When Your Kidneys Fail, What Are Your Options?
Part III
KIDNEY TRANSPLANTATION

In this issue, the last option of kidney replacement therapy after kidney failure will be discussed.

Kidney Transplantation
Kidney transplantation is a surgical procedure during which a healthy kidney from another person is transplanted into an end-stage kidney failure patient’s body to do the work of the two native failed kidneys. The transplanted kidney along with its ureter is placed surgically inside the lower abdomen (right or left). The surgery is done under general anesthesia and typically takes 2-3 hours. The native failed kidneys are usually left in place, unless they cause infection or high blood pressure that is difficult to control with medication alone.

There are three types of kidney transplantation. The first type is a healthy kidney donated from a brain-dead person (usually road traffic accident victim), so called “cadaveric transplant”. The second type is a kidney donated from one of the patient’s living relative who is genetically related to the patient (father, mother, son, daughter, etc). This is called “living-related transplant”. In the last type (living non-related transplant), the healthy kidney comes from a living person not genetically related to the patient. This donor can be the spouse, friend, neighbour, or an executed prisoner (illegal, unethical practice which is not advised by health care provider).

Not all end-stage kidney failure patients are fit to undergo transplantation. All potential kidney recipients must receive extensive medical and psychosocial evaluation to see if they are fit for transplant. This is necessary because certain medications given after the transplantation may worsen the health of the kidney recipient. There are some factors (contraindications) in the kidney recipient that make the transplantation inadvisable. They are

• Cancer
• Severe uncorrectable heart disease
• Impaired blood circulation in the legs
• Chronic infection
• Noncompliant patient
• Psychiatric illness

Lastly, the potential living kidney donors (both related and non-related) also have to undergo the same rigorous medical and psychosocial evaluation to decide whether they are fit to donate.

In order to determine whether the transplanted kidney is acceptable by the recipient’s body immune defense system, there are certain pre-transplant blood tests that are needed to be done. First is to test the blood type (A, B, AB or O) of the donor and the recipient to see if they are compatible. If they are incompatible, then the rest of the pre-transplant workup will not move forward. If the blood type is compatible, then the test for compatibility of the unique genetic markers, human leukocyte antigen (HLA) will be carried out. Each individual inherits a set of three HLA from each parent - a total of 6 HLA. Higher number of matching HLA decreases the chance that the donated kidney will be rejected by the recipient. Ideally, there should be a 6 antigens (HLA) match, but this usually happens only when the donor and recipient are identical twins. The last blood test (cross match test) is done just before the transplant surgery (usually 1/2 - 1 hour before), the purpose is to test whether the recipient produces antibodies that act specifically against something in the donor’s kidney. If the cross match is negative, then the transplant surgery can then proceed.

After successful transplant, the new kidney will often start working immediately to produce urine, but sometimes it may take weeks before it starts working. In order to monitor the progress and condition of the new kidney, kidney recipient is required to have regular medical follow-up with the kidney specialist (nephrologist) and the transplant surgeon. Normally, the body‘s immune system is designed to keep away “foreign invaders” such as bacteria. The immune system will reject and fight these “foreign invaders” of the body. After transplantation, the new kidney is viewed by the recipient’s immune system as “foreign invaders” and the body will reject and fight this new kidney until it is destroyed and failed. In order to keep the immune defense system from rejecting and fighting the newly transplanted kidney, the kidney recipient will have to take immunosuppressive drugs to turn off, or suppress this normally beneficial immune response. Unfortunately, this can also lead to deleterious health effect on the recipient by allowing more dangerous “foreign invaders” such as bacteria, virus and fungus to invade the body. Some of the common immunosuppressive drugs include steroid (prednisolone), cyclosporine (Neoral™, Gengraft™, Sandimmune™), tacrolimus or FK506 (Prograf™), sirolimus (Rapamune™), mycophenolate mofetil (Cellcept™), and azathioprine (Imuran™). These immunosuppressive drugs are to be taken for life after transplantation. Most recipients will be on three immunosuppressive drugs after transplant, but some of them will have only two drugs after one to two years after transplant if the new kidney functions well. In addition to these immunosuppressive drugs, the recipient also needs to be on other drugs such as high blood pressure and cholesterol medications.

There are complications associated with the transplantation. Some of them are life threatening. They can happen during the transplant surgery or immediately after surgery. However, most of them occur 3-6 months after surgery. These complications includes infection, high blood pressure, high cholesterol and triglyceride, elevated blood sugar (diabetes), weight gain, gout, brittle bone, cancer and cardiovascular disease such as stroke, heart attack and heart failure. However, the most worrisome is rejection of the new kidney by the recipient’s body. This process can happen immediately after transplant surgery (acute rejection) or slowly over a period of time (chronic rejection). The causes of the rejection are multiple, including:

• Drug side effect (supernormal dose of cyclosporine and tacrolimus)
• Infection
• Uncontrolled high blood pressure
• Uncontrolled high blood sugar (diabetes)
• Cigarette smoking
• Not enough dose of immunosuppressive drugs
• Patient’s failure to take immunosuppressive drugs
• Reactivation of the original kidney disease that causes the native kidneys to fail in the first place (IgA kidney disease, focal segmental glomerulosclerosis)

A transplanted kidney does not last for ever. However, the lifetime of a properly transplanted and matched kidney is quite excellent. One year after transplant, 90% of the transplanted kidneys are functioning. Five years after transplant, this number decreases to 70%. Fifty percent of the transplanted kidneys are still functioning after 10 years. Looking at it another way, the average life span of a cadaveric transplanted kidney is 8 years. For a living related kidney, it is 11 years. The life span of a living non-related kidney is somewhere between 8-11 years. So, the “best” long lasting kidney transplant is from a genetically related relative, then a spouse or friend, then a cadaver (dead person). After the transplanted kidney failed, the recipient can resume dialysis again and later has another kidney transplantation. There is no limit to the number of kidney transplantation one can have. However, surgical difficulty and risk of rejection increase proportionately with the number of transplantation performed previously.

Conclusion
The kidneys are vital organ of the body. Their functions are essential to the survival of the individual. When their functions are disrupted or failed, the consequence is life-threatening. However, there are treatment options available after the kidneys fail. These treatments are not ideal real cure for kidney failure. Two of the treatment options (haemodialysis and peritoneal dialysis) merely replace the partial functions of a normal kidney. The third option (kidney transplant) replaces all the functions of a normal kidney at the expense of a suppressed immune defense system, thus exposing the body to life threatening infection and cancer.

In Normah Medical Specialist Centre, our Kidney & Urology Centre offers integrative and comprehensive care to our patients with kidney problem. Our services range from evaluation and management of all aspects of medical and surgical diseases that can lead to kidney failure. After the kidneys failed, we offer haemodialysis and peritoneal dialysis treatment to our patients. Our modernized haemodialysis unit is staffed with personnel specifically trained in caring for the kidney failure patients. We also offer pre-kidney transplant evaluation and post-kidney transplant care to our patients. We are in the process of setting up a tissue typing laboratory to do pre-transplant HLA tissue typing and cross-matching. We are looking forward to and have plan for setting up a complete kidney transplant centre in Sarawak to perform the actual kidney transplant surgery in our hospital.