Тенденции смертности от почечной недостаточности среди многих пациентов в возрасте от миэломы ≥ 45 годы, 1999-2023Анализ данных ЦКЗ.

Introduction

MM is a hematologic malignancy caused by the clonal proliferation of malignant plasma cells, accounting for approximately 10% of all hematologic cancers and about 1–2% of all malignancies worldwide 1 , 2 . In the United States, approximately 34,000 new cases of multiple myeloma are diagnosed each year, with an age-adjusted incidence rate of about 7.0 per 100,000 population. Renal impairment is one of the most common and severe complications of MM, occurring in roughly 30% of patients during the disease course. Notably, about 10% of patients present with severe renal failure or oliguria/anuria at the time of diagnosis 3 . Although the introduction of novel therapeutic approaches—such as autologous hematopoietic stem cell transplantation, proteasome inhibitors, and immunomodulatory agents—has markedly improved the prognosis of MM, the clinical burden associated with MM-related renal failure remains substantial. Previous studies have also indicated that survival outcomes among MM patients vary significantly across different population groups 4 – 6 .

Renal failure, encompassing acute kidney injury, chronic kidney disease, and end-stage renal disease, is a major contributor to global morbidity and mortality. It is estimated that nearly 19 million individuals worldwide suffer from renal failure, with 5–11 million deaths annually attributable to this condition. Renal disease accounts for nearly one-tenth of the global disease burden, resulting in more than 41 million disability-adjusted life years (DALYs) lost, and is projected to rank as the fifth leading cause of years of life lost (YLL) globally by 2040 7 , 8 . Notably, kidney disease is the only major noncommunicable disease with a continuously rising age-standardized mortality rate. In the United States, approximately 808,000 individuals live with end-stage renal disease, with a disproportionately higher burden observed among Black populations 9 .

In MM, excessive production of monoclonal immunoglobulins and free light chains leads to their deposition within renal tubules and glomeruli, causing cast nephropathy, light-chain deposition disease, and amyloidosis 10 – 14 . Although previous studies have examined temporal trends and regional variations in kidney disease related to hypertension and diabetes, the changes in mortality due to renal failure among U.S. patients with MM have not been systematically analyzed. This study utilized the CDC WONDER database to examine trends in MM-related renal failure mortality among individuals aged 45 years and older from 1999 to 2023. The analysis further explored differences across sex, race/ethnicity, census region, state, and urbanization level, aiming to identify high-risk populations and persistent disparities, thereby providing data-driven insights to guide clinical management and public health policy.

Materials and methods

Study design and data source

This retrospective analysis used mortality records obtained from the CDC WONDER system 15 . We identified decedents between 1999 and 2023 whose death certificates listed multiple myeloma (ICD-10: C90.0) as the underlying cause of death and renal failure (ICD-10: N17–N19) as a contributing or secondary cause 16 . This definition reflects death certificate coding rather than clinically confirmed MM-related renal failure. Therefore, the observed associations represent co-reporting of MM and renal failure on death certificates, and causal relationships between these conditions cannot be inferred, as renal failure may coexist with MM rather than directly drive death.

Individuals aged ≥ 45 years were included because multiple myeloma is rare in younger populations and this age threshold has been widely adopted in prior CDC WONDER–based mortality studies 16 , 17 . Because this study used de-identified publicly available data, institutional review board approval was not required. Reporting adhered to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.

Data extraction and variable definition

Mortality data were stratified by year, sex, census region, urbanization level, race/ethnicity, and age group. Age groups were categorized in 10-year intervals as 45–54, 55–64, 65–74, 75–84, and ≥ 85 years. Race/ethnicity was classified as Hispanic/Latino, non-Hispanic White, non-Hispanic Black/African American, and other non-Hispanic populations (including non-Hispanic Asian or Pacific Islander and non-Hispanic American Indian/Alaska Native). Census regions were defined according to the U.S. Census Bureau classification as Northeast, Midwest, South, and West. Metropolitan–nonmetropolitan status followed the 2013 National Center for Health Statistics (NCHS) urban–rural classification scheme, distinguishing metropolitan from nonmetropolitan areas. Because data on urbanization were available only from 1999 to 2020, analyses involving this variable were limited to that period.

