Moving from Evidence to Implementation of Breakthrough Therapies for Diabetic Kidney Disease

Abstract

Diabetic kidney disease is the most frequent cause of kidney failure, accounting for half of all cases worldwide. Moreover, deaths from diabetic kidney disease increased 106% between 1990 and 2013, with most attributed to cardiovascular disease. Recommended screening and monitoring for diabetic kidney disease are conducted in less than half of patients with diabetes. Standard-of-care treatment with an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker is correspondingly low. Sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and a nonsteroidal mineralocorticoid antagonist are highly effective therapies to reduce kidney and cardiovascular risks in diabetic kidney disease. However, <20% of eligible patients are receiving these agents. Critical barriers are high out-of-pocket drug costs and low reimbursement rates. Data demonstrating clinical and cost-effectiveness of diabetic kidney disease care are needed to garner payer and health care system support. The pharmaceutical industry should collaborate on value-based care by increasing access through affordable drug prices. Additionally, multidisciplinary models and communication technologies tailored to individual health care systems are needed to support optimal diabetic kidney disease care. Community outreach efforts are also central to make care accessible and equitable. Finally, it is imperative that patient preferences and priorities shape implementation strategies. Access to care and implementation of breakthrough therapies for diabetic kidney disease can save millions of lives by preventing kidney failure, cardiovascular events, and premature death. Coalitions composed of patients, families, community groups, health care professionals, health care systems, federal agencies, and payers are essential to develop collaborative models that successfully address this major public health challenge.

Introduction

Diabetic kidney disease (DKD) is a frequent and severe complication of diabetes. DKD refers to the development of CKD, defined by a sustained elevation of urinary albumin excretion (urine albumin-creatinine ratio >30 mg/g), a reduction in eGFR to <60 ml/min per 1.73 m², or both in a person with diabetes (1,2). In 2021, >37 million Americans and 537 million people worldwide had diabetes. The worldwide number is predicted to rise to 643 million by 2030 and 783 million by 2045 (Figure 1) (3,4). DKD develops in approximately 30% of people with type 1 diabetes and 40% of those with type 2 diabetes, who make up the vast majority of diabetic individuals (≥95%) (5). Accounting for half of all cases, DKD is the most frequent cause of CKD leading to kidney failure worldwide (6,7). Although the prevalence of other diabetic complications is falling, the number of diabetic patients with kidney failure is progressively rising (8–10). Moreover, death from DKD increased 106% worldwide between 1990 and 2013 (11). The most common causes of death in individuals with DKD are heart failure and atherosclerotic cardiovascular disease (12,13). Consequently, only about 10% of patients with DKD survive to reach kidney failure (5).

Figure 1.

The worldwide prevalence of diabetes was estimated at 537 million people in the year 2021. Approximately 40% of people with type 2 diabetes (95% of all diabetes cases) and 30% of those with type 1 diabetes (5% of all diabetes cases) develop diabetic kidney disease. Half of all cases of CKD are attributable to diabetes. Most people with diabetic kidney disease (90%) die, mainly of heart failure or atherosclerotic cardiovascular events, with only a minority (10%) surviving to reach kidney failure.

Given the enormous personal and societal implications, improving DKD care should be a major public health imperative. Unfortunately, current approaches are failing. As recently as 2017–2019, DKD screening and monitoring were conducted in only 10%–40% of patients with or at risk of DKD (Table 1) (7,14,15). Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) have been standard-of-care treatments for DKD since 2001 (1,2,16). However, implementation of ACE inhibitor or ARB therapy has been unsuccessful overall, with only 25%–40% of persons with DKD treated by typical health care systems or in a representative US population sample receiving this recommended therapy (14,17). In contrast, nearly 80% of individuals with DKD received an ACE inhibitor or ARB through the Indian Health Service by a multidisciplinary team intervention with resources for implementation and tracking (18). A corresponding reduction in cases of incident kidney failure by >50% was noted between 1996 and 2013 in the American Indian/Alaska Native population. Older adults also receive these agents more commonly, about 70%, perhaps related to greater access to medication coverage by commercial or federal health insurance programs (19). Recently, a series of large clinical trials have convincingly demonstrated that sodium-glucose cotransporter 2 (SGLT2) inhibitors and finerenone, a nonsteroidal mineralocorticoid antagonist, substantially slow eGFR decline and reduce risks of kidney failure, heart failure, atherosclerotic cardiovascular disease, and death in patients with DKD already treated with ACE inhibitors or ARBs (20–25). Additionally, glucagon-like peptide 1 (GLP-1) receptor agonists reduce the risk of atherosclerotic cardiovascular events and are safe and effective glucose-lowering agents in patients with type 2 diabetes and eGFR as low as 15 ml/min per 1.73 m² (26,27). As such, there are at least three, and likely four, pillars of therapy for DKD treatment (ACE inhibitors/ARBs, SGLT2 inhibitors, finerenone, and GLP-1 receptor agonists). Yet, uptake of SGLT2 inhibitors and GLP-1 receptor agonists has been poor, with 13% and 17%, respectively, of commercially insured patients with DKD receiving these therapies in 2020 (28).

