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Nephrology - Acute Kidney Injury - Fast Facts | NEJM Resident 360

The term acute kidney injury (AKI) has largely replaced the term acute renal failure (ARF).

Diagnosis

Although several sets of diagnostic criteria exist for AKI, The Kidney Disease: Improving Global Outcomes (KDIGO) 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease (CKD) is used most often.

The KDIGO guideline identifies three stages of AKI based on plasma or serum creatinine level or urine output:

Stages of AKI Based on Plasma or Serum Creatinine Level or Urine Output

Stage	Plasma or Serum Creatinine Level	Urine Output
1	1.5–1.9 times baseline OR by ≥0.3 mg/dL (≥26.5 μmol/L) increase	<0.5 mL/kg/hr for 6–12 hours
2	2.0–2.9 times baseline	<0.5 mL/kg/hr for ≥12 hours
3	3.0 times baseline OR initiation of renal replacement therapy (RRT)	<0.3 mL/kg/hr for ≥24 hours OR anuria for ≥12 hours

A few caveats about using these criteria to stage AKI:

• Plasma or serum creatinine concentration may not accurately reflect the glomerular filtration rate (GFR) in patients with AKI who are not in a steady state as kidney injury evolves. Other markers, such as cystatin C, may be more accurate.

• Creatinine is removed by dialysis. Therefore, creatinine level is not a good indicator of kidney function in patients who are receiving dialysis.

• Brief periods of oliguria may have other causes and do not necessarily represent AKI (e.g., in cases in which adequate fluid resuscitation has not occurred).

Types of AKI

• Prerenal AKI generally is due to hypovolemia (e.g., hemorrhage, dehydration) but can also be seen in patients who are hypervolemic yet have low intravascular volume (e.g., heart failure or hepatorenal syndrome). Prolonged prerenal AKI can lead to intrinsic injury such as acute tubular necrosis (ATN).

• Intrinsic AKI can have many causes, including:

  • ATN — a form of tubulointerstitial disease that can be due to toxic or ischemic renal insults, prolonged hypovolemia, or shock; by far the most common etiology

  • tubulointerstitial disease

  • glomerular disease

  • small vessel renal vascular disease (vasculitis)

• Postrenal or obstructive AKI is due to obstruction of the urinary tract, often by prostatic disease, pelvic cancers, kidney stones, and occasionally retroperitoneal fibrosis or other conditions.

• Contrast nephropathy: Patients with reduced kidney function, volume depletion, or both have an increased risk for superimposed AKI from other insults. The iodinated contrast used for cardiac and radiologic imaging has long been associated with AKI, but data indicate that the risk is smaller than previously thought, leading some clinicians and investigators to question whether the risk exists at all. This discrepancy may be related to the use of safer contrast agents, smaller doses of contrast, and more judicious use of contrast in patients with reduced renal function. The pathogenesis of AKI from contrast is considered multifactorial and may be related to both a vasoconstrictive effect of contrast and direct tubular toxicity. Risk factors for contrast-induced AKI include chronic kidney disease, diabetes, heart failure, advanced age, volume depletion, hypotension, use of concurrent nephrotoxic medications, and use of a large-volume or high-osmolality contrast agent. Volume expansion with isotonic fluid (normal saline or sodium bicarbonate) is the only proven method of reducing the risk for contrast-induced nephropathy (see prevention of contrast nephropathy below). 

• AKI in Covid-19: Pleaseseethe****NEJM Coronavirus (Covid-19) topic page.

Workup

• The history and physical exam, including the sequence of events leading to AKI, can help discern the cause. Note: Thoroughly examine the patient’s prescribed and over-the-counter medication list for nephrotoxic drugs.

• Urine testing should include complete urinalysis (dipstick with microscopy for the assessment of the urinary sediment) and, in selected cases, quantification of urine protein or albumin (typically using random or “spot” determinations of the protein-to-creatinine ratio or albumin-to-creatinine ratio, although the accuracy of spot measurement is reduced in AKI).

• • Urinalysis is one of the oldest and most basic tests for evaluation of the presence, severity, and course of diseases of the kidney and urinary tract. Therefore, when a patient is first seen by a nephrologist, a complete urinalysis should always be requested. The microscopic analysis of the urinary sediment can help identify disease etiology, based on the formed elements identified.

