Basic Information

Definition

Acute tubular necrosis (ATN) is a form of acute kidney injury (AKI) characterized by acute tubular cell injury and dysfunction. It is the most common form of AKI. ATN may be secondary to ischemic injury, nephrotoxic injury, or septic injury or may be multifactorial.

Synonyms

1. ATN

2. Acute tubular injury

3. Ischemic or nephrotoxic acute renal failure (ARF)

4. Tubular necrosis, acute

Epidemiology & Demographics

1. •

   Most common cause of AKI among hospitalized patients.

2. •

   In the intensive care setting, more than 50% of cases will require renal replacement therapy.

3. •

   In-hospital mortality rate is approximately 50%.

4. •

   Risk factors: advanced age, diabetes mellitus, chronic kidney disease, preexisting hypovolemia or poor renal perfusion.

5. •

   Early recognition of ATN is important to prevent further tubular injury by repeated exposure to nephrotoxins.

Physical Findings & Clinical Presentation

1. •

   Physical examination is nonspecific

2. •

   Suspect ischemic ATN in the setting of hemorrhage, hypotension, recent surgery, and/or sepsis

3. •

   Suspect nephrotoxic ATN in the setting of iodinated radiocontrast imaging, nephrotoxic medications, rhabdomyolysis, hemolysis, or multiple myeloma

4. •

   Classic progression of ischemic ATN includes three phases, but can be highly variable:

   1. 1.

      Initiation phase (hours to days): Renal hypoperfusion with evolving ischemia. Acute decrease in glomerular filtration rate (GFR), abrupt elevation of BUN and serum creatinine, and/or decrease in urine output.

   2. 2.

      Maintenance phase (1-2 weeks): Renal cell injury established and GFR stabilizes. At the nadir of GFR, urine output is at its lowest rate (usually 40-400 ml/day). ATN is complicated by hyperkalemia, metabolic acidosis, uremia, and sodium and/or fluid overload. Patients are at an increased risk of infection, and approximately 25% of deaths from ATN occur during the maintenance phase.

   3. 3.

      Recovery phase (>2 weeks): Tubular cell repair and regeneration, with gradual, partial or complete return of kidney function to baseline levels, frequently in association with marked osmotic diuresis and polyuria.

Pathologic Findings

1. •

   Vacuolization and loss of brush border in proximal tubular cells, basement membrane disruption, sloughing of tubular cells, and occlusion of the tubular lumen by casts. Interstitial edema and mild leukocyte accumulation are variably present.

Etiology

1. •

   Diagnosis of exclusion. Prerenal, postrenal, and other intrinsic parenchymal causes of AKI must be ruled out first.

2. •

   Ischemic processes that contribute to ATN include hypotension, shock, prolonged prerenal azotemia, and surgery.

3. •

   Renal hypoperfusion may occur without systemic hypotension (normotensive AKI).

4. •

   Medications: NSAIDs, COX-2 inhibitors, antimicrobial agents (acyclovir, foscarnet, tenofovir, cidofovir, adefovir, aminoglycosides, polymixins, vancomycin, amphotericin B, pentamidine), calcineurin inhibitors, cisplatin, ifosfamide, angiotensin–converting-enzyme inhibitors, angiotensin II receptor blockers, and intravenous immunoglobulin.

5. •

   Iodinated radiocontrast medium (contrast nephropathy).

6. •

   Hemoglobin and myoglobin (rhabdomyolysis, intravascular hemolysis).

7. •

   Heavy metals.

8. •

   Synthetic cannabinoids.

9. •

   Cast nephropathy secondary to multiple myeloma.

   Diagnosis

   Differential Diagnosis

   Prerenal disease (e.g., hypovolemia, cirrhosis, nephrosis, heart failure), postrenal disease (e.g., obstructive nephropathy), intrinsic renal vascular diseases (e.g., vasculitis, thrombotic thrombocytopenic purpura [TTP], hemolytic uremic syndrome [HUS], scleroderma, and malignant hypertension, and renal infarction from aortic dissection), acute glomerulonephritis, acute interstitial nephritis, and atheroembolic renal disease.

   Laboratory Tests & Findings

   1. •

      Urinalysis with specific gravity <1.015 and low-grade albuminuria with more severe ATN.

   2. •

      Urine osmolality <450 mOsm/kg (usually <350 mOsm/kg). Urine sediment examination reveals muddy brown casts (Fig. 1) and renal tubular epithelial cells.

      

   3. •

      Fractional excretion of sodium [FE_Na (%) = 100% × (U_Na × P_Cr)/(P_Na × U_Cr)] typically exceeds 1%.

   4. •

      Multiple biomarkers for early diagnosis of ATN are currently under investigation, but none are suitable for routine clinical use.

   Imaging Studies

   No specific studies are indicated, but appropriate studies may be ordered to diagnose the etiology of ATN (e.g., CT scan to search for an infectious process that may be the cause of AKI in a septic patient) or rule out other causes of AKI (e.g., kidney ultrasound to rule out obstruction).

   Treatment

   Acute General Rx

   The general management of ATN is the same as that for acute kidney injury. Hemodynamic abnormalities should be corrected and potentially nephrotoxic agents discontinued. Renal replacement therapy may be required until renal function is restored. There is no significant evidence that diuretic administration reduces the requirement for dialysis or improves renal recovery. However, diuretic use may facilitate fluid balance management.

   Disposition

   Kidney function typically recovers within 2 to 3 weeks after onset. Outcomes are variable and depend on premorbid kidney function, mechanism of injury, and superimposed renal insults. Patients who are younger or nonoliguric have a better prognosis than patients who are older or are oliguric. Patients may remain dialysis-dependent for up to 3 months before sufficient tubular regeneration occurs. Of patients surviving an ATN episode (∼50%), approximately 5% to 10% never recover kidney function and remain dialysis-dependent.

   Referral

   Nephrology consultation

   Pearls & Considerations

   Comments

   Some patients with ATN may have FE_Na <1%: patients taking ACEIs, ARBs, or NSAIDs; cirrhosis; heart failure; radiocontrast injury; heme pigment–induced injury (e.g., myoglobinuria or hemoglobinuria); and early sepsis.

   Prevention

   1. •

      Aggressive intravascular volume resuscitation in hypovolemic surgical/trauma patients

   2. •

      Discontinuation of potentially nephrotoxic agents

   3. •

      Lowest volume of nonionic radiocontrast agents with preprocedural and postprocedural isotonic intravenous fluid administration (e.g., sodium chloride or sodium bicarbonate)

   Related Content

   1. Acute Kidney Injury (Related Key Topic)