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Postrenal AKI occurs when there is an outflow obstruction in the upper or lower

urinary tract. Lower tract obstruction is most common and can be caused by prostatic

hypertrophy, prostate or cervical cancer, anticholinergic drugs that cause bladder

sphincter spasm, or renal calculi. Upper tract obstruction is less common and occurs

when both ureters are obstructed or when one is obstructed in a patient with a single

functioning kidney. Postrenal AKI usually resolves rapidly after the obstruction has

been removed. Postobstructive diuresis can be dramatic (e.g., 3–5 L/day).

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CLINICAL EVALUATION

History and Physical Examination

A detailed history and physical examination often reveal the cause(s) of AKI. The

clinician’s responsibility is to ask specific, open-ended questions regarding the

patient’s chief complaint; history of present illness; medical history; family, social,

and allergy history; and current prescription and nonprescription medication use.

Probing for pertinent information regarding recent surgery, nephrotoxin exposure, or

concurrent medical conditions can aid in rapidly determining the etiology of AKI.

For example, does the patient have preexisting conditions that point toward prerenal

azotemia, such as heart failure (HF) or liver disease? Did the patient receive

prophylactic antibiotics before surgery? Did the patient hemorrhage or have

protracted hypotension during surgery? Furthermore, assessment of the vital sign

flowchart for documented weight loss, hypotensive events, fluid intake, and urine

output may also prove useful.

A thorough physical examination, when used in conjunction with the history, can

be invaluable in confirming the cause of AKI. The patient’s volume status should be

evaluated first. Evidence of dehydration (e.g., syncope, weight loss, orthostatic

hypotension) or decreased effective circulating volume (e.g., ascites, pulmonary

edema, peripheral edema, jugular venous distension) usually indicates prerenal

azotemia. The presence of edema in a patient with normal cardiac function can,

however, signal the early signs of nephrotic syndrome. A more detailed discussion of

nephrotic syndrome is presented in Chapter 28, Chronic Kidney Disease. Concurrent

rash and AKI associated with recent antibiotic exposure suggest drug-induced

allergic interstitial nephritis. The clinician should suspect rhabdomyolysis in a

patient with trauma or crush injuries and AKI. In a patient with suspected AKI the

purpose of ultrasonography early in the diagnostic work-up is to rule out obstructive

causes of oliguria. An enlarged prostate, painful urination, or wide deviations in

urine volume can suggest obstructive AKI causes. Flank and lower abdominal pain

suggest upper obstruction, whereas urinary frequency, hesitancy, dribbling, and

abdominal fullness indicate lower obstruction.

Laboratory Evaluation

QUANTIFYING GLOMERULAR FILTRATION RATE

No estimating equations can provide an accurate estimate of GFR in AKI because the

SCr is fluctuating and not at steady-state. In Chapter 28, Chronic Kidney Disease, the

Modification of Diet in Renal Disease (MDRD) equation and the Cockcroft–Gault

(CG) equation are reviewed, and both require a SCr value at steady-state. The

MDRD equation is used to quantify baseline GFR, to detect or stage the degree of

CKD, and to follow progression. The CG equation is most commonly used to

evaluate the appropriate doses of drugs that are eliminated by the kidney.

9 CG may

significantly overestimate the renal function in the early stages of AKI and may

underestimate the renal function when AKI is resolving.

24 An example of this is a

patient who develops ATN and anuria. Within the first few days, the SCr level may

increase slightly because it takes time for the SCr concentration to achieve a new

steady-state. In fact, the calculated creatinine clearance (ClCr) may even remain in

the normal range, although the true GFR is substantially lower. The converse is true

with patients recovering from ATN. As the diuretic phase of ATN begins, urine

output can be dramatic, but patients may remain markedly azotemic for several days.

Using the CG equation in this setting will produce a falsely low ClCr estimate. The

CG equation is also inaccurate in populations that have low muscle mass—such as

elderly, obese, or cachectic patients. Use of SCr to assess kidney function in patients

with liver disease may also lead to overestimation of GFR.

25 This may be attributed

to decreased production of creatine (the precursor of creatinine) by the liver or

increased tubular secretion of creatinine by the kidney. Therefore, clinicians should

be aware that estimating equations have potential limitations and pitfalls. In the past,

many clinicians advocated the collection of timed urine specimens to calculate ClCr

in AKI. Although this may seem relatively simple, it is susceptible to serious errors,

particularly the timing of the collection and ensuring that the patient has not voided

urine in the commode, resulting in an incomplete urine collection. For these reasons,

the practice of collecting timed urine specimens is no longer routinely performed.

