Treatment with Immunosuppression in Renal Disease
Some types of kidney damage occur through activation of the immune system causing inflammmation. Lupus ( SLE ) affecting the kidney, vasculitis , and Goodpasture’s disease are all diseases in which kidney damage is caused by inflammation. Immunosuppressive drugs and drugs that reduce inflammation are used to treat these diseases. Immunosuppressive drugs are essential in kidney transplants to dampen the immune system and prevent rejection. Some other kidney diseases are slower but also respond to treatment of this type, for example some causes of nephrotic syndrome .
|Azathioprine||Mycophenolate Mofetil (MMF)|
|Cyclosporin and tacrolimus||Plasma exchange|
Steroids, for example prednisolone and methyl prednisolone, are useful and are the most commonly prescribed immunosuppressive drugs. Their full description is corticosteroids . Large doses of these drugs over a long period of time can, however, result in a long and well-known list of side-effects including:
|Weight gain, fluid retention and raised blood pressure|
|Diabetes, in some patients|
|Thinning of bones – osteoporosis|
|Thinning of skin and easy bruising|
|Risk of serious infections|
Doses are reduced as soon as possible but no alternative agent has yet been developed that can completely replace the use of steroids.
If steroids are taken for a long time, the body stops producing its own steroid hormone. Suddenly stopping steroid treatment after it has been taken for a long time can then be dangerous, as the sudden shortage of steroid hormones causes an Addisonian crisis . Therefore steroid treatment is often reduced slowly to allow the adrenal glands to recover. However in the six months after you have stopped steroid treatment, an infection or other illness may increase the body’s need for steroids, and you may need to start treatment with steroids again. It is recommended that anyone who is taking steroids should carry a STEROID CARD so that medical staff will know about your steroid treatment if you have any other health problems. You should continue to carry it for at least six months after stopping treatment, too.
Here are some ways to counteract the bone thinning effects of steroid therapy:
|Bone loss during steroid treatment may be offset by using calcium and Vitamin D|
|Hormone replacement therapy (HRT) may help in women, after the menopause|
|Other treatments may be required if osteoporosis is already proven or in some other circumstances.|
|Bisphosphonates are the most commonly used of these (eg Didronel)|
This is a powerful drug that attacks white blood cells. It has proven to be especially effective in several types of vasculitis that were often fatal in the past, and in SLE and in other conditions. However the drug has some serious side-effects:
|Serious infections and bleeding – blood count must be checked regularly|
|Bladder irritation may cause cystitis and bleeding|
|It may lead to infertility in men through toxic effects of the drug on sperm, (usually following prolonged treatment over more than 3 months of daily treatment). Sperm can be collected before the treatment starts if time permits.|
|In women it may cause infertility and premature menopause through toxic effects on the ovaries (usually after prolonged treatment )|
|It is toxic to unborn babies|
|There is a slightly increased risk of bladder cancer in later life|
|There is a slightly increased risk of leukemia in later life|
Keeping the courses short (three months) reduces the risk of toxic effects from cyclophosphamide. Administering it in the form of an injection every two to four weeks, rather than as a daily dose by mouth, can also keep the total dose down. However this may not be as effective in all circumstances.
