The causes of acute renal failure can be divided into three main categories:
1. Acute renal failure resulting from decreased blood supply to the kidneys; this condition is often referred to as prerenal acute renal failure to reflect the fact that the abnormality occurs in a system before the kidneys. This can be a consequence of heart failure with reduced cardiac output and low blood pressure or conditions associated with diminished blood volume and low blood pressure, such as severe hemorrhage.
2. Intrarenal acute renal failure resulting from abnormalities within the kidney itself, including those that affect the blood vessels, glomeruli, or tubules.
3. Postrenal acute renal failure, resulting from obstruction of the urinary collecting system anywhere from the calyces to the outflow from the bladder. The most common causes of obstruction of the urinary tract outside the kidney are kidney stones, caused by precipitation of calcium, urate, or cystine.
Prerenal Acute Renal Failure Caused by Decreased Blood Flow to the Kidney
The kidneys normally receive an abundant blood supply of about 1100 ml/min, or about 20 to 25 per cent of the cardiac output.The main purpose of this high blood flow to the kidneys is to provide enough plasma for the high rates of glomerular filtration needed for effective regulation of body fluid volumes and solute concentrations. Therefore, decreased renal blood flow is usually accompanied by decreased GFR and decreased urine output of water and solutes. Consequently, conditions that acutely diminish blood flow to the kidneys usually cause oliguria, which refers to diminished urine output below the level of intake of water and solutes. This causes accumulation of water and solutes in the body fluids. If renal blood flow is markedly reduced, total cessation of urine output can occur, a condition referred to as anuria.
As long as renal blood flow does not fall below about 20 to 25 per cent of normal, acute renal failure can usually be reversed if the cause of the ischemia is corrected before damage to the renal cells has occurred. Unlike some tissues, the kidney can endure a relatively large reduction in blood flow before actual damage to the renal cells occurs. The reason for this is that as renal blood flow is reduced, the GFR and the amount of sodium chloride filtered by the glomeruli (as well as the filtration rate of water and other electrolytes) are reduced. This decreases the amount of sodium chloride that must be reabsorbed by the tubules, which uses most of the energy and oxygen consumed by the normal kidney. Therefore, as renal blood flow and GFR fall, the requirement for renal oxygen consumption is also reduced. As the GFR approaches zero, oxygen consumption of the kidney approaches the rate that is required to keep the renal tubular cells alive even when they are not reabsorbing sodium. When blood flow is reduced below this basal requirement, which is usually less than 20 to 25 per cent of the normal renal blood flow, the renal cells start to become hypoxic, and further decreases in renal blood flow, if prolonged, will cause damage or even death of the renal cells, especially the tubular epithelial cells. If the cause of prerenal acute renal failure is not corrected and ischemia of the kidney persists longer than a few hours, this type of renal failure can evolve into intrarenal acute renal failure, as discussed later. Acute reduction of renal blood flow is a common cause of acute renal failure in hospitalized patients. Table 31-2 shows some of the common causes of decreased renal blood flow and prerenal acute renal failure.
Intrarenal Acute Renal Failure Caused by Abnormalities Within the Kidney
Abnormalities that originate within the kidney and that abruptly diminish urine output fall into the general category of intrarenal acute renal failure. This category of
Some Causes of Prerenal Acute Renal Failure
Intravascular volume depletion
Hemorrhage (trauma, surgery, postpartum, gastrointestinal) Diarrhea or vomiting Burns Cardiac failure
Myocardial infarction Valvular damage Peripheral vasodilation and resultant hypotension
Anaphylactic shock Anesthesia
Sepsis, severe infections Primary renal hemodynamic abnormalities
Renal artery stenosis, embolism, or thrombosis of renal artery or vein
Some Causes of Intrarenal Acute Renal Failure
Small vessel and/or glomerular injury
Vasculitis (polyarteritis nodosa) Cholesterol emboli Malignant hypertension Acute glomerulonephritis
Tubular epithelial injury (tubular necrosis)
Renal interstitial injury
Acute allergic interstitial nephritis acute renal failure can be further divided into (1) conditions that injure the glomerular capillaries or other small renal vessels, (2) conditions that damage the renal tubular epithelium, and (3) conditions that cause damage to the renal interstitium. This type of classification refers to the primary site of injury, but because the renal vasculature and tubular system are functionally interdependent, damage to the renal blood vessels can lead to tubular damage, and primary tubular damage can lead to damage of the renal blood vessels. Causes of intrarenal acute renal failure are listed in Table 31-3.
