CAN A BLOOD TRANSFUSION COME IN THE WAY OF GETTING A TRANSPLANT?

The answer is yes.

The body’s immune system forms certain proteins called antibodies that protects us from bacteria and viruses. These antibodies can also be formed after a previous blood transfusion, pregnancy or an organ transplant. The antibodies are formed because the immune system recognizes the new cells after a blood transfusion as “foreign” and tries to protect us from these “invaders”. It is a well known fact that kidney failure patients sometimes require multiple blood transfusions during their dialysis treatments to treat low blood counts or anemia. Every pint of blood that they receive contains different cells or “antigens” to which the immune system will form the antibodies. These antibodies are also called “donor-specific antibodies” and are responsible for an increased chance of a rejection, should the patient receive a kidney from a donor that happens to have these antigens.

Prior to any transplant procedure, physicians check the blood of the recipient for antibodies to the donor kidney. A small sample of blood is mixed with white blood cells from the donor. This is the crossmatch procedure. A positive crosmatch means that the number of antibodies to that particular donor is high and there is a high likelihood of severe rejection of that donor’s kidney if it is used for transplantation. A negative crossmatch means that the number of circulating antibodies to the donor is low and will therefore not result in rejection right after the procedure. Keep in mind that multiple anti-rejection drugs are needed after the transplant and these drugs are required to be taken for life in order to prevent rejection of the transplanted organ.

Some dialysis patients have a very high level of multiple different antibodies. A blood sample can be used to calculate the PRA or panel reactive antibody. A high PRA means that the number of antibodies to potential donors is high, which makes it more difficult to find an appropriate donor. Typically, patients with high PRA have a longer waiting period and are given priority for transplantation. The good news is that most patients have a lower level of PRA and can therefore not have to wait too long for a transplant. The average waiting time today is 3 to 5 years for a kidney transplant in the US.

Pregnancy and previous organ transplants are also known to trigger the formation of antibodies that can cause the PRA to be high and hence a longer wait time. Different strategies to overcome the presence of these antibodies have been used. Some of these strategies include medications such as rituximab, intravenous immunoglobulin (IVIg) and plasma exchange, all of which work to lower the antibody levels so that a timely transplant without the fear of early rejection can be performed.

CMV INFECTION AFTER ORGAN TRANSPLANTATION

CMV (or CytoMegaloVirus) is a common viral infection after an organ transplant operation. It belongs to the same family as the herpes virus and spreads via direct contact of body fluids such as saliva, blood, urine, semen and breast milk. In most people who are healthy, there are no symptoms. A majority of adults have antibodies to the virus, which means that they have had a past infection with CMV. Even when symptoms do occur, healthy people will recover without any need for anti-viral treatments.

A common trait of this virus is its ability to lie dormant or inactive in the body for life. This is called “latent” infection. In people whose immune system is weakened, this virus can get reactivated and can then cause serious disease that can affect various organ systems such as:

1. the retina (the inner lining of the eye that is responsible for our vision), causing blurred vision and blindness
2. the lungs, causing pneumonia
3. the large intestine or colon, causing colitis
4. the nerves, causing weakness and numbness of the legs and feet
5. the esophagus and stomach, causing esophagitis or gastritis, causing pain on swallowing food or liquids or stomach pains
6. the liver, causing hepatitis
7. the brain, causing meningoencephalitis
8. the pancreas, causing pancreatitis
9. the heart, causing myocarditis

Other ways a person can get infected is by receiving an organ from a donor who has CMV or getting a new infection after the transplant procedure.

In a patient whose immune system is weak after an organ transplant, it is common to see flu-like symptoms due to CMV. Symptoms include fever, malaise, body aches, low blood counts and liver dysfunction. These symptoms usually appear from the 3rd to the 16th week after the transplant.

The incidence is higher in patients who have received lung or heart-lung transplants and in patients undergoing pancreas or kidney-pancreas transplants.

Other risk factors include those who have received strong medications to either prevent or treat rejection after the transplant, advanced age of either the donor or the recipient and when there is a greater degree of genetic mismatch between the donor and the recipient

Diagnosis is usually by doing specific blood tests and in certain cases, performing a biopsy to look for the presence of CMV.

It is best to prevent CMV from spreading by giving anti-viral medications to certain high risk patients right after the transplant procedure. It is usually given for three months.

