Risk Of Chronic Kidney Disease Progression Research Articles

Association of Albuminuria With Chronic Kidney Disease Progression in Persons With Chronic Kidney Disease and Normoalbuminuria : A Cohort Study.

Albuminuria is a major risk factor for chronic kidney disease (CKD) progression, especially when categorized as moderate (30 to 300 mg/g) or severe (>300 mg/g). However, there are limited data on the prognostic value of albuminuria within the normoalbuminuric range (<30 mg/g) in persons with CKD. To estimate the increase in the cumulative incidence of CKD progression with greater baseline levels of albuminuria among persons with CKD who had normoalbuminuria (<30 mg/g). Multicenter prospective cohort study. 7 U.S. clinical centers. 1629 participants meeting criteria from the CRIC (Chronic Renal Insufficiency Cohort) study with CKD (estimated glomerular filtration rate [eGFR], 20 to 70 mL/min/1.73 m2) and urine albumin-creatinine ratio (UACR) less than 30 mg/g. Baseline spot urine albumin divided by spot urine creatinine to calculate UACR as the exposure variable. The 10-year adjusted cumulative incidences of CKD progression (composite of 50% eGFR decline or kidney failure [dialysis or kidney transplantation]) from confounder adjusted survival curves using the G-formula. Over a median follow-up of 9.8 years, 182 of 1629 participants experienced CKD progression. The 10-year adjusted cumulative incidences of CKD progression were 8.7% (95% CI, 5.9% to 11.6%), 11.5% (CI, 8.8% to 14.3%), and 19.5% (CI, 15.4% to 23.5%) for UACR levels of 0 to less than 5 mg/g, 5 to less than 15 mg/g, and 15 mg/g or more, respectively. Comparing persons with UACR 15 mg/g or more to those with UACR 5 to less than 15 mg/g and 0 to less than 5 mg/g, the absolute risk differences were 7.9% (CI, 3.0% to 12.7%) and 10.7% (CI, 5.8% to 15.6%), respectively. The 10-year adjusted cumulative incidence increased linearly based on baseline UACR levels. UACR was measured once. Persons with CKD and normoalbuminuria (<30 mg/g) had excess risk for CKD progression, which increased in a linear fashion with higher levels of albuminuria. None.

Dietary Intake of Antioxidant Vitamins and Its Relation to the Progression of Chronic Kidney Disease in Adults With Preserved Renal Function

It is expected that antioxidants contribute to slow the progression of chronic kidney disease (CKD). However, there are no data on the protective effect of dietary antioxidant vitamins on CKD. The purpose of study was to evaluate the renoprotective effect of dietary antioxidant vitamins in the general population. The study participants were 127,081 Korean adults with preserved renal function with estimated glomerular filtration rate ≥60mL/min/1.73m2. They were categorized into 3 groups by tertile levels of dietary antioxidant vitamins intake including vitamins C, E, and A. Cox proportional hazard assumption was used to calculate multivariable hazard ratios and 95% confidence interval for the incident moderate to severe CKD (adjusted hazard ratio [95% confidence interval]) according to tertile levels of dietary intake of antioxidant vitamins. Subgroup analysis was conducted to evaluate the risk of progression from normal to mildly decreased renal function, and from mildly decreased renal function to moderate to severe CKD. The risk of moderate to severe CKD was not significantly associated with the third tertile of dietary antioxidant vitamin intake including vitamin C (1.02 [0.78-1.34]), E (0.96 [0.73-1.27]), and A (0.98 [0.74-1.29]). Additionally, any tertile groups didn't show the significant association with the risk of moderate to severe CKD. Subgroup analysis also didn't show the decreased risk of progression from normal to mildly decreased renal function, and from mildly decreased renal function to moderate to severe CKD in any tertile groups. Dietary intake of vitamins C, E, and A was not significantly associated with the risk of CKD progression.

