Monday, March 08, 2010

Basic Information about Dense Deposit Disease (one of the rarest of the rare diseases . . . )

Introducing Jamie Sue

Jamie Sue Turner of Runnells, Iowa is 8 years old and in the second grade. She’s somewhat of a girly-girl favoring the color pink, singing and dancing, and Disney TV fare such as “Hannah Montana.” Her beauty is certainly more than skin deep, yet her wide smile and large, expressive eyes  no doubt added to the "total package" that won her a tiara in a children's beauty pageant at the Iowa State Fair in 2009. But little girls are made of sugar AND spice, are they not? In addition to hobbies like scrapbooking, Jamie Sue is a tough cookie who plays on a youth softball team in the summer.

Until recently, Jamie Sue has enjoyed the kind of idyllic childhood that we all cherish. Her life has revolved around her large family, many friends, pet dogs, hobbies, school and social activities. Due to circumstances beyond her control, Jamie has spent much more of her time at the University of Iowa Hospital in Iowa City than she has at home over the past 10 weeks. You could say Jamie has added another dimension to her active life, and she’s proving that in addition to everything else, she is a tenacious fighter.

Jamie Sue was the picture of robust health until something alarming occurred on December 15, 2009. That evening her ankles were unaccountably swollen. The next day Jamie Sue was at her doctor's office where it was revealed that her kidneys were responsible for the fluid retention.  Early treatment and intervention didn't resolve the symptoms, and her journey within the medical system was well underway . . .  A kidney biopsy early in the course of her illness established a diagnosis of Dense Deposit Disease, a rare autoimmune condition that affects the kidneys.

Dense Deposit Disease (DDD) is the second, and more serious, type of Membranoproliferative Glomerulonephritis. DDD usually leads to chronic kidney failure and the need for regular kidney dialysis. Typically there is a window of time (8-10 years) before the disease damages the kidneys to that extent. Unfortunately, Jamie Sue is an exception to the rule. Her experience with DDD has been rapid and unrelenting so that she is already battling imminent chronic kidney failure as physicians strive to slow the progression of the disease. At the moment, Jamie Sue is receiving a combination of plasmapheresis and occasional renal dialysis for two purposes: to prevent her immune system from continually damaging her kidneys by removing the certain "bad" proteins from her blood, and to cleanse her blood of toxic waste products and excess fluids. Soon Jamie expects to begin clinical trials to determine whether a hopeful new medication may better spare her kidneys from continued damage by her immune system.

About Dense Deposit Disease
It’s been written that Dense Deposit Disease (DDD) is rare even among rare diseases.  DDD makes its appearance in childhood, usually between the ages of 5 and 15 years of age.  Experts have estimated that DDD occurs in only two to three people out of 1 million. We can do the math to demonstrate how DDD is “rare among rare” diseases. Taking a rough estimate of 304 million U.S. citizens and expecting to find 2 to 3 cases of DDD per 1 million, we can estimate that significantly less than 1,000 Americans would be afflicted with Dense Deposit Disease. To gain even more perspective, keep in mind that in the U.S. diseases are officially designated as “rare” when less than 200,000 Americans are affected. (So even if there were 200 times more cases of DDD in the U.S., this condition would still fall into the “rare” category.)
Basic Information about Dense Deposit Disease
A lot of great scientific articles have been written about Dense Deposit Disease. This blog entry doesn’t pretend to be one of them. Instead, this piece intends to take a complicated disease and break some of the key features into understandable concepts in order to help parents, family, and friends be better informed about this condition. When a serious illness affects a child that we love, we want to learn as much as we can in order to be helpful and supportive. As parents we want to know as much as possible in order to advocate for our children. Scientific literature is written in a language all its own and often with explanations that may include unfamiliar and confusing terms. (It’s always best to jot down specific questions as you think of them to ask your child’s physicians). For a great website written by experts who manage and study Dense Deposit Disease, visit the University of Iowa’s website devoted to DDD, it's called Kidneeds, and if you are affected by DDD in some way, you will want to check it out.

What’s in a Name . . . ?

