HEART VALVE TRANSPLANTATION

The human heart has 4 chambers, which consist of 2 atria and 2 ventricles, one on each side. The upper chamber is the atrium and the lower one is the ventricle. Between each atrium and ventricle is a valve that keeps the blood flowing in the forward direction. Deoxygenated blood is brought to the right atrium, which then flows into the right ventricle, directed by the tricuspid valve. It then flows into the lungs via the pulmonary artery so that it can get oxygenated. The pulmonary valve controls the blood flow from the right ventricle into the lungs. Oxygen rich blood then flows to the left atrium and then into the left ventricle, directed by the mitral valve. The left ventricle, which is the largest and strongest of the four chambers, will then pump the blood into the aorta via the aortic valve to be distributed to the rest of the body.

Heart valves may need to be replaced if a child is born with a congenital defect or in diseased states such as infective endocarditis or mechanical abnormalities that might cause a valve to malfunction, sometimes seen after a heart attack. Options available to replace heart valves include artificial mechanical valves or those obtained either from an animal source such as the pig or from a human donor. Human heart valves can be obtained from hearts that are being replaced after a heart transplant or after a person agrees to becoming a tissue donor upon his death.

In adults, the most common heart valve operations are aortic and mitral valve replacements. A mechanical heart valve is made of synthetic but durable and long lasting materials and is expected to last a person’s lifetime. Persons receiving this kind of valve almost always will require blood thinning medications in order to avoid blood clots from developing and causing malfunction of the valve. These medications also prevent blood clots from getting dislodged and travelling to the brain causing a stroke or to the heart causing a heart attack. The disadvantage of taking a blood thinner is the increased risk of excessive bleeding.

Tissue valves are created from animal tissues (such as pig heart valves and cow valves made from the pericardium of a cow’s heart) and usually last 10-20 years. They do not require blood thinning medications long term. A human donor valve is the least common choice for heart valve replacement today and is also expected to last between 10 and 20 years without requiring blood thinners.

Donation of heart valves fall under the category of tissue donation. Most people are aware that organ donation can save upto 8 lives. Tissue donation can enhance or save over 50 individuals. Each year, approximately 30,000 tissue donors provide lifesaving tissue for transplantation. Over 1.5 million patients are helped with tissue donation every year in the US. Tissues commonly donated include corneas, heart valves, skin, bone, blood vessels and tendons.

Age criteria for heart valve recovery include donors being between newborns to 60 years of age. Valves can be recovered within 15 hours if the body is not refrigerated or within 24 hours if the body is refrigerated within 12 hours of death. After removal, recovery professionals carefully inspect the valves for any abnormality before processing and storage. Processed and packaged heart valves are stored in minus 100 degrees Centigrade or cooler and have an expiration date of 5 years.

BONE TRANSPLANTATION

Bone transplantation or bone grafting, as it is more commonly known is a surgical procedure where surgeons use an external source of a bone or a bone substitute to replace bone tissue lost due to cancer, trauma or infection.

A human bone has the ability to heal itself by forming new bone. Sometimes, this ability is hindered due to extensive bone loss after severe trauma, surgical removal of bone tumors or after removal of bone infections. This leaves a large defect, which typically would not heal without a bone graft.

Bone grafts can usually be obtained from three sources:
A) autologous – bone harvested from a different area from the patient’s own body.
B) allograft – bone harvested either from a deceased donor or from a living donor who has donated a small part of his bony skeleton, as happens after a hip replacement, where the donor agrees to donate a part of the hip bone being removed during the procedure that would normally be discarded.
C) synthetic – using an artificial substance with similar mechanical properties as a bone.
Most bone grafts are finally reabsorbed and replaced as the natural bone heals after a few weeks.

Autologous bone grafts use bone from a non-essential area such as the iliac crest or the hip bone, the leg (fibula), ribs, mandible (jaw) and the skull. Advantages of using one’s own bone is that it reduces the chance of getting an infection from another donor and of graft rejection. Disadvantages include another potential source of pain, infection and other complications at the second site from where the bone graft is obtained.

Allograft bone is obtained either from a deceased or a living donor. These are typically obtained from bone banks after they have gone through stringent testing requirements in order to enhance their safety.

Synthetic bone substitutes include materials like hydroxylapatite, which occurs naturally and can sometimes be used in combination with other minerals or polymers. Ceramics have been used extensively to create artificial bone substitutes as well. Corals from the ocean have been found to be excellent bone substitutes as well.

