Association between progression of coronary artery calcification and development of kidney failure with replacement therapy: Findings from KNOW-CKD study.

BACKGROUND AND AIMS: High coronary artery calcification (CAC) burden is a significant risk factor for adverse cardiovascular and kidney outcomes. However, it is unknown whether changes in the coronary atherosclerotic burden can accompany changes in kidney disease progression. Here, we evaluated the relationship between CAC progression and the risk of kidney failure with replacement therapy (KFRT). METHODS: We analyzed 1173 participants with chronic kidney disease (CKD) G1 to G5 without kidney replacement therapy from the KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD). Participants were categorized into three groups according to the change in the CAC score between enrollment and year 4 (non-progressors, ≤0 AU; moderate progressors, 1-199 AU; and severe progressors, ≥200 AU). The primary outcome was the development of KFRT. RESULTS: During a follow-up period of 4690 person-years (median, 4.2 years), the primary outcome occurred in 230 (19.6 %) participants. The incidence of KFRT was 37.6, 54.3, and 80.9 per 1000 person-years in the non-, moderate, and severe progressors, respectively. In the multivariable cause-specific hazard model, the hazard ratios (HRs) for the moderate and severe progressors were 1.71 (95 % confidence interval [CI], 1.02-2.87) and 2.55 (95 % CI, 1.07-6.06), respectively, compared with non-progressors. A different definition of CAC progression with a threshold of 100 AU yielded similar results in a sensitivity analysis. CONCLUSIONS: CAC progression is associated with an increased risk of KFRT in patients with CKD. Our findings suggest that coronary atherosclerosis changes increase the risk of CKD progression.

Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function with chronic kidney disease.

PURPOSE: Recent advances have led to greater recognition of the role of mitochondrial dysfunction in the pathogenesis of chronic kidney disease (CKD). There has been evidence that CKD is also associated with dysbiosis. Here, we aimed to evaluate whether probiotic supplements can have protective effects against kidney injury via improving mitochondrial function. METHODS: An animal model of CKD was induced by feeding C57BL/6 mice a diet containing 0.2% adenine. KBL409, a strain of Lactobacillus acidophilus, was administered via oral gavage at a dose of 1 × 109 CFU daily. To clarify the underlying mechanisms by which probiotics exert protective effects on mitochondria in CKD, primary mouse tubular epithelial cells stimulated with TGF-ß and p-cresyl sulfate were administered with butyrate. RESULTS: In CKD mice, PGC-1α and AMPK, key mitochondrial energy metabolism regulators, were down-regulated. In addition, mitochondrial dynamics shifted toward fission, the number of fragmented cristae increased, and mitochondrial mass decreased. These alterations were restored by KBL409 administration. KBL409 supplementation also improved defects in fatty acid oxidation and glycolysis and restored the suppressed enzyme levels involved in TCA cycle. Accordingly, there was a concomitant improvement in mitochondrial respiration and ATP production assessed by mitochondrial function assay. These favorable effects of KBL409 on mitochondria ultimately decreased kidney fibrosis in CKD mice. In vitro analyses with butyrate recapitulated the findings of animal study. CONCLUSIONS: This study demonstrates that administration of the probiotic Lactobacillus acidophilus KBL409 protects against kidney injury via improving mitochondrial function.

Association of ketone bodies with incident CKD and death: A UK Biobank study.

AIMS: Although cellular and animal models have suggested a protective effect of ketone bodies (KBs), clinical data are still lacking to support these findings. This study aimed to investigate the association of KB levels with incident chronic kidney disease (CKD) and death. METHODS: This was a prospective cohort study of 87,899 UK Biobank participants without baseline CKD who had plasma levels of ß-hydroxybutyrate, acetoacetate, and acetone levels measured at the time of enrollment. The main predictor was plasma total KB, which was the sum of the aforementioned three KBs. The primary outcome was a composite of incident CKD, or all-cause mortality. Secondary outcomes included the individual components of the primary outcome. RESULTS: During a median follow-up of 11.9 years, a total of 8,145 primary outcome events occurred (incidence rate 8.0/1,000 person-years). In the multivariable Cox model, a 1-standard deviation increase in log total KB was associated with a 7 % [adjusted hazard ratio (aHR), 1.07; 95 % confidence interval (CI), 1.05-1.10] higher risk of the primary outcome. When stratified into quartiles, the aHR (95 % CI) for Q4 versus Q1 was 1.18 (1.11-1.27). This association was consistent for incident CKD (aHR, 1.04; 95 % CI, 1.01-1.07), and all-cause mortality (aHR, 1.10; 95 % CI, 1.07-1.13). Compared with Q1, Q4 was associated with a 12 % (aHR 1.12; 95 % CI 1.02-1.24) and 26 % (aHR 1.26; 95 % CI 1.15-1.37) higher risk of incident CKD and all-cause mortality, respectively. CONCLUSIONS: Higher KB levels were independently associated with higher risk of incident CKD and death.

