Long-Term Trends in Sepsis Mortality Among Older U.S. Adults with Chronic Kidney Disease, 1999–2023
PDF
Supplementary File 1
Supplementary File 2

Keywords

Sepsis
CKD
Mortality
Trends
Disparities

Categories

How to Cite

1.
Aziz U, Memon RR, Mussawir Khuhro M, et al. Long-Term Trends in Sepsis Mortality Among Older U.S. Adults with Chronic Kidney Disease, 1999–2023. ASIDE Int Med. 2026;3(2):1-10. doi:10.71079/ASIDE.IM.030526287

Abstract

Background: Sepsis causes 1 in 3 U.S. hospital deaths, especially deadly among adults ≥65 with CKD, affecting over 30% of over-70s. Long-term trends in this group are understudied. This study examines the national mortality trends (1999–2023) among older U.S. adults with sepsis and CKD.

Methods: We conducted a retrospective cohort study using the CDC WONDER database (1999–2023). Older adults with sepsis and CKD were identified using ICD-10 codes for sepsis (A40-41) and chronic kidney disease (N18). Mortality rates were stratified by geography and demographics. Age-adjusted mortality rates (AAMRs) per 100,000 and 95% confidence intervals were calculated. Annual percent change (APC) and average APC (AAPC) were derived using Joinpoint regression software to assess temporal trends.

Results: Among 201,637 deaths from CKD and sepsis, 83.00% occurred in medical facilities. AAMRs rose from 14.45 (1999) to 20.68 (2023) (AAPC: 1.37%; 95% CI: 0.78-1.97). Men’s average AAMR (22.72) exceeded women’s (15.64). Non-Hispanic Whites had the highest AAPC, and Blacks had the highest AAMR. AAMRs were higher in metropolitan areas, with faster increases in non-metropolitan areas (available only for 1999-2020). The South had the highest average AAMR (19.94), while the Midwest recorded the steepest rise. Substantial variation in AAMRs was observed across U.S. states.

Conclusion: Mortality involving sepsis among older adults with CKD increased between 1999 and 2023. Considerable demographic and geographic disparities were observed, underscoring the need for targeted interventions in high-risk populations.

PDF
Supplementary File 1
Supplementary File 2

References

1. Chan HK, Khose S, Chavez S, Patel B, Wang HE. Updated estimates of sepsis hospitalizations at United States academic medical centers. J Am Coll Emerg Physicians Open. 2022: e12782 [PMID: 35859855, https://doi.org/10.1002/emp2.12782]

2. Ibarz M, Haas LEM, Ceccato A, Artigas A. The critically ill older patient with sepsis: a narrative review. Ann Intensive Care. 2024: 6 [PMID: 38200360, https://doi.org/10.1186/s13613-023-01233-7]

3. Centers for Disease C, Prevention. Chronic Kidney Disease Surveillance System-United States. Atlanta (GA): U.S. Department of Health and Human Services, CDC, 2025.

4. Liyanarachi KV, Mohus RM, Rogne T, Gustad LT, Asvold BO, Romundstad S, Solligard E, Hallan S, Damas JK. Chronic kidney disease and risk of bloodstream infections and sepsis: a 17-year follow-up of the population-based Trondelag Health Study in Norway. Infection. 2024: 1983 [PMID: 38679665, https://doi.org/10.1007/s15010-024-02265-2]

5. Dalrymple LS, Katz R, Kestenbaum B, de Boer IH, Fried L, Sarnak MJ, Shlipak MG. The risk of infection-related hospitalization with decreased kidney function. Am J Kidney Dis. 2012: 356 [PMID: 21906862, https://doi.org/10.1053/j.ajkd.2011.07.012]

6. Multiple Cause of Death Data on CDC WONDER. 2018.

7. Cdc. ICD-10: Classification of Diseases, Functioning, and Disability. 2024.

8. Afzaal Z, Khan A, Patel T, Rauf S, Kritika F, Zaman Khan A, Irshad A, Hashim A, Aslam F, Sohail H, Zaffar H, Khan A, Hassan S, Ahmed U, Rizvi K. Geographic and demographic disparities in sepsis and renal failure mortality: a CDC WONDER-based narrative review of 1999-2020 trends. Ann Med Surg (Lond). 2026: 561 [PMID: 41496986, https://doi.org/10.1097/MS9.0000000000004483]

9. Ahtsham A, Ahmed U, Haider M, Alrashid MM, Tauqeer N. Demographic Disparities in Mortality Trends of Obesity-Related Chronic Kidney Disease Among Adults in the United States From 2018 to 2023. Cureus. 2025: e95300 [PMID: 41287735, https://doi.org/10.7759/cureus.95300]

