Friday, September 25, 2015

We Were on the News!

You've probably already seen this, but in case you haven't, check out the story that Heather Simonsen from KSL 5 did on our family!

Monday, September 14, 2015

Freshly Picked

When I reached out to Freshly Picked and asked if they would donate to our fundraiser, I hoped they would send one pair of moccasins. When they sent four pairs, I was blown away by their generosity. Now I understand that it’s not just the unique, durable, and adorable product that endears Freshly Picked to its customers, but the brand’s generosity as well.
Anything that can simplify our lives is something worth having, and Freshly Picked offers simplicity in spades. The soft leather is easy to clean and doesn’t give Lars any blisters. More importantly, Lars can put them on himself without having to worry about getting the correct shoe on the correct foot. Toddlers have a 50% chance of getting it right, but somehow manage to get the wrong shoe on the wrong foot 90% of the time. The design of Freshly Picked makes their lives, and their mothers’ lives, a little less frustrating.   

Freshly Picked moccasins come in a variety of designs, from super girly to super masculine, and everything in between. Any child can be comfortable with the shoes’ fit and look.The winning bidders for moccasins will be able to choose the style and size from

Pineapple - Picnic Pack Limited Edition MoccasinsHeirloom in Blush and Gold - FP Signature MoccasinsBeehive State - Utah Collection Moccasins

We are incredibly grateful to Freshly Picked for so generously supporting this auction. Sam’s Hope for a Cure benefits greatly from the donations of local artists and companies like Freshly Picked. The money from the winning bid, as well as the money from all other auction items, will go to the Cystinosis Research Foundation. If you miss out on placing the winning bid for the moccs, we encourage you to  visit to find the perfect moccasins for your little one.

Some of our 2015 Sponsors

Thursday, August 27, 2015

Monday, August 17, 2015

Sam and Lars CRF 2015 Outtakes

Many of you have seen the 2015 Cystinosis Research Foundation movie that featured our family.  Lars Wanberg and his son made that movie, and they spent about a week with us in Salt Lake City filming for it.  Lars was nice enough to make an outtakes movie for us with some of the footage that didn't make it into the final cut.  Check it out!

Wednesday, July 22, 2015

a new start

We haven't posted for a while because life has been crazy.  We moved on July 11, and the dust is finally starting to settle.  We loved our home in the Avenues, but we were outgrowing the space and needed a change of scenery.  

We moved to Sugarhouse, the land of families with small children.  I had heard about a certain rental from some other residents, so we called up the landlord and got on the waiting list back in January.  We had given up hope on getting the place, but he called us in June to let us know the unit was available.  We jumped at the chance and Ashton had the whole house packed in a week.  The former tenants moved out June 30, and after some repairs and carpet cleaning the place was ours.  We were lucky to have a lot of help from the 21st North Ward loading up the truck, and Ashton's and my family helped unload on the back end.  Fortunately we don't have that much heavy furniture, just a lot of toys.  So many toys.  And now we finally have the space to play with them!

This place is amazing.  It is a duplex that faces another duplex, with a long driveway in between that is almost as wide as a road.  There are young families across from us, so there are kids outside ALL THE TIME.  And the driveway is the perfect place to ride bikes, scooters, and anything else with wheels, as well as play basketball, soccer, baseball, and anything else you can think of.  The boys have been in heaven with so many accessible playmates, and the neighbors have been so welcoming.  On our third night there they threw a barbecue for us.   

The house is a split-level, with three bedrooms and two bathrooms.  We are excited to have a bathroom that doesn't require traversing our bedroom.  There is a big playroom downstairs, and a nice laundry room (also an upgrade, for any of our friends who ever saw "Gitmo" in our last house).  The kitchen is smaller and we miss our wood floors, but the extra space is making up for it.

We saw our nephrologist recently, and we finally have Sam off prednisone.  We did the longest, slowest taper imaginable, and he is a much happier kid.  It's nice to see his silly smile more often.

Sam had grown a little taller since our last appointment, but only gained 1 lb.  He is soooo skinny.  Gone are the chubby cheeks of prednisone.  We had to put him back on the feeding pump at night time to get extra calories in.  Our dietitian wants him to eat 1600 calories a day, which is quite a bit for a kid who used to be completely dependent on tube feeds.  After the appointment we went to Costco to stock up on all of Sam's favorite fattening foods.  His newest favorite is the parmesan garlic butter spread.  He asks for garlic toast about 5 times a day.  