Treatment in someone who has CMV is by giving intravenous ganciclovir or oral valganciclovir. The treatment is continued till the virus is eradicated.

PERITONEAL DIALYSIS – THE FACTS

What is the peritoneum?

The peritoneum is the thin inner lining of the abdomen that coats all intra-abdominal organs and the inner aspect of the abdominal wall. It consists of two layers, the parietal peritoneum that lines the abdominal and pelvic wall and the visceral peritoneum that lines the organs in the abdomen and pelvis.

How does the peritoneum help with dialysis?

The peritoneum acts as a natural filter and is used to help with the removal of waste products and extra fluid from the body. This function is usually reserved for the kidneys. In the presence of kidney failure, the removal of waste products is accomplished either via the blood (hemodialysis) or by inserting a soft tube (catheter) inside the abdomen and using the peritoneum to perform the filtering function.

How does peritoneal dialysis (PD) work?

After the catheter is inserted, it is ready for use in a few weeks. A special fluid, called the dialysate is placed inside the abdomen via the catheter and allowed to stay there for a few hours. The dialysate has a sugar called dextrose in it that makes it concentrated which then helps in pulling in the waste products and extra fluid from the body into the peritoneal cavity. The amount of time that the dialysate sits in the abdomen is called the dwell time. This is individualized by the nephrologist based on the medical condition of the patient. After a few hours, the fluid is then allowed to drain out and is discarded. A new bag of dialysate is then placed into the abdomen for a fresh dwell time.

The process of placing the dialysate and then draining it is called an exchange.

How many times does PD need to be done every day?

That depends upon the type of PD that is decided upon.

Continuous ambulatory peritoneal dialysis (CAPD) will require 3 to 5 exchanges every day. At the end of the day, an exchange is done before bedtime and the fluid is then drained upon waking up in the morning. CAPD does not require a machine and is done by hooking a plastic bag containing the dialysate to the catheter and then using gravity to drain the fluid at the end of the dwell time. Patients can be ambulatory and go about doing their daily activities while the dialysate is in the abdomen.

Automated peritoneal dialysis (APD) is usually done at night with the help of a cycler that delivers and drains the dialysate fluid during sleep.

What are the pros and cons of peritoneal dialysis?

Peritoneal dialysis is easier on the body because it is done continuously and can therefore mimic the kidney in its function. Removal of the extra fluid is gentler and therefore is less stressful on the heart. Daily activities, work and travel can be done more easily compared to hemodialysis.

PD may not be appropriate for certain individuals- these include morbidly obese patients and patients who have had previous surgeries on their abdomen.

The biggest complication with PD is peritonitis, which can be a life-threatening problem. This happens when the exit site of the catheter becomes infected or the catheter becomes contaminated during the exchanges. Most patients will have abdominal pain, fever, nausea or vomiting and some redness near the exit site. The dialysate might also look unusually cloudy. If this happens, patients may need to be admitted to the hospital for antibiotics to clear the infection. In rare circumstances, the catheter may need to be removed.

Fluid and dextrose absorption can also occur with longer dwell times. This usually leads to weight gain and bloating. A cycler might be necessary in patients who use CAPD during the night.

RECOVERING AFTER A KIDNEY TRANSPLANT

After a prolonged and anxious waiting period on the kidney transplant waiting list, you have finally received a new kidney from a suitable deceased donor. Congratulations, now begins a new chapter in your life where you bear the responsibility of taking good care of this gift of life that you have been lucky to receive. Please remember, some donor, unrelated to you had to die for you to receive this kidney.

Generally, most patients either wake up in the post-operative recovery room or in the ICU, where they are closely monitored for not only how well the kidney is functioning but also other vital signs such as the temperature, heart rate and blood pressure. If everything is stable, oral diet with liquids followed by solid food is initiated in a few hours after the operation. The medications that will prevent rejection, known as immunosuppressive medications are begun in the peri-operative period. Most patients today receive three to four different medications. The risk of rejection is the highest right after the procedure and therefore all these medications are given in higher doses initially. As the days go by and the transplanted kidney is functioning well, the doses are slowly tapered down and you are then put on “maintenance” doses of the different medications. Each transplant center has its own policy regarding what combination of drugs they like to use, so please adhere to the ones they want you to take. In general, you will be on two or three oral medications for the rest of your life in order for the transplanted kidney to work well without any rejection episodes. In addition, there may be additions or changes to the already existing medications that you were taking prior to the procedure. Some medications may no longer be required and will be discontinued.