Novel cardioprotective and nephroprotective combination in patients with type 2 diabetes and chronic kidney disease: perspectives of use

Chronic kidney disease (CKD) is a common complication of diabetes mellitus. It increases significantly cardiovascular risk and decreases the quality of life. CKD requires treatment, and the treatment paradigm for type 2 diabetes has shifted from a glucose-centric approach towards disease-modifying therapy. Attention is being paid to cardioprotective and nephroprotective effects. In patients with type 2 diabetes and CKD, drugs that affect the renin-angiotensin-aldosterone system, as well as sodium-glucose cotransporter type 2 inhibitors (iSGLT2) are widely used. Despite the proven positive effect of these drugs in preservation of renal functions, the pathogenesis of CKD contains links that have not yet been covered. In particular, the activity of fibrosis processes in the renal parenchyma is increased in patients with CKD due to high expression of mineracorticoid receptors. It may be a potential target for nephroprotective drugs. Thus, mineralocorticoid receptor antagonists (MCRA) may influence the residual risk of CKD progression. In particular, the effectiveness of the non-steroid selective AMCR finerenone has been proven in a number of large clinical studies, which confirmed its nephroprotective potential. In this regard, studies aimed at studying the joint effect of known nephroprotective drugs, as well as their combined effect on cardiovascular risk, are highly needed.This review marks the main mechanisms of the combined action of iSGLT2 and finerenone. Discussion of the results of main clinical studies with combined use of standard nephroprotective therapy, SGLT2 and finerenone is also presented.

Validation of the Klinrisk chronic kidney disease progression model in the FIDELITY population.

Chronic kidney disease (CKD) affects >800 million individuals worldwide and is often underrecognized. Early detection, identification and treatment can delay disease progression. Klinrisk is a proprietary CKD progression risk prediction model based on common laboratory data to predict CKD progression. We aimed to externally validate the Klinrisk model for prediction of CKD progression in FIDELITY (a prespecified pooled analysis of two finerenone phase III trials in patients with CKD and type 2 diabetes). In addition, we sought to identify evidence of an interaction between treatment and risk. The validation cohort included all participants in FIDELITY up to 4years. The primary and secondary composite outcomes included a ≥40% decrease in estimated glomerular filtration rate (eGFR) or kidney failure, and a ≥57% decrease in eGFR or kidney failure. Prediction discrimination was calculated using area under the receiver operating characteristic curve (AUC). Calibration plots were calculated by decile comparing observed with predicted risk. At time horizons of 2 and 4years, 993 and 1795 patients experienced a primary outcome event, respectively. The model predicted the primary outcome accurately with an AUC of 0.81 for 2years and 0.86 for 4years. Calibration was appropriate at both 2 and 4years, with Brier scores of 0.067 and 0.115, respectively. No evidence of interaction between treatment and risk was identified for the primary composite outcome (P=.31). Our findings demonstrate the accuracy and utility of a laboratory-based prediction model for early identification of patients at the highest risk of CKD progression.

Metabolic health's central role in chronic kidney disease progression: a 20-year study of obesity-metabolic phenotype transitions

This study investigates the risk of chronic kidney disease (CKD) across four metabolic phenotypes: Metabolically Healthy-No Obesity (MH-NO), Metabolically Unhealthy-No obesity (MU-NO), Metabolically Healthy-Obesity (MH-O), and Metabolically Unhealthy-Obesity (MU-O). Data from the Tehran Lipid and Glucose Study, collected from 1999 to 2020, were used to categorize participants based on a BMI ≥ 30 kg/m2 and metabolic health status, defined by the presence of three or four of the following components: high blood pressure, elevated triglycerides, low high-density lipoprotein, and high fasting blood sugar. CKD, characterized by a glomerular filtration rate < 60 ml/min/1.72 m2. The hazard ratio (HR) of CKD risk was evaluated using Cox proportional hazard models. The study included 8731 participants, with an average age of 39.93 years, and identified 734 incidents of CKD. After adjusting for covariates, the MU-O group demonstrated the highest risk of CKD progression (HR 1.42–1.87), followed by the MU-NO group (HR 1.33–1.67), and the MH-O group (HR 1.18–1.54). Persistent MU-NO and MU-O posed the highest CKD risk compared to transitional states, highlighting the significance of exposure during early adulthood. These findings emphasize the independent contributions of excess weight and metabolic health, along with its components, to CKD risk. Therefore, preventive strategies should prioritize interventions during early-adulthood.

Body mass index modifies the effect of urinary protein-to-creatinine ratio on chronic kidney disease progression.