Based on the last round of labs, his cystinosis is about where it's been.  His WBC cystine test came back at 0.24, which is the best it's ever been on Procysbi.  He's on 8 pills twice a day, though, which is quite a bit for his size, and it comes with a more noticeable sulfur smell.  His potassium and bicarbonate are still on the low side, so we did have to raise Sam's potassium again.  Potassium makes Sam really nauseous, and we have to give it to him every 6 hours.  

The protein in his urine is still really high, this time around 4 g.  I don't think the rituximab is working.  I think all the benefit we've seen so far is from the lisinopril, which we are increasing to 2.5 mg twice a day.  We can't really push that drug much more though because of blood pressure.  The next step will be to check his B-cell counts.  If those are creeping up again, we might do another round of rituximab.  

If the B-cell counts remain low, however, and the proteinuria persists, then we have to try another medication.  Our nephrologist is thinking tacrolimus, an immunosuppressant used for organ transplants.  The drug has lots of downsides.  The major one is tacro is toxic to the kidneys over time, and Sam's kidneys are already getting damaged by cystinosis and membranous nephropathy.  Tacro levels also have to be monitored, which means more blood draws for Sam (he's tough, but they still suck).  Another option would be mycophenolate mofetil (cellcept).  That one isn't hard on the kidneys, but it does give people GI upset, and we have enough of that already.  

Hopefully things will start turning around soon, but at least Sam has been feeling better. 


Friday, May 1, 2015

Is Rituximab Working?

We had a nephrology appointment for Samuel and Lars today.

Lars's portion was very quick.  His kidneys still show no sign of Fanconi syndrome, and his growth trajectory has stayed in the 90th percentile.  He's gaining on Sam in weight pretty quickly.  He was excited to show the doctor the g-tube button I drew on his tummy last night.  Early diagnosis is huge! 

Sam's portion was lengthy, to say the least.  A lot has happened.  Sam got two doses of rituximab, a week apart, the beginning of April.  Then we went to Newport Beach, CA for family vacation and the Cystinosis Research Foundation family conference the third week of April.  Sam had a cough and runny nose when we drove to California, and seemed to be more tired.  We went to Disneyland on that Tuesday, and that totally wore him out by about 3 PM.  He refused to walk anymore and slept in his stroller from about 4 PM to 8 PM while Lars continued going on rides.  That night he vomited multiple times and had trouble keeping his potassium and citrate down.   On Wednesday we slept in and Sam didn't feel well.  He rallied for an afternoon at Laguna Beach with his best buddy Henry Sturgis, but afterwards he was too sick to eat dinner with us.  We thought that he was just exhausted from a busy vacation with lots of days in the hot sun.

That night we met up at the Balboa Bay Resort for the CRF welcome dinner.  He was surrounded by so many old friends, including Henry and Jackson, that he forgot he was sick and went wild.  Friday was the first day of meetings, so we dropped Sam and Lars off at the babysitters, which is Sam's absolute favorite thing (more than Disneyland!).  He said he didn't feel well, and instead of joining in on the fun and games, he sat by the television.  When we went to pick him up he told us his right wrist was hurting, and he refused to move his right arm.  He had pain with walking too, especially on the right side, and had to be carried.  He spent Friday night wrapped up in a blanket, sitting in the stroller, instead of playing on the beach. Henry came and checked on him lots of times to see how he was doing.  He is such a good friend.  When we brought Sam back to the hotel he was in agonizing pain in his right wrist and wouldn't walk because his legs hurt.     

We called our nephrologist back home who thought it sounded like a viral infection.  He recommended supportive care.  We let him sleep in on Saturday morning, hoping some more rest would help.  His wrist was still very painful that morning, and he was acting really sluggish.  Ashton called our nephrologist again, and he became more concerned that this was a possible drug reaction.  He recommended that we take him to a hospital in California to be seen by a doctor.  We knew this carried the risk of him being admitted to the hospital there.  Luckily we were at a conference with many doctors, including Dr. Grimm, who used to see Sam in the RP103 trial.  Dr. Grimm was very kind to evaluate Samuel.  He was concerned that Sam had a reactive arthritis, that could be viral, or it may have something to do with Sam's prednisone taper.  He recommended going back up to 30 mg of prednisone and then driving back to Utah to be seen at Primary Children's.  We agreed that this was probably the best plan so with very heavy hearts we left the conference early to head home.

Sam threw up a lot on the way home, but eventually it stopped.  His wrist stopped hurting too, and suddenly he wanted to eat again.  I think lots of prayers were answered that day.  We made it back in 10 hours.  We went to Primary Children's, and fortunately Sam's nephrologist was there rounding.   Sam's potassium was low, but our nephrologist didn't think he needed to be admitted, especially since his wrist was looking better.  We had been holding Sam's lisinopril because of dehydration, so the protein in his urine had shot up pretty high again.  We went home and hydrated Sam with lots of pedialyte.

