Vitamin B12 uptake in dog kidney: its use as an extracellular reference marker

The renal handling of [3H]cyanocobalamin has been investigated in dogs in vivo using the pulse injection multiple-indicator dilution technique. Simultaneous renal vein and urine outflow curves were obtained for [3H]cyanocobalamin relative to T-1824-albumin (plasma reference) and creatinine (extracellular reference). The renal vein recovery of [3H]cyanocobalamin relative to creatinine was significantly less than unity and increased with increasing intraarterial dose. This indicates a saturable postglomerular uptake mechanism. The urine recovery of [3H]cyanocobalamin relative to simultaneously filtered creatinine is also less than unity and increases with increasing intra-arterial doses. This indicates a saturable interaction at the luminal surface of the nephron. Saturation interaction at the luminal surface of the nephron. Saturation of postglomerular and luminal interactions can also be achieved by systemic preloading with unlabeled vitamin B12. After saturation the renal vein and urine recoveries for [3H]cyanocobalamin and creatinine become equal. However, significant differences can be observed between their renal vein mean transit times, depending on experimental conditions. During hydropenia [3H]cyanocobalamin behaves as a true extracellular marker and emerges in renal vein and urine outflows, superimposing on creatinine. During mannitol diuresis vitamin B12 still behaves as a glomerular marker, but its renal vein mean transit time is now significantly less than that of creatinine and its calculated postglomerular volume of distribution is reduced by approximately 15% of the available interstitial space.