Author : Dr. Amit Goel , HOD at Max Super Specialty Hospital, Gurgaon
The kidneys, often overlooked until they cause problems, play a crucial role in maintaining overall health.
These bean-shaped organs are responsible for filtering blood, removing waste products, and regulating fluid balance.
Sometimes, however, due to renal complications such as acute kidney failure, glomerulonephritis, or nephrotic syndrome, the kidney is unable to filter correctly, leading to renal dysfunction.
If these conditions persist or worsen, they can progress to end-stage renal disease (ESRD).
End-stage Renal Disease (ESRD): Overview and Prevalence
End-stage renal disease (ESRD) occurs when the kidneys become so damaged that they can no longer filter blood adequately, leading to a buildup of waste products in the body.
We measure the kidney efficiency in filtering out the blood in terms of glomerular filtration rate (GFR).
GFR can be determined directly using exogenous filtration markers like inulin and iohexol or indirectly using endogenous filtration markers such as serum creatinine and cystatin C, providing a range of options for accurate measurement.
Based on the GFR range, we estimate how well the kidneys filter blood, and it can be categorised into different clinical stages.
| Name of the stage | GFR range |
| Stage 1 | 90 |
| Stage 2 | 89-60 |
| Stage 3 | 59-30 |
| Stage 4 | 29-15 |
| Stage 5 | 15 or less |
The last stage of Chronic Kidney Disease(CKD 5) is end-stage renal disease (ESRD), in which the kidneys are severely damaged and can no longer adequately filter waste and excess fluids from the blood.
Since ESRD is a life-threatening problem and hence it is essential to accurately identify the underlying renal conditions and treat them as soon as possible to avoid any severe health complications.
We have two possible solutions to treat patients with ESRD. These are renal replacement therapy and renal transplant. Let’s discuss them in brief.
In renal replacement therapy, we perform dialysis, which includes intermittent hemodialysis, continuous hemofiltration and hemodialysis, and peritoneal dialysis.
In patients with severe damage, we often choose renal transplant as a preferred treatment option. The reason behind this is that, compared to dialysis, in renal transplant, there are fewer dietary restrictions, with a success rate of more than 95%. After renal transplant, patients get rid of maintenance hemodialysis and its associated complications along with better quality of life.
Understanding ABO Incompatibility issues in kidney transplantation
Imagine being in immediate need of a life-saving kidney transplant, only to find that the ideal donor isn’t an option due to mismatched blood types and HLA. This has been a daunting challenge for both patients and doctors for years.
Let’s explore what these terms mean and why they are so crucial.
Blood Group Matching: The First Line of Defense
Beginning with a quick quiz: Do you know your blood type? Is it A, B, AB, or O? It’s important to understand the blood type of the patient and donor. Let me tell you how.
If you have a Type A blood group, you can donate to patients with blood type A and AB.
If you have a Type B, you can donate to B and AB.
For patients with blood type AB, you can receive a kidney transplant from any blood type as you are a universal acceptor, but when it comes to donating, you can only donate to the AB blood type.
Blood type O are universal donors, and you can donate to any of the blood types but can only receive from O.
You must have heard about people who say they have a B-positive or B-negative blood type. These are called Rh factors.
Fortunately, when it comes to kidney transplants, you don’t have to worry about your Rh factor! Unlike blood transfusions, where Rh compatibility is a crucial aspect, the Rh antigen doesn’t impact kidney transplants. Why? Because it’s only found on red blood cells, not on the kidney’s parenchymal cells itself. So it doesn’t trigger the immune response that could lead to rejection. You must be thinking that we have at least one less thing to worry about! Let’s move to the next challenge.
HLA Typing: The Next Level of Compatibility
After performing the ABO compatibility tests, in the next step, we perform the HLA typing test.
There are three main types of HLA markers (HLA-A, HLA-B, and HLA-DR), and each person inherits a set from each parent. The goal is to match as many of these markers as possible between the donor and patient.
The more similar the HLA markers between the donor and patient, the less likely the patient’s immune system will reject the transplanted kidney. We have concluded that a close HLA match is associated with better transplant outcomes and, hence, long-term success.
In case of ABO incompatible (ABO-I) transfusion, patients usually suffer from the following symptoms-
- Chest pain
- Lower back pain
- Hypotension
- Disseminated intravascular coagulation (DIC)
Some physical examination indicating ABO incompatibility includes elevated bilirubin level, lactate dehydrogenase (LDH), blood urea nitrogen (BUN) and blood creatinine.
