{"doi":"10.1111/dom.14252","title":"Inter‐individual variability in atrasentan exposure partly explains variability in kidney protection and fluid retention responses: A post hoc analysis of the <scp>SONAR</scp> trial","abstract":"AIM: To evaluate whether atrasentan plasma exposure explains between-patient variability in urinary albumin-to-creatinine ratio (UACR) response, a surrogate for kidney protection, and B-type natriuretic peptide (BNP) response, a surrogate for fluid expansion. METHODS: Type 2 diabetic patients with chronic kidney disease (n = 4775) received 0.75 mg atrasentan for 6 weeks in the active run-in period. Individual area under the concentration-time-curve (AUC) was estimated using a population pharmacokinetic model. The association between atrasentan AUC, other clinical characteristics, and UACR and BNP response, was estimated using linear regression. RESULTS: The median atrasentan AUC was 43.8 ng.h/mL with a large variation among patients (2.5th-97.5th percentiles [P]: 12.6 to 197.5 ng.h/mL). Median UACR change at the end of enrichment was -36.0% and median BNP change was 8.7%, which also varied among patients (UACR, 2.5th-97.5th P: -76.2% to 44.5%; BNP, 2.5th-97.5th P: -71.5% to 300.0%). In the multivariable analysis, higher atrasentan AUC was associated with greater UACR reduction (4.88% per doubling in ng.h/mL [95% confidence interval {CI}: 6.21% to 3.52%], P < .01) and greater BNP increase (3.08% per doubling in ng.h/mL [95% CI: 1.12% to 4.11%], P < .01) independent of estimated glomerular filtration rate, haemoglobin or BNP. Caucasian patients compared with black patients had greater UACR reduction (7.06% [95% CI: 1.38% to 13.07%]) and also greater BNP increase (8.75% [95% CI: 1.65% to 15.35%]). UACR response was not associated with BNP response (r = 0.06). CONCLUSION: Atrasentan plasma exposure varied among individual patients and partially explained between-patient variability in efficacy and safety response.","journal":"Diabetes Obesity and Metabolism","year":2020,"id":69438,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8103,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":367616,"name":"Jasper Stevens","orcid":"0000-0003-1601-9008","position":1,"is_corresponding":false},{"id":6,"name":"George L. Bakris","orcid":"0000-0003-1183-1267","position":2,"is_corresponding":false},{"id":368286,"name":"Ricardo Correa‐Rotter","orcid":null,"position":3,"is_corresponding":false},{"id":289676,"name":"Fan Fan Hou","orcid":"0000-0003-3117-7418","position":4,"is_corresponding":false},{"id":260522,"name":"Dalane W. Kitzman","orcid":"0009-0000-5274-0826","position":5,"is_corresponding":false},{"id":356416,"name":"Donald E. Kohan","orcid":"0000-0002-3981-2941","position":6,"is_corresponding":false},{"id":251777,"name":"Hirofumi Makino","orcid":"0000-0002-1559-3799","position":7,"is_corresponding":false},{"id":2612,"name":"John J.V. McMurray","orcid":"0000-0002-6317-3975","position":8,"is_corresponding":false},{"id":29451,"name":"Hans‐Henrik Parving","orcid":null,"position":9,"is_corresponding":false},{"id":75046,"name":"Vlado Perkovic","orcid":"0000-0002-4257-7620","position":10,"is_corresponding":false},{"id":367617,"name":"Sheldon W. Tobe","orcid":"0000-0001-7848-3872","position":11,"is_corresponding":false},{"id":29444,"name":"Dick de Zeeuw","orcid":"0000-0003-3434-7777","position":12,"is_corresponding":false},{"id":232682,"name":"Hiddo J.L. Heerspink","orcid":"0000-0002-3126-3730","position":13,"is_corresponding":false},{"id":367615,"name":"Jeroen V. Koomen","orcid":"0000-0001-7253-3998","position":0,"is_corresponding":true}],"reference_count":19,"raw_metadata":null,"created_at":"2026-07-18T21:42:22.705573Z","pmid":"33184931","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":[]}