Acute Renal Failure Caused by Glomerulonephritis. Acute glomerulonephritis is a type of intrarenal acute renal failure usually caused by an abnormal immune reaction that damages the glomeruli. In about 95 per cent of the patients with this disease, damage to the glomeruli occurs 1 to 3 weeks after an infection elsewhere in the body, usually caused by certain types of group A beta streptococci. The infection may have been a streptococ-cal sore throat, streptococcal tonsillitis, or even strepto-coccal infection of the skin. It is not the infection itself that damages the kidneys. Instead, over a few weeks, as antibodies develop against the streptococcal antigen, the antibodies and antigen react with each other to form an insoluble immune complex that becomes entrapped in the glomeruli, especially in the basement membrane portion of the glomeruli.
Once the immune complex has deposited in the glomeruli, many of the cells of the glomeruli begin to proliferate, but mainly the mesangial cells that lie between the endothelium and the epithelium. In addition, large numbers of white blood cells become entrapped in the glomeruli. Many of the glomeruli become blocked by this inflammatory reaction, and those that are not blocked usually become excessively permeable, allowing both protein and red blood cells to leak from the blood of the glomerular capillaries into the glomerular filtrate. In severe cases, either total or almost complete renal shutdown occurs.
The acute inflammation of the glomeruli usually subsides in about 2 weeks, and in most patients, the kidneys return to almost normal function within the next few weeks to few months. Sometimes, however, many of the glomeruli are destroyed beyond repair, and in a small percentage of patients, progressive renal deterioration continues indefinitely, leading to chronic renal failure, as described in a subsequent section of this chapter.
Tubular Necrosis as a Cause of Acute Renal Failure. Another cause of intrarenal acute renal failure is tubular necrosis, which means destruction of epithelial cells in the tubules. Some common causes of tubular necrosis are (1) severe ischemia and inadequate supply of oxygen and nutrients to the tubular epithelial cells and (2) poisons, toxins, or medications that destroy the tubular epithelial cells.
Ischemia. Severe ischemia of the kidney can result from circulatory shock or any other disturbance that severely impairs the blood supply to the kidney. If the ischemia is severe enough to seriously impair the delivery of nutrients and oxygen to the renal tubular epithelial cells, and if the insult is prolonged, damage or eventual destruction of the epithelial cells can occur. When this happens,tubular cells "slough off" and plug many of the nephrons, so that there is no urine output from the blocked nephrons; the affected nephrons often fail to excrete urine even when renal blood flow is restored to normal, as long as the tubules remain plugged.The most common causes of ischemic damage to the tubular epithelium are the prerenal causes of acute renal failure associated with circulatory shock, as discussed earlier in this chapter.
Acute Tubular Necrosis Caused by Toxins or Medications.
There is a long list of renal poisons and medications that can damage the tubular epithelium and cause acute renal failure. Some of these are carbon tetrachloride, heavy metals (such as mercury and lead), ethylene glycol (which is a major component in antifreeze), various insecticides, various medications (such as tetracyclines) used as antibiotics, and cis-platinum, which is used in treating certain cancers. Each of these substances has a specific toxic action on the renal tubular epithelial cells, causing death of many of them. As a result, the epithelial cells slough away from the basement membrane and plug the tubules. In some instances, the basement membrane also is destroyed. If the basement membrane remains intact, new tubular epithelial cells can grow along the surface of the membrane, so that the tubule repairs itself within 10 to 20 days.
