Empagliflozin versus Dapagliflozin for Kidney Outcomes in Stage 3 Chronic Kidney Disease: A Propensity Score-Matched Multi-center Cohort Study

Empagliflozin versus Dapagliflozin for Kidney Outcomes in Stage 3 Chronic Kidney Disease: A Propensity Score-Matched Multi-center Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Empagliflozin versus Dapagliflozin for Kidney Outcomes in Stage 3 Chronic Kidney Disease: A Propensity Score-Matched Multi-center Cohort Study Joyita Bharati, Nicholas A. Bosch, Ashish Upadhyay This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7586037/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 19 You are reading this latest preprint version Abstract Background Sodium-glucose cotransporter 2 (SGLT2)-inhibitors are key in chronic kidney disease (CKD) management with empagliflozin and dapagliflozin being the two most commonly used. Comparative data between them in CKD is limited. Methods A propensity score-matched cohort study was conducted using data from a network of 103 North American organizations. Adults with Stage 3 CKD who initiated empagliflozin or dapagliflozin between January 1, 2021 and December 31, 2023, were compared. The primary outcomes was the composite of Stage 5 CKD or end-stage kidney disease (ESKD). Follow-up continued until outcome or up to 3 years (censored on May 4, 2025). Results 60,689 and 34,877 patients with Stage 3 CKD were initiated on empagliflozin and dapagliflozin, respectively. Among matched patients with Stage 3 CKD (N = 33,583 per group) empagliflozin initiation was associated with lower risk of Stage 5 CKD or ESKD (5.2% vs 6.2%; HR: 0.82; 95% CI: 0.77–0.88) over ~ 670 days. All-cause mortality was similar between groups. Stage 5 CKD and ESKD rates were lower in the empagliflozin group. Stage 5 CKD or ESKD was lower for patients initiated on both empagliflozin 25 mg daily and 10 mg daily compared to dapagliflozin 10 mg daily. Conclusion In this multi-center retrospective cohort study, the risk for Stage 5 CKD or ESKD was lower for patients with Stage 3 CKD who initiated empagliflozin versus dapagliflozin over ~ 2.0 years. Prospective studies are needed to confirm our findings. Chronic kidney disease Empagliflozin Dapagliflozin Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Sodium-glucose cotransporter 2(SGLT2)-inhibitors have favorable pleotropic effects on the kidney and are considered a cornerstone of guideline-directed management of chronic kidney disease (CKD)[ 1 , 2 ]. Empagliflozin and dapagliflozin, the two most commonly used SGLT2-inhibitors in clinical practice [ 3 ], reduce the risk of major adverse kidney outcomes by 30–40% over 2–3 years in clinical trials including individuals with CKD, with or without diabetes [ 4 , 5 ]. While the beneficial effects of SGLT2-inhibitors are generally considered to be a class-effect, there are important pharmacodynamic and pharmacokinetic differences between empagliflozin and dapagliflozin that underscore the need for real-world studies directly comparing two agents in patients with CKD [ 6 ]. Prior reports suggest that empagliflozin and dapagliflozin may have differential effects on metabolic parameters in individuals with type 2 diabetes and on clinical cardiovascular disease outcomes in patients with heart failure [ 7 – 9 ]. A recent population-based study from Denmark, however, found that individuals with type 2 diabetes who were initiated on empagliflozin and dapagliflozin had similar long-term kidney outcomes [ 10 ]. Exclusion of individuals without type 2 diabetes, lack of data on end-stage kidney disease (ESKD) or death, and the inclusion of population with a relatively low risk for major adverse kidney outcomes (median estimated glomerular filtration rate [eGFR] of 88 ml/min/1.73m 2 and median urine albumin-to-creatinine ratio [UACR] of 16 mg/g) were important limitations of this study. In this observational propensity score-matched multi-center cohort study involving a large database of patients in North America, we compare major adverse kidney events between patients with Stage 3 CKD who were initiated on empagliflozin versus dapagliflozin. Methods This multicenter retrospective cohort study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines ( https://www.equator-network.org/reporting-guidelines/strobe/ ) ( Supplement eTable 1 ). The institutional review board of Boston University designated this study to not be human subjects research and waived the requirement for informed consent and review. Data Source and Cohort: We used the TriNetX Research Collaborative Network database ( https://live.trinetx.com/ ). A network of 103 healthcare organizations in North America (97% in the United States and 3% in Canada) contributed de-identified electronic medical record data to the TriNetX database for our analyses. We included patients with Stage 3 CKD who were never previously on SGLT2-inhibitors, and were newly initiated on either empagliflozin or dapagliflozin between January 1, 2021 and December 31, 2023. The index event (study day 0) was the day of empagliflozin or dapagliflozin initiation. Stage 3 CKD was defined using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision [ ICD-10 ] code: N18.3 [ 11 ], and an eGFR between 30 and 60 ml/min/1.73m 2 by Modification of Diet in Renal Diseases (MDRD) coded as TNX:8001 or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) coded as LNC:62238-1 . Patients with Stage 4 (ICD-10 code: N18.4) or Stage 5 CKD (ICD-10 code: N18.5) or with ESKD (ICD-10 code: 18.6) before or on the study day 0 were excluded. The start date of January 1, 2021 was chosen because major guidelines began recommending SGLT2-inhibitors for patients with CKD in 2020–2021 [ 12 , 13 ]. Study Groups and Outcomes: The group initiated on empagliflozin was defined as the intervention group and the group initiated on dapagliflozin was defined as the comparator group. The primary outcomes were the time to composite of Stage 5 CKD ( ICD-10 code: N18.5 ) or ESKD, defined as need for dialysis ( ICD-10 code: N18.6, ICD-10 code:Z99.2, CPT:1012740, CPT:1029674, or ICD-10 code:N19) or kidney transplant (CPT:1008098 ). Secondary outcomes were the time to Stage 5 CKD, ESKD, all-cause mortality ( deceased ) and incident acute kidney injury (AKI) ( ICD-10 code: N17 ). Adverse events were defined as occurrence of diabetic ketoacidosis (DKA) ( ICD code: E10.1x or E11.1x ), urinary tract infection (UTI) ( ICD code: N39.0 ), or genital infections ( N77.1 ). Patients were followed until the outcome or end of three years after study day 0, whichever occurred earlier. Analysis was done on May 4, 2025. A 3-month delay for the assessment of outcomes was chosen to allow time for eGFR stabilization and to avoid errors in CKD coding that may occur due to the SGLT2-inhibitor initiation-related early eGFR fluctuations. To assess the possibility of selection bias affecting results in the event of differential all-cause mortality rates or loss to follow-up between two groups in the first three months, a sensitivity analysis was done with the ascertainment of the composite primary outcomes starting one day after the index event. Sensitivity analyses were also conducted in patients who had data on empagliflozin and dapagliflozin dosage to assess the dose-effect relationship of empagliflozin on outcomes. Two separate cohorts were compared: 1. Patients with Stage 3 CKD who were newly initiated on empagliflozin 25 mg daily were compared to those newly initiated on dapagliflozin 10 mg daily, and 2. Patients with Stage 3 CKD who were newly initiated on empagliflozin 10 mg daily were compared to those newly initiated on dapagliflozin 10 mg daily. Incident AKI and adverse events were assessed one day after the index event till the last day of follow-up. Covariates: Baseline covariates considered likely to confound the association between SGLT2-inhibitor selection and the primary outcome were extracted within 365 days of the index event (study days − 365 to 0); a timeline for the assessment of baseline covariates and outcomes relative to day 0 is shown in Supplement eFigure 1 . Covariates comprised of demographics, laboratory and imaging parameters, comorbidities, and medications. A complete list of 42 covariates used in analyses is included in Supplement eTable 2. Statistical analysis: Baseline covariates were summarized using mean (standard deviation) and number (percentage) as appropriate. All 42 covariates were used to generate propensity scores for intervention and comparator groups using multivariable logistic regression. All covariates, except age (which was analyzed as a continuous variable), were included in propensity score models as categorical variables using clinically relevant groupings ( Supplement eTable 2 ). This categorization accounts for multiple testing (e.g., a patient with a urine protein-to-creatinine [UPCR] of 160 mg/g on day − 180 and 1000 mg/g on day − 90 would be coded as having a UPCR between 150–500 mg/g present and between 500–3500 mg/g present in the model) and allows for inclusion of patients in models even when a covariate was not measured (e.g., a patient with no measured UPCR prior to time 0 would have all UPCR categorical variables coded as absent). Propensity score matching was performed using a 1:1 greedy nearest neighbor matching without replacement to create two balanced cohorts. Balance was visualized using density curves of the propensity score and by assessing absolute standardized mean differences (SMD). An absolute SMD of < 0.1 after matching was considered to indicate a good balance. The primary outcome was then analyzed using Kaplan-Meier survival analysis to calculate the hazard ratio with a 95% confidence interval and log-rank test to compare event-free survival probability between intervention and comparator groups. Patients were censored from the Kaplan-Meier analysis after the last entry in their TriNetX record. We also calculated absolute risk-differences between groups. E-value was calculated using the hazard ratio on a freely available online calculator to quantify the risk an unmeasured confounder would need to have to change observed results [ 14 , 15 ]. Consistent with the intention-to-treat analysis principle, patients were analyzed according to the initial empagliflozin or dapagliflozin assignment, regardless of any changes in medications after the initiation. Cohort identification and statistical analyses were conducted using the TriNetX platform Query Builder and Analytics Functions on May 3, 2025. R version 4.2.3 (R Project for Statistical Computing) was used to