Renal amyloidosis-related mortality trends and disparities: A retrospective nationwide analysis using the CDC wonder database

Abstract

Abstract Background Renal amyloidosis is a rare but life-threatening condition characterized by extracellular deposition of amyloid fibrils in the kidneys, leading to progressive proteinuria and renal failure. Despite therapeutic advances in systemic amyloidosis, contemporary nationwide mortality trends related to renal involvement remain poorly defined. This study evaluates temporal, demographic, and geographic disparities in renal amyloidosis-related mortality in the United States over a 22-year period. Methods A retrospective analysis was performed using the CDC WONDER Multiple Cause of Death database from 1999 to 2020. Deaths were identified using ICD-10 code E85 (amyloidosis) in combination with renal-specific codes (N04, N17–N19). Age-adjusted mortality rates (AAMRs) per 100,000 population were calculated using the 2000 U.S. standard population. Data were stratified by year, sex, race, ethnicity, age group, region, urbanization, and place of death. Temporal trends were evaluated using the Joinpoint Regression Program v5.4.0 (National Cancer Institute), with segmented Annual Percent Changes (APCs) selected using the Weighted Bayesian Information Criterion. Results A total of 8,733 renal amyloidosis–related deaths were recorded from 1999 to 2020, with an overall AAMR of 0.117 per 100,000. National mortality declined from 1999 to 2016 at an APC of –1.22% (95% CI: –1.56 to –0.88; p<0.00001), followed by a significant increase from 2016 to 2020 at an APC of +9.60% (95% CI: 6.35 to 12.95; p<0.00001). Among females, AAMR declined significantly from 1999 to 2017 (APC: –3.00%, 95% CI: –7.14 to –1.72; p = 0.0296), followed by a non-significant increase from 2017 to 2020 (APC: +10.56%, 95% CI: –1.66 to +28.70; p = 0.156). Among males, mortality declined from 1999 to 2014 (APC: –0.81%; 95% CI: −1.78 to −0.05, p = 0.038), then rose sharply from 2014 to 2020 (APC: +6.12%; 95% CI: 3.82 to 10.88, p < 0.000001). Stratified analysis revealed marked disparities. Males had significantly higher AAMRs than females (0.163 vs. 0.090), accounting for 62% of deaths. Black/African American individuals exhibited the highest AAMR (0.243), over twice that of White individuals (0.111), followed by Hispanic (0.094), American Indian/Alaska Native (0.065), and Asian/Pacific Islander individuals (0.053). The highest crude mortality was observed in those aged 75–84 years (0.91 per 100,000). Mortality rates were disproportionately elevated in both large central (AAMR: 0.128) and large fringe metropolitan areas (AAMR: 0.117), revealing a striking urban burden. The highest state-level AAMRs were observed in the District of Columbia (0.260) and Washington State (0.215). Inpatient hospital deaths predominated (54.4%), followed by home (24.7%) and long-term care settings (8.2%). Conclusion This study reveals a concerning reversal in renal amyloidosis-related mortality trends in the United States, with recent years showing a sharp and sustained rise following nearly two decades of relative decline. The increase is most evident among males, older adults, and Black or African American individuals, with elevated mortality observed in urban areas and across diverse racial and ethnic groups. These findings highlight an emerging and underrecognized public health issue. Urgent efforts are needed to improve early diagnosis, implement better surveillance strategies, and investigate the drivers of rising mortality to mitigate the widening health disparities associated with this condition.