Kidney transplant for Fabry disease

Last updated May 3, 2024, by Lindsey Shapiro, PhD
Fact-checked by Ana de Barros, PhD

A kidney transplant is a surgical procedure to replace damaged kidneys with a healthy one that can be used in people with Fabry disease whose kidneys no longer function as they should.

In Fabry disease, the enzyme alpha-galactosidase A that’s needed to break down certain fatty molecules, namely globotriaosylceramide (Gb3), into smaller molecules that cells can use is deficient. Alpha-galactosidase A deficiency causes the fatty molecules to accumulate to toxic levels inside cells, causing progressive organ damage.

The kidneys are particularly vulnerable to damage caused by Gb3 buildup and many Fabry patients will develop chronic kidney disease (CKD) as a result of that damage. A kidney transplant is a late-stage intervention that may be used when kidney damage is so extensive that the organs’ function becomes severely impaired.

When is a kidney transplant necessary?

Kidneys are bean-shaped organs located below the rib cage on either side of the spine that are vital for maintaining overall health. Their main function is to filter waste products and excess water out of the bloodstream, which are then eliminated from the body as urine.

In Fabry disease, the accumulation of Gb3 in kidney cells can cause damage and result in symptoms such as the presence of proteins or blood in urine, changes in urination patterns, and swelling in the lower limbs. The first signs of kidney damage may arise in childhood and may be mild at first, but most patients will progress to kidney failure somewhere between their 30s to 50s.

Standard CKD therapies along with Fabry disease treatments, such as enzyme replacement therapy (ERT) and chaperone therapy, may help slow these declines, especially if they’re started early on before irreversible damage has accumulated.

However, Fabry disease is often not diagnosed until kidney declines have already advanced substantially and many patients will still progress to end-stage renal disease, also known as kidney failure. This means the kidneys have lost at least 85%-90% of their function, which is life-threatening.

At this stage, Fabry disease treatment alone won’t save the kidneys and patients will have two treatment options to address their kidney problems — dialysis or a kidney transplant.

Dialysis is a type of filtering process that helps clean waste products from the blood when the kidneys can’t do so on their own. A kidney transplant replaces the damaged organs with a healthy one from a donor that is able to clear waste on its own and produce enough alpha-Gal A enzyme to prevent the accumulation of Gb3 in its cells.

In comparison to dialysis, which requires that patients remain on treatment for the rest of their lives, a kidney transplant may increase a person’s life expectancy, improve life quality, and lower long-term treatment costs.

How does a kidney transplant work?

A kidney transplant involves providing a patient with a healthy kidney from a donor to replace their own dysfunctional ones. While every person has two kidneys, only one is absolutely needed to properly filter waste from the blood. Thus, while both kidneys eventually fail to properly perform their function in people with Fabry, only one healthy one needs to be provided in a transplant.

The donor kidney may be obtained from either:

A living donor: because the body only needs one kidney, a person with two healthy kidneys can donate one to someone who needs a transplant.
A deceased donor: when a live donor isn’t available, a patient will be placed on a national waiting list to receive a kidney from a person who has died.

In either case, the donor kidney must be matched to the recipient regarding blood type and HLA type, that is, certain immune system markers, to ensure the success of the transplant. If a person’s living donor is a family member, they’ll need to test negative for Fabry disease before donating.

Once a kidney is available, it will be harvested from the donor and the recipient will undergo surgery as soon as possible. The procedure typically takes about 3-4 hours, during which a surgeon will cut an opening in a person’s abdomen through which they’ll insert the kidney. The kidney will then be attached to nearby blood vessels, to ensure it has a blood supply, and to the bladder, to enable urine to be removed.

In most cases, the damaged kidneys will be left inside the body unless they’re causing pain or infections.

Preparing for a kidney transplant

Before a kidney transplant, a transplant team first has to make sure they’re healthy enough to undergo the procedure. This is done via a complete medical exam and a series of tests, which may include:

blood tests
prostate exams for men
gynecological exams and mammograms for women
tests of major organ function
mental health evaluations.

