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From the National Magazine

Lupus and the Kidneys

Dr. V. Sat Reddy, Specialist Registrar in Renal Medicine
Wordsley Hospital, West Midlands

Introduction
Systemic Lupus Erythematosus (Lupus) is a disease of the immune system. Normally, our immune system protects us from infections (germs) by production of special proteins called antibodies. These antibodies attach to and destroy the foreign invading germs.

In people with lupus, the immune system, for unknown reasons, produces antibodies that target the body's normal cells. This leads to inflammation and damage to the non-vital (skin and joints) and vital organs (kidneys and nervous system).

If lupus involves the vital organs such as the kidneys, then the outcome is relatively poor. Kidney involvement is one of the most serious complications of lupus. Therefore, it is very important to recognise this complication at early stages before there is significant damage.

What is Lupus Nephritis?
When the lupus involves the kidneys, then your doctor calls it Lupus Nephritis. This simply means inflammation of the kidneys due to lupus.

Why are Kidneys vital organs?
We have two kidneys that perform many important functions. Firstly, the kidneys act as filters and remove the waste products (Urea and Creatinine) from our body. The kidneys are also important organs to maintain the correct mineral, fluid and acid balance in the body. An important hormone called Renin produced in the kidneys regulates our blood pressure. They also release a hormone called erythropoetin which stimulates the bone marrow to produce red cells and prevent us becoming anaemic.

How common is Lupus Nephritis?
The general consensus is that 30-50% of lupus patients will develop Lupus Nephritis at some stage of the illness. Most patients develop nephritis early in their disease and it is less common to develop Lupus Nephritis in patients who have lupus for more than 10 years.

Who is at risk of developing Lupus Nephritis?
Any patient with lupus is at risk of developing Lupus Nephritis. Studies have suggested that there is mild increase in the risk of developing Lupus Nephritis in males as compared to female patients. Africans and Asians are also at increased risk, as compared to other ethnic groups. Research on twins and families suggest that genetics may be involved in predisposing to Lupus Nephritis (HLA-DR2 and HLA-B8).

How will I know if my kidneys are involved?
Kidneys are generally involved when the lupus becomes active. If your kidneys are involved due to lupus, you may not have any symptoms. On the other hand, if Lupus Nephritis is more severe, the symptoms are mostly non-specific. Therefore, Lupus Nephritis can be easily missed. The following are the warning symptoms:

  • Generally unwell
  • Swelling of the ankles, legs and around the eyes
  • Loss of appetite
  • Feeling sick
  • Itching
  • Sometimes foamy appearance of urine
  • Decrease in urine - in advanced stages

What tests can be done to confirm the diagnosis?
1) Urine analysis - It is always very important to take a urine sample in a sterile container when you go to see your doctor. The presence of protein, blood or leucocytes may be the first indication of Lupus Nephritis. However, such abnormal cells can also be found in urinary infection and other conditions which your doctor normally excludes.

2) 24-hour urine collection - If your urine analysis is abnormal, than your doctor asks you to do a 24-hour urine collection. This tells your doctor how much of the protein is leaking from your kidneys and also determines to what extent your kidneys are working.

3) Blood tests

  • ESR - This measures the degree of inflammation. ESR is normally high if lupus is active.
  • Urea and creatinine - These are waste products that are eliminated by the kidneys. The levels are elevated in Lupus Nephritis. Higher the levels of waste products, greater the damage to the kidneys due to inflammation.
  • Blood tests for lupus are normally positive - ANA, Ds DNA

4) Ultrasound scan of the kidneys - The scan tells your doctor if your kidneys are normal size, however, the diagnosis of Lupus Nephritis cannot be made on the scan alone. It helps your doctor to exclude certain other causes of kidney failure which can co-exist in lupus patients.

5) Kidney Biopsy - This involves putting a needle in your back under local Anaesthesia and removing very tiny kidney tissues then the diagnosis can be confirmed by special stains and examination under a microscope.

Is kidney biopsy essential to make the diagnosis of Lupus Nephritis?
Yes. Unfortunately, kidney biopsy is the only way to tell if the kidneys are definitely involved due to lupus. It also determines the degree of inflammation in the kidneys, so that your doctor can decide the correct treatment for you. It can also predict the long term outcome.

