Our CF Matters Hawaii – The Background of UNOS (United Network for Organ Sharing)

The Background of UNOS (United Network for Organ Sharing)

The system of organ donation early in the era of transplantation was focused on local networks.  The receipt of available organs was limited to those in an area hospital’s network.  As the process of organ transplantation became more advanced, and subsequently more of an option for those in need of life saving treatments, the necessity for a system to effectively track organ donors with recipients became necessary.  UNOS (United Network for Organ Sharing) fulfills that need.

The Southeastern Regional Organ Procurement Program was established as a kidney-sharing system in 1969 to increase the efficiency of organ placement (https://www.medscape.com/viewarticle/436539_5).  Later named the Southeastern Organ Procurement Foundation, it became the central depository for data regarding all types of solid organ transplantation in 1977, with the establishment of a computerized database that housed that information.  That database was called UNOS.  Due to more transplantation resources become available, the U.S. Congress passed the National Organ Transplant Act in 1984, which began the Organ Procurement and Transplantation Network (OPTN) to maintain a national registry for organ matching (https://optn.transplant.hrsa.gov/governance/about-the-optn/history-nota/).  UNOS was awarded the contract in 1986 to develop the OPTN, and has operated that network ever since.

In maintaining OPTN, UNOS manages the national transplant waiting list for the United States.  This organ sharing system maximizes the efficient use of deceased organs through equitable and timely allocation.  UNOS also collects, stores, analyzes and publishes data pertaining to every transplant event that occurs in the U.S. (https://unos.org).

To support the organization and its efforts to organize and maintain the organ transplant network nationwide, UNOS bases its operations on three tenents: Education, Technology, and Policy.

For patients who need, or have received, transplants, UNOS fills those individuals’ quest for knowledge through education via the Transplant Living website (https://transplantliving.org/) which offers information about living donations, patient brochures that enable the public to understand the organ transplant process, and education to assist and inform transplant professionals of industry matters.

Technology is an integral component to maintain the nation’s organ transplant network.  UNOS’ electronic network, UNet, provides the vehicle for transplant professionals to register candidates onto the national network, and match them with donor organs as they become available.  In addition, the matching process is enhanced with the application, DonorNet.  While UNet enables candidate registration and matching, DonorNet increases efficiency within the system, as it records information about donor offers, and transmits it to transplant hospitals with compatible transplant candidates.

Finally, policy development that UNOS undertakes can be seen as the underpinning to its operations.  A 42-member Board of Directors addresses issues and develops solutions for matters involving patient and donor family issues, medical issues specific to various transplantable organs, and technical aspects of organ recovery and matching.  Further, ethical principles unique to the industry are identified, discussed and addressed.  Once issues are identified, proposals are drafted, and feedback is received.  Subsequently, the Board of Directors vote on the proposals, and if passed, policies and changes are implemented and communicated to the transplant community.

Until later.

If you would like me to research and post any topic of interest regarding Organ Transplantation, please feel free to e-mail your suggestions to me at ourcfmattershawaii@yahoo.com. I will do my best to place your idea into my queue of topics to cover on this site. Thanks for your feedback.

Topic for Saturday, January 20th posting – Transplantation Firsts, Part 1 – First Kidney Transplants

Check out the YouTube video of this posting at https://youtu.be/HWAkVM76P5o

Brief Overview of the History of Organ Transplantation

Throughout history, society has been intrigued by the prospect of extracting an organ, whether it be from a person or from an animal, and successfully transferring it to another.  This has been documented in Greek, Roman, and Chinese cultures.  Such an example is found in Homer’s The Odyssey, where a creature was created through the weaving together of body parts of a goat, lion, and dragon (http://www.organtransplants.org/understanding/history/).  However, it wasn’t until the mid-20th century that this transplant process began to advance.

Until that point, organ transplants were advanced to the degree that the procedures would come up just short of success, with many failures due to organ rejection.  Examples range from an Italian surgeon in the 16th Century, Gasparo Tagliacozzi, who reconstructed noses and ears using skin from patients’ arms, to the transplant of the first human kidney using an organ from a deceased donor, performed by Ukrainian doctor Yu Yu Voronoy in 1936 (http://www.history.com/news/organ-transplants-a-brief-history).  The development of immunosuppressive drugs in the 1960s, together with tissue typing, became early tools to begin the advance of organ transplantation to where it is today.

