The Lupus Group of WA

Kidney Disease and Lupus

John H. Klippel, M.D. Medical Director, The Arthritis Foundation
A reprint from the Lupus Foundation of America Article Library 2001

The two medical terms for the kidney disease that occurs in systemic lupus erythematosus are lupus nephritis or lupus glomerulonephritis. It is estimated that about one-third of people with lupus will develop nephritis that requires medical evaluation and treatment. Lupus nephritis is an important and potentially serious symptom of lupus.

Clinical course of lupus nephritis
There are very few signs or symptoms of lupus nephritis.

It does not cause pain in the abdomen or back.
However, when protein leaks from the kidneys, it is eliminated from the body in the urine
Foamy, frothy urine and getting up to urinate during the night can suggest excessive protein loss.

The loss of protein in the urine from lupus nephritis may then lead to fluid retention with weight gain and swelling ( edema ). This is often the first symptom noticed of lupus nephritis.

The edema generally appears as puffiness in the feet, ankles and legs.
This swelling will be absent in the morning, but will gradually worsen as the person walks about during the day.

The clinical path of lupus nephritis is highly variable.

Often the signs of lupus nephritis are seen only in urine studies.
- In many people, the urine abnormalities are very mild and may be present during one examination and absent the next.
- This form of lupus nephritis is rather common and generally does not require any special medical evaluation or treatment.
In some people, though, abnormal findings in the urine studies may persist or even worsen over time.
- People with this type of lupus nephritis are at risk for loss of kidney function.
- These individuals will need additional studies to assess the extent of their lupus nephritis and to determine the best treatment for controlling the disease.

It is important to recognize that not all kidney problems in people with lupus are due to lupus nephritis.

Infections of the urinary tract, with burning on urination, are quite common in people with lupus and require antibiotic treatment.
Also, signs or symptoms of kidney disease that can be confused with lupus nephritis may be caused by some medications used in lupus treatment. These problems usually go away when the medications are discontinued. Two medications that can cause fluid retention or loss of kidney function are :
- Salicylate compounds ( e.g., aspirin )
- non-steroidal anti-inflammatory drugs ( NSAIDs ).

Studies to evaluate lupus nephritis
There are a number of studies that can be done to test for kidney disease in a person with lupus :

1. Urinalysis

A urinalysis is by far the simplest and most commonly used study to test for lupus nephritis. In this test, a urine sample is examined for the presence of protein and blood cells which are not normally found in the urine.

The blood cells that may collect in the kidney to form and be excreted in the urine are called casts. Casts are seen when the urine is examined under the microscope.
The presence of protein in the urine is called proteinuria.
The presence of red blood cells in the urine is called hematuria.
The presence of white blood cells in the urine is called leukocyturia.
The presence of any of these in the urine suggest the possibility of lupus nephritis and generally indicate the need for further studies.

2. Blood work

The main function of the kidney is to remove waste products and excess fluids from the body. Blood studies can be done to measure whether the kidney is doing this job properly.

Two studies that are done to indicate whether waste products are being adequately removed by the kidney and not building up in the blood :
- the blood urea nitrogen ( BUN ) study
- the serum creatinine study.
Losing protein in the urine may lead to lower levels of protein in the blood. This is measured by :
- the serum albumin study.
Imbalances of salt and water in the blood are detected by chemistry studies such as :
- the serum sodium study
- the potassium study
- the bicarbonate study.
Blood tests may also be done to detect immune system abnormalities that are commonly seen with lupus nephritis. Two commonly used blood tests are :
- the serum complement test, which measures the levels of proteins in the blood that typically are low in lupus nephritis, and
- the antibodies to DNA test which measures these antibodies that typically are high in lupus nephritis.

3. 24-hour urine collection

Studies of the urine collected by the patient over a 24-hour period determine whether the kidneys are working properly.

These studies measure the kidneys' ability to filter waste products :
- the creatinine clearance test
- the exact amount of protein lost in the urine over a 24-hour period.

4. Imaging studies

There are two ways to examine size and shape of the kidneys, which must be done before a kidney biopsy to help guide the physician doing the biopsy :

an intravenous pyelogram ( IVP ) involves an injection of dye that collects in the kidneys. An x-ray of the abdomen is then taken which shows the outline of the kidneys.
a sonogram uses soundwaves transmitted through the body to show the shape and size of the surfaces of the kidney.

5. Kidney biopsy

If urine or blood studies suggest lupus nephritis, a kidney biopsy may be performed. The biopsy is done to :

confirm the diagnosis of lupus nephritis
to determine the extent and severity of kidney disease.

A kidney biopsy is done in a hospital by inserting a narrow needle through the skin of the back and removing a small piece of the kidney. ( On rare occasions, a kidney biopsy may need to be done surgically in the operating room. )
The specimen of kidney tissue is then examined under a microscope to determine how much inflammation or permanent damage ( scarring ) is present. These findings classify the type of lupus nephritis by using a scoring system devised by the World Health Organization ( WHO ) ( see Table 1 ). Knowing the type of lupus nephritis helps to determine the seriousness of the nephritis and the best approach to treatment.

World Health Organization ( WHO ) classification system for lupus nephritis
The World Health Organization has established a classification system for types of lupus nephritis, which are described in Table 1 below.

