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When SLE affects the kidneys, it is called lupus nephritis

Systemic lupus erythematosus (SLE) is an autoimmune disorder in which your immune system causes damage to various organ systems, including the skin and joints. When SLE affects the kidneys, it is called lupus nephritis.

Lupus nephritis often develops within 5 years of the onset of lupus symptoms. The disorder affects about 40% of patients with SLE and can develop into end-stage renal disease (ESKD) in 22% of patients in 15 years.

What are the symptoms of lupus nephritis?

Symptoms of lupus nephritis may include:

• Fatigue
• Joint pain and swelling
• Muscle pain
• Swelling in the legs, feet, ankles and sometimes, the hands and face (edema)
• Frequent urination, especially at night
• Foamy or bubbly urine (a sign of protein in urine)
• Blood in urine
• Unexplained weight gain
• High blood pressure
• Red rash on the face (butterfly rash)
• Unexplained fever

How is lupus nephritis diagnosed?

Lupus nephritis is diagnosed only if there is underlying lupus. Your doctor will take a complete medical history, evaluate your symptoms, and perform a physical examination to confirm a diagnosis. Tests ordered may include:

• Blood tests
  • Determines whether the kidney is properly eliminating waste materials
  • Can reveal if there are electrolyte imbalances 
  • Can detect antibodies that are generally elevated in people with lupus nephritis
• Urinalysis
  • Checks for red and white blood cells and excessive amounts of protein in the urine
• Imaging studies
  • Intravenous pyelogram: Dye is injected into the body and collected in the kidneys, then an X-ray is performed to show the structure of the kidneys
  • Ultrasonography: An ultrasonography shows the form and size of the kidney surfaces by using soundwaves 
• Kidney biopsy
  • Involves taking a small sample of kidney tissue to examine under a microscope. A biopsy is performed to confirm the diagnosis of lupus nephritis if blood and urine tests show signs of lupus nephritis. A biopsy can help determine the extent and severity of the disease. 
  • The American College of Rheumatology recommends getting kidney biopsies if you have active lupus nephritis but have not yet been treated. Early detection and treatment can help protect the kidneys.

Lupus is an infection.
See Answer

What are the stages of lupus nephritis?

Lupus nephritis is divided into six phases based on the extent of kidney damage. Microscopic examination of the glomeruli will reveal the stage of lupus nephritis. Determining the stage of the disease may help with treatment decisions.

• Class I: Minimal mesangial lupus nephritis: Little to no kidney damage but the presence of some immune activity (immune deposit or complex) in the kidney filtering structures. A person suffering from class I lupus nephritis will often have no symptoms.
• Class II: Mesangial proliferative lupus nephritis: Mild renal illness or kidney disease. A pathologist may find signs of nonspecific inflammation all over the kidney.
• Class III: Focal lupus nephritis: Damage to 50% or less of the glomeruli in the kidneys. A pathologist can identify the presence of kidney lesions. Urinalysis reveals traces of blood or protein.
• Class IV: Diffuse lupus nephritis: Damage to more than 50% of the glomeruli. Larger lesions in the renal tissue may be detected. Blood and excess protein in the urine and elevated blood pressure are indications of class IV lupus nephritis.
• Class V: Lupus membranous nephropathy: Excess immune complexes in the kidneys. High blood pressure, excess protein and blood in the urine, significant edema, and active lesions on the kidneys are signs of class V lupus nephritis.
• Class VI: Advanced sclerotic lupus nephritis: More than 90% of the glomeruli in the kidney are destroyed. End-stage renal disease is common in people with class VI lupus nephritis (ESRD). These individuals are more likely to need dialysis or a kidney transplant. Class VI lupus nephritis symptoms include all the lupus nephritis symptoms and additional symptoms of ESRD, such as nausea, vomiting, fatigue, chest discomfort, shortness of breath, cramping, and itching.

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What are possible complications of lupus nephritis?

Possible complications of lupus nephritis may include:

• Lupus nephritis can result in persistent kidney damage, or chronic kidney disease.
• Proliferative nephritis, the most severe form of lupus nephritis, can cause scarring in the kidneys that prevents them from functioning properly.
• Kidney failure or end-stage renal disease (ESRD) is a progressive chronic kidney condition that causes the kidneys to stop functioning. About 1-3 out of every 10 patients with lupus nephritis develop renal failure or ESRD.
• Patients with lupus nephritis are more likely to develop certain forms of cancer, heart problems, and blood vessel disorders.

