Page 1346 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 97: Acute Kidney Injury 919

■ POSTRENAL ACUTE RENAL FAILURE clamp, systemic endotoxin, amino-glycoside, and temperature eleva-

Postrenal AKI (often called obstructive uropathy) accounts for 5% of all tion) cause azotemia and renal pathologic findings of ATN, but these
22
cases of AKI, and is more common in the elderly. Unilateral obstruction insults individually cause no renal dysfunction or injury. We suspect
is not sufficient alone to cause AKI. Renal insufficiency due to obstruc- that this synergistic injury model accurately reflects the pathogenesis
tion occurs only when the obstruction involves a site that affects both of much AKI in the ICU. Positive pressure mechanical ventilation
kidneys, or a single functioning kidney. The most common cause of alters renal perfusion and function through a variety of mechanisms,
23
postrenal obstruction is bladder neck obstruction (prostatic hypertro- both hemodynamic and inflammatory. Other experimental data
phy, prostate cancer, and neurogenic bladder). Postrenal obstruction is have shown that endotoxin, tumor necrosis factor, and numerous
also caused by bilateral ureteral obstruction or unilateral obstruction in other inflammatory mediators are directly cytotoxic to renal endo-
24
patients with solitary kidney (stones, clots, sloughed renal papillae, ret- thelial and tubular cells.
roperitoneal fibrosis, or retroperitoneal masses). Intratubular obstruc- The diagnosis of ATN is usually made by clinical exclusion of alter-
https://kat.cr/user/tahir99/
tion can be caused by crystals like uric acid, calcium oxalate, calcium native diagnoses such as obstruction or prerenal azotemia, and a lack
phosphate, acyclovir, sulfadiazine, indinavir, methotrexate, or by para- of features suggestive of other intrinsic renal lesions. Characteristic
protein (myeloma cast nephropathy). Volume expansion, sometimes urinalysis and urine chemistry findings frequently support the clini-
with urinary alkalinization (uric acid, methotrexate, or myeloma), is the cal diagnosis, increasingly combined with analysis of novel biomarkers
primary treatment for these causes of intratubular obstruction. of renal tubular damage (although the latter are not currently avail-
Obstruction to urine flow by increased tubular hydrostatic pressure is able for clinical use in the USA). Ischemic ATN is usually reversible
only partly responsible for the reduced GFR of obstructive uropathy. by tubular regeneration in surviving patients with previously normal
AKI is also caused and sustained by renal vasoconstriction that renal function; although, as discussed above, in a significant subset of
occurs in response to ureteral obstruction, mediated by thromboxanes. cases, recovery may be less complete than is clinically apparent. Failure to
Obstruction should be suspected in patients with recurrent urinary tract recover prompts consideration of a differential diagnostic list including
infections, nephrolithiasis, prostate disease, or pelvic tumor. Causes of bilateral cortical necrosis, renal atheroembolism, renal artery stenosis/
obstructive uropathy are listed in Table 97-2. These patients usually have thrombosis/dissection, and severe forms of other intrinsic lesions such
a preceding history of obstructive symptoms followed by sudden onset as rapidly progressive glomerulonephritis (GN). Bilateral cortical necro-
of anuria or oliguria. Polyuria and nocturia due to renal concentrating sis causes irreversible renal failure and is associated with profound shock
defect may be seen in patients with partial or intermittent obstruc- with disseminated intravascular coagulation, obstetric complications,
25
tion. Other features of AKI secondary to obstruction are increased hemolytic uremic syndrome, or snake bites.
BUN : creatinine ratio, hyperkalemia, and defective urinary acidification Cellular mediators that play a role in the pathogenesis of ATN include
with metabolic acidosis. calcium, reactive oxygen species, phospholipases, proteases, adhesion
26
The two most important diagnostic tests when obstruction is suspected molecules, and nitric oxide (NO). ATN has several phases: prerenal,
27
are bladder catheterization and renal ultrasonography. If urinary tract initiation, extension, maintenance, and repair. It is not intuitive that
obstruction is strongly suspected, but ultrasound results are equivocal, renal tubular injury should cause decreased glomerular filtration and
