Description

• Acute tubular injury (ATI) is the new nomenclature, now commonly used in place of acute tubular necrosis to define a sudden reduction in renal functioning, resulting from a myriad of different insults to the renal tubular epithelial cells.
• ATI is the most common cause of acute kidney injury (AKI) in hospitalized patients, responsible for 33–45% of AKI cases. Thus, it becomes vitally important for clinicians to be familiar with this entity.
• Mortality rates in critically ill children are high, ranging from 9% to 67% with most cases representing ATI.
• ATI is a term embodying damage to the renal tubular mechanism, specifically the epithelial cells, from nephrotoxic or ischemic insults.
  • A multitude of different pathologies and mechanisms can result in ATI, ranging from volume depletion states leading to impaired renal perfusion to atherosclerotic or embolic phenomena injuring the renal tubules to iatrogenic damage secondary to vascular interventions.
  • Of note, damage to the renal parenchyma, vasculature, and glomeruli have also been documented in cases of ATI (1).

Epidemiology

Incidence

• A prospective, multicenter, community-based study in Spain estimated the overall incidence of AKI to be 209 cases per million population (PMP), with ATI representing the most common cause at of AKI at 45% (1).
• Three large multicenter administrative databases demonstrated that approximately 2% of hospitalized patients in the United States had a diagnosis of AKI.
• Estimated incidence of AKI globally during hospitalization is 5–7% (2), with up to 40% of critical care patients developing AKI (3).
• The population incidence of AKI rose from 610 PMP in 1988 to 2,888 PMP in 2002, representing an increase of 11% per year since 1988 according to a large multicenter study.
• A recent study characterizing AKI in the United States showed that AKI has been growing at a rate of 14% per year since 2001, with AKI being present in >35% of all in-hospital death cases. This highlights the clinical and public health significance of AKI and the challenges ahead for managing this disease entity.
• A 20-center prospective study on AKI found an incidence of 7.7% in the ICU setting, with the principle cause attributed to ATI.
• The PICARD multicenter study in the United States showed a 50% rate of ATI as the etiology of AKI.
• Mortality rates from ATI in hospitalized and ICU patients are estimated at 37.1% and 78.6%, respectively.

Etiology and Pathophysiology

• Two primary etiologies of ATI are postischemic (“ischemic”) and nephrotoxic, but a mixed picture is the most common presentation (3).
• Septic shock is leading cause of postischemic ATI (1).
• Nephrotoxic agents can be endogenous (hemoglobin and myoglobin) or exogenous (aminoglycosides, radiocontrast media, nonsteroidal anti-inflammatory drugs [NSAIDs], amphotericin B, cisplatinum, etc.) (2).
• Ischemic ATI:
  • The clinical manifestations of ischemic ATI lie on a continuum, which include both changes in glomerular filtration that are traditionally labeled prerenal and direct tubular epithelial cell injury that is traditionally labeled intrarenal.
  • Classically, 1- to 2-week oliguric phase (≤400 mL/24 hr) followed by nonoliguric phase (>400 mL/day) of 10 to 14 days (2)
• Causes of ischemic ATI can be further classified as follows:
  • Decreased effective arterial perfusion, renal vasculature vaso-occlusive disease, and renal vasculature vasoconstriction states
• Decreased effective arterial perfusion:
  • Shock: septic, cardiogenic, hypovolemic, distributive
  • Autonomic dysfunction
  • Low oncotic pressure states: cirrhosis, nephrotic syndrome, protein-losing nephropathies
  • Adrenal dysfunction
  • Iatrogenic: medication induced, perioperative
• Renal vasculature vaso-occlusive disease:
  • Renal artery stenosis
  • Atheroembolic disease
  • Thromboembolic phenomena
• Renal vasculature vasoconstriction states:
  • Medication induced
  • Toxin mediated
• Renal tubular epithelial damage most commonly occurs at the proximal tubules, and damaged cells undergo one of three pathways: repair, apoptosis, and necrosis.
• Four phases of ATI:
  • Initiation—renal blood flow decreases, resulting in decrease in cellular adenosine triphosphate (ATP) and renal tubular epithelial injury
  • Extension—continued corticomedullary junction hypoxia and inflammatory response by tubular cells (TNF-α, IL-1, IL-6, IL-8, etc.) and leukocytes
  • Maintenance—cells undergo repair
  • Recovery (2)
• Biopsy shows detachment of renal tubular epithelial cells from basement membrane, sloughing of cells into tubular lumen, effacement, loss of brush border in proximal tubular segments, formation of tubular casts, and interstitial edema (2).

Risk Factors

• Decreased renal perfusion due to medication effects: NSAIDs, angiotensin-converting enzyme (ACE) inhibitors, cyclosporine (4)
• Cardiovascular surgery, especially with suprarenal aortic clamping (3)
• Risk factors for prerenal disease: hypovolemia, hypotension, and third space sequestration (e.g., heart failure and cirrhosis)
• Additional risk factors: male sex, elderly, those with comorbid conditions, mechanical ventilation, multiorgan dysfunction/failure, sepsis, and oliguria (1)

General Prevention

• Preservation of renal blood flow
• Limit effects of IV contrast media:
  • Avoid contrast studies if possible.
  • Use low-osmolar contrast media (LOCM) in preference to high-osmolar or even iso-osmolar (5)[A].
  • Consider giving a statin, N-acetylcysteine, and saline to patients with chronic kidney disease; the combination has best evidence to prevent nephropathy (5)[A].
• Avoid nephrotoxic antibiotics when able and renally dose antibiotics based on current kidney function and glomerular filtration rate.
• In rhabdomyolysis, use fluids and mannitol if necessary to maintain urine output (UO) >300 mL/hr until no myoglobin in urine (6)[A].
• Hospital protocols for management of hemodynamic and oxygenation parameters in perioperative setting or in patients with septic shock (7)

Commonly Associated Conditions

• Septic shock
• Renal artery stenosis
• Chronic kidney disease
• Rhabdomyolysis