A Silent Epidemic: Recognizing Chronic Kidney Disease as a Public Health Crisis

In recent decades, a quiet, but powerful storm has been brewing under the nose of the US health systems. A silent epidemic, with an expanding foothold and devastating impact on long-term prognosis, chronic kidney disease has established itself as a major public health crisis.

First described in the early 1800s, the management of kidney disease has represented a significant clinical and public health challenge across the globe for nearly 200 years.¹ In the US, the Centers for Disease Control and Prevention estimated more than 1 in 7 adults have chronic kidney disease, with 90% of adults unaware they have the disease and 1 in 3 with severe chronic kidney disease unaware of their condition.²

According to estimates from the National Kidney Foundation (NKF), Medicare spends more than $130 billion annually on management of chronic kidney disease, with 24% of annual spending on patients with kidney disease. A testament to the disproportionate cost burden of the disease on public health systems, the NKF also points out end-stage kidney disease, which accounts for just 1% of Medicare beneficiaries, accounts for 7% of all Medicare spending.³

Although the issue is obvious and costly, the path to a solution is not straightforward.

A Growing Concern

George Bakris, MD
Credit: University of Chicago Medicine

There is no single driver of this growing public health crisis, which makes addressing it even more difficult. Part of the underrecognition of chronic kidney disease as a concern for public health systems and an issue in need of intervention, is its presentation.

A silent disease, lacking many outward symptoms, chronic kidney disease can often go unrecognized in those without prior education, which is evidenced by 90% of patients with the disease being unaware of their condition. Compounding this issue are associations between the presence of other common chronic diseases, such as hypertension, obesity, and diabetes, which are not considered as asymptomatic, with increased risk of chronic kidney disease.²

In fact, the field of nephrology dates back less than 100 years by most accounts. It was not until 1950 when the first dialysis program was launched in Ohio by the inventor of kidney dialysis Willem Kolff, MD, PhD.⁴ Then, on December 23, 1954, the field witnessed the first successful human kidney transplantation when Joseph Murray and colleagues transplanted a kidney into a donor from the recipient’s identical twin.⁵ In the 70 years to follow, the field would experience breakthroughs in pharmacologic therapies, with revelations coming forth supporting the use of surrounding ACEi/ARBs as well as lipid control in chronic kidney disease, but these were insufficient in curbing the ballooning issue chronic kidney disease would become in the 21st century.

According to statistics from the Global Burden of Disease, chronic kidney disease was listed as the 36th leading cause of death in 1990. Between 1990 and 2017, the global all-age mortality rate attributed to chronic kidney disease increased by 41.5%. By 2017, chronic kidney disease had risen to the 12th leading cause of life years lost globally and, by 2040, is expected to become the fifth highest cause of life years lost globally.⁶

The growing prevalence of chronic kidney disease is an issue compounded by the growing prevalence of other common chronic conditions linked to increased risk of chronic kidney disease, including type 2 diabetes and obesity. All of these factors have led to many calling for increased testing efforts. However, some in the space feel these calls have gone unanswered. That is, until recently, when advances in pharmacologic therapies have begun to usher in a new era of treatment.

“Before we didn't have the tools, now we have the tools, but we're still not educated and we're still not informing the patient. And the patient is the one with the problem, not us. So, if they don't know they have a problem, what do you expect them to do?,” explained George Bakris, MD, professor of medicine and director of the American Society of Hypertension's Comprehensive Hypertension Center at the University of Chicago Medicine, in an interview with HCPLive. “They're not necessarily going to be adherent with the medication. They're not going to be here with lifestyle, because you haven't told them much. So if you inform them, they you are empowering them, and they will help you achieve the goals.”

Therapeutic Advances Driving Screening Efforts

Kirsten Johansen, MD
Credit: Hennepin Healthcare

As Bakris describes, the field, for decades, was handcuffed to a management approach where most patients would be placed onto dialysis and, possibly, be considered for transplantation. In the last decade, the status quo in management of chronic kidney disease has flipped, with newer agents, namely the SGLT2 inhibitor class and the nonsteroidal mineralocorticoid receptor agonist finerenone.

