indices’ predictive performance for CKD incidence were assessed using Harrell's concordance index and time-dependent ROC curve analysis. Results A total of 9261 adults aged 40–69 years at baseline and 8243 adults without CKD were included in this study. The AUCs and 95% confidence intervals (CIs) of HOMA-IR and METS-IR for CKD prevalence at baseline were 0.577 (0.537–0.618) and 0.599 (0.560–0.637), respectively, with no significant difference (p = 0.337). The Heagerty's integrated AUC for METS-IR in predicting CKD incidence was 0.772 (95% CI 0.750–0.799), which was significantly higher than that of HOMA-IR (0.767 [95% CI 0.742–0.791], p = 0.015). Conclusion METS-IR surpassed HOMA-IR in predicting CKD incidence and was as effective as HOMA-IR in predicting CKD prevalence. This implies that METS-IR could be a valuable indicator for early detection and prevention of CKD among Korean adults.

#1280 Temporal trends in chronic kidney disease and mortality after acute kidney injury

Abstract Background and Aims In 2015, the International Society of Nephrology formulated the “0by25” initiative, which aims to eliminate all preventable deaths due to acute kidney injury (AKI) by 2025. Numerus publications have added focus to the importance of clinical awareness and improved treatment for AKI. Ideally, this should translate to lower rates of AKI-associated adverse outcomes such as chronic kidney disease (CKD) and death. To our knowledge, there are no studies describing temporal trends in the incidence of CKD following AKI. Moreover, only a few studies have examined the temporal trends in mortality following AKI and these studies included highly selected groups of patients not representative of general hospitalized patients and to an even lesser degree the general population. Hence, further examination of the prognosis after AKI is required to understand temporal trends in the quality of care for AKI and establish a foundation for both preventive and therapeutic measures. Therefore, we examined the temporal trends in CKD and mortality after AKI in Denmark. Method We identified adult individuals with AKI from 1 January 2007 to 31 December 2018 using population-based plasma creatinine (pCr) data covering both the primary care and hospital settings. AKI was defined in accordance with the Kidney Disease: Improving Global Outcomes (KDIGO) creatinine criteria. CKD after AKI was defined as ≥2 eGFR measurements from primary care or planned outpatient hospital visits <60 mL/min/1.73 m2 separated by a period of ≥90 days or by a hospital diagnoses code related to chronic dialysis or kidney transplantation. Information on all-cause death was obtained from the Danish Civil Registration System. Annual crude and sex-and-age-standardized 1-year incidence rates of CKD and mortality after AKI were estimated using direct standardization. Results During the 2007-2018 period, 406,207 AKIs were identified in 274,269 distinct Danish residents. The mean age at the time of first AKI was 72 years (IQR, 61; 81) and 137,185 (50%) of first-time AKIs occurred in males. Twenty-eight percent of individuals had a Charlson Comorbidity Index (CCI) score of 0, while 42% had a CCI score of 1-2, and 30% a CCI score ≥3. The mean age, sex, and CCI score distributions were stable across the study period. The age- and sex-standardized incidence rate of CKD after AKI ranged from 102 (95% CI, 99-106) per 1000 person-years in 2018 to 126 (95% CI, 119-133) per 1000 person-years in 2014. Besides a peak in 2014, the incidence of CKD after AKI showed little variation throughout the period. The age-and sex-standardized mortality rate after AKI ranged from 317 (95% CI, 311-323) per 1000 person-years in 2018 to 392 (95% CI, 379-406) per 1000 person-years in 2007. From 2007 to 2013 there was a stable decline in the mortality rate after AKI. From 2014 to 2018 the rate showed little variation. Conclusion The rate of CKD after AKI was stable throughout the period, while there was a decline in mortality after AKI, especially in the years from 2007 to 2013. The decline in mortality after AKI is encouraging; however, the stable rate of CKD after AKI, despite increasing knowledge on AKI treatment and CKD prevention, warrants an evaluation of the contemporary quality of care for AKI in Denmark.

