PATHOPHYSIOLOGY

A number of factors can cause initial damage to the kidney. The

resulting sequelae, however, follow a common pathway that

promotes progression of CKD and results in irreversible damage

leading to ESKD (Figure 26–1).

Regardless of the initial cause of kidney damage, the result is

a decrease in the number of functioning nephrons. The remain-

ing nephrons hypertrophy to increase glomerular filtration and

tubular function, both reabsorption and secretion, in an attempt

to compensate for the loss of kidney function. Initially, these

adaptive changes preserve many of the clinical parameters of

kidney function, including creatinine and electrolyte excre-

tion. However, as time progresses, angiotensin II is required to

maintain the hyperfiltration state of the functioning nephrons.

Angiotensin II is a potent vasoconstrictor of both the afferent

and efferent arterioles but has a preferential effect to constrict the

efferent arteriole, thereby increasing the pressure in the glomeru-

lar capillaries. Increased glomerular capillary pressure expands

the pores in the glomerular basement membrane, altering thesize-selective barrier and allowing
proteins to be filtered through

the glomerulus.13