ETIOLOGY AND DIAGNOSIS OF PRERENAL DISEASE AND ACUTE TUBULAR NECROSIS IN ACUTE KIDNEY INJURY IN ADULTS
ETIOLOGY
AND DIAGNOSIS OF PRERENAL DISEASE & ACUTE TUBULAR NECROSIS IN ACUTE KIDNEY
INJURY IN ADULTS
The two major
causes of hospitalized ptns with AKI are:
(1) Pre-renal
disease &
(2) Acute
tubular necrosis (ATN).
Kidney function decline related to pre-renal insult occurs when renal ischemia is
part of a general reduction in tissue perfusion and when there’s selective
renal ischemia. ATN can
occur with prolonged and/or severe ischemia. This
can result in histologic changes, including necrosis.
Both pre-renal
disease & ATN can be observed in a variety of settings.
Pre-renal disease may result from:
1) Low
BP,
2) True
volume depletion,
3) Edematous
conditions, &
4) Selective kidney issue ischemia,
While ATN is principally due to ALL the causes of severe pre-renal disease, especially
hypotension, sepsis, & nephrotoxins.
A thorough history & physical evaluation can eventually recognize the event and/or
disease process that is underling the pre-renal insult or ATN, to suggest the underlying diagnosis. Added to a careful history & physical examination, the initial evaluation
to DD ATN from pre-renal
disease may include a number of lab profiles, routine testing of the urine, and
(if there is no contraindication) fluid rehydration therapy. The principal diagnostic tools may
include:
(1) Urinalysis,
(2) Response
to hydration therapy, &
(3) Fractional
excretion of Na+ (FENa).
These three tests are commonly used combined to the clinical situation
to help identifying the underlying insult.
The urinalysis is normal or near normal in pre-renal disease; hyaline
casts may be seen, but these are not
an abnormal finding. In contrary, the classic
urinalysis in ATN may show muddy brown granular, epithelial cell cast & free epithelial cells.
However, the lack of these urinary findings does not exclude ATN. The
ptn with a clinical history consistent with fluid loss,
a physical evaluation consistent with hypovolemia (Low BP
+ tachycardia), and/or oliguria should
be resuscitated with IV fluid therapy,
unless there is contraindication. This fluid optimization attempting to correct
the fluid deficit & optimizing renal
blood reperfusion.
The FENa
is typically < 1 % in pre-renal insult (indicating
sodium retention) and > 2 % in ATN. There’re conditions in which this
distinction is not applicable, e.g. ATN superimposing
upon a chronic pre-renal state e.g. cirrhosis,
a setting where the FENa may remain < 1%. The SCr is widely used in identifying the diagnosis
of AKI. However, since it’s a suboptimal biomarker
for this process, different urinary & serum
proteins have been thoroughly studied. Although there’re promising candidate biomarkers, only one is
approved by Food and Drug Administration (FDA)
in the US but not implemented in many medical
centers (see below).
Investigational biomarkers & evaluation of AKI:
AKI, previously termed ARF, is a commonly seen clinical problem. Despite
testing for SCr is commonly used for
the recognition of AKI, it does NOT provide early Dgx
of ATN, since tubular damage precedes
the significant elevation of SCr. Investigational
biomarkers have been considered
in ptns with possible ATN attempting
to recognize tubular injury at an earlier time.
Several urinary & serum
proteins have been intensively studied as potential biomarkers for the early
identification of ATN. Before any of
these proteins are clinically applied, validity of different stages of AKI & the evolution &
testing of rapid assays are mandated.
It’s accepted that a panel of biomarkers + clinical data should be available for clinical utility or
serial measuring of a certain marker. Moreover, it needs to clarify
if there’s an impact of biomarkers on outcome.
Promising biomarkers
for Dgx of AKI include neutrophil
gelatinase-associated lipocalin (NGAL),
kidney injury molecule-1 (KIM-1), urinary
interleukin (IL)-18,
& liver-type fatty acid-binding protein (L-FABP). Urinary
angiotensinogen may be beneficial as a prognostic one for
severe AKI, and the product of urinary insulin-like growth
factor-binding protein 7 (IGFBP7) & tissue inhibitor of metallo-proteinases-2 (TIMP-2) have been proved to
predict AKI
& long-term DX or death. A point-of-care those two biomarkers have
been approved by FDA (2014).
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