#2494 Pharmacological enhancement of circadian clock ameliorated fibrosis in adenine induced chronic kidney disease

Abstract Background and Aims Circadian clock regulates diverse biological processes. Recent studies demonstrating the important role of dysregulated molecular clock system in several metabolic diseases as well as in chronic kidney disease (CKD) suggest that modulation of clock machinery might be an attractive therapeutic target. Method We optimized a substance (compound X) that enhances the circadian molecular rhythm and validated its effect in HK-2 cells as well as in mouse model of adenine induced CKD. Results By using transcriptome analysis of whole kidneys, we identified that 19% of CKD associated genes showed rhythmic expressions in circadian manner. Gene enrichment analysis revealed that the rhythmic genes involved in extracellular matrix/collagen/myofibroblasts showed upregulation while those involved in transport/brush border/proximal tubule showed downregulation in CKD. Treatment with compound X in HK-2 cells resulted in marked attenuation of epithelial mesenchymal transition upon transforming growth factor-b (TGF- b) stimulation. Along with these in vitro data, we also observed the preserved kidney function and less interstitial fibrosis in compound X treated CKD mice. The protective effect was associated with suppression of inflammation, cell cycle arrest/cellular senescence as well as restoration of several transporters in proximal tubular cells. Conclusion This is the first study that showed that circadian rhythm might be a novel target for CKD progression by suppressing inflammation/fibrosis and enhancing tubular functions. Unlike other strategies targeting single pathway, targeting circadian rhythm seems to be more promising due to its multi-target effects. A better understanding of the complex role of circadian clock in kidney diseases may provide new perspectives for the prevention and treatment of CKD.

#2104 Neutrophil extracellular traps have a pivotal role in tubulointerstitial fibrosis

Abstract Background and Aims Tubulointerstitial fibrosis (TIF) is a typical pathological change in chronic kidney disease (CKD). However, the mechanisms underlying tubulointerstitial fibrosis are still to be fully elucidated. Neutrophil extracellular traps (NETs) participate in the pathophysiological processes of various kidney diseases, but their role in CKD-TIF has not been reported. Here, we investigated the role of NETs in tubulointerstitial fibrosis. Method Immunofluorescence was employed to assess the levels and localization of NETs in the renal tissues of CKD patients. The GSE66494 human CKD microarray dataset was explored to analyze the changes of PAD4 levels. Three CKD mice models, including 14d unilateral ureteral obstruction (UUO), 28d ischemia/reperfusion (I/R) injury, and adenine-induced models were constructed to detect the expression levels of NETs in the kidneys. Then, we established a NETs-deficient (PAD4−/−) CKD mice model and assessed changes in renal function, NETs levels, and renal fibrosis. In vitro, phorbol-12-myristate-13-acetate (the classic inducer of NETs) was used to induce the generation of NETs. Intervention was performed on rat fibroblast NRK49F cells to investigate the mechanism of TIF induced by NETs. Results We first identified NETs levels were significantly elevated in the renal tissues of CKD patients. Additionally, chip data results also indicated elevated PAD4 levels in the renal tissues of CKD patients. NETs levels were elevated in the kidneys of UUO, I/R, and adenine-induced CKD mice, with deposition in the renal interstitium. PAD4-deficient mice did not form neutrophil extracellular traps. Knocking out PAD4 alleviated tubulointerstitial fibrosis in UUO, adenine, and I/R mice after blocking NETs formation. In vitro, NETs intervention in fibroblasts can promote their activation and transformation into myofibroblasts. Conclusion The deletion of NETs by PAD4−/− could significantly improve CKD-TIF. The inhibition of NETs might provide a new molecular target for the prevention and treatment of CKD.

#1637 Diverging trends in kidney replacement therapy (KRT) incidence in Madrid and Catalonia in the past decade