then a “stone protocol” noninfused computed tomography (CT) scan AKI. A decrease in glomerular ultrafiltration coefficient has been shown
should be performed. In some cases where false-negative ultrasound or in several animal models of AKI, but this is a minor contributor to the
28,29
CT scan results are suspected, cystoscopy and retrograde pyelograms observed decrement in GFR. The pathophysiologic mechanisms that
may be required to definitively exclude the diagnosis of obstructive explain the reduction of GFR in ATN are hemodynamic abnormalities,
uropathy. For example, we would request retrograde pyelograms despite tubular obstruction, and tubular back leakage of glomerular filtrate
30
30,31
normal ultrasound images in a patient with anuric, hyperkalemic AKI (Fig. 97-2). Renal vasoconstriction is seen in AKI, caused by acti-
and extensive pelvic tumor, potentially encasing the ureters and prevent- vation of tubuloglomerular feedback; increased distal chloride delivery
ing dilation and hydronephrosis. Retroperitoneal fibrosis can similarly past injured tubular segments is sensed by the macula densa, causing
cause obstructive AKI without hydronephrosis. Early diagnosis is essen- vasoconstriction of the corresponding afferent arteriole. This reversible,
tial, as the extent of parenchymal damage is dependent on the duration functional mechanism seems to be the major cause of decreased GFR
of obstruction; complete recovery is possible up until 10 to 14 days of in ATN, and is in part protective. Severe hypovolemia would rapidly
obstruction. result if injured tubules failed to reabsorb the bulk of filtered sodium
and water; thus the term “acute renal success” has been used to describe
■ INTRINSIC ACUTE RENAL FAILURE the development of decreased GFR (“acute renal failure”) in the pres-
ence of tubular necrosis. Furthermore, reabsorption of filtered sodium
31
Intrinsic acute renal failure can be categorized anatomically, according accounts for the bulk of renal oxygen consumption; continued glomeru-
to the site of the lesion: vascular, glomerular, or tubulointerstitial. We lar filtration of sodium in ATN may aggravate hypoxic damage to sub-
will discuss tubular and interstitial causes first, because they are far more lethally injured tubules. The phenomenon of medullary hypoxia plays
common in hospitalized patients. an important role in the pathogenesis of ATN. Low medullary blood
flow is required for urinary concentration. Reabsorption of sodium
32
Acute Tubular Necrosis: The most common cause of intrinsic AKI in chloride by the medullary thick ascending limb of the loop of Henle
hospitalized patients is acute tubular necrosis (ATN). ATN is caused (mTAL) is the major determinant of medullary oxygen consumption,
by ischemia, nephrotoxins, or a combination of both, and accounts for resulting in a hypoxic environment under normal circumstances. 32,33
approximately 85% to 90% of intrinsic AKI cases. 8,22 Ischemic ATN mTAL is vulnerable to ischemic injury if increased oxygen requirement
is commonly seen in patients with sepsis or severe cardiac failure, or is associated with decreased oxygen delivery. In addition, the inflamma-
postoperative patients, particularly after cardiac and aortic surgeries. tory mechanisms that dominate as ATN progresses from initiation to
Massive trauma or cardiac arrest are other causes of ATN. Prerenal extension and maintenance phases of ATN result in medullary conges-
failure can result in ischemic ATN if renal hypoperfusion is severe tion and hypoperfusion. 27
and not reversed by timely therapy. Although improving renal perfu- The tubular factors that are also involved in the reduction of GFR
sion may reverse prerenal AKI (by definition), and diminish ischemic in AKI are tubular obstruction and tubular back leakage. Necrotic cell
contributions to the pathogenesis of ATN, it is quite conceivable that debris incorporated into casts causes obstruction of proximal and distal
in many cases ATN develops despite appropriate resuscitation and tubules and has been shown to play a significant role in experimental
adequate renal perfusion. Zager has shown in an endotoxemic rat AKI. 34,35 Back leakage of tubular fluid across denuded basement mem-
model of septic AKI that paired combinations of insults (renal cross branes and injured proximal tubule cells has been demonstrated in

section08.indd 919 1/14/2015 8:27:52 AM