C h a p t e r 2 6
Acute Kidney Injury and Chronic Kidney Disease
641
(NSAIDs) can also reduce renal blood flow by inhibiting
the synthesis of prostaglandins, which normally have a
vasodilatory effect on renal blood vessels.
Prerenal injury is manifested by a sharp decrease in
urine output and a disproportionate elevation of blood
urea nitrogen (BUN) in relation to serum creatinine lev-
els. The kidney normally responds to a decrease in the
GFR with a decrease in urine output. Thus, an early sign
of prerenal injury is a sharp decrease in urine output. A
low fractional excretion of sodium (<1%) suggests that
oliguria is due to decreased renal perfusion and that the
nephrons are responding appropriately by decreasing
the excretion of filtered sodium in an attempt to pre-
serve vascular volume. Blood urea nitrogen levels also
depend on the GFR. A low GFR allows more time for
small particles such as urea to be reabsorbed into the
blood. Creatinine, which is larger and nondiffusible,
remains in the tubular fluid, and the total amount of
creatinine that is filtered, although small, is excreted in
the urine. Consequently, there also is a disproportionate
elevation in the ratio of BUN to serum creatinine, from a
normal value of 10:1 to a ratio greater than 20:1.
1
Postrenal Injury
Postrenal injury results from obstruction of urine out-
flow from the kidneys. The obstruction can occur in the
ureter (i.e., calculi and strictures), bladder (i.e., tumors
or neurogenic bladder), or urethra (i.e., prostatic hyper-
plasia). Prostatic hyperplasia is the most common under-
lying problem. Because both ureters must be occluded
to produce renal injury, obstruction of bladder outflow
rarely causes AKI unless one of the kidneys already is
damaged or a person has only one kidney. The treat-
ment of acute postrenal injury consists of treating the
underlying cause of obstruction so that urine flow can be
reestablished before permanent nephron damage occurs.
Intrarenal Injury
Intrarenal injury results from conditions that dam-
age structures within the kidney. The major causes of
intrarenal injury are ischemia associated with prerenal
injury, injury to the tubular structures of the nephron,
and intratubular obstruction. Acute glomerulonephritis
and acute pyelonephritis also are intrarenal causes of
AKI. However, injury to the tubular structures of the
nephron (acute tubular necrosis) is the most common
cause and often is ischemic or toxic in origin.
AcuteTubular Necrosis.
Acute tubular necrosis (ATN)
is characterized by the destruction of tubular epithelial
cells with acute suppression of renal function (Fig. 26-2).
It can be caused by a number of conditions, including
acute tubular damage due to ischemia, sepsis, nephro-
toxic effects of drugs, tubular obstruction, and toxins
from a massive infection.
3–5,10
Tubular epithelial cells are
particularly sensitive to ischemia and toxins. The tubu-
lar injury that occurs in ATN frequently is reversible.
The process depends on recovery of the injured cells,
removal of the necrotic cells and intratubular casts, and
regeneration of tubular cells to restore the normal conti-
nuity of the tubular epithelium.
5,10
Acute tubular necrosis occurs most frequently in per-
sons who have major surgery, severe hypovolemia, or
overwhelming sepsis, trauma, or burns.
3
Sepsis produces
ischemia by provoking a combination of systemic vaso-
dilation and intrarenal hypoperfusion. In addition, sep-
sis results in the generation of toxins that sensitize renal
tubular cells to the damaging effects of ischemia. ATN
complicating trauma and burns frequently is multifac-
torial in origin, resulting from the combined effects of
hypovolemia, myoglobinuria, and other toxins released
from damaged tissue. In contrast to prerenal injury, the
GFR does not improve with the restoration of renal
blood flow in AKI caused by ischemic ATN.
Many drugs are nephrotoxic, causing tubular injury
by inducing varying combinations of renal vasoconstric-
tion, direct tubular damage, or intratubular obstruction.
The kidney is particularly vulnerable to nephrotoxic
injury because of its rich blood supply and ability to con-
centrate toxins to high levels in the medullary portion of
the kidney. In addition, the kidney is an important site
for metabolic processes that transform relatively harm-
less agents into toxic metabolites. Pharmacologic agents
that are directly toxic to the renal tubule include anti-
microbials such as aminoglycosides (e.g., gentamicin),
cancer chemotherapeutic agents such as cisplatin and
Decreased
glomerular
filtration rate
Tubular
injury
Obstruction
Back-leak
Afferent
arteriolar
constriction
Ischemic/toxic
insult
FIGURE 26-2.
Pathogenesis of acute tubular necrosis (ATN).
Sloughing and necrosis of tubular epithelial cells lead to
obstruction and increased intraluminal pressure, which reduce
glomerular filtration. Afferent arteriolar vasoconstriction caused
in part by tubuloglomerular feedback mechanisms results in
decreased glomerular capillary filtration pressure.Tubular
injury and increased intraluminal pressure cause fluid to
move from the tubular lumen into the interstitium (back-leak).
(Modified from Jennette JC.The kidney. In: Rubin R, Strayer
DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of
Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health |
Lippincott Williams &Wilkins; 2012:792.)
