While chronic kidney disease (CKD) afflicts an estimated 14

The prevalence of anemia is high in people with chronic kidney disease (CKD) and increases as the disease advances. The Kidney Disease Outcomes Quality Initiative (KDOQI) convened a work group to review the Kidney Disease: Improving Global Outcomes (KDIGO) 2026 clinical practice guideline for the management of anemia in CKD. The previous KDIGO anemia guideline was published in 2012; in 2019 and 2021 KDIGO convened conferences addressing controversies in iron management and hypoxia-inducible factor-prolyl hydroxylase inhibitor (HIF-PHI) use, respectively. The KDOQI work group provides perspective for implementation of the KDIGO 2026 anemia guideline within the context of clinical practice in the United States. The KDOQI work group agrees with most of the KDIGO recommendations, particularly the proactive use of intravenous (IV) iron in hemodialysis patients and the preference for erythropoiesis stimulating agents (ESAs) over HIF-PHIs for first-line anemia therapy, due to greater familiarity with safety of the former. Specific issues regarding recommendations and practice points for providers in the United States include higher serum ferritin targets and mean levels among people receiving hemodialysis than in the rest of the world; the availability of a single HIF-PHI product with approval only for patients receiving dialysis for ≥3 months; and payment barriers that may drive the choice of therapeutic agents. Additional commentary is provided on topics including IV iron therapy in people receiving hemodialysis and an iron-based phosphate binder, the incidence and significance of hypophosphatemia among people with CKD not on dialysis but receiving IV iron therapy, the physiologic importance of iron repletion in people with CKD and iron deficiency without anemia, possible therapeutic benefits of HIF-PHIs compared with ESAs, and assessing risk versus harm of red blood cell transfusions.

BACKGROUND:The Effect of Sodium Zirconium Cyclosilicate on Arrythmia-Related Cardiovascular Outcomes in Participants on Chronic Hemodialysis with Recurrent Hyperkalemia (DIALIZE-Outcomes) trial evaluated the effect of sodium zirconium cyclosilicate (SZC) on arrhythmia-related cardiovascular outcomes among patients receiving maintenance hemodialysis. The study was terminated early because of a low event rate and high treatment discontinuation. As SZC exchanges sodium for potassium, volume expansion from increased sodium absorption is a potential adverse effect. This post hoc analysis evaluated the effects of SZC versus placebo on volume status. METHODS:Adults receiving maintenance hemodialysis with predialysis hyperkalemia (serum potassium ≥5.5 mmol/L) were randomized 1:1 to SZC (starting dose 5 g once daily on non-dialysis days, titrated as needed; N=1349) or placebo (N=1341). Indicators of volume status included: adverse events (AEs) related to volume status, antihypertensive medication use, change in predialysis blood pressure, and change in interdialytic weight gain (IDWG). RESULTS:For the 2690 randomized participants, 62% were male, mean (SD) age was 56.1 (13.4) years, predialysis weight was 75.3 (19.8) kg, and dialysis vintage was 5.9 (5.3) years. In the SZC and placebo groups, there were similar proportions of participants with AEs of edema (5% versus 5%), heart failure (5% versus 5%), and hypertension (9% versus 8%). Mean (SD) changes from baseline to end of follow-up were similar between SZC and placebo for predialysis systolic (-2.1 [24.3] versus -2.2 [22.2] mm Hg) and diastolic (-0.9 [15.0] versus -0.8 [14.2] mm Hg) blood pressure, and IDWG (+0.2 [2.6] versus +0.1 [2.4] kg). The number of antihypertensive medications used was similar between SZC and placebo at baseline (85% versus 83%) and during follow-up (88% versus 86%). CONCLUSIONS:In this post hoc analysis of a large trial of patients with hyperkalemia receiving hemodialysis, there was no clinical evidence of volume changes with SZC. This supports the use of SZC as hyperkalemia treatment among patients receiving hemodialysis-a population at high risk for hypervolemia.