As the medical technology and techniques improved, organ transplants become more successful and were being performed more frequently.  Due to the greater acceptance and usage of this practice, in the 1980s organizations were established to support the growth and coordination of transplantation.  United Network for Organ Sharing (UNOS) was incorporated to support the efforts of donation and transplantation professionals in 1984 (https://unos.org/transplantation/history/).  Soon thereafter in 1986, UNOS was awarded a national Organ Procurement and Transplantation Network (OPTN) contract by the U.S. Department of Health and Human Services.  As part of UNOS’ mission, under that contract, UNOS has, and continues to:

  • Establish an organ sharing system that maximizes the efficient use of deceased organs through equitable and timely allocation
  • Establish a system to collect, store, analyze and publish data pertaining to the patient waiting list, organ matching, and transplants
  • Inform, consult and guide persons and organizations concerned with human organ transplantation to increase the number of organs available for transplantation.

Until later.


If you would like me to research and post any topic of interest regarding Organ Transplantation, please feel free to e-mail your suggestions to me at ourcfmattershawaii@yahoo.com. I will do my best to place your idea into my queue of topics to cover on this site. Thanks for your feedback.

Topic for Saturday, January 13th posting – The Background of UNOS (United Network for Organ Sharing)

Check out the YouTube video of this posting at https://youtu.be/cY7uKXh6_9I

Cystic Fibrosis Gene CTFR. What is it?

Hi all,

The past two postings have mentioned the CFTR (Cystic Fibrosis Transmembrane Conductance Regulator) gene.

Some mutations to the CFTR causes CF, and CFTR is indeed the primary cause of Cystic Fibrosis. To allow a better understanding of this important root of Cystic Fibrosis, today’s post focuses on this CF gene.

The CFTR gene was identified in 1989 by geneticist Lap-Chee Tsui and his research team. Everyone has two copies of this gene, one from each parent (http://www.nhlbi.nih.gov/health/dci/Diseases/cf/cf_causes.html). Children who inherit a faulty CFTR gene from each parent will have CF. However; those who inherit a faulty CFTR gene from one parent and a normal CFTR gene from the other parent usually have no symptoms of cystic fibrosis, as they will have enough normal copies of the gene to be healthy (https://embryo.asu.edu/pages/cystic-fibrosis-transmembrane-conductance-regulator-cftr-gene).

Breaking down the acronym CFTR provides a glimpse of how it operates. (http://cysticfibrosis.about.com/od/cysticfibrosis101/a/CFTR.htm) –

Cystic Fibrosis – the disease that occurs when two copies of the gene do not function properly
Transmembrane – the prefix “trans” means “across” , so transmembrane means across the membrane (CFTR is a transporter gene)
Conductance – the ease with which electricity, gas, or fluid flows through a substance
Regulator – a mechanism of control

To go into further detail about CFTR, it is part of a family of genes that regulate the energy transfer which enables a cell to open and close its ion channels, and is located on the human chromosome 7. The CFTR gene produces the CFTR protein, which regulates the chloride ion content of certain cells in the body. When chloride ions are not able to leave the cells properly, as is the case with CF patients, water is retained in the cells, and as a result, some fluids, including mucus, are thicker than they should be.

A functioning CFTR gene is critical to normal human development, and mutations to this gene are life threatening in most cases, because they compromise the function of the pancreas, gastrointestinal tract, and respiratory systems. When the respiratory system is compromised, mucus build-up in the lungs result in infections. As for the related dysfunction of the pancreas and gastrointestinal tract, the results are the likely destruction of the pancreatic exocrine function and lack of proper absorption of nutrients (https://embryo.asu.edu/pages/cystic-fibrosis-transmembrane-conductance-regulator-cftr-gene).

Live life.

Check out the YouTube video of this posting at https://youtu.be/dgc_vLpBAaA

BTW – If you would like me to research and post any topic of interest regarding Cystic Fibrosis, please feel free to e-mail your suggestions to me at ourcfmattershawaii@yahoo.com. I will do my best to place your idea into my queue of topics to cover on this site. Thanks for your feedback.


Topic for the next posting – Early Study of CF Medication Formulation CTP-656 Shows Superior Effects Compared to Existing CF Medication Kalydeco

Cystic Fibrosis Gene Mutation DF508. What is it?

