Monthly Archives: June 2025

Mechanisms of Kidney Dysfunction in the Cirrhotic Patient: Non-hepatorenal Acute-on-Chronic Kidney Damage Considerations

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DOI: 10.31038/CST.20251022

 
 

Cirrhosis is a worldwide health problem: by 2019, cirrhosis was associated with 2.4% of global deaths, with obesity and alcohol consumption becoming its leading etiologies as improved outcomes in the treatment of Hepatitis C and hepatitis B virus decreases the number of viral hepatitis associated cirrhosis.

Among patients who live with chronic liver disease, kidney dysfunction spectrum, including kidney frailty, subclinical acute kidney Injury (SAKI), acute kidney injury (AKI), Acute Kidney Disease (AKD), Chronic Kidney Disease (CKD) and End Stage Kidney Disease (ESKD) are among the most common extrahepatic complications along the natural history of cirrhosis.

Given the known nature of the human body as a complex unified homeostatic system, it has been largely recognized that multiple organ involvement is an expected phenomenon in pathologies affecting primarily a specific organ, both because of clinical observation and theoretical biological sense.

However, only in the last decades, advances in molecular biology, imaging technology and large clinical trials have allowed the physiopathological pathways of multiorgan crosstalk to be described.

In cirrhotic patients specifically, kidney involvement has been largely explained in terms of hepatorenal syndrome. However, given the complex natural history of cirrhosis, a myriad of clinical events, as well as newly described histopathological pathways should also be taken into account when evaluating a specific clinical scenario, as multifactorial is the most plausible etiology for most kidney injury events, and mutually exclusive physiopathological pathways are rarely seen.

As an example, during an acute-on-chronic liver failure episode, a single patient may present with both Hepatorenal Syndrome and bile cast nephropathy, while also at risk for contrast-media induced AKI during the diagnostic approach.

In 2020, the manuscript “Mechanisms of Kidney Dysfunction in the Cirrhotic Patient: Nonhepatorenal Acute-on-Chronic Kidney Damage Considerations.” briefly summarizes some of the most important non-prerenal, non-HRS considerations regarding acute-on-chronic kidney dysfunction in cirrhotic patients, including renal manifestations related to non-alcoholic steatohepatitis (NASH), viral hepatitis, cardiorenal syndrome, cirrhotic cardiomyopathy, and corticosteroid-deficiency associated renal dysfunction.

The manuscript highlights the importance of multiorgan crosstalk pathways to be considered as interconnected gears to be understood and described when approaching the clinical trajectory of renal function within the natural history of cirrhosis and, more importantly, within the clinical trajectory of multiorgan interaction during a specific patient’s clinical course.

As an example, endocrine dysfunction—including thyroid dysfunction, metabolic dysfunction-associated steatohepatitis (MASH), and obesity-related kidney dysfunction—should be considered in both the chronic and acute liver dysfunction follow-up of an obese cirrhotic patient.

Most importantly, a change in the basic clinical paradigm must be taken into account, as modern medicine has made evident the existence of the human body as an open homeostatic system, in which changes in the microbiota, pharmacological interventions, surgical procedures, extracorporeal therapies, and even transplantation physiological consequences must also be considered.

Hopefully, within the years to come, the use of computer systems, novel biomarkers and further understanding of multiorgan crosstalk will make feasible the development of novel, more efficient therapeutic approaches for the surveillance, preservation, and restoration of both liver and kidney function in cirrhotic patients, as well as the replacement of both liver and kidney function by either extracorporeal therapies, bioartificial organs, or transplantation [1-23].

