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Nephrotic syndrome with Imatinib?

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Nephrotic syndrome with Imatinib?


I want to know from this forum if Imatinib can cause Nephrotic syndrome and if I can stop Imatinib temporarily


I will explain my case in detail.


I was diagnosed with CML in Feb-2017. My age is 42 years. MY WBC count was 90000 and was put on hydroxyurea for 5 days. After that I was given Dasatinib 140 mg per day. I achieved hematological response within 2 weeks and my WBC was within range of 5k-10k. I took the medicine for 39 days and on 40th day I noticed heavy foam in my urine, which on diagnosis was concluded as Nephrotic syndrome (protein loss/foam in urine).


24 hr. protein test showed 63 gm of heavy protein leak in urine. yes 63 gm and not mg. (normal range of protein in urine is 15-50mg per day)
Dasatinib was stopped temporarily to give time for me to recover from nephrotic syndrome. I was started on steroids (Prednisolone (wysolone- 60 mg) to bring down protein loss.

Renal Biopsy was done to diagnose the cause of Nephrotic syndrome (protein loss/foam in urine). Renal biopsy showed Secondary Membranous nephropathy (means caused due to medication and  in this case from Dasatinib)
After the Biopsy, I was started on Imatinib 400mg per day, along with Prednisolone 60 mg. Protein loss started reducing and within 3 months’ protein loss came down from 63g to 450mg and again shot up to 3gms. Meanwhile, I achieved MR5 response after 8 months of taking Imatinib. I continue to be on Prednisolone 40mg and Imatinib 400mg till now.

But the damage done to the kidneys from Dasatinib remains and I now doubt if Imatinib is the new source cause of my continued Nephrotic syndrome. I want to know if can stop Imatinib/reduce dosage to 200mg per day for few months (having achieved MR5) to check if Nephrotic syndrome/protein loss reduces after stopping Imatinib.

Hi,

I don't know anything about nephrotic syndrome, but you clearly have a good understanding of that.

I was put on 200mg of imatinib rather than 400 about 9 months after diagnosis due to very low WBC, which I had always had. It slowed my progress to MMR and PCRU, so went back up to 400mg, and have now been PCRU for 8 years. Currently just reduced to 200mg and maintaining PCRU afer 4 months.

If your consultant hasn't already done it, I think it would be worth getting the level of imatinib in your blood/serum checked. The toxicology team at Kings College London (Prof Bob Flanagan) have done work which shows imatinib concentration can differ by a factor of up to 10 for people on the same dose. They provide a service to the NHS to measure levels using a new analytical technique they have developed. If you have a high level on 400mg and are MR5 reducing to 200mg might well be worth trying.

I hope this helps 

Hi,

 

Thank you , Will consult our consultant on the dosage.

Sorry you've had to go through this experience with your kidneys as I can only imagine it must be distressing. Fantastic response though reaching MR5!

TKIs can effect kidneys in some people. There are a number of research publications on the topic.

I have pasted a link below to one article that mentions both Dasatinib and Imatinib as well as other drugs. In the full article there is a table that lists recommended strategies. When proteinuria occurs with Dasatinib the authors recommend changing to Imatinib and taking the lowest possible dose. 

Good luck!

https://link.springer.com/article/10.1007/s11523-015-0368-7