BACKGROUND:Medication nonadherence disproportionately affects low-income populations, especially during care transitions, by increasing readmissions, emergency visits, and mortality. These populations face financial, transportation, and coordination barriers that traditional medication therapy management often fails to address, highlighting the need for innovative solutions. We are conducting a pragmatic randomized controlled trial to determine the effectiveness of the patient-centered Medication Affordability, Accessibility, and Availability in Care Transitions (Med AAAction) intervention to improve medication adherence and healthcare utilization among low-income patients with multiple chronic conditions (MCC). METHODS:Low-income adults (≤ 200% federal poverty level) with MCC or using two or more chronic disease medications (N = 388) from two Tennessee hospitals are randomized to usual care or the Med AAAction intervention. Recruitment began in April 2024. This multicomponent intervention provides free (zero-copay) chronic disease medications with bedside and home delivery, health coaching, and care coordination by certified pharmacy technicians to assist with rapid and ongoing primary care follow-up after hospital discharge. The primary outcome is medication adherence measured using pill counts at 3, 6, 9, and 12-month by comparing doses taken with prescription supply and fill dates. Secondary outcomes include 14-day primary care follow-up, 30-day readmissions, and one-year hospitalizations, emergency visits, and healthcare costs. DISCUSSION:By addressing medication affordability, accessibility, and availability, this trial tests whether a patient-centered multicomponent intervention improves medication adherence and reduces healthcare use among low-income adults with MCC. If effective, Med AAAction could be implemented across health systems to support high-risk patients and enhance health outcomes while lowering costs.

The American Heart Association's PREVENT equations estimate risk of total cardiovascular disease (CVD), atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF) to guide lipid-lowering and blood pressure-lowering therapy in people ages 30-79 years in the United States. The SCORE2 risk algorithm is used to estimate CVD risk for similar purposes in people ages 40 and older in Europe. Neither set of equations has been comprehensively validated in global observational cohorts and randomized trials. In this study, in 44 observational cohorts and 18 randomized trials, we assessed discrimination and calibration of the two risk algorithms across geographical regions (North America, Europe and Asia/Other or multiregional trials). We also created scaling factors for risk prediction over 1-9 years using the PREVENT equations, enabling shorter-term risk prediction for research purposes or to facilitate clinical trial enrollment. Over 5.1 years of mean follow-up, 293,737 PREVENT total CVD events (fatal and non-fatal ASCVD or HF) and 258,086 SCORE2 CVD events (myocardial infarction, stroke or cardiovascular death) were observed among 6,422,714 and 5,437,384 individuals, respectively. Despite differences in CVD outcome definitions, target populations and predictor variables, overall discrimination and calibration were similar for both equations, with generally good performance across regions, including in multiregional randomized trials. These findings lend support for adoption of PREVENT or SCORE2 for cardiovascular risk stratification across diverse settings.

APOL1 variants confer increased risk for kidney disease in individuals of African ancestry, particularly in homozygous or compound heterozygous states. A missense variant, p.N264K, has been shown to attenuate this risk when co-inherited with the G2 allele. While these associations are established in adults, data in pediatric populations remain limited. Using the University of Tennessee Health Science Biorepository and Integrative Genomics initiative, we assessed chronic kidney disease (CKD) risk by APOL1 high-risk genotype and the potential protective effect of p.N264K in a diverse pediatric cohort. This is a case–control study of African American children enrolled in the BIG initiative at Le Bonheur Children’s Hospital (2014–2022). Composite CKD was defined by eGFR < 90 mL/min/1.73 m2 or albuminuria (UACR > 30 mg/g) on two occasions ≥ 90 days apart. The p.N264K variant status was assessed in patients with APOL1 high-risk (HR). Logistic regression models adjusted for age, sex, and five principal components of ancestry assessed associations with CKD and albuminuria. CKD cases had 8