Early post-operative complications can sometimes occur. These include:

1. Allergic reaction to the general anesthetic
2. Bleeding – either in the urine (hematuria) which usually stops spontaneously or from around the anastomoses, that is where the renal artery and vein are sewn to the major blood vessels in the pelvis. This can cause a blood clot or hematoma which can press on the kidney and cause dysfunction of the graft. In most circumstances, surgery to evacuate this hematoma is required.
3. Leakage or blocked ureter - this is due to leakage of urine from the site where the ureter is sewn to the bladder, causing renal dysfunction. In most cases, inserting a urinary catheter into the urinary bladder will help with the healing but sometimes surgical intervention may be required.
• A blocked ureter is most likely due to a tight anastomosis or a blood clot within the ureter itself. Both these problems may need surgery.
4. Infections, mainly over the incision can be seen early after a transplant. This is called a surgical site infection and is more likely in obese, diabetic and elderly patients
5. Rejection or failure of donated kidney. Early rejections are uncommon because of the careful pre-operative matching processes that are now in place prior to any kidney transplant. However, they do occur and often need a biopsy to confirm that the dysfunction is from rejection. Treatments with high dose steroids or other special immunosuppressants such as thymoglobulin etc are started to save the kidney from becoming irreversibly damaged. Hyperacute rejection is due to the presence of pre-existing antibodies in the recipient which will lead to an immediate failure of the transplanted kidney, the treatment of which is to surgically remove the kidney.
• A phenomenon known as delayed graft function (DGF) is observed in a few deceased donor kidney transplants. It is defined as the need for dialysis within the first week after the transplant. There are many factors that can give rise to DGF but most kidneys do recover to then have a long half life.
6. Heart attack/stroke –especially if the patient has pre-existing severe vascular disease, diabetes or hypercholesterolemia or due to intra-operative complications such as excessive bleeding.

WHAT HAPPENS WHEN YOUR KIDNEYS START FAILING?

The symptoms of kidney failure vary with the cause and its severity.

In the early stages of the disease, most patients are asymptomatic as the kidneys possess tremendous reserve and are therefore resilient to the changes that are contributing to the kidney dysfunction. However, as the kidneys start to decompensate further, certain features will now show up. These could be:

1. Fluid retention, which means that the body is unable to excrete fluid and this causes puffiness, swelling of the arms and legs and in more advanced cases, fluid buildup in the lungs, called pulmonary edema.
2. Dehydration in its severe form will cause temporary renal dysfunction and manifests as thirst, dry mouth, rapid heart rate and weakness.
3. Low urine output
4. Urinary complaints like frequency and urgency
5. Easy bruising of the skin and bleeding
6. Fatigue and confusion
7. Nausea with or without vomiting
8. Loss of appetite
9. Pain in the muscles, joints and bones
10. Itching
11. Anemia

Causes of kidney failure

Kidney failure could be temporary or permanent.

Temporary kidney failure is usually seen in hospitalized patients who are critically ill from some other cause. Examples include heart failure where the kidneys shut down temporarily because of low blood flow to the kidneys or severe infection in another organ system of the body that can trigger sepsis and cause all major organs, including the kidneys to start failing.

If the medical team feels that the kidney failure is temporary, the treatment is usually supportive and focuses on treating the cause of the kidney failure. If the kidneys are slow to recover, temporary dialysis might be instituted to tide over the acute phase till the kidneys gradually recover their function.

Chronic kidney failure is also known as end stage renal disease (ESRD) where there is irreversible and permanent damage to the kidneys and therefore the patient will now need some form of dialysis or need a kidney transplant to keep him alive.

Common causes of ESRD include:

1. Diabetes
2. High blood pressure
3. Glomerulonephritis, which is a chronic inflammation of the glomeruli, which are responsible for the filtering of the blood in the kidneys
4. Other causes include causes from birth such as vesicoureteral reflux, chronic kidney stones, enlarged prostate or certain cancers

INFECTIONS COMMON AFTER ORGAN TRANSPLANTS

Recipients of organ transplantation are at a higher risk of infections because of the multiple drugs that they take to prevent rejection also can increase their risk of developing infections.  Therefore, a higher index of suspicion is necessary to avoid major infections after the transplant.