In medical jargon, many diseases and conditions have more than one name. When you are looking for information about Dense Deposit Disease, you will also see it referred to as Membranoproliferative Glomerulonephritis Type II (or MPGN II). Scientists originally felt that Dense Deposit Disease was a variation of two similar types of kidney diseases, therefore it was differentiated by calling it “MPGN Type II.” However, in recent years scientific research has discovered that the unique features of this particular variation makes the name Dense Deposit Disease more appropriate. So although MPGN II is an “older” term, you will still see it in literature about this condition.

What are Dense Deposits?

Physical signs and symptoms are present when the kidneys are functioning poorly.  Nephrotic Syndrome, is a term that refers to the combined signs and symptoms that occur when the kidneys are unhealthy.  More information and test results may be necessary before the physician is able to pinpoint a specific reason for the kidney dysfunction.

A kidney biopsy is necessary to diagnose DDD. This procedure gathers evidence of the underlying reason for kidney damage and allows the physician to make a definite diagnosis. When the tissue from the biopsy is examined with an electron microscope, the unique features of Dense Deposit Disease are clear to the trained eye. As the body’s immune system has malfunctioned, certain proteins have "gone crazy" and started to attack an important membrane deep within the kidneys; bits and pieces of the rogue proteins end up "stuck" to the kidney’s membrane in thick ("dense") ribbon-like patches ("deposits").

An Autoimmune Disease

Dense Deposit Disease is an autoimmune disease.  This means that the patient with DDD is suffering an attack  from within; their kidneys are damaged by their own immune system.

In theory our immune system protects our bodies from outside invaders such as viruses and bacteria.  Sometimes, for reasons that are not well understood, a “glitch” in the immune system causes it to go out of sync.  The out-of-sync immune system triggers proteins that usually protect us to, instead, attack healthy tissues within our bodies by mistake. There are more than 80 different types of autoimmune disorders; each one has resulted from a glitch that is aimed at a specific organ or tissue type. Some well-known examples of autoimmune diseases and their specific targets include Multiple Sclerosis in which nerve sheaths are damaged; Lupus, which affects connective tissue throughout the body; Type 1 Diabetes in which insulin-producing cells of the pancreas are destroyed; and Crohn’s Disease and Ulcerative Colitis which both affect the lining of the digestive tract. Autoimmune disorders are chronic in nature meaning they are not reversible, but there are specific treatments for most autoimmune illnesses that can control or manage the condition.

Why an autoimmune illness affects one person and not another is still a mystery. Roughly 5% of the population is afflicted by some type of autoimmune condition. A number of theories have been introduced to try to explain what goes wrong.  Heredity, environmental factors, viruses and certain drugs have been suggested. It may be that a combination of just the “right” factors is all it takes for the immune system to make a mistake that will spiral out of control and direct damage towards a specific tissue in our body. Much research is directed towards unlocking the secrets behind what really triggers an autoimmune disease. It’s intriguing (and frustrating) that over the years evidence shows that even with identical twins, one twin may be afflicted by an autoimmune disease while the other stays completely healthy.

Glomerular Basement Membrane

An anatomy and physiology reference is the best source for an in-depth understanding of the intricate and complex means in which the complement proteins of the immune system attack and damage the glomerular basement membrane (GB Membrane) in Dense Deposit Disease. However, I can give you a few key points in layman’s terms to provide a very basic understanding of what this illness entails.

The glomerular basement membrane is the part of the kidney that filters extra fluid and waste products out of the blood. On one side of the GB Membrane is the bloodstream, on the other side of the GB Membrane is urine. The fluid and waste that are filtered out of the blood cross the GB Membrane to become components in urine and are ultimately eliminated from the body in the usual way. 

When the immune system damages the GB Membrane, it no longer filters properly. Proteins that circulate in our blood have various important "jobs" to perform within the body so we certainly don't want to lose them. When our kidneys are healthy, there is very little chance of that happening.  Proteins are simply too large to go across a healthy GB Membrane. Unfortunately, a damaged GB Membrane does allow those large proteins to be filtered through, and with terrible consequences. When these useful proteins cross the GB Membrane, they are eliminated with the urine.  Because they are gone from the bloodstream, the specific jobs they are supposed to perform in the body are jeopardized.