BACKGROUND:Dyslipidemia, distinctly characterized by hypertriglyceridemia and impaired high-density lipoprotein cholesterol (HDL-C) metabolism in patients with chronic kidney disease (CKD), is associated with kidney disease progression. However, evidence on the renal outcomes of Triglyceride (TG)-targeting lipid-lowering therapies (LLTs), such as fibrates and niacin, often prescribed to patients with non-dialysis-dependent (NDD) CKD, is insufficient and equivocal. METHODS:We designed this retrospective cohort study using a target trial emulation framework and leveraged data from a nationwide cohort of 3,562,882 US Veterans to identify incident CKD patients initiating de novo LLTs. We compared eGFR decline from baseline and the odds of rapid eGFR decline in fibrate and niacin initiators versus statin initiators using the mixed-effects model-predicted 1-year, 3-year, and 10-year eGFR slopes, adjusted for baseline covariates. We also compared the risk of major adverse kidney events [MAKE] (composite of a sustained ≥57% decrease in eGFR from baseline, sustained eGFR<15 mL/min/1.73 m2, incident end-stage renal disease, and all-cause death) using Cox proportional hazards models adjusted for baseline covariates during follow-up of up to 10 years. RESULTS:Among 68,073 patients with incident CKD, 62,866 initiated de novo statin, 3,202 fibrate, or 2,005 niacin therapy. Compared to statin use, de novo fibrate initiators had slower eGFR decline (difference in 10-year slope: 0.26 mL/min/1.73 m2/year [95% CI, 0.11, 0.40], P<0.001), whereas the eGFR decline was not statistically significant in the niacin vs. statin comparison. The risk of MAKE was not significantly different in fibrate (hazard ratio, 0.94 [95% CI, 0.88, 1.01], P=0.09) or niacin (0.96 [0.89, 1.04], P=0.31) users after a median follow-up of 3.69 years. CONCLUSIONS:Among patients with NDD-CKD, unlike niacin, long-term fibrate use (compared to statin use) was associated with slower eGFR decline, suggesting renoprotective effects of fibrates. Further studies are warranted to investigate whether fibrate use is beneficial for preventing other outcomes, such as adverse cardiovascular events.

Chronic kidney disease (CKD) is a significant public health problem worldwide because of its increasing prevalence and strong association with poor outcomes. In particular, patients with CKD have a disproportionately high risk of premature cardiovascular morbidity and mortality, which increases exponentially as CKD progresses to end-stage kidney disease. Whereas traditional cardiovascular risk factors are highly prevalent in patients with CKD, several nontraditional risk factors, such as inflammation, also come into play in cardiovascular diseases, especially in advanced CKD stages. Furthermore, recent advances in high-throughput "omics" technologies and sophisticated bioinformatics and modeling approaches have identified an increasing number of novel cardiovascular risk factors in CKD across various omics levels, including the microbiomics, proteomics, metabolomics, transcriptomics, epigenomics, and genomics. These molecular markers identified from high-dimensional omics data have not only advanced our understanding of cardiovascular disease mechanisms in CKD but also facilitated the development of target-driven therapeutic strategies to reduce excess cardiovascular morbidity and mortality in this population. However, significant challenges to their research and clinical applications remain, including the high cost of multiomics profiling and the complexity of assessing comparative cardiovascular risk between multidimensional omics data across different stages of CKD. In this article, based on a comprehensive literature search on PubMed and Google Scholar, we review emerging cardiovascular risk factors in the era of integrated multidimensional omics approaches, with an emphasis on recent findings from microbiomics, and discuss their prognostic implications, current challenges, and future directions in the context of translational epidemiology toward improving cardiovascular outcomes in patients with CKD.

