Membranous Lupus Nephritis
Mesangial Lupus Nephritis
Systemic lupus erythematosus (SLE) is a disorder in which the immune system produces antibodies against the body’s own healthy cells and tissues (called autoantibodies). These autoantibodies contribute to damage (inflammation) in various parts of the body such as the brain, the joints, the skin and the kidney. This damage alters the normal function of these different organs and tissues. When the inflammation affects the kidneys, it is called lupus nephritis or lupus glomerulonephritis.
Glomerulonephritis refers to diseases that damage the filters or glomeruli of the kidney. Glomeruli are tiny structures composed of blood vessels that are responsible for filtering the blood of harmful or unnecessary substances. There a million glomerular filters within each kidney. In glomerulonephritis, inflammation of some or all of the glomerular filters reduces their ability to clear these substances out of the bloodstream. The damage also allows protein to leak into the urine and this is referred to as proteinuria or albuminuria. Red blood cells can also leak through the filters into the urine and is referred to as hematuria.
Most individuals who are affected by lupus nephritis develop it early on after the diagnosis of SLE but it ca n develop at any time. It is unclear why some people with SLE develop significant kidney problems while others are seemingly unaffected, but genetics likely plays a role. Some individuals do not have a previous diagnosis of SLE when they are found to have kidney problems and it is only through various blood tests that the diagnosis is made. These blood tests detect immune system abnormalities (such as ANA, antibodies directed against DNA/anti dsDNA or complement levels).
Symptoms
Some individuals with lupus nephritis have other symptoms related to active SLE in other parts of the body including fatigue, rash and joint pain. Some develop swelling (edema) of the eyelids in the morning and of the legs late in the day which is due to retention of fluid. Some notice foamy or bubbly urine when they urinate due to the protein in the urine. Other individuals do not have any symptoms and it may first be discovered when there is an abnormal urine test (with blood and protein) or blood test (abnormal kidney function) done by the doctor to screen for kidney problems. Some patients will have high blood pressure.
Diagnosis
Although abnormal blood and urine tests in an individual with SLE usually points to a diagnosis of lupus nephritis, a kidney biopsy is often performed. There are several different patterns (or classes) of kidney damage that can be seen in lupus nephritis. This depends on which part of the glomerular filter is affected by the accumulation of autoantibodies and the degree of the damage. The names of the different patterns are:
- Mesangial lupus nephritis (class II)
- Proliferative lupus nephritis (class III and IV)
- Membranous lupus nephritis (class V)
The only way to know (with certainty) which pattern is present is by looking at a small piece of kidney tissue under a microscope. It is important to know this information because it can influence treatment and can help determine prognosis. Your doctor will spend time talking to you about the type of pattern that you have and what that means. Sometimes, an individual with one pattern of kidney damage can develop a different pattern of injury years later.
Treatment
The decision to treat and the type of treatment usually depends on the results of the kidney biopsy. The result of certain blood test (such as the level of kidney function) and urine tests (such as the amount of protein or blood in the urine) may also be taken into consideration. There are several goals of treatment. Some medications are used to specifically decrease the inflammation that is actively occurring in the kidney. Other medications are given to help alter the immune system to prevent further damage and to try to cure the disease. Steroids are usually used initially. Sometimes, this medication is given intravenously and then it may be given in pill form. Immunosuppression drugs are often used in addition to steroids. One such medication is cyclophosphamide (cytoxan) which is a chemotherapy agent. It is given intravenously sometimes once or twice a month for several months. Other medications that may be given instead of, or after cytoxan, include azathioprine, mycophenolate mofetil (MMF) and cyclosporin. These medications are routinely used in individuals who have received organ transplants. Another medication called rituximab (rituxan) is also being used in some patients. Each of these treatments have different side effects associated with them which should be discussed with the nephrologist. All can increase the risk of infections and this needs to be discussed with your physician. Physicians at the Glomerular Center are very interested in trying to determine which medications are most beneficial to treat the disease with the least side effects. We are actively involved in nationwide clinical trials to help to figure this out and we continue to recruit individuals for these important trials.
Other treatments are used to control the symptoms that can be associated with the disease. Diuretics (“water pills”) are used to help rid the body of excess salt which causes swelling (edema). Other medications are used to help control blood pressure. Sometimes a group of drugs called angiotensin converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) are used for this purpose. These same medications can also help decrease the protein that is lost by the kidney. Other drugs may be used to help reduce high blood cholesterol if this is present.
Prognosis
The natural history of lupus nephritis varies a great deal. It depends on many different factors including the pattern of kidney injury and scarring seen on kidney biopsy. Ethnic background can also have an impact on prognosis. Black and Hispanic individuals may have a worse prognosis than Caucasians.
Treatment may cure the kidney disease (remission) or at least slow the progression of the disease. Some individuals respond to therapy initially but the disease may come back.
As mentioned above, the pattern of kidney injury can change over time and the doctor may recommend further therapy or even another biopsy to detect this. Infrequently, some patients will continue to slowly lose kidney function despite treatment and may need to be on dialysis. Renal transplantation has been very successful in allowing many of these patients to lead normal lives