We were lucky Sam didn't have to be hospitalized.  We continued him on prednisone 30 mg for a total of 5 days, and then tapered down by 5 mg every couple days.  We had to re-live all the tantrums and mood lability again, but his other symptoms improved and he was able to go back to school.  We've tapered him down to 5 mg daily right now, and this doesn't make him too cranky.

At today's visit, Sam's growth has plateaued.  We might have to supplement with tube feeds again, but for now we'll keep monitoring.  His potassium is still pretty low, so we had to go up on that today.  He was on 20 mEq four times a day (a lot!) and now he'll be on 27 mEq four times a day.  Dang that Fanconi's syndrome.  His bicarbonate and phosphate are normal and his glomerular filtration is good.  His albumin has normalized too, which is a good sign.

So is the rituximab working for his membranous nephropathy?  We measured his B-cells before and after starting therapy.  We can confidently say that the rituximab has obliterated his B-cells.  In studies of adults with membranous nephropathy, once the B-cells are gone, you don't have to continue rituximab infusions, so our doctor has decided we can wait on further treatments.

Whether rituximab will lead to disease remission remains unclear.  If Sam continues to have the same level of inflammation in his kidneys and protein in his urine, his kidneys will start to decline, and he would need a kidney transplant in 1-2 years.  That's a scary thought, but even more scary is the notion that kidney transplant isn't necessary curative for this condition.  If the antibodies are still around, they will attack the donor kidney too.  So we really need to get rid of those antibodies.

Dr. Cherqui's strategy to cure cystinosis is to take hematopoietic stem cells from the patient, modify them with gene therapy, and then transplant them back.  In this process, the patient's bone marrow has to be eradicated with chemotherapy before the autologous transplant.  I've been musing about whether this could cure Sam's membranous nephropathy too.  Get rid of the immune cells, including the plasma cells that are making the culprit antibodies, and then transplant back healthy, undifferentiated stem cells, that would grow up to be responsible, kind immune cells, with nothing against Sam's kidneys.  I actually found a small series where autologous stem cell transplant was tried in 12 patients with treatment-refractory membranous nephropathy.  Patients did have an initial significant reduction in the level of protein in their urine, but it didn't last.  The big difference, however, is they did not have bone marrow eradication prior to transplantation, so the bad guy immune cells were still hanging around.  It makes me think that Dr. Cherqui's human trials can't come soon enough.

There was one glimmer of hope today.  When Sam was first diagnosed with membranous nephropathy, his albumin/creatinine ratio was over 14,000 (that's crazy high).  The lowest we could get it with prednisone and lisinopril was 4800.  Today it was actually down to 3600 g.  Not a complete response, but maybe the rituximab is working . . .    

Wednesday, April 22, 2015

Day of Hope CRF Family Conference 2015

We just got back from Newport Beach, California, where we attended the Cystinosis Research Foundation's family conference.  We look forward to it all year.  This year we were really excited to have my parents join us.

The conference kicked off on Thursday with the welcome dinner.  It's one of the best nights because we get to see so many friends from around the country (and world!).  It's like a big family reunion.  Thanks to the internet we can follow along with our many cystinosis family friends, but nothing beats getting together and catching up.

Sam and Lars didn't waste any time getting together with their buddies.  Unfortunately they both insisted on bringing their lightsabers (Disneyland souvenirs) with them.  Sam found Henry Sturgis and they immediately started having lightsaber duels right in the middle of the crowd.  I appointed myself designated babysitter and escorted them, along with Jackson Blum, to the lawn outside where they could be as rowdy as they wanted.  It was fun to see all the little kids running around in herds.  When we left that night Sam was so sad to be separated from Henry.  He cried, "I don't want to be apart from Henry!" all the way to the hotel.  We assured him they could have breakfast together the next morning, which they did.

Friday morning started off early with family introductions.  There was a record number of families this year!  Everyone got up and shared their wishes for themselves and their children.  We wrote our wishes on colorful paper birds and put them on a large picture of a tree.   I wish for the same thing every year, and that is that Sam and Lars will have long, happy and healthy lives.  Ashton wished that some day Sam and Lars would be able to be dads.

Nancy started off the first session by talking about the many milestones accomplished by the Cystinosis Research Foundation so far.  I followed her with a talk about the basics and history of cystinosis -- a little primer to provide context for the research talks.

