Dear Karunarathna,

The first and foremost impact of CKD is the reduced renal function itself. As GFR is decreased this will have a direct impact on elimination of drugs primarily eliminated through passive renal filtration (which elimination is proportional to GFR). CKD can also impact the production of proteins (also in other organs such as the liver), this can impact plasma protein binding of drugs, and hence impact passive filtration. Only the free fraction of drug can be filtered (plasma proteins are large and are not passively filtered), for a low molecular weight compound that is not re-absorbed renal clearance (CLr) is free fraction (fu) times GFR: CLr=fu*GFR. CLr may be the sole contributor to clearance or part of the elimination of a drug.

CKD may impact metabolism in the kidney. This is not a major route of elimination for most drugs.

CKD can also influence expression of metabolic enzymes, typically caused by uremic toxins reducing enzymatic activity (including in the liver) or transporters (in the kidney and other organs). It can then impact the elimination through liver metabolism or active renal secretion.

Overall, CKD has potential to reduce elimination of drugs through different mechanisms. Dose would need to be reduced when the impact is significant.

Inhaled anesthetics are typically exhaled unchanged. This phenomenon should be related to respiratory capacity and not to CKD.

The effect of CKD will therefore depend on the pathways of elimination of the specific drug. This is not the same for different anesthetics. The drug label (PIL, SmPC...) should provide more specific information for a specific drug product.

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