Clinical decision-making often exhibits substantial inter-physician variability when evaluating identical patient data, limiting the reliability of conventional one data-one outcome clinical decision support systems. We developed and validated a Multi Expert Integrated Algorithm (MEIA) designed to preserve and integrate diverse expert decision patterns for kidney biopsy triage. The study included 9598 patients across three cohorts, comprising a developmental cohort of 8228 patients and two external validation cohorts. Three board-certified nephrologists independently annotated biopsy decisions, and expert-specific machine learning models were trained using identical feature sets to replicate each physician's labeling pattern. These models were integrated through a predefined majority voting framework. Individual models closely reproduced expert decisions in internal validation, while MEIA demonstrated strong performance (accuracy 95.3%, F1-score 84.4%). In external validation, MEIA achieved an AUC of 0.933, with significantly higher discrimination than Expert model C (P< 0.001) and comparable performance to Expert models A and B. SHAP analysis revealed heterogeneity in feature importance across experts. In a pathology-confirmed cohort, all MEIA-recommended cases demonstrated histopathological abnormalities. MEIA provides a structured framework for modeling expert variability; prospective validation is required to confirm clinical utility.

The Cardiovascular-Kidney-Metabolic (CKM) syndrome reframes cardiovascular, kidney, and metabolic disease as an integrated continuum, yet its management relies on reactive laboratory markers with substantial resource burdens. Retinal oculomics offers a non-invasive window into this continuum, grounded in structural and functional parallels between the retina and kidney. Their shared vulnerability to metabolic and hemodynamic stressors allows the retina to reflect subclinical CKM injury. Evidence is strongest for cardiovascular endpoints, where retinopathy and quantitative vessel metrics are associated with incident stroke, cardiovascular mortality, and coronary heart disease. Similar associations are reported for new-onset hypertension, diabetes, and incident chronic kidney disease (CKD), although the CKD association attenuates after adjustment for conventional kidney markers. Artificial intelligence (AI) extends retinal analysis beyond categorical grading and predefined vessel metrics by learning latent features from fundus photographs. Systemic biomarker estimation and cardiovascular risk stratification are the most mature, whereas kidney-specific models remain confined to cross-sectional CKD detection and prediction of CKD development. However, retinal AI is supported by evidence that remains largely observational, retrospective, and dependent on cross-sectional surrogates. Albuminuria, sustained decline in estimated glomerular filtration rate, kidney replacement therapy, and kidney-related mortality have not been targeted. Advanced CKD, dialysis, and kidney transplant populations are underrepresented in development and validation cohorts. No retinal model has reported cardiovascular risk prediction in CKD or direct comparison with established kidney risk equations. Discrimination in these models falls in ethnically distinct cohorts, and calibration is infrequently reported. Management-impact trials have not been conducted, and cost-effectiveness remains unevaluated. Algorithmic opacity and imaging standardization remain unresolved. Once these gaps are addressed, retinal AI may support screening, risk stratification, progression monitoring, and treatment prioritization, shifting from screening in early CKM to complementary phenotyping in advanced CKD. Retinal AI would then complement conventional kidney biomarkers as an integrative, low-burden window into CKM injury.