recreate the Kaplan-Meier curves. A 2-sided p-value of < 0.05 was set to indicate statistical significance. Results Baseline characteristics of patients initiated on empagliflozin versus dapagliflozin before and after the propensity score matching A total of 95,566 Stage 3 CKD patients met the study criteria, of whom 60,689 were initiated on empagliflozin and 34,877 were initiated on dapagliflozin between January 1, 2021 and December 31, 2023 (Fig. 1 ). Table 1 summarizes the baseline characteristics of patients before and after the propensity score matching. Prior to matching, mean age in the empagliflozin and dapagliflozin groups was 70.2 years and 69.2 years, respectively. Demographics were similar with approximately 61% identifying themselves as belonging to a White race and 56% as male in both groups. About 50% in each group had a diagnosis of heart failure. More patients in the empagliflozin group had diabetes mellitus (78% vs. 70%). The baseline mean Hemoglobin A1C was higher (7.6% vs. 7.3% [to convert to a proportion of total hemoglobin, multiply by 0.01]) in the empagliflozin group than in the dapagliflozin group. Cardiovascular medication use was similar except for the use of angiotensin-converting enzyme inhibitor being higher in the empagliflozin group (27.7% vs. 23.2%). After 1:1 nearest-neighbor matching using 42 covariates, two balanced cohorts (all SMDs < 0.1 after matching) comprising 33,583 patients in each group were created. Supplement eFigure 2 shows propensity score density curves before and after matching. Table 1 Baseline characteristics of patients with Stage 3 CKD initiating empagliflozin vs. dapagliflozin before and after 1:1 propensity score matching Characteristic Before matching After matching Empagliflozin (N = 63,398) Dapagliflozin (N = 39,048) SMD Empagliflozin (N = 37,115) Dapagliflozin (N = 37,115) SMD Mean age (SD), years 70.2 (10.8) 69.2 (11.6) 0.09 69.4 (11.3) 69.5 (11.4) 0.002 Male sex 55.6% 56.9% 0.03 57.0%% 56.8% 0.004 Race White 61.2% 59.1% 0.04 59.6% 59.9% 0.005 Black 19.4% 20.8% 0.03 20.7% 20.5% 0.007 Asian 5.8% 7.3% 0.06 7.0% 7.0% 0.001 Unknown 9.5% 9.4% 0.005 9.1% 9.2% 0.002 Diabetes mellitus 78.5% 70% 0.19 71.1% 71.3% 0.005 Hypertension 78.5% 75.9% 0.06 75.7% 76.0% 0.007 Mean eGFR (SD), ml/min/1.73m 2 47.1 (13.5) 45.4 (14.0) 0.12 46.2 (13.5) 45.5 (14.0) 0.05 eGFR 30 to < 45 ml/min/1.73m 2 58.7% 64.3% 0.11 63.5%% 63.5% 0.001 eGFR 45 to < 60 ml/min/1.73m 2 69.4% 68.5% 0.02 68.0% 68.2% 0.004 Mean UPCR (SD), mg/g 649.2(1742.2) 700.8(1643.5) 0.03 688.9 (1792.8) 689.8(1668.0) 0.001 UPCR 0 to < 150 mg/g 5.4% 7.2% 0.08 6.9% 6.8% 0.004 UPCR 150 to < 500 mg/g 1.8% 2.9% 0.08 2.6% 2.6% < 0.001 UPCR 500 to < 3500 mg/g 1.8% 3.2% 0.08 2.7% 2.7% 0.002 UPCR ≥ 3500 mg/g 0.7% 1.1% 0.04 1.0% 0.9% 0.006 Mean UACR (SD), mg/g 389.8 (944.4) 438.4 (939.8) 0.05 434.6 ( 999.6) 423.2 ( 930.7) 0.01 UACR 0 to < 30 mg/g 2.1% 2.0% 0.01 2.1% 2.0% 0.003 UACR 30 to 300 mg/g 1.4% 1.5% 0.01 1.5% 1.5% 0.001 Mean Hemoglobin A1C (SD), % 7.6 (1.7) 7.3 (1.7) 0.18 7.4 (1.7) 7.3 (1.7) 0.04 Hemoglobin A1C 0 to < 3% 0.1% 0% 0.006 0% 0% < 0.001 Hemoglobin A1C 3 to < 6% 15.0% 19.9% 0.12 18.8% 18.9% 0.002 Hemoglobin A1C 6 to < 9% 57.6% 50.3% 0.14 51.0% 51.2% 0.005 Hemoglobin A1C 9 to < 12% 16.8% 12.5% 0.12 12.9% 12.9% < 0.001 Hemoglobin A1C ≥12% 3.7% 3.0% 0.04 3.1% 3.0% 0.005 Systolic heart failure 23.5% 28.5% 0.10 27.3% 27.1% 0.004 Diastolic heart failure 20.4% 19.4% 0.02 19.4% 19.5% 0.002 Combined systolic and diastolic heart failure 11.3% 15.0% 0.11 13.8% 14.0% 0.005 Ischemic heart diseases 45.0% 46.2% 0.02 45.8% 45.9% 0.002 Adverse socioeconomic determinants of health* 3.3% 3.6% 0.01 3.4% 3.4% < 0.001 Fibrosis and cirrhosis of liver 2.8% 3.1% 0.02 3.0% 3.0% 0.001 Mean Left Ventricular Ejection Fraction (SD), % 49.2 (16.1) 44.2 (17.8) 0.29 47.1 (16.5) 45.9 (17.7) 0.07 Left Ventricular Ejection Fraction 0 to < 50% 3.7% 7.5% 0.18 5.8% 5.9% 0.003 Left Ventricular Ejection Fraction ≥50% 4.7% 6.5% 0.08 6% 6.1% 0.004 Medication use Cardiovascular medications 86.8% 86.7% 0.001 86.3% 86.5% 0.005 Angiotensin II receptor blockers 37.4% 40.0% 0.05 39.0% 39.4% 0.008 Angiotensin converting enzyme inhibitors 27.7% 23.2% 0.10 23.4% 23.5% 0.001 Loop Diuretics 42.0% 44.5% 0.05 43.8% 43.7% 0.002 Combination Diuretics, including potassium sparing diuretics 19.2% 22.2% 0.07 21.5% 21.5% < 0.001 Beta blockers 57.5% 58.7% 0.02 58.2% 58.2% 0.001 Sacubitril 8.2% 10.8% 0.09 10.4% 10.4% < 0.001 Calcium channel blockers 37.9% 38.0% 0.003 37.9% 37.7% 0.003 Hydralazine 15.9% 19.7% 0.10 18.9% 18.9% < 0.001 Lipid lowering medications 69.4% 65.6% 0.08 65.8% 65.9% 0.001 Platelet aggregation inhibitors 38.9% 39.2% 0.007 39.0% 39.0% < 0.001 Amiodarone 7.2% 8.8% 0.06 8.3% 8.4% 0.003 Digoxin 3.1% 4.1% 0. 06 4.0% 3.9% 0.004 Organic nitrates 21.7% 24.4% 0.06 23.6% 23.7% 0.002 Insulin and analogues 43.3% 39.8% 0.07 40.2% 40.2% 0.001 Metformin 33.2% 24.6% 0.19 25.3% 25.3% < 0.001 Glucagon-like peptide-1 analogues 18.0% 12.9% 0.14 13.4% 13.3% 0.003 Dipeptidyl peptidase 4 inhibitors 10.5% 9.5% 0.03 9.5% 9.8% 0.009 Sulfonylureas 18.1% 14.1% 0.11 14.8% 14.6% 0.005 Thiazolidinediones 3.5% 3.2% 0.01 3.4% 3.3% 0.005 Thiazides/Related diuretics 24.1% 23.2% 0.02 23.1% 23.0% 0.002 Abbreviations: SD, standard deviation; SMD, absolute standardized mean difference; eGFR, estimated glomerular filtration rate by the Modification of Diet in Renal Disease equation; UPCR, Urine-protein-to-creatinine ratio *International Classification of Diseases, Tenth Revision Codes Z-55-Z65 Comparison of outcomes in patients initiated on empagliflozin versus dapagliflozin in propensity score matched cohorts During a mean follow-up of 669.9 ( \(\:\pm\:\) 321) days in the empagliflozin group and 667.5 ( \(\:\pm\:\) 319.7) days in the dapagliflozin group, 1,741 (5.2%) patients in the empagliflozin group compared to 2,089 (6.2%) in the dapagliflozin group experienced the composite outcome of Stage 5 CKD or ESKD (HR: 0.82; 95% CI: 0.77 to 0.86; log-rank P < 0.001; E-value:1.44) (Fig. 2 ). Similarly, patients who were initiated on empagliflozin were less likely to have Stage 5 CKD (1.7% vs. 2.2%; HR: 0.77; 95% CI: 0.69 to 0.88; log-rank P < 0.001) and ESKD (4.5% vs. 5.4%; HR: 0.82; 95% CI: 0.77 to 0.88; log-rank P < 0.001). All-cause mortality did not differ between the groups (9.3% vs. 9.0%: HR1.03; 95% CI: 0.97 to 1.08, log-rank P = 0.30) (Fig. 2 ). Proportional hazard assumption was not violated in any of the above survival analyses (Schoenfeld test P-value > 0.05). The risk of AKI was lower in the empagliflozin group than in the dapagliflozin group (26.8% vs. 28.4%; risk ratio: 0.94; 95% CI: 0.92 to 0.97; P < 0.001). The proportion of patients with DKA was similar in the empagliflozin (1.2%) and dapagliflozin (1.2%) groups ( P = 0.37). Likewise, genital infection rate was the same (0.03%) in two groups ( P = 1.00), but UTI rate was lower in the empagliflozin group (11.6%) than in the dapagliflozin group (13.3%) ( P < 0.001). Consistent with the primary analysis, the sensitivity analysis with the ascertainment of outcomes starting one day after the index event also showed a lower risk for the composite of Stage 5 CKD or ESKD in patients initiating empagliflozin compared to those initiating dapagliflozin (6.3% vs. 7.6%; HR: 0.81; 95% CI: 0.76 to 0.86; log-rank P < 0.001). Supplement eTable 3 and eTable 4 summarizes the baseline characteristics of patients included in the sensitivity analyses assessing the dose-effect relationship of empagliflozin on outcomes before and after the propensity score matching. After the nearest-neighbor propensity score matching using all 42 covariates, 8,414 patients in the empagliflozin 25mg daily group were compared with 8,414 patients in the dapagliflozin 10 mg daily group. Supplement eFigure 3 and eFigure 4 show propensity score density curves before and after the propensity score matching. During a mean follow up of 722 ( \(\:\pm\:\) 322) days in the empagliflozin group and 681 ( \(\:\pm\:\) 310) days in the dapagliflozin group, 370 (4.4%) patients in the empagliflozin group compared to 482 (5.7%) in the dapagliflozin group experienced the composite outcome of Stage 5 CKD or ESKD (HR: 0.72, 95% CI: 0.63, 0.82; log-rank P < 0.001) (Fig. 3 ). All-cause mortality was similar in the empagliflozin and dapagliflozin groups (HR: 0.96, 95% CI: 0.86, 1.07; log-rank P = 0.45). After the nearest-neighbor propensity score matching, 15,563 patients in the empagliflozin 10 mg daily were compared with 15,563 patients in the dapagliflozin 10 mg daily group. During a mean follow up of 665 ( \(\:\pm\:\) 313) days in the empagliflozin group and 663 ( \(\:\pm\:\) 311.2) days in the dapagliflozin group, 761 (4.9%) patients in the empagliflozin group experienced the composite outcome of Stage 5 CKD or ESKD compared to 939 (6.0%) in the dapagliflozin group (HR: 0.80, 95% CI: 0.73, 0.88; log-rank P < 0.001) (Fig. 4 ). All-cause mortality was similar in the empagliflozin and dapagliflozin groups (HR: 1.03, 95% CI: 0.96, 1.12; log-rank P = 0.29). The risk of AKI was lower in both the 10 mg and 25 mg empagliflozin groups than in the dapagliflozin 10 mg group in the above analyses, respectively ( Supplement eTable 5 ). The adverse effect profile including DKA, UTI, and genital infections in the dose-specific analyses are shown in Supplement eTable 6. Discussion In this observational propensity score-matched multi-center cohort study involving a large database of patients in North America, patients with Stage 3 CKD who initiated empagliflozin had a lower risk of experiencing the composite of Stage 5 CKD or ESKD compared to those who initiated dapagliflozin over a follow-up period of approximately 2.0 years. Similarly, the risk of AKI was also lower in patients who initiated empagliflozin. When different dose formulations were compared, patients initiated on both empagliflozin 10 mg daily and 25 mg daily had a lower risk for major adverse kidney events than patients initiated on dapagliflozin 10 mg daily. As for adverse events, the proportion of patients with DKA and genital infections were similar in two groups while UTI rate was lower in the empagliflozin group. Prior studies comparing empagliflozin and dapagliflozin have had varied methodologies and results. A recent large network meta-analysis of 21 clinical trials found that all SGLT2-inhibitors have equivalent efficacy profiles for cardiovascular and kidney outcomes, although there was a suggestion that patients without CKD may benefit more from empagliflozin [ 16 ]. This study was a trial-level meta-analysis without individual-level data and