Common uses of bone grafts include their use as support structures for dental implants and for reconstruction procedures after bone loss from infections, tumors and trauma involving the jaw bone. The fibula is also used as a bone graft for long bone reconstructions involving the lower or upper limbs.

Recent advances in biotechnology has an Israeli company use a lab-grown semi-liquid bone graft, grown from a patient’s own fat cells, be used as a viable replacement for lost areas of the jaw bone in 11 patients, with great long term results. This would undoubtedly lead to more research and innovation to come up with safer, more abundant natural sources of bone substitutes at a lower cost to benefit a wider section of mankind.

WHAT IS INTESTINAL FAILURE?


Intestinal failure is a serious condition that prevents a person from digesting and absorbing food and other essential nutrients, which leads to malnutrition, prevention of normal development (especially in children), a reduced quality of life and even death.

The most common cause of intestinal failure is short bowel syndrome, where at least half or more of the small intestine has been removed surgically. Ideally, a length of at least 200 cms of small bowel would ensure adequate nutrient absorption. If the large bowel is still present, a minimum length of 100 cms of small intestine is needed to ensure that adequate digestion of food occurs that would be enough to sustain life.

In children, conditions such as congenital anomalies, infections of the small bowel, extensive bowel surgeries and an inborn inability to absorb food can lead to intestinal failure.
In adults, extensive bowel surgeries, inflammatory bowel disease such as Crohn’s disease, radiation induced enteritis, severe celiac disease and tumors involving the small bowel or the mesentery can lead to short bowel syndrome and ultimately intestinal failure. The mesentery is a fold of tissue that connects the stomach and intestines to the abdomen.

What are some symptoms of intestinal failure?
These include diarrhea, poor appetite, weight loss, bloating, increased gas, foul smelling stool and vomiting.

What are some of the treatment options for a patient with intestinal failure?
This depends on how much of the small intestine is actually functional in a particular patient. We have already discussed how long the small bowel should be for adequate digestion and absorption of the food one eats.
In its initial stages, most patients require TPN, also known as total parenteral nutrition. This involves placing a catheter in the neck, chest, arm or groin in order to give liquid nutrition directly into the blood stream. TPN fluids are carefully created for each individual patient’s metabolic requirement and contains carbohydrates, fats, proteins, minerals and electrolytes in a precise formula. This can be given over 24 hours when the patient is unable to eat or drink anything by mouth or over a shortened period, say 12 or 18 hours, when a patient can take in some nutrition by mouth but not enough for his or her daily requirements.
Oral intake is then gradually introduced and advanced, as tolerated. Specialized oral solutions providing most of the nutrition is used to wean the patient off the TPN. As much as possible, regular food intake with adequate additional supplements would be the ultimate goal.

In some patients, adequate oral intake is not achievable and therefore the patient is TPN dependent for life. Complications related to TPN occur frequently and include catheter related infection or sepsis, glucose related abnormalities (high glucose or low glucose), liver dysfunction, serum electrolyte and mineral abnormalities, bone disease such as osteoporosis, stones in the kidney or gall bladder (gall stones) and allergic reactions to the contents of TPN. TPN also happens to be expensive and can therefore add to the burden of the disease itself.

Long term outlook for intestinal failure is dependent on how much of the intestine can be used normally without depending on TPN or any other specialized tube feedings. Severe complications related to long term TPN such as liver failure or severe catheter related access issues should prompt an evaluation for intestinal transplantation. This requires a referral to a transplant center that specializes in this procedure. As progress is being made on every front, the results of intestinal transplantation are constantly improving, providing a ray of hope to those afflicted with this dreadful disease.

OBESITY AND KIDNEY TRANSPLANTATION


Obesity in the general population is a growing problem in the US and is especially problematic when viewed from the standpoint of a patient who has chronic kidney disease and is awaiting a kidney transplant. Research has shown that there is a higher chance of death while on dialysis – almost 20 % per year, with this rate almost 9 times higher if you are also obese. This is probably because obese patients with kidney disease happen to be older, have a higher incidence of diabetes and are more likely to be African American. It is estimated that more than 60 % of kidney transplant recipients today are obese or overweight, a number that has almost doubled since 1990.

Obese patients also tend to wait longer for a kidney on the waiting list. Compared to a person who has normal BMI (25 kg/m2), an obese patient (> 30 kg/m2), at an average waits almost a year and a half longer for a transplant. This no doubt increases the chance that he may never get a kidney in time and likely die on the waiting list.

