Permeability of materials in postglomerular capillary bed and distribution to interstitium of kidney in rats

Extracellular reference materials are necessary to estimate tubular transport parameters for drugs which are secreted in the kidney. They must set up the flow-limited distribution between plasma and interstitial space, not be distributed to the intracellular space, and be nondegradable in the extracellular space. The capillary permeability of various molecular weight markers in the post glomerular circulation was investigated by performing pulse-injection multiple indicator dilution experiments on isolated rat kidney, using simultaneous injection of T1824-labeled albumin (the plasma reference) and creatinine (or inulin) as the extracellular reference materials. The permeability constants and the gamma values (ratio of the volume in the space of interstitium to that of capillary plasma) for creatinine and inulin were calculated by a nonlinear least squares regression. The gamma values for creatinine were greater than those for inulin, implying that the volume of distribution for creatinine is different from that for inulin. The capillary permeability clearance (CLinflux) for creatinine was 4 times higher than that of inulin, and was 3 times greater than the perfusion rate. Thus, creatinine satisfies the qualification for the flow-limited distribution between plasma and interstitial space. These findings suggest that in the rat kidney creatinine is more suitable for the extracellular reference material than inulin.