Steroid (prednisolone) - Deltacortil or wysolone: -

At first steroid therapy was used to treat acute rejection episodes only. Later on it was found that when steroid was used concomitantly with azathioprine significant improvement in graft survival occurred. When steroid is used alone, graft surv ival is not satisfactory.

Most of the transplant centres are using prednisolone with cyclosporine and/or azathioprine now. This drug is started two days before the surgery in live donor transplants while in cadaveric donor transplants it is given from the time of surgery. Previously high dose steroid regimen was used (2mg/kg body weight) but now most of the centres are using low to moderate dose only. High dose steroid therapy is commonly associated with side effects and high mortality.

Most of the centres use either 0.5mg/kg to Img/kg and rapidly decrease the dose to maintenance dose of 10mg per day by three to six months. This form of therapy is associated with less side effects. This drug should not be taken on an empty stomach and in early post operative period it is advisable to avoid fried and spicy foods to prevent acidity, many centres use antacid therapy regularly in post operative period to prevent this problem.

Common side effects of prednisolone are:-

1. increase appetite
2. weight gain
3. salt and water retention - Edema

4. acidity burning in epigastric area (STOMACH), peptic (Stomach) ulcer and at times bleeding from the ulcer

5. hypertension
6. acne
7. hyperglycemia or increased sugar level - steroid induced diabetes
8. easy bruisability
9. psychosis
10. mood lability
11. cataract

12. bone problem or avascular necrosis of femoral head requiring replacement of joint after few months to years and

13. increase incidence of all types of infections.

Steroid side effects are more in patients with high dose therapy many times side effects are noticed in patient after they are given high dose steroid therapy for acute rejection episode - like infections or diabetes - cataracts and bone problems occurs after few years of therapy.

CYCLOSPORINE (SANDIMMUNE): -

Cyclosporine is a fungal metabolite and was first described by Dr. Jean Borel in 1972 as a drug with high immunosuppressive property. Intially it was used by carne an co-worker from UK and Starzl and co-worker from USA in 1981. Both these centres used this drug in conjunction with steroid and reported significant improvement in cadaveric graft survival by 15% to 20%.

It can be given orally or intravenously. It is available in capsule or liquid form. It is metabolized by the liver, therefore in patients with liver problem, it should be used cautiously and in lower dosage.

Generally it is given in 10-12 mg/kg body weight to start with and dose is gradually decreased to maintenance dose of 3 mg/kg/day. In India almost all centres use this drug in much lower dose and our maintenance dose is around 0.5 - 1.5 mg/kg/day - This is mainly to reduce expense. Maintenance dose is lower in India as we use this drug in combination with other two drugs like steroid and azathioprine. Its dose should be adjusted as per cyclosporine blood level if possible.

Side effects are many with this drug and these are: -

1. nephrotoxicity or kidney damager when used in higher dose. At times kidney damage can be very severe and irreversible too if not noticed in time

2. hepatotozicity or liver damage - this is also dose related and can produce jaundice

3. abdominal pain
4. pancreatitis
5. increased blood sugar level
6. increase uric acid and at times can produce gouty arthritis
7. hair growth on face and other areas
8. gum hypertrophy
9. tremors
10. fits or convulsions
11. decrease platelet count and
12. incidence malignancy is higher in patient taking this drug like azathioprine compared to normal population.

    Most importantly this drug for our people are its costs. It is available in 50 ml bottle (5000 mg/bottle) and costs around Rs. 6000/-. It may cost patient around Rs. 60,000/- to Rs. 70,000/- or more in first year after transplant and later on it may cost around Rs. 30,000/- per year or so depending upon the dose used.

    In India we try to decrease the cost of this drug by using this drug in combination with prednisolone and azathioprine or what is commonly known as the triple drug regimen. In this regimen we use all three drugs in reduced dosages in order to lessen the side effects of all drugs as well. An other way of decreasing costs of this is to use this with other drugs which increases level of cyclosporine in the blood by interfering with its metabolism - like ketoconazole (antifungal drug) or calcium channel blocking agents.

    An important fact worth knowing is that when a patient is taking this drug, he should consult his nephrologist before taking any other drug. This should be done in all patients with transplantation but much more so in patient who is taking cyclosporine as this drug interacts with many drugs and can produce undesirable side effects - common drugs which interact with cyclosporine are:- erythromycin (antibiotic), ketoconazole (antifungal agents), diltiazim (calcium channel blocker and used for anginal pain and hypertension), oral contraceptives, metoclopromide (used for nausea and vomiting), phenytoin, carbamezapine, phenobarbital (used in patient with convulsions), Rifamycin (Antitubercular therapy)

    Alternative or newer methods to suppress immune systems :-

    Total body radiation, FK506 and other drugs are being tried in various centres at present on an experimental basis. These drugs may be available after two to three years and unfortunately they too have side effects like the drugs used at present.

    The main aim at present is to produce a drug which selectively depresses the immune system for prevention of graft rejection only and does not depress its other function like forming protective antibodies and police force of our body (white blood cells), even experiments are going on to see whether human body can accept organs from genetically different species - from animals.

    WORD OF CAUTION TO ALL TRANSPLANT PATIENTS:

    Immunosuppressive therapy is prescribed to all patients - even those patients with excellent match. These drugs help in controlling or preventing acute rejections. When the patient is taking these drugs, he/she should be under the constant care and management of nephrologist - initially visit will be very frequent and later on at yearly interval - for a follow up.

    Immunosuppressive therapy should be taken life long as stopping these drugs does give rise to rejection of transplanted kidney in more than 20% of patients even after years. So all patients should take these immunosuppressive agents regularly in prescribed dosages - higher dose will make them susceptible to complications like infection and lower dosage may cause rejection of transplanted kidney.

    In this article I have tried to deal with major side effects of all commonly used immunosuppressive drugs. This is not to scare transplant patients but to make them more aware of side effects. These side effects occur in few patients only, and if you are careful and notice any of these side effects, you should contact your nephrologist immediately. Appropriate course of action taken in time will go a long way in preventing serious complication.

    In spite of all problems, most of the transplant patients and all doctors taking care of transplant patients agree that the quality of life with a transplant is better and near normal.

    We are hopeful that in next few years development will be made to use kidney from different species for mankind and this will help use in doing transplants in all patients with kidney failure.