only included placebo-controlled trials as there are no head-to-head trials comparing different SGLT2-inhibitors for major clinical outcomes. The only clinical trial directly comparing two agents tested empagliflozin 25 mg daily versus dapagliflozin 10 mg daily as an add-on therapy to multiple glucose lowering drugs in patients with uncontrolled type 2 diabetes[ 9 ]. This small study from South Korea, which was not powered for hard outcomes, showed a greater reduction in hemoglobin A1C, blood pressure and weight loss with empagliflozin versus dapagliflozin over a 52-week period. Similarly, cohort studies evaluating patients with heart failure also show favorable benefits of empagliflozin over dapagliflozin for important clinical, laboratory and imaging related heart failure endpoints [ 7 , 8 ]. For kidney outcomes, a recent large population-based cohort study from Denmark showed that individuals with type 2 diabetes who were initiated on empagliflozin and dapagliflozin had similar risks for incident CKD, CKD progression, and AKI over 6 years [ 10 ]. Unlike our study, the Danish study did not exclusively evaluate patients with CKD (median eGFR was 88ml/min/1.73m 2 and median UACR was 16mg/g), excluded patients without type 2 diabetes mellitus, and did not report on hard outcomes such as kidney failure or death. In addition, while the racial and ethnic distribution of the patients were not given, as it was a population-based study using the Danish health care data, the patients were likely more racially and ethnically homogeneous than what would be expected in North America. It is also unclear what proportion of patients were on different dose formulations of empagliflozin and dapagliflozin. Therefore, we speculate that the differences in the patient mix and the baseline risks for adverse kidney events may explain the discrepant results between our study and the Danish study. As major clinical trials in CKD for empagliflozin and dapagliflozin used a fixed 10 mg dose formulation for both drugs while the highest dose of empagliflozin available in North America is a 25 mg dose formulation [ 4 , 5 ], we conducted exploratory analyses evaluating the possibility of a dose-effect relationship in those treated with empagliflozin that could explain our primary findings. Prior reports suggest a better blood sugar control and more weight loss with 25 mg versus 10 mg of empagliflozin in patients with type 2 diabetes [ 17 , 18 ]. A clinical trial in patients with type 2 diabetes mellitus and high cardiovascular risks, however, showed that both 25mg and 10mg doses of empagliflozin were equally effective in reducing cardiovascular disease outcomes [ 19 ]. Only 26% of participants in that trial had eGFR < 60 ml/min/1.73m 2 . Hence, while a higher dose of empagliflozin 25mg daily is typically used to improve blood sugar management in patients with type 2 diabetes, heart failure guidelines recommend a target dose of 10 mg daily and CKD guidelines do not endorse any particular dose of empagliflozin [ 2 , 20 ]. Our finding that Stage 3 CKD patients who were comparable at baseline in terms of comorbidities initiated on a dose of empagliflozin 25 mg daily or 10 mg daily were less likely to experience the composite of Stage 5 CKD or ESKD compared to those started on dapagliflozin 10 mg daily is supportive of the existing practice. As Stage 3 CKD is estimated to affect approximately 13 million adults in the United States (~ 5% of the adult population) with a substantial proportion of them meeting the indications for SGLT2-inhibitors based on the most recent clinical practice guidelines [ 2 , 21 ], even the small absolute benefit of empagliflozin over dapagliflozin observed in our study (absolute risk difference of 0.4% for major adverse kidney events; number needed to treat of 250) has a potential for a significant public health implication. Furthermore, the current CKD guidelines do not favor one SGLT2-inhibitor over others nor provide recommendations on the dosage of SGLT2-inhibitors for optimal benefit [ 2 ]. Our findings suggesting a possible difference in real-world efficacy between the two most widely prescribed SGLT2-inhibitors and the dose-effect relationship for kidney outcomes with empagliflozin are expected to provide an impetus for future clinical trials comparing different types and dosage of SGLT2-inhibitors in CKD. Our study has important limitations. We could not determine the indication for starting SGLT2-inhibitors, cause-specific mortality, or the specific cause of AKI given the limitations of the platform. Proteinuria measurements, while balanced between groups, were only available for approximately 13% of patients in each group. We also could not determine the exact onset of Stage 3 CKD, implying that our analysis may have a risk for immortal time bias. The risk for immortal time bias, however, is likely low as cohorts were balanced for key characteristics, including for baseline eGFR, and for comorbidities such as heart failure and type 2 diabetes, two most common indications for SGLT2-inhibitors other than CKD. Despite well-matched cohorts, the risk for unmeasured confounding remains in observational studies. However, the E-value of 1.44 suggests that the observed association would only be nullified in the presence of an unmeasured confounder that is associated with a risk ratio of 1.44 or greater to treatment assignment and outcome. Since multiple measurements of laboratory parameters over time could not be assessed in this platform, we were unable to analyze the eGFR slope or hemoglobin A1C trends in our analysis. Conclusions In this large multicenter cohort study including patients with Stage 3 CKD, empagliflozin initiation compared to dapagliflozin initiation was associated with a lower rate of Stage 5 CKD or ESKD over a follow-up period of approximately 2.0 years. When a specific dose was studied in two separate analyses, both empagliflozin 25 mg daily and 10 mg daily initiation were associated with a lower rate of Stage 5 CKD or ESKD compared to dapagliflozin 10 mg initiation. Further studies are required to validate our findings and understand the mechanisms behind the observed differences on kidney outcomes focusing on patients with CKD, especially those with reduced eGFR (< 60 ml/min/1.73m 2 ). Declarations Ethics approval and consent to participate : The institutional review board of Boston University designated this study to not be human subjects research and waived the requirement for informed consent and review. Conflict of Interest statement: Authors have no conflicts of interest to declare. Funding: None Author Contribution JB conceptualized, analysed data, and wrote the manuscript; NB helped in data analysis, manuscript writing, and supervision; AU conceptualized and supervised manuscript writing. All authors reviewed the manuscript. Acknowledgement: None Data Availability The data on the results is available from the corresponding author upon request. References Upadhyay A. SGLT2 Inhibitors and Kidney Protection: Mechanisms Beyond Tubuloglomerular Feedback. Kidney360 , 5: 771–782, 2024 10.34067/KID.0000000000000425. Kidney Disease. Improving Global Outcomes CKDWG: KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105:S117–314. 10.1016/j.kint.2023.10.018 . Adhikari R, Jha K, Dardari Z, Heyward J, Blumenthal RS, Eckel RH, Alexander GC, Blaha MJ. National Trends in Use of Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-like Peptide-1 Receptor Agonists by Cardiologists and Other Specialties, 2015 to 2020. J Am Heart Assoc , 11: e023811, 2022 10.1161/JAHA.121.023811 The E-KCG, Herrington WG, Staplin N, Wanner C, Green JB, Hauske SJ, Emberson JR, Preiss D, Judge P, Mayne KJ, Ng SYA, Sammons E, Zhu D, Hill M, Stevens W, Wallendszus K, Brenner S, Cheung AK, Liu ZH, Li J, Hooi LS, Liu W, Kadowaki T, Nangaku M, Levin A, Cherney D, Maggioni AP, Pontremoli R, Deo R, Goto S, Rossello X, Tuttle KR, Steubl D, Petrini M, Massey D, Eilbracht J, Brueckmann M, Landray MJ, Baigent C, Haynes R. Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023;388:117–27. 10.1056/NEJMoa2204233 . Heerspink HJL, Stefansson BV, Correa-Rotter R, Chertow GM, Greene T, Hou FF, Mann JFE, McMurray JJV, Lindberg M, Rossing P, Sjostrom CD, Toto RD, Langkilde AM, Wheeler DC, Committees D-CT. Investigators: Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med , 383: 1436–1446, 2020 10.1056/NEJMoa2024816 Tahara A, Takasu T, Yokono M, Imamura M, Kurosaki E. Characterization and comparison of sodium-glucose cotransporter 2 inhibitors in pharmacokinetics, pharmacodynamics, and pharmacologic effects. J Pharmacol Sci. 2016;130:159–69. 10.1016/j.jphs.2016.02.003 . Modzelewski KL, Pipilas A, Bosch NA. Comparative Outcomes of Empagliflozin to Dapagliflozin in Patients With Heart Failure. JAMA Netw Open , 7: e249305, 2024 10.1001/jamanetworkopen.2024.9305 Hao Z, Zhang Y. Dapagliflozin and Empagliflozin in Heart Failure with Reduced Ejection Fraction: A Retrospective Study. Int J Gen Med, 15: 5915–8, 2022 10.2147/IJGM.S366943. Ku EJ, Lee DH, Jeon HJ, Oh TK. Empagliflozin versus dapagliflozin in patients with type 2 diabetes inadequately controlled with metformin, glimepiride and dipeptidyl peptide 4 inhibitors: A 52-week prospective observational study. Diabetes Res Clin Pract. 2019;151:65–73. 10.1016/j.diabres.2019.04.008 . Bonnesen K, Heide-Jorgensen U, Christensen DH, Christiansen CF, Lash TL, Hennessy S, Matthews AA, Pedersen L, Thomsen RW, Schmidt M. Effectiveness of Empagliflozin vs Dapagliflozin for Kidney Outcomes in Type 2 Diabetes. JAMA Intern Med. 2025. 10.1001/jamainternmed.2024.7381 . Friberg L, Gasparini A, Carrero JJ. A scheme based on ICD-10 diagnoses and drug prescriptions to stage chronic kidney disease severity in healthcare administrative records. Clin Kidney J. 2018;11:254–8. 10.1093/ckj/sfx085 . American Diabetes A. 11. Microvascular Complications and Foot Care: Standards of Medical Care in Diabetes-2021. Diabetes Care. 2021;44:S151–67. 10.2337/dc21-S011 . Kidney Disease: Improving Global Outcomes Diabetes, Work G. KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int. 2020;98:S1–115. 10.1016/j.kint.2020.06.019 . How to use this website. E-value calculator., Available at: https://www.evalue-calculator.com// . Accessed 2/2/2025. VanderWeele TJ, Ding P. Sensitivity Analysis in Observational Research: Introducing the E-Value. Ann Intern Med, 167: 268–74, 2017 10.7326/M16-2607. Correction to. Comparison of Effectiveness Among Different Sodium-Glucose Cotransporter-2 Inhibitors According to Underlying Conditions: A Network Meta-Analysis of Randomized Controlled Trials. J Am Heart Assoc. 