Abstract Background and Aims Chronic kidney disease (CKD) is one of the fastest growing global causes of death and the number of persons on KRT is increasing. A critical assessment of current clinical practice across regions may identify best clinical practice, providing a benchmark to improve outcomes. Given the long life expectancy in Spain and its high proportion of the population over 65 y/o, analysis of Spanish data may provide insight for the future for other European countries. Catalonia (Cat) and Madrid (Mad) are two of the most populated Spanish Autonomous Communities, have similar life expectancy (above 83 years) and GDP per capita, and together account for 30% of Spanish population and 38% of GDP. The aim was to set the basis for benchmarking in CKD care and KRT initiation by comparing the evolving KRT incidence of two representative Spanish Autonomous Communities. Method We compared the KRT incidence in Cat and Mad from 2012 to 2021, using data from European Renal Association (ERA) Registry annual reports and the Spanish Instituto Nacional de Estadistica's (INE) census. Results From 2012 to 2021, the incidence of KRT (day 1) adjusted for age and sex increased by 69.7 pmp (59% increase) in Cat (from 118.7 to 188.4 pmp) and by 14.2 pmp (12% increase) in Mad (from 115.5 to 129.7 pmp). The differential incidence of KRT between Cat and Mad increased from 3.2 to 58.7 pmp, i.e., 1734% increase (Fig. 1A). As a result, the incidence of KRT was 45% higher in Cat than in Mad in 2021 (up from 3% higher in 2012). During the same period, the median age to start KRT increased from 67.0 to 69.6 years (2.6 years, 3.9%) in Cat and from 66.1 to 66.9 years (0.8 years, 1.2%) in Mad. Median age at KRT initiation in 2021 was 3 years older in Cat in both men (Cat 70.0 (58.4-77.8), Mad 67.3 (56.9-76.2)) and women (Cat 69.0 (58.4-77.2), Mad 66.1 (51.7-75.8)). In subgroup analysis by age and sex, the largest difference in KRT incidence in 2021 was observed for women and for those aged 75+ years: Cat/Mad KRT incidence (pmarp) ratio was 1.79 in women 75+, 1.62 in men 75+, 1.49 in women <75 y/o, 1.34 in men <75 y/o (Fig. 1B). The gap between Cat and Mad increased progressively with age in both men and women and the slope was steeper for women. The contribution of diabetes to the overall incidence of KRT ranged from 16.8% to 23.2% in Cat and from 24.3% to 29.0% in Mad between 2012 and 2021, remaining grossly stable or decreasing slightly over time. For most causes, the incidence adjusted for age and sex in Cat and Mad was similar, with largest differences observed for unknown cause (the most common cause in Cat: Cat 45.9 pmp, Mad 7.9 pmp) and missing (the 3rd most common cause in Cat after unknown and diabetes: Cat 25.4 pmp, Mad 0) (Fig. 1C). Together, unknown and missing causes of CKD accounted for 38.1% of incident KRT cases in Cat in 2021. Pre-emptive transplantation was 3-fold more common in Cat in 2021 (7.6% vs 2.7%), while incidence of haemodialysis and peritoneal dialysis were similar (Fig. 1D). Conclusion In conclusion, trends for KRT incidence differed for two Autonomous Communities from the same country, broadly comparable in terms of population, life expectancy and GDP. The incidence of KRT was higher in Catalonia, and the gap increasing over time, especially among the elderly and older women, with unknown cause of CKD being the leading cause of incident KRT. An in-depth analysis of the drivers of these differences may bring interesting insight into best practice for CKD prevention, treatment to slow CKD progression and prescription and initiation of KRT.

#1611 Diverging epidemiology of kidney replacement therapy (KRT) prevalence in Madrid and Catalonia between 2012 and 2021

Abstract Background and Aims Chronic kidney disease (CKD) is one of the fastest growing global causes of death and the number of persons on kidney replacement therapy (KRT) is increasing. A critical assessment of current clinical practice in different regions may identify best clinical practice and provide a benchmark to improve outcomes. Given the current long-life expectancy in Spain and its high proportion of elderly population, analysis of Spanish data may provide insight of interest for the future for other European countries. Catalonia (Cat) and Madrid (Mad) are among the three most populated Spanish Autonomous Communities and have similar life expectancy, gross domestic product (GDP) and GDP per capita, accounting for 30% of Spain's population and 38% of GDP. The aim was to set the basis for benchmarking in CKD care and KRT initiation and care by comparing the evolving prevalence of KRT in Cat and Mad. Method We compared KRT prevalence in Cat and Mad over the past years using data from European Renal Association (ERA) Registry annual reports and Spanish Instituto Nacional de Estadística's (INE) census. Results From 2012 to 2021, the adjusted prevalence of KRT per million population (pmp) increased by 275.8 (1221 to 1479, 22.6% increase) in Cat and by 134.8 (1046 to 1118, 12.9% increase) in Mad. The difference between Cat and Mad increased from 175 to 316 pmp (60% increase), resulting in a 26.8% higher KRT prevalence in Cat than in Mad in 2021 (up from 16.7% higher in 2012) (Fig. 1A). During the same period, the median age of prevalent KRT patients increased from 63.2 to 65.4 years (yrs) (2.2 yrs, 3.5%) in Cat and from 62.2 to 63.8 years (1.6 yrs, 2.6%) in Mad. In 2021, median age for prevalent patients on KRT was 1.6 yrs older in Cat (65.4 (53.9, 75.3)) than in Mad (63.8 (52.6, 74.1)), this difference being of 2.5 yrs in women (Cat 65.5 (53.6, 75.7), Mad (63 (51, 73.8), difference) and 1.1 yrs in men (Cat 65.3 (53.9, 75); Mad 64.2 (53.4, 74.3)). In subgroup analysis by age and sex, prevalence of KRT per million age-related population (pmarp) in 2021 was always higher in Cat than in Mad, except for women aged 20-44 yrs (363.7 in Cat, 370.5 in Mad, Cat/Mad ratio 0.98), and the largest gap was observed for women <19 yrs (Cat 77.4, Mad 41.5, Cat/Mad ratio 1.86). The Cat-Mad ratio increased with age in women >45 yrs, but not in men (Fig. 1B) The contribution of diabetes to KRT prevalence remained stable or increased slightly in both Cat (13.9-15.5%) and Mad (17.4-17.7%) between 2012 and 2021. In 2021 for most causes of KRT the prevalence adjusted for age and sex was higher in Cat, except for hypertension and miscellaneous. The largest differences were observed for unknown cause (most common cause in Cat: Cat 330.8, Mad 85.5, difference 245.3 pmp), miscellaneous (most common cause in Mad: Cat 165.9, Mad 271.5, difference −105.6 pmp), and missing (Cat 53.8, Mad 0, difference 53.8 pmp) (Fig. 1C). Prevalence of kidney transplantation in 2021 was higher in Cat than Mad (60.0% vs 54.9%), while prevalence of hemodialysis and peritoneal dialysis was higher in Mad (39.6% and 5.5%, respectively) than in Cat (36.2% and 3.9%) (Fig. 1D). Conclusion In conclusion, a stark difference in prevalence trends and in current KRT was observed for two Autonomous Communities within the same country which are broadly comparable in terms of population, life expectancy and GDP. An in-depth analysis of the drivers of these differences may bring insight into best practices for CKD prevention, treatment to slow CKD progression, timing and criteria for initiation of KRT and standard of care for KRT.