Postrenal Acute Renal Failure Caused by Abnormalities of the Lower Urinary Tract
Multiple abnormalities in the lower urinary tract can block or partially block urine flow and therefore lead to acute renal failure even when the kidneys' blood supply and other functions are initially normal. If the urine output of only one kidney is diminished, no major change in body fluid composition will occur because the contralateral kidney can increase its urine output sufficiently to maintain relatively normal levels of extracellular electrolytes and solutes as well as normal extracellular fluid volume. With this type of renal failure, normal kidney function can be restored if the basic cause of the problem is corrected within a few hours. But chronic obstruction of the urinary tract, lasting for several days or weeks, can lead to irreversible kidney damage. Some of the causes of postrenal acute failure include (1) bilateral obstruction of the ureters or renal pelvises caused by large stones or blood clots, (2) bladder obstruction, and (3) obstruction of the urethra.
A major physiologic effect of acute renal failure is retention in the blood and extracellular fluid of water, waste products of metabolism, and electrolytes. This can lead to water and salt overload, which in turn can lead to edema and hypertension. Excessive retention of potassium, however, is often a more serious threat to patients with acute renal failure, because increases in plasma potassium concentration (hyperkalemia) to more than about 8 mEq/L (only twice normal) can be fatal. Because the kidneys are also unable to excrete sufficient hydrogen ions, patients with acute renal failure develop metabolic acidosis, which in itself can be lethal or can aggravate the hyperkalemia.
In the most severe cases of acute renal failure, complete anuria occurs. The patient will die in 8 to 14 days unless kidney function is restored or unless an artificial kidney is used to rid the body of the excessive retained water, electrolytes, and waste products of metabolism. Other effects of diminished urine output, as well as treatment with an artificial kidney, are discussed in the next section in relation to chronic renal failure.
Chronic Renal Failure: An Irreversible Decrease in the Number of Functional Nephrons
Chronic renal failure results from progressive and irreversible loss of large numbers of functioning nephrons. Serious clinical symptoms often do not occur until the number of functional nephrons falls to at least 70 to 75 per cent below normal. In fact, relatively normal blood concentrations of most electrolytes and normal body fluid volumes can still be maintained until the number of functioning nephrons decreases below 20 to 25 per cent of normal.
Table 31-4 gives some of the most important causes of chronic renal failure. In general, chronic renal
Some Causes of Chronic Renal Failure
Diabetes mellitus Obesity Amyloidosis Hypertension Renal vascular disorders Atherosclerosis Nephrosclerosis-hypertension Immunologic disorders Glomerulonephritis Polyarteritis nodosa Lupus erythematosus Infections
Pyelonephritis Tuberculosis Primary tubular disorders
Nephrotoxins (analgesics, heavy metals) Urinary tract obstruction Renal calculi Hypertrophy of prostate Urethral constriction Congenital disorders
Congenital absence of kidney tissue (renal hypoplasia)
failure, like acute renal failure, can occur because of disorders of the blood vessels, glomeruli, tubules, renal interstitium, and lower urinary tract. Despite the wide variety of diseases that can lead to chronic renal failure, the end result is essentially the same—a decrease in the number of functional nephrons.
Vicious Circle of Chronic Renal Failure Leading to End-Stage Renal Disease
In many 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 be placed on dialysis treatment or transplanted with a functional kidney to survive. This condition is referred to as end-stage renal disease.
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 per cent of normal. Over a period of several years, however, the renal functional changes may lead to further injury of the remaining nephrons, particularly to the glomeruli of these nephrons.
Primary kidney disease
Primary kidney disease
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.
The cause of this additional injury is not known, but some investigators believe that 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 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 circle that eventually terminates in end-stage renal disease (Figure 31-2). The only proven 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 antagonists.
Table 31-5 gives the most common causes of endstage renal disease. In the early 1980s, glomeru-lonephritis in all its various forms was believed to be the most common initiating cause of end-stage renal disease. In recent years, diabetes mellitus and hypertension have become recognized as the leading causes of end-stage renal disease, together accounting for approximately 70 per cent of all chronic renal failure.
Excessive weight gain (obesity) appears to be the most important risk factor for the two main causes of end-stage renal disease—diabetes and hypertension. As discussed in Chapter 78, type II diabetes, which is
Most Common Causes of End-Stage Renal Disease (ESRD)
Diabetes mellitus Hypertension Glomerulonephritis Polycystic kidney disease Other/unknown
Percentage of Total ESRD Patients
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