Let’s look at what happens after an obese patient gets a kidney transplant. There is a higher chance that the transplanted kidney may not work right away, a phenomenon known as delayed graft function or DGF. This is especially true for recipients of a kidney donated by a brain dead donor. This in turn decreases the life span of the transplant in the long term. Obese patients are more likely to suffer from wound infections as well. Because of pre-existing diabetes and hypertension, obese patients also tend to have higher rates of cardiovascular problems such as heart disease and stroke. All these together combine to significantly shorten an obese person’s chances of having a functioning kidney transplant long term. Obesity has also shown to have a direct adverse effect on the functioning of the kidney.

Approximately 50 % of recipients will gain weight after a kidney transplant. This happens because dietary restrictions are no longer in place, there is improvement in a person’s appetite and also due to some post-transplant medications such as steroids that play a role in this weight gain.

Dietary interventions with regular and aggressive follow up have shown to be helpful in the first few months after a kidney transplant in controlling weight. Physical activity is also highly encouraged and has been found to be beneficial in preventing excessive weight gain and increasing the sense of well-being. Some transplant programs have also encouraged pre-transplant bariatric or weight loss surgery which has had beneficial results.

YOU NEED A KIDNEY TRANSPLANT – WHAT WORKUP IS REQUIRED?

Kidney transplantation is offered to patients who are already on dialysis or are going to need this treatment soon. In the latter case, receiving a transplant prior to being on dialysis is called pre-emptive transplantation. Multiple studies have shown that a successful kidney transplant enhances the quality of life and can also add years to your life as well. In short, a kidney transplant can be a life-saving operation, if it is well taken care of.

Exhaustive evaluations are generally required for all potential transplant candidates. This is done to make sure that any potential issue that could harm the transplanted kidney or the patient is identified and corrected prior to listing. After most of the testing has been done, the candidate is required to meet the transplant team which comprises of a transplant nephrologist, transplant surgeon, pre-transplant co-ordinator, transplant social worker and a financial advisor working with the program. Therefore, not only are medical issues looked into, social and financial issues are carefully evaluated as well.

Most work-ups start with lab studies. These include:

a) Blood chemistries (includes electrolytes, kidney function etc)
b) Liver function tests
c) Complete blood count (hemoglobin, platelet and white blood cell counts)
d) Coagulation profile (to check the ability of the blood to clot)

Further testing is ordered to rule out potential infections, especially certain viral infections. These include:

a) Hepatitis B and C
b) Epstein Barr virus
c) Cytomegalovirus
d) Varicella zoster virus
e) Syphilis testing
f) HIV
g) PPD for TB

The transplant team carefully looks at all organ systems, especially the heart, particularly if there is a prior history of heart related issues, if the patient has type 1 diabetes or if high blood pressure is the cause of renal failure.
This starts with:

a) Chest x-ray
b) EKG
c) Stress test
d) Echocardiogram
e) Heart catheterization, if required.
In addition to the blood tests outlined above, tests to identify the blood group and certain pre-existing antibodies that could cause rejection of the organ are done as well. Specifically, the transplant team would want:

a) ABO blood group determination
b) HLA typing
c) Antibodies to HLA phenotypes
d) Crossmatching


While these tests are standard in all potential candidates, further tests may be required, which are:

a) PSA to rule out prostate cancer
b) Pap smear
c) Colonoscopy, if age > 50 years or if  family history of colon cancer is present
d) Upper endoscopy with history of peptic ulcers
e) Dental check up to rule out infections
f) Urine testing in patients who still make some urine
g) Carotid duplex to look at carotid arteries for atherosclerotic plaques
h) Ultrasound of the native kidneys
i) Doppler studies of the arteries in the legs and arms

Any of these tests could reveal abnormalities that could either rule out a patient from being considered for a transplant. For example, a colonoscopy might reveal colon cancer, which will require further treatment and possibly being ruled out from getting a transplant for at least 2-3 years.
Most centers take a very close look at obesity. Most transplant centers will not consider a patient as a candidate if the BMI is more than 40.

A significant part of the evaluation process is looking at the candidate’s psychosocial and family support situation. If there is a history of a major psychiatric condition, this needs to be evaluated by a psychiatrist prior to listing.
Also, it is very important to have some kind of family support for the care that is going to be required for the patient before and after transplantation.
Compliance with treatment is looked at seriously. Any issue with non-compliance may rule a patient out because the transplant team needs to make sure that a scarce resource such as an organ will not be wasted on someone who does not comply with the treatment regimen after the transplant.

During all this, any potential living donor is also worked up with some basic tests and an interview by the transplant team. He is evaluated to see if he would be a good match from the immunologic standpoint and to see if he is under any coercion or pressure to come forward as a donor.

