title: Simplified Method to Measure Glomerular Filtration Rate by Iohexol Plasma Clearance in Conscious Rats.
abstract: OBJECTIVE
  Glomerular filtration rate (GFR) is the best index for evaluating renal function. We aimed to develop a simplified iohexol plasma clearance procedure for GFR measurement in rats without urine collection, animal catheterization or anesthesia, with limited sampling and requiring blood instead of plasma, to further reduce the sample volume and improve animal welfare.
  
  
  METHODS
  After iohexol injection (129.4 mg), samples were drawn according to 2-compartment kinetics and analyzed by high performance liquid chromatography. Healthy male Lewis rats were used to find a correction factor (CF) to obtain the 'reference clearance' from the simplified 1-comparment model. This approach was validated using male or female (Lewis, Sprague-Dawley) rats and animals with renal mass reduction (RMR). In additional rats, different simplified approaches were evaluated.
  
  
  RESULTS
  Iohexol concentrations in blood and plasma strongly correlated (r = 0.9784, p < 0.0001). A CF of 0.90 enabled the calculation of the reference GFR. Validation results in male Lewis rats were 0.99 ± 0.27 for the reference GFR and 1.03 ± 0.29 ml/min/100 g for the simplified approach. Results in female Sprague-Dawley rats confirmed the suitability of the proposed method. In RMR rats, GFR was 0.14 ± 0.05 and 0.14 ± 0.04 ml/min/100 g for the reference and simplified model, respectively.
  
  
  CONCLUSIONS
  The procedure we set up to measure GFR in conscious rats was proven to be reliable, required a small volume of blood at only 4 selected time points, without the need to collect urine or catheterize the animals, was applicable to rats from different strains and sexes, both healthy and with renal function impairment. Moreover, the procedure enables the monitoring of GFR changes over time in the same animal, thereby reducing the number of animals to be used.
authors.affiliation: Clinical Research Center for Rare Diseases x2018;Aldo and Cele Daccx00F2;', IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Bergamo, Italy.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Carrara
authors.forename: Nadia
authors.initials: N
authors.lastname: Azzollini
authors.forename: Giovanni
authors.initials: G
authors.lastname: Nattino
authors.forename: Daniela
authors.initials: D
authors.lastname: Corna
authors.forename: Sebastian
authors.initials: S
authors.lastname: Villa
authors.forename: Domenico
authors.initials: D
authors.lastname: Cerullo
authors.forename: Carlamaria
authors.initials: C
authors.lastname: Zoja
authors.forename: Beatriz
authors.initials: B
authors.lastname: Abrante
authors.forename: Sergio
authors.initials: S
authors.lastname: Luis-Lima
authors.forename: Esteban
authors.initials: E
authors.lastname: Porrini
authors.forename: Antonio
authors.initials: A
authors.lastname: Cannata
authors.forename: Silvia
authors.initials: S
authors.lastname: Ferrari
authors.forename: Matteo
authors.initials: M
authors.lastname: Fois
authors.forename: Nadia
authors.initials: N
authors.lastname: Stucchi
authors.forename: Flavio
authors.initials: F
authors.lastname: Gaspari
mesh_terms: D000818:Animals; D005260:Female; D005919:Glomerular Filtration Rate; D007472:Iohexol / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley
chemical_list: D007472:Iohexol