Clinical Course, Pathogenesis, and Anatomy of Acute Tubular Necrosis



ATN syndrome is characterized by an acute and usually progressive loss of tubular and glomerular function. The vast majority of patients with ATN have as their initiating event either a decrease in renal plasma flow or exposure to a nephrotoxic agent. The vasomotor nephropathy variant of ATN occurs in a patient in whom there is a de­crease in blood pressure and/or in the effective circulating volume. The pathophysiological events in the generation of vasomotor nephropa­thy are not known with certainty (Stein et al., 1978). An initial decrease in renal blood flow ap­pears to be a requisite for the development of ATN. However, blood flow returns nearly to nor­mal within 24 to 48 hours after the initial insult. Despite adequate renal blood flow, tubular dys­function persists and the glomerular filtration rate remains depressed. The factor or factors that sus­tain the renal functional impairment after the pri­mary insult depend upon the the nature of the original insult. Leakage of glomerular ultrafiltrate from the tubular lumen into the interstitium across the damaged renal tubular cells, obstruc­tion to flow due to debris or crystals in the lumen of the tubules, loss of high-energy intermediates in renal tubular cells, and a decrease in the glo­merular capillary ultrafiltration coefficient (Kf) have all been proposed to play a pathophysio­logical role in sustaining the clinical picture of ATN.

The toxic nephropathy variant of ATN occurs in clinical circumstances in which the patient has been exposed to a nephrotoxic agent. These agents impair tubular function and cause a secondary de­crease in filtration. Many drugs have been impli­cated in causing toxic nephropathy. Antibiotics, particularly the aminoglycoside antibiotics, and specific cancer chemotherapeutic agents are two classes of drugs commonly associated with ATN. Specific forms of toxic nephropathy are discussed in Chapter 35.
Histologically, the kidney may appear nearly normal. The brush border membranes of the prox­imal convoluted tubule may be absent and cel­lular debris may be observed in the tubule lu­mens. In patients with rhabdomyolysis and ATN, myoglobin-stained casts may be observed on his­tological examination of the kidney. Cellular in­filtrates are not usually prominent unless there is an associated interstitial nephritis. There is, how­ever, edema of the interstitium. Aminoglycoside antibiotic toxicity may be suggested by the pres­ence of lipid whorls in the cytoplasm of the renal tubular cells. It is to be stressed that in the vast majority of patients with ATN, the histological picture is nondiagnostic. Despite the common use of the term acute tubular necrosis, necrosis of the tubules is rarely observed. The glomeruli appear normal by light microscopy. The functional ab­normalities of ATN are not expressed in the his­tology of the kidney.





Clinical Course, Pathogenesis, and Anatomy of Acute Tubular Necrosis