Magnoflorine Ameliorates Chronic Kidney Disease in High-Fat and High-Fructose-Fed Mice by Promoting Parkin/PINK1-Dependent Mitophagy to Inhibit NLRP3/Caspase-1-Mediated Pyroptosis.

Excessive intake of fat and fructose in Western diets has been confirmed to induce renal lipotoxicity, thereby driving the progression of chronic kidney disease (CKD). This study was conducted to evaluate the efficacy of magnoflorine in a CKD mouse model subjected to high-fat and high-fructose diets. Our results demonstrated that magnoflorine treatment ameliorated abnormal renal function indices (serum creatinine, urea nitrogen, uric acid, and urine protein) in high-fat- and high-fructose-fed mice. Histologically, renal tubular cell steatosis, lipid deposition, tubular dilatation, and glomerular fibrosis were significantly reduced by the magnoflorine treatment in these mice. Mechanistically, magnoflorine promotes Parkin/PINK1-mediated mitophagy, thereby inhibiting NLRP3/Caspase-1-mediated pyroptosis. Consistent findings were observed in the palmitic acid-incubated HK-2 cell model. Notably, both silencing of Parkin and the use of a mitophagy inhibitor reversed the inhibitory effect of magnoflorine on NLRP3 inflammasome activation in vitro. Therefore, the present study provides compelling evidence that magnoflorine improves renal injury in high-fat- and high-fructose-fed mice by promoting Parkin/PINK1-dependent mitophagy to inhibit NLRP3 inflammasome activation and pyroptosis. Our findings suggest that dietary supplementation with magnoflorine and magnoflorine-rich foods (such as magnolia) might be an effective strategy for the prevention of CKD.

Relationship between the longitudinal trajectory of the triglyceride-glucose index and the development of CKD: an 8-year retrospective longitudinal cohort study

