Lupus nephritis is a severe complication of systemic lupus erythematosus (SLE), characterized by kidney inflammation. SLE is a chronic autoimmune disease where the body’s immune system mistakenly attacks its own healthy tissues and organs. Understanding its pathophysiology is important for comprehending how lupus impacts kidney function and the progression of kidney damage.
Understanding Systemic Lupus Erythematosus
Systemic lupus erythematosus is an autoimmune condition where the body’s natural defense system turns against its own healthy cells. This occurs because the immune system becomes overactive and produces proteins called autoantibodies. These autoantibodies mistakenly target the body’s own components, leading to inflammation and damage in various parts of the body.
Lupus is referred to as “systemic” because it can affect multiple organs and tissues throughout the body, including the skin, joints, blood, heart, lungs, brain, and kidneys. The production of autoantibodies is a hallmark of lupus, central to its development and diverse clinical manifestations. Antinuclear antibodies (ANAs), which target components within the cell’s nucleus, are found in nearly all individuals with lupus.
Among autoantibodies, anti-double-stranded DNA (anti-dsDNA) antibodies are particularly significant in lupus and often associated with kidney involvement. These antibodies recognize double-stranded DNA within the body’s cells. Their presence and levels can fluctuate with disease activity, making them important markers.
How Lupus Attacks the Kidneys
Lupus damages kidneys through a complex interplay of immune components. A primary pathway involves immune complex formation and deposition within the kidney’s filtering units, glomeruli. Autoantibodies, particularly anti-dsDNA antibodies, bind to self-antigens (e.g., DNA from dying cells) to create immune complexes. These complexes circulate and become trapped in the glomeruli.
Once deposited, these immune complexes trigger an inflammatory response. They activate the complement system, releasing inflammatory molecules (e.g., C3a, C5a) that recruit immune cells.
Recruited inflammatory cells (e.g., macrophages, lymphocytes) intensify kidney damage by releasing cytokines (e.g., IL-1, IL-6, TNF). This sustained presence of immune cells and mediators directly harms glomerular cells, impairing blood filtration.
Beyond immune complex deposition, anti-dsDNA antibodies can directly interact with kidney cells and extracellular matrix components. This binding triggers cellular activation, contributing to inflammatory and fibrotic processes. For instance, they may bind to proteins on mesangial cells, leading to inflammation and scarring. This combined assault drives lupus nephritis kidney injury.
The Progression of Kidney Injury
Chronic inflammation and immune attack lead to structural changes within the kidneys. Persistent inflammation results in scarring (fibrosis) within the glomeruli (glomerulosclerosis) and surrounding kidney tissue (tubulointerstitium). This irreversible tissue damage replaces normal kidney parenchyma with non-functional connective tissue, a maladaptive response to prolonged injury.
These structural changes impair the kidney’s filtering functions. Damaged glomeruli become less efficient at removing waste products and may allow essential proteins to leak into the urine. This leakage, known as proteinuria, is a characteristic feature of lupus nephritis and indicates glomerular damage. Some individuals may also experience hematuria (blood in urine) due to damaged filtration barriers.
As kidney damage progresses, the glomerular filtration rate (GFR), a measure of kidney filtering efficiency, declines. A reduced GFR indicates the kidneys are losing their ability to clear waste. Unchecked damage can lead to end-stage kidney disease (ESKD), where kidneys no longer function. At this stage, dialysis or a kidney transplant is required.