10. von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, Initiative S. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. J Clin Epidemiol. 2008: 344 [PMID: 18313558, https://doi.org/10.1016/j.jclinepi.2007.11.008]

11. Nasser IA, Asghar S, Masud L, Hafeez MA, Hurjkaliani S, Zulfiqar E, Shahzad M, Ahmed H, Khan S, Ahmed S, Abdul Q, Noushad MA, Nusrat R, Azhar S, Ward CD, Ahmed M, Ahmed R. The Interplay of Cancer and Hypertension: Rising Mortality and Widening Disparities Across the United States (1999-2023). Medicina (Kaunas). 2025: [PMID: 40428874, https://doi.org/10.3390/medicina61050917]

12. Hashmi S, Safdar I, Kazmi MH, Zulfiqar E, Shahzad M, Hurjkaliani S, Ayyad M, Zuberi N, Ahmed T, Sujay GB, Talal H, Kazmi SH, Khan MF, Imbianozor G, Ahmed M, Ahmed R. Rising Mortality Related to Diabetes Mellitus and Hypertension: Trends and Disparities in the United States (1999−2023). Clinical Cardiology. 2025: https://doi.org/10.1002/clc.70132]

13. Race and Ethnicity Measurement Methods - NCHS Rapid Surveys System. 2025.

14. Ingram DD, Franco SJ. 2013 NCHS Urban-Rural Classification Scheme for Counties. Vital and Health Statistics Series 2, Data Evaluation and Methods Research. 2017:

15. Aggarwal R, Chiu N, Loccoh EC, Kazi DS, Yeh RW, Wadhera RK. Rural-Urban Disparities: Diabetes, Hypertension, Heart Disease, and Stroke Mortality Among Black and White Adults, 1999-2018. J Am Coll Cardiol. 2021: 1480 [PMID: 33736831, https://doi.org/10.1016/j.jacc.2021.01.032]

16. Bureau USC. Census regions and divisions of the United States. 1984.

17. Hemida MF, Khan A, Ibrahim AA, Goel A, Patel K, Shahriar Z, Hageen AW, Alsaadi M, Rahman SU, Arafa A, Kholeif Z, Bahnasy A. Trends in Mortality from Leukemia and Ischemic Heart Disease: A 22-Year Analysis in the U.S. (1999-2020). ASIDE Internal Medicine. 2025: 21 https://doi.org/10.71079/aside.Im.091425163]

18. Anderson RN, Rosenberg HM. Age-standardization of death rates: implementation of the 2000 standard. National Vital Statistics Reports. 1998: 1

19. Joinpoint Regression Program. 2025.

20. Mallamaci F, Tripepi G. Risk Factors of Chronic Kidney Disease Progression: Between Old and New Concepts. J Clin Med. 2024: [PMID: 38337372, https://doi.org/10.3390/jcm13030678]

21. Qin K, Qing J, Wang Q, Li Y. Epidemiological shifts in chronic kidney disease: a 30-year global and regional assessment. BMC Public Health. 2024: 3519 [PMID: 39695543, https://doi.org/10.1186/s12889-024-21065-9]

22. Vincent JL. Evolution of the Concept of Sepsis. Antibiotics (Basel). 2022: [PMID: 36358234, https://doi.org/10.3390/antibiotics11111581]

23. Tungsanga S, Ghimire A, Hariramani VK, Abdulrahman A, Khan AS, Ye F, Kung JY, Klarenbach S, Thompson S, Collister D, Srisawat N, Okpechi IG, Bello AK. Global trends in chronic kidney disease-related mortality: a systematic review protocol. BMJ Open. 2024: e078485 [PMID: 38569707, https://doi.org/10.1136/bmjopen-2023-078485]

24. Takeuchi T, Flannery AH, Liu LJ, Ghazi L, Cama-Olivares A, Fushimi K, Chen J, Huen SC, Tolwani AJ, Neyra JA. Epidemiology of sepsis-associated acute kidney injury in the ICU with contemporary consensus definitions. Crit Care. 2025: 128 [PMID: 40114218, https://doi.org/10.1186/s13054-025-05351-5]

25. Oud L, Garza J. The Impact of COVID-19 on Sepsis-Related Mortality in the United States. J Clin Med Res. 2023: 328 [PMID: 37434769, https://doi.org/10.14740/jocmr4937]

26. Antimicrobial Resistance C. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. Lancet. 2022: 629 [PMID: 35065702, https://doi.org/10.1016/S0140-6736(21)02724-0]

27. Bell S, Perkins GB, Anandh U, Coates PT. COVID and the Kidney: An Update. Semin Nephrol. 2023: 151471 [PMID: 38199827, https://doi.org/10.1016/j.semnephrol.2023.151471]

