Proliferative lupus nephritis is a form of kidney disease that occurs as a complication of systemic lupus erythematosus (SLE). This condition involves inflammation in the small blood vessels of the kidneys that filter waste from the blood. The immune-driven damage causes an abnormal increase in cells within these filtering units, which defines the “proliferative” nature of the disease and disrupts kidney function.
The Pathophysiology of Proliferative Lupus Nephritis
The underlying cause of proliferative lupus nephritis is a misdirected immune response. The body produces autoantibodies that mistakenly target its own nuclear antigens, particularly DNA. These autoantibodies bind with the antigens to form immune complexes, which are small particles that circulate in the bloodstream. In SLE, they are produced in such large quantities that they become trapped in various tissues.
When these immune complexes deposit in the glomeruli—the filtering structures within the kidneys—they initiate an inflammatory cascade. This process incites the rapid multiplication of cells within the glomeruli, which obstructs filtration and can lead to scarring. This pattern of damage corresponds to Class III (focal) and Class IV (diffuse) lupus nephritis under the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification, with Class IV being the more severe form affecting over half of the glomeruli.
Signs and Symptoms
A common symptom is edema, or swelling, in the legs, ankles, feet, and sometimes the face or hands. This occurs when damaged kidneys leak large amounts of protein into the urine (proteinuria), causing fluid to shift from the blood into body tissues.
Another frequent sign is a noticeable change in the urine. High levels of protein can cause urine to appear foamy, while inflammation can allow red blood cells to pass into the urine, a condition called hematuria. This may be visible as pink, red, or cola-colored urine, or may only be detectable under a microscope. These renal symptoms are often accompanied by high blood pressure.
Because proliferative lupus nephritis is a manifestation of systemic lupus, patients may also experience general symptoms of an active SLE flare. These can include persistent fatigue, fever, joint pain and swelling, and rashes, particularly the characteristic butterfly-shaped rash across the face. The presence of these systemic symptoms alongside kidney-specific signs can indicate widespread lupus activity.
Diagnostic Process
The diagnostic process begins with laboratory tests. A urinalysis is used to detect protein and red blood cells in the urine, which indicate kidney inflammation. Blood tests assess kidney function by measuring waste products like creatinine and calculating the estimated glomerular filtration rate (eGFR), a measure of how well the kidneys are cleaning the blood.
In addition to assessing kidney function, blood tests identify specific autoantibodies associated with SLE. High levels of anti-double-stranded DNA (anti-dsDNA) antibodies are particularly linked to lupus nephritis and can indicate active disease. Low levels of complement proteins (C3 and C4) in the blood can also suggest that the immune system is overactive.
While blood and urine tests suggest lupus nephritis, a kidney biopsy provides a conclusive diagnosis. During a biopsy, a small sample of kidney tissue is removed with a needle and examined under a microscope. This examination allows pathologists to visualize immune complex deposits, confirm cellular proliferation, and assess the extent of inflammation and scarring, which informs the treatment strategy.
Treatment Approaches
The primary goals of treating proliferative lupus nephritis are to suppress the autoimmune response, reduce kidney inflammation, and prevent the progression of kidney damage. Treatment is structured in two phases: an initial “induction” phase, followed by a longer-term “maintenance” phase. This approach is designed to bring the disease under control and then keep it in remission.
The induction phase aims to halt acute inflammation. This involves high doses of corticosteroids, like prednisone, combined with an immunosuppressive drug. Common choices for this therapy include mycophenolate mofetil (MMF) or cyclophosphamide, which is reserved for more severe cases.
Once the initial inflammation is controlled, the patient transitions to the maintenance phase to prevent the disease from flaring up again. This often involves continuing on a lower dose of MMF or switching to a different immunosuppressant like azathioprine. Newer biologic drugs that target specific components of the immune system may also be considered in cases that are difficult to treat.
Long-Term Management and Outlook
Long-term management focuses on preserving kidney function and preventing relapses. This requires continuous monitoring through regular blood and urine tests to check for returning inflammation. Adherence to prescribed maintenance medications is foundational to long-term success, as stopping them can lead to a flare-up.
Supportive care is another important aspect of long-term management. Controlling blood pressure is a priority, often requiring medications like angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs). These drugs not only lower blood pressure but also help reduce protein loss in the urine. Dietary modifications, such as a low-sodium diet, can also help manage blood pressure and fluid retention.
With modern therapeutic strategies, the outlook for patients with proliferative lupus nephritis has improved. The primary goal is to achieve and maintain remission, thereby preventing the progression to end-stage renal disease (ESRD), which would require dialysis or a kidney transplant. Consistent medical care and patient adherence to treatment plans allow many individuals to maintain stable kidney function.