{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T01:37:14Z","timestamp":1781228234114,"version":"3.54.1"},"reference-count":50,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T00:00:00Z","timestamp":1721174400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Implementing shortened one-compartment iohexol plasma clearance models for GFR measurement is crucial since the gold standard inulin renal clearance technique and the reference two-compartment, 10-hour, 16-samplings iohexol plasma clearance method are clinically unfeasible. Inulin may precipitate anaphylactic shock. Four-hour and 8-hour one-compartment iohexol plasma clearance models with Br\u00f6chner-Mortensen correction provide accurate GFR measurements in patients with estimated GFR (eGFR) &gt; or \u226440 mL\/min\/1.73m<jats:sup>2<\/jats:sup>, respectively. We compared the performance of the simplified 5-hour, 4-samplings, two-compartment population pharmacokinetic model (popPK) with the performance of the reference two-compartment 10-hour iohexol method in 16 patients with GFR 15.2 to 56.5 mL\/min\/1.73 m<jats:sup>2<\/jats:sup>. We also compared the performance of shortened (5, 6 and 7-hour) one-compartment models with the performance of the standard 8-hour one-compartment model in 101 patients with eGFR \u226440 mL\/min\/1.73 m<jats:sup>2<\/jats:sup>. The performance of popPK and shortened methods versus reference methods was evaluated by total deviation index (TDI), concordance correlation coefficient (CCC) and coverage probability (CP). TDI &lt;10%, CCC \u22650.9 and CP &gt;90% indicated adequate performance. TDI, CCC and CP of popPK were 11.11%, 0.809 and 54.10%, respectively. All shortened, one-compartment models overestimated the GFR (p &lt;0.0001 for all) as compared to the 8-hour model. TDI, CCC and CP were 7.02%, 0.815, and 75.80% for the 7-hour model, 7.26%, 0.803, and 74.20% for the 6-hour model, and 8.85%, 0.729 and 64.70% for the 5-hour model. The agreement of popPK model was comparable to that obtained with the Chronic-Kidney-Disease-Collaboration-Epidemiology (CKD-Epi) and the Modification-of-Diet-in-Renal-Disease (MDRD) serum-creatinine based equations for GFR estimation. PopPK model is remarkably unreliable for GFR measurement in stage III-IV CKD patients. In patients with eGFR \u226440 mL\/min\/1.73m<jats:sup>2<\/jats:sup>, shortened one-compartment models, in particular the 5-hour model, are less performant than the reference 8-hour model. For accurate GFR measurements, the iohexol plasma clearance should be measured with appropriate protocols. Over-simplified procedures should be avoided.<\/jats:p>","DOI":"10.1371\/journal.pone.0306935","type":"journal-article","created":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T17:28:51Z","timestamp":1721237331000},"page":"e0306935","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["GFR measurement in patients with CKD: Performance and feasibility of simplified iohexol plasma clearance techniques"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5799-9535","authenticated-orcid":true,"given":"Fabiola","family":"Carrara","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio","family":"Gaspari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1859-1729","authenticated-orcid":true,"given":"Matias","family":"Trillini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobia","family":"Peracchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Fidone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Stucchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silvia","family":"Ferrari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Cugini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norberto","family":"Perico","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneliya","family":"Parvanova","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6194-3446","authenticated-orcid":true,"given":"Giuseppe","family":"Remuzzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piero","family":"Ruggenenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,7,17]]},"reference":[{"key":"pone.0306935.ref001","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1172\/JCI100690","article-title":"The excretion of inulin, xylose and urea by normal and phlorizinized man 1","volume":"14","author":"JA Shannon","year":"1935","journal-title":"J Clin Invest"},{"key":"pone.0306935.ref002","volume-title":"The Kidney: Structure and Function in Health and Disease.","author":"HW Smith","year":"1951"},{"key":"pone.0306935.ref003","doi-asserted-by":"crossref","first-page":"725417","DOI":"10.3389\/fphar.2021.725417","article-title":"Safety of Inulin and Sinistrin: Combining Several Sources for Pharmacovigilance Purposes.","volume":"12","author":"T-V Bui","year":"2021","journal-title":"Front Pharmacol."