In some cases, an initial insult to the kidney leads to progressive deterioration of kidney function and further loss of nephrons to the point where the person must receive dialysis treatment or undergo transplantation with a functional kidney to survive. This condition is referred to as end-stage renal disease (ESRD).
Studies in laboratory animals have shown that surgical removal of large portions of the kidney initially causes adaptive changes in the remaining nephrons that lead to increased blood flow, increased GFR, and increased urine output in the surviving nephrons. The exact mechanisms responsible for these changes are not well understood but involve hypertrophy (growth of the various structures of the surviving nephrons), as well as functional changes that decrease vascular resistance and tubular reabsorption in the surviving nephrons. These adaptive changes permit a person to excrete normal amounts of water and solutes even when kidney mass is reduced to 20 to 25 percent of normal. Over a period of several years, however, these renal adaptive changes may lead to further injury of the remaining nephrons, particularly to the glomeruli of these nephrons.
The cause of this additional injury is not fully under stood, but some investigators believe it may be related in part to increased pressure or stretch of the remaining glomeruli, which occurs as a result of functional vasodilation or increased blood pressure. The chronic increase in pressure and stretch of the small arterioles and glomeruli are believed to cause injury and sclerosis of these vessels (replacement of normal tissue with connective tissue). These sclerotic lesions can eventually obliterate the glomerulus, leading to further reduction in kidney function, further adaptive changes in the remaining nephrons, and a slowly progressing vicious cycle that eventually terminates in ESRD (Figure 1). The most effective method of slowing down this progressive loss of kidney function is to lower arterial pressure and glomerular hydrostatic pressure, especially by using drugs such as angiotensin converting enzyme inhibitors or angiotensin II receptor antagonists.
Fig1. The vicious circle that can occur with primary kidney disease. Loss of nephrons because of disease may increase pressure and flow in the surviving glomerular capillaries, which in turn may eventually injure these “normal” capillaries as well, thus causing progressive sclerosis and eventual loss of these glomeruli.
Table 1 lists the most common causes of ESRD. In the early 1980s, glomerulonephritis in all its various forms was believed to be the most common initiating cause of ESRD. In recent years, diabetes mellitus and hypertension have become recognized as the leading causes of ESRD, together accounting for more than 70 percent of all ESRD.
Table1. Most Common Causes of End-Stage Renal Disease
Excessive weight gain (obesity) appears to be the most important risk factor for the two main causes of ESRD— diabetes and hypertension. As discussed in Chapter 79, type II diabetes, which is closely linked to obesity, accounts for more than 90 percent of all cases of diabetes mellitus. Excess weight gain is also a major cause of essential hypertension, accounting for as much as 65 to 75 percent of the risk for developing hypertension in adults. In addition to causing renal injury through diabetes and hyper tension, obesity may have additive or synergistic effects to worsen renal function in patients with preexisting kidney disease.
