ETIOLOGY AND DIAGNOSIS OF PRERENAL DISEASE AND ACUTE TUBULAR NECROSIS IN ACUTE KIDNEY INJURY IN ADULTS

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).