This study aimed to determine the association between the urinary protein-to-creatinine ratio (UPCR) and chronic kidney disease (CKD) progression in a cohort study, and to determine whether body mass index (BMI) modifies this association. The study population consisted of 856 hypertensive patients with CKD stages 2-5, enrolled between 2010 and 2011 in Japan. Generalized linear models with a logit link were used to evaluate the independent and combined effects of the UPCR and BMI on CKD progression RESULTS: During a median follow-up of 25 months,242 patients developed CKD progression during follow-up. A notably higherrisk of CKD progression was found in participants in tertiles 2 [odds ratio (OR): 5.46, 95% confidence interval (95% CI): 2.49-11.99] and 3 (OR 27.74, 95% CI 12.34-62.38) comparing with tertiles 1 for UPCR levels. Moreover, an interaction was found between UPCR and BMI on CKD progression (P for interaction = 0.006). Participants in both the highest tertile of UPCR and overweight (UPCR ≥ 248.9mg/mmol and BMI ≥ 25kg/m2) had a 45.59-times higher risk of CKD progression compared with those in the lowest tertile of UPCR and nonoverweight (UPCR < 36.2mg/mmol and BMI < 25kg/m2) CONCLUSIONS: The present study demonstrates that the combination of elevated UPCR and BMI may contribute to an increased risk of CKD progression.

Triglyceride-glucose index change and chronic kidney disease progression in a Chinese hypertensive population.

The impact of triglyceride-glucose (TyG) index variations on chronic kidney disease (CKD) progression remains unexplored. To investigate the effects of the TyG index and its dynamic changes on CKD progression. This prospective cohort study included data from 8,418 hypertensive participants. The exposure variable in this study was defined as the difference between the TyG index at the last visit from that at baseline. The study's outcome variable was the progression of CKD, defined as follows: for subjects with an estimated glomerular filtration rate (eGFR) ≥60 mL/min, a ≥30% decrease in eGFR with a final follow-up value <60 mL/min; for those with an eGFR <60 mL/min, a ≥50% decrease in eGFR; or terminal renal failure requiring dialysis. During a median follow-up period of 48 months, 1077 patients were diagnosed with CKD progression. In the fully adjusted Model 3, patients with a change in the TyG index <0 exhibited a significantly decreased 13% risk of CKD progression (HR: 0.87, 95% CI: 0.76-0.98) compared to those with a change in the TyG index≥0 group. Subgroup analyses showed that changes in the TyG index significantly increased the risk of CKD progression only in patients with diastolic blood pressure (DBP) <90mmHg. In the path analysis, baseline TyG was associated with follow-up eGFR (the standard regression coefficient was 1.26 [95% CI, 0.45-2.06]). Our findings suggest that TyG variability may serve as a useful tool for identifying individuals at risk of CKD progression, particularly hypertensive patients with normal DBP levels.

The risk of CKD progression remains high in patients treated with ACE inhibitors and ARBs, MRAs and SGLT2 inhibitors. Have we already achieved the therapeutic ceiling in CKD? (The CON part)

ABSTRACT Renin-Angiotensin-System (RAS) inhibitors remained the only effective nephro-protective treatments until recent landmark trials showed that sodium-glucose co-transporter 2 (SGLT2) inhibitors and non-steroid mineral receptor antagonists added-on RAS inhibitor therapy dramatically slowed renal disease progression in patients with chronic kidney disease (CKD). However, despite this impressive advancement, a substantial proportion of patients remains at high risk of renal and cardiovascular events. Thus, we are still far from achieving the therapeutic ceiling in CKD. However, we are entering a new era in the management of patients with CKD with innovative methodological approaches to test disease-modifying medications in the context of personalized medicine.

New marker for chronic kidney disease progression and mortality in medical-word virtual space

A new marker reflecting the pathophysiology of chronic kidney disease (CKD) has been desired for its therapy. In this study, we developed a virtual space where data in medical words and those of actual CKD patients were unified by natural language processing and category theory. A virtual space of medical words was constructed from the CKD-related literature (n = 165,271) using Word2Vec, in which 106,612 words composed a network. The network satisfied vector calculations, and retained the meanings of medical words. The data of CKD patients of a cohort study for 3 years (n = 26,433) were transformed into the network as medical-word vectors. We let the relationship between vectors of patient data and the outcome (dialysis or death) be a marker (inner product). Then, the inner product accurately predicted the outcomes: C-statistics of 0.911 (95% CI 0.897, 0.924). Cox proportional hazards models showed that the risk of the outcomes in the high-inner-product group was 21.92 (95% CI 14.77, 32.51) times higher than that in the low-inner-product group. This study showed that CKD patients can be treated as a network of medical words that reflect the pathophysiological condition of CKD and the risks of CKD progression and mortality.