Hi all,

As many in the cystic fibrosis community are aware, the new, breakthrough CF medication Orkambi is only approved for those patients who have two copies of the cystic fibrosis gene mutation Delta F508 (Double DF508). But what really is this particular gene mutation? That is the topic of today’s posting.

There are over 1,500 mutations that have been identified on the gene CFTR (Cystic Fibrosis Transmembrane Conductance Regulator). According to the website Medscape.com, only approximately 20 mutations of those 1,500 mutations occur commonly in the Caucasian population (http://www.medscape.com/viewarticle/576200_2). DF508 is just one of those mutations, and is caused by a deletion of the three nucleotides that comprise the codon for phenylalanine (f) at position 508.

DF508 is the most frequently identified CF gene mutation throughout the world. As a point of reference, an estimate of those with CF who carry DF508 on a worldwide basis is said to be at 75% (http://www.who.int/genomics/publications/en/HGN_WB_04.02_report.pdf).

DF508 is a mutant CFTR protein which cannot be folded into its proper shape when produced. The quality control mechanisms within the cell destroy this abnormal protein before it can reach the cell surface where its major normal function is to act as a channel through which chloride ions can pass in and out of the cell (http://www.cfmedicine.com/htmldocs/cftext/genetics.htm). On the other hand, a correctly formed CFTR protein opens channels in the cell membranes that releases chloride ions out of cells, which causes osmosis to draw water out of the cells (https://en.wikipedia.org/wiki/%CE%94F508).

In fact, part of the way that Orkambi works successfully is by one of its combinations assisting to move the defective CFTR protein to its proper place at the cell surface. As well, another combination of Orkambi increases the activity of that protein once it is there, supporting the flow of salt and fluids, which helps thin the thick mucus that builds up in the lungs and other organs (https://www.cff.org/Living-with-CF/Treatments-and-Therapies/CFTR-Modulators/CFTR-Modulator-Basics/).

Scientists have estimated that the DF508 mutation occurred over 52,000 years ago in Northern Europe. A hypothesis that supports the evolvement of this mutation is that it causes a positive effect by reducing water loss, since DF508 inherently does not allow the release of water from the cells, during cholera, which was a common cause of death in Europe when the mutation first appeared (https://en.wikipedia.org/wiki/%CE%94F508).

Please check out the introduction of this posting at Youtube at https://youtu.be/TihjjAhMf2Q

NEXT POST to Our CF Matters Hawaii, September 26th – “Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). What is it?”


FDA Approves Cystic Fibrosis Medication ORKAMBI – July 2, 2015

Hi All,

On July 2, 2015, the FDA approved the break through Cystic Fibrosis drug Orkambi (http://investors.vrtx.com/releasedetail.cfm?ReleaseID=920512).  This CF drug, which is produced by Vertex Pharmaceuticals, together with an earlier developed CF medication, Kalydeco, are the first medications to try and counteract the underlying genetic defect that causes the disease, as opposed to only treating symptoms of this disease, as historic medications have done.

Approximately 30,000 Americans have CF, which is characterized by the buildup of sticky mucus in the lungs, causing frequent infections and a gradual decline in lung function.  Orkambi has been approved for those cystics who have two copies of the CF gene mutation F508del, of which about half of those 30,000 individuals hold these two mutations.   Of that subset, Orkambi has been approved for around 8,500 individuals aged 12 and older.

Orkambi’s approval was based on data from two double blinded, placebo controlled Phase 3 studies (TRAFFIC and TRANSPORT).  Results of those studies experienced statistically significant improvements in lung function, as well as decreases in pulmonary exacerbations (IV and/or hospital treatments) and improvements in Body Mass Index (BMI).

Orkambi combines lumacaftor and ivacaftor to treat these problems with a two-step approach. Lumacaftor helps move the defective CFTR protein to its proper place at the cell surface. Ivacaftor increases the activity of the protein once it is there, supporting the flow of salt and fluids, which helps thin the thick mucus that builds up in the lungs of people with Cystic Fibrosis (https://www.cff.org/News/News-Archive/2015/CF-Foundation-Celebrates-FDA-Approval-of-Orkambi-as-Important-Advance-for-the-CF-Community/ ).

As stated above, at this point, Orkambi has been approved only for those CF patients with two copies of the F508del.  F508del is a deletion mutation on the cystic fibrosis transmembrane conductance regulator or CFTR protein which causes abnormal transport of sodium through membranes, leading to inflammation and mucus deposition in the lungs of patients (http://cysticfibrosisnewstoday.com/orkambi-lumacaftor-ivacaftor-vertex /).