Plasma Levels of Polyunsaturated Fatty Acids and Adverse Kidney Outcomes.

RATIONALE & OBJECTIVE: Many studies have reported polyunsaturated fatty acids (PUFA) as significant predictors of cardiovascular disease, but little is known about the relationship between PUFA levels and chronic kidney disease (CKD). This study explored this relationship among individuals with and without CKD. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 73,419 participants without CKD (cohort 1) and 6,735 participants with CKD (cohort 2) in the UK Biobank Study, with PUFA levels measured between 2007 and 2010. EXPOSURE: Percentage of plasma PUFA, omega-3 fatty acid (FA), omega-6 FA, docosahexaenoic acid (DHA), and linoleic acid relative to total FA. OUTCOME: Incident CKD for cohort 1 and incident kidney failure requiring replacement therapy (KFRT) for cohort 2. ANALYTICAL APPROACH: Cox proportional hazards regression analyses, including a cause-specific competing risk model. RESULTS: In cohort 1, individuals with higher quartiles of plasma PUFA levels had healthier lifestyles and fewer comorbidities. During 841,007 person-years of follow-up (median 11.9 years), incident CKD occurred in 4.5% of participants (incidence rate, 39.1 per 10,000 person-years). For incident CKD in cohort 1, the adjusted cause-specific hazard ratios for quartiles 2, 3, and 4 were 0.83 (95% CI, 0.75-0.92), 0.85 (95% CI, 0.76-0.96), 0.71 (95% CI, 0.62-0.82), respectively, compared with quartile 1. This inverse relationship was consistently observed for all PUFA types. In cohort 2, although total PUFA levels were not associated with KFRT, higher PUFA subtype levels of DHA were associated with a lower risk of KFRT. LIMITATIONS: Observational design and limited generalizability to individuals with higher disease severity; no data on eicosapentaenoic acid. CONCLUSIONS: Among individuals without CKD, higher plasma PUFA levels and all 4 PUFA components were associated with a lower risk of incident CKD. In individuals with CKD, only the omega-3 component of PUFA, DHA, was associated with a lower risk of KFRT. PLAIN-LANGUAGE SUMMARY: Low amounts of polyunsaturated fatty acids (PUFA) in the blood are suspected of increasing the chances of heart disease, but it is not known whether the PUFA relates to kidney disease occurrence. In a large group without kidney disease in the United Kingdom, people with higher levels of PUFA in their blood tended to have a lower risk of developing kidney disease compared to those with lower PUFA levels. This relationship was consistently observed for all PUFA types. However, in the group with kidney disease, only higher levels of docosahexaenoic acid, a subtype of PUFAs, were associated with a lower risk of developing severe kidney problems that required kidney replacement therapy. These findings suggest that higher levels of PUFA, found in certain healthy fats, might protect against the development of kidney disease in the general population. As kidney function declines, only the docosahexaenoic acid, a subtype of PUFA, appears to be associated with preserved kidney function.

Higher potassium intake is associated with a lower risk of chronic kidney disease: population-based prospective study.