Table 1.

Guideline-based recommendations and care gaps for diabetic kidney disease

Recommendations	Indication	Implementation Rate, %	Implications
Albuminuria testing by UACR (1,16)	• Annually in type 2 diabetes • After 5 yr of type 1 diabetes • 3–6 mo after initiation or dose change in ACE inhibitor or ARB	10–40 (7,14,15)	• Underdiagnosis of DKD • Low usage rates of DKD therapies • Inadequate therapeutic monitoring and dose adjustments
ACE inhibitor or ARB (1,2,16)	• UACR >300 mg/g irrespective of hypertension • UACR >30–299 mg/g with hypertension • Consideration for UACR >30–299 mg/g without hypertension	25–40 (14,17)	• Most patients in typical health care settings are not given standard-of-care therapies to prevent DKD progression, kidney failure, and cardiovascular risk
SGLT2 inhibitor (1,2)	• Initiate with eGFR ≥25 ml/min per 1.73 m2 • Initiate with eGFR ≥20 ml/min per 1.73 m2 if used for heart failure (empagliflozin) • SGLT2 inhibitors may be continued until onset of kidney failure	13 (27)	• Patients are not given therapies that substantially reduce risk of DKD progression, kidney failure, cardiovascular risk, and all-cause mortality on top of standard of care • Early in the implementation phase for SGLT2 inhibitors, with first drug approval for DKD in 2019
GLP-1 receptor agonist (1,2)	• Use for glucose lowering and atherosclerotic cardiovascular risk reduction with eGFR ≥15 ml/min per 1.73 m2	17 (27)	• Patients rarely are given therapies that effectively and safely lower glucose and reduce major adverse cardiovascular events with eGFR <60 or ≥60 ml/min per 1.73 m2
Nonsteroidal MRA (2)	• UACR >30 mg/g and eGFR ≥25 ml/min per 1.73 m2 (finerenone) • Not recommended if serum potassium is >4.8 mEq/L prior to initiation or >5.5 mEq/L on treatment	Not yet known	• To be determined

UACR, urine albumin-creatinine ratio; ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; DKD, diabetic kidney disease; SGLT2, sodium-glucose cotransporter 2; GLP-1, glucagon-like peptide 1; MRA, mineralocorticoid antagonist.

The American Society of Nephrology (ASN) Diabetic Kidney Disease Collaborative (DKD-C) Task Force was formed in 2019 to promote strategies to augment awareness, detection, and intervention, with the ultimate goal of improving outcomes and survival for all people with DKD (29–31). To gain input from a broad stakeholder community, the DKD-C Task Force convened a series of three strategy conferences in 2020 and 2021. Each conference assembled a multidisciplinary group of physicians, pharmacists, nurses, federal agency representatives, health care system leaders, and patient advocates. Industry attendees were observers at the conferences. They had no role in the agendas, objectives, discussion topics, or decisions regarding content or publication. Herein, we report the conference proceedings with recommendations to inform practice, policy, and research on the basis of addressing seven critical questions (Table 2). One of the authors of this report (P.O.G.) used his own experience with DKD to illustrate current gaps in care and the urgent need for change in care models. His story is presented in subsequent sections to place our recommendations in the context of a patient journey.

Table 2.

Seven critical questions for delivering new therapies for diabetic kidney disease