BackgroundThe triglyceride-glucose (TyG) index, a simple surrogate marker of insulin resistance, is significantly associated with chronic kidney disease (CKD). However, there is limited research on the longitudinal trajectory of TyG index over time and its relationship with CKD.ObjectiveTo analyse the characteristics of the longitudinal trajectory of the TyG index over time and its association with the development of CKD in a health check-up population.MethodsParticipants who underwent at least three annual health check-ups at the Health Management Center of Sichuan Provincial People’s Hospital from 2015 to 2022 were included in this retrospective cohort study. The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. The latent class mixed model (LCMM) was used to identify the TyG index trajectory of the study population. A Cox proportional hazard model was used to estimate the CKD incidence risk in different quartile groups and the association of changes in the TyG index trajectory with the development of CKD.ResultsA total of 4,921 participants were included in this study, and they were divided into four groups according to the quartiles of the baseline TyG index: Q1 (5.43-6.66), Q2 (6.67-7.04), Q3 (7.05-7.43), and Q4 (7.43-9.97). There was no difference in the risk of CKD occurrence among the TyG groups. Three different TyG index trajectories were identified in this study: a high-level group, middle-level stable group and low-level stable group, respectively. The incidence rate of CKD in the high-level TyG index trajectory group was 2.399 times greater than that in the low-level stable trajectory group (HR=2.399, 95% CI 1.167-4.935).ConclusionIndividuals with long-term exposure to high TyG index levels had a significantly greater risk of CKD. Routine monitoring of the TyG index and its longitudinal trend will aid in the risk stratification of CKD in the general population and will be helpful for CKD prevention and targeted management.

Podocyte involvement in the pathogenesis of preterm-related long-term chronic kidney disease.

With the continuous advancement of neonatal intensive care technology, the survival rate of preterm infants is gradually increasing. However, this improvement in survival is accompanied by long-term prognostic implications in various systems. In the field of renal diseases, current epidemiological data indicate that preterm birth is a significant risk factor for the development of long-term chronic kidney disease (CKD). This not only imposes an economic burden on patients families but also severely impacts their quality of life. Understanding the underlying mechanisms involved in this process could offer potential strategies for early prevention and management of CKD. Although the nephron number hypothesis is currently widely accepted as a mechanism, there has been limited exploration regarding podocytes - one of the most important structures within nephrons - in relation to long-term CKD associated with preterm birth. Therefore, this review aims to summarize current knowledge on how prematurity influences CKD development overall, while specifically focusing on our current understanding of podocytes in relation to prematurity.

Combined effects of blood pressure and glucose status on the risk of chronic kidney disease.

This study aimed to assess the combined effects of blood pressure (BP) and glucose status on chronic kidney disease (CKD) incidence in young and middle-aged adults. We examined data from 1,297,341 Japanese individuals aged <60 years (60.1% men; mean age 41.4 ± 9.3 years) with no history of CKD at baseline. The interval-censored Cox proportional hazards model with covariates was used. During a median follow-up period of 2.1 years, new onset CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2 and/or proteinuria) occurred in 80,187 participants. In participants without antihypertensive treatment (AHT), the adjusted hazard ratios (95% confidence interval) per 1-standard deviation, that is, 15 mmHg increase in systolic BP for CKD incidence, were 1.08 (1.07-1.09), 1.12 (1.10-1.13), and 1.15 (1.12-1.18) in normoglycemia, borderline glycemia, and diabetes groups, respectively. These ratios were significantly higher in the borderline glycemia and diabetes groups compared with those in the normoglycemia group (interaction p < 0.0001). The interaction between BP and borderline glycemia was evident when the outcome definition was restricted to proteinuria. In participants under AHT, systolic BP was most strongly associated with CKD risk in the diabetes group, although no significant interaction was observed. High BP and high glucose status may synergistically increase the incidence of CKD. Strict BP management may play an important role in the early prevention of CKD in individuals with worse glucose status within the young and middle-aged population. This large-scale longitudinal cohort study showed high BP and diabetes synergistically increased the risk of CKD in individuals without AHT. Strict BP management may play an important role in the early prevention of CKD in individuals with worse glucose status within the young and middle-aged population.

Diabetes mellitus is a risk factor for incident chronic kidney disease: A nationwide cohort study

ObjectiveDiabetes mellitus and chronic kidney disease are multifactorial conditions with multiple etiologies that share similar pathophysiologies. This nationwide cohort study examined the impact of diabetes mellitus on the follow-up development of chronic kidney disease. MethodsBy retrieving the Longitudinal Health Insurance Database 2005, 5121 patients with diabetes mellitus were included in this study and 5121 patients without diabetes mellitus, who were matched according to sex, age, and Charlson comorbidity index made up the control group. The adjusted hazard ratios for chronic kidney disease were calculated using Cox proportional hazards regression analysis. Kaplan–Meier analysis was used to estimate the cumulative incidence of chronic kidney disease rate in the diabetes mellitus and control groups. ResultsAfter adjusting for sex, age, and Charlson comorbidity index score, the diabetes mellitus group had a 1.380 times higher (95% CI: 1.277–1.492) risk of developing chronic kidney disease than the control group. Further stratified analysis showed that patients with diabetes mellitus had a significantly higher risk of developing chronic kidney disease regardless of their sex, age, and Charlson comorbidity index score, compared to those without diabetes mellitus. ConclusionsThere is a possibility that diabetes mellitus serves as an independent risk factor for chronic kidney disease development. Early screening and monitoring of diabetes mellitus appear to be of great importance in the prevention of chronic kidney disease.

