Chapter

Nephrotoxicity of chemotherapy agents and chemotherapy administration in patients with renal disease

Carlos D. Flombaum

in Cancer and the Kidney

Second edition

Published on behalf of Oxford University Press

Published in print November 2010 | ISBN: 9780199580194
Published online November 2012 | e-ISBN: 9780191753404 | DOI: http://dx.doi.org/10.1093/med/9780199580194.003.0005

Series: Oxford Clinical Nephrology Series

Nephrotoxicity of chemotherapy agents and chemotherapy administration in patients with renal disease

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The kidneys normally receive 20% of the cardiac output. Drugs are filtered and/or secreted and then progressively concentrated in the urine. Therefore, these organs are especially vulnerable to the toxic effects of many drugs, including chemotherapy agents.

Nephrotoxicity is often a dose-limiting adverse effect of chemotherapy. Chemotherapy agents can affect the microvasculature, the glomerulus, or the tubules. Depending on the site of the nephron more adversely affected, the clinical manifestations may vary from a hemolytic process resembling the hemolytic uremic syndrome (HUS) or a tubular-interstitial injury causing asymptomatic decreases in the glomerular filtration rate (GFR), overt renal failure requiring dialysis, or a variety of electrolyte disorders. Because the kidneys are one of the major routes of elimination of many drugs, nephrotoxicity is a serious complication in patients undergoing chemotherapy. The dose of renally eliminated drugs has to be adjusted in order to prevent systemic toxicity, and the administration of other potentially nephrotoxic drugs, such as chemotherapy agents or antibiotics, may have to be interrupted, making management of the patient more difficult.

This section will review the nephrotoxic effects of different chemotherapy agents and some preventive measures to avoid their nephrotoxicity. The metabolism of those chemotherapy agents that are predominantly renally excreted and the recommended dose modifications in patients with renal insufficiency will be reviewed in the second part of this chapter. The most common methods utilized to estimate GFR are the creatinine clearance (CrCl) or the clearance of radiolabeled compounds. The creatinine clearance can be determined from a 24-hour urine collection or based on formulas which use the plasma creatinine concentration (like the Cockcroft–Gault equation). More recently, clinical laboratories are using the Modification of Diet in Renal Disease (MDRD) equation to report GFR, but it needs to be stressed that up to now, the vast majority of pharmacokinetic studies in oncology did not use this formula and were performed by measuring CrCl or estimating it by the Cockcroft–Gault equation. For practical purposes and because they are close to each other in absolute value, creatinine clearance and GFR are used interchangeably throughout this chapter.

Chapter.  25570 words.  Illustrated.

Subjects: Nephrology

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