Expanding kidney donation
A locally-adapted protocol allows donors with incompatible blood types to still give their kidney to their loved one.
AS far as organ failure goes, those whose kidneys have quit working are fortunate as dialysis can replace the function of the kidneys.
However, it is a lifelong treatment for patients with end-stage kidney failure, requiring the majority to visit a haemodialysis centre three times a week for three to five hours each time to receive the treatment.
Others may opt for peritoneal dialysis, which is done on a daily basis for one to two hours by the patient themselves.
While patients can live a relatively normal life on dialysis, it is not the best solution to their condition.
Ideally, they should receive an actual kidney via transplantation from a living or dead donor, to replace their own.
Says consultant nephrologist Datuk Dr Tan Si Yen: “A transplant is a better form of treatment in terms of survival and quality of life.”
For example, according to the latest Report of the Malaysian Dialysis and Transplantation Registry in 2016, the 10-year survival rate for kidney transplant patients is 71%, compared to 27% for dialysis.
It also notes that there were nearly 40,000 patients on dialysis as of Dec 31, 2016.
Of these, Dr Tan, who heads the nephrology and renal transplant services in a private hospital in Kuala Lumpur, believes that the majority are medically fit for transplant.
However, according to the Report, while the number of patients on dialysis has been increasing steadily from 17,097 in 2007 to 39,711 in 2016, the number of kidney transplants has remained about the same.
In the decade between 2007 and 2016, the number of new kidney transplants ranged from 82 (2016) to 141 (2009). This includes those who went overseas to countries like China and India for their procedures.
Comments Dr Tan: “Our transplant programme here is so weak that the patients have no choice but to go overseas, and I would think about half go overseas.
“They either have no relatives who can donate, or if they have relatives, they’re not suitable – they don’t pass all the tests.”
He notes that in Malaysia, kidney donations are only allowed from relatives or anonymous brain-dead organ donors (also known as cadaveric donors).
“The cadaveric transplant rate is very low – we sometimes don’t even talk about it because it’s almost non-existent (only nine people, or 11%, received a cadaveric kidney in 2016, although 51, or 47.2%, received one in 2015).
“So, the majority of transplants are living transplants, which means, by default, they are from relatives, because we don’t allow unrelated living donors, except for spouses,” he explains.
However, he adds that one-third of potential living donors are rejected because of blood group incompatibility.
Dealing with antibodies
All humans have one of four blood types: A, B, AB or O.
These are classified according to the type of antigen expressed on
the individual’s red blood cells (RBCs).
You are type A if your RBCs have antigen A; type B if your RBCs have antigen B; type AB if your RBCs have both antigens A and B; and type O if your RBCs have neither antigen A nor B.
Similarly, your immune system will express the antibodies opposite to the RBC antigens that you have, i.e. you will express antibody B if you are type A; antibody A if you are type B; neither antibodies if you are type AB; and both antibodies A and B if you are type O.
This is because antibodies will seek out their compatible antigens – i.e. antibody A and antigen A, or antibody B and antigen B – and destroy the red blood cells.
As organs also express ABO antigens, it is crucial to ensure that the donor does not have antigens that are compatible with the recipient’s antibodies.
Otherwise, the antibodies will destroy the donated organ.
However, the last three decades have seen the development of a procedure that enables blood group incompatible, or ABOi, organ transplants, including the kidney.
Having seen one too many cases of potential donors turned away because of blood-group incompatibility in his practice, Dr Tan, in what he describes as “a moment of
madness” seven years ago, decided to pioneer ABOi kidney transplants in Malaysia.
Basically, the patient, or kidney recipient, has to undergo a “desensitisation” protocol, where their ABO antibodies are removed.
After a lot of research, adaptation and discussions with foreign colleagues who have preformed the procedure, Dr Tan came up with a protocol that begins with the patient starting on rituximab, which suppresses the activity of the spleen, about a month before the transplant. This as the spleen is an important source of antibodies, he explains.
The critical component of the protocol is plasmapheresis, which is a procedure that removes antibodies from the blood plasma.
The patient undergoes this procedure on alternate days for two weeks prior to the transplant.
At the same time, the patient receives immunosuppressive drugs to help keep their antibody levels down.
“Once the antibodies are low enough to prevent rejection, I have a very short window of opportunity to go in and perform the transplant, otherwise there is a rebound of the antibody levels,” Dr Tan explains, adding that this period is
24 hours.
The transplant itself and the post-operation treatment is similar to a standard kidney transplant.
While the main risk for the procedure – aside from rejection of the new kidney – is that of infection, which is highest during the first three months after the operation, this is similar for regular kidney transplants as those patients also have to take drugs to suppress their immune system.
Dr Tan notes that due to the extra procedures involved, the cost of an ABOi kidney transplant is double that of a regular kidney transplant.
Donor requirements
Meanwhile, the most important requirement for the donor is that they must be both physically and mentally healthy.
They will be required to go through a series of tests and evaluations to ensure their health status.
Aside from checking their blood type, the donor’s human leukocyte antigens (HLAs) are also compared to the recipient’s.
As HLAs can also trigger an attack by the recipient’s antibodies, the more similar they are between the donor and the recipient, the better the chances of success.
However, Dr Tan notes that this is not as crucial in the ABOi procedure as long as the recipient does not have antibodies against the donor’s HLA antigens.
“If there are HLA antibodies, they can also be removed by plasmapheresis,” he says.
The donor will also be checked for infectious diseases like HIV and hepatitis, certain non-communicable diseases like diabetes, heart disease and cancer, and their kidney function.
In addition, the transplant team will evaluate the donor to ensure that they are mentally healthy and fully aware of the risks and benefits of their decision.
“Once they pass all the tests, they should be okay to lead a normal lifestyle (after the transplant),” says Dr Tan.
“They should be healthy enough to continue working; if they are young, they should be able to start a family (see Pregnant with one kidney on p4); and even if they are old, it should not compromise their longevity – they should continue to progress well (see Age no barrier on p4).”
To date, Dr Tan and his team have performed 11 ABOi kidney transplants, all successful with all donors and recipients still currently healthy and functioning well.
He notes that the programme was launched and maintained without any funding or technical support from external sources – a feat he is proud of as even in developed countries, only certain medical centres can perform the procedure.
“In addition, our success led to Hospital Kuala Lumpur and University Malaya Medical Centre trying to set up their own ABOi transplant programmes,” he says.
“We hope that by our success, we will be able to help reduce the workload and the expenses of public hospitals, as many patients have insurance or can afford it themselves.
“Because the transplant rate is so low, we hope that our programme will help to contribute to the transplant rate and make it less necessary for patients to go overseas,” he adds.