BACKGROUND: High-potassium intake is associated with a lower risk of cardiovascular disease. However, the association between potassium intake and the development of chronic kidney disease (CKD) remains unclear. OBJECTIVE: The objective of this study was to investigate whether potassium intake is associated with outcomes of incident CKD. METHODS: This is a population-based prospective observational cohort study from the UK Biobank cohort between 2006 and 2010. We included 317,162 participants without CKD from the UK Biobank cohort. The main predictor was spot urine potassium-to-creatinine ratio (KCR). The primary outcome was incident CKD, which was defined by the International Classification of Disease 10 codes or Operating Procedure Codes Supplement 4 codes. RESULTS: At baseline, individuals with higher KCR had lower blood pressure, body mass index, and inflammation, and were less likely to have diabetes and hypertension. During a median follow-up of 11.9 y, primary outcome events occurred in 15,246 (4.8%) participants. In the cause-specific model, the adjusted hazard ratio (aHR) per 1-standard deviation increase in KCR for incident CKD was 0.90 [95% confidence interval (CI): 0.89, 0.92]. Compared with quartile 1 of KCR, the aHRs (95% CIs) for quartiles 2-4 were 0.98 (0.94, 1.02), 0.90 (0.86, 0.95), and 0.80 (0.76, 0.84), respectively. In sensitivity analysis with different definitions of CKD, the results were similar. In addition, further analysis with dietary potassium intake also showed a negatively graded association with the primary outcome. CONCLUSIONS: Higher urinary potassium excretion and intake were associated with a lower risk of incident CKD.

Metabolically Abnormal Non-Obese Phenotype Is Significantly Associated with All-Cause Mortality in Hemodialysis Patients.

The association between obesity and all-cause mortality in patients undergoing kidney failure with replacement therapy (KFRT) has shown conflicting results. This study aimed to evaluate whether metabolic abnormalities (MA) increase the risk of all-cause mortality in these patients. Between 2009 and 2015, 1141 patients undergoing KFRT were recruited from the Clinical Research Center for End-Stage Renal Disease dataset. Patients were divided into four groups according to the presence of obesity and MA. Multivariate Cox proportional hazard analysis was performed to determine the association between the phenotypes and all-cause mortality. During a mean follow-up of 4.2 years, all-cause mortality was observed in 491 (43.0%) patients. Obesity had a 24% decreased risk of all-cause mortality compared with non-obesity. In contrast, the presence of MA showed a 1.53-fold increased risk of all-cause mortality. There was a significant interaction between obesity and MA (p = 0.006). In Cox proportional hazard analyses after adjustment of confounding factors, the metabolically abnormal non-obesity (MANO) phenotype showed a 1.63-fold increased risk of all-cause mortality compared with the metabolically healthy non-obesity phenotype. In subgroup analysis, the risk of all-cause mortality was higher in the MANO phenotype; this phenotype was significantly associated with a higher all-cause mortality in patients undergoing KFRT.

Sweetened Beverage Intake and Incident Chronic Kidney Disease in the UK Biobank Study.

