The mystery of PKD - Polycystic Kidney Disease

[okarol]

I often wonder why this family disease was not recognized as being a hereditary problem in my family until 1987 when a nurse told my sister that we were at risk. My dad had died at age 28 of a cerebral hemorrhage in 1963, and my mom seemed to know very little beyond that, except that he had kidney disease. I recently read "historical references to PKD can be found at least as early as the 15th Century, and the genetic basis of PKD was first suggested by Steiner in 1899" but my family seemed clueless. We are not even sure who passed it on to my dad, as his own father died at 31 years old from strep throat. I guess it's possible that my grandfather had PKD and never knew it, but wouldn't his family have an idea that there was kidney disease at some point? My dad's mother lived to 84 years old, and was pretty healthy all along. But I have been told that it's possible to live to an advanced age and never have had the cysts progress to a level where they ever cause symptoms. Is this why some generations pass on this disease without ever knowing? I also read "Dominant PKD: It is one of the most common single-gene disorders in humans, affecting between 1 in 400 and 1 in 1,000 individuals worldwide." Yet it still seems to be a surprise to many people when they are diagnosed. And we still seem to know so little, when you consider "The molecular genetic mechanisms of autosomal dominant polcystic kidney disease (ADPKD) were clarified in the mid-1990s with the discoveries of two genes, PKD1 and PKD2, that when mutated give rise to ADPKD..."
My dad had one brother who did not get PKD (as far as we know, he died at age 78 a few years ago, of a heart condition.) My 2 sisters and my brother have PKD. Two nephews have been diagnosed, but the other 8 cousins have not been checked. It's sad to imagine perpetuating this disease and passing it on to future generations.
I would like to hear other people's experience, how far back in your family was PKD recognized? How many family members have it now?
I hope someday there is a cure.

[twirl]

Okarol did you write this article? Lord, I hope not.
PDK- grandfather
        mother
       me - not twin and not big sister and none of my cousins have it
       stasie--- and Missy my two daughters are PDK+, we do not know about Allen, he is 18
       Trasie--- grandchild has PKD, new baby boy - we do not know yet, nothing seen on sonograms as of yet
 I also had my mom's hole in heart---- had surgery as a child
when having fertility problems , I was told some people have PKD and never know
my grandfather was the first generation to come over from Germany, sometimes I wish he would have stayed in Germany and kept the disease there

[okarol]

Yes, I wrote that - it's my father's side of the family.

When did you learn your grandfather had PKD twirl?

I didn't know about the heredity factor until after Jenna was born. But I did ask a doctor about the chances of my having it, and about the choice to have more children. He said it may never develop to the degree my dad had it (super high blood pressure from age 18 to 28, never really treated, causing the aneurysm) and that it was possible to live a full life with it. Little did I realize what that could mean. Luckily my 2 sister and my brother are doing ok, they control their BP and still have kidney function, and they are 54, 52 and 46 years old.

[okarol]

I found this today: (from http://www.pkdcure.org/tabid/590/Default.aspx)

How come I've never heard of PKD before? Is it a new disease?

In the 1700s and 1800s, PKD was often given the label of Bright's disease. This term encompassed any of several kidney diseases marked by high concentrations of protein in the urine. Today, we know that many of the cases of Bright's disease were actually cases of PKD. The first documented case of PKD dates back to Stefan Bathory, the King of Poland, who lived from 1533 to 1588.

In addition, the PKD Foundation is the only organization in the world that focuses on PKD and it was not formed until the mid-1980s. It wasn't until fairly recently that PKD has gained some momentum in raising awareness and funds for the disease.

Another reason many have not heard of PKD is because it is an “internal disorder” — meaning that it does not have a dramatic affect on a person's outward appearance. A person living with PKD may have pain or trauma on their internal organs, yet they maintain a very “normal” physical appearance that does not attract attention or compassion from the unknowing public.


Do all patients within a family suffering from ADPKD develop renal failure at approximately the same time in the course of their disease?