2024;13:e027762. 10.1161/JAHA.123.027762 . Matsumura T, Makabe T, Ueda S, Fujimoto Y, Sadahiro K, Tsuruyama S, Ookubo Y, Kondo T, Araki E. Clinical Benefit of Switching from Low-Dose to High-Dose Empagliflozin in Patients with Type 2 Diabetes. Diabetes Ther. 2022;13:1621–34. 10.1007/s13300-022-01296-y . Wu Q, Liu M, Fang Z, Li C, Zou F, Hu L, Zhang W. Efficacy and safety of empagliflozin at different doses in patients with type 2 diabetes mellitus: A network meta-analysis based on randomized controlled trials. J Clin Pharm Ther. 2022;47:270–86. 10.1111/jcpt.13521 . Zinman B, Wanner C, Lachin JM, Fitchett D, Bluhmki E, Hantel S, Mattheus M, Devins T, Johansen OE, Woerle HJ, Broedl UC, Inzucchi SE, Investigators E-RO. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med. 2015;373:2117–28. 10.1056/NEJMoa1504720 . Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW, Members AAJC. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2022;145:e895–1032. 10.1161/CIR.0000000000001063 . United States Renal Data System. : 2023 USRDS Annual Data Report: Epidemiology of kidney disease in the United States. National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD. Additional Declarations No competing interests reported. Supplementary Files SupplementTriNetXMay3.docx Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 01 Dec, 2025 Reviews received at journal 29 Nov, 2025 Reviews received at journal 29 Nov, 2025 Reviewers agreed at journal 29 Nov, 2025 Reviews received at journal 29 Nov, 2025 Reviewers agreed at journal 28 Nov, 2025 Reviewers agreed at journal 28 Nov, 2025 Reviews received at journal 25 Nov, 2025 Reviewers agreed at journal 24 Nov, 2025 Reviews received at journal 08 Nov, 2025 Reviews received at journal 08 Nov, 2025 Reviewers agreed at journal 07 Nov, 2025 Reviewers agreed at journal 05 Nov, 2025 Reviewers agreed at journal 30 Oct, 2025 Reviewers invited by journal 25 Sep, 2025 Editor invited by journal 16 Sep, 2025 Editor assigned by journal 12 Sep, 2025 Submission checks completed at journal 12 Sep, 2025 First submitted to journal 10 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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08:04:55","extension":"html","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":121074,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-7586037/v1/02aba5b868b81f0bbb339789.html"},{"id":93017537,"identity":"9dddb014-b5c0-4456-8650-8dd243a2a22e","added_by":"auto","created_at":"2025-10-08 08:12:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":313490,"visible":true,"origin":"","legend":"\u003cp\u003eStudy Flow\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-7586037/v1/eebc0331223b1ec27268e59c.png"},{"id":93017539,"identity":"74ea9ec8-7778-487e-b1a9-3ad7e6146ab5","added_by":"auto","created_at":"2025-10-08 08:12:55","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":138427,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curve comparing the composite outcome of MAKE (Stage 5 CKD or end-stage kidney disease (ESKD)), Stage 5 CKD, ESKD, and all-cause mortality for patients with Stage 3 CKD initiated on empagliflozin versus dapagliflozin.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-7586037/v1/d9f57593b07f365cdaa61d2b.png"},{"id":93016336,"identity":"eed04406-152e-4a48-850b-c328e7d6a480","added_by":"auto","created_at":"2025-10-08 08:04:55","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":137005,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curve comparing the composite outcome of Stage 5 CKD, end-stage kidney disease (ESKD), or all-cause mortalityfor patients with Stage 3 CKD initiated on empagliflozin 25 mg daily versus dapagliflozin 10mg daily.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7586037/v1/5272d289b9076d40b366deaa.png"},{"id":93017538,"identity":"d2354cc9-bff3-466f-9be9-e08b4c0ecb26","added_by":"auto","created_at":"2025-10-08 08:12:55","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":137005,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier survival curve comparing the composite outcome of Stage 5 CKD, end-stage kidney disease (ESKD), or all-cause mortalityfor patients with Stage 3 CKD initiated on empagliflozin 25 mg daily versus dapagliflozin 10mg daily.\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-7586037/v1/e8de7d8ebf8f6de68d56b696.png"},{"id":93019250,"identity":"3a49bb99-92a0-4213-8a4e-2548da66d677","added_by":"auto","created_at":"2025-10-08 08:36:58","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1910440,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7586037/v1/c8f1839b-8c49-438b-a19d-9f0820bb6545.pdf"},{"id":93019003,"identity":"91430735-422d-466e-9e75-4fc4b44adb7b","added_by":"auto","created_at":"2025-10-08 08:28:55","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"supplement","size":344980,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementTriNetXMay3.docx","url":"https://assets-eu.researchsquare.com/files/rs-7586037/v1/17414138a8354f9ca62c8da8.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Empagliflozin versus Dapagliflozin for Kidney Outcomes in Stage 3 Chronic Kidney Disease: A Propensity Score-Matched Multi-center Cohort Study","fulltext":[{"header":"Background","content":"\u003cp\u003eSodium-glucose cotransporter 2(SGLT2)-inhibitors have favorable pleotropic effects on the kidney and are considered a cornerstone of guideline-directed management of chronic kidney disease (CKD)[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Empagliflozin and dapagliflozin, the two most commonly used SGLT2-inhibitors in clinical practice [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], reduce the risk of major adverse kidney outcomes by 30\u0026ndash;40% over 2\u0026ndash;3 years in clinical trials including individuals with CKD, with or without diabetes [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. While the beneficial effects of SGLT2-inhibitors are generally considered to be a class-effect, there are important pharmacodynamic and pharmacokinetic differences between empagliflozin and dapagliflozin that underscore the need for real-world studies directly comparing two agents in patients with CKD [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003ePrior reports suggest that empagliflozin and dapagliflozin may have differential effects on metabolic parameters in individuals with type 2 diabetes and on clinical cardiovascular disease outcomes in patients with heart failure [\u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. A recent population-based study from Denmark, however, found that individuals with type 2 diabetes who were initiated on empagliflozin and dapagliflozin had similar long-term kidney outcomes [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Exclusion of individuals without type 2 diabetes, lack of data on end-stage kidney disease (ESKD) or death, and the inclusion of population with a relatively low risk for major adverse kidney outcomes (median estimated glomerular filtration rate [eGFR] of 88 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e and median urine albumin-to-creatinine ratio [UACR] of 16 mg/g) were important limitations of this study.\u003c/p\u003e\u003cp\u003eIn this observational propensity score-matched multi-center cohort study involving a large database of patients in North America, we compare major adverse kidney events between patients with Stage 3 CKD who were initiated on empagliflozin versus dapagliflozin.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis multicenter retrospective cohort study follows the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.equator-network.org/reporting-guidelines/strobe/\u003c/span\u003e\u003cspan address=\"https://www.equator-network.org/reporting-guidelines/strobe/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e) (\u003cb\u003eSupplement eTable 1\u003c/b\u003e). The institutional review board of Boston University designated this study to not be human subjects research and waived the requirement for informed consent and review.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eData Source and Cohort:\u003c/h2\u003e\u003cp\u003eWe used the TriNetX Research Collaborative Network database (\u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://live.trinetx.com/\u003c/span\u003e\u003cspan address=\"https://live.trinetx.com/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e). A network of 103 healthcare organizations in North America (97% in the United States and 3% in Canada) contributed de-identified electronic medical record data to the TriNetX database for our analyses. We included patients with Stage 3 CKD who were never previously on SGLT2-inhibitors, and were newly initiated on either empagliflozin or dapagliflozin between January 1, 2021 and December 31, 2023. The index event (study day 0) was the day of empagliflozin or dapagliflozin initiation. Stage 3 CKD was defined using \u003cem\u003eInternational Statistical Classification of Diseases and Related Health Problems, Tenth Revision\u003c/em\u003e [\u003cem\u003eICD-10\u003c/em\u003e] code: \u003cem\u003eN18.3\u003c/em\u003e [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], and an eGFR between 30 and 60 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e by Modification of Diet in Renal Diseases (MDRD) coded as \u003cem\u003eTNX:8001\u003c/em\u003e or Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) coded as \u003cem\u003eLNC:62238-1\u003c/em\u003e. Patients with Stage 4 \u003cem\u003e(ICD-10 code: N18.4)\u003c/em\u003e or Stage 5 CKD \u003cem\u003e(ICD-10 code: N18.5)\u003c/em\u003e or with ESKD \u003cem\u003e(ICD-10 code: 18.6)\u003c/em\u003e before or on the study day 0 were excluded. The start date of January 1, 2021 was chosen because major guidelines began recommending SGLT2-inhibitors for patients with CKD in 2020\u0026ndash;2021 [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eStudy Groups and Outcomes:\u003c/h3\u003e\n\u003cp\u003eThe group initiated on empagliflozin was defined as the intervention group and the group initiated on dapagliflozin was defined as the comparator group.