What are the treatment options for lupus nephritis?

There is no cure for lupus nephritis. Treatment varies depending on the stage. With proper treatment, a healthy lifestyle, and frequent check-ups, 80%-90% of people with lupus nephritis can lead a normal life.

Immunosuppressive treatment

Immunosuppressive treatment is often administered to treat:

• Active focal lupus nephritis (class III)
• Diffuse lupus nephritis (class IV)
• Lupus membranous nephropathy (class V)

Immunosuppressive treatment is usually not administered to:

• Minimal mesangial (class I)
• Mesangial proliferative (class II)
• Advanced sclerosing (class VI)

Using potent anti-inflammatory and immunosuppressive medicines as first-line treatment produces a clinical and immunologic renal response that prevents increasing nephron loss and end-stage kidney disease (ESKD). The length of the first treatment varies; it may be as short as 3 months or as long as a year, but it usually lasts 6 months.

Once a renal response is obtained, less aggressive immunosuppressive medication is administered for an extended length of time to avoid recurrence and to treat the systemic autoimmunity.

Mycophenolate or cyclophosphamide

If you have diffuse or localized lupus nephritis, you will be recommended to start with glucocorticoids along with either mycophenolate mofetil or intravenous (IV) or oral cyclophosphamide. Viable options for early treatment include mycophenolate in combination with a calcineurin inhibitor (voclosporin or tacrolimus) or belimumab or cyclophosphamide in combination with belimumab.

Because cyclophosphamide can impair fertility, mycophenolate is preferred for people with reproductive issues. IV cyclophosphamide, however, may be chosen for individuals who have prior gastrointestinal issues or who have trouble taking oral medication.

For promoting renal response and preventing ESKD, IV cyclophosphamide in conjunction with glucocorticoids has become a standard-of-care treatment.

Calcineurin inhibitors

Calcineurin inhibitors, particularly tacrolimus, have shown positive results in the treatment of lupus nephritis. Voclosporin, a calcineurin inhibitor, was the first oral medicine approved by the FDA for lupus nephritis in combination with immunosuppressive therapy.

Monoclonal antibodies

• Belimumab: Belimumab is a monoclonal antibody that is an anti-B-lymphocyte stimulator (BLyS). The FDA has authorized it to treat people with active lupus nephritis who are receiving conventional therapy. Many trials have shown that belimumab showed promising outcomes including complete renal response over 2 years.
• Rituximab: B-lymphocytes play a crucial role in developing systemic lupus erythematosus (SLE) and lupus nephritis. Rituximab depletes B-lymphocytes and provides effective treatment for lupus nephritis. However, the use of rituximab remains controversial due to the lack of evidence of its use and poses negative results. Rituximab is not used as an initial treatment.
• Atacicept: Atacicept (a transmembrane activator and calcium modulator) and cyclophilin ligand interactor-immunoglobulin human fusion protein suppress BLyS while acting as a proliferation-inducing ligand. Atacicept was shown to have biologic effects in individuals with SLE in early phase research, resulting in a dose-dependent decrease in B cells and immunoglobulin levels.
• Abetimus: Abetimus is a B-lymphocyte tolerogen that was shown to be unsuccessful in avoiding lupus nephritis flares in a large, controlled experiment, despite lowering anti-DNA antibody levels.

Hemodialysis

Patients with end-stage renal disease (ESRD) require dialysis and eventually a kidney transplant. Patients with ESRD due to SLE account for 1.5% of all dialysis patients in the United States. The 5-year survival rate of patients on dialysis for SLE is 60%-70%, which is fair compared to dialysis patients without SLE.

Kidney transplantation

SLE patients account for 3% of all kidney transplants in the United States. The patient must not have active SLE at the time of transplantation. In the event of spontaneous renal recovery, a 3-month duration of dialysis is typically recommended.

In terms of transplant survival, there is significant evidence that people with SLE perform worse than individuals without SLE. Organs received from a living person who is not an identical twin (allografts) perform better than organs harvested from a dead body (cadaveric allografts).

Recurrent lupus nephritis and associated antiphospholipid antibody syndrome can cause the loss of the organ or graft received. These are the reasons for a worse prognosis following transplantation in patients with SLE.