Overview Of Acute
Kidney Injury
Acute kidney injury (AKI) consists
of any precipitous decline in renal filtration function, which can occur
secondary to disease affecting the renal vasculature, renal parenchyma, or
urine collecting system. Such a decline is often first evidenced as an increase
in serum creatinine concentration, which may be accompanied by normal urine
output, oliguria, or anuria.
Definition
Over time, various criteria have
been proposed to define what degree of functional impairment constitutes AKI.
The Acute Dialysis Quality Initiative (ADQI) created a consensus definition
known as the RIFLE criteria, which stratifies patients based on serum creatinine
concentration, estimated glomerular filtration rate (GFR), and urine output. A
modification of these criteria was subsequently proposed by the Acute Kidney
Injury Network (AKIN) since smaller changes in serum creatinine than proposed
by the RIFLE criteria can have adverse effects on outcome. The criteria
include:
Stage 1 AKI: increase in serum
creatinine by ≥0.3 mg/dL or by 150% to 200%, OR urine output <0.5 mL/kg/hr for 6 hours Stage
2 AKI: increase in serum creatinine by 200% to 300%, OR urine output <0.5 mL/kg/hr for 12 hours
Stage 3 AKI: increase in serum
creatinine by >300% or to more than 4.0 mg/dL with an acute
increase of greater than 0.5 mL/dL, OR urine output <0.3 mL/kg/hr for 24 hours, anuria for 12 hours
or renal replacement therapy
These diagnoses should be applied
only if the decline in renal function occurs over a rapid time course (i.e.,
less than 48 hours). There are several issues that may complicate application
of these criteria. First, they require knowledge of the patient’s baseline
renal function. Second, serum creatinine concentrations may not be in a steady
state in patients with declining renal function. Research efforts into more
sensitive biomarkers of renal injury, such as cystatin C and neutrophil
gelatinase-associated lipocalin (NGAL), are ongoing but have not yet had a wide
impact on clinical practice.
The various etiologies responsible
for AKI are typically categorized as “prerenal,” “intrarenal,” or “postrenal.” Prerenal.
“Prerenal” AKI, the most common kind (60% of cases), reflects a
significant reduction in renal perfusion. Mild reductions in renal perfusion do
not affect the glomerular filtration rate (GFR) because of compensatory feedback
responses, such as activation of the renin-angiotensin system and release of
vasodilatory prostaglandins (see Plate 3-18). In the setting of markedly
reduced flow, however, these compensatory mechanisms fail, and renal filtration
declines. By definition, however, the renal parenchyma remains intact, and
normal function can be restored with intravascular fluid repletion.
Common causes of prerenal AKI
include excessive diuresis, diarrhea, vomiting, hemorrhage, burns, poor cardiac
output (i.e., congestive heart failure, see Plate 4-38), liver failure (i.e.,
hepatorenal syndrome, see Plate 4-40), and hypercalcemia (due to renal
vasocon-striction). In addition, patients with low baseline renal perfusion may
experience prerenal AKI if their normal compensatory mechanisms are blocked by
either nonsteroidal antiinflammatory drugs (e.g., ibuprofen), which interfere
with tubuloglomerular feedback, or inhibitors of the renin-angiotensin system
(i.e., angiotensin-converting enzyme [ACE] inhibitors, aldosterone
receptor blockers [ARBs]).
Patients with prerenal AKI may
exhibit other signs of volume depletion, such as tachycardia, orthostatic
hypotension, and dry mucous membranes. In addition, prerenal AKI can be
distinguished from other causes by the intense reabsorption of solutes that
results from the normal renal response to decreased perfusion. Specifically the
fractional excretion of sodium (FENa, see Plate 3-6 for formula) should be low
(<1%); the serum blood urea nitrogen (BUN): creatinine
ratio may be elevated (i.e., >20: 1), reflecting increased reabsorption of urea; and the urine should
be concentrated (> 500 mOsm/kg H2O). Note that FENa
values may be invalid among patients who have recently taken diuretics; in this
case, the fractional excretion of urea has been proposed as an alternative
means of assessing tubular reabsorption because it is generally less than 35%
in the prerenal state. Finally, because the renal parenchyma is not damaged,
the urine sediment should not contain red blood cells, white blood cells, or
other markers of renal inflammation. Hyaline casts, however, may be seen; these
occur because low tubular flow rates increase aggregation of Tamm-Horsfall
mucoproteins, which are secreted by the distal tubular epithelium.
