Higher creatine level (kidneys)

Hi Chrissie, 

Increased creatine kinase (CK) levels do seem to be associated with imatinib - so there's a decent chance these two things are related.

Though not new, a well cited paper discusses increased CK with imatinib.

http://www.bloodjournal.org/content/104/11/2933

Conclusions of that paper (amongst others): 

1. Imatinib causes persistent CK elevation of >50% above baseline in the majority of responding pts.
2. Elevated CK correlates with myalgia and cramps

Another paper suggests that this elevation is reversible when imatinib is withdrawn, so if it imatinib causing this in your case it would seem that it's unlikely to be a permanent issue.

https://www.ncbi.nlm.nih.gov/pubmed/26795084

David.

What dose of imatinib are you on at the moment? Would it be possible to drop a bit, see if that helps with the creatine issue and perhaps also maintain your PCR?

PS - yes, strenuous exercise can raise creatinine as it will be elevated by breaking down muscle. Bodybuilders with high muscle mass have elevated creatinine, which is nothing to do with poor kidneys. So yes, it could be part of it (even if you are not, as I assume, a bodybuilder!). 

Hi Chrissie,

Just one comment, I think most specialist CML clinicians would not view your rising PCR results ( 0.002; 0.005; and 0.009) as a reason to put you back on full dose IM. It is my understanding - I think Richard may be more clear on this - that stopping trials protocols - including EURO-Ski and DESTINY - only restarted patients back on full dose when they were very near to - or breached - MMR - which is 0.1%. Your current PCR results are way off that.

Sandy

Thanks for your replies, Richard. Very reassuring. They are going to test my urine so will see if anything shows up. I'll keep up my water intake and speak to my haem in April's clinic.

Do you feel any different from coming off meds?

best

Chrissie

Hi Chrissie

My creatinine levels have increased and my eGFR levels have decreased since starting dasatinib so I've done a fair bit of panicking and research on TKIs and kidney health myself.

In 2016 researchers reported that imatinib increases blood creatinine levels by decreasing the tubular secretion of creatinine by the kidneys. They also found that this returned to normal if a patient stopped imatinib as happened to Richard and another poster on the US site, Buzz, who was on imatinib for many years and found his creatinine and eGFR levels returned to normal after he went into treatment free remission.

The authors recommended that cystatiin c should be used rather than creatinine in blood tests for patients on imatinib because the creatinine increase might be misleading rather than a true indication of kidney function. Unfortunately cystatin c is not available here in Australia, but I do hope this situation changes.

Your levels seem only quite mildly elevated so I wouldn't worry at all, but it is good that your doctors are monitoring you and also checking your urine for protein (and hopefully keeping an eye on your blood pressure).

Here is a link to the research paper and also some useful snippets from it:

https://www.ncbi.nlm.nih.gov/pubmed/26795084

Imatinib Increases Serum Creatinine by Inhibiting Its Tubular Secretion in a Reversible Fashion in Chronic Myeloid Leukemia

"An increase in serum creatinine has been reported under imatinib therapy, but the underlying mechanisms have never been investigated. For the first time, we report that imatinib inhibits the tubular secretion of creatinine. This mechanism, never described or even suspected to date for imatinib, is similar to the pharmacologic inhibition of creatinine secretion known to occur in patients taking trimethoprim and cimetidine.

This study will affect clinical practice because it demonstrates that a rapid increase in plasma creatinine concentration within or above the upper normal limit should occur on initiation of imatinib, independently of any true effect on GFR. Obviously, this does not exclude that renal function itself may be modified (either improved or deteriorated) by various factors during the course of treatment, but this pharmacologic effect should be taken into account when interpreting creatinine variations under imatinib therapy, in particular for interpretation of creatinine- derived eGFR (eg, Cockcroft, Modification of Diet in Renal Disease).

When feasible, renal function also should be monitored from cystatin C derived estimating equations in these patients because the inhibition of the tubular transport of creatinine by imatinib does not affect plasma cystatin C concentration."

Hi,

I wanted to follow up with you to see if your doctor ever found out the cause of the elevation. Currently I’ve been on Gleevec for 8 years with no issues and full MMR remission. However, the last year I have noticed that my creatinine levels have increased from 1.3-1.7 and was recommended to a nephrologist. I spoke with him about the research that showed long term tki usage can cause acute kidney affects but was told that it’s very rare. Just wanted to know if your values went back to normal upon reduction of the medication or if your doctor switched you to a different tki. This has been such a roller coaster having been diagnosed at 25 years old.