Cyclosporin effects on kidneys

[StephM]

Hi everyone! I just found this forum and i've been browsing on it all day. You can't imagine how happy i am to find a place where i can get information and feel like we are not alone. My little brother was diagnosed with AA in july and it seems that he is the only case the hospital has ever had. AA seems to be even less common in france than anywhere else. I could not find anything interesting on the net and there is no forum like this one. Your stories give me hope- some people here with the same disease are doing great years after their diagnosis.
Our doctors are doing everything they can to treat my brother as they should. He has no related donor ,so they decided to give him ATG. They managed to get horse ATG (rabbit ATG is normally the only one available in Europe but they were aware of NIH recent report about the superiority of horse as a first treatment)
He started ATG on Sept 15th and is still in hospital. They keep him at least 5 weeks. He is now on cyclosporin only. He is having serum sickness (first a rash, then terrible joint pain which are gone, now awful stomach ache, a little temperature and high blood pressure). I can't imagine undergoing this at home.
What I'm worried about is his kidneys. His urine is very dark and we were told that it was caused by cyclosporin which seems to be toxic for his kidneys . They diminished the dosage but he will have to take this medicine for months. Does someone know more about that? What is the risk for his kidneys?

[Neil Cuadra]

Steph,

I hope these forums will be helpful to you and your brother. It's too bad you didn't find a French forum for AA too.

I'm glad your brother was able to get horse ATG. I've wondered how soon doctors in Europe would be able to make the switch, based on the evidence you mentioned.

It's ironic that cyclosporine, a drug that's used after kidney transplants to prevent rejection, can damage kidneys. When used with AA patients getting ATG it can also be dangerous to kidneys, but its immunosuppressive effects are a critical part of the ATG treatment. That leaves your brother two bad choices: cyclosporine and no cyclosporine. If he needs it now that doesn't mean he needs it indefinitely, so the key will be how soon he can get off cyclosporine or start tapering the dose. Tapering too quickly can bring relapses, however, and that's where the doctor's experience and expertise is very important. You'll see many forum threads here about tapering cyclosporine.

You, your brother, and the doctors will no doubt keep a close watch on your brother's kidney condition. The doctor may consider tinkering the dose to find the right balance. I suggest asking the doctor whether there are ways to minimize the risks (would extra fluids help?) and what alternatives there are (other immunosuppressants?) if your brother's kidney risk becomes too great.

Remember that your brother shouldn't eat grapefruit or drink grapefruit juice while taking cyclosporine. Grapefruit interferes with the absorption rate. That's a fact that my wife and I learned from other patients even before some of our doctors were aware of it! But keep in mind that information you collect from patients and online forums (yes, that includes what I say) isn't as reliable as what medically trained specialists can tell you. It's best to use sites like this one to gain a broader understanding of the patient experience and to learn about questions to ask the doctor and options to ask the doctor about.

[StephM]

Thank you so much for your answer Neil! I wish i had found this forum earlier. There are so many things we don't know and you're right- knowing from other patient can help us ask the right questions to the doctors.
Your answer is really useful and I didn't know about the grapefruit at all!
I'll tell him right away.
I'm sure they will keep an eye on his kidney. They do ultrasound because they say they can't do a biopsy for the moment. I guess the damage on kidneys is irreversible when it's done.
I will go on browsing the forum and look for the threads about tapering cyclosporin. Thank you.

[Relentless Against SAA]

Thank you for your post. It is very interesting to find that France has less % of SAA than the USA. I wonder why.. Anyone with a theory??

The serum sickness worries me. Is your brother taking Prednisone? This is very important after ATG to prevent serum sickness. The dose is very high: usually starts at 100 mg for about 10 days, following a tapering dose over approx 2 months. I have found people on this forum who have not been given the script for Prednisone by mistake. by the way, this will also help raise his WBC count while on the steroids. The Prednisone does have its own side effects but the doctors feel those side effects are less risky than the serum sickness.
To prevent nausea, I have found the doctors tend start the patient on an acid blocker (H2 blocker) which seems to be very effective. These 2 meds are typically started immediately after the ATG if not during the ATG infusions.
Hope your brother starts feeling better soon.

[Hopeful]

Hi Steph,

What is your brother's dosage of cyclosporine, and what is his weight?

Are they taking cyclosporine trough measurements to ensure that he is not at too toxic a level?

Pay attention to your brother's creatinine. Ideally, it should not rise more than 30% of its pre-ATG levels.

Make sure that he drinks plenty of water!!

Although cyclosporine can cause sub-clinical damage to the kidneys, the effects on creatinine can be reversed when the dosage is lowered. If the dosage is appropriate for a person's body weight, there is less chance of problems. Just remember that more-is-not-always-better when it comes to this drug.

Hope he starts feeling better!

P.S. I love France

[NLJabbari]

Hi StephM, sorry to hear about your brother having to go through this. I was wondering about his dark urine. By any chance did they check your brother for a PNH (Paroxysmal Nocturnal Hemoglobinuria) clone as well. PNH is red cell destruction. Some AA patients present with a PNH clone at diagnosis as well as AA. Besides other symptoms, Dark Urine especially in the morning can be an indicator.

