Patients with Lupus Nephritis are Losing More Than Time Patients with Lupus Nephritis are Losing More Than Time

Lupus nephritis occurs in up to 45% of patients with SLE. Clinical signs may be subtle or silent despite significant damage to the kidneys.1-6

Patients with lupus nephritis are at risk of nephron loss, kidney failure, and premature death. Early diagnosis and treatment are essential to improving outcomes.6-10

Evidence shows that even a single episode of LN can potentially shorten the life span of the kidneys by decades7

Subsequent episodes can cause cumulative damage, further shortening kidney survival7,10

Implied Risk of Nephron Loss in People With LN Over a Lifetime7
Implied Risk of Nephron Loss

Reprinted by permission from Copyright Clearance Center: Nature, Nat Rev Dis Primers, Lupus nephritis, Anders HJ, et al, 2020.

Patients with SLE who have LN are at greater risk for kidney failure and premature death than patients without LN6

In an analysis of patients with SLE, patients with LN had6*:

45x Greater Risk of Kidney Failure
3x Greater Risk of Premature Death

*Adjusting for gender, age at enrollment, and race/ethnicity, a Cox regression analysis on the competing risks of kidney failure and death, with the diagnosis of LN used to define a time-dependent covariate.

CV complications contribute to increased mortality in patients with LN11

In a study of 1644 patients with SLE, LN was associated with an approximately 5x greater risk of CV-related death11

Delayed Diagnosis Can Have Severe Consequences

Delayed diagnosis can have severe consequences12

  • Kidney biopsy is the standard of care for confirming a lupus nephritis diagnosis and should be performed when routine screening reveals any suspected signs of the disease7,10
A kidney biopsy delay longer than 6 months was associated with a
Delayed Kidney Biopsy is Associated With Risk of Kidney Failure
greater risk of progression to kidney failure12
 
Up to 45% of Patients with SLE May Develop LN
35% of Patients May Already Have LN at the Time of SLE Diagnosis

Though LN may occur in any patient with SLE, the risk is higher in6:
• Those with Black, Asian, and Hispanic ancestry
• Younger adults
• Males

LN can shorten kidney survival, and delayed diagnosis increases risk7,12

 

CKD=chronic kidney disease; CV=cardiovascular; GFR=glomerular filtration rate; LN=lupus nephritis; MI=myocardial infarction; SLE=systemic lupus erythematosus.

active
surveillance

The key to good outcomes is active surveillance to identify and diagnose LN early

Early Detection and Diagnosis Require Active Surveillance

LN is not always clinically obvious—early detection and diagnosis require active surveillance1-3

  • Signs of LN can be subtle: presentation ranges from no symptoms to minor laboratory changes and nephrotic-range proteinuria2
  • Even patients with minor proteinuria may have significant disease4
The 2019 EULAR/ERA-EDTA guidelines for LN recommend rigorous testing in patients at risk of kidney involvement1,5
Active Surveillance for LN in Patients with SLE
Active surveillance for LN in patients with SLE
At least every 3 months in those with high risk* of kidney involvement
Criteria for Kidney Biopsy
Criteria for kidney biopsy
  • Proteinuria ≥0.5 g/24 hr
  • Glomerular hematuria and/or cellular casts
  • Unexplained decrease in GFR
Kidney Biopsy is Recommended for Classification and Treatment
Kidney biopsy
Recommended for classification and treatment

*Males, juvenile lupus onset, serologically active disease.5

Early diagnosis of LN can improve outcomes. However, too few patients are being screened as recommended6,7

• Only 42% of patients were tested for LN every 6 months

• Only 67% of patients received kidney biopsy within 1 year of suspected LN

Urinalysis, UPCR, and SCr.
Study evaluated 250 participants across a variety of clinical settings enrolled in the California Lupus Epidemiology Study (CLUES), with the goal of identifying gaps in quality of care for screening, diagnosing, and treating LN.7

The 2019 EULAR/ERA-EDTA guidelines for LN emphasize the importance of active surveillance to identify and treat LN early1,5

The 2019 EULAR/ERA-EDTA Guidelines for LN Recommend More Frequent Screening in Populations at Higher Risk and Expand Criteria for Biopsies as Compared With the 2012 ACR Guidelines1,5,8

Screening and Diagnosis
 
ACR 2012
  • Every 6 months
  • Proteinuria ≥1.0 g/24 hr
  • Proteinuria ≥0.5 g/24 hr and hematuria or cellular cast
  • Unexplained increase in serum creatinine
  • Recommended for classification and treatment
EULAR/
ERA-EDTA 2019
  • At least every 3 months in those with high risk of kidney involvement
  • Proteinuria ≥0.5 g/24 hr
  • Glomerular hematuria and/or cellular cast
  • Unexplained decrease in GFR
  • Recommended for classification and treatment
Monitoring for LN in patients with SLE
  • Every 6 months
  • At least every 3 months in those with high risk of kidney involvement
Criteria for kidney biopsy
  • Proteinuria ≥1.0 g/24 hr
  • Proteinuria ≥0.5 g/24 hr and hematuria or cellular cast
  • Unexplained increase in serum creatinine
  • Proteinuria ≥0.5 g/24 hr
  • Glomerular hematuria and/or cellular cast
  • Unexplained decrease in GFR
Kidney biopsy
  • Recommended for classification and treatment
  • Recommended for classification and treatment