28. Angelo S, Kadri SS. Hospital Strain and Disparities in Sepsis Outcomes. JAMA Netw Open. 2024: e2438526 [PMID: 39405066, https://doi.org/10.1001/jamanetworkopen.2024.38526]

29. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001: 1303 [PMID: 11445675, https://doi.org/10.1097/00003246-200107000-00002]

30. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C, Beginning, Ending Supportive Therapy for the Kidney I. Acute renal failure in critically ill patients: a multinational, multicenter study. JAMA. 2005: 813 [PMID: 16106006, https://doi.org/10.1001/jama.294.7.813]

31. Doi K, Leelahavanichkul A, Hu X, Sidransky KL, Zhou H, Qin Y, Eisner C, Schnermann J, Yuen PS, Star RA. Pre-existing renal disease promotes sepsis-induced acute kidney injury and worsens outcome. Kidney Int. 2008: 1017 [PMID: 18633340, https://doi.org/10.1038/ki.2008.346]

32. Balkrishna A, Sinha S, Kumar A, Arya V, Gautam AK, Valis M, Kuca K, Kumar D, Amarowicz R. Sepsis-mediated renal dysfunction: Pathophysiology, biomarkers and role of phytoconstituents in its management. Biomed Pharmacother. 2023: 115183 [PMID: 37487442, https://doi.org/10.1016/j.biopha.2023.115183]

33. Ou SM, Lee KH, Tsai MT, Tseng WC, Chu YC, Tarng DC. Sepsis and the Risks of Long-Term Renal Adverse Outcomes in Patients With Chronic Kidney Disease. Front Med (Lausanne). 2022: 809292 [PMID: 35280875, https://doi.org/10.3389/fmed.2022.809292]

34. Angele MK, Pratschke S, Hubbard WJ, Chaudry IH. Gender differences in sepsis: cardiovascular and immunological aspects. Virulence. 2014: 12 [PMID: 24193307, https://doi.org/10.4161/viru.26982]

35. Kovats S. Estrogen receptors regulate an inflammatory pathway of dendritic cell differentiation: mechanisms and implications for immunity. Horm Behav. 2012: 254 [PMID: 22561458, https://doi.org/10.1016/j.yhbeh.2012.04.011]

36. Michishita R, Matsuda T, Kawakami S, Tanaka S, Kiyonaga A, Tanaka H, Morito N, Higaki Y. The association between changes in lifestyle behaviors and the incidence of chronic kidney disease (CKD) in middle-aged and older men. J Epidemiol. 2017: 389 [PMID: 28385348, https://doi.org/10.1016/j.je.2016.08.013]

37. Ang SP, Chia JE, Iglesias J. Racial differences in outcomes among patients with septic shock: A national cohort study. World J Crit Care Med. 2025: 106387 [PMID: 40880577, https://doi.org/10.5492/wjccm.v14.i3.106387]

38. Brancati FL. The Excess Incidence of Diabetic End-Stage Renal Disease Among Blacks. Jama. 1992: https://doi.org/10.1001/jama.1992.03490210061036]

39. Laster M, Shen JI, Norris KC. Kidney Disease Among African Americans: A Population Perspective. Am J Kidney Dis. 2018: S3 [PMID: 30343720, https://doi.org/10.1053/j.ajkd.2018.06.021]

40. Law AC, Bosch NA, Song Y, Tale A, Lasser KE, Walkey AJ. In-Hospital vs 30-Day Sepsis Mortality at US Safety-Net and Non-Safety-Net Hospitals. JAMA Netw Open. 2024: e2412873 [PMID: 38819826, https://doi.org/10.1001/jamanetworkopen.2024.12873]

41. Mayr FB, Yende S, Linde-Zwirble WT, Peck-Palmer OM, Barnato AE, Weissfeld LA, Angus DC. Infection rate and acute organ dysfunction risk as explanations for racial differences in severe sepsis. JAMA. 2010: 2495 [PMID: 20571016, https://doi.org/10.1001/jama.2010.851]

42. McMaughan DJ, Oloruntoba O, Smith ML. Socioeconomic Status and Access to Healthcare: Interrelated Drivers for Healthy Aging. Front Public Health. 2020: 231 [PMID: 32626678, https://doi.org/10.3389/fpubh.2020.00231]

43. Ogundipe F, Kodadhala V, Ogundipe T, Mehari A, Gillum R. Disparities in Sepsis Mortality by Region, Urbanization, and Race in the USA: a Multiple Cause of Death Analysis. J Racial Ethn Health Disparities. 2019: 546 [PMID: 30607577, https://doi.org/10.1007/s40615-018-00553-w]

