Introduction: Systemic lupus erythematosus (SLE) is associated with multiple morbidities and premature mortality. Lupus nephritis (LN) affects ~50% of adults with SLE, and despite the introduction of improved, lower-toxicity treatments in the past 15 years, including mycophenolate and low-dose cyclophosphamide regimens (6–8), up to 30% of patients with LN develop end-stage renal disease (ESRD). Mortality among patients with SLE is highest among this subgroup. Compared with white patients, African American patients with ESRD due to LN have increased mortality, mediated in part by socioeconomic factors.
Objective: A prior study found that premature mortality among patients with ESRD due to LN persisted in the U.S. between 1995 and 2006. The present study was undertaken to extend this analysis through 2014 to examine more recent trends, including key cause-specific mortality trends.
Methods: Using the national registry of patients with ESRD, Jorge et al. identified all patients with incident ESRD due to LN between Jan. 1, 1995, and Dec. 31, 2014, divided into four 5-year cohorts of ESRD onset by calendar year (1995–1999, 2000–2004, 2005–2009, 2010–2014). They assessed mortality within each cohort. Temporal trends in all-cause mortality and cause-specific mortality were examined, adjusting for covariates.
Results: Jorge et al. identified 20,974 individuals with incident ESRD due to LN from 1995 through 2014. Mortality trends. A total of 4,131 patients with ESRD due to LN died during study follow-up (19.7%). The mortality rate per 100 patient-years declined from 11.1 (95% confidence interval [95% CI] 10.4–11.8) in 1995–1999 to 6.7 (95% CI 6.2–7.2) in 2010–2014 (P for trend <0.01). Adjusted mortality hazard ratios in 2010–2014, compared with 1995–1999, were 0.68 (95% CI 0.58–0.78) for white patients, 0.67 (95% CI 0.57–0.78) for African American patients, and 0.51 (95% CI 0.38–0.69) for Hispanic patients. Deaths from cardiovascular disease (CVD) and infection declined by 44% and 63%, respectively, from 1995–1999 to 2010–2014 (P for trend <0.01 for both).
Discussion: In this study of nearly all patients with incident ESRD due to LN in the U.S. over the past two decades, Jorge et al. observed a 32% reduction in mortality. These findings expanded on those in previous studies that showed no change in mortality rates from 1995 to 2006 and nonsignificant improvement from 1995 to 2010 among patients with incident LN-associated ESRD in the U.S. Similarly, they discovered a stable trend among patients with ESRD due to LN during the first 10 years (1995–2004). However, a clear trend of improvement in mortality emerged across the latest decade (2005–2014).
These trends persisted after adjusting for age, sex, BMI, smoking status, comorbidities and other potential confounders across the subcohorts. They observed a similar improved mortality rate among African American, Hispanic and white patients.
Finally, they observed a 44% lower risk of cardiovascular deaths and 63% lower risk of infection-related deaths during the study period, contributing to the declining overall mortality trend.
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.
Conclusion: In the more recent years of the period 1995–2014, there was a considerable reduction in all-cause mortality among white, African American and Hispanic patients, with reduced risk of death from CVD and infection. Collectively, these trends provide an important benchmark of improving care in this high-risk population.
Excerpted and adapted from:
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 March;71(3):403–410.