Importance: An increasing body of evidence indicates an association between consuming sugar or its alternatives and cardiometabolic diseases. However, the effects of the consumption of sugar-sweetened beverages, artificially sweetened beverages, and natural juices on kidney health remain unclear. Objective: To investigate the association of the intake of sugar-sweetened beverages, artificially sweetened beverages, and natural juices with the risk of chronic kidney disease (CKD), and the effect of substituting these beverage types for one another on this association. Design, Setting, and Participants: This prospective, population-based cohort study analyzed data from the UK Biobank. Participants without a history of CKD who completed at least 1 dietary questionnaire were included. The follow-up period was from the date of the last dietary questionnaire until October 31, 2022, in England; July 31, 2021, in Scotland; and February 28, 2018, in Wales. Data were analyzed from May 1 to August 1, 2023. Exposures: Consumption of sugar-sweetened beverages, artificially sweetened beverages, and natural juices. Main Outcomes and Measures: The primary outcome was incident CKD. Multivariable Cox proportional hazards models were used to estimate the associations between the 3 beverage types and incident CKD. A substitution analysis was used to evaluate the effect on the associations of substituting one beverage type for another. Results: A total of 127 830 participants (mean [SD] age, 55.2 [8.0] years; 66 180 female [51.8%]) were included in the primary analysis. During a median (IQR) follow-up of 10.5 (10.4-11.2) years, 4459 (3.5%) cases of incident CKD occurred. The consumption of more than 1 serving per day of sugar-sweetened beverages was associated with higher risk of incident CKD (adjusted hazard ratio [AHR], 1.19 [95% CI, 1.05-1.34]) compared with not consuming sugar-sweetened beverages. The AHR for participants consuming more than 0 to 1 serving per day of artificially sweetened beverages was 1.10 (95% CI, 1.01-1.20) and for consuming more than 1 serving per day was 1.26 (95% CI, 1.12-1.43) compared with consuming no artificially sweetened beverages. By contrast, there was no significant association between natural juice intake and incident CKD (eg, for >1 serving per day: HR, 0.99 [95% CI, 0.87-1.11]; P = .10). Substituting sugar-sweetened beverages with artificially sweetened beverages did not show any significant difference in the risk of CKD (HR, 1.03 [95% CI, 0.96-1.10]). Conversely, replacing 1 serving per day of sugar-sweetened beverage with natural juice (HR, 0.93 [95% CI, 0.87-0.97]) or water (HR, 0.93 [95% CI, 0.88-0.99]) or replacing 1 serving per day of artificially sweetened beverage with natural juice (HR, 0.90 [95% CI, 0.84-0.96]) or water (HR, 0.91 [95% CI, 0.86-0.96]) was associated with a reduced risk of incident CKD. Conclusions and Relevance: Findings from this cohort study suggest that lower consumption of sugar-sweetened beverages or artificially sweetened beverages may reduce the risk of developing CKD.

Frequency of Fabry disease in chronic kidney disease patients including patients on renal replacement therapy in Korea.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by the deficient activity of α-galactosidase (α-Gal A), affecting multiple organs including kidney. In this study, we aimed to determine the prevalence of FD in patients with chronic kidney disease (CKD) including those on renal replacement therapy in Korea. METHODS: This is a national, multicenter, observational study performed between August 24, 2017 and February 28, 2020. Patients with the presence of proteinuria or treated on dialysis were screened by measuring the α-Gal A enzyme activity using either dried blood spot or whole blood, and plasma globotriaosylsphingosine (lyso-GL3) concentration. A GLA gene analysis was performed in patients with low α-Gal A enzyme activity or increased plasma lyso-GL3 concentration. RESULTS: Of 897 screened patients, 405 (45.2%) were male and 279 (31.1%) were on dialysis. The α-Gal A enzyme activity was measured in 891 patients (99.3%), and plasma lyso-GL3 concentration was measured in all patients. Ten patients were eligible for a GLA gene analysis: eight with low α-Gal A enzyme activity and two with increased plasma lyso-GL3 concentration. The GLA mutations were analyzed in nine patients and one patient was found with a pathogenic mutation. Therefore, one patient was identified with FD, giving a prevalence of 0.1% (1 of 897) in this CKD population. CONCLUSION: Although the prevalence of FD in the CKD population was low (0.1%), screening tests are crucial to detect potential diseases in patients with relatives who can benefit from early treatment.

Difference Between Estimated GFR Based on Cystatin C Versus Creatinine and Incident Atrial Fibrillation: A Cohort Study of the UK Biobank.