(If you are having trouble visualizing this concept, imagine a trampoline--when the fabric is tight we can hit the surface and bounce back off without fear, but if we happen to bounce on a patch of fabric that is loose and frayed we may fall right through and hit the ground instead.  Instead of "bouncing off" the GB Membrane as they normally would, the large proteins go right on through the weakened membrane and are lost to the body when they are expelled by urination.)

With kidney disease the loss of proteins in urine results in a “Catch 22 scenario.” The same proteins that leave the body when the kidneys are damaged have functions that include absorbing unneeded fluids in the bloodstream. Without these proteins to soak them up, the extra fluid in the blood seeps back into the tissues and causes swelling (edema). Importantly, in addition to fluid, dangerous waste products such as creatinine and urea are also retained in the bloodstream.  These waste products eventually become toxic to tissue.  If the kidneys become too diseased to handle removal of these substances, kidney dialysis is essential.

High Blood Pressure, too . . .
Along with fluid retention from poor kidney function comes sodium retention.  Damage to the kidneys also causes an increase in a hormone the kidneys produce (called renin).  These three factors combine to cause dangerously elevated blood pressure which must be treated by medication. 

Signs and Symptoms of DDD

The early signs and symptoms of poor kidney function may be subtle.  When the kidneys are unhealthy enough to allow protein to enter the urine, the urine that is voided is often fizzy or frothy looking.  Red and white blood cells may also leak into the urine.  White blood cells tend to make the urine cloudy, while red blood cells may cause a red or pinkish hue (or they may only be detected by a lab test and not visible to the naked eye.)

More dramatic and obvious signs of kidney problems include:
  • “Puffiness” or swelling (called edema) around the eyes, feet and ankles, hands, and abdomen.
  • A general inability to concentrate and mental confusion.
  • Dark, "tea-colored" urine. Dark urine is a symptom of glomerular problems and it is related to the inability of the kidneys to properly filter the waste products from the blood.(But dark urine can also be caused by other conditions and can even result from eating certain foods.) 

Plasmapheresis is one way in which DDD is treated. Plasma is the “watery” part of our blood.  Among other things, plasma carries the components of the immune system that cause damage to the "good cells” in people with autoimmune illnesses. In DDD the object is to preserve kidney function for as long as possible, removing the damaging immune components has proven to be a helpful means of doing so.  This is done by plasmapheresis in which the patient’s blood is filtered through a machine that removes their plasma and replaces it with plasma from a donor. The donor plasma doesn’t contain the damaging autoimmune components, so the kidneys get a temporary break. With DDD, the patient's body will eventually produce more of the "bad" immune system proteins which will again be circulated in the bloodstream.  

Over time the damaging effects of DDD leads to chronic renal failure (abbreviated as CRF and also simply called "kidney failure").  About 50% of all individuals diagnosed with DDD will require regular dialysis within 8 to 10 years of diagnosis in order to stay alive. 

Kidney transplants have been performed on patients with DDD, but the nature of the disease makes this only a temporary benefit. The body attacks the donor kidney in the same manner that it attacked the original and the donated organ eventually fails. For patients with DDD and their potential kidney donors, the risk of transplant versus the limited benefit to the recipient makes it difficult for the medical establishment to easily recommend this option. 

Back to Jamie Sue . . .

Lately, as Jamie Sue ponders the future she envisions a career in medicine.  She wants to be a doctor.  She can do that.  She can do anything she wants to do.  Individuals with autoimmune conditions learn to adapt and live life to the fullest while managing their illness and undergoing whatever specific treatments that their disease requires.  Jamie Sue will do this . . . 

How Can You Help?

Support research that aims at finding a cure for DDD.  Participate in Fundraising via the Universtiy of Iowa's Kidneeds program which supports DDD research.

Donate Blood or Plasma.  Plasma donation is a great way to contribute and it costs only your time.  Learn more about the process in the article "Plasma Donation" from LifeShare Blood Centers.  

