Acute kidney injury (AKI) is a common clinical problem consisting of a sudden loss of kidney function. It often comes to the attention of the physician incidentally or during the evaluation of other medical illness when an elevated serum creatinine is noted. The creatinine is usually not in steady state in this setting, and thus calculated glomerular filtration rate (GFR) does not accurately represent a patient’s level of kidney function. This has made it difficult to create a precise definition of AKI.
The Acute Dialysis Quality Initiative (ADQI) proposed a graded definition known as the RIFLE criteria (Risk, Injury, Failure, Loss, and End stage kidney disease). The first three stages of risk, injury, and failure are stratified by the degree of reduction in urine output, percent increase in creatinine from baseline, and decrease in GFR. The Acute Kidney Injury Network (AKIN) then modified the RIFLE criteria, including an absolute increase in creatinine ≥0.3 mg/dL in the diagnostic criteria. They also suggested that these criteria not be applied until after the patient’s volume status has been optimized, and that oliguria should not be the only criterion used for diagnosis unless urinary tract obstruction has been ruled out.
More recently, the Kidney Disease: Improving Global Outcomes (KDIGO) group revised the definition of AKI in their guidelines. They define AKI as:
Increase in serum creatinine by ≥0.3 mg/dL within 48 hours; or
Increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; orRelated Content
Urine volume <0.5 mL/kg/h for 6 hours.
Similar to the RIFLE criteria, the KDIGO guidelines allow for staging the AKI based on degree of change in the urine output and creatinine. However, such staging may not add much to the management of the patient in clinical practice.
It is also worth mentioning that some patients may have a low baseline creatinine which may be problematic in today’s practice since many electronic record systems use absolute cutoffs for “flagging” labs as abnormal. As an example, a patient whose baseline creatinine is in the 0.4-0.5 mg/dL range may have a clinically significant AKI when their creatinine rises to 0.8-0.9 mg/dL, yet many labs will not identify this elevated creatinine as abnormal.
AKI can be divided into three major categories: 1) prerenal disease, which is any state of reduced renal perfusion; 2) intrinsic renal disease; and 3) postrenal disease, in which there is obstruction somewhere along the urinary tract. In reality, this is a simplified approach, as many disorders that lead to AKI will cross categories.
Myocardial infarction and congestive heart failure (CHF) exacerbation are common presenting complaints for inpatients. Acute ischemia, illness, or heart failure decompensation all may result in a reduced cardiac output due to reduced contractility that may be reversible or irreversible.
Hypovolemia is a broad category of conditions that may result in reduced cardiac output as a function of reduced preload or volume depletion.
Excessive volume output via the urinary tract, gastrointestinal tract, or insensible losses such as perspiration and ventilation without humidification may be considered. Patients with cutaneous wounds or burns have an impaired ability to retain interstitial fluid resulting in potentially high volumes of fluid that must be aggressively replaced.
Whole blood extravasation via trauma, iatrogenic/postoperative blood loss, and large volume intrathoracic/intra-abdominal hemorrhage all may occur commonly in the inpatient setting.
Interstitial fluid extravasation reducing the intravascular volume may be related to reduced oncotic pressure from malnutrition or advanced liver disease leading to fluid shifts from the intravascular space. Another common cause of fluid shifts out of the intravascular space in critically ill patients is increased vascular permeability related to systemic inflammatory response/sepsis or anaphylaxis.
Intrinsic renal disease
Intrinsic renal disease may take many forms, and may frequently require consultation from a nephrologist. Renal vascular disease occurs when the vessels themselves are involved, as in embolic disease, renal venous thrombosis, aortic dissection, vasculitides, or even aneurysm. Glomerular disease can be primary (i.e., idiopathic) or secondary to some underlying malignant or rheumatologic problem. Tubulointerstitial disease includes entities such as acute tubular necrosis (ATN; one of the most common causes of AKI), acute interstitial nephritis (AIN), and urate nephropathy from tumor lysis syndrome.
Proximal obstruction within the renal pelvis, ureter or ureterovesicular junction may be caused by nephrolithiasis, trauma or congenital/anatomic abnormalities. Imaging is often necessary for diagnosis of proximal etiologies in AKI.