},{"key":"pone.0306935.ref004","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/S0001-2998(74)80021-8","article-title":"Radionuclide clearance techniques.","volume":"4","author":"ML Cohen","year":"1974","journal-title":"Seminars in Nuclear Medicine"},{"key":"pone.0306935.ref005","doi-asserted-by":"crossref","first-page":"675","DOI":"10.1016\/S0022-5347(17)37891-6","article-title":"Iohexol Clearance for the Determination of Glomerular Filtration Rate in Clinical Practice: Evidence for a New Gold Standard","volume":"146","author":"SCW Brown","year":"1991","journal-title":"Journal of Urology"},{"key":"pone.0306935.ref006","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1080\/00365590701701806","article-title":"Determining \u2018true\u2019 glomerular filtration rate in healthy adults using infusion of inulin and comparing it with values obtained using other clearance techniques or prediction equations.","volume":"42","author":"G Sterner","year":"2008","journal-title":"Scandinavian Journal of Urology and Nephrology"},{"key":"pone.0306935.ref007","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1681\/ASN.V62257","article-title":"Plasma clearance of nonradioactive iohexol as a measure of glomerular filtration rate","volume":"6","author":"F Gaspari","year":"1995","journal-title":"J Am Soc Nephrol"},{"key":"pone.0306935.ref008","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1681\/ASN.V92310","article-title":"Precision of plasma clearance of iohexol for estimation of GFR in patients with renal disease","volume":"9","author":"F Gaspari","year":"1998","journal-title":"J Am Soc Nephrol"},{"key":"pone.0306935.ref009","doi-asserted-by":"crossref","first-page":"1857","DOI":"10.1016\/S0140-6736(96)11445-8","article-title":"Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal renal failure in proteinuric, non-diabetic nephropathy. The GISEN Group (Gruppo Italiano di Studi Epidemiologici in Nefrologia).","volume":"349","year":"1997","journal-title":"Lancet"},{"key":"pone.0306935.ref010","doi-asserted-by":"crossref","first-page":"1252","DOI":"10.1016\/S0140-6736(98)04433-X","article-title":"Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial","volume":"352","author":"P Ruggenenti","year":"1998","journal-title":"The Lancet"},{"key":"pone.0306935.ref011","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/S0140-6736(98)10363-X","article-title":"Renoprotective properties of ACE-inhibition in non-diabetic nephropathies with non-nephrotic proteinuria","volume":"354","author":"P Ruggenenti","year":"1999","journal-title":"The Lancet"},{"key":"pone.0306935.ref012","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/S0140-6736(05)71082-5","article-title":"Blood-pressure control for renoprotection in patients with non-diabetic chronic renal disease (REIN-2): multicentre, randomised controlled trial.","volume":"365","author":"P Ruggenenti","year":"2005","journal-title":"The Lancet"},{"key":"pone.0306935.ref013","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1161\/HYPERTENSIONAHA.111.174474","article-title":"Effects of manidipine and delapril in hypertensive patients with type 2 diabetes mellitus: the delapril and manidipine for nephroprotection in diabetes (DEMAND) randomized clinical trial.","volume":"58","author":"P Ruggenenti","year":"2011","journal-title":"Hypertension"},{"key":"pone.0306935.ref014","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1016\/S0140-6736(13)61407-5","article-title":"Effect of longacting somatostatin analogue on kidney and cyst growth in autosomal dominant polycystic kidney disease (ALADIN): a randomised, placebo-controlled, multicentre trial.","volume":"382","author":"A Caroli","year":"2013","journal-title":"The Lancet"},{"key":"pone.0306935.ref015","doi-asserted-by":"crossref","first-page":"e1002777","DOI":"10.1371\/journal.pmed.1002777","article-title":"Octreotide-LAR in later-stage autosomal dominant polycystic kidney disease (ALADIN 2): A randomized, double-blind, placebo-controlled, multicenter trial.","volume":"16","author":"N Perico","year":"2019","journal-title":"PLoS Med"},{"key":"pone.0306935.ref016","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/S0140-6736(04)16808-6","article-title":"Mycophenolate mofetil versus azathioprine for prevention of acute rejection in renal transplantation (MYSS): a randomised trial.","volume":"364","author":"G Remuzzi","year":"2004","journal-title":"The Lancet"},{"key":"pone.0306935.ref017","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1016\/S0140-6736(02)11042-7","article-title":"Rituximab for idiopathic membranous nephropathy","volume":"360","author":"G Remuzzi","year":"2002","journal-title":"The