KEY POINTS:The Predicting Risk of Cardiovascular Disease EVENTs score outperformed previous models in prediction of cardio-kidney outcomes. Adding albuminuria to the Predicting Risk of Cardiovascular Disease EVENTs score showed further improvement in patients with CKD. Among East Asian participants, Predicting Risk of Cardiovascular Disease EVENTs provided modest gains in cardiovascular prediction but prominent improvements in predicting kidney outcomes. BACKGROUND:CKD substantially increases cardiovascular disease (CVD) and mortality risks, yet few models account for integrated cardio-kidney outcomes (CKOs). The American Heart Association's Predicting Risk of CVD EVENTs (PREVENT) score incorporates kidney-specific measures; however, its accuracy for CKOs in patients with CKD remains unclear. We aimed to evaluate PREVENT for CKOs against the pooled cohort equation (PCE) and systematic coronary risk evaluation 2 (SCORE2) in two ethnically distinct CKD cohorts: KoreaN Cohort Study for Outcome in Patients With CKD (KNOW-CKD) from South Korea and Chronic Renal Insufficiency Cohort from the United States. METHODS:This study included 4,268 patients with CKD and no known CVD (chronic renal insufficiency cohort: 2,530, KNOW-CKD: 1,738). We compared PREVENT (CVD and atherosclerotic CVD versions) with the PCE and SCORE2. The primary outcome was CKO, a composite of major adverse kidney events (≥50% eGFR decline or kidney failure requiring replacement therapy) and four-point major adverse cardiovascular events (4P-MACEs). Secondary outcomes included individual components and all-cause mortality. RESULTS:The PREVENT-CVD score showed superior predictive accuracy for CKO (Harrell C, 0.688; 95% confidence interval [CI], 0.675 to 0.701) compared with PREVENT-atherosclerotic CVD (delta C [ΔC]=-0.009; 95% CI, -0.011 to -0.007), PCE (ΔC=-0.104; 95% CI, -0.113 to -0.095), and SCORE2 (ΔC=-0.106; 95% CI, -0.114 to -0.097). This superiority was driven by robust prediction for major adverse kidney event, along with significant improvements in reclassification and discrimination for 4P-MACE and all-cause mortality. Although predictive gains for 4P-MACE were attenuated in the KNOW-CKD cohort, adding albuminuria further enhanced predictive performance for primary outcome. CONCLUSIONS:The PREVENT-CVD equation outperformed traditional cardiovascular risk models in predicting integrated CKOs in patients with CKD. Its consistent discrimination across both cardiovascular and kidney events suggests that PREVENT may reflect the shared pathophysiology of cardio-kidney disease and support broader risk stratification in CKD. PODCAST:This article contains a podcast at https://dts.podtrac.com/redirect.mp3//www.asn-online.org/media/podcast/JASN/2026_07_29_KTS_July2026.mp3.

INTRODUCTION:While urine protein-to-creatinine ratio (UPCR) is more commonly used than urine albumin-to-creatinine ratio in routine care, and particularly in low-resource settings; its association with kidney function decline and projected time to reach a kidney failure estimated glomerular filtration rate (eGFR) threshold in advanced chronic kidney disease (CKD) remains underexplored. METHODS:We analyzed 2,727 participants with eGFR 15-45mL/min/1.73 m2 without kidney replacement therapy (KRT) from the Chronic Renal Insufficiency Cohort (CRIC) study and the KoreaN Cohort Study for Outcome in Patients with Chronic Kidney Disease (KNOW-CKD). The main exposures were baseline and time-updated UPCR. The primary outcome was CKD progression defined as 50% or more decline in eGFR from baseline measurement or the initiation of KRT. The secondary outcome was eGFR slope (mL/min/1.73 m2/year), whereas the exploratory outcome was projected time to reach the eGFR threshold of 10 mL/min/1.73 m2 for kidney failure. RESULTS:During 17,069 person-years of follow-up (median 4.9 years), the primary outcome occurred in 1,474 participants (54%). Compared with UPCR <0.5 g/gCr, hazard ratios (HRs) (95% confidence intervals [CIs]) for UPCR categories of 0.5-1.0, 1.0-3.0, and ≥ 3.0 g/gCr were 2.08 (1.76-2.45), 3.05 (2.64-3.52), and 6.32 (5.24-7.61), respectively. This association was stronger in analysis with time-updated UPCR, with the corresponding HRs (95% CIs) of 2.58 (2.13-3.12), 5.61 (4.76-6.62), and 12.88 (10.58-15.67), respectively. In secondary analyses, the eGFR slopes for the respective categories were -0.87 (-0.98 to -0.77), -2.32 (-2.56 to -2.07), -3.41 (-3.63 to -3.19), and -5.45 (-5.93 to -4.97) mL/min/1.73 m2 per year. Additionally, projected time to eGFR threshold for kidney failure (95% CIs) was lower progressively with increasing proteinuria categories, estimated at 28.7 (25.6-32.6), 10.3 (9.3-11.5), 6.4 (6.0-6.8), and 3.8 (3.5-4.2) years, respectively. CONCLUSIONS:Higher UPCR levels were strongly associated with accelerated CKD progression and shorter projected time to reach the eGFR threshold for kidney failure, underscoring the prognostic significance of proteinuria in patients with advanced CKD.