Is there any thing I can do to prevent Lupus Nephritis?
Unfortunately, there is nothing specific you can do to prevent Lupus Nephritis. There is no special diet or life style modification that can prevent Lupus Nephritis.

Treatment of Lupus Nephritis
The treatment of Lupus Nephritis depends on the degree of inflammation determined on the biopsy.
A) Mild Lupus Nephritis - Treated with intravenous and oral steroids. Outcome is generally good.
B) Severe Lupus Nephritis - Needs more aggressive treatment and outcome is variable. This is treated initially with intravenous steroids followed by cyclophosphamide. The dose and number of cyclophosphamide injections needed depends on the degree of inflammation in the kidney, which your doctor decides.

The medications used to treat Lupus Nephritis include:
1) Steroids - Lupus Nephritis is initially treated with three doses of intravenous steroids called Methyl-prednisolone on three successive days. This is followed by oral prednisolone.
Steroids normally act by suppressing inflammation in the body and keep lupus under control. Long term use of steroids can lead to side effects from the medication, which your doctor monitors and tries to prevent or lessen.

Side effects of Steroids:

  1. Hypertension
  2. Diabetes
  3. Increased susceptibility to infection
  4. Osteoporosis
  5. Predisposing to ulcers in the stomach
  6. Weight gain due to fluid retention - face and legs become puffy
  7. Muscle weakness
  8. Skin thinning and bruising

Side effects 1 to 3 can be treated, 4 and 5 can be prevented by neutrising medications. Unfortunately, there is neither prevention nor treatment for side effects 6, 7 and 8.

2) Cyclophosphamide - this is a cytotoxic drug normally used to treat certain cancers. It is used in lupus, not because it is a cancerous condition, but to suppress inflammation. It is given intravenously as infusion in pulses once every 1 - 4 weeks or by mouth in tablet form. Normally, the dose used in lupus patients is much less when compared to cancer patients and so the side effects are lessened.

Side effects of cyclophosphamide:

  1. Thinning or brittle hair
  2. Darkened and thickened skin
  3. Loss of appetite or weight
  4. Fever or bleeding due to bone marrow suppression
  5. Nausea and vomiting - need to use anti-sickness medications
  6. Rash
  7. Painful urination or red urine - due to inflammation in the bladder
  8. Risk of developing cancers - Lymphoma (cancer that develops in the lymph system) or skin cancer
  9. Infertility - It is best to preserve eggs or sperm before starting treatment if you are planning for children later.

Is there anything I can do to lessen these side effects?

  1. Cyclophosphamide decreases your ability to fight infections. Therefore, wash your hands frequently and avoid exposure to people who are known to have infections. Report to your doctor immediately if you develop a sore throat or fever.
  2. It is important to have blood tests at frequent intervals, which your doctor orders. These tell your doctor if you are developing complications such as bone marrow suppression or liver failure, in which case, treatment needs to be stopped temporarily. It will also tell if you are responding to the treatment.
  3. To lessen the risk of developing skin cancer, avoid prolonged exposure to sunlight and light therapy. Wear protective clothing, sunglasses and use sun screen lotions. Report to your doctor if you notice any new moles or any change in your birth moles.
  4. Drink plenty of water during treatment. Your doctor will also prescribe a tablet called MESNA to be taken along with cyclophosphamide. This prevents inflammation and bleeding from the bladder.

Are there any new treatments available for Lupus Nephritis?

  1. Bindarit and LJP 394 - Good results in experimental Lupus Nephritis mice. Clinical trials are in progress in humans.
  2. Co-stimulation inhibitors

    • Anti C 5
    • Anti CD 40 - Good results in humans
  3. Mycophenolate Mofetil (MMF) - Good results in humans

What happens if the treatment fails?
5 -10% of patients do not respond to the treatment and eventually develop kidney failure. Such patients would need dialysis or kidney transplantation. This must be taken in context that 90 - 95% of patients do respond well to treatment and, in some cases where transplantation is necessary, can continue to live a good life and, even, have children.

Our thanks go to Dr. Sat Reddy for this overview of the responses given to questions raised at a Meeting of the West Midlands Lupus Group.

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