The Research of Risk Factor Prediction of Chronic Kidney Disease

Kidney diseases, particularly chronic kidney disease (CKD), represent a significant health concern, particularly as one ages. This paper delves into an in-depth analysis of CKD, exploring its prevalence, risk factors, and the complex interplay of conventional and nontraditional determinants. Notably, socioeconomic, genetic, and lifestyle factors are pivotal in understanding CKD's multifaceted etiology. The research employs a diverse dataset from Bangladesh, applying statistical techniques including ANOVA, logistic regression, recursive feature elimination, and random forest to identify and evaluate crucial factors associated with CKD. The study aims to construct a robust predictive model for CKD risk assessment, integrating traditional and lesser-explored variables. This comprehensive approach holds promise in refining risk assessment models and guiding targeted intervention strategies for enhanced CKD prevention and management. The findings emphasize the necessity for a holistic understanding of CKD, emphasizing personalized approaches for effective disease management and prevention.

Physical exercise: a polypill against chronic kidney disease.

We are currently facing a pandemic of physical inactivity that might contribute to the growing prevalence of chronic kidney disease (CKD). Here, we summarize currently available evidence on the association between physical activity and CKD, and also review the effects of exercise intervention in affected patients. Physical activity/exercise might act as a polypill against CKD, preventing its development or even exerting beneficial effects once it is established (i.e. improvements in patients' physical fitness and cardiovascular risk, as well as in kidney function). Exercise benefits are also found at advanced CKD stages or in patients under hemodialysis. The biological mechanisms behind the clinical evidence are also discussed. An active lifestyle appears as a cornerstone in CKD prevention and management.

Diet quality in relation to kidney function and its potential interaction with genetic risk of kidney disease among Dutch post-myocardial infarction patients.

We examined the relation between diet quality, its components and kidney function decline in post-myocardial infarction (MI) patients, and we explored differences by genetic risk of chronic kidney disease (CKD). We analysed 2169 patients from the Alpha Omega Cohort (aged 60-80 years, 81% male). Dietary intake was assessed at baseline (2002-2006) using a validated food-frequency questionnaire and diet quality was defined using the Dutch Healthy Diet Cardiovascular Disease (DHD-CVD) index. We calculated 40-months change in estimated glomerular filtration rate (eGFR, mL/min per 1.73m2). We constructed a weighted genetic risk score (GRS) for CKD using 88 single nucleotide polymorphisms previously linked to CKD. Betas with 95%-confidence intervals (CIs) were obtained using multivariable linear regression models for the association between DHD-CVD index and its components and eGFR change, by GRS. The average DHD-CVD index was 79 (SD 15) points and annual eGFR decline was 1.71 (SD 3.86) mL/min per 1.73 m2. The DHD-CVD index was not associated with annual eGFR change (per 1-SD increment in adherence score: -0.09 [95% CI -0.26,0.08]). Results for adherence to guidelines for red meat showed less annual eGFR decline (per 1-SD: 0.21 [0.04,0.38]), whereas more annual eGFR decline was found for legumes and dairy (per 1-SD: -0.20legumes [-0.37,-0.04] and - 0.18dairy [-0.34,-0.01]). Generally similar results were obtained in strata of GRS. The DHD-CVD index for overall adherence to Dutch dietary guidelines for CVD patients was not associated with kidney function decline after MI, irrespective of genetic CKD risk. The preferred dietary pattern for CKD prevention in CVD patients warrants further research.