A long-time staple in the management of type 2 diabetes, the SGLT2 inhibitor class celebrated the 10-year anniversary of its first approval in type 2 diabetes during 2023, with the US Food and Drug Administration first awarding approval to canagliflozin (Invokana) as an adjunct in type 2 diabetes on March 29, 2013. If not for the FDA requiring cardiovascular safety trials in light of the risk associated with agents such as thiazolidinediones, the community may never have realized the potential of the class, which began with the EMPA-REG Outcome trial.⁷

Following positive results from EMPA-REG Outcome detailing use of empagliflozin was associated with a 14% (HR, 0.86 [95.02% CI, 0.74-0.99]; P=.04) relative risk reduction for the primary composite outcome of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, the class had captured the attention of the medical community. Subsequent trials were launched to examine the role of empagliflozin and other SGLT2 inhibitors in the management of both heart failure and chronic kidney disease among populations with type 2 diabetes. Once these trials produced positive results, the focus shifted to populations with or without type 2 diabetes.⁷

With the FDA expanding the indication of empagliflozin to reflect data from the EMPA-KIDNEY trial in late September 2023, the class now boasts a pair of agents with approvals for the management of chronic kidney disease in patients at risk of progression.⁸

As the SGLT2 inhibitor class was being praised for its cardiorenal protective benefits based on the results of phase 3 programs in chronic kidney disease and heart failure, finerenone was blazing its own trail in the FIDELIO-DKD trial. A randomized, double-blind, placebo-controlled trial enrolling more than 5600 patients, FIDELIO-DKD compared finerenone versus placebo therapy and found use of finerenone was associated with an 18% reduction in risk for progression of chronic kidney disease and a 16% reduction in risk of the composite cardiovascular endpoint.⁹

Although indicated for chronic kidney disease associated with type 2 diabetes at the time of writing, the ongoing FIND-CKD trial was launched in 2021 to examine the effects of finerenone in a population of patients with chronic kidney disease without diabetes.¹⁰

Now, with new agents boasting significant safety and efficacy in hand, the focus has shifted to improvements in screening, but the community has recognized their goal of optimized screening efforts is not achievable on their own given the current workforce of nephrologists. In the face of this shortage, the nephrology community has keyed on education surrounding testing and management as a key priority and has called for an all-hands-on-deck approach to the issue.

“I think it's education. And it's education of primary care providers, be they physicians or advanced practice providers. We don't have the capacity for nephrologists to be caring for all the chronic kidney disease patients,” explained Kirsten Johansen, MD, director of nephrology and codirector of the Chronic Disease Research Group at Hennepin Healthcare as well as the deputy editor for the Clinical Journal of the American Society of Nephrology, in an interview with HCPLive. “Screening typically falls within the domain of primary care, but I think that for early treatment of kidney disease, because there just aren't enough nephrologists to be doing it all, we need to make sure that primary care providers are doing it and understand what to do. And I think that's happening.”

Beyond Kidney Disease

Joseph Vassalotti, MD
Credit: X.Com

Even with ongoing efforts to maximize screening efforts and improve access to care, nephrology and management of kidney disease is plagued with the same systemic problems plaguing other public health efforts, including battles against obesity, type 2 diabetes, and cardiovascular disease.

In late August 2023, data published in Mayo Clinic Proceedings: Innovations, Quality & Outcomes journal brought forth data highlighting notable pitfalls in the screening practices for albuminuria among people with diabetes. An analysis of data from the OptumLabs Data Warehouse, which included 5,635,619 Medicare fee-for-service beneficiaries, 736,875 Medicare advantage beneficiaries, and 660,987 commercial patients, results of the study suggested less than 40% of adults with diabetes received guideline-recommended testing for chronic kidney disease in 2017. However, even those who undergo guideline-recommended screening still face significant disparities in accessing optimal care.¹¹

A recent analysis of data from more than 52,000 patients with end-stage kidney disease on dialysis within the US Renal Data System Registry receiving care from 2005-2019 provided a snapshot of these disparities. Conducted by investigators at the Columbia University Medical Center and published in JAMA Internal Medicine, results of the study suggest women, those of advanced age, Hispanic, and Black individuals were significantly less likely to be waitlisted for transplantation following initiation of dialysis.¹²

