{"doi":"10.1681/asn.2022020207","title":"Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and Their Combination in Patients with Chronic Kidney Disease: A Randomized Crossover Clinical Trial","abstract":"\n Background\n Sodium glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs) reduce the urinary albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with CKD. We assessed efficacy and safety of the SGLT2 inhibitor dapagliflozin and MRA eplerenone alone and in combination in patients with CKD.\n \n \n Methods\n \n We conducted a randomized open-label crossover trial in patients with urinary albumin excretion ≥100 mg/24 hr, eGFR 30–90 ml/min per 1.73 m\n 2\n , who had been receiving maximum tolerated stable doses of an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB). Patients were assigned to 4-week treatment periods with dapagliflozin 10 mg/day, eplerenone 50 mg/day, or their combination in random order, separated by 4-week washout periods. Primary outcome was the correlation in UACR changes between treatments. Secondary outcome was the percent change in 24-hour UACR from baseline.\n \n \n \n Results\n \n Of 57 patients screened, 46 were randomly assigned (mean eGFR, 58.1 ml/min per 1.73 m\n 2\n ; median UACR, 401 mg/g) to the three groups. Mean percentage change from baseline in UACR after 4 weeks of treatment with dapagliflozin, eplerenone, and dapagliflozin-eplerenone was –19.6% (95% confidence interval [CI], –34.3 to –1.5), –33.7% (95% CI, –46.1 to –18.5), and –53% (95% CI, –61.7 to –42.4;\n P\n <0.001 versus dapagliflozin;\n P\n =0.01 versus eplerenone). UACR change during dapagliflozin or eplerenone treatment did not correlate with UACR change during dapagliflozin-eplerenone (\n r\n =–0.13;\n P\n =0.47;\n r\n =–0.08;\n P\n =0.66, respectively). Hyperkalemia was more frequently reported with eplerenone (\n n\n =8; 17.4%) compared with dapagliflozin (\n n\n =0; 0%) or dapagliflozin-eplerenone (\n n\n =2; 4.3%;\n P\n between-groups\n =0.003).\n \n \n \n Conclusions\n Albuminuria changes in response to dapagliflozin and eplerenone did not correlate, supporting systematic rotation of these therapies to optimize treatment. Combining dapagliflozin with eplerenone resulted in a robust additive UACR-lowering effect. A larger trial in this population is required to confirm long-term efficacy and safety of combined SGLT2 inhibitor and MRA treatment.\n \n \n Clinical Trial registry name and registration number:\n European Union Clinical Trials Register, EU 2017–004641–25.\n ","journal":"Journal of the American Society of Nephrology","year":2022,"id":645078,"datarank":0.782240363641348,"base_score":5.214935757608986,"endowment":5.214935757608986,"self_citation_contribution":0.782240363641348,"citation_network_contribution":0.0,"self_endowment_contribution":0.782240363641348,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":183,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":2,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1679482,"name":"Maria Jesús Puchades","orcid":"0000-0001-6927-071X","position":1,"is_corresponding":false},{"id":1679483,"name":"Carlo Garofalo","orcid":"0000-0001-9362-0281","position":2,"is_corresponding":false},{"id":814151,"name":"Niels Jongs","orcid":"0000-0002-0882-3656","position":3,"is_corresponding":false},{"id":1679486,"name":"Luis D’Marco","orcid":"0000-0003-0148-891X","position":4,"is_corresponding":false},{"id":1679488,"name":"Michele Andreucci","orcid":null,"position":5,"is_corresponding":false},{"id":1554993,"name":"Luca De Nicola","orcid":null,"position":6,"is_corresponding":false},{"id":814152,"name":"José Luis Górriz","orcid":"0000-0002-1134-9051","position":7,"is_corresponding":false},{"id":232682,"name":"Hiddo J.L. Heerspink","orcid":"0000-0002-3126-3730","position":8,"is_corresponding":false},{"id":1554994,"name":"Michele Provenzano","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Albuminuria-Lowering Effect of Dapagliflozin, Eplerenone, and Their Combination in Patients with Chronic Kidney Disease: A Randomized Crossover Clinical Trial","abstract":"\n Background\n Sodium glucose cotransporter 2 (SGLT2) inhibitors and mineralocorticoid receptor antagonists (MRAs) reduce the urinary albumin-to-creatinine ratio (UACR) and confer kidney and cardiovascular protection in patients with CKD. We assessed efficacy and safety of the SGLT2 inhibitor dapagliflozin and MRA eplerenone alone and in combination in patients with CKD.\n \n \n Methods\n \n We conducted a randomized open-label crossover trial in patients with urinary albumin excretion ≥100 mg/24 hr, eGFR 30–90 ml/min per 1.73 m\n 2\n , who had been receiving maximum tolerated stable doses of an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB). Patients were assigned to 4-week treatment periods with dapagliflozin 10 mg/day, eplerenone 50 mg/day, or their combination in random order, separated by 4-week washout periods. Primary outcome was the correlation in UACR changes between treatments. Secondary outcome was the percent change in 24-hour UACR from baseline.