Questions	Challenges	Recommendations	Considerations
(1) How should roles and responsibilities for implementing therapies for DKD be determined?	• DKD management overlaps between primary care, cardiology, endocrinology, and nephrology • Patients lack education about DKD and therapeutic options	• Interprofessional collaborative care models • Therapeutic choices driven by patient preferences and priorities • Trusted community voices to provide information and build trust among patients	• Specialties may differ in therapeutic adoption and risk-benefit acceptance • Involvement of advocacy groups and community health organizations in patient outreach
(2) What are current barriers and facilitators to use of DKD therapies?	• Shortage of primary care professionals and inconsistent access to specialists • Suboptimal professional communication and unavailability of patient information	• A multipronged learning and action collaborative founded on implementation science to develop coordinated teams • Interoperable electronic health record technologies between different health care systems and professionals	• Clinician training by didactic courses and experiential learnings • Team science models for collaborative care
(3) How can DKD care be prioritized in health care?	• Time constraints imposed by current care models • Many patients have financial barriers to DKD care	• New financial models to support care delivery • Expansion of technology access, especially in rural and deprived areas	• Health policy support for insurance coverage for DKD therapies • Reorganization of care delivery • Availability of telemedicine and remote technologies
(4) What can health care systems and payers do to support DKD care?	• A major barrier for payers and health care systems is the expense and complexity of DKD care delivery	• Real-world datasets to determine clinical outcomes and costs • Conduct demonstration projects that improve clinical outcomes at lower costs	• Pharmacoeconomic studies to make the case for health care system and payer endorsement • Health care systems and payers partner in reimbursement models to support therapeutic uptake and streamline DKD care delivery
(5) How can DKD care be equitable and inclusive across patient communities?	• Trust of the health care system and patient engagement is lacking in communities at high risk of DKD • Race-based diagnosis of CKD contributes to disparities in awareness, diagnosis, and treatment	• Community advisory boards and peers provide guidance and promote patient activation and clinical trial participation • Ongoing research to improve eGFR and other diagnostic methods • Pharmacists provide referrals to health care professionals and community resources	• Community advocates and peer mentors interface with patients in comfortable environments • Apply race-agnostic eGFR for CKD diagnosis and classification • The pharmacy as a location for on-site DKD testing, medication reconciliation, and provision
(6) What are dissemination and implementation strategies to improve DKD care?	• Different specialties may seek narrow solutions that lessen opportunities for optimal care • Patients feel disconnected from care when health care professionals are not coordinated in their approaches	• Share knowledge from implementation models between health care systems • Focus on wellness, quality of life, and hope to engage patients, families, and communities	• Dissemination and implementation efforts tailored to local health care delivery systems • Patient perspectives inform design of implementation strategies
(7) How can other patient groups be included in therapeutic development on the basis of DKD therapies?	• People with kidney transplants or type 1 diabetes and CKD have been excluded from the clinical trials of new DKD therapies • For expanded indications and comparative effectiveness studies, it is critical to determine safety as well as efficacy	• Pharmaceutical industry should cosponsor these efforts as well as supply study drug and placebo • Existing electronic health record data and registries could be used to examine safety and efficacy signals in patients who received therapies “off label”	• Collaborative sponsorship for clinical trials across federal agencies and institutes and the pharmaceutical industry • Advocacy and professional organizations as cooperative supporters for funding from charitable foundations and philanthropy

DKD, diabetic kidney disease.

Unmet Needs for Practice, Policy, and Research in Diabetic Kidney Disease

Numerous barriers contribute to subpar DKD identification and uptake of therapies ranging from the health care system to individual professional and patient levels. A shortage of primary care professionals is compounded by inconsistent access to cardiologists, endocrinologists, and nephrologists in the United States (32). Lack of access to care limits widespread and equitable implementation. The subspecialty referral system functions in “silos,” with limited crosstalk between clinicians. Care is further fragmentated by suboptimal communication and inconsistent availability of patient information. Current health care systems prioritize high procedural volumes over value-based care, thus impeding management of complex chronic conditions. Emphasis on specialties rather than on a holistic patient-centered approach results in low implementation rates and inconsistent therapeutic application.

To facilitate optimal DKD care, constructive disruption of current systems is needed. Solutions include implementation of multidisciplinary team care models (physicians, pharmacists, advanced practitioners, nurses, therapists, educators, nutritionists, and mental health professionals) with readily accessible communication technologies across health care systems and professionals, as demonstrated by the Indian Health Service (18,33,34). Defining roles and responsibilities for DKD care is essential to strategies for implementation considering the involvement of primary care along with specialists in endocrinology, cardiology, and nephrology. Pediatric nephrologists also need to be included in this approach considering the dramatic increase in types 1 and 2 diabetes along with DKD in adolescents (35,36). Most importantly, patients must be at the center of deliberations with their caregivers to ensure that they are fully informed and given the opportunity for their preferences and priorities to drive therapeutic choices.

Delay Does Not Mean Denial (P.O.G.)

My journey with type 2 diabetes has been challenging to say the least. It began in May 2003 when I was at work and noticed that I was feeling more sluggish and tired than usual. I went to the medical department for an evaluation only to discover that my glucose level was 755 mg/dl. I was taken to a hospital emergency department, where I found out that my hemoglobin A1c was 12%. I was extremely overwhelmed and confused because I was not familiar with any terminology regarding glucose, hemoglobin A1c, or what it meant to be “diabetic.”

Upon release from the hospital emergency department, the attending physician recommended consulting with an endocrinologist to help manage my type 2 diabetes. The endocrinologist prescribed two different forms of insulin and a pill to treat my diabetes. I was managing as best as I could until April 2013. During a routine clinic visit, my endocrinologist told me that I had CKD stage 3b. Shockingly, in that 10-year period since my diabetes diagnosis, I was never told that diabetes was the leading cause for kidney failure or screened for CKD. By December 2013, just 8 months later, I began peritoneal dialysis.

