Lupus Renal Disease Mortality Rates Dip

Apr 16, 2019

Mortality rates for white, African American and Hispanic patients with end stage lupus-related renal disease are down. The findings contradict a previous analysis conducted in 2006.

Mortality rates for white, African American and Hispanic patients with end stage lupus-related renal disease are down, shows a study published March 7 in Arthritis and Rheumatology. The findings contradict a previous analysis conducted in 2006. The authors attribute the improvement to improved management.

The first study looked at trends in death from lupus nephritis (LN)-related end stage renal disease (ESRD), over the last two decades in the U.S.

Researchers analyzed data from the national ESRD registry, which includes over 94 percent of patients on renal dialysis in the U.S.

The analysis included 20,974 individuals diagnosed with LN-related ESRD between January 1995 and December 2014. Included individuals had a mean age at ESRD diagnosis of 40 years, were 82 percent female and 48 percent African American. Results were adjusted for age, sex, BMI, smoking, medical comorbidities, geographic region, and initial treatment for ESRD.

Mortality from lupus nephritis-related ESRD remained about the same between 1995-2004, and decreased significantly between 2005-2014 (P for trend < 0.01).  Comparing 2010-2014 to 1995-1999, mortality from LN-related ESRD decreased by 32% (HR 0.68 (95% CI 0.58–0.78). 

While African Americans are at increased risk for death from LN-associated ESRD,3 this study found that improvements in death rates occurred across racial/ethnic groups.  For 2005-2014 compared to 1995-2004, risk of death declined by 33% among African Americans (HR 0.67 (95% CI 0.57–0.78), by 49% among Hispanics  (HR 0.51 (95% CI 0.38–0.69) and by 38% among whites (HR 0.62, 95% CI 0.53-0.72) (P for trend < 0.01 for all).

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The leading cause of death was CVD followed by infection, both of which also declined. For 2010-2014 compared to 1995-1999, death from CVD decreased by 44% (HR 0.56 [95% CI 0.48–0.67]) and death from infection decreased by 63% (HR 0.37 [95% CI 0.29–0.47]; P for trend < 0.01 for both).

“This improved survival among patients with ESRD due to LN may be explained by a combination of improvements in the management of ESRD and of underlying SLE,” wrote first author April Jorge, M.D., of Harvard Medical School, and colleagues.

“Collectively, these trends provide an important benchmark of improving care in this high-risk population,“ they added.

However, the study could not analyze the impact of lupus disease activity and treatment on survival.

To test whether decreased disease activity―presumably by improving care―can improve outcomes in lupus, another group of researchers analyzed data from the Tromsø Lupus Cohort, a longitudinal study of individuals with lupus who live in the two northern-most counties in Norway. The cohort was mostly Caucasian females, with a median follow up of 125 months.

In the study, researchers used the Lupus Low Disease Activity State (LLDAS) to evaluate patients who were able to achieve low disease activity.  The LLDAS is defined as:5
• “SLEDAI-2K ≤4 [an indication of low disease activity], with no activity in major organ systems
• No new features of lupus disease activity
• SELENA-SLEDAI physician global assessment (PGA, scale 0–3) ≤1 [an indication of low disease activity]
• Current prednisolone (or equivalent) dose ≤7.5 mg daily
• Well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents”

About 34% of the cohort achieved LLDAS over 50% of the time and were considered to have achieved LLDAS-50.

Analyses adjusted for age and sex showed that patients who achieved LLDAS-50 had 63% lower risk of severe organ damage (HR 0.37; 95%CI 0.19 – 0.73, p < 0.01), and 69% lower risk of death (HR 0.31; 95%CI 0.16 – 0.62, p < 0.01), compared to those who did not achieve LLDAS-50.

Results confirm past studies suggesting less organ damage in patients who achieve low disease activity.  But the findings go beyond past studies by being the first to suggest that achieving low disease activity may actually decrease the risk of death.

“The most significant finding is that for the first time a reduction in mortality has been demonstrated for those patients with SLE who achieve a low disease activity state,” wrote first author Chanakya Sharma, MB BS, FRACP, of Sir Charles Gairdner Hospital in Perth, Australia and colleagues.

REFERENCES
Jorge A, Wallace ZS, Zhang Y, et al. All-Cause and Cause-Specific Mortality Trends of End-Stage Renal Disease Due to Lupus Nephritis From 1995 to 2014. Arthritis Rheumatol. 2019 Mar;71(3):403-410. doi: 10.1002/art.40729
Costenbader KH, Desai A, Alarcón GS, et al. Trends in the incidence, demographics, and outcomes of end-stage renal disease due to lupus nephritis in the US from 1995 to 2006. Arthritis Rheum. 2011 Jun;63(6):1681-8. doi: 10.1002/art.30293

Sule S, Fivush B, Neu A, et al. Increased risk of death in African American patients with end-stage renal disease secondary to lupus. Clin Kidney J 2014;7:40–4.

Sharma C, Raymond W, Eilertsen G, et al. Achieving Lupus Low Disease Activity State (LLDAS-50) is associated with both reduced damage accrual and mortality in patients with Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). 2019 Mar 1. doi: 10.1002/acr.23867

Franklyn K, Lau CS, Navarra SV, , et al. Definition and initial validation of a Lupus Low Disease Activity State (LLDAS). Annals of the Rheumatic Diseases. 2016;75(9):1615-21.

Zen M, Iaccarino L, Gatto M, Saccon F, Larosa M, Ghirardello A, et al. Lupus low disease activity state is associated with a decrease in damage progression in Caucasian patients with SLE, but overlaps with remission. Annals of the rheumatic diseases. 2018;77(1):104-110

Tsang ASMW, Bultink IE, Heslinga M, et al. Both prolonged remission and Lupus Low Disease Activity State are associated with reduced damage accrual in systemic lupus erythematosus. Rheumatology (Oxford, England). 2017;56(1):121-8.

Ugarte-Gil MF, Wojdyla D, Pons-Estel GJ, Catoggio LJ, Drenkard C, Sarano J, et al. Remission and Low Disease Activity Status (LDAS) protect lupus patients from damage occurrence: data from a multiethnic, multinational Latin American Lupus Cohort (GLADEL). Annals of the Rheumatic diseases. 2017;76(12):2071-4

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