\n \n \n \n Results\n \n Of 57 patients screened, 46 were randomly assigned (mean eGFR, 58.1 ml/min per 1.73 m\n 2\n ; median UACR, 401 mg/g) to the three groups. Mean percentage change from baseline in UACR after 4 weeks of treatment with dapagliflozin, eplerenone, and dapagliflozin-eplerenone was –19.6% (95% confidence interval [CI], –34.3 to –1.5), –33.7% (95% CI, –46.1 to –18.5), and –53% (95% CI, –61.7 to –42.4;\n P\n <0.001 versus dapagliflozin;\n P\n =0.01 versus eplerenone). UACR change during dapagliflozin or eplerenone treatment did not correlate with UACR change during dapagliflozin-eplerenone (\n r\n =–0.13;\n P\n =0.47;\n r\n =–0.08;\n P\n =0.66, respectively). Hyperkalemia was more frequently reported with eplerenone (\n n\n =8; 17.4%) compared with dapagliflozin (\n n\n =0; 0%) or dapagliflozin-eplerenone (\n n\n =2; 4.3%;\n P\n between-groups\n =0.003).\n \n \n \n Conclusions\n Albuminuria changes in response to dapagliflozin and eplerenone did not correlate, supporting systematic rotation of these therapies to optimize treatment. Combining dapagliflozin with eplerenone resulted in a robust additive UACR-lowering effect. A larger trial in this population is required to confirm long-term efficacy and safety of combined SGLT2 inhibitor and MRA treatment.\n \n \n Clinical Trial registry name and registration number:\n European Union Clinical Trials Register, EU 2017–004641–25.\n ","is_dataset_classified":null,"base_score":5.214935757608986,"endowment":5.214935757608986,"datacite_reuse_total":2,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35440501","pmcid":"PMC9342643","openalex_id":"https://openalex.org/W4224290456","authors":[],"funders":[],"total_grants":0,"fwci":19.4634,"citation_percentile":0.99591582,"influential_citations":0,"citation_trend":[{"year":2022,"count":15},{"year":2023,"count":49},{"year":2024,"count":51},{"year":2025,"count":40},{"year":2026,"count":28}],"oa_status":"green","license":"other-oa","oa_locations":[{"url":"https://research.rug.nl/files/224342062/Albuminuria_Lowering_Effect_of_Dapagliflozin_Eplerenone_and_their_Combination_in_Patients_with_Chronic_Kidney_Disease_A_Randomized_Cross_Over_Clinical_Trial.pdf","host_type":"repository"},{"url":"https://research.rug.nl/files/224342062/Albuminuria_Lowering_Effect_of_Dapagliflozin_Eplerenone_and_their_Combination_in_Patients_with_Chronic_Kidney_Disease_A_Randomized_Cross_Over_Clinical_Trial.pdf","host_type":"repository"},{"url":"https://www.ovid.com/10.1681/ASN.2022020207","host_type":"publisher"},{"url":"https://research.rug.nl/en/publications/ba56a8ea-68f6-4e78-8a70-7b15df783f43","host_type":"repository"},{"url":"https://doi.org/10.1681/asn.2022020207","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35440501","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9342643","host_type":"repository"},{"url":"https://hdl.handle.net/11370/ba56a8ea-68f6-4e78-8a70-7b15df783f43","host_type":"repository"},{"url":"https://doi.org/10.1681/ASN.2022020207","host_type":"repository"},{"url":"https://hdl.handle.net/10550/121277","host_type":"repository"}],"fields_of_study":["Hormonal Regulation and Hypertension","Diabetes Treatment and Management","Chronic Kidney Disease and Diabetes"],"mesh_terms":["Sodium-Glucose Transporter 2 Inhibitors","Eplerenone","Albuminuria","Angiotensin-Converting Enzyme Inhibitors","Benzhydryl Compounds","Glomerular Filtration Rate","Glucosides","Humans","Cross-Over Studies","Renal Insufficiency, Chronic","Angiotensin Receptor Antagonists"],"keywords":["Dapagliflozin","Eplerenone","Medicine","Albuminuria","Mineralocorticoid receptor","Urology","Kidney disease","Internal medicine","Renal function","Crossover study","Endocrinology","Creatinine","Pharmacology","Aldosterone","Type 2 diabetes","Diabetes mellitus","Placebo","Pathology","Randomized controlled trials","Chronic Kidney Disease","Mineralocorticoid Receptor Antagonist","Sodium Glucose Co Transporter"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[{"doi":"10.6084/m9.figshare.26461800.v1","title":"Additional file 1 of Hyperkalemic effect of drug–drug interaction between esaxerenone and trimethoprim in patients with hypertension: a pilot study","publisher":"figshare","resource_type":"JournalArticle"},{"doi":"10.6084/m9.figshare.26461800","title":"Additional file 1 of Hyperkalemic effect of drug–drug interaction between esaxerenone and trimethoprim in patients with hypertension: a pilot study","publisher":"figshare","resource_type":"JournalArticle"}],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"eudract"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-09T02:48:37.819710Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}