Porth's Essentials of Pathophysiology, 4e

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Kidney and Urinary Tract Function

U N I T 7

FIGURE 25-12. Chronic pyelonephritis. (A) The cortical surface contains many irregular depressed scars (reddish areas). (B) There is marked dilation of calyces caused by inflammatory destruction of papillae, with atrophy and scarring of the overlying cortex. (From Jennette JC.The kidney. In: Rubin R, Strayer DS, eds. Rubin’s Pathology: Clinicopathologic Foundations of Medicine. 6th ed. Philadelphia, PA: Wolters Kluwer Health | Lippincott Williams &Wilkins; 2012:797.)

B

A

state of hydration, blood pressure, and the pH of the urine. Elderly persons are particularly susceptible to kidney damage caused by drugs and toxins. The dan- gers of nephrotoxicity are increased when two or more drugs capable of producing kidney damage are given at the same time. Drugs and other toxic substances can damage the kid- neys by causing a decrease in renal blood flow, directly damaging tubulointerstitial structures, producing hyper- sensitivity reactions, or obstructing urine flow. Some drugs, such as diuretics, high–molecular-weight radiocon- trast media, the immunosuppressive drugs cyclosporine and tacrolimus, and the nonsteroidal anti-inflammatory drugs (NSAIDs), can cause acute kidney injury by decreasing renal blood flow (discussed in Chapter 26). Other drugs such as sulfonamides and vitamin C supple- ments can form crystals that cause kidney damage by obstructing urinary flow in the tubules. Acute drug-related hypersensitivity reactions produce tubulointerstitial nephritis, with damage to the tubules and interstitium. This condition was observed initially in persons who were sensitive to the sulfonamide drugs; currently, it is observed most often with the use of meth- icillin and other synthetic antibiotics, and with the use of furosemide and the thiazide diuretics in persons sensi- tive to these drugs. The condition begins approximately 15 days (range, 2 to 40 days) after exposure to the drug. 4 At the onset, there is fever, eosinophilia, hematuria, mild proteinuria, and, in approximately one fourth of cases, a rash. In approximately 50% of cases, signs and symp- toms of acute renal failure develop. Withdrawal of the drug commonly is followed by complete recovery, but there may be permanent damage, usually in older per- sons. Drug nephritis may not be recognized in its early stage because it is relatively uncommon. Chronic analgesic nephritis , which is associated with analgesic abuse, causes tubulointerstitial nephritis with

renal papillary necrosis. Prostaglandins (particularly PGI 2 and PGE 2 ) are potent renal vasodilators that contribute to the regulation of renal blood flow. The deleterious effects of aspirin and other NSAIDs are thought to result from their ability to decrease prostaglandin synthesis and thus decrease renal blood flow. The susceptibility of the papil- lae to damage is believed to be related to the establishment of a renal gradient in which the papillary concentration of the drug is higher than in the cortex. Persons particu- larly at risk are the elderly because of age-related changes in renal function, individuals who are dehydrated or have a decrease in blood volume, and those with preexisting kidney disease or renal insufficiency. Chinese herbal drugs have also been implicated in drug-related kidney damage. Early recognition of the problem surfaced in the early 1990s with reports of an unusually rapid and progressive form of renal failure in women with a shared history of chronic ingestion of slimming herbs, such as ephedra (ma huang), from China as part of a weight loss program. 23 Growing evi- dence from both clinical and animal models suggests that this form of kidney damage is attributable, at least in part, to the presence of aristolochic acid in the slim- ming herb preparations. Illicit drug use has also been implicated in a wide spectrum of kidney diseases. 26 For example, acute renal failure has been reported in persons presenting with acute cocaine intoxication. The cause is probably mul- tifactorial and involves direct vasoconstriction, altered systemic hemodynamics, and myoglobin-induced renal failure. The chronic inhalation of solvents (e.g., glue, paint thinner), aerosols, gases, and nitrates has also been associated with a variety of toxic kidney effects, including acute and chronic renal failure. The tubular manifestations of solvent abuse probably result from the interference with intracellular metabolic processes involved in membrane transport.