Sergio Luis-Lima1, Flavio Gaspari2, Natalia Negrín-Mena1, Fabiola Carrara2, Laura Díaz-Martín1, Alejandro Jiménez-Sosa1, Federico González-Rinne1, Armando Torres3,4, Esteban Porrini4. 1. Research Unit Department, Hospital Universitario de Canarias, Tenerife, Spain. 2. Renal Medicine Department, IRCCS- Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases 'Aldo & Cele Daccò', Ranica (BG), Italy. 3. Nephrology Department, Hospital Universitario de Canarias, Tenerife, Spain. 4. Dermatology, Medicine and Psychiatry Department, Clinical Medicine Department, Instituto de Tecnologías Biomédicas (ITB), Faculty of Medicine, Universidad de La Laguna, Tenerife, Spain.
Abstract
Background: Renal function can be estimated with formulas, which are inaccurate, or measured with gold standard methods, which are reliable but unpractical. We propose to simplify the plasma clearance of iohexol, a gold standard method to measure renal function, by dried blood spot (DBS) testing. Methods: We compared glomerular filtration rate (GFR) values assessed by DBS and the reference plasma analysis technique. We tested in vitro the agreement between non-volumetric and volumetric DBS with the reference technique. Then, we performed a clinical validation in vivo between volumetric DBS and plasma analysis in 203 patients. The agreement was evaluated with the concordance correlation coefficient (CCC), the total deviation index (TDI) and the coverage probability. We defined acceptable agreement as a TDI <10%. Results: In the in vitro studies, the non-volumetric DBS showed moderate agreement, TDI = 26.0%, while the volumetric method showed better but insufficient agreement, TDI = 13.0%, with the reference method in plasma. The non-volumetric DBS was rejected. To improve the agreement of the volumetric DBS, iopamidol was used as an internal standard. This method showed acceptable agreement, TDI = 9.0% with the analysis in plasma, and was selected as the definitive DBS method. In the in vivo studies, the agreement between the final DBS method and the reference technique was acceptable: TDI = 9.5%. This indicates that 90% of the GFR values ranged from -9.5% to + 9.5% compared with the reference method. Conclusions: We simplified the plasma clearance of iohexol using DBS without losing accuracy and precision with respect to the reference technique. This may facilitate the use of a reliable determination of renal function to the medical community.
Background: Renal function can be estimated with formulas, which are inaccurate, or measured with gold standard methods, which are reliable but unpractical. We propose to simplify the plasma clearance of iohexol, a gold standard method to measure renal function, by dried blood spot (DBS) testing. Methods: We compared glomerular filtration rate (GFR) values assessed by DBS and the reference plasma analysis technique. We tested in vitro the agreement between non-volumetric and volumetric DBS with the reference technique. Then, we performed a clinical validation in vivo between volumetric DBS and plasma analysis in 203 patients. The agreement was evaluated with the concordance correlation coefficient (CCC), the total deviation index (TDI) and the coverage probability. We defined acceptable agreement as a TDI <10%. Results: In the in vitro studies, the non-volumetric DBS showed moderate agreement, TDI = 26.0%, while the volumetric method showed better but insufficient agreement, TDI = 13.0%, with the reference method in plasma. The non-volumetric DBS was rejected. To improve the agreement of the volumetric DBS, iopamidol was used as an internal standard. This method showed acceptable agreement, TDI = 9.0% with the analysis in plasma, and was selected as the definitive DBS method. In the in vivo studies, the agreement between the final DBS method and the reference technique was acceptable: TDI = 9.5%. This indicates that 90% of the GFR values ranged from -9.5% to + 9.5% compared with the reference method. Conclusions: We simplified the plasma clearance of iohexol using DBS without losing accuracy and precision with respect to the reference technique. This may facilitate the use of a reliable determination of renal function to the medical community.
Authors: Sergio Luis-Lima; Tomás Higueras Linares; Laura Henríquez-Gómez; Raquel Alonso-Pescoso; Angeles Jimenez; Asunción María López-Hijazo; Natalia Negrín-Mena; Candelaria Martín; Macarena Sánchez-Gallego; Sara Judith Galindo-Hernández; Raquel Socas Fernández Del Castillo; Manuel Castilla-Marrero; Santiago Domínguez-Coello; Vanesa Vilchez de León; Rafael Valcárcel-Lopez; Nerea Insausti-Garmendia; Beatriz Escamilla; Sara Estupiñán; Patricia Delgado-Mallén; Ana-María Armas-Padrón; Domingo Marrero-Miranda; Ana González-Rinne; Rosa María Miquel Rodríguez; María Angeles Cobo-Caso; Laura Díaz-Martín; Federico González-Rinne; Alejandra González-Delgado; Marina López-Martínez; Alejandro Jiménez-Sosa; Armando Torres; Esteban Porrini Journal: J Clin Med Date: 2019-09-26 Impact factor: 4.241
Authors: Ana Elena Rodríguez-Rodríguez; Sergio Luis-Lima; Javier Donate-Correa; Laura Diaz-Martín; María Rosa Arnau; Alejandro Jiménez-Sosa; Flavio Gaspari; Alberto Ortiz; Esteban Porrini Journal: Sci Rep Date: 2021-02-25 Impact factor: 4.379