Background:Chronic kidney disease (CKD) is prevalent among patients with heart failure with preserved ejection fraction (HFpEF), significantly affecting their outcomes. Although the prognostic risk factors remain unclear, peak oxygen consumption (peak VO2) may be used to objectively assess the risk of kidney damage due to overlapping factors affecting kidney function and aerobic exercise capacity. This study aimed to evaluate the association between peak VO2 levels and incident CKD risk among patients with HFpEF. Methods:A total of 342 patients with HFpEF and an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 who underwent cardiopulmonary exercise testing between January 2012 and April 2021 were included. Aerobic exercise capacity was evaluated using the peak VO2 values. Incident CKD development was defined as two consecutive eGFR measurements <60 mL/min/1.73 m2 separated by ≥90 days. Results:The mean patient age was 62.9 ± 10.6 years, with 35.7% being male. Baseline left ventricular ejection fraction and eGFR were 66.7% ± 6.9% and 88.4 ± 12.6 mL/min/1.73 m2 , respectively. For over 940.0 person-years of follow-up (median, 2.9 years), 51 patients developed CKD. CKD incidence rate gradually increased with lower peak VO2 levels. Multivariable Cox analysis showed an association between a 1-standard-deviation peak VO2 increase and a 51% reduction in CKD risk. The adjusted hazard ratio (95% confidence interval) for the lowest peak VO2 tertile group was 3.29 (1.23-8.84) compared with the highest tertile group. Conclusion:Reduced aerobic exercise capacity, indicated by lower peak VO2 levels, is closely associated with an increased CKD risk in patients with HFpEF.

Despite numerous studies investigating the effects of antidiabetic medications on cardiovascular outcomes, the optimal second-line oral antidiabetic medication for atrial fibrillation (AF) prevention remains unclear. This study aims to compare the effects of second-line oral antidiabetic medications including sodium-glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones, dipeptidyl peptidase-4 (DPP-4) inhibitors, or sulfonylureas, on the risk of incident AF in patients with type 2 diabetes. This retrospective study analyzed data from the National Health Insurance Service data on adults with type 2 diabetes who simultaneously initiated metformin and second-line oral antidiabetic medication (SGLT2 inhibitors, thiazolidinediones, DPP-4 inhibitors, or sulfonylureas) between September 2014 and December 2017. Exact matching by sex and age categories was conducted in a 1:1:5:5 ratio corresponding to SGLT2 inhibitor, thiazolidinedione, DPP-4 inhibitor, and sulfonylurea users, with inverse probability of treatment weighting used to balance the baseline characteristics. The primary outcome was incident AF, which was analyzed using a Fine–Gray model treating all-cause mortality as a competing risk. During a mean follow-up of 6.2 years, 774 cases of AF occurred among the 36,744 participants (mean age 55.3 years; 33.6

Key Points Risk of all-cause mortality was significantly lower in KoreaN Cohort Study for Outcome in Patients with CKD group than that in the Chronic Renal Insufficiency Cohort group. Asian cohorts exhibited steeper eGFR decline slopes than that of the Black and White cohorts. Tailored clinical approaches and ethnicity-stratified studies are required to improve CKD management. Background Ethnic differences in CKD progression remain understudied, particularly between Asian and Western populations. Therefore, we aimed to investigate ethnic disparities in CKD progression by comparing nationwide cohorts from South Korea (the KoreaN Cohort Study for Outcome in Patients with CKD [KNOW-CKD]) and the United States (the US Chronic Renal Insufficiency Cohort [CRIC]). Methods A total of 4953 participants were included (69% from CRIC and 31% from KNOW-CKD). The primary outcome was CKD progression, defined as a 50% or greater decline of eGFR or kidney failure requiring KRT. In the secondary outcome analysis, we compared eGFR decline rates and all-cause mortality. Results Of the 4953 participants, CKD progression occurred in 1285 and 570 in the KNOW-CKD and CRIC cohorts, with incidence rates of 67.9 and 41.7 per 1000 person-years, respectively. The hazard ratio for the KNOW-CKD compared with CRIC was 1.66 (95% confidence interval [CI], 1.45 to 1.89). The annual eGFR decline was steeper in KNOW-CKD participants than in CRIC participants (−2.51 versus −1.14 ml/min per 1.73 m 2 ). Asian participants from the CRIC cohort exhibited a similar eGFR slope (95% CIs) (−2.10 [−2.69 to −1.52]) to those from KNOW-CKD (−2.50 [−2.67 to −1.52]), while the slope was −1.47 (−1.61 to −1.33) and −0.81 (−0.92 to −0.70) ml/min per 1.73 m 2 per year for Black and White participants, respectively. However, the risk of mortality was significantly lower in KNOW-CKD participants compared with CRIC participants (hazard ratio, 0.51; 95% CI, 0.38 to 0.68). Conclusions CKD progression was faster in the Korean cohort than in the US cohort, with Asian participants in both cohorts showing similar eGFR decline rates. However, the Korean cohort had a lower risk of mortality, indicating potential ethnic or regional differences in disease progression and survival.