Background: Rapid identification of patients at risk of contrast-associated acute kidney injury (AKI) is essential in acute settings such as acute myocardial infarction and ischemic stroke. Point-of-care (POC) creatinine testing provides immediate assessment of kidney function; however, its reliability for clinical risk stratification relative to standard laboratory measurements remains uncertain. This study evaluated the agreement between laboratory- and POC creatinine-based risk stratification and their association with subsequent AKI after contrast angiography. Methods: In this prospective observational study, 295 adults undergoing contrast-enhanced angiography for acute myocardial infarction or acute ischemic stroke were enrolled. Serum creatinine was measured using both standard laboratory methods and a POC device before contrast administration. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI 2021 equation, and predicted risk of post-contrast AKI was assessed using the Mehran risk score. AKI was defined according to KDIGO criteria (≥1.5-fold increase from baseline or ≥26.5 µmol/L increase within 7 days). Agreement between laboratory- and POC-derived risk categories was evaluated using weighted Cohen’s kappa. Results: The median age was 64 years (interquartile range 57–70), and 66.8% of participants were male. Based on laboratory measurements obtained in the hospital central laboratory, categories were low in 8.8%, moderate in 37.3%, high in 25.4%, and very high in 28.5% of patients. Among patients with available follow-up creatinine measurements (n = 127), CA-AKI occurred in 11.0% (14/127). Agreement between laboratory- and POC-based risk classifications was near-perfect (κ = 0.97, 95% CI 0.95–0.98). The correlation between laboratory and POC creatinine values was moderate (r = 0.63, p < 0.001). Conclusion: POC creatinine–based Mehran risk stratification shows excellent diagnostic agreement with laboratory-based assessment for identifying patients at risk of post-contrast AKI. POC testing may facilitate rapid bedside risk assessment in patients undergoing angiography for acute myocardial infarction or ischemic stroke without compromising risk classification reliability.

BACKGROUND:In patients with chronic kidney disease (CKD), lower and subfunctional high-density lipoprotein cholesterol (HDL-C) is associated with poor cardiovascular outcomes. Notwithstanding such poor outcomes, the primary therapeutic target in patients with CKD is low-density lipoprotein cholesterol (LDL-C), and the comparative effectiveness of commonly used lipid-lowering therapies (LLTs) in changing HDL-C levels in patients with non-dialysis-dependent CKD (NDD-CKD) remains unclear. METHODS:In this retrospective cohort study, using a target trial emulation framework, we examined a nationwide cohort of 3,562,882 US Veterans with normal kidney function enrolled between October 2004 and September 2006 and identified 247,270 incident CKD patients eligible for de novo LLT exposure, occurring during longitudinal follow-up until October 2019. We defined de novo LLT initiation using pharmacy dispensation data and followed patients for up to 1 year. We compared the intraindividual slopes of HDL-C levels in de novo fibrates and niacin users with those in statin users, using mixed-effects models adjusted for baseline and time-varying covariates. We also compared the odds of having a clinically meaningful (>10% from baseline) increase in HDL-C following LLT initiation. RESULTS:A total of 38,223 patients with incident CKD initiated de novo LLT (statin [n = 35,284], fibrate [n = 1,805], and niacin [n = 1,134]). The mean (standard deviation) age was 67.3 (10.5) years; 95.0% were men, and 20.6% were Black. Compared to statin users, the multivariable-adjusted annualized intraindividual increase of HDL-C was significantly higher following fibrate {1.15 mg/dL/year (95% confidence interval [CI]: 0.43, 1.87); p = 0.002} and niacin monotherapy (2.51 mg/dL/year [95% CI: 1.62, 3.41]; p < 0.001). Furthermore, niacin (OR: 1.37 [95% CI: 1.07, 1.75]; p = 0.012) was more likely than statins to provide a clinically meaningful elevation in HDL-C. Our findings were consistent in several sensitivity analyses. CONCLUSION:Among patients with NDD-CKD, de novo prescriptions of fibrates or niacin are associated with a greater increase in HDL-C levels compared to statins. Further studies are warranted to investigate whether such differences have meaningful effects on clinical outcomes.

