Lupus Nephritis

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What is Lupus Nephritis?

Lupus nephritis (LN) is inflammation of the kidneys that results from an autoimmune disease known as systemic lupus erythematosus (SLE). Lupus is a latin word for wolf since some patients develop a skin rash on the nose, which resembles a wolf bite. Lupus is a form of vasculitis (i.e., the inflammation of blood vessels). In the case of lupus nephritis, there is inflammation of the filtering units (glomeruli) and the blood vessels in the kidney.

Lupus Nephritis

An autoimmune disease is a condition in which the immune system of an individual begins to attack his or her own body cells by considering them foreign. A normal immune system is the body’s defence network and attacks any foreign objects that enter the body in the form of infection. In SLE, the blood vessels are mistaken as foreign by the immune system, leading to vasculitis throughout the body.

SLE damages the kidney causing nephrotic syndrome, interstitial nephritis, and membranous nephropathy. Nearly 60% of the patients with SLE have lupus nephritis. One-tenth of this population is affected by chronic kidney disease. Grave illness or even mortality are observed in patients with lupus nephritis. Young adults and adolescents are primarily affected with lupus and women form a major part of this category.

Causes of Lupus Nephritis

Lupus nephritis (LN) is a result of the autoimmune disorder called systemic lupus erythematosus (SLE). This autoimmune condition affects the skin, kidneys, and joints. When the kidneys are inflamed, it causes lupus nephritis.

Classification of Lupus Nephritis

Based on the 2004 guidelines of the International Society of Nephrology/Renal Pathology Society (ISN/RPS), lupus nephritis is classified into 6 classes (LN class I to class VI). Each class has distinct pathological characteristics and are listed below:

Class I – In this condition, the appearance of the kidney glomeruli (the capillaries that filter blood to form urine) is normal under the light microscope (LM), however, immune deposits are observed in mesangial cells under greater magnification with an electron microscope (EM) or an immunofluorescence microscope (IFM).

Class II – There is increased growth of the mesangial cells (cells that are surrounded by the glomeruli in the kidney) in addition to the immune deposits that are observed in the cells.

Class III – In this condition, the number of lesions in the glomeruli are less than 50% with accompanying vasculitis (inflamed blood vessels).

Class IV – In this condition, the number of lesions in the glomeruli are greater than 50% with accompanying vasculitis.

Class V – This is also known as membranous LN. The condition displays a combination of lesions in the glomeruli and immune deposits.

Membranous Lupus Nephritis

Class VI – Absence of active lesions and the presence of more than 90% lesions in the glomeruli result in the classification of class VI LN.

Symptoms of Lupus Nephritis

As mentioned above, “lupus” is a Latin for the word wolf. One of the symptoms for lupus is a skin rash that appears on the nose as a butterfly rash and resembles the bite of a wolf. Additional symptoms include:
  • Fever
  • Muscle pain
  • Joint swelling or pain
  • Edema in the feet, ankles, or legs
  • High blood pressure
  • Urine that foams
  • Excess protein in the urine (Proteinuria)
  • Blood in the urine (hematuria)
  • Pleuropericarditis – Inflammation of the pleura and the pericardium (lining surrronding the heart).

Diagnosis of Lupus Nephritis

A physical exam tends to indicate the signs of LN. Blood pressure is high in individuals with LN along with body swelling or edema due to kidney damage. There are abnormal sounds when the doctor listens to the heartbeat.

Lupus nephritis may be diagnosed with a kidney biopsy, blood tests, or with urine tests.

Kidney biopsy – This is mainly used to determine the kind of treatment for LN based on the disease progression. In this case, a small piece of kidney tissue is acquired with the help of an ultrasound or computed tomography that guides the needle to the kidney. The biopsy is performed by a health service provider and the patient is anesthetized during the procedure. The tissue is examined by a pathologist under the miscroscope to detect signs of lupus nephritis. Based on the stage of progression, the appropriate treatment can be prescribed.

Blood tests - The main blood test of interest when considering the diagnosis of LN is creatinine. Creatinine is released when muscle breaks down and is filtered out of the body by the kidneys. Creatinine builds up if there is a defect in kidney function. The blood is drawn in a commercial organization or a healthcare provider’s office and sent to a lab for accurate analysis. Blood urea nitrogen levels can also be tested to understand the functioning of the kidneys. High levels of complement proteins in the blood indicate an increase in the activity of the immune system. There are many serum biomarkers (indicators of a disease) that can be used to detect LN. Recently, the protein, soluble urokinase plasminogen activator receptor (suPAR) was shown to be an effective biomarker for LN.

Diagnosis of Lupus Nephritis

Urine tests - Urine tests are performed by collecting urine in a commercial organization or a healthcare provider’s office. The urine may be tested at the same facility or sent to a diagnostic lab. A chemically-treated strip (dipstick) is placed in the urine. Excess protein or blood cells causes a change in the the colour of the dipstick. Kidney damage is indicated by an increase in protein or blood cells in the urine. The appearance of the urine is analyzed (pale or cloudy). The urine is also analyzed microscopically for bacteria, crystals, and other germs. The urine specific gravity test checks the dilution of the urine.

Treatment for Lupus Nephritis

It has been reported that nonsteroid immunotherapy in combination with steroids is effective in treating and causing complete or partial remission in individuals with membranous lupus nephritis.

Cyclophosphamide treatment is the most common form of treatment for lupus nephritis. Currently, cyclophosphamide is combined with corticosteroids. Cyclophosphamide is an immunosuppressant that is effective in suppressing the immune system in lupus nephritis. Corticosteroids are prescribed to reduce the inflammation in the kidneys that results from SLE. Cyclophosphamide therapy has drastically reduced the mortality rate of LN individuals to below 10%. The combination of cyclophosphamide and corticosteroids maintains the function of the kidneys, although infections, toxicity to bladder, increased risk of cancer, and ovarian damage may occur.

Corticosteroids for Lupus Nephritis

Mycophenolate mofetil (MMF) also reduces toxicity in lupus nephritis with similar remission rates as the cyclophosphamide and corticosteroid therapy. Ovarian damage and alopecia are reduced with MMF treatment. A larger follow-up study is required to verify the data. Azathioprine is another medication used to treat lupus. However, there is an increased risk of relapse.

Calcineurin inhibitors are also another form of medication for lupus nephritis. Data from recent research studies have shown that calcineurin inhibitors, such as cyclosporine, tacrolimus, are more effective and less toxic compared with cyclophosphamide. There is a better response to the cyclosporine inhibitors and an enhanced remission rate is observed compared with cyclophosphamide treatment.

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