Chronic kidney disease (CKD) is a condition in which an initial injury is superseded by a more gradual, chronic process of decreasing function that, in the most extreme cases, ultimately leads to the need for renal replacement therapy. An important consideration is that, while the initiating causes are quite varied, as CKD progresses the mechanisms involved become increasingly similar, so that eventually a set of common events contributes to inexorable loss of functional nephron mass. The mechanisms that are involved can be described as those that disrupt normal renal physiology and those by which decreasing structural integrity renders such disruption irreversible. Thus, the key to understanding progression is examining how function becomes dysregulated and how this dysfunction interacts with the process of renal scarring. This chapter will review these mechanisms.
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