Dr. Paul Grimm talked about the nuances of cysteamine therapy.  He talked about both Cystagon and Procysbi, and the proper way to take them.  One of the important points he made was the effects of food on the absorption of cysteamine.  Many people find if they take it with food, they have fewer side effects.  That's because food interferes with absorption of cysteamine, so it's not working as well.  Protein and fatty foods are the worst things to take with Cystagon.  Procysbi works best if you take it with something acidic, like orange juice.  The beads dissolve early if you take it with something with a basic pH, like milk, so you get reduced efficacy.  Procysbi should be taken at least 2 hours after eating, and you should wait at least a half hour after taking it before eating again.  Dr. Grimm also made the point that the goal is not to get WBC cystine levels all the way to zero.  Carriers of the cystinosis gene (like me) don't have cystine levels of zero.  If you use too much cysteamine you run the risk of developing copper deficiency, which leads to collagen abnormalities, skin lesions and poor wound healing.  

Dr. Mary Leonard, a nephrologist from Stanford, talked about the new study she is doing with Dr. Grimm on bone and muscle health in cystinosis.  This is a really important topic that has not received a lot of research attention in the past, especially bone health.  People with cystinosis have lots of risk factors for abnormal bone density and structure.  They are planning to do a comprehensive evaluation of 30 children and adults with cystinosis using high-resolution quantitative CT scans, DXA scans, and exercise equipment to assess muscle strength.  This study will provide background data needed to do future studies on possible interventions like mineral supplementation and hormones.  The most important things we can do now for good bone health include adequate nutrition, phosphorus and vitamin D supplementation, and weight-bearing activity.

Dr. Bruce Barshop from UCSD talked about a new white blood cell cystine test he has developed.  The old WBC cystine test has a lot of variability because there are two main types of white blood cells: granulocytes and lymphocytes.  The granulocytes contain the cystine.  The ratio of granulocytes and lymphocytes varies from person to person and day to day.  During a viral illness, lymphocytes spike to a higher number, so much less cystine is recovered in the lab test, which can give a falsely low cystine level (a little troubling!).  Dr. Barshop has developed a new test using immunomagnetic beads to separate the granulocytes from the lymphocytes, giving a more pure preparation with more reliable cystine levels.  With the new test, individual hospital labs won't have to process the blood anymore.   This means any lab can send blood in a yellow top tube express overnight to Barshop's lab to be analyzed.  This will be a huge blessing to people in smaller towns or rural areas where hospital labs are not trained to process blood for WBC cystine testing.  There will also be a new reference range for target cystine levels.  Basically 1.7 will become the new 1.0.  

After Dr. Barshop's talk, we had a Q&A panel with representatives from Raptor Pharmaceuticals and Sigma Tau.  People were able to voice their concerns about drug access (especially outside the U.S.), cost and insurance coverage, and side effects.  

Dr. Sergio Catz from the Scripps Research Institute talked about his lysosome research.  Typically we think of cystinosis as a disease of cystine accumulation INSIDE the lysosome.  He has found, however, that because another receptor (LAMP-2A) in the lysosome membrane is impaired, there is also accumulation of proteins OUTSIDE the lysosome, and this also leads to cellular dysfunction.  He has also found a drug that improves cystine emptying from the lysosome by stabilizing a protein called Rab27, which is expressed at lower levels in cystinosis.  This work has been done in cell cultures, so the next step is to test the drug in knockout mice.

Dr. Francesco Emma, all the way from Bambino Gesu Children's Hospital in Rome, Italy, talked about screening existing drug libraries for new molecules for treating cystinosis.  His lab looked at 1280 different drugs in cystinosis cells to find molecules that reduce cystine levels and protect the cells from apoptosis (a type of cell death).  They found one drug that does both of these things, and it could be a potential new therapy for cystinosis.  The good news is it's already approved by the FDA for something else.  His lab is testing it now in knockout mice.  Hopefully in the next year he will be able to reveal the identity of this exciting mystery drug!

Next we heard from Dr. Stephanie Cherqui, who gave us an update on her stem cell research.  She explained the mechanism of how hematopoietic stem cell transplantation rescues organ function in mice with cystinosis, which I broke down in previous blog posts (here and here).  She gave us progress updates on the safety studies that the FDA requires prior to human trials, and so far, everything has gone smoothly.  She predicts that she will be done with the safety studies in 8 months, and then she can go back to the FDA to start the phase I trial.  The plan is to recruit two people per year, with a total of 6 people.  She has organized the Cystinosis Stem Cell and Gene Therapy Consortium, which is large group of physicians and scientists who will design the trial and evaluate the participants throughout the study.  2016 is going to be a big year!!

