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Renal Morphogenesis


Renal morphogenesis is a complex, temporally and spatially regulated 3-dimensional stochastic process by which precursor cells develop into a structurally and functionally normal kidney. Abnormal or dysregulated renal morphogenesis results in a wide range of renal abnormalities including renal agenesis, dysplasia, hypoplasia, and structural anomalies such as ectopic kidneys, fused kidneys, duplicated collecting systems, and vesicoureteral reflux; these are collectively known as congenital anomalies of the kidney and urinary tract (CAKUT). Together they comprise the most common cause of end-stage renal disease (ESRD) in children. It is likely that more subtle forms of abnormal renal morphogenesis contribute to the development of chronic kidney disease (CKD), ESRD, and “essential” hypertension in the adult population, although this hypothesis remains unproven. Much of our understanding of the complexities of renal morphogenesis comes from either experiments of nature, ie, naturally occurring genetic mutations linked with specific forms of CAKUT (see Chapter 465), or from decades of investigation using in vitro or in vivo model systems. With the advent of modern molecular targeting techniques, murine models and human culture systems have revolutionized our understanding of renal morphogenesis using tissue, cell, and temporal-specific gene modification. The regulation of renal morphogenesis spans the entire spectrum of human biology from transcriptional regulation, intracellular signaling, paracrine and autocrine responses, cell-cell induction, repression, epigenetic modification, and even environmental factors.


In humans, renal morphogenesis begins at approximately 3 weeks of gestation with the formation of the initial urinary excretory precursor, the pronephros, followed by the mesonephros at 4 weeks and the metanephros at 5 weeks. These structures arise from the intermediate mesoderm. By 32 to 34 weeks of gestation, nephrogenesis is complete, and the structural and functional relationships of each nephron segment are fully developed. The human kidney continues to grow after 34 weeks of gestation, but this occurs by growth and maturation of existing nephrons, rather than formation of new nephrons. On average, 1,000,000 (range 200,000–2,700,000) individual nephrons in each kidney arise from a few embryonic precursor cells. Each individual nephron is a structurally and functionally distinct system consisting of a vascularized glomerulus—afferent and efferent arterioles, mesangial cells with supporting matrix, parietal epithelial cells lining Bowman’s capsule, specialized endothelial and epithelial cells, and a filtration barrier comprised of podocyte-derived slit processes and glomerular basement membrane (GBM)—connected to series of contiguous, sequential, specialized tubular epithelial cell segments whose function is critically dependent on the precise spatial and structural development of the tubular segments that precede and follow it. Finally, the nephron segments are supported by a vascularized parenchyma consisting of interstitial cells and extracellular matrix. Thus, disturbances in the normal processes of renal morphogenesis can result in both functional as well as structural abnormalities.

The pronephros, the first transient urinary structure arising from the intermediate mesoderm, appears at 3 weeks of gestation. Located in the cervical region of the embryo, this rudimentary structure consists of ...

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