\u003c/p\u003e\u003cp\u003eThe primary outcomes were the time to composite of Stage 5 CKD (\u003cem\u003eICD-10\u003c/em\u003e code: \u003cem\u003eN18.5\u003c/em\u003e) or ESKD, defined as need for dialysis (\u003cem\u003eICD-10\u003c/em\u003e code: \u003cem\u003eN18.6, ICD-10 code:Z99.2, CPT:1012740, CPT:1029674, or ICD-10 code:N19)\u003c/em\u003e or kidney transplant \u003cem\u003e(CPT:1008098\u003c/em\u003e). Secondary outcomes were the time to Stage 5 CKD, ESKD, all-cause mortality (\u003cem\u003edeceased\u003c/em\u003e) and incident acute kidney injury (AKI) (\u003cem\u003eICD-10\u003c/em\u003e code: \u003cem\u003eN17\u003c/em\u003e). Adverse events were defined as occurrence of diabetic ketoacidosis (DKA) (\u003cem\u003eICD code: E10.1x or E11.1x\u003c/em\u003e), urinary tract infection (UTI) (\u003cem\u003eICD code: N39.0\u003c/em\u003e), or genital infections (\u003cem\u003eN77.1\u003c/em\u003e). Patients were followed until the outcome or end of three years after study day 0, whichever occurred earlier. Analysis was done on May 4, 2025. A 3-month delay for the assessment of outcomes was chosen to allow time for eGFR stabilization and to avoid errors in CKD coding that may occur due to the SGLT2-inhibitor initiation-related early eGFR fluctuations. To assess the possibility of selection bias affecting results in the event of differential all-cause mortality rates or loss to follow-up between two groups in the first three months, a sensitivity analysis was done with the ascertainment of the composite primary outcomes starting one day after the index event. Sensitivity analyses were also conducted in patients who had data on empagliflozin and dapagliflozin dosage to assess the dose-effect relationship of empagliflozin on outcomes. Two separate cohorts were compared: 1. Patients with Stage 3 CKD who were newly initiated on empagliflozin 25 mg daily were compared to those newly initiated on dapagliflozin 10 mg daily, and 2. Patients with Stage 3 CKD who were newly initiated on empagliflozin 10 mg daily were compared to those newly initiated on dapagliflozin 10 mg daily. Incident AKI and adverse events were assessed one day after the index event till the last day of follow-up.\u003c/p\u003e\n\u003ch3\u003eCovariates:\u003c/h3\u003e\n\u003cp\u003eBaseline covariates considered likely to confound the association between SGLT2-inhibitor selection and the primary outcome were extracted within 365 days of the index event (study days \u0026minus;\u0026thinsp;365 to 0); a timeline for the assessment of baseline covariates and outcomes relative to day 0 is shown in \u003cb\u003eSupplement eFigure 1\u003c/b\u003e. Covariates comprised of demographics, laboratory and imaging parameters, comorbidities, and medications. A complete list of 42 covariates used in analyses is included in \u003cb\u003eSupplement eTable 2.\u003c/b\u003e\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis:\u003c/h2\u003e\u003cp\u003eBaseline covariates were summarized using mean (standard deviation) and number (percentage) as appropriate. All 42 covariates were used to generate propensity scores for intervention and comparator groups using multivariable logistic regression. All covariates, except age (which was analyzed as a continuous variable), were included in propensity score models as categorical variables using clinically relevant groupings (\u003cb\u003eSupplement eTable 2\u003c/b\u003e). This categorization accounts for multiple testing (e.g., a patient with a urine protein-to-creatinine [UPCR] of 160 mg/g on day \u0026minus;\u0026thinsp;180 and 1000 mg/g on day \u0026minus;\u0026thinsp;90 would be coded as having a UPCR between 150\u0026ndash;500 mg/g present and between 500\u0026ndash;3500 mg/g present in the model) and allows for inclusion of patients in models even when a covariate was not measured (e.g., a patient with no measured UPCR prior to time 0 would have all UPCR categorical variables coded as absent).\u003c/p\u003e\u003cp\u003ePropensity score matching was performed using a 1:1 greedy nearest neighbor matching without replacement to create two balanced cohorts. Balance was visualized using density curves of the propensity score and by assessing absolute standardized mean differences (SMD). An absolute SMD of \u0026lt;\u0026thinsp;0.1 after matching was considered to indicate a good balance.\u003c/p\u003e\u003cp\u003eThe primary outcome was then analyzed using Kaplan-Meier survival analysis to calculate the hazard ratio with a 95% confidence interval and log-rank test to compare event-free survival probability between intervention and comparator groups. Patients were censored from the Kaplan-Meier analysis after the last entry in their TriNetX record. We also calculated absolute risk-differences between groups. E-value was calculated using the hazard ratio on a freely available online calculator to quantify the risk an unmeasured confounder would need to have to change observed results [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Consistent with the intention-to-treat analysis principle, patients were analyzed according to the initial empagliflozin or dapagliflozin assignment, regardless of any changes in medications after the initiation. Cohort identification and statistical analyses were conducted using the TriNetX platform Query Builder and Analytics Functions on May 3, 2025. R version 4.2.3 (R Project for Statistical Computing) was used to recreate the Kaplan-Meier curves. A 2-sided p-value of \u0026lt;\u0026thinsp;0.05 was set to indicate statistical significance.\u003c/p\u003e\u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eBaseline characteristics of patients initiated on empagliflozin versus dapagliflozin before and after the propensity score matching\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA total of 95,566 Stage 3 CKD patients met the study criteria, of whom 60,689 were initiated on empagliflozin and 34,877 were initiated on dapagliflozin between January 1, 2021 and December 31, 2023 (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes the baseline characteristics of patients before and after the propensity score matching. Prior to matching, mean age in the empagliflozin and dapagliflozin groups was 70.2 years and 69.2 years, respectively. Demographics were similar with approximately 61% identifying themselves as belonging to a White race and 56% as male in both groups. About 50% in each group had a diagnosis of heart failure. More patients in the empagliflozin group had diabetes mellitus (78% vs. 70%). The baseline mean Hemoglobin A1C was higher (7.6% vs. 7.3% [to convert to a proportion of total hemoglobin, multiply by 0.01]) in the empagliflozin group than in the dapagliflozin group. Cardiovascular medication use was similar except for the use of angiotensin-converting enzyme inhibitor being higher in the empagliflozin group (27.7% vs. 23.2%). After 1:1 nearest-neighbor matching using 42 covariates, two balanced cohorts (all SMDs\u0026thinsp;\u0026lt;\u0026thinsp;0.1 after matching) comprising 33,583 patients in each group were created. \u003cb\u003eSupplement eFigure 2\u003c/b\u003e shows propensity score density curves before and after matching.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eBaseline characteristics of patients with Stage 3 CKD initiating empagliflozin vs. dapagliflozin before and after 1:1 propensity score matching\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"7\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u003cp\u003eCharacteristic\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e\u003cp\u003eBefore matching\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e\u003cp\u003eAfter matching\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEmpagliflozin\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;63,398)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDapagliflozin\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;39,048)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSMD\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eEmpagliflozin\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;37,115)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003eDapagliflozin\u003c/p\u003e\u003cp\u003e(N\u0026thinsp;=\u0026thinsp;37,115)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSMD\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean age (SD), years\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e70.2 (10.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e69.2 (11.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e69.4 (11.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e69.5 (11.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMale sex\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e55.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e56.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e57.0%%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e56.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eRace\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eWhite\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e61.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e59.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e59.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e59.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBlack\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e19.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e20.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e20.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e20.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAsian\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUnknown\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e9.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiabetes mellitus\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e78.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e70%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.19\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e71.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e71.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHypertension\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e78.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e75.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e75.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e76.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean eGFR (SD), ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e47.1 (13.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e45.4 (14.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.12\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e46.2 (13.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e45.5 (14.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.05\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eeGFR 30 to \u0026lt;\u0026thinsp;45 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e58.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e64.