References

  1. Huang DQ, Terrault NA, Tacke F, et al. (2023) Global epidemiology of cirrhosis – aetiology, trends and predictions. Nat Rev Gastroenterol Hepatol. [crossref]
  2. Nadim MK, Garcia-Tsao G (2023) Acute Kidney Injury in Patients with Cirrhosis. N Engl J Med. [crossref]
  3. Nadim MK, Kellum JA, Forni L, et al. (2024) Acute kidney injury in patients with cirrhosis: Acute Disease Quality Initiative (ADQI) and International Club of Ascites (ICA) joint multidisciplinary consensus meeting. J Hepatol. [crossref]
  4. Flamm SL, Wong F, Ahn J, Kamath PS (2022) AGA Clinical Practice Update on the Evaluation and Management of Acute Kidney Injury in Patients With Cirrhosis: Expert Review. Clin Gastroenterol Hepatol. [crossref]
  5. Juanola A, Pose E, Ginès P (2025) Liver Cirrhosis: ancient disease, new challenge. Med Clin (Barc). [crossref]
  6. Trapecar M (2022) Multi-organ microphysiological systems as tools to interrogate interorgan crosstalk and complex diseases. FEBS Lett. [crossref]
  7. Kumar R, Priyadarshi RN, Anand U (2021) Chronic renal dysfunction in cirrhosis: A new frontier in hepatology. World J Gastroenterol. [crossref]
  8. Somaguna MR, Jain MS, Pormento MKL, et al. (2022) Bile Cast Nephropathy: A Comprehensive Review. Cureus. [crossref]
  9. Belcher JM (2023) Hepatorenal Syndrome: Pathophysiology, Diagnosis, and Treatment. Med Clin North Am. [crossref]
  10. Hisamune R, Yamakawa K, Umemura Y, et al. (2024) Association Between IV Contrast Media Exposure and Acute Kidney Injury in Patients Requiring Emergency Admission: A Nationwide Observational Study in Japan. Crit Care Explor. [crossref]
  11. Piantanida E, Ippolito S, Gallo D, et al. (2020) The interplay between thyroid and liver: implications for clinical practice. J Endocrinol Invest. [crossref]
  12. Ortiz-Olvera N, Muñoz-Bautista A, Molina-Ayala M, Gómez-Díaz RA, Morán-Villota S (2024) Disfunción tiroidea oculta en pacientes ambulatorios con cirrosis hepática. Rev Med Inst Mex Seguro Soc. [crossref]
  13. Do A, Zahrawi F, Mehal WZ (2025) Therapeutic landscape of metabolic dysfunction-associated steatohepatitis (MASH). Nat Rev Drug Discov. [crossref]
  14. Sandireddy R, Sakthivel S, Gupta P, Behari J, Tripathi M, Singh BK (2024) Systemic impacts of metabolic dysfunction-associated steatotic liver disease (MASLD) and MASH on heart, muscle, and kidney. Front Cell Dev Biol. [crossref]
  15. Yau K, Kuah R, Cherney DZI, Lam TKT (2024) Obesity and the kidney: mechanistic links and therapeutic advances. Nat Rev Endocrinol. [crossref]
  16. Raj D, Tomar B, Lahiri A, Mulay SR (2020) The gut-liver-kidney axis: Novel regulator of fatty liver-associated chronic kidney disease. Pharmacol Res. [crossref]
  17. Muciño-Bermejo MJ (2022) Extracorporeal organ support and the kidney. Front Nephrol. [crossref]
  18. Dong V, Nadim MK, Karvellas CJ (2021) Post-Liver Transplant Acute Kidney Injury. Liver Transpl. [crossref]
  19. Rasaei N, Malekmakan L, Mashayekh M, Gholamabbas G (2022) Chronic Kidney Disease Following Liver Transplant: Associated Outcomes and Predictors. Exp Clin Transplant. [crossref]
  20. Zhai Y, Hai D, Zeng L, et al. (2024) Artificial intelligence-based evaluation of prognosis in cirrhosis. J Transl Med. [crossref]
  21. Juanola A, Ma AT, Pose E, Ginès P (2022) Novel Biomarkers of AKI in Cirrhosis. Semin Liver Dis. [crossref]
  22. Nair G, Nair V (2022) Simultaneous Liver-Kidney Transplantation. Clin Liver Dis. [crossref]
  23. De Bartolo L, Mantovani D (2022) Bioartificial Organs: Ongoing Research and Future Trends. Cells Tissues Organs. [crossref]

Diversity in Continuing Care Retirement Communities’ Leadership

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DOI: 10.31038/AWHC.2025823

 

In 2020, one in six Americans were age 65 or older, with this segment expected to grow to one in five by 2030. Moreover, within the next 25 years, the number of Americans age 65 and over is expected to increase 47 percent to 82 million in 2050. Over this 25-year period, the U.S. also is projected to become significantly more racially and ethnically diverse. For example, those who identify as something other than a non-Hispanic white are expected to increase from 25 percent to 40 percent over this period. With this increase in the aging population, it is predicted that there will be a sharp increase in the need for both healthcare and housing for the elderly [1-5].

