Biliary and Total Extrarenal Clearance of Inulin and Iohexol in Pigs

Abstract

Biliary clearance, total extrarenal clearance, body and renal clearance of inulin and iohexol were determined in 11 normal and 11 nephrectomized pigs. The biliary clearance of inulin, calculated as biliary excretion divided by the plasma concentration, was 0.04 and 0.01 ml min^–1 10 kg^–1 and of iohexol 0.21 and 0.1 ml min^–1 10 kg^–1 , in normal, respectively, nephrectomized pigs (p < 0.05). The extrarenal clearance of inulin, calculated as body minus renal clearance, was 2.7 and 0.7 ml min^–1 10 kg^–1 and of iohexol 3.7 and 0.7 ml min^–1 10 kg^–1 in normal, respectively, nephrectomized pigs (p < 0.05). Some hours after injection of the markers their plasma concentrations were much higher in the nephrectomized pigs. This higher plasma concentration was not matched by an equally higher biliary excretion and therefore biliary clearance decreased. The smaller total extrarenal clearance in nephrectomized pigs, i.e. the overestimation of GFR when calculated as body clearance, indicates that this source of error decreases with decreasing renal function.

Clinical Implications of Estimating Glomerular Filtration Rate with Three Different Equations among Older People. Preliminary Results of the Project “Screening for Chronic Kidney Disease among Older People across Europe (SCOPE)”

“…Thus, we cannot draw any definitive conclusion about the diagnostic accuracy of the study equations against a gold standard assessment. Indeed, experimental evidence suggests that intravenous inulin and iohexol may partially undergo extrarenal clearance [42,43], which may represent a not negligible potential source of error when measuring GFR for developing or validating eGFR equations. Nevertheless, the amount of extrarenal clearance of GFR markers in humans is unknown and is worthy of future investigations.…”

Nephrectomized and Hepatectomized Animal Models as Tools in Preclinical Pharmacokinetics

“…Glomerular filtration rate has been studied in nephrectomized mice by the means of inulin clearance, and as expected, both GFR and inulin clearance were found to be abolished . However, conflicting findings have also been reported . As a pharmacokinetic model, nephrectomy can be used to assess renal and extrarenal clearance.…”

“…Nephrectomy has been used as a model of acute renal failure , whereas partial nephrectomies, typically 5/6 nephrectomies, have been used to study chronic renal failure . Nephrectomy models have also been used in metabolism and clearance studies . Rats and mice are most commonly used for nephrectomy, but other species have also been employed (table ).…”