To learn more about blood donation opportunities and find a location near you:

All rights reserved for written content, Carolyn Cooper, MPH, RN, March 2010.
Photos of Jamie Sue Turner used by permission of Misty Turner; photos copyright of Misty Turner.

For Additional Reading:
National Kidney and Urologic Diseases Clearinghouse, "The Kidneys and How They Work"

National Organization for Rare Diseases, Membranoproliferative Glomerulonephritis Type II

Ferrario, F. & Rastaldi, M. P. (undated), Renal Pathology Learning, Type II Membranoproliferative Glomerulonephritis; Accessed online Mar. 3, 2010.

Appel, G.B.; Cook, H.T.; Hagerman, G.; Jeannette, J.C.; Kashgarian, M., Kirschfink, M.; et al. (2005 May; Epub 2005 Mar 30). Membranoproliferative glomerulonephritis type II (dense deposit disease): an update.  Journal of the American Society of  Nephrology, 16(5):1392-403.

Plasmapheresis, The free dictionary online, medical dictionary. 

. .. .


Anonymous said...

My daughter was diagnosed in Sept. 2009. The disease also progress fast. Her kidneys were removed in March 2010. I read your blog and like the way it was put into terms that could be understood.

Anonymous said...

I too suffer with DDD, started when I was 5 years old then stablied for several years until I became pregnant then it progressed to end stage over 10 years to which I started peritoneal dialysis for 2 years then my kidney function picked up for 18 months but now back on dialysis- I'm now 36 years old and found out recently (through my own research) that the deposits that collect and damage the kidneys can deposit in the back of your eyes- seen an Optometrist (eye doctor) and sure enough this is happeneing to me! although my sight isn't effected yet - so hard to find people with the same condition as me, loved ur blogg :)

Cheri said...

I was diagnosed in 1988 when I was 8 years old. I was generally stable for several years. When I was 19 I gave birth to my son. I started dialysis about 11 months later. I went to dialysis for 10 years before I got a transplant. It has been just over a year since the transplant and the biopsy I had last month showed DDD in the kidney again so now we have to decide whether to ride this kidney to its end, and then attempt the use of a new drug, or try it now and possibly damage the kidney in the process. My immune system is already pretty weak. I was rejecting the kidney very quickly and underwent many plasmapheresis treatments and had my spleen removed. Time will tell what happens. I am sending in the consent form today to participate in the study with the University of Iowa. I hope my DNA is helpful so we can learn more about this disease.

Anonymous said...

My 7 year old was diagnosed today. I was feeling overwhemled but have a better understanding of what is going on after reading this. Thank you for putting it into plain english for us.

Sarah said...

I was diagnosed with this disease right after my son was born. My kidney function has always been stable, (except druing the pregnancy) but the protein levels in my urine are always horrible, with severe edema a normal part of my day. I've just found Kidneeds and Dr. Smith, and for the first time in a few years I feel like I atleast have some hope. I feel for your daughter and I hope that that new treatment helps. My doctor says their are many new promising things just on the horizon.

Philip said...

My wife had the DDD diagnosis when she was about 14 years old. She required dialysis since 7 years now and wants to fight for a transplantation. Her brother suffers from the same situation and already lost his transplated kidney after only six month.

You call to raise money to fund the research on a therapy. My wife's doctor believes that there already exists a drug: eculizumab. There are several experts who promote that as a working therapy and already treated patients successfully. But because life is alway hard: our healthcare system does not pay because the drug is not tested and confirmed for this certain disease. And it will never get, because for a rare disease they can not invoke any random studies or whatever they need. We're now going to sue our healthcare system in order to make them pay - it is our only way.

Carolyn Cooper, MPH, RN said...

Hi, Philip, Thanks for sharing the information about Eculizumab. You inspired me to look for information about Eculizumab (Soliris) and I see that Columbia University is in process of conducting Phase 1 clinical trials for this medication in DDD:

There was also a recent letter to the editor about this in the New England Journal of Medicine:

Eculizumab, a monoclonal antibody, is one of the class of called "biological" drugs. More and more medications of this type are coming on the market. They work in autoimmune diseases by essentially turning down the bodies immune response (a very basic explanation for sure). These medications do place the recipient at risk for infections that can be (in some cases) very severe. The risk of anaphylactic reactions to these types of medication also exists.