44. Oud L, Garza J. Temporal Trends in Rural vs Urban Sepsis-Related Mortality in the United States, 2010-2019. Chest. 2022: 132 [PMID: 35181278, https://doi.org/10.1016/j.chest.2022.02.015]

45. Rhee C, Jones TM, Hamad Y, Pande A, Varon J, O'Brien C, Anderson DJ, Warren DK, Dantes RB, Epstein L, Klompas M, Centers for Disease C, Prevention Prevention Epicenters P. Prevalence, Underlying Causes, and Preventability of Sepsis-Associated Mortality in US Acute Care Hospitals. JAMA Netw Open. 2019: e187571 [PMID: 30768188, https://doi.org/10.1001/jamanetworkopen.2018.7571]

46. Lippert AM. System Failure: The Geographic Distribution of Sepsis-Associated Death in the USA and Factors Contributing to the Mortality Burden of Black Communities. J Racial Ethn Health Disparities. 2023: 2397 [PMID: 36171498, https://doi.org/10.1007/s40615-022-01418-z]

47. Esper AM, Moss M, Lewis CA, Nisbet R, Mannino DM, Martin GS. The role of infection and comorbidity: Factors that influence disparities in sepsis. Crit Care Med. 2006: 2576 [PMID: 16915108, https://doi.org/10.1097/01.CCM.0000239114.50519.0E]

48. Burdick KJ, Rees CA, Lee LK, Monuteaux MC, Mannix R, Mills D, Hirsh MP, Fleegler EW. Racial & ethnic disparities in geographic access to critical care in the United States: A geographic information systems analysis. PLoS One. 2023: e0287720 [PMID: 37910455, https://doi.org/10.1371/journal.pone.0287720]

49. Yoshida S, Babazono A, Liu N, Yamao R, Ishihara R. Regional Differences and Mortality-associated Risk Factors among Older Patients with Septic Shock: Administrative Data Analysis with Multilevel Logistic Regression Modelling. JMA J. 2025: 708

50. Cirik MO, Doganay GE, Doganci M, Ozdemir T, Yildiz M, Kahraman A, Hazer S, Tunc M, Ensarioglu K, Ozanbarci A, Mentes O. Comparison of Intensive Care Scoring Systems in Predicting Overall Mortality of Sepsis. Diagnostics (Basel). 2025: [PMID: 40647659, https://doi.org/10.3390/diagnostics15131660]

51. Levy MM, Rhodes A, Phillips GS, Townsend SR, Schorr CA, Beale R, Osborn T, Lemeshow S, Chiche JD, Artigas A, Dellinger RP. Surviving Sepsis Campaign: association between performance metrics and outcomes in a 7.5-year study. Intensive Care Med. 2014: 1623 [PMID: 25270221, https://doi.org/10.1007/s00134-014-3496-0]

52. Global antibiotic resistance surveillance report 2025: summary. 2025.

53. Rudd KE, Johnson SC, Agesa KM, Shackelford KA, Tsoi D, Kievlan DR, Colombara DV, Ikuta KS, Kissoon N, Finfer S, Fleischmann-Struzek C, Machado FR, Reinhart KK, Rowan K, Seymour CW, Watson RS, West TE, Marinho F, Hay SI, Lozano R, Lopez AD, Angus DC, Murray CJL, Naghavi M. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet. 2020: 200 [PMID: 31954465, https://doi.org/10.1016/S0140-6736(19)32989-7]

54. Reinhart K, Daniels R, Kissoon N, Machado FR, Schachter RD, Finfer S. Recognizing Sepsis as a Global Health Priority - A WHO Resolution. N Engl J Med. 2017: 414 [PMID: 28658587, https://doi.org/10.1056/NEJMp1707170]

55. Saito H. Sepsis in Global Health: Current global strategies to fight against sepsis. Acute Med Surg. 2025: e70045 [PMID: 39975520, https://doi.org/10.1002/ams2.70045]

56. Haley M, Foroutan NK, Gronquist JM, Reddy R, Wusirika R, Khan A. Fluid Resuscitation and Sepsis Management in Patients with Chronic Kidney Disease or End-Stage Renal Disease: Scoping Review. Am J Crit Care. 2024: 45 [PMID: 38161173, https://doi.org/10.4037/ajcc2024756]

57. DiMeglio M, Dubensky J, Schadt S, Potdar R, Laudanski K. Factors Underlying Racial Disparities in Sepsis Management. Healthcare (Basel). 2018: [PMID: 30463180, https://doi.org/10.3390/healthcare6040133]

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Copyright (c) 2026 Umar Aziz, Roshni Riaz Memon, Muhammad Mussawir Khuhro, Huda Ahmed, Sarah Azhar, Hamama Waseem, Maryam Waqar, Muhammad Waaiz, Mominah Majid, Raveen Mujeeb