Prioritization in Health Care Systems

A major barrier to optimal DKD treatment in the United States is the paltry investment in primary and secondary preventative care. Unless systems are in place to identify and treat individuals at risk, there will be little benefit from new therapies. Implementing effective DKD screening will be well worth the expense, as recent cost-effectiveness analyses have clearly demonstrated that SGLT2 inhibitor therapy provides a favorable return on investment in people with type 2 diabetes. In an analysis from a cardiovascular outcomes trial of dapagliflozin, SGLT2 inhibitor treatment increased projected lifetime quality-adjusted life years (QALYs) and decreased costs of overall care that met UK thresholds for cost-effectiveness (37). The QALY gain in the United Kingdom was predominantly driven by reducing rates of CKD progression and kidney failure (64% of QALY gain) (37). Moreover, an analysis of both real-world evidence and cardiovascular outcome trial data showed that SGLT2 inhibitor use in the United States was cost effective primarily because of reduced costs for CKD progression and kidney failure, despite the fact that costs for SGLT2 inhibitors were substantially higher than in the United Kingdom or other countries (38). For the United States, SGLT2 inhibitors were deemed cost effective by meeting a willingness-to-pay threshold of $100,000 per QALY gained (38). Focusing specifically on a subset of participants with DKD in the cardiovascular outcomes trial of empagliflozin, this drug was deemed cost effective in the United States by showing an increase in life years (1.27) with an incremental cost-effectiveness ratio of $25,974 per QALY, an amount far below cost-effectiveness thresholds (39). Data on cost-effectiveness for new DKD therapies are central to increasing payer and health care system support of a concerted move toward preventative and value-based care. More favorable drug pricing would markedly improve the cost-effectiveness of new therapies. However, in the current US health care system, there are inadequate incentives for the pharmaceutical industry to lower drug prices.

Creating a convincing case for use of DKD therapies as part of a health care system strategy for value-based care is essential to translating theoretical cost-effectiveness analyses into reality. The Medicare Comprehensive End-Stage Renal Disease Care Innovation Model demonstrated improved care when providers assumed the consequent financial risks for patients. The coronavirus disease 2019 pandemic has exposed the financial vulnerability of health care systems’ fee-for-service models and will accelerate movement to value-based care (40). An obvious corollary is that expanding accessibility to DKD therapies by leveraging a larger pool of shared savings will be possible in an increasingly capitated environment. Health care systems that do not address high-cost chronic conditions, such as DKD, in a more longitudinal manner will be jeopardized by external risk-bearing vendors and rivals (41). Health care systems and payers actively seeking solutions to lower total cost of care should be keen to collaborate in promoting upstream DKD therapies in order to mitigate downstream costs (42).

It is imperative for health care systems, payers, and pharmaceutical companies to partner in financial models that increase access to DKD therapies and associated monitoring. Aligning goals, reorganizing care delivery, and changing practices will require dedication of greater resources by all stakeholders. At the health care system level, consultations with specialists in endocrinology, cardiology, and nephrology should be made readily available to primary care professionals for guidance on uptake of DKD screening, therapies, and follow-up. Real-world datasets from electronic health records and payer databases should be used to determine benefits on clinical outcomes as well as costs for implementation of DKD therapies in daily practice. Support from payers should be facilitated by demonstration projects of integrated care models that deliver improved clinical outcomes for DKD at lower costs. Federal agencies that conduct CKD surveillance should also track the population-level effect of changes in health care delivery on clinical outcomes. The pharmaceutical industry should contribute to value-based care with affordable pricing structures.

At the individual professional level, a key impediment to DKD care is the time constraints imposed by present models. Visits for patients with DKD are complex, requiring attention to details of conventional risk factors and new therapies for kidney and heart protection. Other contributors to low rates of prescribing DKD therapies are the additional time and effort involved with negotiating prior authorizations or completing medication assistance program requests, monitoring and dose adjustments, and patient financial burdens from high out-of-pocket copayments (28). Finerenone, in particular, has requirements for dose adjustment by eGFR and serum potassium that necessitate intensive monitoring that can be a barrier to clinician prescribing and patient acceptance. Addressing even one or two of these issues requires more time than is available in a conventional clinic visit. Balancing this lengthy agenda with other health concerns while also addressing patient priorities and preferences is exceedingly challenging. Moreover, discrepancies in clinical practice guideline recommendations from various professional organizations add to confusion that impedes understanding of best practices. To address this concern, the Kidney Disease Improving Global Outcomes and the American Diabetes Association have formed a consensus working group that will harmonize, publish, and promote a summation of their shared recommendations for CKD screening, diagnosis, and therapeutic approaches in diabetes.

Patients with DKD typically take multiple medications, and often, the new therapies are prohibitively expensive. In the United States, the retail pharmacy price for a 1-month supply of an SGLT2 inhibitor ranges from $530 to $650 (Table 3) (43,44). Finerenone is comparably priced at $580 to $690 per month (43). GLP-1 receptor agonists are even more expensive at $770 to $1300 per month (43). Therefore, the low rates of clinical uptake are quite likely the result of insurers’ reluctance to pay the costs of these medications and the often daunting preauthorization processes. Even after insurance support is formally requested and obtained, monthly copayments can still be hundreds of dollars per month for a single one of these medications. A study from the Urban Institute and the Robert Wood Johnson Foundation found that nearly 13 million adults in the United States skipped or delayed filling prescriptions due to high costs in 2018–2019 (45). Online retail pharmacies from Canada and international markets price SGLT2 inhibitors and GLP-1 receptor agonists 70%–90% lower than in the United States (Table 3) (46). In most other countries, drug prices are regulated and capped (47). Drug pricing in the United States is complicated by many factors, including inflated retail prices, the number of commercial entities involved between the pharmaceutical company and the patient, and nontransparent negotiations. Retail prices of prescription drugs are considerably higher than prices given to pharmacy benefit managers, insurers, hospitals, and governmental organizations, which receive discounts and rebates in exchange for favorable formulary placements. Uninsured patients and those with high-deductible insurance plans pay the most for prescription drugs. As a vital strategy to provide equitable access and reduce pervasive racial and ethnic disparities, the DKD-C Task Force is partnering with the ASN policy committee on an action plan for health policies to directly address high drug prices and to facilitate adequate insurance coverage for all.