Populations in whom estimation of GFR using a 24-hour urine collection is more

reasonable include patients with variation in dietary intake of creatine sources (such

as vegetarians) or persons with poor muscle mass (e.g., malnourished individuals or

amputees).

26 Alternatively, shorter collection times or spot untimed urine samples are

sometimes used to determine creatinine excretion.

Because an acute decline in kidney function may not be reflected by a rise in SCr

for several hours, the recent emergence of novel serum and/or urinary AKI

biomarkers is expected to aid in the early diagnosis of AKI. Neutrophil gelatinaseassociated lipocalin (NGAL), Kidney Injury Molecule-1 (KIM-1), interleukin-18

(IL-18), and cystatin C have been shown to detect AKI in different patient cohorts.

Future clinical trials are needed to identify and validate their prognostic role in AKI

and estimating GFR.

27–31

Many drugs are eliminated at least in part by the kidneys and must be dosed

according to renal function. A more detailed discussion of drug dosing in the

presence of compromised renal function is provided in Chapter 31, Dosing of Drugs

in Renal Failure. Thus, standard doses and dosing intervals of many agents in the

presence of AKI may lead to increased drug exposure of the active drug or

metabolites. It is important to recommend appropriate drug doses in the presence of

AKI. Some clinicians make renal dosing recommendations based on eGFR <15

mL/minute as an initial guide for drug therapy in an AKI patient not receiving CRRT

when no other information is available. Drugs not essential for care should be

discontinued to avoid potential drug-induced toxicity in the presence of AKI.

Careful monitoring of clinical and biochemical surrogate parameters associated

with efficacy and toxicity and therapeutic drug monitoring (TDM), especially for

drugs with a narrow therapeutic index eliminated by the kidneys, are required. Highrisk medications such as aminoglycosides, vancomycin and calcineurin inhibitors

(e.g., cyclosporine, tacrolimus), those with

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known nephrotoxicity, or other potential toxicities associated with

supratherapeutic serum concentrations should be closely monitored. It is also

important to note the volume of distribution (Vd) of drugs such as aminoglycosides,

vancomycin, β-lactams (e.g., most cephalosporins, carbapenems) is dramatically

increased in the presence of AKI. Therefore, larger loading doses may need to be

administered to avoid subtherapeutic responses from lower than desired serum

concentrations.

32–34 For most drugs, clinically useful serum drug assays are

unavailable. Therefore, trends in renal function indices (e.g., SCr and urine output)

along with volume status and response to therapy should be utilized to guide drug

dosing. Further dose adjustments may be necessary when RRT is provided.

BLOOD TESTS

Assessment of blood urea nitrogen (BUN) and SCr concentrations is crucial for

guiding the diagnosis, treatment, and monitoring of AKI. Measurement of BUN is

discussed in Chapter 2, Interpretation of Clinical Laboratory Tests. The BUN:SCr

ratio can delineate prerenal causes from intrinsic and postrenal causes. Urea

reabsorption is inversely proportional to the urine flow rate. The normal steady-state

BUN:SCr ratio is approximately 10:1. In prerenal conditions, the BUN:SCr ratio is

greater than 20:1 because sodium and water are actively reabsorbed in the renal

tubules to expand the effective circulating volume. Urea, an ineffective osmole, is

reabsorbed as a result of increased water reabsorption, whereas creatinine is not

reabsorbed. Although SCr may increase owing to decreased glomerular filtration,

BUN increases to a greater degree as a result of increased proximal reabsorption.

The presence of hypercalcemia or hyperuricemia can indicate a hematologic

malignancy. Tumor lysis syndrome is a condition that occurs in patients with

leukemia after chemotherapy induction. The destruction of cancerous cells results in

the release of large quantities of cellular contents (e.g., potassium, uric acid) into the

bloodstream, which can overwhelm the kidney’s functional ability, especially in

dehydrated states.

Other elevated enzymes may also aid in the diagnosis of AKI. An increased level

of creatine kinase or myoglobin in the face of AKI usually indicates rhabdomyolysis.

Eosinophilia may suggest acute allergic interstitial nephritis from drug exposure.

High levels of circulating immune complexes in the presence of AKI suggest

glomerulopathies.