Income Level and Impaired Kidney Function Among Working Adults in Japan

Chronic kidney disease (CKD) is a major public health issue, affecting 850 million people worldwide. Although previous studies have shown the association between socioeconomic status and CKD, little is known about whether this association exists in countries such as Japan where universal health coverage has been mostly achieved. To identify any association of income-based disparity with development of impaired kidney function among the working population of Japan. This was a nationwide retrospective cohort study of adults aged 34 to 74 years who were enrolled in the Japan Health Insurance Association insurance program, which covers approximately 40% of the working-age population (30 million enrollees) in Japan. Participants whose estimated glomerular filtration rate (eGFR) had been measured at least twice from 2015 to 2022 were included in the analysis, which was conducted from September 1, 2021, to March 31, 2023. Individual income levels (deciles) in the fiscal year 2015. Odds ratios were calculated for rapid CKD progression (defined as an annual eGFR decline of more than 5 mL/min/1.73 m2), and hazard ratios, for the initiation of kidney replacement therapy (dialysis or kidney transplant) by income level deciles in the fiscal year 2015. The study population totaled 5 591 060 individuals (mean [SD] age, 49.2 [9.3] years) of whom 33.4% were female. After adjusting for potential confounders, the lowest income decile (lowest 10th percentile) demonstrated a greater risk of rapid CKD progression (adjusted odds ratio, 1.70; 95% CI, 1.67-1.73) and a greater risk of kidney replacement therapy initiation (adjusted hazard ratio, 1.65; 95% CI, 1.47-1.86) compared with the highest income decile (top 10th percentile). A negative monotonic association was more pronounced among males and individuals without diabetes and was observed in individuals with early (CKD stage 1-2) and advanced (CKD stage 3-5) disease. The findings of this retrospective cohort study suggest that, even in countries with universal health coverage, there may be a large income-based disparity in the risk of rapid CKD progression and initiation of kidney replacement therapy. These findings highlight the importance of adapting CKD prevention and management strategies according to an individual's socioeconomic status, even when basic health care services are financially guaranteed.

Association between the trajectory of ideal cardiovascular health metrics and incident chronic kidney disease among 27,635 older adults in northern China–a prospective cohort study

BackgroundThere is a lack of relevant studies evaluating the long-term impact of cardiovascular health factor (CVH) metrics on chronic kidney disease (CKD).ObjectiveThis study investigates the long-term change in CVH metrics in older people and explores the relationship between CVH metrics trajectory and CKD.MethodsIn total, 27,635 older people aged over 60 from the community-based Tianjin Chronic Kidney Disease Cohort study were enrolled. The participants completed five annual physical examinations between January 01, 2014, and December 31, 2018, and a subsequent follow-up between January 01, 2019, and December 31, 2021. CVH metrics trajectories were established by the group-based trajectory model to predict CKD risk. The relationships between baseline CVH, CVH change (ΔCVH), and CKD risk were also explored by logistic regression and restricted cubic spline regression model. In addition, likelihood ratio tests were used to compare the goodness of fit of the different models.ResultsSix distinct CVH metrics trajectories were identified among the participants: low-stable (11.19%), low-medium-stable (30.58%), medium-stable (30.54%), medium-high-decreased (5.46%), medium-high-stable (18.93%), and high-stable (3.25%). After adjustment for potential confounders, higher CVH metrics trajectory was associated with decreased risk of CKD (P for trend < 0.001). Comparing the high-stable with the low-stable group, the risk of CKD decreased by 46%. All sensitivity analyses, including adjusting for baseline CVH and removing each CVH component from the total CVH, produced consistent results. Furthermore, the likelihood ratio test revealed that the model established by the CVH trajectory fit better than the baseline CVH and Δ CVH.ConclusionThe higher CVH metrics trajectory and improvement of CVH metrics were associated with decreased risk of CKD. This study emphasized the importance of improving CVH to achieve primary prevention of CKD in older people.

Systemic immune-inflammation Index is associated with chronic kidney disease in the U.S. population: insights from NHANES 2007-2018.

The systemic immune-inflammation index (SII), a novel and systematic inflammatory biomarker that is associated with chronic kidney disease (CKD), has not received much attention. This study aimed to investigate the relationship between SII and CKD in the United States (U.S.) population. Our study ultimately included a nationally representative sample of 10,787 adults who participated in the 2007-2018 National Health and Nutrition Examination Survey. Weighted multivariate logistic regression was used to assess the correlation between SII and CKD, and a restricted cubic spline (RCS) model was subsequently used to explore the non-linear relationship between SII and CKD. Subgroup analyses were performed to further the effects of other covariates on the relationship between SII and CKD. Following confounder adjustment, a higher SII was related to the incidence of CKD (OR =1.36; 95% CI, 1.07-1.73; p =0.01), as validated by multivariable logistic regression. The RCS curve revealed a non-linear positive correlation between SII/1000 and CKD incidence (p for non-linear =0.0206). Additionally, subgroup analysis confirmed a stronger correlation for male participants (OR =2.628; 95% CI, 1.829-3.776) than for female participants (OR =1.733; 95% CI, 1.379-2.178) (p for interaction =0.046). SII is positively associated with the incidence of CKD among U.S. adults, especially in males. However, further studies are needed to confirm our findings and explore the causal factors that can contribute to the prevention and treatment of CKD.