RATIONALE & OBJECTIVE: The difference between cystatin C-based and creatinine-based estimated glomerular filtration rate (eGFRdiff) has been suggested to reflect factors distinct from kidney function that are associated with cardiovascular risk. However, the association between eGFRdiff and atrial fibrillation (AF) risk has not been extensively evaluated. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Using data from the UK Biobank, this study included 363,494 participants with measured serum creatinine and cystatin C levels and without a prior diagnosis of AF or a history of related procedures. EXPOSURE: Estimated GFRdiff, calculated as cystatin C-based eGFR minus creatinine-based eGFR. Estimated GFRdiff was also categorized as negative (<-15mL/min/1.73m2), midrange (-15 to 15mL/min/1.73m2), or positive (≥15mL/min/1.73m2). OUTCOME: Incident AF. ANALYTICAL APPROACH: Subdistribution hazard models were fit, treating death that occurred before development of AF as a competing event. RESULTS: During the median follow-up period of 11.7 years, incident AF occurred in 18,994 (5.2%) participants. In the multivariable-adjusted model, participants with a negative eGFRdiff had a higher risk of incident AF (subdistribution HR [SHR], 1.25 [95% CI, 1.20-1.30]), whereas participants with a positive eGFRdiff had a lower risk of AF (SHR, 0.81 [95% CI, 0.77-0.87]) compared with those with a midrange eGFRdiff. When eGFRdiff was treated as a continuous variable in the adjusted model, every 10mL/min/1.73m2 higher eGFRdiff was associated with a 0.90-fold decrease in the risk of incident AF. LIMITATIONS: A single measurement of baseline serum creatinine and cystatin C levels. CONCLUSIONS: The difference between cystatin C- and creatinine-based eGFRs was associated with the risk of AF development. A higher eGFRdiff was associated with a lower risk of AF. These findings may have implications for the management of patients at risk of incident AF. PLAIN-LANGUAGE SUMMARY: The difference between cystatin C-based estimated glomerular filtration rate (eGFR) and creatinine-based eGFR has recently gained attention as a potential indicator of cardiovascular outcomes influenced by factors other than kidney function. This study investigated the association between the differences in 2 eGFRs (cystatin C-based eGFR minus creatinine-based eGFR) and incident atrial fibrillation (AF) among>340,000 participants from the UK Biobank Study. Compared with those with a near zero eGFR difference, participants with a negative eGFR difference had a higher risk of AF, while those with a positive eGFR difference had a lower risk. These findings suggest that measuring eGFR differences may help identify individuals at a higher risk of developing AF.

Presence of periodontal disease and the incidence of inflammatory arthritides in the general population: data from the UK Biobank.

OBJECTIVES: To investigate the association between periodontal disease and the development of inflammatory arthritides in the general population. METHODS: In total, 489 125 participants from the UK Biobank without a previous history of RA, AS and PsA were enrolled. The primary outcome was the incidence of inflammatory arthritides, which was a composite of RA, AS and PsA according to the presence of periodontal disease based on self-reported oral health indicators. Multivariate Cox proportional hazard regression analyses using four different models were performed to assess the association between periodontal disease and inflammatory arthritides development. RESULTS: In all, 86 905 and 402 220 individuals were categorized as with and without periodontal disease, respectively. Cox hazard analysis indicated that the presence of periodontal disease was an independent predictor of the occurrence of composite outcomes of inflammatory arthritides, which was also consistent for RA and AS. Significant associations were found to be consistent in the four Cox models and were replicated even when different criteria were used to define periodontal disease. Subgroup analyses indicated that periodontal disease was associated with an increased RA risk in those aged <60 years, and this risk was persistent for both male and female patients and for patients with seropositive/seronegative RA. CONCLUSION: Self-reported periodontal disease is associated with inflammatory arthritides incidence in participants included in the UK Biobank, particularly for RA and AS. Higher clinical attention and optimal dental care in patients with signs of periodontal disease may be recommended for early disease detection and for reducing this risk.

Proteinuria, measured or estimated albuminuria for risk prediction in patients with chronic kidney disease?

BACKGROUND: Although albuminuria is the gold standard for defining chronic kidney disease (CKD), total proteinuria has also been widely used in real-world clinical practice. Moreover, the superiority of the prognostic performance of albuminuria over proteinuria in patients with CKD remains inconclusive. Therefore, we aimed to compare the predictive performances of albuminuria and proteinuria in these patients. METHODS: From the Korean Cohort Study for Outcome in Patients with CKD we included 2099 patients diagnosed with CKD grades 1-5 who did not require kidney replacement therapy. We measured the spot urine albumin:creatinine ratio (mACR) and protein:creatinine ratio (PCR) and estimated the ACR (eACR) using the PCR. Kidney failure risk equation (KFRE) scores were calculated using the mACR, PCR and eACR. The primary outcome was the 5-year risk of kidney failure with replacement therapy (KFRT). RESULTS: The eACR significantly underestimated mACR in patients with low albuminuria levels. The time-dependent area under the receiver operating characteristics curve showed excellent predictive performance for all KFRE scores from the mACR, PCR and eACR. However, eACR was inferior to mACR based on the continuous net reclassification index (cNRI) and integrated discrimination improvement index (IDI) in all CKD cause groups, except for the group with an unclassified aetiology. Moreover, the cNRI and IDI statistics indicated that both eACR and PCR were inferior to mACR in patients with low albuminuria (<30 mg/g). Conversely, the predictive performance of PCR was superior in severe albuminuria and nephrotic-range proteinuria, in which the IDI and cNRI of the PCR were greater than those of the mACR. CONCLUSIONS: The mACR, eACR and PCR showed excellent performance in predicting KFRT in patients with CKD. However, eACR was inferior to mACR in patients with low albuminuria, indicating that measuring rather than estimating albuminuria is preferred for these patients.