It is the recognition of these issues that has led to organizations like the National Kidney Foundation launching programs the like Kidney Equity for All Initiative. As part of this initiative, the NKF is circulating a petition calling for the elimination of race as a factor in the Kidney Donor Risk Index screening equation by the Organ Procurement and Transplantation Network. Additionally, the initiative will allocate resources with the intent of improving healthcare access and outcomes in communities of color.¹³

“There are many health inequities across kidney disease that start with the testing go all the way to less access to dialysis, home dialysis, and kidney transplantation, said Joseph Vassalotti, MD, chief medical officer of the NKF and a clinical professor of medicine in the Division of Nephrology at Icahn School of Medicine at Mount Sinai. “So the delivery of the testing the diagnosis and the treatment in an equitable way, I think it's going to be really important.”

References:

1. Reubi F. Zur Geschichte der Nierenkrankheiten [On the history of kidney disease]. Schweiz Med Wochenschr. 1987;117(10):369-76contd.
2. Chronic kidney disease in the United States, 2023. Centers for Disease Control and Prevention. May 30, 2023. Accessed October 4, 2023. https://www.cdc.gov/kidneydisease/publications-resources/ckd-national-facts.html.
3. Federal investment. National Kidney Foundation. June 2, 2022. Accessed October 4, 2023. https://www.kidney.org/advocacy/legislative-priorities/federal-investment.
4. Cleveland Clinic History: 1950s - The Golden Age of medical innovation. Cleveland Clinic. Accessed October 4, 2023. https://my.clevelandclinic.org/about/history/1950s.
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6. Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl (2011). 2022 Apr;12(1):7-11. doi: 10.1016/j.kisu.2021.11.003. Epub 2022 Mar 18. PMID: 35529086; PMCID: PMC9073222.
7. Campbell P, Iapoce C. 10 years of SGLT2 inhibitors: A Decade of Redefining Cardiometabolic Care. HCP Live. March 29, 2023. Accessed October 4, 2023. https://www.hcplive.com/view/10-years-of-sglt2-inhibitors-a-decade-of-redefining-cardiometabolic-care.
8. Campbell P. Empagliflozin (Jardiance) receives CKD approval from US FDA. HCP Live. September 28, 2023. Accessed October 4, 2023. https://www.hcplive.com/view/empagliflozin-jardiance-receives-ckd-approval-from-us-fda.
9. Campbell P. Finerenone (Kerendia) approved for chronic kidney disease associated with type 2 diabetes. HCP Live. July 9, 2021. Accessed October 4, 2023. https://www.hcplive.com/view/finerenone-kerendia-approved-chronic-kidney-disease-associated-with-type-2-diabetes.
10. Bayer extends Clinical Development Program for Kerendia® (finerenone) with phase III study to investigate use in patients with nondiabetic chronic kidney disease. Business Wire. September 20, 2021. Accessed October 4, 2023. https://www.businesswire.com/news/home/20210920005126/en/Bayer-Extends-Clinical-Development-Program-for-KERENDIA%C2%AE-finerenone-With-Phase-III-Study-to-Investigate-Use-in-Patients-With-Nondiabetic-Chronic-Kidney-Disease.
11. Ferrè S, Storfer-Isser A, Kinderknecht K, et al. Fulfillment and Validity of the Kidney Health Evaluation Measure for People with Diabetes. Mayo Clin Proc Innov Qual Outcomes. 2023;7(5):382-391. Published 2023 Aug 29. doi:10.1016/j.mayocpiqo.2023.07.002
12. Husain SA, Yu ME, King KL, Adler JT, Schold JD, Mohan S. Disparities in Kidney Transplant Waitlisting Among Young Patients Without Medical Comorbidities. JAMA Intern Med. Published online October 02, 2023. doi:10.1001/jamainternmed.2023.5013
13. NKF is transforming the fight against kidney disease with kidney equity for allTM. National Kidney Foundation. October 3, 2023. Accessed October 4, 2023. https://www.kidney.org/newsletter/nkf-transforming-fight-against-kidney-disease-kidney-equity-all-tm.