Effect of medication in renal impairment

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As a route of elimination, the kidneys are important for many drugs and human metabolism. In the USA, it has been calculated for the 200 most commonly prescribed drugs that around one third of them are excreted from the body unchanged by at least 25% - renal insufficiency, however, can restrict this process, which can lead to side effects.

Human kidney cross section on scientific background. 3D illustration

shutterstock.com / crystal light

Renal insufficiency defined:

Renal insufficiency (i.e., kidney weakness) is defined by the impaired functioning or total nonfunctioning of the kidneys. The main function of the kidneys is to filter and clean the blood. In doing so, the kidneys remove excess water and toxic metabolites (i.e. metabolic products) from the blood, which are subsequently excreted in the form of urine. This makes the bean-shaped organs vital for water and salt balance regulation and for body detoxification.

Weakness of the kidneys can lead to edema (i.e. water retention in the tissues), high blood pressure, nervous system dysfunction and bone loss, among other things. If the kidneys fail completely, only dialysis (i.e. blood purification) or a kidney transplant can ensure the patient's survival.

Kidney as an elimination pathway for drugs:

Different processes are involved in drug degradation:

  • Passive glomerular filtration
  • Active secretion in renal tubules (i.e. tubule)
  • Tubular reabsorption

Glomerular filtration is a so-called ultrafiltration of the blood, during which the primary urine is formed. During this process, substances that are freely present in the blood (i.e. not bound to proteins) are also passed over. The substance quantity of this excretion therefore depends on the protein binding and on the glomerular filtration rate (short: GFR). The GFR describes the efficiency of all renal corpuscles (i.e. glomeruli) in the organ.

Active secretion into renal tubules can occur with the help of different transporters (e.g.: ABC transporters). Tubular reabsorption can also occur by transporters - but primarily by diffusion. Renal insufficiency can affect all three degradation processes, causing drugs to be excreted more poorly and leading to side effects or even intoxication.

Renal insufficiency in numbers:

According to a study of adult health in Germany published in the German Medical Journal, about 2.3% aged 18 to 79 have limited kidney function, but only 16% of these sufferers are under a doctor's care. Another study in Germany showed that in nursing homes, about two-thirds of residents with an average age of 83.3 years have limited kidney function - 20% of these were receiving at least one permanent medication with an inappropriate dosage or a contraindication (i.e. an occurring circumstance that prohibits a diagnostic or therapeutic measure).

This suggests that renal insufficiency may be unknown or inadequately considered in a proportion of patients.

Determination of renal function:

In everyday life, a very accurate determination of renal function is not easy to implement, as this would require so-called exogenous markers (i.e. substance that provides information about the biological state) to measure GRF (glomerular filtration rate). For routine diagnostics, renal function is therefore determined using the endogenous marker creatinine (i.e. substance responsible for supplying energy to the muscles). Healthy adults usually have a GFR of more than 120 ml/min, which decreases with age. Renal insufficiency is defined as a GFR of less than 60 ml/min, and the drug dose is also based on the glomerular filtration rate. Common dosages are found at 30 to 60 ml/min, 15 to 30 ml/min and below 10 or 15 ml/min - the last category is in the range of so-called permanent renal insufficiency.

Do pharmacists recognize renal insufficiency?

In a French study published in 2015, general pharmacists identified patients with renal insufficiency only according to the criteria: Age over 65 years and prescription of at least two antihypertensives (i.e., antihypertensive drugs) or antidiabetics. By recognizing such patients, pharmacists could potentially counsel more effectively on self-medication and correct inappropriate dosages or recognize contraindications. A multicenter observational or cross-sectional design study published in 2013 examined 40 Spanish pharmacies and determined that such a medication dosage adjustment service for elderly patients with renal insufficiency, may increase the proportion of adjusted dosing and avoid drug-related problems as a result.

Dangerous self-medication:

A common problem seen is that most people identify painkillers as harmless without a prescription. The mineral calcium can be problematic in some circumstances for patients with impaired renal function, as several mechanisms of calcium level regulation are impaired in chronic renal insufficiency. As a result, absorption through the gastrointestinal tract and also renal calcium excretion may be reduced. Consequently, a possible low calcium level could promote bone metabolism disorders with increased risk of osteoporosis in chronic renal insufficiency. However, excessive calcium levels may lead to storage of calcium salts in blood vessels, promoting possible atherosclerosis or hypertension.

Conclusion:

Patients with renal insufficiency should therefore take calcium supplements only after consultation with their physician and perform regular monitoring of serum levels. Both the correct adjustment of the dose and the avoidance of high-risk drugs are of great significance. Especially in elderly patients, with the help of close monitoring of pain medications by pharmacists, a more complex side effect or even intoxication can possibly be avoided.


References:

Brunton L. L., Lazo, J. S., Parker, K. L., (ed.). The Pharmacological Basis of Therapeutics. Mc Graw Hill Education. 2010.

Lepist, E. I., et al. Renal transporter-mediated drug-drug interactioons: are they clinically relevant? J. Clin. Pharmacol 56. 2016. p73-S81.

Girndt M, Trocchi P, Scheidt-Nave C, Markau S, Stang A. The prevalence of renal failure-Results from the German Health Interview and Examination Survey for Adults. 2008-2011 (DEGS1). Dtsch Arztebl Int 2016. 113: 85-91. DOI: 10.3238/arztebl.2016.0085.

Hoffmann, F., et al, Renal insufficiency and medication in nursing home residents. Dtsch. Ärzteblatt Int. 2016.

Pourrat X, Sipert AS, Gatault P, Sautenet B, Hay N, Guinard F, Guegan F, Halimi JM. Community pharmacist intervention in patients with renal impairment. Int J Clin Pharm. Dec 2015.

https://www.netdoktor.de/krankheiten/niereninsuffizienz/

https://www.pharmazeutische-zeitung.de/ausgabe-292017/folgen-fuer-die-medikation/

Sources:

  • Brunton L. L., Lazo, J. S., Parker, K. L., (ed.). The Pharmacological Basis of Therapeutics. Mc Graw Hill Education. 2010.
  • Lepist, E. I., et al. Renal transporter-mediated drug-drug interactioons: are they clinically relevant? J. Clin. Pharmacol 56. 2016. S73-S81.
  • Girndt M, Trocchi P, Scheidt-Nave C, Markau S, Stang A. The prevalence of renal failure—Results from the German Health Interview and Examination Survey for Adults. 2008–2011 (DEGS1). Dtsch Arztebl Int 2016. 113: 85–91. DOI: 10.3238/arztebl.2016.0085
  • Hoffmann, F., et al., Niereninsuffizienz und Medikation bei Pflegeheimbewohnern. Dtsch. Ärzteblatt Int. 2016.
  • Pourrat X, Sipert AS, Gatault P, Sautenet B, Hay N, Guinard F, Guegan F, Halimi JM. Community pharmacist intervention in patients with renal impairment. Int J Clin Pharm. Dez. 2015.
  • Niereninsuffizienz (Netdoktor) (accessed on 4.3.2021)
  • Folgen für die Medikation (Pharmazeutische Zeitung) (accessed on 4.3.2021)

Author

Danilo Glisic

Last Update

08.03.2021

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