{"doi":"10.1016/j.ekir.2020.01.020","title":"Ritonavir-Boosted Protease Inhibitors Do Not Significantly Affect the Performance of Creatinine-Based Estimates of GFR","abstract":"Chronic kidney disease (CKD) is more common among HIV-positive individuals.S1–S4 Accurate estimation of glomerular filtration rate (GFR) is important for appropriate antiretroviral (ART) regimen selection and dose adjustment, and for the identification of patients with CKD who may benefit from more intensive modification of HIV-related and traditional CKD risk factors.1Lucas G.M. Ross M.J. Stock P.G. et al.Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America.Clin Infect Dis. 2014; 59: e96-e138Crossref PubMed Scopus (193) Google Scholar,2Swanepoel C.R. Atta M.G. D'Agati V.D. et al.Kidney disease in the setting of HIV infection: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.Kidney Int. 2018; 93: 545-559Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar Commonly used estimates of GFR are based on serum creatinine, a product of skeletal muscle metabolism that is primarily eliminated by glomerular filtration. The generation of creatinine by muscle, with substantial variability in muscle mass between and even within individuals over time, is well recognized as an important limitation of creatinine-based GFR estimates (eGFRCr) in HIV-positive individuals.1Lucas G.M. Ross M.J. Stock P.G. et al.Clinical practice guideline for the management of chronic kidney disease in patients infected with HIV: 2014 update by the HIV Medicine Association of the Infectious Diseases Society of America.Clin Infect Dis. 2014; 59: e96-e138Crossref PubMed Scopus (193) Google Scholar,2Swanepoel C.R. Atta M.G. D'Agati V.D. et al.Kidney disease in the setting of HIV infection: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference.Kidney Int. 2018; 93: 545-559Abstract Full Text Full Text PDF PubMed Scopus (102) Google Scholar Until recently, the impact of active tubular secretion on eGFRCr has rarely been a clinically relevant concern. In early-phase clinical trials, the newer pharmacoenhancer cobicistat and the ART agents dolutegravir, raltegravir, and rilpivirine were observed to cause an early rise in serum creatinine and a corresponding decrease in eGFRCr.3German P. Liu H.C. Szwarcberg J. et al.Effect of cobicistat on glomerular filtration rate in subjects with normal and impaired renal function.J Acquir Immune Defic Syndr. 2012; 61: 32-40Crossref PubMed Scopus (151) Google Scholar,S5–S15 In vitro studies have demonstrated that cobicistat and dolutegravir interfere with the tubular secretion of creatinine by inhibiting specific tubular transporters.4Lepist E.I. Zhang X. Hao J. et al.Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicistat.Kidney Int. 2014; 86: 350-357Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar As such, a small increase in serum creatinine is expected with the initiation of these agents and is not thought to reflect a decline in true kidney function. This can complicate the interpretation of eGFRCr or calculated creatinine clearance, particularly near dosing thresholds or in patients with or at risk for progressive CKD. In the same series of in vitro experiments, ritonavir was also shown to inhibit the tubular transport of creatinine.4Lepist E.I. Zhang X. Hao J. et al.Contribution of the organic anion transporter OAT2 to the renal active tubular secretion of creatinine and mechanism for serum creatinine elevations caused by cobicistat.Kidney Int. 2014; 86: 350-357Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar Although the physiologic relevance is unknown, particularly with low-dose ritonavir used as a pharmacoenhancer, this raises the possibility that ritonavir-boosted protease inhibitors (PI/r) could also affect serum creatinine and eGFRCr ind","journal":"Kidney International Reports","year":2020,"id":114950,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9611,"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":540513,"name":"Juhi Chaudhari","orcid":null,"position":1,"is_corresponding":false},{"id":539529,"name":"Shiyuan Miao","orcid":"0009-0007-9784-5542","position":2,"is_corresponding":false},{"id":306131,"name":"Zipporah Krishnasami","orcid":null,"position":3,"is_corresponding":false},{"id":12078,"name":"James Hellinger","orcid":null,"position":4,"is_corresponding":false},{"id":58425,"name":"Andrew S. Levey","orcid":"0000-0003-1491-501X","position":5,"is_corresponding":false},{"id":540514,"name":"Michael J. Ross","orcid":null,"position":6,"is_corresponding":false},{"id":364591,"name":"Lene Ryom","orcid":"0000-0002-6436-6461","position":7,"is_corresponding":false},{"id":364614,"name":"Amanda Mocroft","orcid":"0000-0001-8316-1122","position":8,"is_corresponding":false},{"id":539530,"name":"Laurence Brunet","orcid":"0000-0001-8467-4835","position":9,"is_corresponding":false},{"id":539531,"name":"Jennifer S Fusco","orcid":"0000-0003-1556-811X","position":10,"is_corresponding":false},{"id":19370,"name":"Lesley A. Inker","orcid":"0000-0003-2820-9482","position":11,"is_corresponding":false},{"id":303937,"name":"Christina Wyatt","orcid":"0000-0002-2900-8140","position":0,"is_corresponding":true}],"reference_count":9,"raw_metadata":null,"created_at":"2026-07-18T23:13:33.226937Z","pmid":"32405595","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":[]}