Why do newborn infants have a high plasma creatinine?

Background. Plasma creatinine (Pcr) levels at birth are greatly elevated in relation tb the size (and the muscle mass) of the newborn infant and remai n so for 1 to 2 weeks, particularly intriguing is the fact that Pcr levels are higher in preterm than in term infants and for a longer postnatal perio d. The smaller the birth weight, the higher the Pcr. This cannot be explain ed by maternal transfer of Pcr or by the absolute and relative (to adult bo dy surface area) reduced glomerular filtration rate of the newborn. Perhaps the renal handling of creatinine is involved. Design. In 522 pairs of mothers and fetuses, maternal and fetal Per were co mpared from 16 weeks of gestation until term. Per was measured in 66 newbor ns of various birth weights and followed for 1 month. Creatinine clearance (Ccr) and inulin clearance (Cin) were measured simultaneously in adult (n = 8) and newborn (n = 20) New Zealand White rabbits. In the latter, nephroge nesis continues after birth and they are therefore a good animal model for the study of the renal function in premature infants. Patient. A case of a premature male infant is presented (gestation: 29 week s; birth weight: 1410 g) suspected of having sepsis because of premature ru pture of membranes and postpartum maternal fever. This suspicion was not co nfirmed, blood chemistry evaluation showed a high Per at birth (0.85 mg/dL, 75 mu mol/L), even higher than that of the mother (0.77 mg/dL, 68 mu mol/L ). The Pcr started to decrease after similar to 1 week but remained elevate d throughout 1 month of follow-up. Results. From the maternal-fetal Pcr measurements it was quite evident that during the second half of gestation the small molecular weight creatinine (113 dalton, 0.3 nm radius) of the mother and fetus equilibrates at all mat ernal Pcr levels. The newborn Pcr levels were not only high at the time of birth but remained so for more than 3 weeks. It was also shown that the sma ller the infant the higher the Pcr levels. The results of the animal experi mental data showed that adult rabbits had the normal physiologic pattern in which Ccr overestimates Cin (Ccr/Cin ratio >1.0). In contrast, the results in the newborn rabbits showed an unexpected underestimation of the Ccr vis -a-vis Cin (Ccr/Cin ratio <1.0). This means, as is explained at length in t he "Discussion" of this article, that the preterm newborn infant reabsorbs creatinine along the renal tubule. Conclusion. The riddle of the high Pcr levels in term and particularly in p reterm newborns seems to be solved. Once the umbilical cord is severed, the perfect intrauterine maternal-fetal biochemical balance is disturbed. Ther eafter, the already transferred exogenous, adult-level creatinine will rapi dly disappear in the first urine specimens passed by the now autonomous new born infant. A new steady state is achieved in due time, based on independe nt neonatal factors. One of these factors is the unusual occurrence of tubu lar creatinine reabsorption. We hypothesize that this latter temporary phen omenon is attributable to back-flow of creatinine across leaky immature tub ular and vascular structures. With time, maturational renal changes will im pose a barrier to creatinine. From that point onwards, total body muscle ma ss, glomerular filtration rate, and tubular secretion will in health determ ine the Pcr level of the individual.