5 replies to this topic

[kat73]

Trey - I don't know how to move Buzzm1's external link to the abstract I'm referencing - see his post under "Lower left abdominal pain."  This happened to me - after about 5 months on Gleevec, my creatinine level rose into abnormal territory, after having never been there before.  Cut to the chase, I had a nephrology workup - all was well - conclusion was it was an unknown kind of hit by Gleevec and as long as I stayed stable at a low abnormal creatinine and didn't have any protein in the urine, I would be fine.  I'm followed by him twice a year.  This would have been about five years ago.  Four years ago, approximately, I switched to Sprycel.  I have been stable at about 1.1 (creatinine) for those four years.  There never seemed to be any data before now, but I felt somewhat vindicated by Dr. Cortes' retrospective study.  What I want to ask you is, what could possibly be the reason Tasigna actually improved GFR, when Gleevec lowers it?  I have always thought Tasigna was basically the same as Gleevec only stronger - maybe a better binder for ATP.  Any thoughts?  Should I think about switching to Tasigna?  (I just got my first PCRU reading a week or so ago, on Sprycel 70 mg.)  Thanks.

[Buzzm1]

Trey - I don't know how to move Buzzm1's external link to the abstract I'm referencing 

 

 

TKIs Have Kidney Effects in Long-Term CML Treatment http://bit.ly/1HjTaap

 

Treatment of chronic myeloid leukemia (CML) with various tyrosine kinase inhibitors (TKIs) can induce changes in glomerular filtration rate (GFR) over time and have other kidney-related effects, according to a new study. Imatinib and dasatinib were associated with a decrease in GFR, while nilotinib was associated with an increase. 

[Trey]

The report by Dr Cortes concluded: "but this GFR change is not clinically significant".  So although I would not dismiss it entirely, the importance of this is questionable.  The report showed the impact by TKI drugs on the kidneys was almost immediate, which leads me to conclude it is not real.  There could not be actual kidney damage in such a short time.  Given the inaccuracies of using GFR and creatinine as measures of kidney function, I am not sure how useful the report is.

 

Trying to determine kidney function using GFR and creatinine is not necessarily accurate, although they can be useful.  The fact that your creatinine went up to "abnormal" levels does not mean your kidneys were damaged.  Sometimes TKI drugs just mess with the markers by other means.  We see this with ALT/AST as well, where the higher levels do not mean liver damage. 

 

I do not use the term "stronger" when comparing Sprycel and Tasigna to Gleevec.  They are not stronger, just different, and different people respond differently to each.  Your point about side effects also shows this to be true.  Tasigna side effects are not merely the same ones but "stronger" than Gleevec's side effects.

 

We know that TKI drugs can change the way the body processes sugar, and that can affect the kidneys.  Mineral usage is also affected, which can affect the kidneys.  Some of this is temporary. 

 

Kidney function may also be tested by measuring the blood level of cystatin C. Several studies compared calculations of eGFR using creatinine, cystatin C, or both. The National Kidney Foundation concluded that cystatin c is superior to creatinine as a marker of kidney function, and that a formula for calculating eGFR that includes both blood creatinine and cystatin C values may be a better approach.  So ask about testing cystatine C.

 

 

 

https://www.kidney.o...ent/kidneytests

[kat73]

Thanks, Trey.  I did a little more reading about cystatin-c -- very interesting.  I will ask my nephrologist about the test at my next visit in November, although I'm not at all sure I even want to open that can of worms, what with the implications for cardiovascular and Alzheimer stuff.  I take your point about real damage vs the appearance of it on the test via some unknown effect of the tki; the docs have certainly taken the latter approach with me.  I may just let this one go. I still do think it's mighty interesting that Cortes found that Tasigna had the effect of raising the GFR reading and the other two lowered it.  If they could tease out the reason for the differences, it might tell us something useful for the future.

[Trey]

Remember also that GFR is almost always estimated, not actually measured.  To actually measure GFR a person needs to have the pee flow tracked at specific intervals for 24 hours, which is why they instead estimate using creatinine times the angle of dangle plus pie r round, as follows:

"GFR - glomerular filtration rate is the best test to measure your level of kidney function and determine your stage of kidney disease. Your doctor can calculate it from the results of your blood creatinine test, your age, body size and gender."

 

So if the TKI messes with the creatinine levels, which it can, it fakes out the GFR equation.  So I doubt Tasigna improves GFR, just messes with creatinine in the opposite direction (angle of dangle).  Or is the angle of dangle related to gender -- I forget.  Anyhoo, pie are not always squared except at the Starvin' Marvins store.

 

That makes Dr Cortes' conclusions a bit questionable in this instance. 

[kat73]

Hilarious.  Thanks.  I definitely like my pie squared.