Medical use of finererone in patients with diabetes mellitus and chronic kidney disease

Chronic hyperglycemia is one of the factors that contributes significantly to the complications associated with diabetes mellitus. Excess glucose causes an imbalance in cellular oxidation/reduction reactions, as well as systemic inflammation and inflammation in the renal parenchyma, playing a critical role in the pathogenesis of diabetic kidney disease, which today is the main reason for dialysis (hemodialysis/peritoneal) in the world. The pathogenesis of the disease is a difficult process to understand and is integrated with other organic and systematic factors; despite the different mechanisms involved in diabetes mellitus-related kidney damage, the biochemical and cellular mechanisms involving the oxidative and inflammatory pathways are widely recognized by science. There is evidence that the persistent state of hyperglycemia triggers oxidative stress and inflammation mediated by deregulated metabolic pathways, in a cycle that repeats itself, promoting the progression of cell damage and kidney disease. Chronic kidney disease (CKD) is an extremely serious condition that is often underdiagnosed. It is one of the most frequent and serious complications of diabetes. More than 40% of patients with type 2 diabetes mellitus develop CKD. Despite the existence of therapies recommended by the guidelines, patients with CKD and type 2 diabetes have a high risk of CKD progression and cardiovascular events with unfavorable outcomes. It is estimated that CKD affects more than 160 million people with diabetes worldwide. Chronic kidney disease resulting from type 2 diabetes is one of the main causes of advanced kidney disease, requiring dialysis or kidney transplantation. For these reasons, science has set itself the goal of conducting serious and impactful studies into the evolution of kidney disease, in which the key points are the use of drugs aimed at reducing the severity and the rapid natural history of the disease, which as a rule evolves into outcomes that are not always favorable to the patient. Many scientific studies have advanced in this century with an important impact on medicine, such as the FIGARO-DKD and FIDELIO-DKD studies, which seriously analyzes the impact and relevance of the use of mineralcorticoid receptor antagonists, specifically finerenone, in patients with type 2 diabetes mellitus and chronic kidney disease.

Medical use of finererone in patients with diabetes mellitus and chronic kidney disease

Chronic hyperglycemia is one of the factors that contributes significantly to the complications associated with diabetes mellitus. Excess glucose causes an imbalance in cellular oxidation/reduction reactions, as well as systemic inflammation and inflammation in the renal parenchyma, playing a critical role in the pathogenesis of diabetic kidney disease, which today is the main reason for dialysis (hemodialysis/peritoneal) in the world. The pathogenesis of the disease is a difficult process to understand and is integrated with other organic and systematic factors; despite the different mechanisms involved in diabetes mellitus-related kidney damage, the biochemical and cellular mechanisms involving the oxidative and inflammatory pathways are widely recognized by science. There is evidence that the persistent state of hyperglycemia triggers oxidative stress and inflammation mediated by deregulated metabolic pathways, in a cycle that repeats itself, promoting the progression of cell damage and kidney disease. Chronic kidney disease (CKD) is an extremely serious condition that is often underdiagnosed. It is one of the most frequent and serious complications of diabetes. More than 40% of patients with type 2 diabetes mellitus develop CKD. Despite the existence of therapies recommended by the guidelines, patients with CKD and type 2 diabetes have a high risk of CKD progression and cardiovascular events with unfavorable outcomes. It is estimated that CKD affects more than 160 million people with diabetes worldwide. Chronic kidney disease resulting from type 2 diabetes is one of the main causes of advanced kidney disease, requiring dialysis or kidney transplantation. For these reasons, science has set itself the goal of conducting serious and impactful studies into the evolution of kidney disease, in which the key points are the use of drugs aimed at reducing the severity and the rapid natural history of the disease, which as a rule evolves into outcomes that are not always favorable to the patient. Many scientific studies have advanced in this century with an important impact on medicine, such as the FIGARO-DKD and FIDELIO-DKD studies, which seriously analyzes the impact and relevance of the use of mineralcorticoid receptor antagonists, specifically finerenone, in patients with type 2 diabetes mellitus and chronic kidney disease.

Associations between the Serum Triglyceride Level and Kidney Outcome in Patients with Chronic Kidney Disease: The Fukuoka Kidney disease Registry Study.

