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CHAPTER OBJECTIVES

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  • List the common causes of chronic kidney disease (CKD) and describe how CKD affects drug elimination.

  • Compare the advantages and disadvantages of the use of drugs or endogenous substances as markers for the measurement of renal function.

  • Describe the relationships between creatinine clearance, serum creatinine concentration, and glomerular filtration rate.

  • Explain and contrast the methods of Cockcroft–Gault and Modification of Diet in Renal Disease (MDRD) for the calculation of creatinine clearance.

  • List the causes for fluctuating serum creatinine concentration in the body.

  • Calculate the dose for a drug in a patient with renal disease.

  • Describe quantitatively using equations how renal or hepatic disease can alter the disposition of a drug.

  • Describe hemoperfusion and the limitations for its use.

  • Distinguish between hemodialysis and peritoneal dialysis and calculate dose adjustments of a drug in patients undergoing dialysis.

  • Describe the principle of the fraction of drug excreted unchanged (fe) method and how it is applied to adjust doses in renal disease.

  • Explain the principle involved in the Giusti–Hayton method.

  • Describe the effects of hepatic disease on the pharmacokinetics of a drug.

  • List the reasons why dose adjustment in patients with hepatic impairment is more difficult than dose adjustment in patients with renal disease.

  • Explain how liver function tests relate to drug absorption and disposition.

  • List the pharmacokinetic properties of a drug for which dose adjustment would not be required in patients with renal or hepatic impairment.

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RENAL IMPAIRMENT

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Chronic kidney disease (CKD) is a worldwide public health problem affecting more than 50 million people, and more than 1 million of them are receiving kidney replacement therapy (Levey et al, 2009). The kidney is an important organ in regulating body fluids, electrolyte balance, removal of metabolic waste, and drug excretion from the body. Impairment or degeneration of kidney function affects the pharmacokinetics of drugs. Some of the more common causes of kidney failure include disease, injury, and drug intoxication. Table 24-1 lists some of the conditions that may lead to chronic or acute renal failure. Acute diseases or trauma to the kidney can cause uremia, in which glomerular filtration is impaired or reduced, leading to accumulation of excessive fluid and blood nitrogenous products in the body. Uremia generally reduces glomerular filtration and/or active secretion, which leads to a decrease in renal drug excretion resulting in a longer elimination half-life of the administered drug.

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Table Graphic Jump Location
TABLE 24-1Common Causes of Kidney Failure

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