Also, besides Cyclosporine, many patients also take some type of prophylaxis to prevent pneumonia. Something like Bactrim or Pentamidine.

Well, take care--hope your brother does well with this treatment.

[StephM]

Thanks for your answers.

RelentlessAgainstSAA: He was taking prednisone after ATG and they stopped afetr a few days and that's when serum sickness started. He is now back on prednisone but I don't know the dosage. I phoned him this morning and he is feeling a little better. He ate a slice of bread.He hasn't eaten for days! He has "primperan" to prevent nausea
I'll ask about Prednisone next time.The hospital is quite far away from home and I try to go as often as I can but I can't go everyday.
Apparently the WBC is rising a little. (around 1000. It was 100 a few days ago)

Hopeful:He weighs around 75kg and he told me his cyclosporin (Neoral) was reduced to 0.75ml (and no longer the 100mg tablet he was taking twice a day)
I will check that too. It seems to be a low dosage compared to what I read in the forum.
Glad you like France. My greatest dream is to go to California!!

NLJabbari:thanks! I'll ask the question about PNH clone. His urine was almost black a few days ago. Very impressive.

Thank you all! It really helps!

[SAA Sister]

Hey Steph,

I'm so sorry to hear about your brother, just wanted to say as I was reading your post I couldn't help but say something because it sounded exactly like what has been happening to us. I'm new to this too and have been doing so much reading these past 2 months since my brothers diagnosis, only now have I started to post!

My brother has been taken off the cyclosporine for a few days because of his kidneys, we're hoping after his tests tomorrow we are able to recommence but on a lower dose. Still not sure if that's a good thing because we had just got it to the right level in his system and I wonder what will happen if we can't get it back there. We're from Sydney, I haven't found many Australians going through this, so I don't know what we would do without these forums!

[curlygirl]

StephM,

My son's urine was also very dark for about a week after his ATG in JUL. I remember asking in my thread (it's at the top of the pediatric section), because I thought it may be the cyclosporine, and my doctors eventually decided that it was hemolysis (the destruction of red blood cells) from his PNH clone. His bilirubin went up to 1.7, the doctors took it as a sign that his liver was breaking down red blood cells faster. About two weeks later my son's urine and bilirubin returned to normal. He's been on cyclosporine since then and his kidneys are fine. He drinks a lot of liquids, luckily. If his creatinine creeps up they would give him intravenous fluids at a visit to get it back down again.

From what I've read in articles on Aplastic Anemia, the theory of why it's more common in Asia than in Europe or the US (we are in the US) is that Asian countries are much more crowded. The close proximity of everyone to each other makes it much more likely that people will catch a virus that will set off their Aplastic Anemia, simply because they catch more viruses in general. My son did catch a nasty respiratory virus that started his Aplastic Anemia so the theory makes sense to me.

[StephM]

Curlygirl: thanks for your answer. I read a lot these last weeks but I don't know much about this PNH clone thing. And how dangerous it can be. And if you can get rid of it. It seems to be quite common in SAA. I'll do some research and read your thread.
I remember the doctor saying that my brother had a high rate of something related to the liver. I guess it was bilirubin.
They are currently running some other urine tests.I told him to drink more water.

SAA Sister: That's funny to see how similar our stories are! Our brothers about the same age getting the exact same disease and same treatment at the same time. And both feeling isolated...
Did the doctors consider BMT before starting ATG? My other brother and I are no match. Now if ATG doesn't work, they will do a BMT with an unrelated donor and this is really scary. I read the chances for BMT to work were higher when you've had no previous treatment and few tranfusions. That won't be the case in 6 months.
Is your brother still in hospital? How are his blood counts? My brother should leave hospital in one or two weeks but his WBC are still so low (we were told today that his neutrophils were around 300)
It is so difficult to cope with all that and not to fall apart, especially in front of him. He had just found a job that he loved. I have to behave as if I were strong but I can't help crying as soon as I am alone.
It really helps to write about it.

[triumphe64]

Check with your doctor about using aspirin or Naproxen. I was told these can cause kidney failure.

http://www.nlm.nih.gov/medlineplus/d...s/a601207.html

[Relentless Against SAA]

StephM;:" thanks for your answer. I read a lot these last weeks but I don't know much about this PNH clone thing. And how dangerous it can be. And if you can get rid of it. It seems to be quite common in SAA
Steph,
I understand what you are going thru. I feel for your heartache. I hope this will help explain a few things about PNH.
Once you have PNH it rarely goes away. The PNH cells are made with a missing part on the cell. Without this piece, the compliment portion of the immune system easily destroys the cells. The degree of danger is usually directly related to the clone size. If they test your brother, the lab will report it by the number of cells effected. The higher the percentage of cells effected, the more cells can be easily destroyed by compliment, the more side effects can be seen. Please let us know if your brother is tested and if he is positive. They monitor the PNH cells thru a blood draw, not a bone marrow biopsy. If your brother would happen to have PNH, there are certain tests the docs need to order to monitor his bodies response to PNH.

The Aplastic Anemia MDS Foundation website has excellent webnars explaining PNH. They are worth your time.

Remember: we are here for you

[StephM]

Thank you Relentless Againste SAA. Your explanation is very clear!
I'll ask the doctors if they intend to test him for PNH.