Kidneys in SLE

Fast Facts

Kidneys have the following functions:

  • Filtering blood and removing toxic substances.
  • Maintaining a balance of electrolytes and pH in the blood.
  • Regulating blood pressure.
  • Converting Vitamin D into a more active form.
  • Supporting the production of red blood cells in the bone marrow

Lupus Nephritis

When kidneys are involved by disease, its functions are compromised. Kidneys however have tremendous functional reserve and there are usually no symptoms associated with kidney disease until very late.

In people with Systemic Lupus Erythematosus (SLE), the kidneys may be affected in about 50% to 80% of patients. In the majority of cases, kidney involvement is mild and usually not a problem, although it can be serious in some patients. However, treatment has dramatically altered the prognosis of severe lupus in the last 30 to 40 years. Nowadays, with proper treatment, many patients with severe lupus nephritis do very well and can lead normal lives.

Lupus nephritis occurs when there is deposition of proteins (immune complexes) in the delicate filtering apparatus of the kidneys and inflammation of the blood vessels supplying the kidneys. This may lead to the appearance of red blood cells and protein in the urine, the blood pressure may rise, and (only in the more severe cases) chemical waste products normally excreted in the urine accumulate in the blood.

Unlike the involvement of joints, skin or the brain, SLE kidney involvement tends to remain silent (the patient will not have any symptoms) until damage has already occurred. Then the patient will complain of weight gain and swelling, particularly of the feet and legs. Doctors call this fluid retention or oedema or nephritic syndrome and this is the most common symptom of major kidney involvement. The most feared complication is kidney failure and fortunately this is uncommon. When kidney failure is advanced, patients may complain of fatigue, loss of appetite, nausea, and vomiting. If left untreated, alterations in mental status, seizures, and other life-threatening problems may occur.

Assessing Kidney Involvement

It is very important to detect kidney involvement early. For this reason, regular tests of kidney function (simple urine and blood tests) will be ordered from time to time by the doctor. Urine analysis can show various signs of inflammation in the kidney such as clumps of red blood cells (casts) or the presence of excessive amounts of proteins. To determine the degree of kidney involvement, a 24-hour urine collection is often required. Blood tests will provide information on increased levels of waste products in the blood if there is impairment of kidney function. Anti-DNA antibody titres and complement (C3 and C4) levels are also measured from time to time as they can help in the assessment of lupus activity.

Kidney Biopsy

A kidney biopsy is a useful test to see how much protein deposition and inflammation there is. This will influence the choice of treatment. A biopsy is performed by inserting a thin needle into the kidney, with the patient lying on his/her abdomen, to obtain a small piece of tissue for examination under the microscope. Only a local anaesthetic is required.

Six distinct histological classes of lupus nephritis are recognised under the more common WHO classification (although a later classification by the International Society of Nephrology was published in 2004, it has not been widely adopted yet).

Class I Nil or minimal change lesion
Class II Mesangial proliferative lupus nephritis (LN)
Class III Focal segmental proliferative LN
Class IV Diffuse proliferative LN
Class V Membranous LN
Class VI Sclerosing LN

Nowadays, pathologists also score the biopsy findings which can be classified as being “active” (indicating active inflammation) or “chronic” (showing scarring). These will help determine if aggressive treatment is worthwhile.


Very mild involvement of the kidneys may not require treatment. General measures are as for other SLE patients. The management of patients with active involvement of the kidneys is generally more aggressive in order to control the disease quickly and prevent permanent damage. A treatment plan is developed on the basis of the kidney biopsy.


Corticosteroids such as prednisolone remain the mainstay of treatment of lupus nephritis. It may be given initially as intravenous “pulse” therapy in severe cases or as oral steroids in less severe cases. This drug is one of the best inflammation fighting drugs available and is responsible for the very much improved outcome and rehabilitation of SLE patients.

Prednisolone is prescribed by the doctor when the degree of kidney involvement is significant or when there is concern that it may progress and become life-threatening. The decision to prescribe the drug is never made lightly by the doctor as it can cause a variety of side-effects. Some short-term effects are increased appetite, weight gain, and “moon-face”, while long-term effects include softening of the bones, rise in blood pressure, and thinning of the skin.

At times, patients may be tempted to stop taking prednisolone or to reduce its dose – perhaps because they are fed up with its side-effects or are feeling better or worse. It is important that patients taking prednisolone understand how it works and why stopping or changing the medication without supervision from the doctor is dangerous.

Other Immunosuppressive Drugs

A significant advance in the treatment of lupus related kidney disease has been the use of immunosuppressive drugs, specifically cyclophosphamide. Immunosuppressive drugs reduce the production of antibodies which cause inflammation. Cyclophosphamide is usually given in combination with moderate doses of prednisolone and are only prescribed for the more active and aggressive classes of lupus nephritis. It may be given orally or intravenously. In severe cases, extremely large doses of corticosteroids and cyclophosphamide are given intravenously (pulse therapy). In many cases, it has led to clear improvement in the lupus kidney disease. This has been demonstrated by observing improvement in biopsy specimens, reduction in the amount of protein in the urine, and improvement in kidney function.

Cyclophosphamide also has many side-effects. These include a decrease in white blood cell count which makes patients more susceptible to bacterial and other infections. It can also cause bleeding from the bladder (haemorrhagic cystitis), hair loss, failure of the ovaries to produce their normal output of hormones (ovarian failure) in females, and azoospermia in males. In the long term, there is also a slightly increased risk of developing certain types of cancers. Therefore, periodic blood tests are necessary and patients are closely followed up by their doctors.

Azathioprine (Imuran) is also sometimes used in combination with prednisolone, often for its steroid-sparing effect. However, its use is not as popular as cyclophosphamide because it is less effective in inducing a remission in severe lupus nephritis.

Other newer and less toxic immunosuppressive drugs for the treatment of severe lupus nephritis include mycophenolate (Cell-Cept, Mifortic), tacrolimus (Prograf), and rituximab (Mathera), among others.

Diuretics and Anti-hypertensive Agents

For patients who develop fluid retention or oedema, medications such as Lasix or Burinex may be needed. These drugs can help to reduce fluid overload by increasing urine output. Similarly, patients who develop hypertension should ensure that they take their blood pressure pills regularly. Untreated high blood pressure can result in further damage to the kidney.

Dialysis and Transplantation

Occasionally, patients are diagnosed only when inflammation has progressed to a point of irreversible damage. Sometimes, but very rarely, some patients do not respond to treatment and may progress to kidney failure. Although these are unfortunate outcomes, treatment is possible with dialysis and kidney transplant.

Both dialysis and transplantation have shown favourable results. Patients who have kidney failure which is advanced enough to require dialysis or transplantation develop a natural immunosuppression and their lupus improves and rarely cause further problems.


Although the kidney is frequently involved in SLE, in the majority of cases, the involvement is mild and easily treated. However, in some patients it can be serious. Therefore, it is always important to monitor blood and urine tests of kidney function in order to detect early signs of kidney involvement. In many patients, a kidney biopsy is needed to help plan treatment. On the basis of the results of the kidney biopsy as well as clinical and other laboratory findings, some patients need only prednisolone treatment while others require a combination of prednisolone and one or more immunosuppressive agents (depending on the doctor and the centre).

With appropriate treatment, outcome of lupus nephritis is generally good. If kidney failure does occur, the systemic disease activity usually diminishes. Useful and productive life can be maintained with kidney transplantation or dialysis. Lupus nephritis is a subject of great interest to researchers and, with improved understanding of SLE, considerable improvement in its management is anticipated.