Statistical analysis

The primary outcome measure was the AAMR per 100,000 population, standardized to the 2000 U.S. standard population to allow fair comparisons across groups and over time. For age-stratified analyses, CMR were used instead of AAMR due to the inability to perform age standardization within age groups 18 . Temporal trends in mortality were assessed using Joinpoint regression software (version 5.2.0.0), which estimated the APC and AAPC with corresponding 95% CI 19 . A maximum of 4 joinpoints was allowed, and a heteroscedastic error variance model was applied. Significant joinpoints in mortality trends were identified using the Monte Carlo permutation test. An APC significantly different from zero ( P < 0.05) was interpreted as a statistically significant increasing or decreasing trend. Mortality rates based on fewer than 10 deaths were suppressed in accordance with CDC WONDER data-use standards. Subgroup analyses were conducted to evaluate trends stratified by sex, census region, urbanization level, race/ethnicity, and age group.

Results

Sex-specific analysis

From 1999 to 2023, a total of 60,788 deaths were recorded. By sex, 26,045 deaths occurred in females and 34,743 in males. Among females, mortality increased before 2002 (APC = 4.32%, 95% CI: − 3.51 to 12.79), declined significantly from 2002 to 2018 (APC = − 3.57%, 95% CI: − 4.22 to − 2.91, P < 0.05), and slightly increased from 2018 to 2023 (APC = 1.51%, 95% CI: − 2.22 to 5.37). Among males, changes were not significant before 2005 (APC = 1.25%, 95% CI: − 1.64 to 4.23), followed by a significant decline from 2005 to 2018 (APC = − 3.22%, 95% CI: − 4.18 to − 2.26, P < 0.05), and a slight increase from 2018 to 2023 (APC = 0.95%, 95% CI: − 2.73 to 4.76). Overall, AAPC indicates a long-term declining trend in both sexes, with minor recent increases (Fig. 1 , Table 1 and Supplementary Tables 1 and 2 ). Fig. 1 The number of deaths related to multiple myeloma with renal failure in the United States, grouped by gender, and the trends of these numbers from 1999 to 2023. Table 1 The number of deaths related to multiple myeloma and renal failure in the United States from 1999 to 2023 and the trend of its changes. Measure Deaths_1999 Deaths_2023 percent.change AAMR_1999 AAMR_2023 AAPC (95% CI) Both 2285 2474 8.27 2.39 (2.29 to 2.48) 1.60 (1.54 to 1.66) −1.30 (−2.36 to −0.22)* Female 1058 1049 −0.85 1.87 (1.75 to 1.98) 1.26 (1.18 to 1.34) −1.57 (−2.78 to −0.35)* Male 1227 1425 16.14 3.16 (2.98 to 3.34) 2.14 (2.03 to 2.25) −1.26 (−2.34 to −0.16)* Northeast 448 406 −9.38 2.25 (2.04 to 2.46) 1.47 (1.33 to 1.62) −1.63 (−2.83 to −0.43)* Midwest 551 551 0.00 2.43 (2.23 to 2.64) 1.76 (1.61 to 1.91) −1.44 (−2.38 to −0.49)* South 840 945 12.50 2.47 (2.30 to 2.64) 1.64 (1.53 to 1.74) −1.56 (−3.20 to 0.11) West 446 572 28.25 2.34 (2.13 to 2.56) 1.68 (1.54 to 1.82) −1.95 (−2.45 to −1.44)* Hispanic 103 196 90.29 2.14 (1.71 to 2.58) 1.27 (1.09 to 1.46) −2.37 (−2.90 to −1.84)* NH Black 489 539 10.22 6.09 (5.55 to 6.64) 3.71 (3.38 to 4.03) −2.04 (−2.94 to −1.13)* NH White 1648 1643 −0.30 2.04 (1.94 to 2.14) 1.48 (1.41 to 1.56) −1.07 (−2.18 to 0.04) NH Other 41 81 97.56 1.56 (1.10 to 2.14) 0.93 (0.74 to 1.16) −2.68 (−3.67 to −1.67)* Metropolitan 1832 1924 5.02 2.37 (2.26 to 2.48) 1.59 (1.52 to 1.66) −2.06 (−2.85 to −1.25)* Nonmetropolitan 453 439 −3.09 2.53 (2.30 to 2.76) 1.82 (1.65 to 2.00) −2.04 (−2.49 to −1.58)* 45–54 years 147 99 −32.65 0.40 (0.34 to 0.47) 0.24 (0.20 to 0.30) −2.40 (−3.02 to −1.78)* 55–64 years 358 306 −14.53 1.51 (1.35 to 1.66) 0.73 (0.65 to 0.81) −3.02 (−3.47 to −2.57)* 65–74 years 651 667 2.46 3.53 (3.26 to 3.81) 1.92 (1.78 to 2.07) −2.41 (−3.65 to −1.16)* 75–84 years 822 906 10.22 6.72 (6.26 to 7.18) 4.93 (4.61 to 5.25) −1.46 (−2.49 to −0.42)* 85 + years 307 496 61.56 7.39 (6.56 to 8.22) 8.01 (7.30 to 8.71) 0.57 (−0.71 to 1.87) The statistically significant AAPC was marked with *. In the Urbanization section, the 2023 data used the 2020 data as a substitute, and the AAPC was calculated for the period from 1999 to 2020. In the age group section, AAMR used the crude mortality rate as a substitute, and the AAPC calculated the crude mortality rate. MM, Multiple myeloma; AAMR, age-adjusted mortality rate; CI, confidence interval; AAPC, average annual percent change; NH, non-Hispanic.