Table 3.

International retail prices for a 1-month supply of guideline-based therapies for diabetic kidney disease

Drug Classes	Retail Price for a 1-mo Supply, US$
	United States	Canada	United Kingdom	India	Australia and New Zealand	Turkey
SGLT2 inhibitors
Empagliflozin	550–660	40–90	90	30–150	80–90	30–50
Dapagliflozin	530–650	40–180	90–120	40–80	100–150	40–80
Canagliflozin	560–650	70–170	100–140	60–140	ND	ND
Finerenone	580–690	ND	ND	ND	ND	ND
GLP-1 receptor agonists
Dulaglutide	770–1050	ND	ND	ND	ND	ND
Semaglutide	880–1300	320–340	200	ND	ND	ND
Liraglutide	1000–1220	ND	ND	ND	ND	ND

The sources were the PharmacyChecker (46) and GoodRx (43) websites (accessed April 11, 2022) (41,44). Prices are rounded to nearest $10. Semaglutide prices are for subcutaneous and oral formulations. SGLT2, sodium-glucose cotransporter 2; ND, no data; GLP-1, glucagon-like peptide 1.

As the number of guideline-recommended therapies for DKD grows, polypharmacy becomes another barrier to optimal care due to complexity, safety concerns, and costs. Furthermore, delivery of care for persons with diabetes worsened during the coronavirus disease 2019 pandemic particularly among persons younger than 60 years of age, who frequently reported missing medical care (63%–87%) or decreased access to medication (26%–44%) (48). This decline in care reveals many additional barriers, especially for patients who reside in rural or deprived areas. There is often confusion about differing recommendations from health care professionals as well as contradictory information gleaned from the internet, social media, and advertisements. Even with the availability of electronic health record portals, patient adoption of remote communication strategies with care teams has been limited by lack of technology, language barriers, and low health literacy. ASN and the National Kidney Foundation (NKF) have launched national kidney disease awareness campaigns (united4kidneyhealth.org; www.kidney.org/newsletter/are-you-33-percent). To improve patient access to care and resources, technology access must be improved, expanded, and made available in underserved regions.

There Is Hope (P.O.G.)

After dialyzing for 4 years, I received a kidney transplant in April 2017. During a routine appointment at my transplant center, a nurse recommended that I enroll in a weight loss program. Doing so would help me manage my diabetes and teach me about a healthier lifestyle. While enrolled in the program, my endocrinologist released me from both forms of insulin and pill medication. I successfully lost >70 pounds in this program. However, it was not until I joined the DKD-C Task Force that I learned about new diabetes innovations in the form of SGLT2 inhibitors and GLP-1 receptor agonists.

At the first DKD-C Task Force conference in January 2020, I learned more about these medical innovations. That discussion led me to make an appointment with my weight loss doctor to discuss new therapies. Because of having a family history of coronary heart disease, I requested one of them. I began taking a GLP-1 receptor agonist in February 2020. Since using this medicine, my hemoglobin A1c went from >11% to 5%, and I no longer use insulin. I am encouraged by having added protection for my heart and new kidney with this therapy and a long-awaited advance that can positively affect those suffering from DKD.

Implementation Strategies and Health Justice

Dissemination and implementation efforts must be tailored to local health care systems. One system may find a specialist-driven multidisciplinary clinic most attractive, whereas another may favor a primary care–based model. Either way, interprofessional dialogue to establish shared priorities and a business case for DKD care is essential. With alignment, implementation materials and tools can be developed to address care gaps and promote collaboration. Knowledge from these projects can be disseminated between health care systems to implement optimal DKD care. Local pharmacists are in a prime position to identify patients early in their DKD journey when therapies are most effective. They can readily identify people with diabetes via prescriptions for glucose-lowering agents. The pharmacy is an ideal location for on-site testing of serum creatinine, albuminuria, hemoglobin A1c, and BP. As follow-up after testing, pharmacists can provide referrals to health care professionals and community resources. They can also provide medication reconciliation between prescribers as well as medication management for safety, effectiveness, and convenience. Social workers and pharmacists are valuable resources to assist patients with accessing medication assistance programs. Professional organizations, such as the DKD-C Task Force, are creating educational resources in user-friendly formats to provide practical, evidence-based education with a focus on the patient journey. Additionally, with the recent regulatory approvals of new DKD therapies, the pharmaceutical industry has fresh opportunities to raise public awareness, educate clinicians, and provide patient educational resources. However, partnerships between industry, professional organizations, and academia must be thoughtfully crafted to avoid conflicts of interest.

