Renal impairment and Drug Metabolism

Renal diseases can cause considerable variability in drug response, which may present as enhanced or diminished drug response. Renal diseases (kidney diseases) affect the glomerular blood flow, glomerular filtration, tubular reabsorption and secretion. Renal bioactivation affects the drug metabolism, which causes alterations in drug absorption, bioavailability, distribution, binding of drugs to proteins and renal or non-renal clearance. Accumulation of drug metabolites and exogenous substances may make it necessary for the clinician to adjust the dose of drugs for the renal disease and associated ailments otherwise this variability can lead to either enhanced efficacy or enhanced toxicity depending on the drug characteristics. Renal diseases (renal disorders) may affect both pharmacokinetic and pharmacodynamic characteristics of a drug (as thiopental has been observed to cause prolongation of its anesthetic action and gentamycin to cause increased toxicity).

Dosage adjustment is usually needed if >30% drug is excreted unchanged in urine or is removed by dialysis in patients with renal impairment or renal failure. Impaired and compromised renal function effects the drug elimination and leads to accumulation of drug. The accumulation of drug further depends on the frequency of drug administration and half life of drug. The treating physician needs to know the pharmacokinetics and pattern of accumulation of drugs in renal failure and tentative time to achieve the steady concentration in plasma for the adequate dose adjustments.

Primary influence of renal disease on drug absorption is almost negligible. However, a few secondary influences like vomiting and diarrhoea due to uremia lead to dehydration and further lead to decreased perfusion and absorption of drugs from intramuscular and intestinal sites. Diabetic and uremic gastroparesis leads to altered rates of absorption of short acting drugs like sulfonylureas. Acid base imbalance and alteration in the levels of potassium in serum affects gastrointestinal tract mobility and rate & extent of drug absorption. Commonly used antacids bind and chelate dietary phosphates and lead to hypophosphatemia, also impair the absorption of drugs like iron and ketaconazole which need an acidic pH for optimal absorption. Impaired protein binding may also impair absorption of drugs. Edema caused by nephrotic syndrome or congestive heart failure has been documented to slowdown the drug absorption and cause increased bioavailability of drugs.