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Kidney Disease & Lupus Riteesha Guttikonda, M.D. Tammy O. Utset, M.D., M.P.H. Associate Professor of Medicine, University of Chicago Introduction Kidney disease in patients with systemic lupus erythematosus (SLE) is common. The normal kidney controls blood pressure, filters out waste products from blood and excretes (removes) them as urine, and produces hormones important for red blood cell growth and Vitamin D metabolism. Lupus nephritis, or lupus glomerulonephritis, is the medical term used to describe inflammation of the kidney caused by lupus. Symptoms and Clinical Course Lupus nephritis has a variable course, ranging from mild disease to kidney failure requiring dialysis. Some patients may develop high blood pressure, urinary frequency, foamy urine, or fluid retention and weight gain with swelling (edema) in the feet, ankles, and legs. Often, patients do not have any symptoms and the only signs of lupus nephritis are seen in urine studies. Urine studies may demonstrate mild abnormalities during one evaluation and may be normal the next. Patients with persistently abnormal findings on urine studies are at risk for loss of kidney function and may need additional studies to assess the extent of kidney involvement and determine the best treatment. Studies to Evaluate Kidney Disease There are a number of studies used to determine kidney involvement in patients with lupus. Blood Studies Blood studies are often normal in patients with lupus nephritis and do not become abnormal until kidney disease is at a more advanced stage. A major role of the kidney is to filter and remove waste products from the blood. A blood urea nitrogen (BUN) and creatinine can be used to determine whether the kidney is properly handling waste products or if they are building up in the blood. Another role of the kidney is to prevent loss of protein in the urine. A low serum albumin level may indicate that excessive protein is being lost in the urine. Complement levels and DNA antibodies are additional blood tests used in lupus and may correlate with kidney disease in lupus. Urine Studies Urinalysis is the most routine and commonly used test to screen for lupus nephritis. A urine sample is collected and examined for protein and blood cells that are not present in normal urine. Abnormal findings may include proteinuria (protein in the urine), hematuria (red blood cells in the urine), or pyuria (white blood cells in the urine). Red blood cell casts may also be seen in patients with more active kidney disease. Kidney stones, urinary tract infections, and menstrual periods in women may demonstrate similar abnormalities on urinalysis and are important to rule out as causes of the abnormal urine findings. If the urinalysis shows that a significant amount of protein is leaking from the kidneys into the urine, then the patient may be asked to collect urine over a 24-hour period. This 24-hour urine collection will be analyzed to determine the creatinine clearance (ability of the kidneys to filter waste products) and the exact amount of protein lost in the urine. Kidney Biopsy When abnormalities in blood and urine studies are suggestive of lupus nephritis, a kidney biopsy may be performed to confirm the diagnosis. Kidney biopsy is the only means to definitively establish the diagnosis of lupus nephritis, and it is used to determine the extent and severity of inflammation and disease in the kidney. Often, biopsy is performed in a hospital setting and patients may either be able to go home the same day or be kept overnight to monitor for bleeding. Patients receive local anesthesia and pain medications prior to biopsy. Often CT scan or ultrasound guidance is used to image the kidney, and then a needle is inserted into the patient's back and a piece of kidney is removed. The kidney tissue specimen is analyzed under a microscope to determine the extent of inflammation and damage caused by lupus nephritis. Kidney damage caused by other diseases such as high blood pressure and diabetes can also be determined. Types of Lupus Nephritis Lupus nephritis ranges from mild disease that does not require treatment to more severe disease that requires aggressive drug therapy to prevent permanent damage and kidney failure. The World Health Organization (WHO) has classified lupus nephritis into six main categories as follows: CLASS I: Normal. CLASS II: Mesangial. This is the mildest form of lupus nephritis, has an excellent prognosis, and requires no additional treatment. Urine studies may show microscopic amounts of protein or blood. CLASS III: Focal Proliferative. This is characterized by patchy areas of more aggressive inflammation in the kidney and can progress to severe kidney disease. Patients generally have microscopic amounts of blood and protein in the urine. They can also have high blood pressure. CLASS IV: Diffuse Proliferative. This is the most common and severe form of lupus nephritis and requires aggressive treatment. Almost all patients have hematuria and proteinuria. Excessive protein loss in the urine (nephrotic syndrome), high blood pressure, and progressive renal insufficiency associated with an elevated serum creatinine are also common. CLASS V: Membranous. These patients typically develop edema and swelling due to excessive protein loss in the urine. This type of nephritis can occur alone or in combination with Class III or Class IV nephritis. It has an unpredictable course, improving in some, remaining chronic/stable in others, and progressing slowly to renal failure over many years in some cases. CLASS VI: Advanced Sclerosing. This represents damage and scarring from prior inflammatory injury, and active inflammation is not observed. Treatment and Prognosis of Kidney Disease Treatment of kidney disease in lupus is guided by the type of lupus nephritis and is tailored to each individual patient's needs. WHO Classes I and II generally do not require additional treatment and have an excellent prognosis. Corticosteroids may be given for Class II nephritis in some cases. Class III and Class IV are the most severe forms of lupus nephritis and must be treated aggressively to avoid development of kidney failure. Patients initially receive an induction regimen to treat the inflammation followed by a maintenance regimen to prevent disease relapse. The induction phase usually includes high-dose corticosteroids in combination with immunosuppressive medications. Cyclophosphamide is the strongest and most commonly used medication but also has potential longterm side effects of infertility and slightly increased risk of specific cancers. Several alternative regimens with a safer side effect profile are currently under investigation and may be as effective as cyclophosphamide. These regimens include the use of newer medications such as mycophenolate mofetil and rituximab. Depending on the severity of disease, Class V nephritis may be treated with a combination of low-dose corticosteroids with or without immunosuppressive medications. Class VI is residual scarring from prior inflammation. This is considered "burnt-out" disease and requires no specific therapy. Additional Therapy Patients with lupus nephritis have variable amounts of protein loss in the urine (proteinuria). Excessive protein loss can develop into nephrotic syndrome that consists of edema (swelling), proteinuria, increased risk of blood clots, and elevated lipids. Medications known as ACE (angiotensin converting enzyme) inhibitors are used to reduce proteinuria. Some patients may require cholesterol-lowering medications as well as anticoagulation to prevent blood clots. High blood pressure is also common in lupus nephritis, and aggressive blood pressure control is always important. Kidney Failure Dialysis Despite aggressive treatment, some patients have progressive loss of kidney function. Patients who develop complete kidney failure require dialysis in order to remove excess fluid and waste products from the body. There are two main types of dialysis. Hemodialysis filters blood directly through a dialysis machine and is usually done three times a week at a dialysis center. Peritoneal dialysis places dialysis fluid in the abdominal cavity (stomach area) and then removes it. Kidney Transplantation Kidney transplantation is an alternative to long-term dialysis for some patients. Lupus is not a contraindication for kidney transplantation, and outcomes are better for patients with transplantation than with long-term dialysis. While the best transplantation outcomes are with kidneys from living donors (usually family members), kidney transplantation from cadavers (deceased donors) also improves survival and quality of life for lupus patients with kidney failure.  |
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