Background Finerenone, a nonsteroidal mineralocorticoid receptor antagonist, improves renal and cardiovascular outcomes in patients with chronic kidney disease (CKD) and type 2 diabetes (T2D). However, evidence on its use in clinical practice remains limited. Within the FOUNTAIN platform (NCT05526157; EUPAS48148), this study aimed to characterize the profiles and treatment patterns of patients initiating finerenone in the United States following its regulatory approval in 2021. Methods This observational study used Optum’s de-identified Clinformatics® Data Mart Database to identify adults with T2D and CKD who initiated finerenone between July 2021 and September 2023. Baseline demographic and clinical characteristics (e.g., estimated glomerular filtration rate, urine albumin-to-creatine ratio [uACR]) were assessed, and treatment utilization patterns were described. Results Among 3,591 new finerenone users, mean age was 72.2 years and 47.5% were female. Most (62.4%) had stage 3 CKD, and of those with recorded uACR, 86.5% had moderate/severe albuminuria (≥30 mg/g). Renin-angiotensin-aldosterone system inhibitors (RAASi; 80.0%), sodium-glucose cotransporter 2 inhibitors (SGLT2i; 41.4%), and glucagon-like peptide-1 receptor agonists (GLP-1 RA; 30.2%) usage was common in the 90 days preceding finerenone initiation. Finerenone was typically initiated as an add-on to RAASi (58.5%), SGLT2i (28.0%), or GLP-1 RA (21.1%); monotherapy usage was infrequent (8.5%). Among those with ≥ 12 months’ follow-up, 56.0% remained on finerenone at 12 months and 16.7% had titrated from 10 mg to 20 mg. Conclusions Finerenone was primarily prescribed as a pillar of therapy that is used in combination with complementary medications in patients with T2D and CKD, aligning with clinical guidelines and regulatory labeling.

Rationale & Objective The long-term outcomes associated with IV vs. oral iron replacement therapy in patients with chronic kidney disease (CKD) are unclear. We investigated the association of IV vs oral iron replacement therapy with incident end-stage kidney disease (ESKD) and with all-cause mortality in a national cohort of US Veterans with eGFR <60ml/min/1.73m2. Study Design National VA historical cohort study. Setting & Participants 17,428 incident new users of oral iron replacement therapy and a comparable group of 879 incident new users of IV iron replacement therapy during October 1, 2004, through September 30, 2006, with longitudinal follow-up until September 30, 2019. Predictor Incident new use of oral vs. IV IRT. Outcomes ESKD and mortality. Analytical Approach We examined the association of oral vs IV IRT with outcomes using competing risk regression and Cox models. We used propensity score matching to account for differences in baseline characteristics. Results Event rates were overall higher in patients receiving IV iron replacement, but the risk was mitigated after PS matching, with no significant association observed between the type of iron therapy and ESKD (subhazard ratio: 1.07, 95%CI: 0.82-1.39, p=0.6), or all-cause mortality (hazard ratio: 1.07, 95%CI: 0.96-1.20, p=0.2). Limitations Potential selection bias and residual confounding. Conclusions In this large national cohort of patients with chronic kidney disease, IV iron was not significantly associated with higher risk of incident ESKD and all-cause mortality when compared to oral iron therapy. The comparative effectiveness of the different iron replacement modalities will need to be studied further in clinical trials.

OBJECTIVE Patients receiving dialysis who have diabetes have a high burden of dysglycemia. Whereas traditional glycemic markers have limited accuracy and convenience in dialysis, continuous glucose monitoring (CGM) provides automated, less invasive, and more comprehensive glycemic data than do conventional measures. However, it remains unclear whether CGM is associated with improved clinical outcomes in patients undergoing dialysis. RESEARCH DESIGN AND METHODS We examined the association between CGM use versus non-CGM use and survival among U.S. veterans receiving dialysis who also have diabetes, using linked national Veterans Affairs, U.S. Renal Data System, and Medicare data. We examined data from veterans undergoing dialysis and with diabetes with incident CGM use (newly prescribed CGM) versus non-CGM use over the period January 2012 to December 2023 matched by propensity score (PS) to address confounding by indication and who were followed for all-cause mortality events through February 2025. Associations of CGM use versus non-CGM use with death were evaluated using complete case analysis and multiple imputation. RESULTS Among 2,008 patients in the complete case analysis cohort, CGM use was associated with a lower mortality risk in PS-matched unadjusted and doubly adjusted Cox models (reference: non-CGM use; hazard ratio [HR] 0.86 [95% CI 0.76, 0.98]; and 0.83 [95% CI 0.75, 0.92], respectively). Among 3,088 patients in the multiple imputation cohort, CGM use was also associated with greater survival in PS-matched unadjusted and doubly adjusted Cox models (HR 0.88 [95% CI 0.77, 0.99]; and 0.84 [95% CI 0.73, 0.96], respectively). CONCLUSIONS In veterans receiving dialysis who also had diabetes, incident CGM use was associated with better survival versus non-CGM use. Further studies are needed to determine underlying mechanisms and the impact of CGM on other dialysis outcomes.