Considering these complications, you must be thinking that we need to avoid ABO incompatible transplantation.
Fortunately, recent advances in medical science have developed measures to deal with this challenge in kidney transplants. Let’s understand this better.
ABO incompatible (ABO-I) Kidney transplantation: A Breakthrough
Since kidney transplantation provides a considerable survival advantage compared to hemodialysis in patients with ESRD, it is a more preferred method.
Thus, the demand for organs is continuously growing. Still, a considerable gap exists between compatible organ availability and waiting-listed patients.
For those facing End-Stage Renal Disease (ESRD), the journey to find a compatible kidney donor can feel like a race against time. In my 22 years of experience, I have seen how challenging it is to find a suitable donor.
Historically, ABO blood group incompatibility (ABO-I) was considered an absolute contraindication to transplantation due to the significant risk of acute antibody-mediated rejection (AAMR) and early graft loss.
Modern medicine is gradually overcoming this hurdle with the development of specific desensitisation strategies for ABO incompatible (ABO-I) transplantation.
Over 100 renal transplants, which I performed were ABO-I and by adopting patient specific desensitisation strategies, successful outcome for each kidney transplant was achieved.
These strategies refer to the patient's preconditioning which consists of a combination of treatments and procedures, aiming to reduce the antibody levels responsible for organ rejection. When the antibody level reaches 1:8 in the blood, we consider that it’s safe to perform ABO-I kidney transplant.
Nowadays, the preconditioning consists of the following procedures:
Use of immunosuppressive agents
- These medications are used to suppress the immune system, preventing it from attacking a transplanted organ.
- Administered before transplantation, it prohibits the recipient's immune system from recognising the transplanted organ as foreign and attacks it.
- Some of the common immunosuppressive agents include corticosteroids, monoclonal antibodies etc.
Plasmapheresis techniques
In this technique, the anti-A and anti-B antibodies and other proteins involved in the immune response are removed, and then the blood supply is restored. It is often used in transplantation to prepare recipients for surgery and to minimise the episodic rejections of the transplanted organ.
Immunoadsorption
In this technique, specific antibodies responsible for organ rejection are removed while preserving plasma proteins and clotting factors.
B-cell population depletion
Rituximab is a chimeric (20% rodent and 80% human) monoclonal antibody that binds to the CD20 antigen present on the cell surface and depletes mature B-cells. Its vital role has expanded to include the kidney transplantation field, either as induction/desensitization therapy or as a treatment of antibody-associated rejection.
Maintenance of immunosuppression after transplantation
After the transplant is over, lifelong adherence to immunosuppressive medication is crucial for the success of organ transplantation.
However, using these desensitisation techniques along with potent modern immunosuppression, ABO incompatible (ABO-I) kidney transplants have achieved graft and patient survivals similar to those seen in ABO compatible transplants.
Success rates of ABO incompatible kidney transplant
ABO incompatible kidney transplantation has seen significant advancements in recent years, with improved outcomes and increased acceptance.
While still considered a complex procedure, and to be done under care of experienced doctors, at equipped centres only, it offers hope to many patients who would otherwise have limited options.
Understanding the risks associated with ABO incompatible (ABO-I) Kidney transplantation
Though ABO incompatible, Kidney transplantation holds great promise for kidney patients with a lack of ABO compatible donors. Sometimes, patients may face bleeding and a sudden surge of antibody titre after plasmapheresis. However, we can avoid this by using the immunoadsorption method in which we only specific antibodies responsible for graft rejection are removed. This, along with hyperacute rejection, delayed graft function, and hemolytic transfusion reaction, are some of the complications that may arise and hence need to be addressed.
As far as infections are considered, ABO-I Kidney Transplants may have comparatively higher infection rate and longer hospitalisation than the ABO-C group. Polyomavirus (BKV), cytomegalovirus (CMV), herpes simplex virus and varicella zoster virus, are the most common viral causes.
Conclusion
In order to make ABO Incompatible Kidney Transplantation successful, the critical part is removing the preformed antibody, which may otherwise elicit an immune response against the transplanted kidney by creating more antibodies which may lead to graft rejection.
With time, we have developed enough measures to deal with the complications and risks and aim to generate more precise solutions to avoid other related complication that may arise in ABO-I Kidney transplants.
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