Regional and urban–rural analysis

By region, the South had the highest total deaths (22,603), followed by the Midwest (13,887), West (13,115), and Northeast (11,183), with the highest AAMR in 2023 observed in the Midwest. In the Northeast, mortality slightly increased from 1999 to 2003 (APC = 3.68%, 95% CI: − 1.61 to 9.27), declined significantly from 2003 to 2018 (APC = − 3.94%, 95% CI: − 4.71 to − 3.17, P < 0.05), and remained stable from 2018 to 2023 (APC = 1.27%, 95% CI: − 2.74 to 5.45). The Midwest showed no significant change from 1999 to 2005 (APC = 1.25%, 95% CI: − 1.30 to 3.86), followed by a significant decline from 2005 to 2015 (APC = − 3.95%, 95% CI: − 5.28 to − 2.60, P < 0.05), and a slower decline from 2015 to 2023 (APC = − 0.24%, 95% CI: − 1.95 to 1.49). In the South, mortality slightly increased from 1999 to 2003 (APC = 2.11%, 95% CI: − 1.55 to 5.91), declined from 2003 to 2018 (APC = − 3.17%, 95% CI: − 3.69 to − 2.64, P < 0.05), slightly increased from 2018 to 2021 (APC = 4.76%, 95% CI: − 6.59 to 17.49), and showed no significant change from 2021 to 2023 (APC = − 5.70%, 95% CI: − 15.52 to 5.26). The West experienced a continuous decline throughout the study period (AAPC = − 1.95%, 95% CI: − 2.45 to − 1.44, P < 0.05) (Fig. 2 , Table 1 and Supplementary Tables 1 , 2 ). Fig. 2 The number of deaths related to multiple myeloma with renal failure in the United States, grouped by region, and the trends of these numbers from 1999 to 2023.

Metropolitan–nonmetropolitan analyses were restricted to the period from 1999 to 2020 due to data availability. By residential setting, 43,519 deaths occurred in urban areas and 9563 in non-urban areas. Mortality in urban areas declined significantly from 2003 to 2020 (APC = − 3.18%, 95% CI: − 3.63 to − 2.73, P < 0.05), whereas non-urban areas showed a continuous decline over the entire period (APC = − 2.04%, 95% CI: − 2.49 to − 1.58, P < 0.05). Overall, despite the general decline in mortality over the past two decades, certain older age groups and specific periods exhibited episodic increases or fluctuations (Fig. 3 , Table 1 and Supplementary Tables 1 , 2 ). Fig. 3 The number of deaths related to multiple myeloma with renal failure in the United States, grouped by urbanized areas, and the trends of these numbers from 1999 to 2023.

