Lupus Nephritis

Lupus nephritis is a serious complication of systemic lupus erythematosus (SLE), an autoimmune disorder that causes the body's immune system to attack its own tissues and organs. When SLE affects the kidneys, it leads to inflammation and damage, a condition known as lupus nephritis or lupus nephritis associated with SLE. If left untreated, this condition can progressively worsen, leading to impaired kidney function and potentially kidney failure. Understanding the symptoms, diagnosis, and treatment options for lupus nephritis is crucial for effective management of this condition.

What is Lupus Nephritis?

Lupus nephritis is a type of kidney inflammation that occurs as a result of systemic lupus erythematosus (SLE). In SLE, the body's immune system mistakenly identifies the body's own tissues as foreign and launches an attack, causing inflammation and damage. When this autoimmune response targets the kidneys, it leads to lupus nephritis. The inflammation can affect different parts of the kidneys, including the small blood vessels, glomeruli, and tubules, impairing their ability to filter waste and excess fluids from the blood. If not properly treated, lupus nephritis can lead to scarring of the kidneys, reduced kidney function, and eventually, kidney failure.

The symptoms of lupus nephritis can vary from person to person and may include:

• Fatigue and malaise: Patients with lupus nephritis may experience general symptoms such as fatigue and malaise. This overall feeling of unwellness is often linked to the combined effects of lupus and reduced kidney function.
• Oedema: Swelling, or oedema, particularly in the legs, ankles, and around the eyes, is a common symptom. This occurs due to the kidneys' inability to effectively remove excess fluid and sodium from the body.
• Changes in urine: Changes in urine characteristics include foamy or bubbly urine, indicating proteinuria (excess protein in the urine) and haematuria (blood in the urine), which may cause the urine to appear pink or reddish. There may also be increased frequency of urination; however, urgency or pain is not typical unless infection is present.
• High blood pressure: Lupus nephritis can lead to high blood pressure (hypertension) because of the kidneys' impaired ability to regulate blood pressure. This can exacerbate other symptoms and lead to additional health problems.
• Flank pain: Flank pain is uncommon in lupus nephritis but may occur in certain cases with significant inflammation or complications.
• Nausea and vomiting: In more severe cases, lupus nephritis may cause nausea and vomiting due to the buildup of waste products in the body. This can impact appetite and overall nutritional status.
• Skin rash: Lupus nephritis can be associated with skin rashes, which are part of the broader lupus symptoms. These rashes often appear as red, scaly patches or a butterfly-shaped rash across the cheeks and nose.
• Joint pain: Joint pain, or arthritis, is another symptom that can accompany lupus nephritis. This pain affects various joints and reflects the systemic nature of lupus, contributing to overall discomfort and inflammation.

Lupus nephritis is classified into six classes (I–VI) based on the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification system, as determined by kidney biopsy. This system guides treatment and prognosis KDIGO (2024). These classes reflect histopathological patterns and help guide treatment decisions. These include:

• Class I (minimal mesangial lupus nephritis): In this stage, there is minimal damage to the kidneys, and patients usually do not experience any obvious symptoms.
• Class II (mesangial proliferative lupus nephritis): Some damage to the kidneys is present, and patients may have microscopic amounts of blood and/or excess protein in their urine.
• Class III (focal lupus nephritis): Less than 50% of the glomeruli are affected. Patients may experience higher amounts of blood and/or protein in their urine and possibly high blood pressure.
• Class IV (diffuse lupus nephritis): More than 50% of the glomeruli are affected. High blood pressure is common, and as kidney function worsens, dialysis may be necessary.
• Class V (membranous lupus nephritis): Thickening of the glomerular basement membrane occurs. Blood and/or excess protein in the urine and high blood pressure are possible symptoms. As the condition progresses, dialysis or a kidney transplant may be required.
• Class VI (advanced sclerosing lupus nephritis): More than 90% of glomeruli are globally sclerosed, and patients may need dialysis or a kidney transplant to manage the condition.