Lancet"},{"key":"pone.0306935.ref018","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/ki.2009.398","article-title":"Optimizing iohexol plasma disappearance curves to measure the glomerular filtration rate in children with chronic kidney disease","volume":"77","author":"GJ Schwartz","year":"2010","journal-title":"Kidney International"},{"key":"pone.0306935.ref019","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.1093\/ndt\/gfx345","article-title":"Single- versus multiple-sample method to measure glomerular filtration rate","volume":"33","author":"P Delanaye","year":"2018","journal-title":"Nephrology Dialysis Transplantation"},{"key":"pone.0306935.ref020","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1038\/ki.2011.155","article-title":"Universal GFR determination based on two time points during plasma iohexol disappearance","volume":"80","author":"DKS Ng","year":"2011","journal-title":"Kidney International"},{"key":"pone.0306935.ref021","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1111\/j.1475-097X.1983.tb00712.x","article-title":"A method for the calculation of renal clearance based on a single plasma sample.","volume":"3","author":"L. Jacobsson","year":"1983","journal-title":"Clin Physiol"},{"key":"pone.0306935.ref022","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1007\/s00467-016-3436-z","article-title":"Iohexol plasma clearance in children: validation of multiple formulas and two-point sampling times","volume":"32","author":"C T\u00f8ndel","year":"2017","journal-title":"Pediatr Nephrol"},{"key":"pone.0306935.ref023","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1681\/ASN.V7122689","article-title":"Glomerular filtration rate determined from a single plasma sample after intravenous iohexol injection: is it reliable","volume":"7","author":"F Gaspari","year":"1996","journal-title":"J Am Soc Nephrol"},{"key":"pone.0306935.ref024","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ekir.2019.11.012","article-title":"Measured GFR by Utilizing Population Pharmacokinetic Methods to Determine Iohexol Clearance","volume":"5","author":"A \u00c5sberg","year":"2020","journal-title":"Kidney International Reports"},{"key":"pone.0306935.ref025","doi-asserted-by":"crossref","first-page":"271","DOI":"10.3109\/00365517209084290","article-title":"A Simple Method for the Determination of Glomerular Filtration Rate","volume":"30","author":"J. Br\u00f6chner-Mortensen","year":"1972","journal-title":"Scandinavian Journal of Clinical and Laboratory Investigation"},{"key":"pone.0306935.ref026","article-title":"Effects of Octreotide\u2013Long-Acting Release Added-on Tolvaptan in Patients with Autosomal Dominant Polycystic Kidney Disease: Pilot, Randomized, Placebo-Controlled, Cross-Over Trial.","author":"M Trillini","year":"2023","journal-title":"CJASN."},{"key":"pone.0306935.ref027","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.cca.2013.12.028","article-title":"Measurement of glomerular filtration rate: Internal and external validations of the iohexol plasma clearance technique by HPLC","volume":"430","author":"S Luis-Lima","year":"2014","journal-title":"Clinica Chimica Acta"},{"key":"pone.0306935.ref028","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1001\/archinte.1916.00080130010002","article-title":"Clinical calorimetry: tenth paper a formula to estimate the approximate surface area if height and weight be known","volume":"XVII","author":"D. Du Bois","year":"1916","journal-title":"Arch Intern Med (Chic)."},{"key":"pone.0306935.ref029","doi-asserted-by":"crossref","first-page":"604","DOI":"10.7326\/0003-4819-150-9-200905050-00006","article-title":"A new equation to estimate glomerular filtration rate","volume":"150","author":"AS Levey","year":"2009","journal-title":"Ann Intern Med"},{"key":"pone.0306935.ref030","first-page":"155A","article-title":"A simplified equation to predict. A simplified equation to predict glomerular filtration rate from serum creatinine (Abstract).:","volume":"11","author":"for the MDRD Study Group","year":"2000","journal-title":"J Am Soc Nephrol"},{"key":"pone.0306935.ref031","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S0140-6736(86)90837-8","article-title":"Statistical methods for assessing agreement between two methods of clinical measurement","volume":"1","author":"JM Bland","year":"1986","journal-title":"Lancet"},{"key":"pone.0306935.ref032","doi-asserted-by":"crossref","first-page":"255","DOI":"10.2307\/2532051","article-title":"A Concordance Correlation Coefficient to Evaluate Reproducibility","volume":"45","author":"LI-K Lin","year":"1989","journal-title":"Biometrics"},{"key":"pone.0306935.ref033","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4614-0562-7","volume-title":"Statistical Tools for Measuring Agreement","author":"L