Hypertriglyceridemia is a risk factor for chronic kidney disease (CKD). However, whether or not it predicts the risk of CKD progression is unknown. This study evaluated the association between serum triglyceride (TG) levels and kidney disease progression in patients with non-dialysis-dependent CKD. The Fukuoka Kidney disease Registry (FKR) study was a multicenter, prospective longitudinal cohort study. In total, 4,100 patients with CKD were followed up for 5 years. The primary outcome was the incidence of CKD progression, defined as a ≥ 1.5-fold increase in serum creatinine level or the development of end-stage kidney disease. The patients were divided into quartiles according to baseline serum TG levels under non-fasting conditions: Q1 ＜87 mg/dL; Q2, 87-120 mg/dL; Q3, 121-170 mg/dL, and Q4 ＞170 mg/dL. During the 5-year observation period, 1,410 patients met the criteria for CKD progression. The multivariable-adjusted Cox proportional hazards model showed a significant association between high serum TG level and the risk of CKD progression in the model without macroalbuminuria as a covariate (multivariable hazard ratio[HR] for Q4 versus Q1, 1.20; 95% CI, 1.03-1.41; P=0.022), but the significance disappeared after adjusting for macroalbuminuria (HR for Q4 versus Q1, 1.06; 95% CI, 0.90-1.24; P=0.507). The present findings suggest that individuals with high serum TG levels are more likely to develop CKD progression than those without; however, whether or not higher serum TG levels reflect elevated macroalbuminuria or lead to CKD progression via elevated macroalbuminuria is unclear.

Interpretable machine learning for predicting chronic kidney disease progression risk.

Chronic kidney disease (CKD) poses a major global health burden. Early CKD risk prediction enables timely interventions, but conventional models have limited accuracy. Machine learning (ML) enhances prediction, but interpretability is needed to support clinical usage with both in diagnostic and decision-making. A cohort of 491 patients with clinical data was collected for this study. The dataset was randomly split into an 80% training set and a 20% testing set. To achieve the first objective, we developed four ML algorithms (logistic regression, random forests, neural networks, and eXtreme Gradient Boosting (XGBoost)) to classify patients into two classes-those who progressed to CKD stages 3-5 during follow-up (positive class) and those who did not (negative class). For the classification task, the area under the receiver operating characteristic curve (AUC-ROC) was used to evaluate model performance in discriminating between the two classes. For survival analysis, Cox proportional hazards regression (COX) and random survival forests (RSFs) were employed to predict CKD progression, and the concordance index (C-index) and integrated Brier score were used for model evaluation. Furthermore, variable importance, partial dependence plots, and restrict cubic splines were used to interpret the models' results. XGBOOST demonstrated the best predictive performance for CKD progression in the classification task, with an AUC-ROC of 0.867 (95% confidence interval (CI): 0.728-0.100), outperforming the other ML algorithms. In survival analysis, RSF showed slightly better discrimination and calibration on the test set compared to COX, indicating better generalization to new data. Variable importance analysis identified estimated glomerular filtration rate, age, and creatinine as the most important predictors for CKD survival analysis. Further analysis revealed non-linear associations between age and CKD progression, suggesting higher risks in patients aged 52-55 and 65-66 years. The association between cholesterol levels and CKD progression was also non-linear, with lower risks observed when cholesterol levels were in the range of 5.8-6.4 mmol/L. Our study demonstrated the effectiveness of interpretable ML models for predicting CKD progression. The comparison between COX and RSF highlighted the advantages of ML in survival analysis, particularly in handling non-linearity and high-dimensional data. By leveraging interpretable ML for unraveling risk factor relationships, contrasting predictive techniques, and exposing non-linear associations, this study significantly advances CKD risk prediction to enable enhanced clinical decision-making.

Circadian syndrome is associated with the development of chronic kidney disease and rapid decline in kidney function in middle-aged and elder adults: a China nationwide cohort study.