The 2019 EULAR/ERA-EDTA guidelines for LN emphasize reducing the cumulative glucocorticoid dose to reduce the risk of end-organ damage5

View the guidelines for screening and diagnosing your patients:
2012 ACR guidelines
2019 EULAR/ERA-EDTA guidelines

Better outcomes for patients with LN start with active surveillance and early diagnosis1,5

ACR=American College of Rheumatology; ERA-EDTA=European Renal Association-European Dialysis and Transplant Association; EULAR=European League Against Rheumatism; GFR=glomerular filtration rate; LN=lupus nephritis; SCr=serum creatinine; SLE=systemic lupus erythematosus; UPCR=urine protein-to-creatinine ratio.

Clinical
Response

Recent guidelines encourage an immediate proteinuria reduction

Recent guidelines provide definitive treatment targets to optimize outcomes1

Target Proteinuria Decrease of1*
EULAR/ERA-EDTA 2019 Proteinuria Decrease Targets EULAR/ERA-EDTA 2019 Proteinuria Decrease Targets

*Patients with nephrotic-range proteinuria at baseline may require an additional 6 to 12 months of treatment to reach complete clinical response; in such cases, prompt switches of therapy are not necessary if proteinuria is improving.2

Early Decreases in Proteinuria Levels are Highly Predictive of Better Long-term Outcomes

Early decreases in proteinuria levels are highly predictive of better long-term outcomes2

  • The predictive value of good outcomes with proteinuria decreases of ≤0.5 g/day at 3 months was 89%
  • Proteinuria levels of >0.5 g/day at 3 months were predictive of poor outcomes

In a retrospective analysis, 10-year patient and kidney survival were significantly better in patients who achieved complete response (P<0.0001)3

Partial response also improved outcomes

Patient Survival Based on Response Status
Kidney Survival Based on Response Status
Kidney Survival Based on Response Status
Kidney Survival Based on Response Status

Reprinted by permission from Copyright Clearance Center: American Society of Nephrology, Clin J Am Soc Nephrol, Value of a complete or partial remission in severe lupus nephritis, Chen YE, et al, 2008.

The 2019 EULAR/ERA-EDTA guidelines for LN emphasize the importance of active surveillance to identify and treat LN early1,4

The 2019 EULAR/ERA-EDTA Guidelines for LN Recommend Specific Treatment Targets as Compared With the 2012 ACR Guidelines1,4,5

Treatment Targets
 
ACR 2012
Treatment Targets
Not defined:
  • Response is determined by physician’s own judgment and clinical impression
EULAR/
ERA-EDTA 2019
Treatment Targets
Proteinuria decrease:
  • At least 25% by 3 months
  • At least 50% by 6 months
  • UPCR target below 0.5 to 0.7 mg/mg by 12 months
Treatment Targets
Not defined:
  • Response is determined by physician’s own judgment and clinical impression
Proteinuria decrease:
  • At least 25% by 3 months
  • At least 50% by 6 months
  • UPCR target below 0.5 to 0.7 mg/mg by 12 months

The 2019 EULAR/ERA-EDTA guidelines for LN emphasize reducing the cumulative glucocorticoid dose to reduce the risk of end-organ damage4

View the guidelines for treatment targets your patients:
2012 ACR guidelines
2019 EULAR/ERA-EDTA guidelines

ACR=American College of Rheumatology; AZA=azathioprine; BL=baseline; CR=complete response; CYC=cyclophosphamide; ERA-EDTA=European Renal Association‐European Dialysis and Transplant Association; EULAR=European League Against Rheumatism; GFR=glomerular filtration rate; IV=intravenous; LN=lupus nephritis; MMF=mycophenolate mofetil; NR=no response; PR=partial response; SCr=serum creatinine; SLE=systemic lupus erythematosus; UPCR=urine protein‐to‐creatinine ratio.

Achieving early decreases in proteinuria can improve outcomes2

Improving the
Outlook For LN

Register for important updates on LN

Even though LN is a challenging disease that can potentially shorten kidney life span and patients’ lives, significant progress over the past decade has led to a greater understanding of the disease and better ways to manage it.

The quest to improve the outlook for LN is ongoing. Research is focused on improving diagnostic and monitoring methods, and elucidating the pathophysiology of LN—all with the goal of diagnosing LN early, minimizing impact on kidney function, and improving long-term outcomes for every patient with LN.1



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Support for your patients: ALL IN™ for LN

To help support your patients with SLE with LN, ALL IN provides disease education, personal stories, helpful resources, and a way to connect to the LN community. Your patients can connect by visiting
allinforlupusnephritis.com.

LN=lupus nephritis; SLE=systemic lupus erythematosus.

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