The primary factors contributing to the development of lupus nephritis include:

• Autoimmune response: In SLE, the immune system produces autoantibodies that target and damage healthy tissues, including the kidneys. These autoantibodies can cause inflammation and scarring in the kidney's filtration units, called glomeruli, leading to impaired kidney function.
• Genetic predisposition: Certain genetic factors may increase an individual's susceptibility to developing SLE and, consequently, lupus nephritis.
• Environmental triggers: Exposure to certain environmental factors, such as ultraviolet light, infections, and certain medications, may trigger the onset of SLE and lupus nephritis in genetically susceptible individuals.
• Hormonal factors: SLE and lupus nephritis are more common in women, particularly during their reproductive years.
• Immune complex deposition: In lupus nephritis, immune complexes (combinations of autoantibodies and their target antigens) can accumulate in the kidneys, causing inflammation and damage to the glomeruli. This process can lead to impaired kidney function and the development of various symptoms associated with lupus nephritis.

If left untreated or inadequately managed, lupus nephritis can lead to several serious complications that can significantly impact your health and quality of life. Some of the potential complications include:

• Chronic kidney disease (CKD): Persistent inflammation and damage to the kidneys can cause scarring and loss of function over time, leading to chronic kidney disease. CKD can progress to end-stage kidney disease (ESKD) if not properly managed.
• End-stage kidney disease (ESKD): This is the most severe form of kidney damage, where the kidneys can no longer function adequately to sustain life. People with ESKD require dialysis or a kidney transplant to survive.
• Hypertension: Kidney damage can cause high blood pressure, which can further worsen kidney function and increase the risk of cardiovascular complications.
• Anaemia: Lupus nephritis can lead to decreased production of erythropoietin, a hormone that stimulates red blood cell production, resulting in anaemia.
• Increased risk of infections: Immunosuppressive medications used to treat lupus nephritis increase the risk of severe and life-threatening infections. Vaccination and infection prevention strategies are essential (Teoh, 2025).
• Cardiovascular disease: People with lupus nephritis have a higher risk of developing cardiovascular problems, such as heart attacks and strokes, due to the combined effects of inflammation, hypertension, and kidney dysfunction.
• Pregnancy complications: Lupus nephritis can increase the risk of complications during pregnancy, such as preeclampsia, preterm birth, and low birth weight.

Diagnosing lupus nephritis involves a combination of clinical evaluation, laboratory tests, and imaging studies to confirm the presence and extent of kidney involvement. Your doctor may perform the following tests:

• Clinical evaluation: Your doctor will assess your symptoms and medical history to identify signs of SLE and potential kidney involvement, such as oedema, hypertension, and systemic symptoms like joint pain, rash, and fever.
• Urine tests: These check for high levels of protein (proteinuria) and other abnormalities in your urine, which can indicate kidney damage. A urine albumin-creatinine ratio (uACR) test may be done to quantify the amount of albumin relative to creatinine in your urine. Microscopic examination of urine can reveal red blood cells, casts, and other signs of kidney involvement.
• Blood tests: An estimated glomerular filtration rate (eGFR) measures your kidney function by estimating how efficiently your kidneys filter waste from the blood. Anti-nuclear antibodies (ANA) and anti-dsDNA autoantibody tests can confirm autoimmune activity associated with lupus. Low complement levels (C3 and C4) often indicate active lupus nephritis.
• Kidney biopsy: This is the gold standard for diagnosing lupus nephritis. A small piece of kidney tissue is removed using a needle under ultrasound or CT scan guidance and examined by a pathologist to classify the disease and guide treatment. The biopsy helps classify lupus nephritis into six different classes based on the type, location, and extent of kidney damage, guiding treatment and prognosis.
• Imaging studies: A renal ultrasound may be done to rule out hydronephrosis or obstructive causes of kidney dysfunction.

