Abstract
Primitive emunctory functions to expel harmful substances from cells and the interstitial space of multicellular organisms evolved over the past billion and a half years into the complex physiology of the metanephric kidney. Integrative biology allows empirical testing of hypotheses of the origins of renal structures from homologous single-celled precursors. Emunctory cell complexes called nephridia evolved in metazoan (cnidarian) ancestors 750 million years ago (mya). The pronephric kidney was a metameric structure that evolved some 700 mya in early bilaterians to excrete waste products through nephridial slits in the body wall from head to tail. The mesonephric kidney evolved 635 mya when pharyngeal slits differentiated into filter-feeding gills and a heart-kidney evolved in later bilaterians. The mesonephric filtering glomeruli lost their external exits through the body wall and now drained through an internal mesonephric duct into the coelom. When chordates moved into fresh water from the sea 588 mya the high-pressure glomerulus evolved in the mesonephros, increasing water excretion. Tetrapods moved onto land losing the buoyancy of water. Blood pressure and glomerular filtration rose and the metanephric kidney evolved in amniotes. The high pressure-flow glomerulus predisposes podocytes to injury and detachment leading to sclerosis, whereas the high mitochondrial activity of the tubule contributes to susceptibility to ischemia, hypoxia, and oxidative injury. The kidney evolved a counter-current mechanism and urea cycle to optimize water retention. Perturbations in the complex development of the metanephric kidney, which parallels its phylogeny, explain many renal pathologies, which are traceable to these adaptations.