ADPKD is a disease in which individuals within a family can demonstrate a wide range of disease severity. Sometimes there are three generations of individuals alive: the grandparent is not on dialysis, doing well, while their offspring have reached ESRD or dialysis and their grandchildren are found at birth to have advanced disease.  This suggests that other genetic or environmental contributions besides the inherited gene are important with regard to progression of renal failure in ADPKD. These contributors could be other unrelated genes, or environmental factors or other second-hit processes (mutations in the good copy of the PKD1 or PKD2 gene) that affect the kidneys in these individuals.

[RuthWells]

Okarol, my dad was the first in our family with PKD.  Both of his parents lived to ripe ages (late 70s and early 80s) without any hint of kidney issues, so we assume the mutation begain with Dad.  He was diagnosed in the late '70s and was already fairly far along with the disease's progression at that point.  He had his first kidney transplant in 1981, at the age of 40.

At the time, there was no discussion of the genetic nature of the disease.  It wasn't until the late 1980s, when I was diagnosed with ovarian cysts, that a lightbulb went off in my mother's head and she insisted that my brothers and I all get screened for PKD.  Luckily, I am the only one of my siblings with PKD.

Of my two sons, one has been diagnosed (by accident -- he was receiving an abdominal ultrasound for something unrelated) and the other has not been tested.

I am now at the age my father was at the time of his first transplant, and my PKD is progressing much more slowly than his did.  I attribute this mainly to lifestyle factors -- since Dad didn't know about the disease early, he didn't make any changes (such as quitting smoking, caffeine, and animal proteins).  I've never been a smoker and quit caffeine almost 20 years ago, so I figure that that has played a part in my disease's progression.  I've been off animal proteins for a couple of years, now, as well.  Don't really know whether that's helping, but it can't be hurting!  Dad was a pack-a-day smoker and drank plenty of black coffee.  Who knows how much any of it contributed -- medical research has quite a ways to go with this.

[stauffenberg]

Just a note from the history of science:  Right up until the beginning of the 20th century "Bright's Disease" was used as a generic term for ALL renal disease of non-traumatic etiology.  Generally over time there has been a tendency to move from naming diseases not after the first person who accurately described them and instead according to a more accurate medical characterization based on the Latin or Greek terms which describe the pathological changes or disease mechanisms involved.  Thus Addison's Disease has become adrenal insufficiency; Bright's Disease has become renal failure; Cushing's Disease has become overactive adrenal activity; von Recklingshausen's Disease has become neurofibromatosis, etc.  There are still a few notable hold-outs, however, such as Bell's Palsy and Alzheimer's Disease.

[KR Cincy]

I had PKD...what role it had in my renal cancer, who knows, but it couldn't have helped.
Not sure which parent has PKD...my dad had a long history of kidney stones and had many tests and no one said anything, but he's still my odds on favorite. Mom's never had a problem with kidneys to speak of and we don't think my brother has it.

I know the PKD Foundation is funding some very good research so maybe they can make a dent in how this is treated, because now the only thing treated are the symptoms.

[charee]

we are not sure where my pkd came from, dad died 14 years ago from a heart attack, he was a diabetic had lots of scans over years and nothing was ever picked up, when i found out 8 years ago mum and my brother and sister were tested but lucky they were clear, but both my sons have it which pisses me off  i would really hate them to do dialysis but who knows they might be lucky and escape it.

[Ken Shelmerdine]

PKD has never presented in my family apart from myself. Although there are other members of my family on my father's side who have simple cysts on their kidneys. Is it possible that simple cysts can mutate over a gerneration to polycysts?

[ahamner]

The known origin of PKD for my family came from my paternal grandmother who died in her thirties of a brain aneurism apparently associated with PKD.  I've been told her father died of "Brights Disease".  My father was 16 at the time of her death.

I have been aware of PKD since my father was diagnosed with the disease in 1957.

The following members of my family have or had PKD:
Father, died at age 48 with kidney failure in 1965.
Uncle, died at age 68 with kidney failure.
Brother, died at age 64 in 2006 after 2 years on PD and 4 years on Hemo.
Cousin, still going strong after a kidney transplant more than 20 years ago now 66.
Me, kidney tranplant in 2006.

