Complex systems view of renal function and the role of the kidney in whole body physiology

Physiology has always taken a “complex systems” approach to the understanding of bodily function. This is especially true for renal physiology, given the mammalian kidney’s complicated anatomy, it’s many different cell types, and the intricate nephro-vascular relationships which vary in the different zones (cortex, outer medulla, inner medulla). The kidneys play a central role in whole-body salt and water balance (and hence regulation of blood pressure) and acid-base regulation thanks to several hormonal and nervous feedback systems that regulate renal blood flow, intra-renal blood distribution, and the transport of water and various salts and other solutes in the different segments of the nephron. At the cellular and molecular levels, we now know an enormous amount about the transporters, receptors, intra-cellular signaling cascades, and metabolism of the numerous different renal cell types. The functioning of individual nephron segments has been largely worked out thanks to techniques such as in vitro microperfusion, membrane vesicle studies, and modern sophisticated in vitro and in vivo imaging techniques. The anatomical details of nephro-vascular relationships have advanced greatly thanks to painstaking 3D reconstructions from thin serial slices of rat and mouse kidneys, which have in some instances overturned long-accepted concepts concerning, for instance, inner medullary solute and water counter-current exchange, central to the still unsolved problem of the mechanism underlying the medullary osmotic gradient responsable for urine concentration.