Chronic kidney disease (CKD) encompasses a spectrum of different pathophysiologic processes associated with abnormal kidney function and a progressive decline in glomerular filtration rate (GFR). Table 280-1 provides a widely accepted classification, based on guidelines of the National Kidney Foundation [Kidney Dialysis Outcomes Quality Initiative (KDOQI)], in which stages of CKD are defined according to the estimated GFR.

Table Graphic Jump Location
Table 280-1 Classification of Chronic Kidney Disease (CKD) 

The term chronic renal failure applies to the process of continuing significant irreversible reduction in nephron number and typically corresponds to CKD stages 3–5. The pathophysiologic processes and adaptations associated with chronic renal failure will be the focus of this chapter. The dispiriting term end-stage renal disease represents a stage of CKD where the accumulation of toxins, fluid, and electrolytes normally excreted by the kidneys results in the uremic syndrome. This syndrome leads to death unless the toxins are removed by renal replacement therapy, using dialysis or kidney transplantation. These latter interventions are discussed in Chaps. 281 and 282. End-stage renal disease will be supplanted in this chapter by the term stage 5 CKD.


Pathophysiology of Chronic Kidney Disease


The pathophysiology of CKD involves two broad sets of mechanisms of damage: (1) initiating mechanisms specific to the underlying etiology (e.g., genetically determined abnormalities in kidney development or integrity, immune complex deposition and inflammation in certain types of glomerulonephritis, or toxin exposure in certain diseases of the renal tubules and interstitium) and (2) a set of progressive mechanisms, involving hyperfiltration and hypertrophy of the remaining viable nephrons, that are a common consequence following long-term reduction of renal mass, irrespective of underlying etiology (Chap. 278). The responses to reduction in nephron number are mediated by vasoactive hormones, cytokines, and growth factors. Eventually, these short-term adaptations of hypertrophy and hyperfiltration become maladaptive as the increased pressure and flow predisposes to distortion of glomerular architecture, associated with sclerosis and dropout of the remaining nephrons (Fig. 280-1). Increased intrarenal activity of the renin-angiotensin axis appears to contribute both to the initial adaptive hyperfiltration and to the subsequent maladaptive hypertrophy and sclerosis, the latter, in part, owing to the stimulation of transforming growth factor β (TGF-β). This process explains why a reduction in renal mass from an isolated insult may lead to a progressive decline in renal function over many years (...

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