| Kidney Disease and Lupus John H. Klippel, M.D. Clinical Director, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health Bethesda, Maryland |
| Lupus nephritis, or lupus glomerulonephritis, is the medical term for the kidney disease that occurs in systemic lupus erythematosus (SLE). 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 abdonmen or back. However, foamly frothy urine and getting up to urinate during the night can suggest excessive protein loss. When protein leaks from the kidneys it is eliminated from the body in the urine. The loss of protein in the urine from lupus nephritis may then lead to fluid retention with weight gain and swelling (edema). 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. This often is the first symptom noticed of lupus nephritis. The clinical path of lupus nephritis is highly variable. Often the signs 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 presist 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 pulus nephritis. For instance, infections of the urinary tract, with burning on urination, are quite common in people with lupus and require antibiotic treatment. Also, medications used in lupus treatment may produce signs or symptoms of kidney disease that can be confused with lupus nephritis. Salicylate compounds (e.g., aspirin), or non-steroidal anti-inflammatory drugs (NSAIDs) can cause fluid retention or loss of kidney function. These problems usually go away when the medications are discontinued. 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. 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. These cells may collect in the kidney to form and be excreted in the urine as casts. Casts are seen when the urine is examined under the mircoscope. the presence of protein (proteinuria), red blood cells (hematuria), white blood cells (leukocyturia), or casts in the urine suggest the possibilty of lupus nephritis and generally indicate the need for further studies. BLOOD STUDIES 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. The blood urea nitrogen (BUN) and serum creatinine are two studies that indicate whether waste products are being adequately removed by the kidney and not building up in the blood. Losing protein in the urine may lead to lower levels of protein in the blood; this is measured by the serum albumin. Imbalances of salt and water in the blood are detected by chemistry studies such as the serum sodium, potassium, and bicarbonate. Blood tests may also be done to detect immune system sbnormalities that are commonly seen with lupus nephritis. Measuring the levels of serum complement (proteins in the blood which typically are low on lupus nephritis) and antibodies to DNA (which typically are high in lupus nephritis) are two blood tests commonly used. 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 (creatinine clearance), and the exact amount of protein lost in the urine over a 24-hour period. IMAGING STUDIES The size and shape of the kidneys can be examined with an intravenous pyelogram or sonogram. These studies are done before a kidney biopsy to help guide the physician doing the biopsy. A pyelogram involves an injection of dye that collects in the kidneys. A sonogram uses soundwaves transmitted through the body to show the shape and size of the surfaces of the kidney. 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, and 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 the 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) (Table 1). Knowing the type of lupus nephritis helps to determine the seriousness of the nephritis and the best approach to treatment. Treatment and Therapy Treatment for lupus nephritis must be individualized to the needs of the specific person. The amount of edema (swelling), urine abnormalities, amount of protein in the urine, reduction of kidney function, and findings of the kidney biopsy must all be taken into consideration. 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. Finally, changes in the diet can be made to control the intake of salt, proteins and calories. The two major forms of drug therapy used for lupus nephritis are corticosteroids (to control inflammation), and cytotoxic or immunosuppressive drugs (to suppress the activity of the immune system). Corticosteroids are necessary in the initial treatment in virtually all forms of lupus nephritis, and are the only type of drug required for those with Class II (mesangial nephritis). Most people with Class III (focal proliferative nephritis), Class IV (diffuse proliferative nephritis) or advanced Class V (membranous nephropathy) are tested with a combination of corticosteroids and immunosuppressives (Table 1). Corticosteroids, such as prednisone, prednisolone or methylprednisolone (Medrol) are often used to treat lupus nephritis. 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 (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. High doses of corticosteroids, or even corticosteroids given fo extended periods of time, may cause a number of side effects. These include increased appetite, fluid retention with weight gain, puffy face, easy bruising, moodiness, loss of mineral from the bones, cataracts, thinning hair, and an increased risk of infection and diabetes. Some of these side effects can be lessened by a low calorie and low salt diet. Cytotoxic or immunosuppressive drugs are generally regarded as standard treatment for people with serious lupus nephritis. The most commonly used one is cyclophosphamide (Cytoxan). Immunosuppressives that are used less frequently include: azathioprine (Imuran), chlorambucil (Leukeran), and cyclosporine (Sandimmune or Neoral). these drugs block the function of the immune system, which in turn prevents further damage to the kidneys. 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; and 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 with kidney failure from lupus nephritis. Usually they are kept on artifical dialysis until there is little or no evidence of active lupus befroe the transplantation procedure is performed. Afterwards, immunosuppressive drugs will be used to prevent rejection of the transplanted kidney. Over the past several decades, there have been ajor advances in the understanding of what causes lupus nephritis and, in particular, improvements in treatment. More than 80 percent of people with lupus nephritis will live a normal life span. |
| Class I II III IV V |
| Table 1. World Health Organization (WHO) System for Lupus Nephritis |
| Designation Normal Mesangial Nephritis Focal Proliferative Nephritis Diffuse Prolierative Nephritis Lupus Membranous Nephropathy |
| Comment No evidence of lupus nephritis on the kidney biopsy Most mild form of lupus nephritis; typically responds completely to treatment with corticosteroids Very early stage of more advanced lupus nephritis; typically treated with high doses of corticosterois, with excellent outcome Advanced stage of lupus nephritis with definite risk of loss of kidney function; typically treated with high doses of corticosteroids combined with immunosuppressive drugs Generally associated with excessive protein loss and edema; typically treated with high doses of corticosteroids, with or without immunosuppressive drugs |
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