Postnatal Renal Development

Renal Blood Flow

The renal blood flow in the adult human is 660 ml/min which is 20–25% of the cardiac output. In contrast, the fetal kidney receives only 2% of the cardiac output from mid-gestation to term. The developmental increase in renal blood flow is due in part to an increase in cardiac output, but predominantly to a decrease in renal vascular resistance. When corrected for a body surface area of 1.73 m ² , the human neonate has a renal blood flow of only 15–20% of that measured in adults. Renal blood flow doubles in the first month of life, and is comparable to adults by one to two years of age when corrected for body surface area. The maturational changes in renal vascular resistance are due to anatomical changes in the renal vasculature, as well as changes in the balance between vasoconstrictors, such as catecholamines and angiotensin II, and vasodilators, such as nitric oxide. The kidney develops in a centrifugal fashion. Juxtamedullary nephrons are formed before those in the superficial cortex. The renal blood flow distribution, measured by both xenon washout and injection of microspheres, shows a paucity of blood flow to the outer cortex compared to the deep cortex in neonates. During postnatal maturation there is a redistribution of blood flow, with enhanced perfusion of the outer cortex due to a decrease in renal vascular resistance.

Autoregulation

Renal blood flow (RBF) and glomerular filtration rate (GFR) remain stable over a wide range of perfusion pressures. As perfusion pressure falls there is vasodilatation of the afferent arteriole and vasoconstriction of the efferent arteriole which maintains RBF and GFR. As blood pressure increases during development, the range in pressure where autoregulation of renal blood flow and GFR occurs shifts accordingly. While neonates can autoregulate GFR in response to changes in blood pressure, this protective mechanism is far less developed than the autoregulatory capability of adults due, at least in part, to an attenuated release and efferent arteriolar response to angiotensin II.

Glomerular Filtration Rate

Initiation of glomerular filtration, as evidenced by the flow of urine, begins between nine and twelve weeks gestation in the human. The glomerular filtration rate (GFR) is lower in neonates than adults, even when corrected for body surface area. In premature human infants creatinine clearance increases as a function of postconceptual age (the sum of gestational age and postnatal age). GFR is constant at ~0.5 ml/min in infants with a postconceptional age of 28–34 weeks, despite the increase in renal size. GFR increases to 1.0 ml/min at 34–37 weeks and to 2 ml/min at a postconceptional age of 40 weeks. In absolute terms, the GFR increases 25-fold from birth to adulthood. Corrected for a surface area of 1.73 m ² , the GFR in the human term neonate is 30 ml/min/1.73 m ² in the first week of life. GFR continues to increase during the first ~1–2 years of life to reach adult levels when factored for body surface area ( Figure 27.1 ).

At birth, juxtamedullary glomeruli have a larger volume and greater single nephron GFR than superficial nephrons. In the guinea pig there is a 7-fold increase in GFR in the first month of life. The increase in total kidney GFR during the first week of life, a time when superficial nephron GFR is relatively constant, is predominantly due to an increase in juxtamedullary nephron GFR. After two weeks of age, however, the rise in total kidney GFR is predominantly due to an increase in GFR in superficial nephrons ( Figure 27.2 ).

The increase in single nephron GFR with postnatal maturation is due to a number of factors. Single nephron GFR is the product of the net ultrafiltration pressure and the glomerular ultrafiltration coefficient, K _f . The effective ultrafiltration pressure is the difference between the hydrostatic and oncotic pressures across the glomerular capillary bed. Studies comparing newborn rats and guinea pigs to adults have shown a maturational increase in effective ultrafiltration pressure. However, these changes contribute at most 10% to the 20-fold increase in single nephron GFR. The maturational increase in GFR is predominantly the result of the increase in K _f , which is the product of the hydraulic permeability of the glomerular capillary and the glomerular capillary surface area. Studies using neutral dextrans have found that the permeability characteristics change only slightly with maturation. The increase in K _f , and thus single nephron GFR, is predominately due to the 7.5-fold increase in glomerular capillary surface area during renal maturation.

Glomerulotubular Balance

Glomerulotubular balance remains fairly constant under a number of conditions which alter the GFR in the adult. During postnatal development, the maturational increase in the GFR is paralleled by a concomitant increase in the rate of tubule solute absorption. If this did not occur, there would be loss of essential solutes which would jeopardize the life of the neonate as GFR increases during development.

In the fetus, however, the GFR and delivery of solutes and water to the tubules can surpass the reabsorptive capacity of the tubules. In a clearance study examining the fractional reabsorption of volume and sodium after salt-loading in fetal, young, and adult guinea pigs, the fractional reabsorption of volume and sodium were lower in the fetus and in one-day-old animals. By 2–5 days of age, the fractional reabsorption of sodium and water were at the adult level. The glomerular–tubular imbalance is not only present in the fetus, but can also be manifest in the premature neonate. This is exemplified by the fact that glucosuria is frequently present in premature human neonates born before 30 weeks of gestation. In human neonates born before 34 weeks gestation, 93% of the filtered glucose is reabsorbed, which is comparable to the fractional reabsorption in the guinea pig fetus. By 34 weeks of gestation, the human neonate can reabsorb over 99% of the filtered glucose load.

Maturation of Proximal Tubule Volume Reabsorption

The developing kidney exhibits a centrifugal pattern of nephron maturation, with juxtamedullary nephrons being formed before superficial nephrons. The glomerular and tubular morphology of juxtamedullary nephrons are more mature than those in the superficial cortex. In many species, including the mouse, rat, and rabbit, nephrogenesis continues after birth in the superficial cortex. Nephrogenesis also continues postnatally in humans born prior to 34 weeks gestation.

The reabsorptive capacity of the neonatal superficial and juxtamedullary proximal tubule is less than that of adults. The rate of volume absorption in superficial proximal convoluted tubules increases two-fold between a 22–24-day-old weanling and a 40–45-day-old adult rat. In rabbit superficial proximal tubules the rate of volume absorption increased four-fold between one week and one month of age, while the rate of volume absorption in rabbit juxtamedullary proximal convoluted tubules did not change appreciably during that time. However, there is a two-fold increase in volume absorption in juxtamedullary nephrons between 4 and 6 weeks of age in the rabbit. Proximal tubule transport for each solute is the sum of transport mediated by passive diffusion, solvent drag, and active transport, which are discussed below.