Distal obstruction may also be difficult to diagnose without external or superficial signs of the causative agent. One must consider outlet obstruction (stones, anticholinergic effect) and bladder flaccidity (neurogenic bladder in spinal cord injury). Gender specific etiologies include benign prostate hyperplasia (BPH) and prostatitis in men, and bladder neck angulation, vaginal cystocele, and anteverted uterus in women.
Obtain a complete history and execute an appropriate physical exam to reveal causes for reduced renal perfusion, nephrotoxin exposure, urinary tract infection, chronic renal insufficiency, and urinary tract obstruction. Based on the findings, a plan for further evaluation may be developed.
Excessive output: emesis, diarrhea, polyuria, excessive diaphoresis
Insufficient volume intake (may be seen more frequently in patients with dementia or patients who obtain nutrition intravenously or via percutaneous feeding tube)
Chronic kidney disease
Recent nephrotoxin exposure including iodinated contrast (i.e., recent heart catheterization or contrast-enhanced computed tomography [CT] scans)
Congenital genitourinary abnormality
Changes in urination: hematuria, dysuria, frequency, foul urine odor, difficulty initiating or maintaining a stream
Abdominal pain (especially suprapubic)
Evaluate each patient for signs of decompensated heart failure, including an elevated jugular venous pressure, a positive abdominojugular test, a displaced apical impulse, an S3 gallop, and a heart rate >100 bpm at rest. All of these signs increase the likelihood of elevated left heart filling pressures if present.
History will often suggest a hypo- or hypervolemic state. On examination, however, volume status can be challenging to determine. Historically cited findings of decreased capillary refill time and poor skin turgor may not be helpful. Moist mucous membranes and absence of furrows on the tongue may help to rule out volume depletion. Presence of dry axilla may be helpful in supporting a volume depleted state.
Auscultation of an abdominal bruit, particularly one extending from systole into diastole, can strongly increase the likelihood of renovascular hypertension which may be indirectly helpful in evaluating AKI. Flank palpation and costovertebral angle tenderness can provide signs of pyelonephritis. Pain with palpation of the suprapubic area may support a diagnosis of cystitis. Occasionally, one can readily palpate a distended bladder as might occur in some postrenal diseases. In this setting, bladder catheterization with return of a large volume of urine may be diagnostic. Lower quadrant tenderness in a renal transplant patient may indicate abnormality in the transplant kidney including infection and transplant rejection.
Congenital or acquired defects of the inspectable urethral outflow tract may demonstrate edema or mass effect. A prostate examination in men may demonstrate signs of prostatic hyperplasia or malignancy that may cause proximal urethral outflow obstruction.
On a general skin exam, look for a new rash that may be associated with an immune process or drug reaction. As noted in the previous section, some diffuse skin processes may lead to increased insensible volume losses.
Pyuria on urinalysis is useful in the diagnosis of urinary tract infections (UTIs), hematuria can increase suspicion for nephrolithiasis, and proteinuria may increase suspicion for a glomerular disorder.
Microscopic examination of a spun sample can demonstrate muddy brown casts consistent with ATN. Granular or hyaline casts may point to pyelonephritis or chronic renal disease, respectively. Dysmorphic red blood cells may be evident if there is a glomerular defect or injury causing the hematuria sometimes found in nephritic syndromes.
While there are limitations and exceptions when using the fractional excretion of sodium (FENa), this formula may be calculated for patients not on diuretics to aid in distinguishing prerenal disease from ATN: FENa (%) = (serum creatinine x urine sodium) / (serum sodium x urine creatinine). A value <1% suggests prerenal disease whereas a value >2% suggests ATN.
Given the limitation above, a fractional excretion of urea (FEUrea) is typically calculated when patients are on diuretics, since it does not require the urine sodium: FEUrea (%) = (serum creatinine x urine urea) / (serum urea x urine creatinine). A value <35% suggests prerenal disease and a value >50% suggests ATN.
Work-up for multiple myeloma may be appropriate in older patients with no obvious cause for AKI. On first pass, this typically includes SPEP, UPEP, and serum free light chains.
Retroperitoneal ultrasound may reveal small kidneys and cortical atrophy; indicators of chronic kidney disease; which itself makes a patient higher risk for developing AKI. Edematous or enlarged kidneys may be seen in infectious or inflammatory causes for AKI. Hydronephrosis may be seen as a result of obstruction.
