title: Development of renal function tests for measurement of urine concentrating ability, urine acidification, and glomerular filtration rate in female cynomolgus monkeys.
abstract: This study was conducted to develop tests for evaluation of uri ne concentratingability, urine acidification ability, an dglomerular filtration rate in cynomolgus macaques. In female cynomolgus macaques, baseline urine specific gravity ranged from 1.005 to 1.031, and urine osmolality ranged from 182 to 1081 mOsm/kg. A dose of 0.4 microg/kg desmopressin acetate resulted in a urine specific gravity that ranged from 1.019 to 1.043 and an osmolality that ranged from 432 to 1298 mOsm/kg. Desmopressin acetate administration increased urine specific gravity and osmolality in each animal evaluated. Baseline urine pH in these animals ranged from 6.4 to 8.2. A dose of orally administered ammonium chloride (0.1 g/kg) resulted in a urine pH that ranges from 4.1 to 7.1. Ammonium chloride administration decreased urine pH in each animal tested. Evaluation of glomerular filtration rate was accomplished through urine collection and timed blood and urine samples after oral hydration with 0.45% sodium chloride. Blood samples were analyzed for creatinine, osmolality, sodium, potassium, and chloride. Urine samples were analyzed for volume, creatinine, osmolality, sodium, potassium, and chloride. Creatinine clearance, osmolality clearance, and electrolyte fractional clearance were calculated from the values. Osmolality clearance ranged from 0.03 to 0.07 ml/kg/min, creatinine clearance ranged from 1.84 to 2.53 ml/kg/min, fractional excretion of sodium ranged from 0.17% to 0.77%, fractional excretion of potassium ranged from 4.46% to 19.87%, and fractional excretion of chloride ranged from 0.25% to 1.08%. The response to desmopressin acetate and ammonium chloride and the osmolality, creatinine concentration, and fractional electrolyte excretion were consistent in individual animals with repeat testing. No adverse events were associated with the tests. The results of these tests are consistent with repeat testing in individual animals. These tests likely can be used for clinical assessment of renal function in cynomolgus macaques or for collection of experimental data.
authors.affiliation: Department of Comparative Medicine, Lilly Research Laboratories, Eli Lilly and Co., Inc., Greenfield, Indiana 46140, USA.
authors.forename: L Bruce
authors.initials: LB
authors.lastname: Weekley
authors.forename: Ahmed
authors.initials: A
authors.lastname: Deldar
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tapp
mesh_terms: D000818:Animals; D005260:Female; D005919:Glomerular Filtration Rate / Q000662:veterinary*; D007668:Kidney / Q000502:physiology*; D007671:Kidney Concentrating Ability / Q000502:physiology*; D007677:Kidney Function Tests / Q000662:veterinary*; D008252:Macaca fascicularis / Q000502:physiology*; D014556:Urine / Q000737:chemistry*