Lupus nephritis is one of the most serious complications of systemic lupus erythematosus (SLE). It occurs when the immune system mistakenly attacks the kidneys, leading to inflammation and possibly to organ damage. Inflammation of the kidneys can harm the ability of the overall renal (kidney) system to properly remove waste from blood, maintain the correct amount of body fluids, and regulate hormone levels for controlling blood pressure and blood volume. 

Lupus nephritis most often develops within five years from when lupus symptoms first appear. Symptoms include weight gain, swelling, increase in urination (especially at night), blood and foamy appearance in the urine, and high blood pressure. In its early stages, however, the symptoms of lupus nephritis can go unnoticed. If lupus nephritis is not treated symptoms can get worse and lead to kidney failure. People experiencing serious kidney complications like kidney failure may need either dialysis or a kidney transplant.

Who can develop lupus nephritis?

Studies have shown that over time up to 60% of lupus patients will develop lupus nephritis, including over half of children with lupus. Lupus nephritis is more common in women than in men, and there is an even higher prevalence and severity of the disease among African American, Asian and Hispanic women between 15-44, who tend to develop the disease earlier and experience more serious complications.

Diagnosis and treatment

Getting tested and treated as soon as possible is extremely important. Testing used in evaluating and diagnosing kidney issues include a urine test or urinalysis, blood test, and kidney biopsy. Your doctor or a special doctor called a nephrologist can help you find the right treatment if you have lupus nephritis.

There are medications used to help control the inflammation and reduce kidney damage like immunosuppressive drugs, corticosteroids, and even blood thinning supplements. Two drugs, Benlysta and Lupkynis, have been approved specifically to treat lupus nephritis.

In addition, you can help protect your kidneys by controlling your blood pressure, diabetes and high cholesterol levels. Every person with lupus is different, make sure to talk to your doctor about the treatment plan that is right for you. 

Explaining the Lupus Nephritis Classification System

When the immune system mistakenly attacks the kidneys in a person with lupus, causing lupus nephritis, doctors need to know exactly how severe the kidney damage is so that they can put together the most effective treatment plan. To help with this, the International Society of Nephrology and Renal Pathology Society (ISN/RPS) has made a classification system to group lupus nephritis into one of six different categories.^[1]

What information does a doctor use to group lupus nephritis into one of the six different classifications?^[1,2]

Doctors perform a kidney biopsy when deciding how to categorize your lupus nephritis. This is done by using a thin needle (usually inserted through the back) to remove a small piece of the kidney and then looking at the tissue with a microscope. To understand this a little better, it’s helpful to first know a few things about how the kidneys work in people who don’t have lupus and in people with lupus.

What happens in normal kidneys?

The kidneys are two bean-shaped organs in your lower back, one on each side of your spine. The kidneys are made of many tiny parts called nephrons that help clean your blood and make urine. Each nephron contains small tufts of blood vessels (glomeruli) and tiny tubes (or tubules).

Blood from the bloodstream passes through the glomeruli where it gets filtered so that leftover water and waste can then move into the tubules. Some parts of the filtered blood, like small proteins and other important nutrients, are still needed by the body and get reabsorbed. The leftover water and waste are released through the tubules to leave the kidneys and become urine.

What happens in kidneys damaged by lupus?

When you have lupus, your immune system makes special proteins (antibodies) that are supposed to fight germs (antigens), but they mistakenly attack your own body’s proteins (“self” antigens) instead. These form tiny microscopic clumps, which are called “complexes.” The complexes then travel through the bloodstream and get stuck in the glomeruli of the kidneys where they cause inflammation and damage. 

Different amounts of damage happen in different patients with lupus nephritis, and once your glomeruli become damaged and “leaky,” important proteins can be lost in the urine. Over time, the kidneys may not work as well, and this can lead to kidney failure.

The tiny nephrons containing damaged glomeruli and tubules are what doctors view and measure underneath a microscope to classify how severe your lupus nephritis is!

What are the different classifications of lupus nephritis?^[1]

Your lupus nephritis will be classified into one of six different categories, based on how much inflammation or damage is seen underneath the microscope. It’s important to know that your lupus nephritis classification may change over time, from one class to another.

• Class I, Minimal Mesangial Lupus Nephritis (minimal damage): 
  The glomeruli look almost normal under a microscope with very little damage. The kidneys work well.
• Class II, Mesangial Proliferative Lupus Nephritis (mild damage): 
  The glomeruli show small areas of swelling or irritation, but still work well.
• Class III, Focal Lupus Nephritis (moderate damage):
  Some glomeruli are more inflamed with swelling and irritation. Scars may be seen, and the kidneys may not work as well as before.
• Class IV, Diffuse Lupus Nephritis (severe damage): 
  This is the most common type, with many glomeruli that are swollen and inflamed with scars. This is a serious form of lupus nephritis that can cause significant kidney problems.
• Class V, Lupus Membranous Nephropathy (extra protein leakage): 
  This class of lupus nephritis is not necessarily more severe than other classes, but the glomeruli are damaged in a way that lets too much protein leak into the urine, and swelling in the body occurs. The severity of this type of lupus nephritis varies from person to person.
• Class VI, Advanced Sclerosing Lupus Nephritis (end-stage damage): 
  The kidneys have been severely damaged, with a lot of scars, and may stop working, which can lead to kidney failure.

Besides the six classes of lupus nephritis above, there are other forms of lupus kidney disease that damage different parts of the nephron besides the glomeruli. Underneath a microscope, these abnormalities may be found in the capsule surrounding the glomeruli, in the tubules, or in other nearby tissues and blood vessels.

How do treatments for lupus nephritis protect my kidneys?^[3-6]

All patients with lupus nephritis usually take a medicine called hydroxychloroquine. Hydroxychloroquine has anti-inflammatory properties, decreasing inflammation and subsequent damage, which can help prevent flare-ups of lupus disease.

Treatment of other problems associated with lupus nephritis is also important. Your healthcare provider may prescribe a blood pressure medicine, since lower blood pressures are gentler on the kidneys and help to preserve kidney health. You may also be prescribed a medication to lower your cholesterol or lipid levels since high cholesterol is common with lupus nephritis.

Certain vitamins and supplements like vitamin D, E, omega-3 fatty acids, and curcumin may also be helpful. Other medicine recommendations usually depend on which class of lupus nephritis you have and at what rate it is improving or worsening over time:

Class I or class II lupus nephritis usually has a good prognosis, and no other special treatment is needed unless the condition gets worse, which can happen when other disease factors aren’t controlled.

For class III, class IV, and class V lupus nephritis, which are more serious, glucocorticoids (“steroids”) and other medicines that slow down the immune system, lessening its ability to make harmful antibodies, are used. The names of some of these  immunosuppressive medicines are mycophenolate mofetil, cyclophosphamide, belimumab, voclosporin, tacrolimus, and cyclosporine.

For class VI lupus nephritis, hemodialysis (using a special machine that cleans the blood by connecting to the body through a soft tube in the arm or neck) and/or kidney replacement surgery (or transplant) is often required in addition to some of the measures mentioned above.

Talk to your health care team!

Staying informed about the different classifications of lupus nephritis and how they affect your treatment is important. The more details you know about your kidney biopsy and lupus nephritis diagnosis, the better understanding you’ll have regarding your  prognosis or long-term outcome. You’ll also be more equipped to ask your healthcare provider questions about monitoring and treatments that are best for your stage of disease.