Nocturnal systolic blood pressure dipping and progression of chronic kidney disease.

The relationship between declining nocturnal blood pressure (BP) and adverse cardiovascular outcomes is well-recognized. However, the relationship between diurnal BP profile and the risk of chronic kidney disease (CKD) progression is unclear. Herein, we examined the association between nocturnal systolic SBP (SBP) dipping and CKD progression in 1061 participants at the Cardiovascular and Metabolic Disease Etiology Research Center-High Risk (CMERC-HI). The main exposure was diurnal systolic BP (SBP) profile and diurnal SBP difference ([nighttime SBP-daytime SBP] × 100/daytime SBP). The primary outcome was CKD progression, defined as a composite of ≥ a 50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy. During 4749 person-years of follow-up (median, 4.8 years), the composite outcome occurred in 380 (35.8%) participants. Compared to dippers, the hazard ratios (HRs) for the risk of adverse kidney outcomes were 1.02 (95% confidence interval [CI], 0.64-1.62), 1.30 (95% CI, 1.02-1.66), and 1.40 (95% CI, 1.03-1.90) for extreme dipper, non-dipper, and reverse dipper, respectively. In a continuous modeling, a 10% increase in diurnal SBP difference was associated with a 1.21-fold (95% CI, 1.07-1.37) higher risk of CKD progression. Thus, decreased nocturnal SBP decline was associated with adverse kidney outcomes in patients with CKD. Particularly, patients with non-dipping and reverse dipping patterns were at higher risk for CKD progression than those with a dipping pattern.

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.

Direct oral anti-Xa anticoagulants versus warfarin in newly diagnosed atrial fibrillation and CKD: the Korean National Health Insurance Data.

Introduction: Despite the benefits of direct oral anti-Xa anticoagulants (DOACs), the risk-benefit profile of DOAC therapy compared to warfarin therapy in patients with non-valvular atrial fibrillation (AF) and chronic kidney disease (CKD), including end-stage renal disease (ESRD), is uncertain. Methods: We conducted a retrospective study using the Korea National Health Insurance Database from 2013 to 2018. We evaluated patients with incident non-valvular AF and CKD. The primary and secondary effectiveness outcomes were ischemic stroke and all-cause mortality. The primary safety outcomes included intracranial hemorrhage, gastrointestinal bleeding, and extracranial or unclassified major bleeding. Results: Among the 1,885 patients evaluated, 970 (51.5%) initiated warfarin therapy, and 915 (48.5%) initiated DOAC therapy. During a mean follow-up period of 23.8 months, there were 293 and 214 cases of ischemic stroke and all-cause death, respectively. Kaplan-Meier survival analysis showed significantly lower all-cause mortality in DOAC users than in warfarin users. In multivariate Cox regression analyses, DOAC therapy had a hazard ratio for all-cause mortality of 0.41 (95% CI, 0.30-0.56; p < 0.001) compared to warfarin therapy. Additionally, DOAC therapy significantly reduced intracranial hemorrhage and gastrointestinal bleeding. Discussion: Our study demonstrates that DOAC therapy has a better risk-benefit profile than warfarin therapy in patients with AF and CKD. Further well-designed clinical trials are needed to clarify the benefits of DOACs in this patient population.

Effectiveness of a Smartphone Application for Dietary Sodium Intake Measurement.