TISSUE DONATION

Every year, there are approximately 20,000 tissue donors in the United States. Nearly a million tissue transplant surgeries are performed each year in the US and it is estimated that 1 in 20 Americans will need some type of tissue transplant. Almost 2.5 million people are helped through tissue and eye donation every year.

Tissues that can be donated include bone, heart valves, veins, skin, ligaments and tendons. These can be recovered upto 24 hours after death has occurred.

Tissue donation is different from organ donation. Organs that can be recovered for transplantation include kidneys, liver, heart, lungs, pancreas and intestine. Usually a tissue donor has died a biological death, meaning the person’s heart and lungs have permanently stopped functioning. In many instances, an organ donor has had a sudden death and is declared “brain dead” prior to becoming an organ donor. Approximately 24.000 people are declared brain dead each year. Only 2-3 % of all deaths meet the criteria for organ donation.

One tissue donor can enhance the lives of more than 50 recipients. Anyone, regardless of age is a potential tissue donor. Donated heart valves can help replace damaged ones and special bone grafts can help patients with spinal deformities. Skin/bone grafts can help replace tissue lost due to trauma, congenital deformities, cancer, arthritis and other conditions. Skin donations could be life saving for burn victims and are also used for reconstructive and plastic surgery applications

SALLY’S STORY – THE MIRACLE OF PAIRED KIDNEY DONATION

Sally M. (not her real name) was born with polycystic kidney disease (PKD), a condition that afflicts almost 600,000 people in the US. She was diagnosed with this dreadful disease when she was in her early 30’s. Just a few years ago, she had had her second child and she was busy being a mom and having a thriving small business that she ran with her husband, Chris.

Sally had known about PKD ever since she was a child.  Her own father also had PKD, which caused him to stop working when he was in his 40’s as his kidneys had stopped working completely and he had to undergo dialysis three times a week to stay alive. Upon the insistence of his kidney doctor, he was put on the transplant waiting list since he did not have anybody who could donate a kidney to him. After waiting for about four years, Sally’s father received a deceased donor kidney and he went on to live on for many years without having to be on dialysis.

Sally’s own family physician had referred her to a nephrologist many years ago so that he could keep an eye on her kidney function. At some point, he warned her, her own kidneys were going to start to shut down and she was going to have to be on dialysis, just like her dad. Now in her early 40’s, Sally’s kidneys had begun to get larger because of the growing cysts, which meant that she was moving closer to being on dialysis and needed to be evaluated for a kidney transplant.

Chris could no longer see his wife’s medical condition decline in front of his very eyes. He went to Sally’s nephrologist to be evaluated for being a live kidney donor. Based on the initial blood tests, he was found to have a different blood group and was therefore not a match for Sally. The nephrologist suggested paired donation and referred them to the university medical center for this procedure.

Paired donation is a relatively recent concept as a treatment option for kidney failure. The first live donor kidney transplant was between a set of identical twins in Boston. Transplant between these two brothers meant that as they were genetically identical, the donated kidney would not have any rejection episodes in the new recipient. Chris could not be a donor to Sally because his kidney would be immediately rejected by Sally’s body as their blood groups were not identical. With the help of paired donation, the transplant center was able to link them up with Jane and Fred (not their real names) who also were in a similar situation. Based on extensive testing, Jane could donate her kidney to Sally and Chris could donate his kidney to Fred. In this way, both Sally and Fred could avoid going on dialysis and receive healthy, live donor kidneys and have a long productive lives ahead of them.

The two couples lived approximately forty miles from each other. Therefore, on the day of the transplants, Chris became a donor to Fred at his transplant center while Sally received a kidney from Jane at her own hospital.  Both pairs did extremely well after their respective surgeries and continue to live healthy productive lives.

Paired donation has been able to save countless lives since it was first thought of in 1986. The first formal paired donation program was started in South Korea in 1991 and the first US paired donation was carried out at Rhode Island Hospital in 2000. After Johns Hopkins started the first US paired donation program in the US, many other similar programs have been started in different parts of the country. The National Kidney Registry carried out the longest chain of paired transplants in the country by having a 70 participant chain in 2014.

Today, both Sally and Jane are close friends, as are Chris and Fred. They serve as an inspiration to the power of collaboration and progressive scientific innovation to help combat the critical organ shortage in this country. More such pairs are needed to not only save lives but also millions of dollars that can serve to advance education and research to help end the agonizing wait for a transplant that thousands of people have to endure every year.