BACKGROUND:Growth differentiation factor-15 (GDF-15) has been implicated in adverse outcomes in cardiovascular disease and diabetes, highlighting its potential as a prognostic marker. However, its association with chronic kidney disease (CKD) development remains unclear. Therefore, we investigated the association between GDF-15 and incident CKD and explored potential causal mechanisms. METHODS:We analyzed 31,965 UK Biobank participants without pre-existing CKD. The primary outcome was incident CKD, defined by diagnostic codes or an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 (eGFR-based CKD). Proteomics-based mediation and protein-protein interaction analyses identified potential mediators linking GDF-15 to CKD. A bidirectional two-sample Mendelian randomization (MR) analysis using genome-wide association study summary statistics evaluated the potential causal relationship between GDF-15 and eGFR. RESULTS:In multivariable cause-specific analyses, higher GDF-15 levels were significantly associated with increased CKD risk (hazard ratios: Q2, 1.05 [0.87-1.26]; Q3, 1.21 [1.01-1.45]; Q4, 1.87 [1.56-2.26] vs. Q1; P-for-trend <0.001). Similar results were observed for eGFR-based CKD. Mediation analysis identified candidate proteins potentially involved in TNF receptor signaling, extracellular matrix organization, and immune cell chemotaxis. MR analysis demonstrated a significant association between genetically predicted higher GDF-15 levels and higher eGFR (IVW coefficient: 0.003; 95% confidence interval [CI]: 0.001-0.004; P =0.004). Conversely, higher genetically predicted eGFR was associated with lower GDF-15 levels (IVW coefficient: -1.238; 95% CI: -1.591 to -0.886; P <0.001). CONCLUSIONS:This study provides evidence supporting the role of GDF-15 as a prognostic biomarker for CKD and MR analyses provide suggestive evidence of a possible protective association of GDF-15 with kidney function. Further studies are needed to explore the mechanistic pathways and therapeutic implications of GDF-15 in kidney diseases.

Colchicine, a well-known anti-inflammatory drug, has emerged as a therapeutic option in various inflammatory diseases. However, its role in chronic kidney disease (CKD) remains unclear. This study aims to investigate the reno-protective effects of colchicine in an experimental CKD model and its potential role in modulating the NOD-like receptor, pyrin domain containing protein 3 (NLRP3) inflammasome pathway. A CKD animal model was established in C57BL/6 mice by feeding a 0.2

Key Points Plasma proteome profiling identified distinct signatures across biopsy-proven primary glomerular disease subtypes. An elastic net model using 93 proteins classified primary glomerular disease subtypes and controls, with external validation. Integrating proteomics with machine learning yields biologically interpretable insights in primary glomerular diseases. Background Primary GN is a heterogeneous group of kidney disorders where understanding of their pathophysiology remains incomplete. Despite the diagnostic potential of high-throughput proteomics, constrained proteomic depth and a reliance on binary comparisons have left the feasibility of using systemic signatures to differentiate multiple GN subtypes largely unexplored. Methods To identify protein signatures that noninvasively differentiate major primary glomerular disease subtypes and provide mechanistic insights, we performed large-scale systemic proteome profiling of 5416 plasma proteins via Olink Explore HT in a discovery cohort ( n =147) and an external validation cohort ( n =85) of Korean participants (mean age, 41±13 years; 46% female). The study population included patients with four GN subtypes—focal segmental glomerulosclerosis, IgA nephropathy, minimal change disease, and membranous nephropathy—alongside healthy controls. We developed a machine learning (ML) model using logistic regression with elastic net regularization to classify disease groups based on proteomic profiles and evaluated its performance in the independent validation cohort. Results Plasma proteome profiles were distinct among disease subtypes, emerging as a significant source of data variation independent of conventional markers such as eGFR or proteinuria levels. The ML model performed robustly in both the discovery and validation cohorts, achieving an area under the receiver operating characteristic curve >0.8 for differentiating minimal change disease, membranous nephropathy, and IgA nephropathy. The model, even without clinical information, correctly identified 93% of minimal change disease cases (14 of 15) and 63% of IgA nephropathy cases (20 of 32), but its performance was limited for focal segmental glomerulosclerosis, with only 21% of cases (three of 14) correctly classified. Functional analysis of key proteins highlighted distinct biologic pathways, such as hemostasis in minimal change disease. Conclusions We identified distinct systemic proteome signatures for primary glomerular diseases, where disease subtype served as a major determinant of proteomic variance alongside conventional clinical markers. ML models demonstrated robust discriminatory performance for minimal change disease, membranous nephropathy, and IgA nephropathy, underscoring the potential for proteome-based classification.