A thorough pre-transplant work-up is necessary to identify and treat any pre-existing infections and to educate the recipient on what to look for once he has received the transplant. This includes:

1. A thorough history and physical

Questions on past infections, vaccinations, allergies to antibiotics, potential exposure to infections trough travel in the US and abroad, animal contact, contact with TB

2. Tests that need to be done prior to listing for a transplant

PPD for TB, chest x-ray, blood tests to test for immunity to certain viruses such as CMV, varicella zoster, herpes simplex and HIV.

Post transplant infections

It is helpful to divide the timeline into three time periods. Certain infections occur more frequently within one period of time than the others.

First month (early)

This is the time that the immune system is most suppressed in order to prevent early organ rejection. The majority of the infections are either hospital acquired or due to surgery.

Infections may be: urinary tract because of a urinary catheter wound infection on the surgical wound pneumonias bloodstream infections because of pre-existing catheters

Yeast infections from candida and herpes simplex viral infections can also occur.

Months 2 to 6

During this time period, infections from Pneumocystis carinii pneumonia (PCP) or TB can occur. Reactivations of certain viral infections such as CMV, varicella zoster, Epstein Barr virus and hepatitis virus can occur as well.

After 6 months

At this point, most transplant recipients are at risk for community acquired infections such as urinary tract infections, influenza and bacterial pneumonias.

REJECTION OF THE TRANSPLANTED KIDNEY – HOW IS IT TREATED ?

Rejection of the kidney transplant is caused by the immune response of the body to destroy the graft. The immune system consists of a network of cells, tissues and organs whose only job is to protect the body against “foreign invaders”. These invaders are usually bacteria, parasites, viruses and fungi. In case of a person who has received a transplant, it is that new organ that is considered “foreign” that the immune system wants to protect against.

This process of this “rejection” of the “foreign” organ starts the minute the kidney  receives its blood supply in the patient. A protective system in the body known as “innate immunity” is the first to react against the transplant by introducing a group of cells known as lymphocytes and other complex chemicals to the new kidney. This kind of rejection is called “cellular rejection” which is different from another form called “humoral rejection” where the recipient has pre-existing antibodies that attack the new kidney. Antibodies are proteins that the body’s immune system produces against a specific antigen on the transplanted kidney.

Hyperacute rejection is an uncommon phenomenon today but describes the earliest form of rejection due to pre-existing antibodies in the blood of the recipient to the donor kidney. Right after the blood starts to flow into the new kidney, the kidney swells up, turns pale or blue and essentially becomes non-functional. The only treatment at this point is to remove and discard the kidney. This type of rejection is seen within minutes to hours after the transplant.

Hyperacute rejection is prevented by testing the recipient’s blood for the pre-existing antibodies to the donor by a process called as a crossmatch, which is done just prior to the transplant between the recipient’s blood and the lymph tissue procured from the donor.

Acute rejection is usually seen in the first few months after the transplant and can be caused by cells known as lymphocytes or by antibodies to the new kidney. The crossmatch process helps to identify pre-existing specific antibodies against the kidney and will help in starting appropriate anti-rejection medications to prevent rejection episodes.

Chronic rejection is observed months to years after the transplant and represents a slow decline in the function of the kidney. It can be delayed by ensuring adequate doses of medications that will prevent acute rejection and by protecting the graft from high blood pressure, diabetes, high cholesterol and certain viral infections, such as CMV.

How is acute rejection diagnosed?

Patients with a kidney transplant who suffer an acute rejection episode will usually have the following clinical features:

1. Flu like symptoms with chills, mild fever, body aches or nausea
2. Decrease in the amount of urine made by the kidney
3. Pain over the transplant
4. General feeling of unease

With these symptoms, blood work is ordered and may show a rise in the serum creatinine with a definitive diagnosis reached after a biopsy. This is usually done with the help of an ultrasound in the radiology department. In addition to the biopsy, the ultrasound looks for any anatomical issues like hydronephrosis (swelling in the kidney due to backed up urine) or any blood vessel abnormalities within the kidney as well.

How is acute rejection treated?

Most patients, especially with biopsy confirmed rejection episodes early after transplantation are admitted to the hospital for a short stay in order to adequately treat and closely monitor the response to the treatment.

