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Source: Matzke GR. Drug Therapy Individualization for Patients with Chronic Kidney Disease. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th edition. and Dager W, Halilovic J. Acute Kidney Injury. In: DiPiro, JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM. Pharmacotherapy: A Pathophysiologic Approach. 8th edition. Accessed August 15, 2012.


  • Chronic kidney disease (CKD) causes changes in disposition of some drugs as result of changes in bioavailability, distribution volume, and metabolic activity.
  • Drug therapy individualization (DTI) may involve:
    • Simple proportional dose adjustment based on creatinine clearance (CLcr) or glomerular filtration rate (GFR)
    • Complex adjustments for drugs extensively metabolized or undergoing dramatic changes in protein binding and distribution volume.
  • Patient response to given drug may differ because of physiologic and biochemical changes associated with CKD.
  • Goals of DTI: design drug regimens to optimize therapeutic outcomes and minimize adverse effects.


  • Drug absorption
    • Little quantitative information available
    • Bioavailability theoretically affected by:
      • Alterations in gastrointestinal (GI) transit time
      • Gastric pH
      • Edema of GI tract
      • Vomiting and diarrhea
      • Concomitant drug therapy, especially antacid or H2-antagonist administration
  • Drug distribution
    • CKD significantly increases or decreases volume of distribution.
    • Plasma protein binding of acidic drugs (e.g., warfarin, phenytoin) is decreased in end-stage renal disease (ESRD).
      • Monitor drug concentrations of free (unbound) drug.
    • Binding of basic drugs (e.g., quinidine) is usually normal or slightly increased or decreased.
    • Method to calculate volume of distribution (VD) can be influenced by renal disease.
      • Use distribution at steady state (VSS) to compare patients with renal insufficiency to others with normal renal function.
      • VSS is independent of drug elimination.
  • Metabolism
    • CKD may decrease nonrenal clearance of drugs to greater degree than seen in AKI (Table 1).
    • Severe renal insufficiency can cause accumulation of metabolites that contributes to pharmacologic activity or toxicity.
  • Excretion
    • Renal clearance of drug is composite of GFR, tubular secretion, and reabsorption.
    • Importance of altered renal function on drug elimination depends on fraction of drug normally eliminated unchanged by kidneys and degree of renal insufficiency.
    • Difficult to quantify contribution of tubular function to renal drug clearance.
    • Clinical measurement or estimation of CLcr or GFR remains guiding factor for drug dosage regimen design.

Table Graphic Jump Location
Table 1. Nonrenal Clearance of Many Drugs Is Reduced in Patients with End-Stage Renal Disease

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