Background:Optimized supportive therapy, including maximal renin-angiotensin-aldosterone system (RAAS) inhibition, is not always adequate in patients with IgA nephropathy (IgAN). This study evaluated the early effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is) on kidney function in patients with IgAN receiving RAAS inhibitors. Methods:Adult patients who were newly diagnosed with IgAN during 2020-2024, with baseline estimated glomerular filtration rate (eGFR) ≥35 mL/min/1.73 m2 , urine protein-to-creatinine ratio (UPCR) ≥0.8 g/g, and receiving RAAS inhibitors for ≥28 days were selected. The primary exposure was the incident use of SGLT2i. Changes in UPCR, urine albumin-to-creatinine ratio (UACR), and eGFR at 12 months were examined using mixed-effect models for repeated measures with inverse probability of treatment weighting. Results:SGLT2i use was associated with an early eGFR decline (mean difference, -5.39 mL/min/1.73 m2 ; 95% confidence interval [CI], -9.51 to -1.26) but was not significantly associated with the reduction in UPCR (geometric mean ratio [GMR], 0.90; 95% CI, 0.68-1.18) or UACR (GMR, 0.94; 95% CI, 0.67-1.34) at 12 months compared with non-users. However, subgroup and sensitivity analyses suggested a potential relationship between SGLT2i use and the reduction in proteinuria in patients with S0 lesions according to the Oxford Classification and baseline systolic blood pressure ≥130 mmHg, indicating possible benefits despite the absence of consistent statistical significance across analyses. Conclusion:In this real-world IgAN cohort, although SGLT2i use was not significantly associated with proteinuria reduction at 12 months, differential subgroup responses suggest that antiproteinuric benefits may be greater in patients without segmental glomerulosclerosis or with elevated systolic blood pressure.

BACKGROUND:Postoperative acute kidney injury (AKI) is a significant complication following cardiac surgery, with limited preventive measures. AIMS:Our aim was to evaluate the association between preoperative serum ionized calcium levels and postoperative AKI in patients undergoing cardiac surgery. METHODS:This retrospective cohort study included adult patients (≥18 years) who underwent elective or non-elective cardiac surgery at two tertiary hospitals between 2006 and 2020. Patients with an estimated glomerular filtration rate ≥15 ml/min/1.73 m2 who were not receiving maintenance dialysis were eligible. Preoperative serum ionized calcium levels were categorized 2 / 25 into quartiles (Q1-Q4). The primary outcome was postoperative AKI within 48 hours, defined according to Kidney Disease: Improving Global Outcomes criteria. Multivariable logistic regression and mediation analyses were performed. RESULTS:Among 9779 patients (median age, 64 years; 60.1% male; 42.6% coronary artery bypass grafting, 57.4% valvular surgery with or without coronary artery bypass grafting; 4.6% emergency surgery; 10.0% chronic kidney disease stages 3-4), mild AKI (Kidney Disease: Improving Global Outcomes stage 1) and moderate-to-severe AKI (Kidney Disease: Improving Global Outcomes stage 2-3) occurred in 3848 (39.3%) and 719 (7.4%) patients, respectively. Acute kidney injury requiring dialysis occurred in 197 (2.0%) patients, and in-hospital mortality was 2.5%. Compared with Q4 (highest calcium), the adjusted odds ratios (95% confidence intervals) for mild AKI were 1.58 (1.38-1.80), 1.21 (1.06-1.38), and 1.05 (0.92-1.20) for Q1, Q2, and Q3, respectively (P for trend < 0.001). For moderate-to-severe AKI, the corresponding adjusted odds ratios were 2.11 (1.65-2.69), 1.44 (1.12-1.87), and 1.16 (0.88-1.51) (P for trend < 0.001). The association was stronger in patients with congestive heart failure and those undergoing prolonged cardiopulmonary bypass (both P for interaction < 0.05). Mediation analyses suggested that intraoperative vasopressor use, cardiopulmonary bypass time, and red blood cell transfusion partially mediated the association between calcium levels and AKI outcomes. The lowest ionized calcium quartile was also independently associated with higher in-hospital mortality (Q1: adjusted odds ratio, 2.32; 95% confidence interval, 1.53-3.54). CONCLUSIONS:Lower preoperative serum ionized calcium levels were independently associated with higher risk of postoperative AKI following cardiac surgery. These findings suggest that ionized hypocalcemia may serve as a hemodynamic risk factor for AKI in this population.

