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Overview of Tubulointerstitial Diseases

by Navin Jaipaul, MD, MHS

Tubulointerstitial diseases are clinically heterogeneous disorders that share similar features of tubular and interstitial injury. In severe and prolonged cases, the entire kidney may become involved, with glomerular dysfunction and even renal failure. The primary categories of tubulointerstitial disease are acute tubular necrosis and acute or chronic tubulointerstitial nephritis.

Pathophysiology

The kidneys are exposed to unusually high concentrations of toxins. The kidneys have the highest blood supply of all tissues (about 1.25 L/min or 25% of cardiac output), and unbound solutes leave the circulation via glomerular filtration at 100 mL/min; as a result, toxic agents are delivered at a rate 50 times that of other tissues and in much higher concentrations. When urine is concentrated, the luminal surfaces of tubular cells may be exposed to molecule concentrations 300 to 1000 times greater than those of plasma. The fine brush border of proximal tubular cells exposes an enormous surface area. A countercurrent flow mechanism increases ionic concentration of the interstitial fluid of the medulla (and thereby increases urine concentration) up to 4 times the plasma concentration.

In addition, factors can affect cellular vulnerability after exposure to toxins. Tubular transport mechanisms separate drugs from their binding proteins, which normally protect cells from toxicity. Transcellular transport exposes the interior of the cell and its organelles to newly encountered chemicals. Binding sites of some agents (eg, sulfhydryl groups) may facilitate entry but retard exit (eg, heavy metals). Chemical reactions (eg, alkalinization, acidification) may alter transport in either direction. Blockade of transport receptors may alter tissue exposure (eg, diuresis from blockade of adenosine A1 receptors may decrease exposure). Finally, the kidneys have the highest O 2 and glucose consumption per gram of tissue and are therefore vulnerable to toxins affecting cell energy metabolism.

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