Kidneys are the central regulators of organismal homeostasis. These organs filter enormous amounts of fluid from plasma; excrete toxic waste products; maintain salt, water, and volume balance; coordinate blood pressure regulation; and maintain the acid-base equilibrium essential for life. Although it has been known for decades that renal glomeruli serve as the site of plasma ultrafiltration and urine production, both the molecular design and function of the kidney filtration barrier have remained elusive. Indeed, the past two decades have witnessed enormous breakthroughs in our fundamental understanding of kidney filtration and the critical role that podocytes, specialized terminally differentiated epithelial cells at the glomerular capillaries, fulfill in the function of the kidney filtration barrier. Here we discuss recent advances in this field that will change the way we think about plasma ultrafiltration in health and proteinuria as a manifestation of glomerular diseases.
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