Section 5 -

Acute Tubular Necrosis Donna J. Lager, M.D. Matthew Lewin, M.D.

Case 4: Acute Tubular Necrosis A 61 year old man with a history of alcohol abuse presented with chest pain and acute renal failure. His serum creatinine was 3.2 mg/dl. Acute tubular necrosis (ATN) is one of the most common causes of acute renal failure. Of all causes of acute renal failure, ATN comprises a majority of cases, however of biopsied causes of renal failure, ATN comprises a minority. ATN as a diagnostic category defines acute renal failure caused be damage to the tubular epithelium. ATN can be divided into two broad categories, (1) ischemic and (2) toxic causes. Clinical Presentation and Diagnosis: Acute renal failure is a common diagnosis, especially in hospitalized patients. Acute renal failure most commonly presents as progressive oliguria and azotemia though it can sometimes present as polyuria. Acute renal failure has many causes, and when caused by damage to the tubular epithelium, is termed acute tubular necrosis. Since the main therapy for ATN is supportive, other treatable causes of acute renal failure should be excluded clinically, serologically and by obtaining a needle biopsy of the kidney, if necessary. It is important to keep in mind when a kidney biopsy is performed for acute renal failure that the patient's physician is looking for treatable causes of acute renal failure. Laboratory Findings: Typically ATN presents with increased creatinine and BUN. No single serum test can define ATN, however negative results for several serologic tests including ANCAs and anti-GBM are helpful. On urinalysis, granular and cellular casts are often seen, though these findings are not specific for ATN. A mild amount of hematuria can be seen with ATN and this finding should not rule out the diagnosis of ATN. Mild proteinuria can also be observed, however nephrotic range proteinuria is not expected. Morphologic Findings Ischemia Related ATN: Ischemic causes of ATN demonstrate patchy tubular damage, especially to the proximal segment of the tubules. The tubules themselves demonstrate necrosis of single cells and denudation of the tubule epithelium. Sloughed necrotic and non-necrotic cells are observed in the tubules, especially the distal collecting system. Though the word "necrosis" is in the diagnosis, necrosis of individual cells is not always observed, and is not required for the diagnosis. The most common histologic finding is tubular simplification (best observed on Trichrome Stain). Simplification probably has several causes including loss of the brush border in the proximal tubules (seen best on PAS Stain). Tubular simplification can be observed in other processes such as urinary tract obstruction. Ischemic damage is caused by lack of proper oxygenation of the epithelium and sometimes the cause of ATN can be observed morphologically (for example atheroemboli). Toxin Related ATN: Toxic injury more commonly causes severe damage to all segments of the tubules. Toxins that can injure the kidney are numerous and varied. They include industrial related toxins, substances identified in herbal medicines/remedies, and medications. Often the offending agent will not be identified. Some histologic findings will give clues to the cause of ATN: Calcium oxalate crystals Ethylene Glycol Dark intranuclear inclusions Lead Lysosomal myeloid bodies (on EM) Aminoglycoside therapy The differentiation between toxic and ischemic causes of ATN can be difficult and can not always be determined on biopsy. Differential Diagnosis: Tubular damage is a common pathway of renal injury and once identified, other causes of acute renal failure should be excluded. Other causes include acute crescentic glomerulonephritis, light chain cast nephropathy and atheroemboli. The morphologic finding of ATN should be correlated with the clinical and laboratory findings to ensure no treatable cause of ATN is missed. For example a biopsy that shows ATN but only has a limited number of glomeruli in a patient with acute renal failure and massive hematuria, the possibility of an under sampled crescentic glomerulonephritis should be considered. One diagnostic problem is differentiating ATN with mild inflammation and edema in the interstitium, from early acute interstitial nephritis (AIN). The line between ATN and AIN can be difficult to determine. Usually the ATN demonstrates patchy very mild inflammation, mostly confined to the capillary lumens and surrounding areas of tubular damage. References: Renal Biopsy Interpretation, Ed. FG Silva, VD D'Agati, T Nadasdy, Churchill Livingstone, 1996. Lameire NH. Vanholder R. Pathophysiology of ischaemic acute renal failure. Best Practice & Research. Clinical Anaesthesiology. 18(1):21-36, 2004 Mar Solez K. Racusen LC. Role of the renal biopsy in acute renal failure. Contributions to Nephrology. (132):68-75, 2001. Racusen LC. The histopathology of acute renal failure. New Horizons. 3(4):662-8, 1995 Nov.