Background: Hematological cancers (HC), including leukemia, lymphoma, and multiple myeloma often contribute to renal failure (RF) due to mechanisms such as tumor lysis syndrome, nephrotoxic chemotherapy, hypercalcemia, and light-chain cast nephropathy. The co-occurrence of HC and RF significantly worsens prognosis, yet the temporal and geographic patterns of mortality involving both conditions remain poorly characterized. This study investigates long-term mortality trends and demographic disparities in HC-related deaths involving renal failure across the United States.

Methods: We extracted mortality data from the CDC WONDER platform for U.S. adults aged ≥25 years from 1999 to 2023. Deaths with hematological cancers (ICD-10: C81-C96) and renal failure (ICD-10: N17-N19) as contributing causes were included. Age-adjusted mortality rates (AAMRs) were standardized to the 2000 U.S. population. Trends were analyzed using Joinpoint regression to estimate Annual Percent Change (APC) and Average Annual Percent Change (AAPC) with 95% confidence intervals. Stratified analyses included sex, age, race/ethnicity, census region, urbanization, and U.S. states.

Results: Between 1999 and 2023, there were 158,243 HC-related deaths with RF among adults aged ≥25 years. The national AAMR declined slightly from 3.02 to 2.90 per 100,000, with a non-significant AAPC of –0.23. A significant decline was observed from 1999 to 2019 (APC: -1.46, p < 0.001), followed by a borderline-significant rise from 2019 to 2023 (APC: 6.19, p = 0.05). Males had a higher mean AAMR than females (4.14 vs. 1.96), with significant mortality increases among males from 2016 to 2023 (APC: 4.13, p = 0.001518) and among females from 2018 to 2023 (APC: 5.09, p = 0.012367). Racial disparities were pronounced, with Black individuals showing the highest mean AAMR (4.34), followed by White (2.76), Hispanic (2.30), American Indian (2.03), and Asian/Pacific Islander (1.74). Significant declines were seen among Black individuals from 1999–2018 (APC: –2.60, p < 0.000001), while White individuals showed a significant increase from 2018–2023 (APC: 5.42, p = 0.012536), and Hispanics also experienced an increase from 2015–2023 (APC: 2.76, p = 0.006781). Age-specific analysis showed the highest crude mortality rates in older adults (11.46), followed by middle-aged (1.53) and younger adults (0.20). Younger adults declined significantly from 1999–2017 (APC: -3.56, p < 0.000001), then rose from 2017-2023 (APC: 7.50, p=0.011607); middle-aged adults showed a similar trend with a significant decline from 1999–2019 (APC: -2.57, p<0.000001) and rise thereafter (APC: 7.65, p = 0.005887); older adults increased significantly from 2016–2023 (APC: 4.10, p = 0.003139). Regionally, the Midwest had the highest mean AAMR (3.03), followed by the West (2.98), South (2.75), and Northeast (2.70). Urbanization analysis showed higher mean AAMRs in non-metropolitan areas (3.01) than in metropolitan areas (2.81), with significant declines in both: metro from 2003–2020 (APC: –1.95, p=0.000004) and non-metro from 1999–2020 (APC: –1.03, p=0.000297). State-level variation was notable: the highest AAMRs were seen in North Dakota (3.76), District of Columbia (3.45), Nebraska (3.42), Indiana (3.38), South Dakota (3.34), and Minnesota (3.39), while the lowest were in Arizona (1.98), New Mexico (1.98), Florida (2.02), Nevada (2.17), Montana (2.22), and New York (2.25).

Conclusion: Although overall mortality from hematological cancers with renal failure has declined slightly over the past two decades, recent uptrends, especially among males, White and Hispanic populations, and younger age groups signal emerging clinical and systemic vulnerabilities. Persistent disparities across race, region, and urbanization level suggest uneven access to oncology-nephrology care and delayed detection of renal dysfunction. Addressing these disparities requires equitable resource distribution, targeted screening, and integrated management strategies in high-risk communities.

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2025
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