Once prerenal AKI is suspected, the
diagnosis can be confirmed by documenting normalization of renal function upon
resuscitation of intravascular volume.
Intrarenal. “Intrarenal” AKI, the second most common kind
(35% of cases), reflects direct damage to the renal parenchyma. Acute tubular
necrosis (ATN, see Plate 4-3) accounts for nearly 90% of cases and is by far
the most common cause. ATN occurs in the setting of either severe renal
ischemia or direct toxic damage to the renal tubules by either extrinsic toxins
(such as aminoglycosides or radiocontrast agents) or intrinsic toxins (such as
myoglobin or hemoglobin). The many other causes of intrarenal AKI include acute
or rapidly progressive glomerulonephritis (GN, see Plate 4-14), thrombotic
microangiopathy (see Plate 4-32), disseminated intravascular coagulation,
malignant hypertension (see Plate 4-44), acute interstitial nephritis (AIN, see
Plate 4-28), and post-transplant renal allograft rejection.
Unlike prerenal AKI, intrarenal AKI
does not improve in response to an intravenous fluid
bolus. In addition, it generally does not produce evidence of increased tubular
reabsorption. Thus the FENa is often >2%, the BUN :
creatinine ratio is 10 to 15 : 1, and the urine osmolality is ≤400 mOsm/kg.
Intrarenal AKI may also be
distinguished by findings on urine microscopy that indicate glomerular or
tubular damage. ATN, for example, is often (but not always) associated with
“muddy brown” pigmented granular casts or tubular epithelial cell casts. GN is
associated with evidence of glomerular bleeding (dysmorphic red blood cells
[RBCs], red blood cell casts; see Plate 4-14 for details). AIN is associated
with white blood cell casts, white blood cells, and RBCs. In addition,
glomerular and interstitial diseases are often associated with proteinuria,
unlike prerenal or postrenal disease.
Finally, several
glomerulonephritides cause abnormal complement levels, which are generally not
seen in prerenal or postrenal disease unless the patient has other comorbidities.
Additional details are available later in this section.
Once intrarenal AKI is suspected,
the diagnosis of ATN is often reached based on history and laboratory findings.
If a cause other than ATN appears likely, however, and the patient’s renal
function is not improving, a renal biopsy is often performed.
Postrenal. “Postrenal” AKI, the least common kind (5% of cases), reflects
obstruction to urine flow from both kidneys (or in a solitary kidney). The
obstructions must therefore affect the urethra, bladder neck, or both ureters.
Such obstructions are often associated with intense flank and groin pain, which
results from stretching of the proximal collecting system. Although flank intrinsic
renal diseases, referred pain to the groin indicates lower tract
inflammation and is more suggestive of obstruction. The patient may offer a
history of weak urine stream or incomplete emptying. On examination, an
enlarged bladder or prostate (in men) may be palpable. Microscopic analysis of
urine may be unremarkable or may reveal RBCs in the case of nephrolithiasis.
Once postrenal AKI is suspected,
the patient should undergo further evaluation with radiographic imaging to
further characterize the obstruction.
Management
The specific management of these
various etiologies is discussed later in this book. Irrespective of the cause,
however, clinicians should be cognizant of the common sequelae of severely
impaired renal function, such as fluid retention (with subsequent hypertension
and edema), hyperkalemia, and metabolic acidosis. Any of these conditions, if
not correctable wit medications, may require renal replacement therapy.
