Chronic kidney disease (CKD) encompasses a spectrum of pathophysiologic processes associated with abnormal kidney function and a progressive decline in glomerular filtration rate (GFR). The risk of CKD progression is closely linked to both the GFR and the amount of albuminuria. Figure 305-1 provides a staging of CKD stratified by the estimates of both of these parameters.
Kidney Disease Improving Global Outcome (KDIGO) classification of chronic kidney disease (CKD). Gradation of color from green to red corresponds to increasing risk and progression of CKD. GFR, glomerular filtration rate. (Reproduced with permission from Kidney Int Suppl 3:5–14, 2013.)
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 leads to death unless the toxins are removed by renal replacement therapy, using dialysis or kidney transplantation. These interventions are discussed in Chaps. 306 and 307. End-stage renal disease will be supplanted in this chapter by the term stage 5 CKD.
The pathophysiology of CKD involves two broad sets of mechanisms of damage: (1) initiating mechanisms specific to the underlying etiology (e.g., 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) hyperfiltration and hypertrophy of the remaining viable nephrons, that are a common consequence following long-term reduction of renal mass, irrespective of underlying etiology and lead to further decline in kidney function (Chap. 333e from the 19th edition of Harrison’s). The responses to reduction in nephron number are mediated by vasoactive hormones, cytokines, and growth factors. Eventually, these short-term adaptations of hyperfiltration and hypertrophy to maintain GFR become maladaptive as the increased pressure and flow within the nephron predisposes to distortion of glomerular architecture, abnormal podocyte function, and disruption of the filtration barrier leading to sclerosis and dropout of the remaining nephrons (Fig. 305-2). Increased intrarenal activity of the renin-angiotensin system (RAS) appears to contribute both to the initial compensatory hyperfiltration and to the subsequent maladaptive hypertrophy and sclerosis. 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 (Fig. 305-3).
Left: Schema of the normal glomerular architecture. Right: Secondary glomerular changes associated with a reduction in nephron number, including enlargement of capillary lumens and focal adhesions, which are thought to occur consequent to compensatory hyperfiltration and hypertrophy in the remaining nephrons. (Modified from JR Ingelfinger: N Engl J Med 348:99, 2003.)
Left: Low-power photomicrograph of a normal kidney showing normal glomeruli and healthy tubulointerstitium without ...