Monday, December 8, 2008

Bactrim & elevated creatinine

The antibiotic Bactrim is frequently associated with an increase in creatinine shortly after starting it. While Bactrim is a not uncommon cause of acute interstitial nephritis (AIN), the most frequent reason for a Bactrim-associated creatinine increase is actually artifactual one. Bactrim inhibits a particular cationic transporter in the proximal convoluted tubule which is also responsible for creatinine secretion. By doing this, serum creatinine elevates without an acutal decrease in GFR. This is the same mechanism by which cimetidine (Tagamet, also an organic cation) results in an elevated creatinine. For the most part, this mild elevation in creatine is inconsequential and is not a reason for discontinuing the antibiotic.

In addition to an elevated creatinine, Bactrim is also associated with hyperkalemia. The mechanism is felt to be a decreased aldosterone-mediated Na reabsorption via the ENac channel in the collecting duct.

10 comments:

Anonymous said...

The increase in creatinine associated with TMP is mild: 10% and reversible with drug discontinuation.

The mechanism of Bactrim induced hyperkalemia is via Trimethoprim inhibition of the sodium channel located on the luminal surface of the principal cells, independent of aldosterone blockade. ( Same site of action of amiloride , triameterene and pentamidine). This will decrease sodium reabsorption and the electro negativity in the lumen thus decreasing the driving force for the secretion of potassium through an apically located potassium channel on the same principal cells. This side effect is most common in HIV infected patients who are treated with high doses of TMP-SMX. However hyperkalemia can occur with lower doses used to treat routine infections. Be cautious thus when using TMP-SMX in patients with preexisting renal dysfunction or in those taking concurrent medications (such as angiotensin-converting enzyme inhibitors and potassium-sparing diuretics) that may exacerbate this hyperkalemic effect to potentially dangerous levels.

nathanhellman said...

Very interesting, thanks for your comments.

If Bactrim does act at the ENac, then that would in fact mean that it could be considered a potassium-sparing diuretic, much alike amiloride.

A quick glance at the literature would seem to support this.

http://www.ncbi.nlm.nih.gov/pubmed/10423629?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSum

Anonymous said...

Great website, thank you! Will be checking in on a regular basis.

Kidney_Boy said...

When I was a fellow, I was a subject in a couple of research studies where the subjects took cimetidine while collecting a 24-hour urine in order to allow the urinary creatinine to better reflect glomerular filtration (i.e. block proximal tubule creatinine secretion).

Anonymous said...

I'm a practicing nephrologist.
Just saw a patient 2 days ago,
stage 4 CKD, Cr 2.2

was on Acei/Spironolactone/ also had type 4 rta from DM.

Podiatrist placed on Bactrim. 3 days later in ER with Cr 4 and K 7.9.

I saw BActrim used indiscriminately with CKD patients by urologist especially.

We need to educate them.

Dr. Helbert Rondon said...

Trimethoprim, Triamterene, Amiloride, and Pentamidine have the same effect over ENaC, and therefore can cause hyperkalemia

Unknown said...

I am a patient with CKF (stage 3)and non-alcoholic cirrhosis of the liver and on diuretics. I went into the ER yesterday complaining of pain at a 7-8 level in a umbilical hernia that has developed. The ER doctor sent me to have a CT and told me they saw cellulitis in the area of my hernia. He gave me an antibiotic that I filled today. When I looked at the bottle I was very surprised to see that it was Bactrim, which I knew was a sulfur based drug. I asked the pharmacist is this safe for persons with chronic kidney failure and he told me to call my nephrologist before I take it to confirm. It is too late now to call, so I am writing to ask what information is available regarding this question or does anyone know? Isn't there a more sensible antibiotic to take for cellulitis or to treat this type of infection, it has to be sulfur based? I thank those who answer, in advance.

margaret said...

I hope someone is still answering posts on this site. My husband had stage 2 CKD and was prescribed Bactrim DS 800 mg BID for a toe infection by the podiatrist. Shouldn't the podiatrist have thought to check w/ his nephrologist first? My husband wound up in hospital for 7 weeks w/ ARF and had multiple complications, almost died. He has been in rehab two weeks then to a nursing home for more rehab - due to becoming weak in hospital. He is still having problems (now has CKD stage 4, BUN, Creatinine still running high). He now has critically low platelets and was taken off his Tegretol abruptly (which is used for pain management - has neuropathy). How might the kidneys be effecting the platelets? Was that podiatrist neglegent in ignoring his KD in prescribing the Bactrim? What would be the best way to approach the podiatrist? I am with you about educating prescribers about being careful with Bactrim. Thanks for any help you can provide.

Unknown said...

We did a cadaveric combined liver kidney transplant for cryptogenic cirrhosis and diabetic nephropathy and today is day 14.The patient LFT has normalised and the kidneys has started passing urine.
The issue is that though the patient has started passing urine,why there is a rise in the creatinine and pottasium.The patients Tac level 6.9.

PersonalInjuryBoston said...

A lot of my upcoming research is focused on creatinine and its fluctuating levels, so this was a really interesting tibid to read up on. Definitely good to note Bactrium's affects are artifactual, though I wonder as to what further underlying mechanisms might cause this.