I did a lot of research into the effect of TKIs on kidney function after starting Dasatinib. I was freaked out when my eGFR decreased, blood creatinine level increased and urine protein levels increased. This was particularly distressing to me because I have had type one diabetes for almost 38 years which puts me at risk for renal failure but I had been extremely lucky with my kidney function up until CML diagnosis.
So far, for me, it looks like Dasatinib's effect on my eGFR and blood creatinine level has continued but stabilised, and the urine protein seems to have stabilised at a low level which is good news. I just did a new set of tests yesterday, so if this board is still up and running next week (!!!!) I can report on the results if anyone's interested.
I found several in-depth research papers outlining the probable mechanisms for effects of TKIs on kidney function and a couple of scary individual case studies (in those patients, kidney function was restored once the TKI was stopped) but here is one that looks a little more positive...
It seems to confirm (as Trey has indicated previously) that the TKI increases the concentration of creatinine in the blood by inhibiting its secretion by the tubules of the kidneys. It's this creatinine that is measured in our regular blood tests and is used to estimate eGFR. The paper suggests creatinine is not a good measure of kidney function in patients on TKIs and suggests using cystatin c instead of creatinine as a measure of kidney function. It also says apparent decreases in kidney function should be reversed on cessation of TKI (as Buzz has found and I hope you find too one day Kat).
Here's the paper:
Imatinib Increases Serum Creatinine by Inhibiting Its Tubular Secretion in a Reversible Fashion in Chronic Myeloid Leukemia (2016)
Monitoring renal function is important in imatinib-treated patients with chronic myeloid leukemia because serum creatinine may increase during the course of therapy. The mechanism of this increase and its reversibility on treatment cessation have never been investigated.
In 4 imatinib-treated patients who underwent thorough renal exploration, the part of creatinine clearance due to tubular secretion was negligible (2.4, 3.1, −1.3, and 2.8 mL/min) and significantly lower than that measured in their respective controls (17.7 ± 5.6, 43.0 ± 18.0, 23.1 ± 6.7, and 18.6 ± 5.6 mL/min, P < .001). In 1 patient, exploration was repeated after imatinib discontinuation and evidenced a recovery of creatinine tubular secretion (20.3 vs. 17.9 ± 5.2 mL/min in the control population, P = .2). In 15 patients of imatinib discontinuation studies, a median decrease in serum creatinine of 17.9% was observed after imatinib cessation. Resumption of treatment in 6 patients led to a median increase in serum creatinine of 18.8%.
Imatinib completely blunts tubular secretion of creatinine, a previously unreported pharmacologic property. This inhibition increases serum creatinine independently of any glomerular dysfunction and is fully reversible on imatinib cessation.