Acute Tubular Necrosis

Acute Tubular Necrosis
Presented by Dr Gagandeep K Heer, MD

* Definition: ARF is defined as an abrupt or rapid decline in the renal function.
* A rise in serum BUN or creatinine concentration, with or without decrease in urine output, usually is evidence of ARF.
* ARF is often transient and completely reversible.

Background
* The causes of ARF are divided into 3 categories:

Prerenal
Renal
Postrenal
* ATN is the most common cause of ARF in the renal category.
* ATN is the 2nd most common cause of all categories of ARF in hospitalized patients, with only prerenal azotemia occurring more frequently.
* In outpatients, obstruction (ureteric, bladder neck or urethral) is the 2nd most common cause of ARF after prerenal azotemia.
* Other causes of ARF include acute interstitial nephritis, acute glumerulonephtitis, vasculitis, HUS, TTP, DIC, accelerated HTN, radiation nephritis, acute on chronic renal failure, renovascular obstruction (bilateral or unilateral in the setting of single functioning kidney), renal allograft rejection, intratubular deposition and obstruction (myeloma proteins, urate, oxalate crystals, etc.)

Pathophysiology
* ATN usually occurs after an acute ischemic or toxic event, and it has a well-defined sequence of events.
* Initiation phase characterized by acute decrease in GFR to very low levels, with a sudden increase in serum Cr and BUN concentrations.
* Maintenance phase is characterized by sustained severe reduction in GFR and the BUN and Cr continue to rise.
* Recovery phase, in which the tubular function is restored, is characterized by an increase in urine volume (if oliguria was present) and gradual decrease in Cr and BUN to their pre-injury level.

Ischemic ATN
* Ischemic ATN is often described as a continuum of prerenal azotemia. Response to fluid repletion can help distinguish between the two: return of renal function within 24-72 hours usually indicate prerenal disease although short-lived ATN can recover within similar timeframe (e.g. self limited insult such as transient aortic clamping during suprarenal aortic aneurysm surgery).
* Initiation phase: Hypoperfusion initiates cell injury that often leads to cell death. It is most prominent in straight portion of the proximal tubules and thick ascending limb of loop of Henle. The reduction in the GFR occurs not only from reduced filtration due to hypoperfusion but also from casts and debris obstructing the lumen, causing back leak of filtrate through the damaged epithelium (ineffective filtration). In addition, ischemia leads to decreased production of vasodilators (i.e. nitric oxide, prostacyclin) by tubular epithelial cells, leading to further vasoconstriction and hypoperfusion.
* Maintenance phase is characterized by stabilization of GFR at a very low level, and it typically lasts 1-2 weeks. Uremic complications typically develop during this phase. In addition to the above mentioned mechanism of injury, tubulo-glomerular feedback also plays a role by causing constriction of afferent arterioles by the macula densa cells, which detect and increased salt load in the distal tubules.
* During Recovery phase, there is regeneration of tubular epithelial cells. An abnormal diuresis sometimes occurs, causing salt and water loss and volume depletion. The mechanism of the diuresis is not completely understood, but it may in part be due to delayed recovery of tubular cell function in the setting of increased glomerular filtration. In addition, continued use of diuretics (often administered during initiation and maintenance phases) may also add to the problem.

Nephrotoxic ATN
* Most of the pathophysiological features of ischemic ATN are shared by the nephrotoxic forms and it has the same three phases.
* Nephrotoxic injury to tubular cells occurs by multiple mechanisms including direct toxicity, intrarenal vasoconstriction, and intratubular obstruction.
* Ischemic ATN

Nephrotoxic ATN
Frequency
History
Physical Exam
* Physical exam may be unremarkable because ARF is often found incidentally during routine laboratory studies (i.e. elevated BUN and Cr).
* Look for pericardial friction rub (pt may have pericarditis), asterixis and/or excoriation marks related to uremic pruritis.
* Hypertension or edema may be noted.
* Physical findings related to the underlying disease.

Causes of ATN
Causes of Ischemic ATN
Causes of Nephrotoxic ATN
Exogenous toxins
Aminoglycosides:
Amphotericin B:
Exogenous Toxins
Radiocontrast media:
Endogenous toxins
Myoglobinuria
Hemoglobinuria
Crystals:
Workup
Lab studies
Laboratory Findings Used to Differentiate Prerenal Azotemia from ATN
Plasma BUN/Cr ratio
Imaging Studies
Renal biopsy
Complications
Prevention
Treatment
Mortality and Morbidity
Prognosis

Acute Tubular Necrosis.ppt