To promote equity in implementation as well as in clinical trial participation, culturally competent outreach is needed to overcome barriers to acceptance of medical care and research (49,50). Trust of the health care system is lacking in many underserved and minority communities at high risk of DKD. Patient and community perspectives are essential to the design of implementation strategies. Emphasis on wellness, quality of life, and hope helps to engage people concerned about DKD. Advocacy groups and community health organizations play important roles in patient education and are trusted voices with relationships that reflect common histories, cultures, beliefs, norms, and values. Community advisory boards and peer mentors interface with patients in environments where they feel comfortable and help to determine local needs. These groups are also an invaluable resource for guidance on tools and outreach. Community health workers can promote health literacy, acceptance of health care, patient activation, and clinical research participation (51). Furthermore, ASN and NKF have partnered on recommendations for race-agnostic methods to diagnose and classify CKD as a path toward health justice (52). This has resulted in a new eGFR equation that does not include a term for race given the fact that race is a social construct and not a biologic construct. It is hoped that this change will increase CKD awareness and more timely CKD detection and therapeutic intervention for all people (53,54).

Clinical trials of SGLT2 inhibitors, GLP-1 receptor agonists, and finereone have heretofore excluded individuals with diabetes and kidney transplants or those with type 1 diabetes and CKD who could possibly benefit from these therapies. Appropriate trials in these groups should be initiated and will need to include expanded monitoring, especially considering the known risks of genital mycotic infections, volume depletion, and diabetic ketoacidosis with SGLT2 inhibitors and hyperkalemia with finerenone. Adverse events from SGLT2 inhibitors of particular concern for kidney transplant trials could include alloimmune events of acute rejection or donor-specific antibodies, acute eGFR changes as a lingering concern despite reassuring protection in CKD, fractures given signals in early trials and high background risk of bone disease, and ketoacidosis or other metabolic acidoses considering specific tubular dysfunction (55,56). Trials in type 1 diabetes with SGLT2 inhibitors will need to focus on the greater risk of ketoacidosis and added burden of ketone monitoring, medication stopping rules, and diabetes management (57). Identification of a single entity that would support clinical trials for kidney transplant and type 1 diabetes populations is difficult. Considering overlapping goals across specialties and patient centeredness, studies of new DKD therapies in these populations could arise by collaborative support from different institutes within the National Institutes of Health or the Patient-Centered Outcomes Research Institute. Private sector partners from the pharmaceutical industry should cosponsor these efforts as well as supply study drug and placebo. In addition, existing data from electronic health records and clinical registries could be used to examine safety and effectiveness signals in patients with kidney transplants or type 1 diabetes who have received these therapies “off label.”

Similar considerations apply to prioritizing treatments for persons with type 2 diabetes and CKD. Formation of a consortium of advocacy and professional organizations could promote research including comparative effectiveness studies to identify optimal approaches, including therapeutic combinations (e.g., ACE inhibitor or ARB and SGLT2 inhibitor with or without finerenone or a GLP-1 receptor agonist), as well as how to individualize treatment as we move toward precision medicine. Such a consortium could leverage charitable foundations, philanthropic organizations, the pharmaceutical industry, and federal agencies to encourage clinical trials and facilitate drug development pathways.

DKD has enormous personal and societal consequences in terms of worsened quality of life, mortality, and health care costs. Access to care and implementation of breakthrough therapies for DKD can save millions of lives by preventing kidney failure, cardiovascular events, and premature death. The DKD-C Task Force calls for coordinated patient-centered care models incorporating these therapies for all people living with DKD. Coalitions of patients, families, community groups, health care professionals, health care systems, federal agencies, and payers need to develop collaborative models of care (Figure 2) that will effectively and equitably address this major public health problem.

Figure 2.

Collaborative model of care recommended by the American Society of Nephrology Diabetic Kidney Disease Collaborative Task Force inclusive of patients, families, community groups, health care professionals, health care systems, federal agencies, and payers. DKD, diabetic kidney disease.

