Elimination at the kidney
The kidneys, along with the liver, play a central role in the elimination of pharmaceutical agents. They can be filtered at the glomerulus of the nephron, actively secreted at the proximal tubule, and reabsorbed at various tubular segments. In renal insufficiency, these processes are impaired. This may result in a renally eliminated drug remaining in the organism for a longer period of time, an increase in plasma concentration, and accumulation. Possible consequences include adverse effects and potentially life-threatening toxicity, especially for drugs with a narrow therapeutic range. In addition, renal insufficiency may also affect other pharmacokinetic parameters, for example, distribution and protein binding. In addition to the drug, its active metabolites are also involved in this process, for example, the glucuronides of morphine or oxypurinol, the metabolite of allopurinol.
Dose Adjustment
Depending on the pharmacokinetic and pharmacodynamic properties of the drug, dose adjustment may be necessary. However, it should be noted that this does not automatically apply to all drugs, but mainly to those with relevant renal elimination. Some can be administered without adjustment as in healthy individuals. The adjustment depends on the extent of renal dysfunction, which is expressed by the glomerular filtration rate (GFR). The lower the GFR, the greater the need for adjustment. Measurement of serum creatinine can be used for a rough estimate of GFR. The value obtained by a conversion is called eGFR (estimated GFR) or estimated creatinine clearance. Other parameters such as age, weight, gender and ethnicity are also taken into account (methods: Cockcroft-Gault, MDRD, CKD-EPI). Due to the function of the kidneys as elimination organs, a dose reduction is generally required in the case of renal insufficiency. This involves lowering the single dose and the maximum daily dose. The dosing interval can also be extended, so that a drug is administered only once instead of twice a day, for example, or only every other day. Less frequently, plasma concentrations are also measured as part of therapeutic drug monitoring. Some drugs are contraindicated in renal insufficiency, i.e. must not be given for safety reasons (toxicity). Renal impairment may also be a contraindication for regulatory reasons in the absence of data. Patients should not receive drugs that are harmful to the kidneys (nephrotoxic) if possible. These include, for example, the nonsteroidal anti-inflammatory drugs (NSAIDs), the aminoglycosides, vancomycin, certain contrast agents, lithium, cidofovir, and cytostatic agents. In some rare cases, a dose increase may be indicated because the site of action is in the kidney. Typical examples are the loop diuretics torasemide and furosemide.
Clarification before therapy
Before initiating drug treatment, it must be clarified individually for each drug whether a dose adjustment is necessary due to renal insufficiency. This applies to both self-medication and prescription drugs. Especially in the elderly, possible renal dysfunction must always be considered, as the incidence increases with age. Studies have shown that dose adjustments are still made too infrequently (e.g., Dörks et al., 2017). In principle, the guidelines can be found in the drug information leaflets. However, sufficient and adequate data are not available for all drugs. In addition, the scientific literature can be consulted and databases such as DOSING (http://www.dosing.de) are available.