OBJECTIVE:To compare the effects of nondialytic care vs dialysis on hospitalization outcomes in advanced chronic kidney disease (CKD), given that dialysis, as the predominant treatment paradigm for patients with advanced CKD transitioning to end-stage kidney disease, may be associated with high early mortality, health care utilization, and withdrawal. PATIENTS AND METHODS:We examined a national cohort of veterans with advanced CKD (≥2 estimated glomerular filtration rates <25 mL/min per 1.73 m2 separated by ≥90 days from October 1, 2010, to September 30, 2019) categorized according to receipt of dialysis vs nondialytic care, defined as those who did vs did not receive dialysis within 2 years of their index estimated glomerular filtration rate. Propensity score matching was used to account for differences in baseline characteristics across exposure groups. We examined associations of nondialytic care vs dialysis with hospitalization rates and rates of days hospitalized (separately) using Poisson regression. Among hospitalized patients, we examined associations with length of stay (LOS) using linear mixed-effects models. RESULTS:In the 1:1 propensity score-matched cohort of 13,020 nondialytic and 13,020 dialysis patients, dialysis transition was associated with higher rates of hospitalization and days hospitalized (reference: nondialytic care): incident rate ratios (95% CIs), 1.64 (1.61 to 1.66) and 1.71 (1.70 to 1.72), respectively. Dialysis was also associated with longer average LOS vs nondialytic care: 8.6 vs 8.1 days, respectively. In secondary analyses of timing of dialysis transition, incrementally earlier dialysis transitions were associated with increasingly higher hospitalization rates vs nondialytic care, with similar patterns observed for rates of days hospitalized and LOS. CONCLUSION:Compared with nondialytic care, dialysis was associated with higher rates of hospitalization and days hospitalized and longer LOS.

Rationale & Objective:The long-term outcomes associated with intravenous (IV) versus oral iron replacement therapy in patients with chronic kidney disease are unclear. We investigated the association of IV versus oral iron replacement therapy with incident end-stage kidney disease (ESKD) and with all-cause mortality in a national cohort of US veterans with an estimated glomerular filtration rate of < 60mL/min/1.73m2. Study Design:A national Veterans Affairs (VA) historical cohort study. Setting & Participants:Total of 17,428 incident new users of oral iron replacement therapy and a comparable group of 879 incident new users of IV iron replacement therapy during October 1, 2004, through September 30, 2006, with longitudinal follow-up until September 30, 2019. Predictor:Incident new use of oral versus IV IRT. Outcomes:ESKD and mortality. Analytical Approach:We examined the association of oral versus IV IRT with outcomes using competing risk regression and Cox models. We used propensity score matching to account for differences in baseline characteristics. Results:Event rates were overall higher in patients receiving IV iron replacement, but the risk was mitigated after propensity scores matching, with no significant association observed between the type of iron therapy and ESKD (subhazard ratio: 1.07; 95% CI, 0.82-1.39; P = 0.6), or all-cause mortality (hazard ratio: 1.07; 95% CI, 0.96-1.20; P = 0.2). Limitations:Potential selection bias and residual confounding. Conclusions:In this large national cohort of patients with chronic kidney disease, IV iron was not significantly associated with a higher risk of incident ESKD and all-cause mortality when compared to oral iron therapy. The comparative effectiveness of the different iron replacement modalities will need to be studied further in clinical trials.

