Background Kidney involvement is common in lupus. Lupus and kidney diseases incur poor outcomes in people from racial/ethnic minority groups. Previous studies have utilized the national registry of patients with end-stage renal disease (ESRD) to examine mortality in lupus nephritis. However, the ESRD database may not have lupus nephritis patients who may have died of infections or other complications prior to developing ESRD. There are a few population-based studies, but they are limited to small regions with a small sample size. There are no nationwide population-based studies on causes of death in all, unselected, patients with lupus nephritis across the entire U.S. population.

Objective Assess the impact of demographic and geographic determinants on lupus nephritis mortality.

Methods We performed an ecologic study using United States population-based data from the Center for Disease Control and Prevention using Multiple-Cause-of-Death datafiles. We obtained data on lupus nephritis deaths using ICD-10 codes for SLE + a renal condition that could occur in patients with SLE, overall and by sex, three age groups, four census regions, six urban-rural codes, and 5 race/ethnic groups. We calculated age- standardized mortality rate (ASMR), and performed logistic regression analysis including interactions to assess any effect modification.

Results From 1999 through 2019, 8,899 deaths were attributed to lupus nephritis. The top 10 underlying cause of death recorded among 8,899 lupus nephritis deaths were SLE (62.5%), ischemic heart disease (9.7%), kidney conditions (5.5%), infections (3.3%), neoplasms (2.2%), cerebrovascular disease (1.4%), diabetes mellitus without organ complications (1.0%), chronic lower respiratory disease (0.9%), accidents/poisoning (0.8%), and chronic liver disease (0.8%). Lupus nephritis ASMRs were significantly higher in females than males (2.16 [95% confidence interval, 2.11 to 2.21] vs 0.41 [0.38 to 0.43] per million persons), in ≥65-year age group followed by 45–64 and ≤44-years age groups, and in South census region followed by the West, and Midwest/Northeast regions. Lupus nephritis ASMRs were higher in large central metro areas (inner cities) than in all other regions and in black persons than in other race/ethnicities. Non-Hispanic black persons had the highest lupus nephritis ASMR (4.28 [4.13 to 4.42]), followed by American Indian/Alaska Natives (1.90 [1.50 to 2.38]), Hispanics (1.56 [1.46 to 1.65], Asian/Pacific Islanders (1.42 [1.28 to 1.56]), and non-Hispanic white persons (0.70 [0.67 to 0.72]. Multivariable logistic regression analysis showed that the adjusted odds of lupus nephritis deaths were the highest in large central metro (inner cities) and the lowest in large fringe metro (suburbs), and in non-Hispanic black persons than in all other race/ethnic groups. Furthermore, significant interactions between urbanization and race/ethnicity modified the risk of renal lupus mortality. The largest disparity was seen in Hispanic persons in inner cities who had a 15.1-times the odds of death compared to white persons. Black persons had 4.6 to 4.9 times the odds of death from renal lupus compared to white persons, regardless of their rural-urban region. White persons experienced the highest odds of death in nonmetro, black persons and Hispanic persons in inner cities, Asian/Pacific Islanders in medium metro, and American Indians/Alaska Natives in small metro and nonmetro areas.

Conclusions We report substantial differences in lupus nephritis mortality rates by sex, age, geographic region, urbanization level, and race/ethnicity. This study suggests strong, independent and interactive, association between urban-rural residence and race/ethnicity on lupus nephritis mortality. Urbanization modified the impact of race/ethnicity on the risk of death from lupus nephritis. These findings demand research and policy planning to address healthcare access and sociodemographic factors in the highest renal lupus mortality risk groups, such as Hispanic persons in large central metro, white persons in nonmetro, Asian/Pacific Islanders in medium metro, and American Indian/Alaska Natives in small metro and nonmetro areas. The high renal lupus mortality in black persons across all regions warrants prospective analyses of individual/biologic factors as well as differential healthcare in this subpopulation.