Acute Tubular Necrosis

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Contents 1 Etiology 2 Epidemiology 3 Pathology 4 Clinical-manifestations 5 Laboratory 6 Complications 7 Management 8 More General Terms 9 Additional Terms 10 References

Etiology

• ischemia

• hypovolemia
• low cardiac output
• renal vasoconstriction
• systemic vasodilatation
• obstetric complications

• abruptio placentae
• postpartum hemorrhage

• recent hemorrhage
• hypotension
• surgery (30%) [7]

• pharmaceutical agents ( nephrotoxic agents)

• aminoglycosides
• amphotericin B
• colistin
• cyclosporine
• methoxyflurane
• polymixins
• radioiodinated contrast medium
• sulfonamides
• tetracyclines
• cisplatin
• acetaminophen

• toxins: ethylene glycol
• endogenous toxins

• rhabdomyolysis
• hemolysis
• uric acid
• oxalate
• multiple myeloma

Epidemiology

• most common form of acute renal failure

Pathology

• oliguric phase

• intratubular obstruction secondary to oncosis of renal tubular epithelial cells
• backleak of glomerular filtrate through a disrupted proximal tubular barrier
• decreased glomerular permeability & GFR

• diuretic phase

• improved GFR
• inability of regenerating tubules to reabsorb Na+ & water normally
• alterations in fluid & electrolyte balance may occur

Clinical-manifestations

• 60% of patients are not oliguric
• oliguric phase

• duration 1-2 weeks
• seldom > 4 weeks
• consider biopsy to seek other causes of renal failure if oliguric phase lasts more than 4 weeks

• diuretic phase

• increases in urine flow not necessarily associated with improvement in serum creatinine early
• serum creatinine improves as glomerular filtration rate ( GFR) increases
• severe hypercalcemia may occur in rhabdomyolysis-induced renal failure during this phase

• recovery phase

• glomerular filtration rate improves over 3-12 months
• generally, GFR stabilizes at a reduced rate, especially in patient who have been oliguric for > 16 days

Laboratory

• urinalysis

• muddy brown granular or tubular epithelial cell casts
• urinary [[[Na+]]] > 20 meq/L
• specific gravity < 1.015
• fractional excretion of sodium ( FENA) > 2% [4]
• urine osmolality similar to serum osmolality
• urine creatinine is generally low ( oliguric phase)

• serum chemistries

• K+ ( hyperkalemia)
• phosphorous ( hyperphosphatemia)
• Ca+2 ( hypocalcemia)
• uric acid ( hyperuricemia)
• myoglobin (increased)
• creatine kinase (increased)
• Na+ ( hyponatremia)
• HC03- ( metabolic acidosis)
• urea nitrogen ( uremia)
• serum creatinine (increased)

• serum protein electrophoresis ( SPE)/immunofixation electrophoresis ( IFE) if indicated
• osmolal gap (if ethylene glycol is suspected)

Complications

• infection is the most common morbidity
• GI bleeding ( platelet dysfunction secondary to uremia)
• hypervolemia with congestive heart failure ( CHF)
• hyponatremia

Management

• restore systemic hemodynamics & renal perfusion
• eliminate nephrotoxins
• consider specific methods

• forced alkaline diuresis to remove uric acid, myoglobin ( rhabdomyolysis), methotrexate
• chelation therapy
• hemodialysis [5] QD is better than QOD
• fenoldopam may benefit a subgroup of patients [6]

• once injured, renal tubular epithelial cells take 3-4 weeks to regenerate

• dialysis
• fluid & electrolyte management

• once tubular regeneration occurs, the patient enters a diuretic phase

• closely monitor for Na+ & K+ loss

• trial of low dose (renal) dopamine plus Lasix
• prognosis: non oliguric patients have better prognosis than oliguric patients
• see acute renal failure

More General Terms

• acute renal failure (ARF)
• renal tubular disease

Additional Terms

• aminoglycoside nephrotoxicity
• fractional excretion of sodium (FENA)
• oncosis (ischemic cell death)

References

1. Harrison's Principles of Internal Medicine, 13th ed. Companion Handbook, Isselbacher et al (eds), McGraw-Hill Inc. NY, 1995, pg 829-39
2. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 1504-1513
3. Applied Laboratory Medicine, Teitz NW, Conn RB & Pruden EL editors, WB Saunders, Philadelphia, 1992
4. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, American College of Physicians, Philadelphia 1998, 2009
5. Journal Watch 22(5):38, 2002 Schiffl H et al Daily hemodialysis and the outcome of acute renal failure. N Engl J Med 346:305, 2002 PMID: [1] Bonventre JV et al, Daily hemodialysis-will treatment each day improve the outcome in patients with acute renal failure? N Engl J Med 346:362, 2002 PMID: [2]
6. Journal Watch 25(17):135, 2005 Tumlin JA, Finkel KW, Murray PT, Samuels J, Cotsonis G, Shaw AD. Fenoldopam mesylate in early acute tubular necrosis: a randomized, double-blind, placebo-controlled clinical trial. Am J Kidney Dis. 2005 Jul;46(1):26-34. PMID: [3]
7. Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010

acute tubular necrosis (ATN)