When the kidney comes from a live donor, the donor is also required to undergo these tests. Patients with severe heart or lung disease, active drug abusers, or those with uncontrolled psychiatric diseases, cancer, or uncontrolled infections may not be eligible for transplant.

Once eligibility is established, if a living donor is available, the procedure is scheduled ahead of time on a day both the patient and donor are able to have surgery. If a person is on the waiting list for a kidney from a deceased donor, they must be ready to have surgery whenever a compatible organ becomes available, at which point they’ll be told to head to the hospital.

Immediately before the procedure, patients will undergo another round of tests to re-establish that they’re healthy enough for a transplant. A serum crossmatch test, wherein a donor’s cells are mixed with the recipient’s blood, will also be performed. If the blood has high levels of antibodies that bind to the donor’s cells, it is a sign they are incompatible and the transplant cannot occur.

Post-surgery recovery

After the transplant, a person usually stays at the hospital for about four to 10 days for close monitoring of overall and kidney health. A kidney from a live donor typically starts working right away, while an organ from a deceased donor might take a few weeks. A transplanted person may need dialysis until the new kidney starts to function and produce urine.

Immunosuppressive medications will immediately be started after surgery to prevent graft rejection, where the immune system recognizes the new kidney as foreign and launches a damaging immune attack against it. These medications will be continued for as long as the new kidney remains functional. Other medications also may be needed to prevent infection or manage other health conditions.

After going home, patients still need to attend frequent checkups to make sure the new kidney is working as it should and that the body is not rejecting the new organ. In the first weeks, appointments may be as frequent as 2-3 times a week, but this will decrease over the first year to about 2-4 annual visits.

A person’s transplant team will help them decide when it’s appropriate to return to work or other daily activities after a transplant, which usually happens within a few months if no complications arise.

Organizations such as the American Association of Kidney Patients and the National Kidney Foundation offer support and resources to help patients understand what to expect before, during, and after a kidney transplant.

Potential complications

Advances in technology and healthcare mean that transplant surgeries are usually successful. However, as with any major surgery, a number of complications may develop during or after the procedure, including:

infection
bleeding or blood clots
damage to other organs
blockage or leakage from connections between the new kidney and blood vessels or bladder
undetected cancer in the donated kidney
cardiovascular complications, such as heart attack and stroke.

Some complications also may arise from the immunosuppressive medications themselves, including:

bone damage
diabetes
high blood pressure
high cholesterol levels
weight gain
increased risk of cancer, mainly skin cancer and lymphoma.

While the list of potential complications is long, organ rejection is the post-transplant complication for which patients receive closer monitoring. The chances of this happening are highest immediately after surgery (acute rejection), but a patient can also experience chronic rejection, wherein the body gradually rejects the transplanted organ over time.

It’s estimated that about 10% to 15% of patients experience organ rejection in the first year after a kidney transplant. Symptoms of this complication may include fever and flu-like symptoms, reduced urination, swelling, lack of energy, or pain around the transplant site, but some patients may have no noticeable symptoms at all.

Organ rejection doesn’t always mean a person will lose their transplant. Prompt intervention with stronger immunosuppressive medications can help quell these immune reactions and prevent damage to the new kidney.

Long-term outlook

Because Fabry disease is a rare condition, there is limited evidence related to survival and long-term outcomes after a kidney transplant in this population. Still, recent analyses indicate survival rates and the length of time the new kidney lasts are similar in Fabry disease patients compared with people who receive a transplant for other reasons.

On average, a donated kidney will last around 10-20 years, but this can be maximized by staying active, following a healthy diet, and adhering to any medications prescribed by a doctor.

Available evidence suggests that alpha-Gal A activity in the new kidney is enough to prevent Gb3 accumulation in the donated organ, and recurrence of significant kidney disease after transplant is not common in Fabry patients.

Still, a kidney transplant is not a cure for Fabry disease and continued ERT is recommended to prevent the progression of extra-renal manifestations, such as heart disease, which remains a leading cause of death even after a kidney transplant.

Fabry Disease News is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.