The correlation between circadian syndrome (CircS) and kidney outcomes is currently supported by limited empirical evidence. Thus, the objective of this study was to determine the potential relationship between CircS and the development of chronic kidney disease (CKD), as well as the rapid decline in renal function. We utilized data from the 2011 China Health and Retirement Longitudinal Study (CHARLS), which involved 6002 Chinese adults ≥40 years of age. Among these participants, 3670 subsequently had follow-up evaluations in the 2015 survey. The primary outcome was the development of CKD, as defined by an estimated glomerular filtration rates decrease to a level <60ml/min/1.73m2, while the secondary outcome was rapid decline in renal function, as defined by an estimated glomerular filtration rates decrease of >5ml/min/1.73m2 per year. Multivariable logistic regression analysis was utilized to determine the association between CircS and kidney outcomes. Compared to participants without CircS, those with CircS had a higher risk of CKD in the cross-sectional studies conducted in 2011 (OR, 1.292; 95% CI, 1.053-1.585) and 2015 (OR, 1.860; 95% CI, 1.469-2.355). Participants with CircS in the longitudinal cohort study had a higher risk of progressing to CKD (OR, 3.050; 95% CI, 2.052-4.534) and a rapid decline in renal function (OR, 1.959; 95% CI, 1.433-2.677) after 4 years of follow-up evaluations and adjustment for covariates. Moreover, participants who had CircS with ≥6 CirS components had the highest risk of a rapid decline in renal function (OR, 1.703; 95% CI, 1.054-2.753). CirS significantly increased the risk of CKD progression and rapid decline in renal function among middle-aged and elder individuals. Our study findings highlights the importance of recognizing and managing CirC as a preventative strategy for CKD.

Findings from the KNOW-CKD Study indicate that higher systolic blood pressure time in target range is associated with a lower risk of chronic kidney disease progression

Time-in-target range (TTR) of systolic blood pressure (SBP) is determined by the proportion of time during which SBP remains within a defined optimal range. TTR has emerged as a useful metric for assessing SBP control over time. However, it is uncertain if SBP-TTR can predict the progression of chronic kidney disease (CKD). Here, we investigated the association between SBP-TTR during the first year of enrollment and CKD progression among 1758 participants from the KNOW-CKD (KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease). Baseline median estimated glomerular filtration rate (eGFR) was 51.7 ml/min per 1.73 m2. Participants were categorized into four SBP-TTR groups (0%, 1–50%, 51–99%, and 100%). The primary outcome was CKD progression defined as 50% or more decline in eGFR from baseline measurement or the initiation of kidney replacement therapy. During the follow-up period (9212 person-years over a median 5.4 years), the composite outcome occurred in 710 participants. In the multivariate cause-specific hazard model, a one-standard deviation increase in SBP-TTR was associated with an 11% lower risk of the composite outcome with hazard ratio, 0.89 (95% confidence interval, 0.82–0.97). Additionally, compared to patients with SBP-TTR 0%, the respective hazard ratios for those with SBP-TTR 1–50%, 51–99%, and 100% were 0.85 (0.68–1.07), 0.76 (0.60–0.96), and 0.72 (0.55–0.94), and the respective corresponding slopes of eGFR decline were –3.17 (–3.66 to –2.69), –3.02 (–3.35 to –2.68), –2.62 (–2.89 to – 2.36), and –2.33 (–2.62 to –2.04) ml/min/1.73 m2 . Thus, higher SBP-TTR was associated with a decreased risk of CKD progression in patients with CKD.

Adherence to Plant-Based Diets and Risk of CKD Progression and All-Cause Mortality: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Studies have shown that generally healthy individuals who consume diets rich in plant foods have a lower risk of incident chronic kidney disease (CKD) and cardiovascular disease. This study investigated the prospective associations of plant-based diets with the risk of CKD progression and all-cause mortality in individuals with CKD. Prospective cohort study. 2,539 participants with CKD recruited between 2003-2008 into the Chronic Renal Insufficiency Cohort (CRIC) Study. Responses on the Diet History Questionnaire were used to calculate scores for the overall plant-based diet index, healthy plant-based diet index, and unhealthy plant-based diet index. (1) CKD progression defined as≥50% estimated glomerular filtration rate decline from baseline or kidney replacement therapy (dialysis, transplant) and (2) all-cause mortality. Cox proportional hazards models to compute hazard ratios and 95% confidence intervals adjusting for lifestyle, socioeconomic, and clinical covariates. There were 977 CKD progression events and 836 deaths during a median follow-up period of 7 and 12 years, respectively. Participants with the highest versus lowest adherence to overall plant-based diets and healthy plant-based diets had 26% (HR, 0.74 [95% CI, 0.62-0.88], P trend<0.001) and 21% (HR, 0.79 [95% CI, 0.66-0.95], P trend=0.03) lower risks of all-cause mortality, respectively. Each 10-point higher score of unhealthy plant-based diets was modestly associated with a higher risk of CKD progression (HR, 1.14 [95% CI, 1.03-1.25) and all-cause mortality (HR, 1.11 [95% CI, 1.00-1.23). Self-reported diet may be subject to measurement error. Adherence to an overall plant-based diet and a healthy plant-based diet is associated with a reduced risk of all-cause mortality among individuals with CKD. An unhealthy plant-based was associated with an elevated risk of CKD progression and all-cause mortality. Plant-based diets are healthful dietary patterns that have been linked to a lower risk of chronic diseases. However, the impact of plant-based diets on clinical outcomes in patients with chronic kidney disease (CKD) is not well established. In 2,539 individuals with CKD, we examined the associations of adherence to 3 different types of plant-based diets with the risks of CKD progression and all-cause mortality. We found that following an overall plant-based diet and a healthy plant-based diet was associated with a lower risk of all-cause mortality. By contrast, following an unhealthy plant-based diet was associated with a higher risk of CKD progression and all-cause mortality. These results suggest that the quality of plant-based diets may be important for CKD management.

