Published: 6 December 2019
Revised:  8 January 2020

Publications

Some medicines increase serum creatinine without affecting glomerular function

Prescriber Update 40(4): 91–92
December 2019

Inhibition of active secretion in proximal tubule

Creatinine is a waste product that is formed during normal muscle catabolism. It is removed from the blood by the kidneys, primarily by glomerular filtration. An increase in serum creatinine usually reflects a reduction in glomerular function.

A small proportion (approximately 15 percent) of creatinine is actively secreted into the urine by the proximal tubule. Inhibition of transporter proteins located in the proximal tubule cell membrane can result in an elevated serum creatinine level and a corresponding fall in the creatinine clearance, without affecting glomerular function^1,2.

In patients with impaired glomerular filtration, a greater proportion of creatinine is excreted via active secretion. Inhibition of the transporter proteins in the proximal tubule cell membrane may have a more significant effect on serum creatinine in patients with chronic kidney disease (CKD), compared to individuals with normal glomerular function².

Medicines that interfere with active secretion of creatinine

Some medicines interfere with the active secretion of creatinine through competition for certain transporter proteins in the proximal tubule cell membrane.

Trimethoprim is one such medicine known to inhibit the secretion of creatinine in the proximal tubule^1,3.

Other currently approved medicines that have been reported to compete with the active secretion of creatinine include amantadine⁴, cobicistat⁵ dolutegravir⁶ and olaparib⁷.

The increase in serum creatinine is usually reversible on stopping the medicine concerned.

References

1. Delanaye P, Mariat C, Cavalier E, et al. 2011. Trimethoprim, creatinine and creatinine-based equations. Nephron Clin Pract 119(3): c187–93; discussion c93–4. DOI: 10.1159/000328911 (accessed 21 October 2019).
2. Inker LA, Perrone RD. 2018. Drugs that elevate the serum creatinine concentration 14 September 2018 (Topic 2361 Version 13.0). In UpToDate. URL: www.uptodate.com/contents/drugs-that-elevate-the-serum-creatinine-concentration (accessed 21 October 2019).
3. Mylan New Zealand Ltd. 2019. TMP New Zealand Data Sheet 9 July 2019. URL: www.medsafe.govt.nz/profs/Datasheet/t/tmptab.pdf (accessed 21 October 2019).
4. Novartis New Zealand Ltd. 2019. Symmetrel New Zealand Data Sheet 15 May 2019. URL: www.medsafe.govt.nz/profs/datasheet/s/symmetrelcap.pdf (accessed 21 October 2019).
5. Gilead Sciences (NZ). 2019. Stribild (tenofovir disoproxil fumarate/ emtricitabine/ elvitegravir/cobicistat) tablets New Zealand Data Sheet 5 February 2019. URL: www.medsafe.govt.nz/profs/datasheet/s/stribildtab.pdf (accessed 21 October 2019).
6.  GlaxoSmithKline (NZ) Ltd. 2019. Tivicay New Zealand Data Sheet 29 October 2019. URL: www.medsafe.govt.nz/profs/Datasheet/t/tivicaytab.pdf (accessed 7 January 2020).
7. AstraZeneca Ltd. 2019. Lynparza New Zealand Data Sheet 5 February 2019. URL: www.medsafe.govt.nz/profs/datasheet/l/lynparzacap.pdf (accessed 21 October 2019).