Racial/ethnic analysis

By race/ethnicity, the majority of deaths occurred in non-Hispanic (NH) White individuals (42,559), followed by NH Black (12,645), Hispanic (3869), and NH Other (1584). In 2023, NH Black populations had the highest AAMR (3.71). Mortality among Hispanics declined significantly over the study period (AAPC = − 2.37%, 95% CI: − 2.90 to − 1.84, P < 0.05), as did NH Other (AAPC = − 2.68%, 95% CI: − 3.67 to − 1.67, P < 0.05). NH Black individuals showed a significant decline from 1999 to 2018 (APC = − 3.01%, 95% CI: − 3.56 to − 2.46, P < 0.05) and a slight increase from 2018 to 2023 (APC = 1.76%, 95% CI: − 2.41 to 6.11). NH White populations exhibited multi-phase changes: slight increase from 1999 to 2003 (APC = 3.66%, 95% CI: − 1.05 to 8.60), significant decline from 2003 to 2019 (APC = − 3.06%, 95% CI: − 3.67 to − 2.44, P < 0.05), and slight increase from 2019 to 2023 (APC = 2.37%, 95% CI: − 2.55 to 7.53) (Fig. 4 , Table 1 and Supplementary Tables 1 , 2 ). Fig. 4 The number of deaths related to multiple myeloma with renal failure in the United States, grouped by race, and the trends of these numbers from 1999 to 2023.

Age-specific analysis

Mortality increased with age, with the highest deaths among those aged 75–84 (21,345) and 65–74 (17,209). The 45–54 (2945) and 55–64 (8956) age groups showed significant declines throughout the study period (AAPC = − 2.40% and − 3.02%, P < 0.05). The 65–74 and 75–84 age groups displayed multi-phase trends with early slight increases followed by long-term declines (65–74: 1999–2002 APC = 5.05%, 2002–2023 APC = − 3.43%, P 0.05; 75–84: 1999–2003 APC = 3.51%, 2003–2023 APC = − 2.42%, P < 0.05). Those aged ≥ 85 (10,333) exhibited a complex “rise–fall–rise” pattern (1999–2006 APC = 2.51%, 2006–2018 APC = − 2.52%, 2018–2023 APC = 5.53%, P < 0.05) (Fig. 5 , Table 1 and Supplementary Tables 1 , 2 ). Fig. 5 The number of deaths related to multiple myeloma with renal failure in the United States, grouped by age, and the trend of these deaths from 1999 to 2023.

Discussion

This study provides a comprehensive analysis of mortality trends among U.S. decedents with MM listed as the underlying cause of death and renal failure (RF) listed as a contributing cause from 1999 to 2023. Although AAMR remain high in this population, we observed a significant long-term decline over the past two decades. This improvement likely reflects advances in MM treatment and supportive care rather than a direct reduction in renal disease incidence.

Therapeutic progress has played a pivotal role in this trend. The widespread use of immunomodulatory drugs (e.g., thalidomide and lenalidomide), proteasome inhibitors (e.g., bortezomib), and high-dose melphalan with autologous stem cell transplantation has substantially prolonged survival and reduced renal-related complications 4 , 5 , 20 . Enhanced supportive strategies—including early diagnosis, aggressive hydration, avoidance of nephrotoxic agents, and routine monitoring of serum free light chains—have further improved renal recovery. In recent years, the introduction of denosumab and high-cutoff hemodialysis has expanded treatment options for patients with severe renal impairment 21 – 23 . Collectively, these advances likely contributed to the observed decline in mortality.

Despite overall improvement, marked disparities persist. Mortality was consistently higher in males than females, potentially reflecting differences in comorbidity burden, renal functional reserve, and healthcare-seeking behavior 24 , 25 . Older adults, particularly those aged ≥ 85 years, exhibited episodic increases in mortality in recent years. These recent upticks may be influenced by population aging, survivorship bias, and competing risks, as well as changes in death certification practices, rather than deterioration in therapeutic effectiveness 26 , 27 .

Racial and ethnic disparities remain substantial. Non-Hispanic Black populations continue to bear a disproportionately high mortality burden. MM incidence among Black individuals is approximately twice that observed in White populations, and disease presentation is often more aggressive, with higher susceptibility to renal impairment 28 , 29 . These differences likely reflect both genetic predisposition and structural inequities in healthcare access, including delayed diagnosis and reduced availability of novel therapies 30 – 33 . In contrast, Hispanic populations exhibit lower AAMR, which may be partly attributed to better metabolic health and culturally influenced lifestyle differences, though potential underreporting and diagnostic gaps should also be considered 34 .