Lin","year":"2012"},{"key":"pone.0306935.ref034","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1198\/016214502753479392","article-title":"Statistical Methods in Assessing Agreement: Models, Issues, and Tools","volume":"97","author":"L Lin","year":"2002","journal-title":"Journal of the American Statistical Association"},{"key":"pone.0306935.ref035","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1038\/s41581-018-0080-9","article-title":"Estimated GFR: time for a critical appraisal.","volume":"15","author":"E Porrini","year":"2019","journal-title":"Nat Rev Nephrol"},{"key":"pone.0306935.ref036","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12874-020-01022-x","article-title":"Using multiple agreement methods for continuous repeated measures data: a tutorial for practitioners.","volume":"20","author":"RA Parker","year":"2020","journal-title":"BMC Med Res Methodol"},{"key":"pone.0306935.ref037","first-page":"67","author":"D Bates","year":"2015","journal-title":"Fitting Linear Mixed-Effects Models Using lme4"},{"key":"pone.0306935.ref038","volume-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2019"},{"key":"pone.0306935.ref039","first-page":"525","article-title":"A simple, graphical method to evaluate laboratory assays","volume":"33","author":"JS Krouwer","year":"1995","journal-title":"Eur J Clin Chem Clin Biochem"},{"key":"pone.0306935.ref040","article-title":"Assessment of glomerular filtration rate, in Comprehensive Clinical NephrologySevent Edition.","author":"A. Lesley"},{"key":"pone.0306935.ref041","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1093\/ckj\/sfw070","article-title":"Iohexol plasma clearance for measuring glomerular filtration rate in clinical practice and research: a review. Part 1: How to measure glomerular filtration rate with iohexol?","volume":"9","author":"P Delanaye","year":"2016","journal-title":"Clin Kidney J"},{"key":"pone.0306935.ref042","first-page":"1","article-title":"Safety of Iohexol Administration to Measure Glomerular Filtration Rate in Different Patient Populations","volume":"140","author":"F Gaspari","year":"2018","journal-title":"A 25-Year Experience. Nephron"},{"key":"pone.0306935.ref043","first-page":"48","article-title":"Iohexol Clearance for the Determination of Glomerular Filtration Rate: 15 Years\u2019 Experience in Clinical Practice.","volume":"13","author":"P. Nilsson-Ehle","year":"2001","journal-title":"EJIFCC"},{"key":"pone.0306935.ref044","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1056\/NEJMoa2203769","article-title":"Cystatin C-Based Equation to Estimate GFR without the Inclusion of Race and Sex","volume":"388","author":"H Pottel","year":"2023","journal-title":"N Engl J Med"},{"key":"pone.0306935.ref045","article-title":"Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease","author":"KDIGO","year":"2012"},{"key":"pone.0306935.ref046","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1053\/j.ajkd.2015.08.020","article-title":"Discordance Between Iothalamate and Iohexol Urinary Clearances","volume":"67","author":"JC Seegmiller","year":"2016","journal-title":"American Journal of Kidney Diseases"},{"key":"pone.0306935.ref047","first-page":"955","article-title":"Plasma clearance of a new contrast agent, iohexol: a method for the assessment of glomerular filtration rate","volume":"104","author":"E Krutz\u00e9n","year":"1984","journal-title":"J Lab Clin Med"},{"key":"pone.0306935.ref048","first-page":"33","article-title":"Physicochemical properties and degree of protein binding of iopentol.","volume":"370","author":"K. Skinnemoen","year":"1987","journal-title":"Acta Radiol Suppl"},{"key":"pone.0306935.ref049","doi-asserted-by":"crossref","first-page":"1839","DOI":"10.1007\/s00467-006-0358-1","article-title":"Glomerular filtration rate measurement and estimation in chronic kidney disease","volume":"22","author":"GJ Schwartz","year":"2007","journal-title":"Pediatr Nephrol"},{"key":"pone.0306935.ref050","first-page":"35","article-title":"The use of iohexol clearance to determine GFR in patients with severe chronic renal failure\u2014a comparison between different clearance techniques.","volume":"43","author":"B Frennby","year":"1995","journal-title":"Clin Nephrol."}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0306935","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,17]],"date-time":"2024-07-17T17:29:29Z","timestamp":1721237369000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0306935"}},"subtitle":[],"editor":[{"given":"Emmanuel A.","family":"Burdmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2024,7,17]]},"references-count":50,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,7,17]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0306935","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,17]]}}}