Association Between Elevated Blood Eosinophils and Chronic Kidney Disease Progression: Analyses of a Large United States Electronic Health Records Database.

Blood eosinophils can increase in response to infection, inflammation, and hypersensitivity reactions, yet their involvement in the progression of chronic kidney disease (CKD) is poorly understood. This study explores the relationship between blood eosinophils and CKD progression among patients in a real-world setting. This retrospective study analyzed data obtained from the Optum® de-identified electronic health records dataset in the United States. Patients diagnosed with CKD stage 3 or 4 (International Classification of Diseases diagnosis code or estimated glomerular filtration rate [eGFR] <60 mL/min) between January 2011 and March 2018 were included and followed until progression to the next CKD stage, death, or dropout. The primary objective of this study was to assess the relationship between blood eosinophil counts (bEOS) and CKD progression, adjusting for clinical and demographic features as well as known risk factors for CKD stages 3-4. The primary outcomes were CKD progression and all-cause mortality. We found that high eosinophilic levels (bEOS ≥300 cells/µL) were associated with CKD progression from stage 3 to stages 4 or 5 (hazard ratio [HR] ranging from 1.30 to 1.50) and from stages 4 to 5 (HR ranging from 1.28 to 1.50). Among patients with CKD progression, those with blood eosinophils ≥300 cells/µL appeared to have a relatively lower eGFR, higher all-cause mortality, and reduced time to CKD progression and death than those with <300 cells/µL. Factors including sex, race, hypertension, anemia, and treatments for cardiovascular and hematopoietic drugs were associated with CKD progression. Elevated eosinophils may increase the risk for CKD progression. Larger studies are needed to assess whether the risk of mortality is increased among patients with elevated eosinophils.

Cost-effectiveness of finerenone in chronic kidney disease associated with type 2 diabetes in The Netherlands

BackgroundIn the Netherlands, more than one million patients have type 2 diabetes (T2D), and approximately 36% of these patients have chronic kidney disease (CKD). Yearly medical costs related to T2D and CKD account for approximately €1.3 billion and €805 million, respectively. The FIDELIO-DKD trial showed that the addition of finerenone to the standard of care (SoC) lowers the risk of CKD progression and cardiovascular (CV) events in patients with CKD stages 2–4 associated with T2D. This study investigates the cost-effectiveness of adding finerenone to the SoC of patients with advanced CKD and T2D compared to SoC monotherapy.MethodsThe validated FINE-CKD model is a Markov cohort model which simulates the disease pathway of patients over a lifetime time horizon. The model was adapted to reflect the Dutch societal perspective. The model estimated the incremental costs, utilities, and incremental cost-effectiveness ratio (ICER). Sensitivity and scenario analyses were performed to assess the effect of parameter uncertainty on model robustness.ResultsWhen used in conjunction with SoC, finerenone extended time free of CV events and renal replacement therapy by respectively 0.30 and 0.31 life years compared to SoC alone, resulting in an extension of 0.20 quality-adjusted life years (QALYs). The reduction in renal and CV events led to a €6136 decrease in total lifetime costs per patient compared to SoC alone, establishing finerenone as a dominant treatment option. Finerenone in addition to SoC had a 83% probability of being dominant and a 93% probability of being cost-effective at a willingness-to-pay threshold of €20,000.ConclusionBy reducing the risk of CKD progression and CV events, finerenone saves costs to society while gaining QALYs in patients with T2D and advanced CKD in the Netherlands.