My daughter has PKD and is doing okay for now.  My son does not appear to have inherited this disease.  Overall the disease appears to be following the 50% probability of inheriting this disease for each child for each parent who has the disease.  There have been no instances of PKD in any of the children of those not having PKD themselves.

My daughter has three children so I am of course concerned about her health and that of her children.  Hopefully her children will beat the odds and avoid this disease.

[pelagia]

While I am certain that living an unhealthy life invites problems, genetic diseases are genetic diseases.  For many the dice have already been rolled.  My husband has PKD and has taken good care of himself for as long as I have known him.

As noted in the text Karol excerpted below, members of the same family may exhibit different timelines of symptoms.  My father-in-law was diagnosed with high blood pressure, likely due to PKD, when he was in high school.  His mother died early, before he graduated from high school, of a brain aneurysm which was almost certainly due to PKD.  My father-in-law was on the high school track team and then went on to seminary and became a minister.  He didn't drink much except an occasional glass of wine or beer and didn't smoke. He ran many miles a week most of his life with his blood pressure under control by meds.  By the time he was 50 he was on dialysis.  At 52 he had a transplant.  He died of a heart attack at 59 with his transplant functioning well.  The heart attack may have been made more likely by health characteristics inherited from his father's side of the family.  His older sister didn't have much in the way of symptoms for most of her life.  She did not go on dialysis until she was in her mid 60s.  She is still on dialysis in her mid 70s. 

My husband's PKD progressed on a course remarkably similar to his dad's.  My husband's younger brothers, one who was a vegetarian for much of his life, and who is extremely health conscious, meditates, does yoga, and does not smoke, and the other who was much less health conscious are both now beginning to lose kidney function.  They both seem to be on courses remarkably similar to Stephen and his dad.  We don't know about our next generation of kids...
 
Also, just for clarification, when they state that a child has a 50% chance of inheriting a disease, it does not mean that 50% of the kids in a family will inherit the disease.  It means that 50% of the kids in a population (for example, the population of the US), that have a parent with the disease, will inherit the disease.  (Think of tossing a coin - you have a 50% chance of heads, but you might get heads 5 times in a row every once in awhile).   

I learned about the PKD Foundation when I read a newspaper clipping that I found on my father-in-law's desk after he passed away.  They are working hard to educate the public about this disease, which is more common than many other genetic diseases you have heard of such as cystic fibrosis and multiple sclerosis.  PKD affects most people when they are middle age or older -- this may be why many of us have never heard of this very common disease.  The PKD Foundation site offers much information on the disease, summaries of current research, diet recommendations and more.  http://www.pkdcure.org

 

[kimcanada]

Insert dumb question here...

I don't have PKD, is this the most common type of KD?

[pelagia]

Looks like PKD (cystic kidneys) accounts for less than 5% of all ESRD in the US:

from the US National Institutes of Health (http://kidney.niddk.nih.gov/kudiseases/pubs/kustats/index.htm)

End-stage Renal Disease (ESRD)

Prevalence (2005): 485,012 U.S. residents were under treatment as of the end of the calendar year.

Resulting from these primary diseases:
Diabetes: 179,157
Hypertension: 117,438
Glomerulonephritis: 78,345
Cystic kidney: 22,458
All other: 87,614

[okarol]

Insert dumb question here...

I don't have PKD, is this the most common type of KD?

From The PKD Foundation http://www.pkdcure.org:

Polycystic Kidney Disease (PKD) affects 600,000 Americans and 12.5 million children and adults, worldwide. ADPKD affects more people than Down syndrome, cystic fibrosis, muscular dystrophy and sickle cell anemia combined.

Autosomal dominant (ADPKD),  is one of the most common life-threatening genetic diseases.  ADPKD affects between 1 in 500 people. It does not skip a generation. There is usually a family history of ADPKD.  Parents with ADPKD have a 50 percent chance of passing the disease on to each of their children.

Although ADPKD is an inherited disease, not all patients progress to end-stage renal disease in their lifetime.
Approximately 50% of patients will begin dialysis or require a transplant in their sixth decade of life.

From the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health:
In the United States, about 600,000 people have PKD, and cystic disease is the fourth leading cause of kidney failure.