After Dr. Cherqui, we heard from Dr. Celine Rocca, who works with Dr. Cherqui at UCSD.  She presented her research on the effects of HSC transplantation on corneal cystinosis.  She showed that after allogeneic HSC transplant, cystinosis knockout mice had significant reduction in cystine crystals, restoration of normal corneal thickness and lower intraocular pressure 12 months later.  This is the first time someone has shown that HSC transplantation can treat an inherited corneal disease.

Dr. Jennifer Simpson from UC Irvine spoke about the many ways cystinosis affects the eyes.  We usually only think about the corneal crystals, but every compartment of the eye is affected, including the retina, conjunctiva, iris and ciliary bodies.  One of the biggest take home message was that we shouldn't blame all eye symptoms on the cystaran eye drops.  Dry eyes, red eyes or painful eyes can be signs of other eye diseases, like keratitis and glaucoma.  She is working on cystinosis guidelines for ophthalmologists, many of whom have little experience treating ocular cystinosis.

Next Dr. Ghanashyam Acharya, from Baylor College of Medicine, updated everyone on the nanowafer his lab has developed to treat corneal cystinosis.  He recently published a paper on the nanowafer technology, which the popular media received with a great deal of excitement (see the NPR article here).  The nanowafer is so effective, it may replace eye drops for many diseases. Fortunately Ghanashyam worked with Baylor to give the Cystinosis Research Foundation the license for the nanowafer to treat cystinosis, so the CRF is working on filing with the FDA to start a human trial.  The hope is to enroll people in December! 

Next we had the physician/scientist panel.  We asked many of the questions that people posted on Facebook.  Many people had questions about muscle wasting and what can be done to stop it.  Dr. Trauner, a neurologist, noted we don't have an effective treatment for muscle wasting, so further research needs to be done. Levocarnitine, vitamin D, vitamin B complex and CoEnzyme Q10 are all thought to help muscle function, but there isn't any hard evidence. 

Some people asked when was the best time to start eye drops, and whether waiting till the child is symptomatic was too late.  Dr. Simpson said children should be started as soon as they are diagnosed.  

Several people also had questions regarding male infertility, since boys with cystinosis develop hypogonadism.  No one on the panel had much experience in this field, but Dr. Leonard said she would talk with her colleagues in hematology/oncology, since they have a lot of experience with preserving fertility in young children prior to chemotherapy.  We need to recruit a reproductive endocrinologist to the CRF family! 

Someone asked the question about what supplements we need to be careful with, and Dr. Grimm noted that giving someone too much phosphorus at one time can drop the calcium in the blood and cause tetany.

After the panel, Betty Cabrera, who is working with Stephanie Cherqui on the stem cell trial, spoke to us about the Cure Cystinosis International Registry.  It's really important for everyone with cystinosis to register and fill out the survey on CCIR so that scientists will have the baseline information they need to do more research.  She noted that it's one of the most important things we can do as a community to help find a cure.  Even if you've registered before, it's important to update your information annually.  The CRF has recently revamped the survey to include more pertinent questions for the nanowafer and stem cell trials.  To register, click here.        
While we were listening to grown-up talks, the kids were back with the babysitters getting royal treatment.  They watched movies, played games, did crafts, and ate all the potato chips they could cram in.  They received a visit from the "Rad Hatter," a mad scientist, Captain America and a princess named Elsa from some movie I'd never heard of.  The kids loved it. 

Friday night we had dinner on the beach and lawn.  Lars headed straight for the water and spent the night digging holes on the beach.  Sam usually does the same, but that night he was feeling sick, so he spent the night wrapped up in a blanket in our stroller. 

Nancy and Natalie Stack surprised Dr. Grimm with a short film highlighting his life and dedication to pediatric nephrology and patients with cystinosis.  They presented him with a special book of photos and letters from his cystinosis patients.  There was ice cream, frozen bananas and those wonderful light-up cotton candy wands.  Soon the beach was covered with flashing green, red and blue lights as the kids ran around with their wands.  

Unfortunately that was the extent of our participation this year.  Sam became too sick that night, and Saturday morning we had to get in the car and rush back to Salt Lake City so he could be seen at Primary Children's.  

We missed the Saturday morning sessions, including the teen and adult panel, which is always one of my favorite parts.  We also missed the big Natalie's Wish gala, which really bummed us out.  They showed the new 2015 CRF movie, which featured our family. They raised an incredible $2.3 million dollars that night.  My parents were still there and presented the check from our 2014 fundraiser, where we raised over $18,000 for cystinosis research.  I was really jealous when I learned my parents got to sit with Ghanashyam at dinner.  That dude is my hero.  

Only 350 days until next year's conference!

Tuesday, April 21, 2015

Cystinosis Research Foundation 2015 Movie

CRF 2015 from Nancy Stack on Vimeo.

