Costas D. Lallas, MD, FACS
BASICS
DESCRIPTION
• Acute tubular necrosis is the most common type of intrarenal acute renal injury (AKI)
– Usually due to prolonged ischemia or administration of nephrotoxins
• A syndrome of intrinsic renal failure secondary to ischemic or toxic insults
• Histopathologic findings of ATN variable
• Decreased urine output:
– Can be nonoliguric, oliguric >500 mL/d, or anuric. Mortality increases from 20–60% to 80% if the patient is oliguric or anuric.
• Signs of underlying disorder:
– Signs of sepsis or of hypotensive events secondary to trauma, cardiac disease, surgery with excessive blood loss, or interruption of blood supply to kidneys
EPIDEMIOLOGY
Incidence
• ARF is present in 209 per million population.
• ARF may affect 2–5% of patients in a tertiary care hospital, and the incidence of ARF in the surgical or medical ICU may exceed 20–30%
• Breakdown of ARF: ATN, 45%; prerenal causes, 21%; acute or chronic renal failure, 13%; urinary tract obstruction, 10%; glomerulonephritis or vasculitis, 4%; acute interstitial nephritis, 2%; atheroembolism, 1%
RISK FACTORS
• Decreased renal perfusion from:
– Prolonged hypotension, surgical interruption of blood flow, NSAIDs, ACE inhibitors, cyclosporine
• Nephrotoxic agents:
– Radiocontrast media (low osmolality is possibly safer), aminoglycosides, cisplatin, amphotericin, drug intoxications with acetaminophen or ethylene glycol
– The most commonly seen nephrotoxins in the hospitalized patient include radiographic contrast material, antibiotics (especially aminoglycosides and amphotericin B), chemotherapeutic agents, NSAIDs, and ACE inhibitors
Genetics
N/A
PATHOPHYSIOLOGY (1)
• Acute tubular injury
• Renal hypoperfusion and renal ischemia are the most common causes of ATN
• The ischemic form is due to the reductions in glomerular filtration rate (GFR) are secondary to vascular and tubular factors
– Ischemia from reductions in GFR from decreased renal plasma flow or dilatation of the efferent arteriole. After return of normal blood flow, ATN persists secondary to tubular changes
– In addition, both exogenous and endogenous nephrotoxic compounds exist.
• Tubular factors: Backleak and tubular obstruction. Tubular obstruction secondary to a sloughed brush border, cellular debris, Tamm–Horsfall protein, and decreased filtration pressure contribute to obstruction and maintenance of ATN
ASSOCIATED CONDITIONS
• Sepsis
• Hemorrhage (operative, obstetric, trauma)
• Pre-existing renal insufficiency (diabetes, hypertension)
• Edematous states such as CHF
GENERAL PREVENTION
• Avoid prolonged renal ischemia by timely management of hemorrhage, dehydration and other causes of renal hypoperfusion
• Avoidance of contrast agents in the setting of renal insufficiency (contrast-induced nephropathy)
• Appropriate management of potentially nephrotoxic medications
DIAGNOSIS
HISTORY
• Specific attention to:
– Hypotensive episodes, blood transfusions, intravenous contrast exposure
• Meticulous listing of medications to include dosage to assure appropriate dosing for level of renal function
• Make sure other medications which depend on renal metabolism are also given at appropriate doses to avoid side effects
PHYSICAL EXAM
• Vital signs and hemodynamic parameters should be critically assessed.
• A patient’s weight is helpful information, and its daily measurement is important in the diagnosis and management of ARF.
• Evaluate the volume status of the patient.
• Evaluate neck veins and auscultation of heart and lungs; assess extremities and the presacral area for edema.
• General exam
• Evaluate for bladder distention and assess for signs of vasculitis or cutaneous rashes.
