Lupus Nephritis - Causes, Symptoms and Treatment

What is Lupus Nephritis?

Lupus nephritis is an inflammation of the kidneys caused by the autoimmune disease systemic lupus erythematosus (SLE). In SLE, the immune system mistakenly attacks the body's own tissues. When this attack targets the kidneys, it leads to lupus nephritis -- a progressive kidney disorder that can result in permanent damage or kidney failure. Approximately 40 to 60 percent of all SLE patients develop lupus nephritis at some point during their illness.

Causes

Lupus nephritis is caused by the deposition of immune complexes -- aggregates of antibodies and antigens produced in excess during SLE -- within the kidney's filtering units, known as glomeruli. These deposits trigger an inflammatory response that damages the delicate filtration tissue of the kidneys.

• Genetic factors: Certain gene variants increase the risk of developing SLE and its complications, including lupus nephritis.
• Hormonal influences: Women of childbearing age are disproportionately affected, suggesting a role for estrogens in disease susceptibility.
• Environmental triggers: UV radiation, infections, and certain medications can trigger or worsen SLE and related complications.

Symptoms

The symptoms of lupus nephritis often develop gradually and may go unnoticed for some time. Common signs include:

• Protein in the urine (proteinuria): Damaged kidneys can no longer retain protein, which then leaks into the urine. Foamy urine may be an early indicator.
• Blood in the urine (hematuria): Red blood cells pass through the damaged kidney barrier into the urine.
• Fluid retention (edema): Swelling commonly occurs in the legs, ankles, and around the eyes.
• High blood pressure (hypertension): Damaged kidneys lose their ability to regulate blood pressure effectively.
• Elevated creatinine levels: A rise in blood creatinine signals reduced kidney function.
• General SLE symptoms: Some patients also experience joint pain, skin rashes (e.g., the characteristic butterfly rash), or fatigue.

Diagnosis

Diagnosing lupus nephritis requires a combination of clinical evaluation, laboratory testing, and kidney biopsy.

• Urinalysis: Detection of protein, red blood cells, or cellular casts in the urine.
• Blood tests: Measurement of creatinine, complement levels (C3, C4), anti-double-stranded DNA antibodies (anti-dsDNA), and other autoantibodies.
• Kidney biopsy: Removal of a small kidney tissue sample is the gold standard for diagnosis. It enables precise classification of lupus nephritis according to the ISN/RPS classification system (Classes I through VI), which is essential for treatment planning.
• Imaging: Ultrasound examination of the kidneys to assess size and structure.

Classification

Lupus nephritis is classified according to the internationally recognized ISN/RPS classification into six classes:

• Class I: Minimal mesangial lupus nephritis
• Class II: Mesangial proliferative lupus nephritis
• Class III: Focal lupus nephritis
• Class IV: Diffuse lupus nephritis (the most severe and most common form)
• Class V: Membranous lupus nephritis
• Class VI: Advanced sclerosing lupus nephritis

Treatment

Treatment of lupus nephritis aims to suppress the overactive immune response, preserve kidney function, and prevent flares. Therapy is tailored to the severity and class of the disease.

Induction Therapy

During the acute phase, intensive treatment is initiated to rapidly control inflammation:

• Corticosteroids (e.g., prednisolone): Given at high doses to quickly suppress inflammation.
• Mycophenolate mofetil (MMF): An immunosuppressant that inhibits immune cell production and is now the preferred first-line agent in many guidelines.
• Cyclophosphamide: A potent immunosuppressant used in severe cases.
• Voclosporin or belimumab: Newer agents that can be combined with standard therapies for enhanced efficacy.

Maintenance Therapy

Once the acute flare is controlled, long-term therapy is initiated to prevent relapse:

• Hydroxychloroquine: An antimalarial drug that reduces long-term disease activity in SLE and is routinely recommended for all SLE patients.
• Mycophenolate mofetil or azathioprine: Used as immunosuppressive maintenance therapy.
• ACE inhibitors or ARBs: To control blood pressure and reduce proteinuria.

Advanced Kidney Failure

In cases of severe kidney damage, dialysis or, in end-stage disease, a kidney transplant may become necessary.

Prognosis and Outlook

The course of lupus nephritis varies greatly between individuals. With modern treatment, many patients achieve complete or partial remission. However, a proportion of patients remain at risk of developing chronic kidney failure. Regular monitoring of kidney function, blood pressure, and laboratory parameters is therefore essential. Early diagnosis and consistent treatment significantly improve long-term outcomes.

References

1. Fanouriakis A. et al. - 2019 Update of the Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of lupus nephritis. Annals of the Rheumatic Diseases, 2019.
2. Bajema IM. et al. - Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney International, 2018.
3. Fanouriakis A. et al. - 2024 Update of the EULAR recommendations for the management of systemic lupus erythematosus. Annals of the Rheumatic Diseases, 2024.