This year the Cystinosis Research Foundation made a short film about our family for the 2015 Natalie's Wish event.  The filmographer, Lars Wanberg, spent a week with our family back in January.  The film talks about living with cystinosis and the amazing research the CRF is funding to make life better for our boys and every person with cystinosis.  Take a look!  

Sunday, April 5, 2015

Sam and Buddy

Here is a story Sam wrote today.  He wanted to play Plants vs. Zombies on the i-Pad for the millionth time, so we told him he needed to write for 30 minutes.  This is what he came up with:

Sam and Buddy  

Buddy was Sam's dog.
Sam loved Buddy.  Buddy was a homeless dog.
He came to me in the woods.  I was taking a walk.

"Do you have a home?" And Buddy said, "Ruff!"

I knew he did not have a home.  I took him home.

The End.

Tuesday, March 31, 2015

Plan B: Rituximab

Today Sam got his first infusion of rituximab.

Let me back up.  Our plan was to try high dose prednisone for 3 months to see whether that could shut down the antibody response that is damaging Sam's kidneys.  Sam was on 30 mg of prednisone daily.  It was terrible.  We have so much sympathy now for anyone who has to take prednisone, especially high doses.

We had heard it could make you ornery, but we still weren't ready for the unpredictable mood swings and tantrums.  It was like Mt. Vesuvius every fifteen minutes.  Sam is a stubborn kid at baseline, but there was a noticeable change on prednisone.  And worst of all, it didn't really work.  He still has really high levels of protein in his urine.  There was a modest decrease that was most likely due to the ACE inhibitor he started taking, lisinopril.  His protein/creatinine ratio dropped from 14 to 5.  And his serum albumin came back up into the normal levels.  But his kidneys are still inflamed and dumping protein like it's going out of style.

There were some benefits to prednisone.  Sam started eating a lot more.  We were able to stop all his night tube feeds, which was nice.  His face definitely got chubbier, with little chipmunk cheeks.  We'll see if those hang around now that we are tapering off.  We are currently down to 10 mg daily, and it will take us another month to get off prednisone completely.

So prednisone didn't work.  That meant we had to move to plan B.  Our nephrologist didn't want to use cyclosporine, which is the usual treatment for membranous nephropathy, because it can be toxic to the kidneys.  This would be especially risky in a child with cystinosis who is constantly at risk for dehydration.  So that left two other options: mycophenolate or rituximab.  Our nephrologist went with rituximab.

Rituximab is an antibody against the cells that make antibodies (wrap your head around that).  It targets the precursors to B-cells.  B-cells are important immune cells that recognize bad guys like bacteria and viruses, and they make antibodies against them.  Sometimes they get confused and make antibodies against things in the human body.  That's how autoimmune diseases like rheumatoid arthritis and Crohn's disease happen.  Rituximab is an effective treatment for autoimmune diseases because it takes out the B-cell precursors.  No B-cells, no antibodies.  Rituximab was actually originally developed for B-cell lymphomas.  In lymphoma the B-cells start proliferating out of control, so rituximab can be given in addition to chemotherapy to get rid of the cancer cells.

Rituximab is expensive, so our nephrologist had to make a special case for Sam to get it.  Then Ashton had to call our insurance and Primary Children's a million times to get the pre-authorization processed.

Since rituximab is given through an IV, Sam had to come to the hospital for his infusion.  We were admitted to the Rapid Treatment Unit (RTU), which is where he stayed after he got his kidney biopsy.  It's like an observation unit for short stays.  Since rituximab is an antibody there is always the risk of an allergic reaction.  To minimize this risk, Sam got benadryl, tylenol and solumedrol before his infusion.  Then they ran the rituximab really, really slow.  Luckily Sam didn't have any reactions to it.

Sam was pretty apprehensive about the IV.  He brought five of his stuffed animal dogs with him for support.  Luckily the IV team got it placed on their first try.  Then it was just room service and movie marathon after that.  He watched Frozen, Matilda and the Nightmare Before Christmas while chowing down on a cheeseburger and Pringles.  We haven't been watching TV at home so this was his opportunity to binge.

The plan from here is to do an infusion once a week for three more weeks.  That will be a full course of treatment, and it should knock his immune system down for three to six months.  We'll track the protein in his urine and see if it slows down in the next month.  If it doesn't work, I don't know what plan C is.

Rituximab has to work.  We'll be praying for that and we appreciate your prayers too.

