Background/Purpose: Patients with lupus nephritis may die of active systemic lupus erythematosus (SLE) disease, end-stage renal disease (ESRD) and its complications as well as of comorbidities and treatment complications. Previous studies have utilized the national registry of patients with ESRD to examine causes of death in lupus nephritis, identifying cardiovascular disease and infection as the two leading causes of death. However, the ESRD database may not have information on lupus nephritis patients who may have died of infections or other complications prior to developing ESRD. Furthermore, there are no nationwide population-based studies on causes of death in all, unselected, patients with lupus nephritis across the entire U.S. population.

Methods: We used the Center for Disease Control and Prevention’s WONDER database, which compiles data on over 99% deaths from all 50 states and the District of Columbia. We used ICD-10 codes for SLE + a renal condition from the Multiple-Causes-of-Death files to obtain lupus nephritis death counts, overall and by the leading underlying causes of death. We then compared the underlying causes of death in two 10-year periods: 1999-2008 (period 1) versus 2011-2020 (period 2) using the Fisher’s exact test.

Results: 4,423 and 4,225 deaths were attributed to lupus nephritis during the first and second 10-year periods, respectively. The 10 leading underlying causes of death in lupus nephritis during 1999-2020 in the decreasing order were SLE (61.5%), diseases of heart (9.7%), renal disease (5.5%), malignant neoplasms (2.2%), septicemia (2.0%), diabetes mellitus (1.6%), cerebrovascular disease (1.4%), chronic lower respiratory disease (0.9%), chronic liver disease (0.8%), and hypertension with hypertensive renal disease (0.7%). The most significant decrease was seen in acute myocardial infarction (102 deaths [2.31%] in period 1 to 45 deaths [1.07%] in period 2, p< 0.0001), followed by SLE (64.5% in period 1 to 59.4% in period 2, p< 0.0001). Diabetes mellitus (p, 0.002) and chronic ischemic heart disease (p, 0.01) also significantly decreased. However, malignant neoplasms significantly increased from 72 deaths (1.63%) in period 1 to 113 deaths (2.67%) in period 2 (p, 0.0008). Chronic lower respiratory diseases (p, 0.006), chronic obstructive pulmonary disease (p, 0.006), unintentional injuries (p, 0.007), hypertensive renal/heart disease with renal failure (p< 0.05), and enterocolitis due to Clostridium difficile (p< 0.05) also increased during period 2 compared to period 1. Infections as the underlying causes of death remained unchanged during the study period.

Conclusion: A focus on cardiovascular disease risk in lupus over the past two decades has resulted in decreasing ischemic heart disease as the underlying cause of death in lupus nephritis. However, increased cancers and respiratory diseases and persistent infections among the leading causes of death in lupus nephritis are concerning. Prospective studies are needed to verify these findings and to identify patients at high risk for these complications.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/decreasing-ischemic-heart-disease-but-increasing-cancer-among-the-underlying-causes-of-death-in-decedents-with-lupus-nephritis/