One option that combines both healthcare and housing for this segment is the continuing care retirement community (CCRC), sometimes called a life plan community. CCRCs offer a combination of healthcare, hospitality, insurance, and residential services to the aging population. Furthermore, most CCRCs offer an amalgamation of living arrangements and services including independent living, assisted living or personal care, memory care, short-term rehabilitative services, long term care, and hospice or end-of-life care. There are about 2,000 CCRCs in operation in the United States (U.S.), with this setting expected to increase considerably to meet the growing demand [6-8].

An issue (and an opportunity) for many of these CCRCs is the lack of diversity among their residents. Two recent surveys [9,10] find that 95 to 97 percent of all CCRCs’ residents are non-Hispanic white. It has been suggested that one barrier to CCRC diversity is due to the lack of diversity of its leadership [10]. Senior housing executives have begun to address this issue seeking to expand the percentage of senior executives and residents who identify as persons of color and female [11].

With this in mind, we surveyed chief executive officers (CEOs) of non-profit CCRCs. We surveyed non-profits as they represent 80 percent of all CCRCs in the U.S. [8]. Specifically, we surveyed CCRC CEOs whose organizations were members of Leading Age. Leading Age is an organization representing 5,000 non-profit and government organizations which offer aging services in adult day care centers, CCRCs, home health services, and other outreach programs.

Our interest, here, was to determine the demographic composition of CCRC CEOs and to discern their organizations’ efforts related to promoting diversity in their leadership ranks. This was a subset of questions that were part of a broader survey we did on CEO characteristics and skillsets [7]. We sent surveys to 999 CCRC CEOs. Related to our questions on diversity, 173 to 233 CEOs responded to the individual diversity questions. Thirty-eight percent of the CEOs who responded to our survey were women and 62 percent were men (N=233). Four percent identified as a person of color (N=230). We asked CEOs five questions related to expanding their CEO recruitment and other efforts related to underrepresented groups. These questions and their responses are:

  • Does your organization collaborate with recruiters who have expertise in sourcing racially and ethnically diverse candidates for the CEO position? 31 percent responded in the affirmative (N=189);
  • Does your organization have a formal succession planning process that considers racial and ethnic diversity for the CEO position? 35 percent responded in the affirmative (N=187);
  • On a scale of 1 to 10 with 1 as “not at all” and 10 as “extremely well,” how well do you believe the organization supports the career advancement and leadership aspirations of individuals from an underrepresented racial and ethnic minority Average score was 7.1 (N=173);
  • Does your organization have a formal mentorship program in place to support the career development of individuals from underrepresented groups into leadership roles? A mentor acts as a career guide and provides guidance, advice, feedback on skills, coaching, and strategizes career moves and professional 24 percent responded in the affirmative (N=189); and
  • Does your organization have a formal sponsorship program in place to support the career development of individuals from underrepresented groups into leadership roles? A sponsor invests in the person’s success and promotes them to other people to help advance their career. 21 percent responded in the affirmative (N=189).

As seen above, 21 to 35 percent of the CEO participants responded that their organizations are actively engaged in developing, mentoring, and sponsoring diverse leaders. Given this, it is apparent that more work is needed. We believe that CEOs should examine this as both a moral imperative and business opportunity. We agree with Garcia et al.’s overall statement about healthcare when they say “understanding and respecting diverse cultural backgrounds, including non-English languages and non-traditional health beliefs, is fundamental in ensuring equitable and effective healthcare services for the aging population. This can be achieved by…promoting diverse representation in the healthcare workforce to increase cultural competency and care”[2: 2]. Given this growing population, there is also a business case to be made as well, as the non-white population is growing significantly but remains grossly underrepresented as CCRC residents . Similar arguments can be made related to gender. Thus, our survey results of 38 percent female CEOs signifies that females are underrepresented in this role, as historically, female residents outnumber male residents four to one and almost three-fourths of all CCRC employees are female [11-14].

