We investigated the process of neonatal hyperprolinuria in dog and rat. Plasma proline varied only 2-fold in the puppy whereas prolinuria increased up to 12-fold from birth to the 10th day declining thereafter to reach adult values (< 0.1 μmole/mg creatinine) by the third wk. Stop-flow analysis in puppies (< 17 days old, n= 3) and one adult dog revealed that backflux of proline in distal nephron is not the source of neonatal hyperprolinuria. Prolinuria occurs in the Long-Evans rat pup during the first postnatal wk. We measured net uptake of L-proline at low (0.2 mM) and high (5 mM) concentrations by tubule fragments prepared from newborn and adult kidneys. At both concentrations and at initial rates, uptake was similar in newborn and mature tubules; at or near steady-state, tubules of newborn kidney had greater net uptake relative to mature kidney, apparently because efflux is attenuated. A difference in metabolic runout did not explain the difference in proline uptake by newborn kidney. Tubules from pups less than 7 days old did not exclude the competitive inhibitor AIB from interacting with proline during uptake at 0.2 mM when compared with mature kidney,(p= 0.005). These findings imply that transport of proline on the previously described proline-preferring high-affinity system is deficient in proximal nephron of newborn kidney.

Speculation: Maturation of proline reabsorption after birth requires 1 wk in the rat, about 1 month in the dog and 3 months or more in man. Deficient activity during these intervals on one among several carriers in brush-border and basal-lateral membranes in proximal tubule segments is sufficient to explain neonatal hyperprolinuria.