Kidney disease, drug-induced

See Chapter 49, Drug-Induced Kidney Disease, authored hy Thomas D. Nolin and Jonathan Himmelfarb, for a more detailed discussion of this topic. 

We call attention also to the web site for the Drug-Induced Liver Injury Network (DILIN) sponsored since 2003 by the National Institutes of Health (NIH), Liver Disease Branch of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). 

Pearson J (2008) Drug-induced kidney disease. In Ashley C, Morlidge C (eds) Introduction to Renal Therapeutics. London Pharmaceutical Press, 139-144. 

Factors that put patients at risk of lithium intoxication are those that increase intake (deliberately or accidentally), reduce excretion (kidney disease, dehydration, low sodium intake, drug interactions), or reduce body water (dehydration secondary to fluid restriction, vomiting, diarrhea, or polyuria) (66). Patients with lithium-induced polyuria are at a particular risk of toxicity if their ability to replace fluids is compromised (for example by anesthesia, over-sedation, CNS trauma). 

Fleury D,Vanhille P, Pallet IL, Kleinknecht D. Drug induced acute renal failure a preventable disease linked to drug misuse. Kidney Inti 990 38 1238. 

Izzedine H, Launay-VacherV, and Deray G. Antiviral drug-induced nephrotoxicity. American Journal of Kidney Diseases 45 804-817,2005. 

Heroin nephropathy/clinical course Amyloidosis associated with intravenous drug abuse HIV nephropathy and its relationship to heroin nephropathy Acute kidney injury due to drug-induced rhabdomyolysis Cocaine-induced renal disease 598 599 601 603 605... 

Almost half of the reported patients with acute kidney injury due to rhabdomyolysis have required dialy tic support. Nevertheless, the majority of patients regain significant renal function. The mortality from drug-induced rhabdomyolysis and ATN has been low despite the common occurrence of intercurrent infection. This may be related to the patients being young and without prior multisystem disease. 

Calcineurin inhibitor nephrotoxicity presents as two distinct forms of renal injury. Acute nephrotoxicity is a dose-dependent, hemodynamically mediated disorder, not accompanied by particular or permanent structural changes which is reversible with decrease or discontinuation of the offending drug. On the other hand, calcineurin inhibitor-induced chronic nephrotoxicity is an insidious lesion, characterized by an irreversible and progressive renal interstitial fibrosis, which may cause important impairment in renal function and even stage 5 chronic kidney disease. 

Excretion is the process by which drugs are eliminated from the body. Excretion occurs primarily via the kidneys, although other routes include the gastrointestinal tract, the respiratory system, and sweat, saliva, and breast milk. Adequate excretion is dependent on effective kidney function. Disease- or drug-induced damage to the kidneys can lead to kidney failure, resulting in a toxic accumulation of medications in the bloodstream. 

One side effect unique to hydralazine is a dose-dependent drug-induced lupus-like syndrome. Hydralazine is eliminated by hepatic A-acetyltransferase. This enzyme displays genetic polymorphism, and slow acetylators are especially prone to develop drug-induced lupus with hydralazine. This syndrome is more common in women and is reversible on discontinuation. Drug-induced lupus may be avoided by using less than 200 mg hydralazine daily. Other side effects of hydralazine include dermatitis, drug fever, peripheral neuropathy, hepatitis, and vascular headaches. For these reasons, hydralazine has limited usefulness in the treatment of hypertension. However, it is still used with isosorbide dinitrate in patients with heart failure (especially African-Americans) and is useful in patients with severe chronic kidney disease and kidney failure. 

The initial diagnosis of drug-induced kidney disease typically involves detection of elevated serum creatinine and blood urea nitrogen, for which there is a temporal relationship between the toxicity and use of a potentially nephrotoxic drug. 

Mechanisms of drug-induced kidney disease include immune-mediated toxicities (e.g., glomerulonephritis and allergic interstitial nephritis) and nonimmunologic-mediated toxicities which effect specialized characteristics of normal renal physiology. 

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