Background: The impact of facility-level comorbidity burden on the prognosis of hemodialysis patients remains unclear. This study aimed to investigate the association between facility-level comorbidity burden and hemodialysis outcomes. Methods: We examined 15,481 participants receiving hemodialysis at primary clinics participating in the Periodic Hemodialysis Quality Assessment by Health Insurance Review and Assessment Service in Korea. Facility-level comorbidity burden, defined as the sum of the Charlson Comorbidity Index of all patients divided by the number of nurses in each hemodialysis center, was the primary predictor. The primary outcome was major adverse cardiac and cerebrovascular events (MACCE). Results: During a median follow-up of 6.8 years, MACCE and all-cause mortality occurred in 9,797 (63.3%) and 8,513 participants (55.0%), respectively. Participants in the highest facility-level comorbidity burden had the highest incidence rates of both MACCE and all-cause mortality. Hazard ratios (HRs) of MACCE and all-cause mortality in the highest vs. the lowest quartile were 1.10 (95% confidence interval [CI], 1.03–1.18) and 1.14 (95% CI, 1.06–1.22), respectively. Applying the facility-level comorbidity burden as a continuous variable, each 10-unit increase in facility-level comorbidity burden was associated with a 4% and 8% higher risk of MACCE and all-cause mortality, respectively. These associations remained consistent across subgroups. Conclusion: Our findings revealed that the facility-level comorbidity burden in hemodialysis centers was associated with a higher hazard of poor outcomes in patients undergoing hemodialysis.

AIMS:Finerenone is approved for the treatment of diabetic kidney disease (DKD), but real-world evidence remains limited. We evaluated the effectiveness and safety of finerenone in routine clinical practice. MATERIALS AND METHODS:This retrospective observational study included patients with DKD who were prescribed finerenone. Effectiveness was assessed by measuring changes in urine protein-to-creatinine ratio (UPCR) and urine albumin-to-creatinine ratio (UACR) over the 6-month period following initiation of finerenone. Changes in estimated glomerular filtration rate, blood pressure, potassium levels, renin, and aldosterone were also monitored. RESULTS:A total of 404 patients with DKD were analysed. After 6 months of finerenone treatment, UPCR and UACR decreased substantially, with mean within-subject changes of -820.2 ± 1528.3 and -606.4 ± 1119.6 mg/g, respectively. 59.9% of patients achieved a ≥ 30% reduction in UPCR from baseline. Patients who were older, had lower baseline potassium levels, and received a higher mean daily dose of finerenone exhibited a more favourable response to finerenone. The mean increase in potassium levels was 0.3 mEq/L at 6 months, and the treatment discontinuation rate due to hyperkalemia was 5.4%. The aldosterone-to-renin ratio showed a modest decrease at 3 months (mean within-subject change, -3.79 ± 13.76 ng/dL per ng/mL/h), with borderline statistical significance. CONCLUSIONS:Finerenone treatment was associated with a significant reduction in proteinuria in patients with DKD. The safety profile was comparable to that reported in previous studies.