Accurate estimation of sodium intake is a key requirement for evaluating the efficacy of interventional strategies to reduce salt intake. The effectiveness of a smartphone application in measuring dietary sodium intake was assessed. This study included 46 participants who consented to register in Noom's food-logging program. All participants were followed up for six months from the day of enrollment. The mean age of the participants was 40.2 ± 12.3 years, and 22 (48%) participants were male. The average number of times/weeks the meals were logged was 16.2 ± 10.3. At baseline, the mean 24-h urine sodium was 124.3 mmol/24 h. The mean sodium intake measured by the smartphone application and calculated using the 24-h urine sodium was 2020.9 mg/24 h and 2857.6 mg/24 h, respectively. During the second visit, the mean 24-h urine sodium was 117.4 mmol/24 h. The mean sodium intake measured by the smartphone application and calculated using the 24-h urine sodium was 1456.0 mg/24 h and 2698.3 mg/24 h, respectively. Sodium intake measured using the smartphone application positively correlated with that calculated using the 24-h urine sodium at baseline (r = 0.464; p < 0.001) and follow-up (r = 0.334; p= 0.023). Dietary sodium intake measured using a smartphone application correlated well with that estimated using 24-h urine sodium level.

Exosome-Based Drug Delivery: Translation from Bench to Clinic.

Exosome-based drug delivery is emerging as a promising field with the potential to revolutionize therapeutic interventions. Exosomes, which are small extracellular vesicles released by various cell types, have attracted significant attention due to their unique properties and natural ability to transport bioactive molecules. These nano-sized vesicles, ranging in size from 30 to 150 nm, can effectively transport a variety of cargoes, including proteins, nucleic acids, and lipids. Compared to traditional drug delivery systems, exosomes exhibit unique biocompatibility, low immunogenicity, and reduced toxicity. In addition, exosomes can be designed and tailored to improve targeting efficiency, cargo loading capacity, and stability, paving the way for personalized medicine and precision therapy. However, despite the promising potential of exosome-based drug delivery, its clinical application remains challenging due to limitations in exosome isolation and purification, low loading efficiency of therapeutic cargoes, insufficient targeted delivery, and rapid elimination in circulation. This comprehensive review focuses on the transition of exosome-based drug delivery from the bench to clinic, highlighting key aspects, such as exosome structure and biogenesis, cargo loading methods, surface engineering techniques, and clinical applications. It also discusses challenges and prospects in this emerging field.

The 2021 KDIGO blood pressure target and the progression of chronic kidney disease: Findings from KNOW-CKD.

BACKGROUND: The 2021 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the management of blood pressure (BP) in chronic kidney disease (CKD) recommends a target systolic BP of <120 mmHg as this target can provide cardiovascular benefits. However, it remains unclear whether implementing the new BP target could improve kidney outcomes. METHODS: The association between the 2021 KDIGO BP target and CKD progression was examined and compared with the 2012 KDIGO BP target among 1724 participants included in the KoreaN Cohort Study for Outcomes in Patients With CKD. The main exposure was the BP status categorized according to the 2012 or 2021 KDIGO guideline: (1) controlled within the 2021 target, (2) controlled within the 2012 target only, and (3) above both targets. The primary outcome was a composite kidney outcome of ≥50% decline in the estimated glomerular filtration rate from baseline or the initiation of kidney replacement therapy during the follow-up period. RESULTS: Composite kidney outcomes occurred in 650 (37.7%) participants during the 8078 person-years of follow-up (median, 4.9 years). The incidence rates of this outcome were 55, 66.5, and 116.4 per 1000 person-years in BP controlled within the 2021 and 2012 KDIGO targets, and BP above both targets, respectively. In the multivariable cause-specific hazard model, hazard ratios for the composite outcome were 0.76 (95% confidence interval (CI), 0.60-0.95) for BP controlled within the 2021 target and 1.36 (95% CI, 1.13-1.64) for BP above both targets, compared with BP controlled within 2012 target only. CONCLUSION: The newly lowered BP target by the 2021 KDIGO guideline was associated with improved kidney outcome compared with BP target by the 2012 KDIGO guideline.

Diagnosis and treatment of hypertension in dialysis patients: a systematic review.