Orkambi is taken as a dose of two tablets every 12 hours (morning and evening) with fat-containing foods.

Please see the video introduction of this topic at YouTube – https://youtu.be/Z2hSS0wjZt8


NEXT POST to Our CF Matters Hawaii, September 19th – “Cystic Fibrosis gene mutation F508del.  What is it?”

RE-POST – Final Data: Phase 2 Combo Study VX-809 & Cystic Fibrosis Drug Kalydeco – 2012 North American CF Conference



Hi all,

Earlier this month at the at the 26th Annual North American CF Conference, final data from a Phase 2 study of a trial involving a treatment with the CF drug compound VX-809 and Kalydeco was discussed by Dr. Michael Boyle of Johns Hopkins School of Medicine. Overall, Dr. Boyle stated that the final results showed statistically significant improvements in lung function for cystic fibrosis patients treated with this potential drug.

The final results from this trial that enrolled 109 people with CF aged 18 years and older with one or two copies of DF508 were based on the last 28 days of the 56-day study were initially released this past June by the manufacturer of Kalydeco, Vertex Pharmaceuticals, Inc. (http://investors.vrtx.com/releasedetail.cfm?ReleaseID=687394). Participants were divided into five treatment groups of approximately 20 individuals each. Three groups of those with two copies of DF508 received the experimental drug VX-809 alone for 28 days, then in combination with Kalydeco for an additional 28 days. A group with one copy of DF508 followed the same regime. A placebo group holding both one and two copies of the mutation was also involved in this trial.

The three groups with members who had two copies of DF508, the most common cystic fibrosis gene mutation, were treated with varying doses of VX-809 (200mg, 400mg, 600mg) in combination with Kalydeco. One of the primary endpoints to this study focused on the improvement of lung function, defined as the percent predicted FEV1 (the amount of oxygen that can be forcibly exhaled in one second). These final results showed that the most significant improvement was found with those who received 600mg of VX-809. To quantify this, from day 28 to 56, when patients began to receive Kalydeco in addition to VX-809, as opposed to the first 28 days when the group was dosed only with VX-809, it was revealed that 55% of participants witnessed a greater than 5% improvement in FEV1. Further, from day 28 to 56, 25% of the 600mg group showed a 10% improvement in FEV1.

Patients in this study who hold just one of copy of DF508 also responded positively with VX-809, albeit at a lower success rate than individuals who had two copies of DF508. Based on this information, Vertex is planning additional studies of VX-809 and Kalydeco for people with just one copy of the mutation.

Another primary endpoint of this study was to determine the improvement of sweat chloride in the study population. A reduction of sweat chloride shows that this drug combination is likely causing a positive change in the function of the CFTR protein. An improper function of the CFTR is the known cause of CF, which would mean that a reduction in the chloride certifies that the medication is performing as expected, and is treating the underlying cause of CF. However, although improvements were shown for participants who had two copies of DF508 during the first 28 days of this study, results from the final 28 study days found no statistically significant reduction of sweat chloride.

Per the website seekingalpha.com, the success of this drug combination could boost the eligible pool of individuals with CF by up to ten times (http://seekingalpha.com/article/566421-vertex-this-patent-king-is-the-stock-du-jour). In early 2013, Vertex plans to begin a type of trial on Kalydeco and VX-809 on the CF population with two DF508 mutations that is designed to provide the U.S. Food and Drug Administration, and similar authorities in other countries, with data to decide whether or not to approve this potential drug (http://www.nasdaq.com/article/vertex-reports-final-data-from-phase-2-combination-study-of-vx-809-and-kalydeco-20120628-00206).
A slideshow of Dr. Boyle’s presentation can be found at http://nacfcdl.cff.org/Documents/NACFC%202012_Boyle_Phase%202%20VX809-ivacaftor%20results.pdf.

Live life.

A brief video introducing this posting can be seen on YouTube at http://www.youtube.com/watch?v=8LXieAyEAyc.

BTW – If you would like me to research and post any topic of interest regarding Cystic Fibrosis, please feel free to e-mail your suggestions to me at ourcfmattershawaii@yahoo.com. I will do my best to place your idea into my queue of topics to cover on this site. Thanks for your feedback.