This drug has similar side-effects to cyclophosphamide but is less powerful and generally safer. It does not affect fertility or the bladder, and has been used safely in pregnancy. Azathioprine must be monitored with blood counts and has an increased risk of infection. It is often used after a course of cyclophosphamide in severe vasculitis, or at the outset in milder vasculitis or milder SLE. Azathioprine is also used to prevent rejection in kidney transplants and can be used in some kinds of glomerulonephritis. There is an important side effect for people who are taking azathioprine for a long time:
|People on azathioprine for a long time are at risk of developing some skin tumours. It is important to avoid sunbathing and to use sun blocking creams.|
This is a newer drug which works in a similar way to azathioprine. It is more powerful, but may carry extra risks. It is used in transplantation to prevent rejection, but has also been used in vasculitis and SLE, mainly to stop the disease from returning after an initial course of treatment with cyclophosphamide. Trials of MMF as a first treatment are under way, but its use in this way is relatively new. It is also being used in some other kidney diseases. MMF is usually used with steroids. Most of its serious side effects are similar to other drugs of this type. Side effects include:
|Stomach upset, including diarrhoea and vomiting. Improves with dose reduction.|
|Risk of serious infections|
|Risk of bleeding and easy bruising|
|Risk of some cancers with long term treatment|
|Risk to baby in pregnancy|
Methotrexate is used to treat some cancers. It can be used to treat inflammation in some types of arthritis and sometimes in vasculitis. In vasculitis and arthritis it is usually given once a week, with folic acid (a vitamin) being given 1-3 days later. Regular tests for blood count and liver function are required. It should not be used in pregnancy. Side effects can include:
|Mouth ulcers and diarrhoea|
|Liver damage (rare)|
|Lung damage causing shortness of breath and cough (rare)|
|Risk of infections and bleeding|
Cotrimoxazole is an antibiotic combination (also known as Septrin, Bactrim) which can sometimes be used in some types of vasculitis, particularly Wegener’s disease (Wegener’s granulomatosis). Some patients have an improvement in vasculitis affecting the nose, sinuses and throat. It is probably less useful in kidney and lung vasculitis. The main side effects are gastric upset and occasional allergic reactions.
The same antibiotic is often used to prevent ‘Pneumocystis’ pneumonia in patients who are heavily immunosuppressed (e.g. receiving high doses or several of the drugs on this page). Pneumocystis pneumonia can be a problem in people with a weakened immune system.
Cyclosporin (now officially spelled ciclosporin) and tacrolimus are powerful drugs to dampen the immune response. They are mainly used in transplantation, but occasionally are used in kidney diseases, especially in nephrotic syndrome . Side-effects may be troublesome. Cyclosporin can sometimes cause tremor, and excessive hair growth, especially on the face, and gum swelling. There are some other rarer side effects. Tacrolimus may also cause tremor, and can cause upset sleep or headaches. Occasionally it causes feeling sick, and pins and needles in the arms and legs. Both of them can cause kidney damage themselves.
Both medications work in a similar way and may make infections worse. Being on these tablets over a long time can increase the risk of some tumours and it is recommended to avoid sunbathing and always wear sunblock in sunny weather to protect against skin cancer. You should watch out for the development of lumps and bumps on the skin and report these to your doctor if they occur. Women should have regular cervical smears.
This is a treatment in which a volume of plasma is removed and discarded and replaced by a plasma substitute taken from blood donors. It involves pumping blood through a machine for between one and two hours, and is usually given every day and then perhaps on alternate days for a short period. It is most useful during severe disease before other treatments have had time to work, and is not usually effective on its own. Usually the patient’s plasma is replaced with a very pure protein called albumin. However it may be necessary to use frozen plasma or other proteins from plasma. These carry similar risks to blood transfusions. There is some risk of causing or worsening bleeding, because clotting factors are removed, and thinning of the blood is required to allow the machine to work.
Immunoadsorption is a treatment in which antibodies are removed without removing plasma. Less replacement is therefore required, and the treatment may be more efficient at removing antibodies. However the treatment is complex and long, and the machines required (and skilled operators) are not widely available. For some diseases it may not be as good as plasma exchange, but if antibody removal is very important it may be more effective.
Other drugs that are occasionally used include anti white cell antibodies such as antihuman thymocyte globulin ( ATG ) or Campath 1H. IVIG (intravenous immunoglobulin) is an injection of mixed antibodies collected from blood donors. It is only of proven benefit in Kawasaki disease (a type of vasculitis that usually occurs in children), although it helps in a number of autoimmune conditions where antibodies attack parts of the body. Anti-TNF antibodies and other similar treatments are under investigation in a number of aggressive types of kidney inflammation.
Please be aware that while we have made all effort to ensure that this information is accurate, we cannot guarantee that there are no mistakes. Also that the best management for individual patients may differ from that outlined here. Only the doctors caring for the patient will be able to advise on this.