DIAGNOSTIC TESTS & INTERPRETATION
Lab
• Serum tests (2)
– BUN/plasma creatinine ratio: The ratio is normal at 10 to 15:1 in ATN, but >20:1 in prerenal disease due to the increase in passive reabsorption of urea, the ratio may also be increased with GI bleed, muscle breakdown, and administration of corticosteroids or tetracycline
– Rate of rise of plasma creatinine: Rise of >0.3–0.5 mg/dL in ATN vs. slower rise with fluctuations with prerenal disease
• Urine tests
– Urinalysis: Muddy brown granular and epithelial cell casts and free epithelial cells secondary to sloughing of the tubular epithelium vs. near-normal in prerenal disease
– The classic sediment of ATN includes pigmented (muddy brown) granular casts and renal tubular epithelial cells, which may be seen in nearly 80% of cases of oliguric ARF
– Urine sodium concentration: High >40 mEq/L due to tubular injury vs. <20 mEq/L in prerenal disease in an attempt to conserve sodium
– Fractional excretion of sodium (FENa): Above 2% in ATN while <1% in prerenal disease, measured as urine Na divided by plasma Na times plasma CR divided by urine CR, although causes of ATN associated with a low FENa are that due to intravenous contrast material, rhabdomyolysis, sepsis, and multisystem organ failure
– Urine osmolality: Urine osmolality <450 mOsm/kg in ATN secondary to loss of concentrating ability; >500 mOsm/kg in prerenal disease
• Urine creatinine concentration divided by plasma creatinine concentration: Ratio is <20 in ATN while >40 in prerenal disease, reflecting loss of tubular water reabsorption
Imaging
• Renal ultrasonography
– Sensitive test to determine obstruction. Doppler can detect gross blood flow in renal vein and artery
• Plain abdominal film
– Identifies the presence or location of renal calculi and is particularly helpful to discern the proper position of stents and drains
• Functional studies
– Nuclear scans can determine perfusion or tubular secretion; MRI can give some functional information while providing anatomic information
Diagnostic Procedures/Surgery
N/A
Pathologic Findings
• Tubule cell injury (2):
– Tubular epithelial cells are particularly sensitive to ischemia and are also vulnerable to toxins. The structural changes include those of reversible injury (such as cellular swelling, loss of brush border and polarity, blebbing, and cell detachment) and those associated with lethal injury (necrosis and apoptosis)
• Disturbances in blood flow:
– Intrarenal vasoconstriction results in both reduced glomerular blood flow and reduced oxygen delivery to the functionally important tubules in the outer medulla (thick ascending limb and straight segment of the proximal tubule)
DIFFERENTIAL DIAGNOSIS
• Prerenal azotemia
• Postrenal azotemia
• Other forms of renal azotemia
• Glomerulonephritis, disseminated intravascular coagulopathy, arterial or venous obstruction, intrarenal precipitation
TREATMENT
GENERAL MEASURES
• Define and treat the underlying cause.
• Discontinue any nephrotoxic agents.
• Prophylaxis and treatment of complications of ARF.
• Early nephrology consultation.
• Management of fluid disturbances.
• Maintain a euvolemic state by restricting total fluids to no more than urine output plus insensible losses.
MEDICATION
First Line
• High-dose loop diuretics (1–3 g/d) may convert oliguric to nonoliguric ATN in some patients; it has not been determined that this conversion decreases the duration of ATN or mortality. Dopamine may increase urine output, but its benefit is in question.
– Studies suggest that patients who respond to mannitol, furosemide, or dopamine with an increased urine output have better outcomes than nonresponders.
• Management of electrolyte disturbances
– Electrolyte disturbances can be minimized by prophylactic institution of a low-potassium, low-protein diet accompanied by fluid restriction and oral phosphate binders.
• Hyperkalemia is the most common and most dangerous abnormality and should be treated aggressively with calcium supplementation until potassium levels can be reduced with combinations of insulin and glucose or potassium-binding resins.
