The effects of many drugs get altered in renal impairment particularly when a drug has renal clearance. Drug doses should be altered in renal disease in accordance with the predicted reduction in the clearance of the drug. Some patient factors also influence the decision to adjust drug doses, such as the degree of renal disease and patient size. There are some drug factors to be considered to adjust doses including the drug excretion and the therapeutic index. Estimation of renal function is helpful in the dosing of renally excreted drugs.
Renal disease can alter the drug concentration in the body and the effects of many drugs, sometimes reducing their effects but more commonly escalating their effects and thus causing potential toxicity. Most of these changes are predictable and may be prevented by altering drug doses in accordance with the established guidelines.
Mainly, there are three ways in which renal disease affects a drug:
- Patient susceptibility - patients with renal impairment may be more vulnerable to a certain drug effect
- Pharmacodynamic change - a drug effect may be increased or decreased in patients with renal disease
- Pharmacokinetic changes - some drugs, when given at usual doses, have higher steady-state concentrations in patients with renal impairment
Increased drug clearance leads to lower drug concentrations and decreased drug clearance leads to higher drug concentrations; hence greater drug effects. To avoid harm, the dose of renally cleared drugs should be decreased in patients with renal disease.
Chronic kidney disease (CKD) is a form of kidney disease in which there is a gradual loss of kidney function occurring over a period of months to years. Although many sites of drug metabolism and excretion exist, the chief organ of metabolism is the liver, whereas the organ primarily tasked with excretion is the kidney.
By definition, the presence of both factors (glomerular filtration rate [GFR] less than 60 mL/min and albumin greater than 30 mg per gram of creatinine) accompanied by abnormalities of kidney structure or function for longer than three months signifies chronic kidney disease. End-stage renal disease, furthermore, is defined as a GFR less than 15 mL/min.
Renal impairment modifies the effects of many medications, occasionally diminishing them but more usually enhancing or even multiplying them, thus leading to accumulation and potential toxicity. Many of these alterations can be and should be predicted and subsequently alleviated by adjusting drug doses.
Summarizing the above: The medication dose should be decreased equivalently to the calculated reduction of drug clearance.