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e63.5%%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e63.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eeGFR 45 to \u0026lt;\u0026thinsp;60 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e69.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e68.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e68.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e68.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean UPCR (SD), mg/g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e649.2(1742.2)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e700.8(1643.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e688.9 (1792.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e689.8(1668.0)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUPCR 0 to \u0026lt;\u0026thinsp;150 mg/g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e5.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUPCR 150 to \u0026lt;\u0026thinsp;500 mg/g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUPCR 500 to \u0026lt;\u0026thinsp;3500 mg/g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUPCR\u0026thinsp;\u0026ge;\u0026thinsp;3500 mg/g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean UACR (SD), mg/g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e389.8 (944.4)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e438.4 (939.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e434.6 ( 999.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e423.2 ( 930.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUACR 0 to \u0026lt;\u0026thinsp;30 mg/g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUACR 30 to \u0026lt;\u0026thinsp;300 mg/g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e2.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eUACR\u0026thinsp;\u0026gt;\u0026thinsp;300 mg/g\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e1.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean Hemoglobin A1C (SD), %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7.6 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.3 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.18\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e7.4 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e7.3 (1.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin A1C 0 to \u0026lt;\u0026thinsp;3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e0.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin A1C 3 to \u0026lt;\u0026thinsp;6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e15.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e18.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e18.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin A1C 6 to \u0026lt;\u0026thinsp;9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e57.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e51.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e51.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin A1C 9 to \u0026lt;\u0026thinsp;12%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e16.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e12.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e12.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHemoglobin A1C \u0026ge;12%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSystolic heart failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e23.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e28.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.10\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e27.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e27.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDiastolic heart failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e20.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e19.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e19.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCombined systolic and diastolic heart failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e11.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e15.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.11\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eIschemic heart diseases\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e45.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e45.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e45.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAdverse socioeconomic determinants of health*\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFibrosis and cirrhosis of liver\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean Left Ventricular Ejection Fraction (SD), %\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e49.2 (16.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44.2 (17.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.29\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e47.1 (16.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e45.9 (17.7)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLeft Ventricular Ejection Fraction 0 to \u0026lt;\u0026thinsp;50%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLeft Ventricular Ejection Fraction \u0026ge;50%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e4.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMedication use\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCardiovascular medications\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e86.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e86.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e86.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e86.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAngiotensin II receptor blockers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e37.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e39.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e39.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.008\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAngiotensin converting enzyme inhibitors\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e27.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.10\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e23.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLoop Diuretics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e42.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e44.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.05\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e43.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e43.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCombination Diuretics, including potassium sparing diuretics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e19.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e21.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e21.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBeta blockers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e57.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e58.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e58.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e58.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSacubitril\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e8.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.09\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e10.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e10.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCalcium channel blockers\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e37.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e38.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e37.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e37.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eHydralazine\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e15.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e19.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.10\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e18.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e18.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLipid lowering medications\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e69.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e65.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e65.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e65.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePlatelet aggregation inhibitors\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e38.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.007\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e39.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e39.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAmiodarone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e7.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e8.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e8.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDigoxin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0. 06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.004\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOrganic nitrates\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e21.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.06\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e23.7%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInsulin and analogues\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e43.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e40.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e40.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMetformin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e33.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.19\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e25.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e25.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eGlucagon-like peptide-1 analogues\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e18.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12.9%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.14\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e13.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e13.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.003\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eDipeptidyl peptidase 4 inhibitors\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e10.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.03\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e9.