Here is a link to the Soliris website with details: If the ongoing research comes to a conclusion that will endorse this medication, that will be fantastic! Medications like these are terrifically expensive, so insurance companies, etc. will not pay for them to be given to a patient unless the industry has all the clinical documentation standing beind the fact that this medication is effective and safe for the condition being treated. Right now there are only two kidney conditions that this medication is officially sanctioned to treat.

I was looking at the Soliris prescribing information available on their website. It is a IV infusion given over no less than 35 minutes, weekly x 5 weeks, then every other week (indefinitely).

Anonymous said...

I also have DDD.
I was diagnosed at 23 years old , just 2 weeks after having my first child.
Up until 2 weeks before my labour I had no previous problems with my kidneys, that I knew of anyway !!. I am very fortunate I was put on high doses of steroids, and after 1 year my condition stabilized. It has now been 20 years without any major incidence and I have been able to lead a relative normal life and be around to watch my son grow up , something I am very thankful for.
I like Sarah suffer from swelling, and aches and pains that I think were caused from being on the steroids for so long , but I can live with that. I wish you all the very best in your treatments xxx

Anonymous said...

I also have DDD.
I was diagnosed at 23 years old , just 2 weeks after having my first child.
Up until 2 weeks before my labour I had no previous problems with my kidneys, that I knew of anyway !!. I am very fortunate I was put on high doses of steroids, and after 1 year my condition stabilized. It has now been 20 years without any major incidence and I have been able to lead a relative normal life and be around to watch my son grow up , something I am very thankful for.
I like Sarah suffer from swelling, and aches and pains that I think were caused from being on the steroids for so long , but I can live with that. I wish you all the very best in your treatments xxx

Anonymous said...

Iam a dense deposite diease patient my name is Nikhil. I also have enlarged heart. I am doing now (CAPD). Is this is better treatment....?

Carolyn Cooper, MPH, RN said...

Dear Nikhil, Thank you for posting. To find the best, most current treatment for Dense Deposit, I would recommend getting in touch with the leading expert regarding this disease and that is Dr. Richard J. H. Smith, at the University of Iowa:

I have never met him, but I am aware that he is a kind expert in this disease and he will take sincere interest in your questions and concerns.

Wishing you improved health in this new year.


Unknown said...

My daughter was diagnosed with DDD six months ago (now 18). She is being aggressively treated with high dose steroids and mycophenolate and has had improved protein levels in urine and serum creatinine. I am hesitant to see her go away to college but she is very responsible with her current treatment and says she doesn't want to live in a bubble. I am relieved somewhat to see people have been able to manage this illness for years but still nervous for her health. Our physician is starting the paperwork for possible Eculizumab therapy but it still is not indicated for this illness.

Carolyn Cooper, MPH, RN said...

I understand your worry, and I understand her need for independence and autonomy. I am sure whe will be approved for the Eculizumab therapy. Hopefully, your daughter might consider a compromise for at least the first year and go to school close to home??

Also, and update on Jamie Sue ... She had a kidney transplant earlier this year, is battling rejection after several months of great health, so she is back on plasmapheresis and dialysis at the moment. Jamie Sue's course of DDD was extremely aggressive, and not the typical progression. She remains upbeat and positive from what I hear.

Star Doney said...

I know these are old posted but my daughter has DDD she was diagnosed with it 7 months ago and they used the drug eculizumab it did not work my daughter is an ending renal diesae and has perineal dialysis first she was on hemo dialysis

Carolyn Cooper, MPH, RN said...

Star, I am so sorry to hear about your daughter. It sounds like her disease process has moved very rapidly, much like Jamie Sue's did. You will be glad to know that Jamie Sue underwent a successful kidney transplant a little more than a year ago, and her health has improved and she is doing really well.