Second Line
N/A
SURGERY/OTHER PROCEDURES
• Hemodialysis (HD), peritoneal dialysis (PD), and continuous arteriovenous hemofiltration (CAVH)
– CAVH: Need ICU, limited mobility, need anticoagulation, removes fluid well but slow correction of electrolyte abnormalities
– PD: No anticoagulation needed but slower correction of electrolyte abnormalities
– HD: Expensive, anticoagulation necessary, vascular access necessary but allow rapid correction of fluid and electrolyte abnormalities
ADDITIONAL TREATMENT
Radiation Therapy
N/A
Additional Therapies
N/A
Complementary & Alternative Therapies
N/A
ONGOING CARE
PROGNOSIS
• Slight improvements in survival in those patients with ATN requiring dialysis in an ICU setting
– The Mayo Clinic compared 1977–1979 with 1991–1992 showed high survival both in hospital (52% vs. 32%) and at 1 yr (30% vs. 21%)
– Higher mortality rates are seen in elderly patients and in patients with respiratory failure, multiple organ failure, pre-existing chronic diseases, and systemic hypotension
• Major causes of death are infection and underlying disease, not renal failure
– Patients at risk are generally very ill, with evidence of multiple organ dysfunction
• Of patients who survive ATN, nearly half will have a complete recovery of renal function and a majority of the remainder have an incomplete recovery. Only about 5% of all ARF patients require chronic maintenance dialysis
COMPLICATIONS
• Fluid overload, electrolyte disturbances, metabolic acidosis
– Hypertension, edema, acute pulmonary edema, hyponatremia, hyperkalemia, hypermagnesemia, hypercalcemia, hyperphosphatemia, hyperuricemia
– Uremic signs and symptoms
• GI: Nausea, vomiting, GI bleed; neurologic: Encephalopathy, coma, seizures, peripheral neuropathy; cardiac: Pericarditis uremic pneumonitis; hematologic: Bleeding, anemia; immunologic: Impaired granulocyte/lymphocyte function
FOLLOW-UP
Patient Monitoring
• Duration
– Renal failure phase usually lasts 7–21 days if the primary insult (ischemia, nephrotoxin) can be corrected. Recovery is usually heralded by a progressive increase in urine output and a return of BUN and CR to the previous baseline.
• Recovery of renal function
– Irreversible loss of renal function can occur if the combination of pre-existing renal disease and prolonged ARF secondary to repeat ischemic insults and/or nephrotoxin administration
– If the patient survives, baseline CR is usually only 1–2 mg/dL above baseline.
• Those patients that need dialysis and have bioincompatibility with the dialysis membrane or have repeat episodes of hypotension have a worse prognosis.
Patient Resources
N/A
REFERENCES
1. Goldfarb DA, Poggio ED. Etiology, pathogenesis, and management of renal failure. In: Wein AJ, Kavoussi LR, Novick AC, Partin AW, Peters CA, eds. Campbell-Walsh Urology, 10th ed. Philadelphia, PA: WB Saunders, 2012.
2. Erdbruegger U, Okusa, MD. Etiology and diagnosis of prerenal disease and acute tubular necrosis in acute kidney injury (acute renal failure). UpToDate. Accessed August 4, 2014
ADDITIONAL READING
Belcher JM, Parikh CR. Is it time to evolve past the prerenal azotemia versus acute tubular necrosis classification? Clin J Am Soc Nephrol. 2011;6:2332–2334.
See Also (Topic, Algorithm, Media)
• Acute Kidney Injury, Adult (Renal Failure, Acute)
• Acute Kidney Injury, Pediatric (Renal Failure, Acute)
• Contrast Induced Nephropathy (CIN)
CODES
ICD9
584.5 Acute kidney failure with lesion of tubular necrosis
ICD10
N17.0 Acute kidney failure with tubular necrosis
CLINICAL/SURGICAL PEARLS
• High-dose loop diuretics (1–3 g/d) may convert oliguric to nonoliguric ATN in some patients; it has not been determined that this conversion decreases the duration of ATN or mortality.
• Of patients who survive ATN, nearly half will have a complete recovery of renal function and a majority of the remainder have an incomplete recovery. Only about 5% of all ARF patients require chronic maintenance dialysis.
• A patient’s weight is helpful information, and its daily measurement is important in the diagnosis and management of ARF.