Background Although the association between diet-induced inflammation and the risk of cardiovascular disease or cancer has been previously reported, its contribution to CKD and the underlying biologic mechanisms remain unclear. This study aimed to elucidate the mechanistic role of the dietary inflammatory index (DII) in CKD through multiomics-based mediation analyses and to provide clinically relevant insight. Methods This study included 158,722 UK Biobank participants without underlying CKD (median age 57 years; 53% female). The DII was assessed through a 24-hour dietary recall and categorized into quartiles. Incident CKD was identified using International Classification of Diseases-10 and Office of Population Censuses and Surveys Classification of Interventions and Procedures-4 codes. In a subcohort with creatinine follow-up, CKD was also defined as an eGFR <60 ml/min per 1.73 m(2) . Mediation analyses using proteomics and metabolomics data were conducted to explore potential mechanisms linking diet-induced inflammation to CKD. Individual food item analyses were performed to identify their association with CKD through diet-induced inflammation. Results During a median of 11.2 years of follow-up, CKD occurred in 4382 patients. Cox regression revealed that the adjusted hazard ratios for incident CKD were higher in a stepwise fashion across higher DII quartiles (adjusted hazard ratio and 95% confidence interval: Q2, 1.08 [0.99 to 1.18]; Q3, 1.15 [1.05 to 1.26]; Q4, 1.17 [1.06 to 1.29]) relative to Q1 (P-for-trend < 0.001). Similar results were observed with eGFR-defined CKD. Proteomics-based mediation analysis identified death receptor and TNF receptor-related proteins as mediators linking diet-induced inflammation to CKD. Metabolomics analysis highlighted omega-3 fatty acids, especially docosahexaenoic acid, as protective mediators. Oily fish intake was inversely associated with CKD risk, while sugar-rich and high-fat dairy consumption showed positive associations, partly through inflammatory pathways. Conclusions The association between the DII and incident CKD risk may be partly mediated by alterations in circulating protein profiles involving TNF receptor superfamily-related pathways and plasma omega-3 fatty acids. Dietary counseling aimed at lowering the consumption of sugar-rich and high-fat dairy products may be beneficial.

Blood pressure (BP) control is important in the management of chronic kidney disease (CKD). However, in patients with advanced CKD, the benefits of BP control in delaying the progression of CKD remains uncertain. We aimed to explore the association of BP levels with kidney outcomes in patients with advanced CKD. We analyzed 2,939 participants with chronic kidney disease (CKD) G3b to G5 (estimated glomerular filtration rate [eGFR] <45 ml/min/1.73 m2) without kidney replacement therapy (KRT) from the Chronic Renal Insufficiency Cohort (CRIC) study and the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD). The main predictors were baseline and time-updated systolic BP (SBP) and diastolic BP (DBP). The primary outcome was a composite kidney outcome of ≥50% decline in eGFR from baseline measurement or the initiation of KRT. In the analyses, multivariate cause-specific hazards models and marginal structural models were fitted for baseline and time-updated BPs, respectively. During 17755 person-years of follow-up (median, 4.7 years), the composite outcome occurred 1,627 (55.4%) participants. Compared with baseline SBP <120 mmHg, the hazard ratios (HRs) (95% CIs) for 120–129, 130–139, and ≥140 mmHg were 1.33 (1.15–1.54), 1.48 (1.27–1.72), and 1.82 (1.58–2.10), respectively. This association was more evident in analysis with time-updated SBP, where the corresponding HRs (95% CIs) were 1.29 (1.09–1.54), 1.75 (1.46–2.10), and 2.79 (2.36–3.29), respectively. Furthermore, the slopes of eGFR decline were −1.20 (−1.36 to −1.04), −1.77 (−1.97 to −1.57), −2.11 (−2.35 to −1.88), and −2.48 (−2.70 to −2.27) for respective SBP categories. Additional analyses with DBP also showed similar results. In patients with advanced CKD, higher BP levels were associated with an increased risk of CKD progression.

Kidney function declines faster in patients with type 2 diabetes mellitus (T2DM) than in those without, and coronary artery calcification is a risk factor for adverse kidney outcomes. Thus, we examined whether T2DM modified the relationship between coronary artery calcification and chronic kidney disease (CKD) progression. Among 2067 participants from the KoreaN Cohort Study for Outcome in Patients With CKD, the main exposures analyzed were T2DM and coronary artery calcification. The primary outcome was CKD progression, which was a composite of > 50