[RuthWells]

While I am certain that living an unhealthy life invites problems, genetic diseases are genetic diseases.  For many the dice have already been rolled.  My husband has PKD and has taken good care of himself for as long as I have known him.

Pelagia, I hope I didn't imply in my post that my father's PKD was attributable to lifestyle factors -- I certainly know that PKD does not discriminate!  However, my PKD has not progressed as quickly as my dad's, and I often wonder whether his smoking and excessive caffeine intake served to hasten his progression (as compared with mine).

When my creatinine started to rise, I immediately stopped my ocassional caffeine intake and reduced the animal proteins in my diet to almost nil.  That was in October 2005, and since then, my creatinine has only increased by .25.  So I think (hope!) that the dietary changes are having some affect in slowing the progression.

I'm sorry if I wasn't clear in my original post.  : )

[pelagia]

You are definitely doing the right thing to take good care of your health and pamper your kidneys.  It can't hurt and might help.   

For as long as we have had good access to the web, we have tried to keep track of the thinking on diet and PKD.  I never found much that was very compelling except the advice to maintain a healthy diet (healthy carbs, low fat, some protein), limit salt, avoid caffeine and alcohol.  There was some research going on about soy products, and we are soymilk drinkers, but I haven't followed any of the most recent developments.  Once my husband moved into ESRD and dialysis, the dietary guidelines were pretty well set by the docs.    For the others in my family I am doing what I can to support research for a cure, or at least a treatment that slows the progression of this disease.  Until that happens, it would be great if the research community could find dietary or other factors that slow down the progression of the disease.

I know there isn't an "average trajectory" for anyone with PKD, but here is my husband's trajectory in case anyone is interested in how it was for one person with PKD.  Between 1988 (age 32) and late June 2002 his creatinine went from 1.1 to 1.9.  At that point his kidneys started getting noticeably larger as the cysts (we presume) started to proliferate or grow faster.  Many folks thought he was getting a beer belly, but we knew better.  His creatinine jumped to 2.6 by September 2003 and had tripled by late 2007. 

When my husband went for the all the tests prior to being listed for his transplant, the docs told him that aside from PKD and the accompanying high blood pressure, he is in incredibly good health.  This means faster healing and more resilience overall.  So, I completely agree that taking care of our health is really important, especially since we never really know what we might have to deal with.

[RuthWells]

Pelagia, thank you for sharing your husband's trajectory with PKD.  I'm astonished that after 4 years of relatively slow progression, that he had such big jumps in creatinine between 2002 and 2003, and through 2007.  I've been assuming (with no real basis, mind you!), that my rise in creatinine would more or less follow a smooth curve (it's been about 2/10s of a point on average every 2 years or so).  I guess I shouldn't be so complacent....

You mention that your husband has high blood pressure.  I hope that his doctors are treating that separately?  My nephrologist has told me that leaving high BP uncontrolled can actually hasten the decline of the kidneys.

[pelagia]

My husband has been on blood pressure meds since his mid-20s.  And yes, absolutely, keeping the blood pressure under control is very important.  In the distant past his docs aimed for keeping his bp below 140/90 and then about 5 or 6 years ago (or maybe it was longer ago than that) they started really working to keep it under 140/80.  Unfortunately, as his kidney function went down his blood pressure became more and more difficult to keep below 140/80. 

The great news is that post-transplant he is having to drop out some of the blood pressure meds in order to keep his bp above 100/60!  He likes subtraction much better than addition when it comes to meds.

As far as the PKD trajectory goes, it was 14 years, not 4, of slow progression (1988-2002).  Not sure if that was a typo or mis-read.

[RuthWells]

As far as the PKD trajectory goes, it was 14 years, not 4, of slow progression (1988-2002).  Not sure if that was a typo or mis-read.

Thanks for pointing that out -- that was me reading your too quickly.   

