We got the preliminary results back on Sam's kidney biopsy from the nurse practitioner. We still haven't heard back from our nephrologist (!!!), so we have a lot of unanswered questions. It was not what we were expecting at all. The most common cause of nephrotic range proteinuria in kids is minimal change disease, something that responds pretty well to a course of steroids. That would've been "good" news. The bad news we predicted was that the biopsy would show scarring from cystinosis, something irreversible and an indicator of progressive kidney dysfunction, likely requiring transplant earlier in life. What we found was a whole new version of bad news.
The pathologist found membranous nephropathy, a microscopic pattern that makes doctors cringe with painful memories of cramming for exams. Membranous nephropathy is certainly on the list of things that cause protein in the urine, but it wasn't on our list. It's fairly uncommon in adults, and from what I've read, it's pretty rare in children. So how about that? Sam has two rare diseases.
What causes membranous nephropathy? The most common cause is "idiopathic," meaning doctors don't know exactly. Other causes include lupus, diabetes, certain drugs including gold salts and NSAIDs, hepatitis B, and some cancers. But what causes it in kids? The most common cause in children is the autoimmune variety. That means Sam's body has probably made antibodies against something in his kidneys. A possible target is the phospholipase A2 receptor. Sam is getting tested for that antibody today.
Autoimmune diseases are treated with immunosuppressant medications. Membranous nephropathy is treated with cyclophosphamide, a chemotherapy drug, or tacrolimus, cyclosporine or mycophenolate, all drugs commonly used in organ transplants. We will also most likely have to use an ACE inhibitor too, to help reduce protein leakage. New medications with new side effects, some of which are pretty terrible. With therapy, about half of cases will go into remission. About a third of cases go into remission and then relapse later. The rest are progressive, leading to end-stage renal disease.
So you can see how this is bad news. Before we were "just" battling a rare genetic disease, with a glimmer of hope that it could be cured with stem cell transplant. Worse case scenario before was that Sam would still have to get a kidney transplant, but we were going to beat the odds. Now he has something else attacking his kidneys -- his own immune system. Now if he gets a kidney transplant, there's a chance the antibodies will attack the new kidney too.
We were finally feeling adjusted to our life with cystinosis. This is the kind of situation that makes you look up into the heavens and ask, "Anything else?" We have always tried to be optimistic, but this feels a little like running into a brick wall.
The silver lining is that there wasn't a lot of scarring. There was some "focal" glomerulosclerosis, but not widespread. And there weren't a lot of cystine crystals, either. So I guess we can feel okay about the efficacy of Procysbi. We had been worried about that, blaming ourselves for getting Sam in the trial when he was so young, before it had been tested in children. At least we can put that to rest.
Sam is a fighter. Literally, you should see him beat up Lars. This is the biggest curveball yet in our journey with chronic disease. If there's one thing I have faith in, it's that Sam is not going to let some histologic mouthful stop him from living life to its fullest. He can still become a ninja, doctor, pilot, spy, or whatever else he comes up with next.