In patients with end-stage renal disease (ESRD) undergoing dialysis, hypertension is common but often inadequately controlled. The prevalence of hypertension varies widely among studies because of differences in the definition of hypertension and the methods of used to measure blood pressure (BP), i.e., peri-dialysis or ambulatory BP monitoring (ABPM). Recently, ABPM has become the gold standard for diagnosing hypertension in dialysis patients. Home BP monitoring can also be a good alternative to ABPM, emphasizing BP measurement outside the hemodialysis (HD) unit. One thing for sure is pre- and post-dialysis BP measurements should not be used alone to diagnose and manage hypertension in dialysis patients. The exact target of BP and the relationship between BP and all-cause mortality or cause-specific mortality are unclear in this population. Many observational studies with HD cohorts have almost universally reported a U-shaped or even an L-shaped association between BP and all-cause mortality, but most of these data are based on the BP measured in HD units. Some data with ABPM have shown a linear association between BP and mortality even in HD patients, similar to the general population. Supporting this, the results of meta-analysis have shown a clear benefit of BP reduction in HD patients. Therefore, further research is needed to determine the optimal target BP in the dialysis population, and for now, an individualized approach is appropriate, with particular emphasis on avoiding excessively low BP. Maintaining euvolemia is of paramount importance for BP control in dialysis patients. Patient heterogeneity and the lack of comparative evidence preclude the recommendation of one class of medication over another for all patients. Recently, however, ß-blockers could be considered as a first-line therapy in dialysis patients, as they can reduce sympathetic overactivity and left ventricular hypertrophy, which contribute to the high incidence of arrhythmias and sudden cardiac death. Several studies with mineralocorticoid receptor antagonists have also reported promising results in reducing mortality in dialysis patients. However, safety issues such as hyperkalemia or hypotension should be further evaluated before their use.

Fibroblast growth factor-23 and cardiovascular disease among prevalent hemodialysis patients focusing on residual kidney function.

Background: In patients undergoing incident hemodialysis, increased fibroblast growth factor-23 (FGF-23) levels are associated with the development of cardiovascular disease (CVD), but the influence of residual kidney function (RFK) on this association is unclear. This study aimed to investigate the association between FGF-23 levels, RKF, and CVD in patients undergoing prevalent hemodialysis. Methods: This cross-sectional and longitudinal observational study included 296 patients undergoing maintenance hemodialysis for at least three months who were followed up for a median of 44 months. RKF was defined as 24-h urine output >200 mL, left ventricular (LV) diastolic dysfunction as E/E' >15 on echocardiographic parameters. CVD was defined as hospitalization or emergency room visits due to cardiovascular causes, such as angina, myocardial infarction, or congestive heart failure. Results: The median intact FGF-23 (iFGF-23) level was 423.8 pg/mL (interquartile range, 171-1,443). Patients with an FGF-23 level > 423.8 pg/mL significantly had a lower proportion of RKF (39.2% vs. 60.1%, P < 0.001) and a higher proportion of LV diastolic dysfunction (54. 1% vs. 29.1%, P < 0.001) than those with an iFGF-23 level ≤ 423.8 pg/mL. The odds ratio (OR) for LV diastolic dysfunction was significantly higher in patients with RFK (OR per one-unit increase in the natural log-transformed iFGF-23 levels, 1.80; 95% confidence interval [CI]: 1.11-2.93) than in patients without RKF (OR per one-unit increase in the natural log-transformed iFGF-23 levels: 1.42; 95% CI: 1.01-1.99) in multivariate analysis (p < 0.001). During the follow-up period, 55 patients experienced CVD. The hazard ratio (HR) for CVD development was also significantly higher in patients with RKF (HR per one-unit increase in the natural log-transformed iFGF-23 levels, 2.64; 95% CI: 1.29-5.40) than those without RKF (HR per one-unit increase in the natural log-transformed iFGF-23 levels: 1.44; 95% CI: 1.04-1.99) in multivariate analysis (p = 0.05). Conclusions: Increased iFGF-23 levels were associated with LV diastolic dysfunction and CVD development in patients undergoing prevalent hemodialysis; however, the loss of RKF attenuated the magnitude of these associations. Therefore, in these patients, RKF strongly influenced the detrimental role of iFGF-23 in the development of CVD.