CT can be used for some morphology characteristics as with ultrasound, but can give added detail including signs of perinephric inflammation.
Bladder scan, in particular after a patient attempts to void, should be performed if there is any suspicion for urinary retention. Volumes may be inaccurate when patients also have ascites.
Renal artery duplex can reveal vessel stenosis, but this is generally of more value when evaluating chronic kidney disease.
Electrocardiography or continuous heart rhythm monitoring may reveal arrhythmias that perfuse poorly.
Renal biopsy in the setting of AKI is often not necessary for the diagnosis and thus is not performed commonly. It may be indicated when the diagnosis is unclear and this decision will generally always be made in consultation with a nephrologist.
In general, adults need a minimum amount of fluid to maintain appropriate bodily functions. Volumes below this amount may lead to renal hypoperfusion over time. Patients with fever or open wounds with greater insensible volume loss may need higher levels of hydration. For the average adult, the daily maintenance amount can be calculated as (lean body weight (Kg) + 40) x 24 = daily maintenance volume needed in millilitres.
AKI with urine volumes of less than 400 cc in a 24-hour period or less than 0.5 cc/kg/hour using the patient’s lean body weight is considered oliguric renal failure.
As noted in the previous section, FENa and FEUrea can assist in distinguishing prerenal disease from ATN.
Random scans will be variably effective, but significantly elevated volumes may indicate severe obstruction or neurogenic bladder (greater than 800-900 cc).
There is no consensus on exact volume, but higher residuals are associated with increased risk of infection and potentially bladder dysfunction. Consider in and out catheterization or Foley catheterization for volumes greater than 250-300 cc.
This test is frequently ordered but rarely positive, with a low sensitivity for AIN. Clinical history and disease onset are more reliable guides to determining the likelihood of AIN. If there is a high suspicion of AIN from a medication, consider discontinuation of the offending agent or use of an alternative medication.
This test in combination with manual prostate inspection may be a useful screening tool in males but is unlikely to aid in the early evaluation of AKI. It may be more useful once prostate enlargement is found and malignancy is suspected.
AKI related to a prerenal state can frequently be managed with intravenous fluids alone. Given the low risk of intravenous fluids, these are often given empirically even when the exact mechanism of AKI has not yet been elucidated.
Covering the management of the different causes of intrinsic renal disease is beyond the scope of this chapter, however, it is worth mentioning ATN given that it is so common. In fact, there are no pharmacologic therapies that have conclusively demonstrated benefit in treating ATN. Often, treatment is supportive, in that patients with established ATN should have special attention paid to ensure their volume status is optimized, further toxic agents are avoided, etc.
Injury from bilateral ureteral obstruction and proximal ureteral obstruction may have more benefit from urgent resolution or bypass of the obstruction via Foley catheter, percutaneous drainage, and/or cystoscopy.
All categories of injury benefit from close monitoring of blood chemistries given the common associated problems of metabolic acidosis, hyperkalemia, hyperphosphatemia, and so on. When these problems cannot be managed medically, it is an indication for dialysis and nephrology consultation. Other indications for dialysis include volume overload or overdose of dialyzable toxins such as salicylates, aldehydes, lithium, and theophylline. Also consider early input from a nephrology specialist if the injury is severe or there is high suspicion for underlying systemic process.
CHF patients need special care in determining their volume status, as patients in decompensated heart failure with volume overload and AKI may benefit from diuresis to improve their cardiac output, just as overdiuresed CHF patients in AKI may benefit from hydration. This simultaneous presence of cardiac and renal dysfunction is known as the cardiorenal syndrome.
GFR is not accurately reflected by the serum creatinine in AKI. Caution must be used in dosing medication that is renally excreted.
Be sure to review medication doses with any significant change in GFR. Some medications may require significant reduction in dose or even discontinuation. Antibiotics such as vancomycin may contribute to renal dysfunction if trough levels are not monitored appropriately.
In general, patients that are dialysis-dependent require dosing for a GFR of 15 unless otherwise indicated by pharmaceutical recommendations.
A nephrology or transplant specialist should be involved in the management of these patients. Frequent monitoring of immunosuppressant agents and specific imaging may be required for evaluation.
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(Updates definition for AKI and discusses treatment. Specifically includes comments that diuretics not be used for treating ATN.)
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