Disclosures

The following companies provided support to ASN for the planning and conduct of the DKD-C strategy conferences: AstraZeneca, Bayer, Boehringer Ingelheim, Janssen, and Lilly. C. Argyropoulos reports consultancy agreements with Alkahest, Baxter, Bayer, and Momenta Pharma; research funding from Akebia and Alkahest; and serving in an advisory or leadership role for Baxter Healthcare, Bayer, the Health Services Advisory Group, and Quanta. C. Argyropoulos reports other interests or relationships with AbbVie (Sub-Investigator in a phase 3 study of an experimental agent in diabetic nephropathy), Akebia (PrincipaI Investigator in two phase 3 trials of an investigational product for the correction and maintenance of anemia in patients with nondialysis-dependent CKD and one phase 3 study of the same agent in dialysis), DCI Inc. (Medical Director of the Outpatient Dialysis Unit in Cuba, NM), and the Chronic Kidney Disease Dialysis Outcomes and Practice Patterns Study (PI for CKD-DOPP). F.C. Brosius reports consultancy agreements with the Gilead Sciences Diabetic Kidney Disease Advisory Board (2021; completed); research funding from the National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases; honoraria from various universities; serving as an associate editor of Diabetes; serving on the editorial board of American Journal of Physiology and JCI; and other interests or relationships with ASN, the Diabetic Kidney Disease Advisory Board (Gilead Pharmaceuticals; spring 2021, no longer active), and the DKD-C Task Force. D. Cherney reports ownership interest in Abbvie, AstraZeneca, Bayer, Bristol Myers Squibb (BMS), Boehringer Ingelheim-Lilly, CSL-Behring, Janssen, Maze, Merck, Mitsubishi-Tanabe, Novartis, Novo Nordisk, Prometic, Sanofi, Otsuka, and Yeungene; research funding from AstraZeneca, Boehringer Ingelheim-Lilly, Janssen, Merck, Novo Nordisk, and Sanofi; honoraria from Abbvie, AstraZeneca, Bayer, BMS, Boehringer Ingelheim-Lilly, CSL-Behring, Janssen, Maze, Merck, Mitsubishi-Tanabe, Novartis, Novo Nordisk, Otsuka, Prometic, Sanofi, and Yeungene; and serving in an advisory or leadership role for AstraZeneca, Bayer, BMS, Boehringer Ingelheim-Lilly, CSL-Behring, Janssen, Lexicon, Maze, Merck, Novartis, and Novo Nordisk. K. Fowler reports employment with The Voice of the Patient, Inc.; consultancy agreements with Akebia, Bayer, CSL-Behring, eGenesis, Gilead, Hansa Biopharma, Natera, Otsuka, Palladio Biosciences, Responsum CKD, Talaris, Travere Therapeutics, ValenzaBio, and Veloxis; serving in an advisory or leadership role for the Global Renal Exercise Group, the Kidney Health Initiative Board of Directors, the Kidney Research Institute, and the NKF (A) Kidney Health Community and (B) Kidney Advisory Committee; and serving as a member of International Society of Nephrology (ISN) and as a patient editor for CJASN. P.O. Gee reports being self-employed by iAdvocate, Inc., a health and wellness organization; consultancy agreements with Evidation Health; honoraria from AMGEN, the APOL1 Long-Term Kidney Transplantation Outcomes Network (APOLLO) Community Advisory Council, Bayer International, CareDx, the Center for Dialysis Innovation (CDI) Patient Advisory Board, NephCure International, Patient Family Center Care Partners (PFPC Partners), Otsuka Pharmaceutical, Patient Family Advisors Network, Traverse, and Vertex International; serving in an advisory or leadership role for the APOLLO Community Advisory Council, ESRD Network 5 the Food and Drug Administration MedTech Color Collaborative Steering Committee on Health Equity in Medical Devices, the HTIC Health Equity Advisory Board, the Human Factors Working Group, the NephCure International/HEAL Collaborative Health Equity Steering Committee, the NephCure International/HEAL Collaborative Patient Advisory Board, the Patient Family Centered Care (PFCC) Partners Advisory Board, and the University of Washington CDI Patient Advisory Board; speakers bureau for CareDx, Evidation Health, and Project TECH; and other interests or relationships as an American Association of Kidney Patients (AAKP) ambassador, an American Kidney Foundation (AKF) ambassador and kidney health coach, an ASN DKD-C Task Force member, a CareDx ambassador, a KHI PFPC member, a Kidney360 patient perspective ambassador, a Kidney Political Action Committee (PAC) member, NKF Kidney Advisory Council, a PCORI ambassador, a PFCC Partners Diversity, Equity, and Inclusion Work Group member, Quality Insights Renal Network 5- Political Action Committee chair, and a UNOS ambassador. R.C. Harris reports employment with the Nashville Veterans Administration Hospital; consultancy agreements with Bayer, Fibrocor, and Nicoya; ownership interest in Apple; research funding from Bayer; patents or royalties for endothelial nitric oxide synthase db/db mouse; serving in an advisory or leadership role for the Kidney Health Initiative (KHI; paid); and other interests or relationships as the KHI co-chair and a member of the board of directors. A.S. Kliger reports employment with Metabolism Associates, New Haven; consultancy agreements with ASN; multiple equity positions