Effective management of lupus nephritis aims to reduce kidney inflammation, suppress the immune response, preserve renal function, and prevent long-term complications. Treatment is typically divided into induction (to control active disease) and maintenance (to prevent relapse). Below is an overview of key therapeutic strategies.

1. Reducing Immune System Activity

Immunosuppressive medications are used to dampen the immune attack on kidney tissues.

• Mycophenolate mofetil: It inhibits purine synthesis in lymphocytes to reduce autoimmune activation.
• Cyclophosphamide: It alkylates DNA to suppress rapidly dividing immune cells involved in kidney inflammation.
• Azathioprine: It interferes with DNA replication in immune cells to maintain disease remission with lower toxicity.

These medicines help:

• Prevent further immune-mediated kidney damage
• Induce remission in moderate to severe cases
• Support long-term disease control with fewer flares

2. Controlling Inflammation

Corticosteroids are a cornerstone of treatment during active disease (flares) to quickly reduce inflammation.

• Prednisone: Suppresses cytokine production and immune cell activity to ease acute kidney inflammation.

Corticosteroids help:

• Control symptoms during active phases
• Reduce proteinuria and systemic flare signs
• Prevent irreversible kidney damage if started early

3. Targeted Biological Support

Biologic therapies are used when standard immunosuppressants are insufficient or poorly tolerated.

• Belimumab: A monoclonal antibody that inhibits B-lymphocyte stimulator (BLyS) to reduce autoantibody production.

4. Advanced Calcineurin Inhibitors

These are newer therapies that offer immune regulation with renal protection benefits.

• Voclosporin: Inhibits calcineurin to block T-cell activation and lower proteinuria while preserving glomerular function.

Voclosporin supports:

• Stabilisation of renal function with faster remission
• Reduction in urinary protein loss
• Safe combination with other immunosuppressants

5. Long-Term Disease Management

• Once remission is achieved, long-term maintenance typically involves continued immunosuppression (mycophenolate mofetil or azathioprine) for at least 3–5 years, with regular monitoring to prevent relapses and protect kidney health (American College of Rheumatology, 2025).

Lupus nephritis requires careful monitoring and management to prevent long-term damage to the kidneys. If you have been diagnosed with this condition, it is crucial to attend all scheduled appointments with your doctor and to undergo regular blood and urine tests to assess your kidney function (KDIGO, 2024). You may also need to make lifestyle changes, such as following a low-sodium diet, limiting protein intake only if advised by your doctor, and avoiding excessive protein intake if advised by your doctor, and avoiding certain medicines that can be harmful to the kidneys. Women with lupus nephritis who are pregnant or planning to become pregnant should work closely with their doctor to ensure the best possible outcomes for both mother and baby.

If you have been diagnosed with lupus nephritis, it is essential to consult with your doctor. You should promptly inform your doctor if you experience any new or worsening symptoms, such as increased swelling, weight gain, decreased urine output, or blood in the urine. These symptoms may indicate that your lupus nephritis is progressing or that you are developing complications. Additionally, if you have a fever, severe fatigue, or joint pain that is not well controlled with your current treatment plan, you should contact your doctor for further evaluation and management.

• Lupus nephritis is a serious complication of systemic lupus erythematosus (SLE) that occurs when lupus autoantibodies attack the kidneys, causing inflammation and damage.
• Symptoms of lupus nephritis may include swelling, foamy urine, high blood pressure, and decreased kidney function.
• Diagnosis of lupus nephritis involves blood tests, urine tests, and sometimes a kidney biopsy.
• Treatment for lupus nephritis depends on the class and severity of the disease and may include medicines to control inflammation, suppress the immune system, and manage symptoms.
• Regular monitoring and follow-up with a rheumatologist and nephrologist are essential for managing lupus nephritis and preventing complications.
• Maintaining a healthy lifestyle, staying up-to-date with vaccinations, and seeking support when needed are important considerations for people living with lupus nephritis.