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.009\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSulfonylureas\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e18.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e14.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003e0.11\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e14.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e14.6%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThiazolidinediones\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e3.5%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.01\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e3.4%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e3.3%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.005\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eThiazides/Related diuretics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e24.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e23.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e\u003cp\u003e0.02\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e23.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e23.0%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e\u003cp\u003e0.002\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: SD, standard deviation; SMD, absolute standardized mean difference; eGFR, estimated glomerular filtration rate by the Modification of Diet in Renal Disease equation; UPCR, Urine-protein-to-creatinine ratio\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"7\"\u003e*International Classification of Diseases, Tenth Revision Codes Z-55-Z65\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eComparison of outcomes in patients initiated on empagliflozin versus dapagliflozin in propensity score matched cohorts\u003c/h2\u003e\u003cp\u003eDuring a mean follow-up of 669.9 (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e321) days in the empagliflozin group and 667.5 (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e319.7) days in the dapagliflozin group, 1,741 (5.2%) patients in the empagliflozin group compared to 2,089 (6.2%) in the dapagliflozin group experienced the composite outcome of Stage 5 CKD or ESKD (HR: 0.82; 95% CI: 0.77 to 0.86; log-rank \u003cem\u003eP\u003c/em\u003e \u0026lt;\u0026thinsp;0.001; E-value:1.44) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Similarly, patients who were initiated on empagliflozin were less likely to have Stage 5 CKD (1.7% vs. 2.2%; HR: 0.77; 95% CI: 0.69 to 0.88; log-rank \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and ESKD (4.5% vs. 5.4%; HR: 0.82; 95% CI: 0.77 to 0.88; log-rank \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). All-cause mortality did not differ between the groups (9.3% vs. 9.0%: HR1.03; 95% CI: 0.97 to 1.08, log-rank \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.30) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Proportional hazard assumption was not violated in any of the above survival analyses (Schoenfeld test P-value \u0026gt;\u0026thinsp;0.05). The risk of AKI was lower in the empagliflozin group than in the dapagliflozin group (26.8% vs. 28.4%; risk ratio: 0.94; 95% CI: 0.92 to 0.97; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The proportion of patients with DKA was similar in the empagliflozin (1.2%) and dapagliflozin (1.2%) groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.37). Likewise, genital infection rate was the same (0.03%) in two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;1.00), but UTI rate was lower in the empagliflozin group (11.6%) than in the dapagliflozin group (13.3%) (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Consistent with the primary analysis, the sensitivity analysis with the ascertainment of outcomes starting one day after the index event also showed a lower risk for the composite of Stage 5 CKD or ESKD in patients initiating empagliflozin compared to those initiating dapagliflozin (6.3% vs. 7.6%; HR: 0.81; 95% CI: 0.76 to 0.86; log-rank \u003cem\u003eP\u003c/em\u003e \u0026lt;\u0026thinsp;0.001).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eSupplement eTable 3 and eTable 4\u003c/b\u003e summarizes the baseline characteristics of patients included in the sensitivity analyses assessing the dose-effect relationship of empagliflozin on outcomes before and after the propensity score matching. After the nearest-neighbor propensity score matching using all 42 covariates, 8,414 patients in the empagliflozin 25mg daily group were compared with 8,414 patients in the dapagliflozin 10 mg daily group. \u003cb\u003eSupplement eFigure 3 and eFigure 4\u003c/b\u003e show propensity score density curves before and after the propensity score matching. During a mean follow up of 722 (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e322) days in the empagliflozin group and 681 (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e310) days in the dapagliflozin group, 370 (4.4%) patients in the empagliflozin group compared to 482 (5.7%) in the dapagliflozin group experienced the composite outcome of Stage 5 CKD or ESKD (HR: 0.72, 95% CI: 0.63, 0.82; log-rank \u003cem\u003eP\u003c/em\u003e\u0026lt; 0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e). All-cause mortality was similar in the empagliflozin and dapagliflozin groups (HR: 0.96, 95% CI: 0.86, 1.07; log-rank \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.45). After the nearest-neighbor propensity score matching, 15,563 patients in the empagliflozin 10 mg daily were compared with 15,563 patients in the dapagliflozin 10 mg daily group. During a mean follow up of 665 (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e313) days in the empagliflozin group and 663 (\u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e311.2) days in the dapagliflozin group, 761 (4.9%) patients in the empagliflozin group experienced the composite outcome of Stage 5 CKD or ESKD compared to 939 (6.0%) in the dapagliflozin group (HR: 0.80, 95% CI: 0.73, 0.88; log-rank \u003cem\u003eP\u003c/em\u003e \u0026lt;\u0026thinsp;0.001) (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e4\u003c/span\u003e). All-cause mortality was similar in the empagliflozin and dapagliflozin groups (HR: 1.03, 95% CI: 0.96, 1.12; log-rank \u003cem\u003eP\u003c/em\u003e= 0.29). The risk of AKI was lower in both the 10 mg and 25 mg empagliflozin groups than in the dapagliflozin 10 mg group in the above analyses, respectively (\u003cb\u003eSupplement eTable 5\u003c/b\u003e). The adverse effect profile including DKA, UTI, and genital infections in the dose-specific analyses are shown in \u003cb\u003eSupplement eTable 6.\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this observational propensity score-matched multi-center cohort study involving a large database of patients in North America, patients with Stage 3 CKD who initiated empagliflozin had a lower risk of experiencing the composite of Stage 5 CKD or ESKD compared to those who initiated dapagliflozin over a follow-up period of approximately 2.0 years. Similarly, the risk of AKI was also lower in patients who initiated empagliflozin. When different dose formulations were compared, patients initiated on both empagliflozin 10 mg daily and 25 mg daily had a lower risk for major adverse kidney events than patients initiated on dapagliflozin 10 mg daily. As for adverse events, the proportion of patients with DKA and genital infections were similar in two groups while UTI rate was lower in the empagliflozin group.\u003c/p\u003e\u003cp\u003ePrior studies comparing empagliflozin and dapagliflozin have had varied methodologies and results. A recent large network meta-analysis of 21 clinical trials found that all SGLT2-inhibitors have equivalent efficacy profiles for cardiovascular and kidney outcomes, although there was a suggestion that patients without CKD may benefit more from empagliflozin [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. This study was a trial-level meta-analysis without individual-level data and only included placebo-controlled trials as there are no head-to-head trials comparing different SGLT2-inhibitors for major clinical outcomes. The only clinical trial directly comparing two agents tested empagliflozin 25 mg daily versus dapagliflozin 10 mg daily as an add-on therapy to multiple glucose lowering drugs in patients with uncontrolled type 2 diabetes[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. This small study from South Korea, which was not powered for hard outcomes, showed a greater reduction in hemoglobin A1C, blood pressure and weight loss with empagliflozin versus dapagliflozin over a 52-week period. Similarly, cohort studies evaluating patients with heart failure also show favorable benefits of empagliflozin over dapagliflozin for important clinical, laboratory and imaging related heart failure endpoints [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. For kidney outcomes, a recent large population-based cohort study from Denmark showed that individuals with type 2 diabetes who were initiated on empagliflozin and dapagliflozin had similar risks for incident CKD, CKD progression, and AKI over 6 years [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Unlike our study, the Danish study did not exclusively evaluate patients with CKD (median eGFR was 88ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e and median UACR was 16mg/g), excluded patients without type 2 diabetes mellitus, and did not report on hard outcomes such as kidney failure or death. In addition, while the racial and ethnic distribution of the patients were not given, as it was a population-based study using the Danish health care data, the patients were likely more racially and ethnically homogeneous than what would be expected in North America. It is also unclear what proportion of patients were on different dose formulations of empagliflozin and dapagliflozin. Therefore, we speculate that the differences in the patient mix and the baseline risks for adverse kidney events may explain the discrepant results between our study and the Danish study.