managed by UBS; and other interests or relationships with ASN and the Renal Physicians Association. A. Kliger reports serving in an advisory or leadership role for ASN (chair, Nephrolgists Transforming Dialysis Safety (NTDS), the Coronavirus Disease 2019 (COVID-19) Response Team (co-chair), and the Excellence in Patient Care Advisory Committee (chair). A. Mottl reports consultancy agreements with Bayer; research funding from Alexion, Aurinia, Bayer, Calliditas, and Pfizer; honoraria from Bayer and UpToDate; and serving in an advisory or leadership role for Bayer. S.E. Quaggin reports consultancy agreements with AstraZeneca, Boehringer-Ingelheim, Genentech, Janssen, Johnson and Johnson, the Lowy Medical Research Foundation, Novartis, Pfizer, Roche, and UNITY; ownership interest in Mannin Research; serving in an advisory or leadership role for AstraZeneca, Genentech/Roche, JCI, the Karolinska Cardiovascular and Renal Medicine Institute, the Lowy Medical Research Institute, Mannin, Novartis, Pfizer, the Pfizer ASPIRE program committee, and UNITY; and other interests or relationships as Chief Scientific Officer and founder of Mannin Research. J. Rangaswami reports consultancy agreements with AstraZeneca, Boehringer-Lily, Edwards LifeSciences, and Procyrion Inc. (Aortix); serving in an advisory or leadership role on the medical advisory board for Procyrion Inc. (Aortix); and other interests or relationships as chair-elect of the Council on the Kidney in Cardiovascular Disease for American Heart Association. G. Roberts reports owning 50% of Options Unlimited International and serving on the AAKP speakers bureau. G. Roberts reports serving in an advisory or leadership role for the APOLLO Community Advisory Board, the ASN COVID-19 Response Team and Transplant Subcommittee, the Center for Dialysis Innovation Patient Advisory Board, the Center for Innovations in Cancer & Transplants (chair of the community engagement committee and member of the steering committee), the Chronic Renal Insufficiency Cohort study Expert Patient Panel, the C-Path Patient Engagement Committee and DIKI Project (paid), the Home Dialyzers United Advisory Committee, the Kidney Disease Improving Global Outcomes Clinical Practice Guideline Update Working Group, the KHI APOL1 Steering Committee, KHI PFPC Partners, and the KRI Patient Advisory Committee. G. Roberts reports other interests or relationships with the AAKP, the APOLLO Recruitment and Dissemination Committees, the ASN NTSD Quality, Assessment, Improvement and Education Work Group, the Canadian Strategy for Patient Oriented Research (Can-SOLVE) CKD International Research Advisory Committee, the ISN Patient Group, NKF as an ambassador, the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney, the NKF Kidney Action Committee Diversity Work Group, and the NKF Patient Education Series. G. Roberts’s spouse reports consultancy agreements with Vortex. W. St. Peter reports consultancy agreements with Total Renal Care, Inc.; honoraria from the American Nephrology Nursing Association, Integritas Group, Letters and Sciences, and OptumLabs; serving as a scientific advisory board member for NKF; and other interests or relationships with the Centers for Medicare and Medicaid Services Technical Expert Panel on Development of a Quality Measure Assessing Delay in Progression of CKD, the NKF and ASN Task Force on eGFR and Race, and the Technical Expert Panel for the Quality Insights Kidney Care Pilot Project. K.R. Tuttle reports consultancy agreements with AstraZeneca, Bayer, Boehringer Ingelheim, Goldfinch Bio, Janssen, Novo Nordisk, and Travere; research funding from Bayer, Goldfinch Bio, and Travere; and honoraria from Bayer, Boehringer Ingelheim, Gilead, and Novo Nordisk. K.R. Tuttle reports relationships with Astra Zeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Gilead, Goldfinch Bio, Novo Nordisk, and Travere for research and other support regarding diabetes and CKD. L. Wong reports employment with DaVita, Inc.; consultancy agreements with Fresenius Medical Therapies; ownership interest in DaVita, Inc.; honoraria from Fresenius Medical Therapies; serving in an advisory or leadership role for the BMC Nephrology editorial board and the NTDS Board of Directors; and serving as a member at large on the ASN Excellence in Patient Care Committee.

Funding

None.

Author Contributions

C. Argyropoulos, F.C. Brosius, D. Cherney, K. Fowler, P.O. Gee, R.C. Harris, A.S. Kliger, A. Mottl, S.E. Quaggin, J. Rangaswami, G. Roberts, W. St. Peter, K.R. Tuttle, and L. Wong conceptualized the study; K.R. Tuttle was responsible for methodology; K.R. Tuttle was responsible for project administration; S.E. Quaggin and K.R. Tuttle provided supervision; C. Argyropoulos, F.C. Brosius, D. Cherney, K. Fowler, P.O. Gee, R.C. Harris, A.S. Kliger, A. Mottl, S.E. Quaggin, J. Rangaswami, G. Roberts, W. St. Peter, K.R. Tuttle, and L. Wong wrote the original draft; and C. Argyropoulos, F.C. Brosius, D. Cherney, K. Fowler, P.O. Gee, R.C. Harris, A.S. Kliger, A. Mottl, S.E. Quaggin, J. Rangaswami, G. Roberts, W. St. Peter, K.R. Tuttle, and L. Wong reviewed and edited the manuscript.