Monday, December 15, 2014

The Plan

On Thursday we met with our nephrologist.  He spent about an hour going over his thoughts and what the plan is from here.  He is just as baffled by the diagnosis of membranous nephropathy as we are.  He sees it in adolescents, but not in kids Sam's age.  He is fairly confident it's an autoimmune process in Sam.  We are still waiting for the phospholipase A2 antibody test to come back, but he doubts that this is the real problem in Sam.  He thinks it's a drug.

What drug?  The one that is supposed to be prolonging Sam's life by helping get cystine out of the lysosomes.  Cysteamine, also called Cystagon (the short-acting 6-hour pill that Lars is on) or Procysbi (the long-acting $350,000-a-year drug that Sam is on) has a sulfhydryl group on it.  The most common drugs (besides NSAIDs) that have been implicated in membranous nephropathy have a sulfhydryl group, including captopril and penicillamine.  Something about the way the sulfhydryl interacts with proteins in the body triggers an immune response that has downstream effects that damage the kidneys.  This is all speculation, but it's the best hypothesis our nephrologist has.  It's a hypothesis that's impossible to prove, and we can't really take him off the drug anyway.

Everyone with cystinosis takes this drug.  Why hasn't anybody else every developed membranous nephropathy?  Good question.  If you search the published literature for a case of cystinosis with membranous nephropathy, you won't find one.  Our nephrologist is going to write a case report about Sam, to get it on the books.  Just because it's never been published before, doesn't mean it doesn't happen.  Other kids with cystinosis do get protein in their urine.  Usually it's during the teen years, when the kidney is progressing toward needing a transplant.  At that point, people rarely get biopsies.  The doctor just blames it on cystinosis and the patient gets a transplant.  A lot of patients don't routinely get their urine checked, either, so if there is protein in the urine, it is not being detected.  It would be a really interesting study to collect urine samples from a bunch of cystinosis patients to see what the prevalence of albuminuria in the general cystinosis population is . . . I might have to do that study one day.

Enough of the speculation.  What is the plan?  Well, since it's an autoimmune disease, our nephrologist wants to start with prednisone.  We are going to try three months of high dose prednisone to see if we can shut it all down.  Prednisone is cheap and it's been around forever.  Anyone who has ever taken it will tell you it has side effects.  One of the side effects in children is "orneriness."  At least we have something to blame when Sam throws a tantrum!  Another side effect, and maybe a silver lining, is increased appetite.  Sam has only been on the medicine for 4 days, but we can already see this in action.  He shovels in the food, and then comes back for seconds and thirds.  

The other medicine Sam is starting is lisinopril, an ACE inhibitor.  This medicine decreases filtration through the kidney, reducing how much protein leaks out.  It is a blood pressure medicine, so we are starting on a real small dose to make sure Sam can tolerate it.  It can bump the creatinine too, so we have to be really careful when he gets dehydrated.  

We got some more bad news last week as well.  Sam's cystine level came back at 1.99.  It is supposed to be below 1.  His levels have been really hard to control ever since he switched to swallowing pills, and since he started school.  It screwed up our whole schedule.  We went up on the dose of Procysbi, and we are also stopping night feeds, since the Boost formula negatively affects Procysbi absorption.  It's nice for Sam to not have to do night feeds anymore, but we do worry about him getting enough calories.  Hopefully starting the prednisone will balance that out.

So that's the plan. Prednisone for 3 months, lisinopril probably indefinitely.  We'll be checking labs every 2-4 weeks and hopefully get things under control.  If prednisone doesn't work, we'll be moving to the next line, which would probably be rituximab and cellcept.  Our nephrologist said he would never use cyclophosphamide or cyclosporine in someone Sam's age (sigh of relief).  Too many side effects.  He is actually pretty optimistic that we can get the disease into remission, which is reassuring.  We'll just have to wait and see.  

Thanks for all your prayers and kind words of support.  They mean a lot.   

Friday, December 5, 2014

Membranous Nephropathy

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.  

Tuesday, November 25, 2014

Kidney Biopsy

At Sam's last nephrology appointment, everything was looking great.  His height and weight had moved up percentiles into the 40s.  His electrolyte levels were stable.  His albumin was a little low, but still in the "normal" range.  It had been low a few months ago too.  Our nephrologist ordered a urine test, and this showed protein in the urine.  A LOT of protein.  This took us completely by surprise.

We checked a first morning urine again, hoping it was a fluke.  The massive proteinuria persisted.  We waited almost two weeks to hear back from our nephrologist.  In the mean time, we panicked.  What did this mean?