  • Fractional excretion of sodium (FE_Na) testing is often ordered, but its utility is questionable. It is most useful for distinguishing prerenal AKI from ATN in oliguric states. Calculate the FE_Nahere. Fractional excretion of urea (FE_Urea) testing should be used in patients who have received diuretics, which cause obligate natriuresis and inappropriately high urine sodium concentrations.

  • Urine specific gravity is ordered as part of the urinalysis and is a surrogate for osmolality. Either urine specific gravity or osmolality can be useful in assessing hydration status or determining if there is a problem with urinary concentration. Random urine specific gravity is generally 1.010 to 1.025, and urine osmolality should average 300–900 mOsm/kg of water.

• Imaging (often renal ultrasound) is performed to rule out obstructive etiologies and catastrophic vascular compromise when there is no obvious cause of renal dysfunction.

• Kidney biopsy should be considered (with a nephrology consult) if creatinine level continues to rise with no obvious cause. The most common indications for kidney biopsy in the setting of AKI are rapidly progressive glomerulonephritis and nephrotic syndrome.

The National Institute for Health and Care Excellence (NICE) provides a good visual overview of the AKI workup here. (Note: These are U.K. guidelines, and some aspects may differ from U.S. guidelines.)

Management

• Volume status:

  • In patients who are volume depleted, fluid resuscitation (preferably with a crystalloid solution such as isotonic saline) should be initiated in an attempt to reverse the AKI and prevent further progression.

  • In patients who are volume overloaded, diuretics can be used, but they may be ineffective or useful only as a temporizing measure before initiation of renal replacement therapy (RRT).

• Hyperkalemia: Patients with hyperkalemia refractory to medical management (e.g., furosemide, insulin and dextrose [D50], sodium polystyrene sulfonate, calcium bicarbonate) may require urgent RRT.

• Metabolic acidosis: If severe, metabolic acidosis usually requires RRT, but occasionally you can give bicarbonate (consult nephrology before starting it). Generally, acidosis improves as the AKI resolves. Relative contraindications to bicarbonate administration include volume overload, lactic acidosis, and diabetic ketoacidosis — in the latter two conditions, the focus should be treatment of the underlying disorder to correct the acidosis, while providing support.

• Renal replacement therapy (RRT): RRT may include intermittent hemodialysis (iHD), continuous renal replacement therapy (CRRT), or acute peritoneal dialysis. Indications for RRT include:

  • fluid overload refractory to diuretics

  • severe hyperkalemia or hyperkalemia refractory to medical therapy

  • acidemia refractory to treatment

  • signs of uremia or an otherwise unexplained decline in mental status

CRRT is preferred over iHD in patients with hemodynamic compromise (e.g., patients with sepsis or who are receiving vasopressors).

Prevention

Identifying patients at high risk of developing AKI is important, particularly those who may be hospitalized.

Persons at high risk for AKI include:

• Patients undergoing major surgery

• Patients with conditions causing hemodynamic instability (e.g., sepsis, cardiogenic or hemorrhagic shock)

• Patients with comorbidities (e.g., malignancy, heart failure, and diabetes)

• Patients with cardiovascular disease who are undergoing imaging with contrast

Administration of nephrotoxic drugs should be avoided, and fluid volume status must be carefully managed in high-risk patients.

Prevention of contrast nephropathy: Infusion of isotonic saline is the only strategy that has consistently been shown to reduce the incidence of contrast-induced AKI in at-risk patients. Oral N-acetylcysteine is sometimes used in addition to isotonic fluid but not as a replacement for it. However, the data regarding N-acetylcysteine are controversial and some evidence indicates that acetylcysteine may not be effective in reducing the risk of contrast nephropathy. Intravenous N-acetylcysteine occasionally causes hypersensitivity reactions and is generally avoided in this setting. The 2012 KDIGO guideline recommends adequate hydration with saline and makes no recommendations regarding the use of acetylcysteine.

Do contrast enhanced CT studies lead to kidney injury? A retrospective cohort study demonstrated that patients who underwent contrast-enhanced CT were no more likely to develop AKI than those who did not undergo CT.

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