Are we ready for an adipocentric approach in people living with type 2 diabetes and chronic kidney disease?

We are entering a new era in the management of adiposity-based chronic disease (ABCD) with type 2 diabetes (T2D) and related chronic kidney disease (CKD). ABCD, T2D and CKD can affect almost every major organ system and have a particularly strong impact on the incidence of cardiovascular disease (CVD) and heart failure. ABCD and the associated insulin resistance are at the root of many cardiovascular, renal and metabolic (CKM) disorders, thus an integrated therapeutic framework using weight loss (WL) as a disease-modifying intervention could simplify the therapeutic approach at different stages across the lifespan. The breakthrough of highly effective WL drugs makes achieving a WL of >10% possible, which is required for a potential T2D disease remission as well as for prevention of microvascular disease, CKD, CVD events and overall mortality. The aim of this review is to discuss the link between adiposity and CKM conditions as well as placing weight management at the centre of the holistic CKM syndrome approach with a focus on CKD. We propose the clinical translation of the available evidence into a transformative Dysfunctional Adipose Tissue Approach (DATA) for people living with ABCD, T2D and CKD. This model is based on the interplay of four essential elements (i.e. adipocentric approach and target organ protection, dysfunctional adiposity, glucose homeostasis, and lifestyle intervention and de-prescription) together with a multidisciplinary person-centred care. DATA could facilitate decision-making for all clinicians involved in the management of these individuals, and if we do this in a multidisciplinary way, we are prepared to meet the adipocentric challenge.

A New Hope on the Horizon for Kidney and Cardiovascular Protection with SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Mineralocorticoid Receptor Antagonists in Type 2 Diabetic and Chronic Kidney Disease Patients.

Type 2 diabetes (T2D) is the leading cause of chronic kidney disease (CKD). In addition, the cardiovascular prevalence in diabetic patients is around 32.2%, with a two-fold increased mortality risk compared to those without diabetes. Recent investigations have shed light on the promising cardioprotective and nephroprotective benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and nonsteroidal mineralocorticoid receptor antagonists (nsMRAs) for individuals with T2D. The evidence robustly indicates that SGLT2i and GLP-1RA significantly reduce the risk of CKD and cardiovascular disease (CVD), all while effectively managing blood glucose levels. Furthermore, combining SGLT2i with nsMRAs amplifies the benefits, potentially offering a more profound reduction in cardiovascular and renal outcomes. The data analysis strongly supports the integration of these pharmacological agents in the management strategies for CKD and CVD prevention among T2D patients, highlighting the importance of awareness among nephrologists, especially in regions with limited healthcare resources.

Validation of the Kidney Failure Risk Equation in the Colombian Population.

Chronic kidney disease prevention programs must identify patients at risk of early progression to provide better treatment and prolong kidney replacement therapy-free survival. Risk equations have been developed and validated in cohorts outside of Colombia, so this study aims to evaluate the discrimination and calibration of the four-variable kidney failure risk equation in a Colombian population where it has yet to be validated. External validation study of a kidney failure risk equation using a historical cohort of patients with CKD stages 3, 4, and 5, adults without a history of dialysis or kidney transplantation with a two-year follow-up, belonging to the Baxter Renal Care Services Colombia network. The discriminatory capacity of the model was evaluated by the concordance index using Harrell's C statistic, and the time-dependent area under the receiver operating characteristic (ROC) curve was estimated using the nearest neighbor method, as well as the optimal cut-off point for sensitivity and specificity. Calibration was determined by the degree of agreement between the observed outcome and the probabilities predicted by the model using the Hosmer-Lemeshow statistic. A total of 5,477 patients were included, with a mean age of 72 years, 36.4% diabetic, and a mean baseline eGFR of 36 ml/min/1.73 m2. The rate of dialysis initiation was three events per 100 patient-years, 95% CI (2.9-3.6). The optimal cutoff for sensitivity was 0.94, for specificity, 0.76, and the area under the ROC curve was 0.92. Harrell's C-statistic was 0.88 for the total population, 0.88 for diabetic patients, and 0.93 for those 65 years or older. The validation of the model showed good calibration. In this Colombian cohort, the four-variable KFRE with a two-year prediction horizon has excellent calibration and discrimination, and its use in the care of CKD Colombian patients is recommended.