In order to increase diversity executive efforts, CCRCs may wish to create more diverse boards. As noted elsewhere, CCRC board members are less diverse than CCRC CEOs [12]. The election of a more diverse board may increase the number of CEOs with a diverse background. As Dr. Patricia Maryland, CEO of St. John Health, notes “a diverse board is more apt to hold the organization accountable and insist on recruitment of diverse leaders” [15: 303]. In addition, CCRCs also may wish to develop more focused marketing campaigns for these types of residents and executive candidates [13], and provide richer more diverse program offerings [9], the latter of which may be unknown to the current population of CCRC CEOs.

The present study has sought to show the efforts of CCRCs related to leadership diversity development. Some improvement has been made in this regard; yet more progress is needed.

References

  1. Administration for Community Living (2022) 2021 profile of older Available from: https://tinyurl.com/yeymrnv5.
  2. Garcia C, Brown, LL, Garcia, MA (2024) How can America support the health of its diverse aging population. Center for Aging and Policy Studies, Syracuse Available from: https://surface.syr.edu/cgi/viewcontent.cgi?article=1257& context=lerner.
  3. Mather, Scommegna P (2024) Fact sheet: aging in the United States. Population Reference Bureau. Available from:  https://tinyurl.com/ya7wy9da
  4. S. Census Bureau (2023) 2023 National population projections datasets. Available from: https://www.census.gov/data/datasets/2023/demo/popproj/2023-popproj.html.
  5. Rogoz A (2024) The road ahead: senior housing trends to watch in Multi- Housing News, December 18, 2024.
  6. Hurley RE, Brewer KP (1991) The continuing care retirement community executive: a manager for all seasons. Hospital & Health Services Administration, 36(3), 365-381. [crossref]
  7. Williams, R, Fleming, S. P, Stone R (2025) Non-profit Continuing Care Retirement Center CEOs: Who Are They and What Do They Do. Journal of Health and Human Services Administration.
  8. Miller KEM, Zhao J, Laine LT, Coe NB (2023) Growth of private pay senior housing communities in metropolitan statistical areas in the United States: 2015–2019. Medical Care Research and Review, 80(1): 101-108. [crossref]
  9. Khan M, O’Brien C, Desai P (2023) Working toward greater resident diversity in life plan Mather Institute. Available from: https://www.matherinstitute.com/wp-content/uploads/.2023/06/MI_DiversityInLPCReportFNL.pdf?hsCtaTracking=6ee9bac2-4d84-4f8e-a6d0-3ee3186d6ea0%7C008edbff-6638-4a40-a3fa-daa45c4ce9a8.
  10. Love (2018) Diversity in Senior Living Communities: insights into creating a more diverse Available From: https://loveandcompany.com/flipbooks/ diversity/?page=1.
  11. Ferguson Partners (2023) 2023 senior living DEIB survey, executive summary. Available From: https://www.argentum.org/wp-content/uploads/2024/01/2023-Senior-Living-DEIB-Executive-Summary-003.pdf?hsCtaTracking=c46bd7ca-7abd-46f4-9e3b-7ded8ab47429%7Cd1227f98-600c-48f8-a455-0c4a0c639608.
  12. Regan T (2018) Life plan communities failing to attract diverse resident Senior Housing News. July 23, 2018. Available From: https://rb.gy/9eo1x9 respectively.
  13. Johnson JH, Parnell AM, Johnson TJ (n.d.) Race and residence in continuing care retirement communities/life plan Frank Hawkins Kenen Institute of Private Enterprise Conference Proceedings. Found at https://cdn.ymaws.com/www.leadingagenc.org/resource/resmgr/inclusioninsights/raceandresidenceinccrcs.pdf.
  14. McCann M, Kafader S, Rose J, Dellaria D (2013) The hidden male: challenges for men entering and living in a retirement community. McKnights Long Term Care News. November 20, 2013. Available from: https://www.mcknights.com/blogs/ guest-columns/the-hidden-male-challenges-for-men-entering-and-living-in-a- retirement-community/.