If the biopsy shows acute cellular rejection, the first line of treatment is steroids through the intravenous route. Each day, the blood work is checked to look for a decrease in the creatinine and to monitor the white blood count, blood glucose levels and a change in the urine output. Usually 3 to 5 doses via the intravenous route are given. Once the parameters improve, the steroids are converted to oral form and the patient is then discharged with a change in the doses of the immunosuppression medications in order to adequately quell the rejection. Frequent follow up visit are set up to ensure adequate treatment.

If the biopsy shows antibody mediated rejection, treatment with special medications such as thymoglobulin are given to treat this more severe form of rejection. During this treatment, admission is definitely warranted and close monitoring of the kidney function and the development of new infections is closely monitored as well. Once the kidney function improves, the patient is discharged with frequent follow up visits planned.

LUNG TRANSPLANTATION

HISTORICAL PERSPECTIVE

Dr. James Hardy is credited with performing the first successful human lung transplant at the University of Mississippi in 1963. The recipient lived for only 18 days after the procedure and several other attempts around the world failed because of rejection and problems with healing. Lung transplantation has come a long way since then, with the introduction of many new anti-rejection medications, newer operative techniques and better patient and donor selection. Current data from the International Society for Heart and Lung Transplantation Registry reports a 1 year survival of 78 % and a 5 year survival rate of 51 %.

PATIENTS THAT BENEFIT FROM A LUNG TRANSPLANT

Advanced and irreversible lung disease which include chronic obstructive lung disease (COPD), restrictive lung diseases such as cystic fibrosis and pulmonary hypertension are the usual patients who are considered for this procedure provided they meet the following criteria:

1. > 50 % risk of death in 2 years without the transplant
2. > 80 % survival for at least 3 months after the transplant
3. > 80 % 5 year survival from the general medical perspective provided the transplanted lung functions well

PATIENTS FOR WHOM LUNG TRANSPLANT IS NOT AN OPTION

Absolute contraindications for lung transplantation include:

1. Cancer within the last two years (except non-melanoma localized skin cancer)
2. Untreatable severe dysfunction of another major organ system (unless a combined procedure can be performed)
3. Severe atherosclerotic heart disease
4. Uncorrectable bleeding disorder
5. Acute sepsis
6. Active chronic infections such as TB
7. Obesity with a BMI > 35
8. Non-compliance with medical treatments
9. Psychiatric issues
10. Substance abuse
11. Absence of reliable social support system

Relative contraindications include:

1. Older age (> 75 years)
2. BMI 30 to 34.9
3. Severe malnutrition
4. Prior chest surgery with lung resection
5. Infections with resistant or virulent micro-organisms

WHAT IS THE USUAL WORK UP PRIOR TO THE TRANSPLANT

This includes laboratory studies and other tests.

Lab work includes:

1. Complete blood count
2. Liver and kidney function
3. Viral studies to look for HIV, hepatitis B, hepatitis C, CMV, EBV
4. Room air blood gas
5. Coagulation profile

Imaging studies include:

1. High resolution CT of the chest
2. Echocardiogram
3. Right and left heart catheterization
4. Lung perfusion scan
5. Bone density scan
6. Pap smear/PSA
7. Bronchoscopy
8. Pulmonary function tests

HOW DOES THE WAITING LIST WORK FOR LUNG TRANSPLANTATION

The lung allocation system was recently revised in 2016. Each candidate 12 years or older receives an individualized score between 0 to100. The higher the score, the earlier a candidate is likely to receive a transplant in the geographic area of the patient’s residence. Criteria that go into calculating the score is the patient’s medical information (such as lab values, test results and disease diagnosis). The patient’s blood type and the distance from where they live to the hospital where they will receive the transplant are also factored in. This score is used to estimate the severity of the illness and the patient’s chances of success after the transplant has been received.

WHAT SPECIAL DRUGS ARE NEEDED AFTER THE TRANSPLANT

Special medications known as immunosuppressive drugs are started right away after the transplant procedure. These drugs fight the body’s immune system so that the transplanted lung does not suffer a rejection. These drugs are extremely powerful and need to be taken life long in order to avoid rejection. These drugs can themselves cause side - effects such as increased chances of infections, renal dysfunction, cancer, heart and vascular disease, to name a few.