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Renal function evaluation in an integrative cardio‐renal pharmacology model using Culex Empis® automated drug infusion system and radio telemetry

Recently we showed utility of a novel integrative pharmacology system (CUlex TElemetry: CUTE) that allows simultaneous evaluation of CNS/CV/Renal functions with automated blood sampling in the same rat. To evaluate potential risk of drug‐induced renal and cardiac dysfunction, or their bidirectional effects, a new procedure was developed for simultaneous estimation of heart and global renal function. Briefly, inulin‐FITC (2.5 mg/mL) and p‐aminohippuric acid (PAH; 40 mg/mL) were continuously co‐administered (i.v., 0.5 mL/hour) in conscious, unrestrained Han Wistar rats using Empis® automated drug infusion system combined with CUTE. Steady state was reached after 60 min, and 11 blood samples were collected over the next 3 days. Plasma clearance of inulin and PAH were determined using Fick's principle (renal clearance = infusion rate/plasma level). There were no significant differences in estimated glomerular filtration rate (eGFR) between plasma clearance (0.95 ± 0.05) vs. reference urinary clearance method (1.07 ± 0.14 mL/min/100g BW). Mean blood pressure (102.6 ± 3.54 mmHg) and heart rate (422.9 ± 8.26 bpm) were not altered by infusion of markers for 3 days. This new approach allows simple, rapid and reproducible evaluation of renal function with respect to traditional procedures, making it a useful model for preclinical cardio‐renal safety assessment.