[twirl]

so I found out in college that I had PKD and was not concerned---- was told sometimes you die and never know you have it---had ten years of miscarriages and told every doc about the disease----- never seemed to be a big deal-------- little, did I know------ I was so focused on having a baby, that is all I could think of------my children have  a 50/50 chance, or so I have been told
my second child, Missy, was born with a diaphramatic hernia which is devastating and she is lucky to be alive with one lung, my grandfather was the first generation to come from Germany when he was an adult------- sometimes I find myself wondering if we ever married our kinfolks down the line somewheres, my mom and I have both had heart surgeries
I was only tested in college on account of my mother finding out she had it

[stauffenberg]

When you found out about having PKD in college didn't you immediately go to the library and read all about the disease and its genetics?  I can't imagine getting a diagnosis like that and not wanting to know everything about it.

[twirl]

I lived thru a god-awful childhood by learning to live in denial, so I let it go. I am not saying I am proud of it, it is just what I did.Denial can become comfortable and unthreathening. Had I had a normal or more normal life, I am sure I would have made a better choice. I knew when I wrote about this you would have a comment. But oh well, can't worry about what you think, I feel bad enough on my own for having children and continuing this shit, on the other hand, I can not imagine life worth living without my children. I let myself skip over the dreading of PKD when doctors made no big deal out of it when I was trying to have children. The opinions seemed to be sometimes you do; sometimes you don't. I wanted to believe don't. I know it was wrong. What should I do ? Shoot all myself and all the family members I have contaminated?    Rid out the weak? I worry about your comments, you seem so intelligent to me but where is your heart?
In the year I found out about this PKD there was no hope unless you were rich. Noteveryone got dialysis.
I worked with very troubled students. I would tell them to remember their childhoods and the way they were treated and to do better for their children. I accomplished that only worse, I gave my children GD PKD which I did not understand and I could have stopped it but I chose to bury my head in the ground and pretend of think everything would be okay. Yes, I am a monster, I undestand that. I don't decide who gets the death card------ my sisters did not get it or my cousins---- so am I like the omen? I hadhope, which I know now know is not enough.

[pelagia]

Twirl, I sent you this on another thread, but I am going to post it here on this one because this is a PKD thread that someone might come across looking for information.

"I hope you know that they are running a number of drug trials for PKD therapies.  We all need to keep hopeful that they are going to find treatments for PKD before it has a chance to cause kidney failure in our kids.

Here's a link for info on the pkd foundation site about drug trials:
http://www.pkdcure.org/tabid/142/default.aspx

and one of the many articles on the web about some of the latest findings that offer hope:
http://www.healthcarerepublic.com/news/PHARMACIST/817576/RA-drug-offers-fresh-hope-polycystic-kidney-disease/

These articles are a little dense to read, but they all point in the same direction.  Hope!"

And another thing we should not forget -- Hindsight is 20/20.  Let's all remember that we did not get most of our information with the push of a button even a decade ago.  I once sent a letter requesting an information packet on PKD from one of the big kidney organizations and never got anything back.  I remember reading about PKD in the Encyclopedia Brittanica during the early 1980s and I don't remember that the information was especially enlightening.  Things were not like they are now in terms of having incredible information at our fingertips. 

[monrein]

Twirl, please don't beat yourself up over past history that is just that...in the past.  It is very easy to hear what we want to hear especially around things that are difficult and hard to accept.  Denial can sometimes be very functional and sometimes it isn't the best way of coping.  Whatever, but it doesn't make you a monster, not even a little bit in my book.  It makes you a human being and as human beings we are often blinded to certain realities by our biological or emotional urges.  Hindsight is 20/20 and life is a risky business.

We love you Twirl, you're funny and honest and real.  I don't even know you personally but I'm glad you're on this planet and that I have a virtual friendship with you through IHD.  Your absence would be our loss.

By the way, I don't think that Stauffenberg is heartless.  I think he's a very analytical, statistically-minded person and I think he's probably highly ethical and altruistic in fact.  Academic training may be responsible for the way he writes as academic writing is by its very nature quite impersonal as it seeks to be objective and rational rather than subjective and emotional.  I want you both here and part of my world.
 

[MIbarra]

Yeah.. what Monrein said. She's so smart.

I believe everyone is on this earth for a purpose and everyone has their burden to carry and learn from. I don't ask God, "Why me?" but rather thank him for having kidney disease (which can be treated to some extent) instead of something more unbearable.