\u003c/p\u003e\u003cp\u003eAs major clinical trials in CKD for empagliflozin and dapagliflozin used a fixed 10 mg dose formulation for both drugs while the highest dose of empagliflozin available in North America is a 25 mg dose formulation [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], we conducted exploratory analyses evaluating the possibility of a dose-effect relationship in those treated with empagliflozin that could explain our primary findings. Prior reports suggest a better blood sugar control and more weight loss with 25 mg versus 10 mg of empagliflozin in patients with type 2 diabetes [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. A clinical trial in patients with type 2 diabetes mellitus and high cardiovascular risks, however, showed that both 25mg and 10mg doses of empagliflozin were equally effective in reducing cardiovascular disease outcomes [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Only 26% of participants in that trial had eGFR\u0026thinsp;\u0026lt;\u0026thinsp;60 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e. Hence, while a higher dose of empagliflozin 25mg daily is typically used to improve blood sugar management in patients with type 2 diabetes, heart failure guidelines recommend a target dose of 10 mg daily and CKD guidelines do not endorse any particular dose of empagliflozin [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Our finding that Stage 3 CKD patients who were comparable at baseline in terms of comorbidities initiated on a dose of empagliflozin 25 mg daily or 10 mg daily were less likely to experience the composite of Stage 5 CKD or ESKD compared to those started on dapagliflozin 10 mg daily is supportive of the existing practice.\u003c/p\u003e\u003cp\u003eAs Stage 3 CKD is estimated to affect approximately 13\u0026nbsp;million adults in the United States (~\u0026thinsp;5% of the adult population) with a substantial proportion of them meeting the indications for SGLT2-inhibitors based on the most recent clinical practice guidelines [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], even the small absolute benefit of empagliflozin over dapagliflozin observed in our study (absolute risk difference of 0.4% for major adverse kidney events; number needed to treat of 250) has a potential for a significant public health implication. Furthermore, the current CKD guidelines do not favor one SGLT2-inhibitor over others nor provide recommendations on the dosage of SGLT2-inhibitors for optimal benefit [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Our findings suggesting a possible difference in real-world efficacy between the two most widely prescribed SGLT2-inhibitors and the dose-effect relationship for kidney outcomes with empagliflozin are expected to provide an impetus for future clinical trials comparing different types and dosage of SGLT2-inhibitors in CKD.\u003c/p\u003e\u003cp\u003eOur study has important limitations. We could not determine the indication for starting SGLT2-inhibitors, cause-specific mortality, or the specific cause of AKI given the limitations of the platform. Proteinuria measurements, while balanced between groups, were only available for approximately 13% of patients in each group. We also could not determine the exact onset of Stage 3 CKD, implying that our analysis may have a risk for immortal time bias. The risk for immortal time bias, however, is likely low as cohorts were balanced for key characteristics, including for baseline eGFR, and for comorbidities such as heart failure and type 2 diabetes, two most common indications for SGLT2-inhibitors other than CKD. Despite well-matched cohorts, the risk for unmeasured confounding remains in observational studies. However, the E-value of 1.44 suggests that the observed association would only be nullified in the presence of an unmeasured confounder that is associated with a risk ratio of 1.44 or greater to treatment assignment and outcome. Since multiple measurements of laboratory parameters over time could not be assessed in this platform, we were unable to analyze the eGFR slope or hemoglobin A1C trends in our analysis.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn this large multicenter cohort study including patients with Stage 3 CKD, empagliflozin initiation compared to dapagliflozin initiation was associated with a lower rate of Stage 5 CKD or ESKD over a follow-up period of approximately 2.0 years. When a specific dose was studied in two separate analyses, both empagliflozin 25 mg daily and 10 mg daily initiation were associated with a lower rate of Stage 5 CKD or ESKD compared to dapagliflozin 10 mg initiation. Further studies are required to validate our findings and understand the mechanisms behind the observed differences on kidney outcomes focusing on patients with CKD, especially those with reduced eGFR (\u0026lt;\u0026thinsp;60 ml/min/1.73m\u003csup\u003e2\u003c/sup\u003e).\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cb\u003eEthics approval and consent to participate\u003c/b\u003e:\u003c/strong\u003e\u003cp\u003eThe institutional review board of Boston University designated this study to not be human subjects research and waived the requirement for informed consent and review.\u003c/p\u003e\u003ch2\u003eConflict of Interest statement:\u003c/h2\u003e\u003cp\u003eAuthors have no conflicts of interest to declare.\u003c/p\u003e\u003ch2\u003eFunding:\u003c/h2\u003e\u003cp\u003eNone\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eJB conceptualized, analysed data, and wrote the manuscript; NB helped in data analysis, manuscript writing, and supervision; AU conceptualized and supervised manuscript writing. All authors reviewed the manuscript.\u003c/p\u003e\u003ch2\u003eAcknowledgement:\u003c/h2\u003e\u003cp\u003eNone\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe data on the results is available from the corresponding author upon request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eUpadhyay A. SGLT2 Inhibitors and Kidney Protection: Mechanisms Beyond Tubuloglomerular Feedback. \u003cem\u003eKidney360\u003c/em\u003e, 5: 771\u0026ndash;782, 2024 10.34067/KID.0000000000000425.\u003c/span\u003e\u003c/li\u003e\u003cli\u003e\u003cspan\u003eKidney Disease. Improving Global Outcomes CKDWG: KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. 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National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Chronic kidney disease, Empagliflozin, Dapagliflozin","lastPublishedDoi":"10.21203/rs.3.rs-7586037/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7586037/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e\u003cp\u003eSodium-glucose cotransporter 2 (SGLT2)-inhibitors are key in chronic kidney disease (CKD) management with empagliflozin and dapagliflozin being the two most commonly used. Comparative data between them in CKD is limited.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eA propensity score-matched cohort study was conducted using data from a network of 103 North American organizations. Adults with Stage 3 CKD who initiated empagliflozin or dapagliflozin between January 1, 2021 and December 31, 2023, were compared. The primary outcomes was the composite of Stage 5 CKD or end-stage kidney disease (ESKD). Follow-up continued until outcome or up to 3 years (censored on May 4, 2025).\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003e60,689 and 34,877 patients with Stage 3 CKD were initiated on empagliflozin and dapagliflozin, respectively. Among matched patients with Stage 3 CKD (N\u0026thinsp;=\u0026thinsp;33,583 per group) empagliflozin initiation was associated with lower risk of Stage 5 CKD or ESKD (5.2% vs 6.2%; HR: 0.82; 95% CI: 0.77\u0026ndash;0.88) over ~\u0026thinsp;670 days. All-cause mortality was similar between groups. Stage 5 CKD and ESKD rates were lower in the empagliflozin group. Stage 5 CKD or ESKD was lower for patients initiated on both empagliflozin 25 mg daily and 10 mg daily compared to dapagliflozin 10 mg daily.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eIn this multi-center retrospective cohort study, the risk for Stage 5 CKD or ESKD was lower for patients with Stage 3 CKD who initiated empagliflozin versus dapagliflozin over ~\u0026thinsp;2.0 years. Prospective studies are needed to confirm our findings.\u003c/p\u003e","manuscriptTitle":"Empagliflozin versus Dapagliflozin for Kidney Outcomes in Stage 3 Chronic Kidney Disease: A Propensity Score-Matched Multi-center Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-08 08:04:50","doi":"10.21203/rs.3.rs-7586037/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-01T07:12:30+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-30T02:06:44+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-29T13:31:16+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"30669248338173988874000533386927251520","date":"2025-11-29T13:29:21+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-29T10:38:29+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"41472773603895942368925113472920613307","date":"2025-11-29T02:53:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"150137113465169387027593198248113185674","date":"2025-11-28T06:36:51+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-26T02:59:15+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"254826176614497104023370970944950691403","date":"2025-11-25T02:56:05+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-08T12:05:40+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-11-08T10:07:10+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"91871022305296096513343917484037711418","date":"2025-11-08T04:08:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"74837092976426988333935300220365106424","date":"2025-11-05T11:00:34+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"156543379773479223011735185457941368436","date":"2025-10-30T08:29:10+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-25T05:58:31+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-09-16T10:40:14+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-12T10:38:05+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-12T10:37:36+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Nephrology","date":"2025-09-10T20:58:59+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-nephrology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bnep","sideBox":"Learn more about [BMC Nephrology](http://bmcnephrol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bnep/default.aspx","title":"BMC Nephrology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"f3f65279-6a98-4469-abd7-d6172902e1a1","owner":[],"postedDate":"October 8th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[],"tags":[],"updatedAt":"2026-05-20T09:54:50+00:00","versionOfRecord":[],"versionCreatedAt":"2025-10-08 08:04:50","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7586037","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7586037","identity":"rs-7586037","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}