Table 1. World Health Organization ( WHO ) classification system for lupus nephritis
Class Designation Comment
I Normal No evidence of lupus nephritis on the kidney biopsy.
II Mesangial Nephritis Most mild form of lupus nephritis; typically responds completely to treatment with corticosteroids.
III Focal Proliferative Nephritis Very early stage of more advanced lupus nephritis; typically treated with high doses of corticosteroids, with excellent outcome.
IV Diffuse Proliferative Nephritis Advanced stage of lupus nephritis with definite risk of loss of kidney function; typically treated with high doses of corticosteriods combined with immunosuppressive drugs.
V Lupus Membranous Nephropathy Generally associated with excessive protein loss and edema; typically treated with high doses of corticosteroids, with or without immunosuppressive drugs.

Treatment and therapy
Treatment for lupus nephritis must be individualized to the needs of the specific person. All of the following must be taken into consideration :

the amount of edema ( swelling )
urine abnormalities
amount of protein in the urine
reduction of kidney function
findings of the kidney biopsy.

Diuretic agents may be used to help eliminate excess fluid.
Anti-hypertensive drugs can control increased blood pressure.
Anticoagulation drugs are used in case of complications arising from blood clots.
Changes in the diet can be made to control the intake of salt, proteins, and calories. There are two major forms of drug therapy used for lupus nephritis : corticosteroids to control inflammation, and cytotoxic or immunosuppressive drugs to suppress the activity of the immune system.

Corticosteroids
Corticosteroids have been used to manage lupus nephritis for nearly forty years. Still, there are many unanswered questions as to exactly how they work and how they may be most effectively used.
High doses of corticosteroids, or even corticosteroids given for extended periods of time, may cause a number of side effects ( some side effects can be lessened by a low calorie and low salt diet ) :

increased appetite
fluid retention with weight gain
puffy face
easy bruising
moodiness
loss of mineral from the bones
cataracts
thinning hair
an increased risk of infection and diabetes.

High doses of corticosteroids ( taken orally or intravenously ) are given until the lupus nephritis improves.
The dose of corticosteroids is then slowly reduced under close watch of a physician to make certain that the nephritis doesn't worsen.

Cytotoxic or immunosuppressive drugs
These are generally regarded as standard treatment for people with serious lupus nephritis. These drugs block the function of the immune system, which in turn prevents further damage to the kidneys.
The most commonly used is cyclophosphamide ( Cytoxan ).
Immunosuppressives that are used less frequently include : azathioprine ( Imuran ), chlorambucil ( Leukeran ), and cyclosporine ( Sandimmune or Neoral ).
The application of these drugs typically varies according to classification :

Corticosteroids ( such as prednisone, prednisolone and methylprednisolone, or Medrol ) are considered necessary in the initial treatment in virtually all forms of lupus nephritis.
Corticosteroids are the only type of drug required for those with Class II ( mesangial nephritis ).
A combination of corticosteroids and immunosuppressives are used to treat most people with Class III ( focal proliferative nephritis ), Class IV ( diffuse proliferative nephritis ) or advanced Class V ( membranous nephropathy ).

Several promising experimental therapies for lupus nephritis are currently being studied. These include :

newer immunosuppressive drugs like cyclosporine and mycophenolate mofetil ( CellCept )
the removal of antibodies associated with lupus nephritis by selective plasmapheresis
the administration of biologic agents that suppress the immune system.

Kidney failure
Despite the prescribed treatment, some people with lupus nephritis do have progressive loss of kidney function. In the case of complete failure of both kidneys, dialysis, and eventually kidney transplantation will be required.
Dialysis can be done in two ways :

Hemodialysis passes the blood through a dialysis machine and filters it directly.
Peritoneal dialysis places fluid in the abdominal cavity and subsequently removes it.

Kidney transplantation has been very successful in people who have had kidney failure from lupus nephritis. Usually they are kept on artificial dialysis until there is little or no evidence of active lupus before the transplantation procedure is performed. Afterwards, immunosuppressive drugs will be used to prevent rejection of the transplanted kidney.

Conclusion
Over the past several decades, there have been major advances in the understanding of what causes lupus nephritis and, in particular, improvements in treatment. Today, more than 80 percent of people with lupus nephritis will live a normal life span.

Disclaimer :
The Lupus Group of WA ( Inc ) does not recommend or endorse any products, drugs, treatments, procedures, medical or health professional in this article. We suggest you discuss this information with your doctor or specialist.

Table 1. World Health Organization ( WHO ) classification system for lupus nephritis
Class	Designation	Comment
I	Normal	No evidence of lupus nephritis on the kidney biopsy.
II	Mesangial Nephritis	Most mild form of lupus nephritis; typically responds completely to treatment with corticosteroids.
III	Focal Proliferative Nephritis	Very early stage of more advanced lupus nephritis; typically treated with high doses of corticosteroids, with excellent outcome.
IV	Diffuse Proliferative Nephritis	Advanced stage of lupus nephritis with definite risk of loss of kidney function; typically treated with high doses of corticosteriods combined with immunosuppressive drugs.
V	Lupus Membranous Nephropathy	Generally associated with excessive protein loss and edema; typically treated with high doses of corticosteroids, with or without immunosuppressive drugs.