Lupus Nephritis

Lupus Nephritis Is Among the Most Severe and Dangerous Complications of Systematic Lupus Erythematosus

Systematic lupus erythematosus (SLE), commonly known as lupus, is a chronic autoimmune disease where the body's immune system mistakenly attacks its own healthy tissues and organs. Over 200,000 people in the United States are estimated to have SLE, ^a of which 20% to 60% develop lupus nephritis (LN). ^b

Infographic titled “LN Affects Up to 120,000 People in the U.S.” showing information about Lupus Nephritis (LN), a condition caused by the immune system attacking the kidneys. On the left, a diagram of the human body highlights affected systems: skin (malar/discoid rash), CNS (neurological damage, affective disorder), lungs (inflammation), blood (anemia, thrombocytopenia, IFN signature), serum (anti-nuclear antibodies), spleen (splenomegaly), joints (arthritis), and kidneys (glomerulonephritis). On the right, four key facts are listed:

LN occurs when the immune system attacks the kidneys.
SLE/LN disproportionately affects women and people of color.
Measuring proteinuria (protein in the urine) is critical for monitoring disease activity and therapy response.
Inflammation causes blood and protein in urine, impaired kidney function, and potential kidney failure.

^aU.S. Centers for Disease Control and Prevention 2024
‍^b KDIGO Lupus Nephritis Work Group, Kidney Int 2024
‍^c Tamirou et al., Ann Rheum Dis 2016

Proteinuria Is a Significant Risk Factor for Kidney Damage

Kidney damage from LN can be progressive and is associated with long-term adverse outcomes. Nearly 90% of patients with proteinuria <0.5 g/day have been reported to have class III, IV, or V (alone or in combination with class III or IV) on biopsy.

Bar chart titled “LN Class by Proteinuria in Patients with SLE.” The chart compares the percentage of patients with different classes of Lupus Nephritis (LN) based on their proteinuria level at the time of kidney biopsy. The x-axis shows two proteinuria groups:

"<0.5 g/day (n=46)"
"≥0.5 g/day (n=176)"
The y-axis represents the percentage of patients (0% to 100%).

For the <0.5 g/day group:

10.9% had LN class II (blue bar)
89.1% had LN class III, IV, or V (orange bar)
For the ≥0.5 g/day group:

0% had LN class II (blue bar)
99.4% had LN class III, IV, or V (orange bar)
The legend indicates that blue represents class II, and orange represents classes III, IV, or V (alone or in combination with III/IV). The data suggest that higher proteinuria levels are strongly associated with more severe LN classes.

^aDe Rosa et al., Kidney Int Rep. 2020

Even a Single Flare of LN Can Cause Irreversible Nephron Loss, Which Can Potentially Shorten the Lifespan of the Kidneys by Decades

Nephron loss and podocyte damage often lead to loss of kidney function as measured by glomerular filtration rate and proteinuria.

Line graph titled “Even a Single Flare of LN Can Reduce the Lifespan of the Kidney.”
The x-axis shows age in years (0 to 100), and the y-axis shows glomerular filtration rate (GFR) in mL/min (0 to 140), with chronic kidney disease (CKD) stages 1 to 5 indicated on the right.

Three lines are shown:

Orange line with squares – labeled “Gradual podocyte and nephron loss with aging.” GFR gradually declines from 120 mL/min at age 20 to about 60 mL/min by age 100.
Blue line with circles – labeled “Nephron loss with a single LN episode.” GFR drops sharply to ~70 mL/min by age 20, then declines steadily to reach kidney failure (0 mL/min) by age 100.
Purple line with circles – labeled “Nephron loss with ongoing LN.” GFR drops rapidly to ~65 mL/min by age 20 and reaches 0 mL/min by around age 60, indicating earlier kidney failure.
The graph illustrates that even one flare of Lupus Nephritis (LN) can shorten kidney function lifespan, and ongoing LN causes more rapid decline compared to normal aging.

CKD=chronic kidney disease; GFR=glomerular filtration rate
‍^aAdapted with permission from Anders et al., Nat Rev Dis Primers 2020

Proteinuria Reduction Is Associated with Long-Term Renal Protection

The larger the initial reduction in proteinuria in the first several months of management, the lower the risk of end-stage kidney disease.

Kaplan-Meier survival curve titled “Kidney Survival Based on Proteinuria Response Status.”
The x-axis shows time from study entry in months (0 to 200), and the y-axis shows kidney survival percentage (0% to 100%).

Three survival curves are displayed:

Teal line – labeled “Complete Response”: Shows consistently high kidney survival over time, ending with 94% survival at 10 years.
Blue line – labeled “Partial Response”: Shows a gradual decline in kidney survival, with 45% survival at 10 years.
Light purple line – labeled “No Response”: Shows a steep decline in kidney survival, with 19% survival at 10 years.
Three orange circles highlight the 10-year kidney survival rates for each group:

94% for complete response
45% for partial response
19% for no response
The graph demonstrates a strong correlation between proteinuria response and long-term kidney survival, with better outcomes in patients who achieve a complete response.

^a Adapted with permission from Chen et al., Clin J Am Soc Nephro 2008
‍^b Retrospective analysis of patients (N=86) enrolled in the prospective, controlled study of plasmapheresis in severe LN to determine long-term prognosis of achieving partial response. Complete response was defined as SCr ≤1.4 mg/dL and proteinuria ≤0.33 g/day within 5 years of study entry, and partial response was defined as ≤25% increase in baseline SCr and ≥50% reduction in baseline proteinuria to ≤1.5 g/day (but >0.33 g/day) within 5 years of entering the study. Kidney survival was determined by kidney failure (≥6 mg/dL SCr or the initiation of kidney replacement therapy).