Longitudinal changes in renal function in patients with chronic hepatitis B on antiviral treatment.

Patients with chronic hepatitis B (CHB) on nucleos(t)ide analogues (NUCs) often experience renal function decline. Conflicting results regarding the impact of NUC use and renal function have recently been reported. To examine longitudinal changes in renal function according to the NUC treatment type compared with untreated patients METHODS: From 2014 to 2022, we retrospectively analysed 10,642 patients with CHB. The primary outcome was chronic kidney disease (CKD) progression, which was defined as a minimum one-stage elevation. We applied propensity score (PS) matching for outcome comparisons. In the PS-matched cohort of 1996 pairs, the NUC-treated group (7.6/100 person-years [PYs]) had a significantly higher CKD progression risk than the untreated group (4.4/100 PYs), with a hazard ratio (HR) of 1.70 (p < 0.001). The tenofovir disoproxil fumarate (TDF)-treated group (7.9/100 PYs) showed a 1.76-fold increased CKD progression risk compared with the untreated group (4.5/100 PYs) in the PS-matched cohort (p < 0.001). Both the entecavir- and tenofovir alafenamide (TAF)-treated groups showed CKD progression risks comparable to those of the untreated group in the PS-matched cohorts of 755 and 426 pairs, respectively (p = 0.132 and p = 0.120, respectively). No significant CKD progression risk was found between the entecavir- (6.0/100 PYs) and TAF-treated (5.2/100 PYs) groups in the PS-matched cohort of 510 pairs (p = 0.118). NUC-treated patients, especially those on TDF, faced a higher CKD progression risk than untreated patients. Entecavir- and TAF-treated patients had comparable CKD progression risks to untreated patients. No difference was observed between entecavir and TAF in the risk of CKD progression.

The evolution of type 2 diabetes management: glycemic control and beyond with SGLT-2 inhibitors and GLP-1 receptor agonists.

Diabetes mellitus (DM) is one of the most prevalent diseases encountered by the primary care physician on a daily basis. Complications associated with DM can include nephropathy, neuropathy, and retinopathy ("microvascular complications"), along with cardiovascular disease (CVD), which can include myocardial infarction (MI) and strokes ("macrovascular complications"). In the 1990s, landmark clinical trials demonstrated that intensive glycemic control can reduce the risk of developing microvascular complications, but reduction in macrovascular complications with intensive glycemic control was not clearly demonstrated. At this point, intensive glycemic control became the standard of care (SOC). In the 2000s, additional trials evaluating the effect of intensive glycemic control in patients with type 2 diabetes mellitus (T2D) and established CVD, or risk factors for CVD, subsequently failed to identify a macrovascular benefit from intensive glycemic control, and one of the trials was terminated early because of an increase in the risk of mortality observed among patients assigned to receive intensive glycemic control. These results led to less strict glycemic targets being recommended in older patients, particularly those with established CVD. In 2007, everything changed after a report surfaced suggesting that rosiglitazone was associated with a significant increase in the risk of MI, as well as an increase in the risk of cardiovascular death that was of borderline significance. As a result, in 2008, the FDA mandated that all new diabetes medications must exclude an unacceptable level of risk for atherosclerotic cardiovascular disease (ASCVD) prior to drug approval, and thus undergo additional cardiovascular safety trials. Accordingly, through these trials, some of the newer agents, particularly sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA), were demonstrated to reduce the risk of major adverse cardiovascular events (MACEs), independent of their effect on glycemic control. These findings subsequently led to further trials to evaluate the effects of some of these therapies on the risk of chronic kidney disease (CKD) progression, as well as adverse heart failure-related outcomes. SGLT-2 inhibitors have been demonstrated to reduce the risk of CKD progression, as well as a reduction in the risk of cardiovascular death or hospitalization secondary to heart failure in patients with both reduced ejection and preserved ejection fractions. A trial evaluating the effects of GLP-1RA on CKD outcomes is ongoing. The aim of this narrative review article, compiled by identifying relevant studies via the utilization of PubMed, is to provide a broad overview over the various clinical trials and analyses that have led to current diabetes management guidelines, and ultimately, help guide primary care physicians in selecting therapies that will not only improve glycemic control and reduce the risk of microvascular complications, but also reduce the risk of macrovascular disease in their patients with T2D.