Geographic and urban–rural disparities further highlight the role of healthcare accessibility and social determinants of health. Higher mortality in the Midwest and South may be driven by regional burdens of hypertension, diabetes, and obesity 35 – 37 . Nonmetropolitan areas exhibited significantly higher mortality than metropolitan areas, consistent with limited access to specialty care, delayed diagnosis, and resource constraints in rural settings 38 – 40 . Consistent with prior analyses, Ibrahim et al. reported that MM patients with co-existing renal impairment exhibited a distinct mortality trend, highlighting the persistent burden of renal complications in this population 41 . In contrast, previous studies including our own work focused on overall MM mortality trends, providing important context for understanding broader disease patterns. Our findings extend these observations by specifically examining deaths complicated by renal failure and demonstrating a long-term decline in age-adjusted mortality rates, likely reflecting improvements in MM-targeted therapies and supportive care tailored for patients with renal dysfunction 42 . These results underscore the clinical importance of early renal function assessment, close monitoring, and individualized treatment strategies to mitigate mortality risk in this high-risk subgroup, while situating MM + RF mortality trends within the broader context of MM-related deaths.

Importantly, this study does not establish a causal relationship between renal failure and MM-related death. Rather, it characterizes temporal patterns in deaths in which renal failure co-occurred with MM on death certificates. These findings complement prior studies that focused on MM mortality alone or on MM with chronic kidney disease and provide a population-level perspective on the evolving burden of renal complications among MM decedents.

Future research should evaluate emerging therapies, such as bispecific antibodies and CAR-T cell therapy, in patients with renal impairment and integrate clinical, social, and environmental factors into predictive models. Such efforts may further reduce mortality and promote equity in outcomes across populations.

Limitation

This study relied on death certificate data from the CDC WONDER database and ICD-10 coding, which are subject to potential misclassification bias and underreporting. Errors in the recording of the underlying cause of death or contributing causes may lead to misclassification of multiple myeloma– and renal failure–related mortality, particularly when multiple comorbidities coexist. In addition, changes in ICD coding practices and death certification standards over time may have affected the consistency of cause-of-death reporting across the study period, which could influence temporal trend analyses. The CDC WONDER database does not provide individual-level clinical information, including laboratory measures, disease severity, treatment regimens, or socioeconomic characteristics. The absence of such data limited our ability to adjust for important confounders and to explore potential mechanisms underlying observed disparities. Moreover, this analysis did not account for competing risks, such as deaths from cardiovascular disease or other malignancies, which may bias mortality estimates, particularly in older populations with high levels of multimorbidity. Age-stratified analyses used crude mortality rates due to the unavailability of standardized rates within age groups, which may be influenced by population structure. In addition, urban–rural analyses were restricted to the period from 1999 to 2020 because more recent urbanization classifications were unavailable.

Conclusion

Over the past 25 years, mortality in the study population has generally declined, but notable differences exist across sex, age, region, race/ethnicity, and residential setting. Mortality among both females and males has shown a long-term downward trend, though with a slight recent increase; mortality in younger to middle-aged groups has continued to decline, whereas older adults, particularly those aged 85 and above, have exhibited episodic increases during certain periods. Mortality in the Southern region and among non-Hispanic White populations has experienced multi-phase fluctuations, while both urban and non-urban areas have shown long-term declines. Overall, despite favorable trends, certain high-risk groups and specific periods remain vulnerable to increased mortality, highlighting the need for more targeted public health interventions for the elderly and disadvantaged populations.

Supplementary Information

Supplementary Information 1. Supplementary Information 2.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Author contributions

Ye Jiang designed experiments; Ye Jiang and Zhichao Meng wrote the manuscript; Guanghua Liang carried out experiments; Ye Jiang analyzed the results of the experiments. Yongping Cao supervised the study and contributed to data analysis.

Funding

This study was not funded.

Data availability

All data used in this study are publicly available from the CDC WONDER database ( https://wonder.cdc.gov/ ).

Declarations

Competing interests

The authors declare that they have no competing interests.

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