Monday, November 5, 2007

Kidney Development and the Recapitulation Theory

The Recapitulation Theory. A debunked postulate first popularized in the middle of the nineteenth century, the recapitulation theory famously states that "ontogeny recapitulates phylogeny." Simply put, during development, the human embryo was thought to fully repeat its evolutionary development. A human embryo would climb out of the primordial ooze, so to speak, and pass through different phases of evolution on its way to becoming a grown fetus. This recapitulation of "lower" forms is commonly demonstrated by comparing embryos at various ages between species, from fish to reptile to mammal, and seeing the similar morphology of the embryos. Granted, this theory has long since been rejected. However, I think it has provides an interesting lens through which to view the development of the kidneys.

Over the course of development, we actually have three different pairs of kidneys, which all have parallels to a different evolutionary form. The most basic of these is the pronephros, which is the most rostral (closest to the head) of the kidneys and is a functioning kidney in immature fish and amphibians. In mammals, however, it doesn't seem to do much but serve as a transitory structure before the mesonephros, the second kidneys, develop during the 4th week. The mesonephros is similar to the functioning kidney in adult amphibians, and is functional in birds and reptiles until they hatch. The mesonephros in mammals is a rudimentary, functional kidney--it has glomeruli, which are the filtering units, and which drain into the mesonephric, or Wolffian, duct, running through the center of the mesonephric tissue. This duct is the great legacy of the mesonephros, because near the distal end it sprouts a little bud, called the ureteric bud, which stimulates the metanephrogenic blastema (the precursor to the kidney) during the 5th week to form the metanephros, the third and final kidney. This metanephros will become the bean shaped organ we have all grown fond of, and then rise upward out of the pelvis and to the costovertebral angle as the fetus grows.

It is easy to see how this process apparently recapitulates lower evolutionary forms, going from amphibian to avian to a final mammalian state, and yet further inquiry has shown that this is not exactly true and that while these are important developmental stages, a human fetus does not undergo all steps of evolution during its time in the womb. What I find fascinating is how two distinct parts of this system, the ureteric bud and the metanephrogenic blastema, interact so precisely to create a connection for the kidneys. The ureteric bud induces the metanephrogenic mesenchyme to form the nephric tubules, the DCT, loop of Henle, PCT, and Bowman's capsule. This mesenchyme reciprocally acts on the ureteric bud causing it to branch and form a tree-like system of collecting ducts. Many growth factors are involved in this nephrogenesis, but of interest is the role of angiotensin II, a vasoconstrictor that interacts with the kidney to help regulate blood pressure. Angiotensin II is often blocked with ACE inhibitor or angiotensin receptor blocker (ARB) medications in people who have hypertension, effectively lowering blood pressure. Recent studies suggest that angiotensin, by interacting with receptors on the ureteric bud, stimulates branching morphogenesis as well as collecting duct elongation and papillogenesis. Therefore, patients are taken off of ACE inhibitors and ARBs when pregnant, because there can be failure of the ureteric bud to stimulate correct nephrogenesis and a wide array of kidney defects may result.

Although the recapitulation theory is defunct, there is something to be said for thinking of the kidneys evolutionarily, since they allow us to concentrate our urine, and regulate body water, so that we can live on land in the first place. An impressive feat, given the extensive multistep process it takes for a single adult kidney to develop.