Key Points. Many people with CKD are unaware of the condition. We estimated the time to CKD documentation after two eGFR measurements taken at least 90 days apart. Among many persons with early stage CKD, there are considerable delays in documenting the diagnosis in electronic health record-linked claims data. Background. An estimated 14% of US adults have CKD with over 90% unaware of their condition. Health care professionals diagnose CKD after two abnormal laboratory test results taken at least 3 months apart. Although there is evidence that delays from CKD onset to documentation are common, these delays remain unquantified. The objective of this study was to quantify the time from laboratory-based evidence of CKD to the documentation of CKD using International Classification of Diseases codes. Methods. A retrospective longitudinal cohort study was conducted using 2009–2020 Optum Market Clarity data. Adults aged 18 years and older were followed from the date of the second of two eGFRs <60 ml/min per 1.73 m2, 3–12 months apart until the first International Classification of Diseases Ninth or Tenth revision diagnosis of CKD, or censoring. Survival analysis was used to compare time to documentation among Kidney Disease Improving Global Outcomes (KDIGO) categories considering while analyzing deaths as competing risks. Results. A total of 1.39 million adults with laboratory evidence of CKD and a mean age of 71 years (SD, 10; 63% women; 87% White) were included. Over 94% were in KDIGO stage G3, 5% in stage G4, and 1% in stage G5. The median time to CKD documentation was 3.6 years (interquartile range, 1.0–8.4), ranging from 4.8 years for those in KDIGO G3a, 2 years in KDIGO G3b, and <1 year in KDIGO G4 and G5. Patient characteristics associated with longer time to CKD diagnosis included absence of diabetes or heart failure, less severe CKD, older age, and female sex. Conclusions. There was a substantial delay between laboratory evidence of CKD and the diagnosis being documented via coding. Reducing this delay offers a target for earlier recognition and management of CKD.

BACKGROUND:This secondary analysis of the CONFIDENCE (combination effect of fInerenone and empagliflozin in participants with chronic kidney disease and type 2 diabetes using a UACR endpoint) trial (REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05254002) assessed systolic blood pressure (SBP) changes with empagliflozin/finerenone combination therapy versus monotherapy in people with chronic kidney disease and type 2 diabetes across baseline SBP categories. We assessed SBP response predictors and whether early (day 30) SBP changes mediate urinary albumin-to-creatinine ratio reductions. METHODS:Participants (n=800) were stratified by baseline SBP (<130 mm Hg; ≥130 mm Hg). Outcomes included SBP response (≥10 mm Hg reduction from baseline at day 180) and longitudinal SBP changes, analyzed by linear mixed-effects models and logistic regression. Causal mediation analysis, a secondary exploratory analysis, evaluated the effect of day 30 SBP change on day 180 urinary albumin-to-creatinine ratio reduction. RESULTS:At baseline, 532 (66%) participants had SBP ≥130 mm Hg; 268 (34%) had SBP <130 mm Hg. Combination therapy increased SBP response odds versus finerenone (odds ratio, 1.83 [95% CI, 1.21-2.76]; P=0.004) or empagliflozin (odds ratio, 1.45 [95% CI, 0.97-2.17]; P=0.07). The strongest predictor of response was baseline SBP (odds ratio, 2.04 per 10 mm Hg higher SBP; P<0.0001). Combination therapy significantly reduced SBP versus monotherapies in the ≥130 mm Hg (P<0.0001) but not in the <130 mm Hg group. SBP reduction mediated <10% of the total urinary albumin-to-creatinine ratio reduction. Acute kidney injury and hyperkalemia incidences were similar across SBP subgroups. CONCLUSIONS:Combination therapy reduced SBP more than monotherapies in participants with SBP ≥130 mm Hg. Urinary albumin-to-creatinine ratio reduction appeared largely independent of SBP changes at day 30; though this secondary analysis was limited by reliance on clinic blood pressure measurement. Prospective studies with ambulatory blood pressure monitoring are required.