Cystinosis is a disease of the kidney tubules, which normally reabsorb electrolytes, glucose and small proteins from filtered urine.  It is normal in cystinosis to have leakage of small proteins, but these proteins aren't even detected by normal urine dipsticks.  Sam is losing albumin in his urine, which suggests that the glomeruli are damaged.  The glomerulus is the part of the kidney that filters blood to make urine.  The glomerulus can be damaged by a lot of things.  The most common diseases in kids are minimal change disease and glomerulonephritis.  Other causes include autoimmune diseases, like lupus.  

We hadn't heard of other kids with cystinosis having nephrotic range proteinuria before.  We knew that proteinuria occurred with end stage kidney disease, before transplant time.  Usually the proteinuria is more gradual, however.  Did this mean Sam was going to need a transplant sooner?

It's possible that Sam has something completely unrelated to cystinosis causing the proteinuria.  But it's also possible that the cystine crystals have damaged the glomeruli too.  But why would this happen?  We never miss a dose of Sam's medications.  We are neurotic about that.  We do have some concerns about Procysbi's efficacy compared to Cystagon because Sam did have a really high cystine level several months back.  The effect of Procysbi seems to be more unpredictable depending on what you eat and how strictly you follow rules about eating before and after.

We talked to Dr. Grimm about it via e-mail, and he said that it's possible Sam had sustained enough damage to his kidneys when he was a baby, prior to diagnosis, that now as he grows bigger his remaining functioning nephrons can't compensate.  He may actually be showing signs of "hyperfiltration injury."  He said that sometimes no matter how strict you are with giving medicines on time, the disease just progresses.  It seemed to us that if the cystinosis is progressing, however, then Sam wouldn't be growing so well, and his other electrolytes, like potassium and bicarbonate, would be dropping too.

We heard back from our nephrologist, Dr. Nelson, and discussed the options.  He was baffled by the degree of proteinuria as well, and thought the best thing to figure out what is going on was to get a kidney biopsy.  This meant a short stay in the hospital.  We prepped Sam for it a couple weeks out by telling him he got to have a sleepover at the hospital.  A week before the biopsy he packed a suitcase with pajamas, underwear and movies.

On Friday morning Sam walked in wearing his ninja costume, carrying his suitcase and his stuffed dog, Piratesbandofmisfits (Pirates for short).  First he had to get labs and an IV.  Since he needed to have an empty stomach for the procedure, we had to hydrate him for a few hours before because he drinks a lot of water.  He was pretty nervous about the IV, but once it was in, it didn't seem to bother him.  Ashton's mom watched Lars all day, which was really wonderful so we could both be with Sam.  Around noon Sam was brought back to ultrasound, where he got some versed and ketamine.  Dr. Nelson performed the biopsy and took 4 small core samples.  Usually they do 3, but he wanted to prepare one extra sample to look for cystine crystals in the glomeruli.

The procedure went smoothly without complications.  Sam was taken to the RTU observation unit where he had to lie flat on his back for 6 hours.  We surprised him with a new stuffed animal, a big golden retriever from Ikea that he had been wanting for months.   When Sam saw the new dog he was still waking up from the anesthesia, so he was a little giddy and confused.  "Wait, wait, wait, wait," he repeated with disbelief.  "When did you buy that??"  He named the dog Ivy, after his IV, and then Ivy Scooby-Doo, and eventually he shortened it to just Scooby-Doo.  

Sam spent the rest of the day watching a Scooby-Doo marathon and ordering food from the room service.  He ate an entire personal pizza and serving of french fries for lunch, and a corn dog and fries for dinner.  So healthy.  We had to collect all of his urine to monitor it for significant bleeding.  It started out pretty yellow but by night time it was strawberry colored.  He had some soreness at the biopsy site which got better with tylenol.  He did great overnight and was discharged the next morning.  He was jumping on his hospital bed before he left.  Dr. Nelson told him to avoid rough housing, wrestling and even recess for the next 10 days to make sure he doesn't develop any bleeding at the biopsy site.

So now it's just a waiting game for the pathology results. We are really hoping they find something else on the biopsy, like minimal change disease, that we could just treat with steroids for a while.  If all they see is glomerulosclerosis, or scarring of the glomeruli, then we'll have to accept that it's the cystinosis causing more kidney damage.  The only treatment for that is an ACE inhibitor like enalapril to reduce filtration through the glomeruli, which also decreases how much protein leaks out.

Thanks to everyone who visited, sent messages of support and asked how Sam is doing.  We are fortunate to have such a great community of friends and family.  Now please put your blood types in the comments.       

Wednesday, November 19, 2014

Our friend, Macey

 She is just so darn cute.

Dress Up

First, he told me to get the dress ups.  Then, in his bossy voice, he told me to get the camera.  I started snapping photos and he said, "give me candy corn".

Halloween was this good

hedgehog, batman, monster, phantom of the opera, ninja