The First attempt to treat apatient with kidney failure using kidney transplantation was made in USA 40 years ago. At that time transplantation was still in an experimental stage and results were poor in majority of cases. Today renal transplantation has progressed considerably and is a preferred mode of therapy in patient with kidney failure. The quality of life with successful transplantation is far better than life on dialysis.

In the last decade significant progress in technology has occurred in assuring the success rate of kidney transplantation. This is primarily due to
(1) Better tissue typing (HLA - A, B,C & DR) and cross match facilities and
(2) Availability of new and powerful immunosuppressive drugs.

IMMUNE SYSTEM: -

The human body has an inherent mechanism in identifying its own tissue (self) from foreign tissue. When foreign tissue (bacteria, viruses, fungi or even transplanted tissue) enters or are placed in the human body, the body reacts to it by identifying it as a foreign tissue (not self) and tries to destroy that by either sending white blood cells - mononuclear cells - initially and later on by forming antibodies against invading cells (Tissue). Thus immune system acts as a police force in our body. In some diseases like lupus (SLE) - our body fails to identify our own tissue and destroys its own tissue by forming antibodies. Unfortunately our body cannot differentiate graft put in to help the body and destroys it the same way as it destroys invading infecting organisms like bacteria, viruses or fungi.

Thus foreign tissue put in our body is destroyed in a majority of cases in a few hours to few weeks time. The phenomena which destroys the graft is known as rejection and is caused by immune system.

Rejection occurs more commonly and early when the tissue matching is poor - like with unrelated donor transplantation. This rejection can be controlled to a certain extent in our body by giving patients certain drugs - like Prednisolone, azathioprine and cyclosporine. These drugs are commonly known as immunosuppressive drugs. These drugs act by depressing the immune system. Unfortunately these drugs do not work selectively but depresses all functions of the immune system and hence makes our body more susceptible to infection.

REJECTION: -

There are three types of rejection. These are (1) hyperacute rejection (2) acute rejection and (3) chronic rejection. Each is caused by different mechanism and has different outcome.

HYPERACUTE REJECTION: -

This is caused by the presence of preformed antibodies in the patient. Antibodies are formed with previous exposure to foreign tissue - like blood transfusions, previous unsuccessful transplantation or in female patients due to previous pregnancies. When transplantation is done on patient with preformed antibodies, graft is destroyed in a matter of few minutes to few hours time. The graft is invariable lost in such cases.

With to better tissue typing and cross matching facilities available at most centres, occurrence of this type of rejection is fortunately rare.

ACUTE REJECTION: -

This occurs in few days to few months time after the transplant surgery. With this type of rejection, graft is invaded by cells the mononuclear cells - and the kidney function deteriorates rapidly in few days time unless recognised early and treated correctly. This type of rejection can be reversed in majority of patients - either completely or partially - by treating patients with high dose steroid therapy or giving them more powerful agents like antithymocytic globulins (ATG) or even OKT-3. The last two drugs are very expensive and used in cases where steroid therapy has failed in our country.

CHRONIC REJECTION: -

This occurs after few weeks to few years. This is caused by antibody formation and is not treatable. Kidney function deteriorates slowly with this type of rejection and cannot be halted even with recently developed powerful immunosuppressive agents. In this creatinine increases slowly over a period of few months to years time.

Many grafts in live unrelated donor transplants are lost now a days due to chronic rejection after few months of success - as cyclosporine is able to control acute rejection well. This form of rejection occurs less commonly in related donor transplants due to better matching kidneys.

SIGNS AND SYMPTOMS OF REJECTIONS: -

ln this I will mainly deal with acute rejection episodes mainly and briefly mention about chronic rejection.

ACUTE REJECTION EPISODES: -

Acute rejection episodes used to be very common before cyclosporine came in as an immunosuppressive agent. At that time critical period of rejection was around five to seven days after the surgery and patient used to have sudden decrease in urine output with high fever. If rejection occurs later on, patient may have following symptoms like less urine output, swelling, fever and at times pain in the graft area. Now with use of cyclosporine these symptoms are much less and many times rejection episodes are suspected on laboratory examination reports only. Laboratory reports show increase bun and creatinine level. At times increase creatinine level may be due to higher dose of cyclosporine level also (cyclosporine toxicity) and differentiation can only be made after complete check up with blood reports, sonography examination (doppler study) and even renal biopsy.

Rejection may be mild to severe and once suspected patients are treated with high dose prednisolone therapy. Fortunately this episodes are reversed in majority of cases with prednisolone and/or antithymocytic globulins and renal function returns to near normal value. At times kidney is lost. Patient should be careful after high dose antirejection therapy as they are susceptible to infection.

CHRONIC REJECTION: -

Occurs any time after first few months. In this only thing patient has is slowly increasing level of creatinine level. Generally this type of rejection advances slowly and graft function is lost in few years time. It does not respond to any kind of therapy and it is best to just take maintenance amount of immunosuppressive therapy.

IMMUNOSUPPRESSIVE AGENTS: -

AZATHIOPRINE (AZORAN OR IMURAN): -

Initially azathioprine was the main stay of immunosuppressive therapy and was used for the first time in 1961. Later on steroid was added. Till the introduction of cyclosporine in 1981. This was the main immunosuppressive, therapeutic agent. This drug is very effective and helps in preventing acute cellular type of rejection in many patients. It is usually well tolerated by most patients and is given in once a day dosage.

Previously when used with steroid therapy alone. The commonly used dose was 2 to 3mg/kg. body weight with maximum dose of 150 mg per day. This drug is available in tablet form - 50mg per tablet. Now most centres are using this drug in combination with prednisolone and cyclosporine and so commonly used dose is I to 2mg/kg. body weight. Dose of this drug is adjusted as per total white cell count. Drug is stopped if white cell count goes below 4000/-c.mm. and later on restarted at lower dose when white cell count goes above 5000/c.mm

Common side effects on azathioprine are:-

1. diminished white cell count
2. susceptibility to infection
3. liver toxicity-jaundice
4. anaemia
5. loss of hair and
6. pancreatitis. Incidence of Malignancy (cancer) is higher in patient taking this drug.