Testing Interventions that Address Kidney Health Disparities

CKD and kidney failure disproportionately affect marginalized racial and ethnic populations because of structured inequalities. Studies have demonstrated marked racial, gender-based, and socioeconomic disparities in kidney disease–related morbidity and mortality, as well as disparities in access to evidence-based kidney care, including nephrology referral, timely preparation for KRT, and kidney transplantation.¹ The multifactorial and synergistic root causes of kidney health disparities have made the development, implementation, and rigorous evaluation of interventions challenging. There is a critical need for clinical trials to identify effective interventions and develop sustainable, evidence-based strategies that reduce kidney health disparities. Recognizing this gap in knowledge, the National Institute of Diabetes, Digestive, and Kidney Diseases (NIDDK) and partner institutes convened a consortium to design and conduct clinical trials and build infrastructure for future clinical trials addressing structural racism and downstream social and biologic effects to promote kidney health equity.

The Eliminating RAcism and Structural inEquities in Kidney Disease Consortium

The Eliminating RAcism and Structural inEquities in Kidney Disease (ERASE-KD) consortium will conduct five phase 2 randomized clinical trials to address structural racism as a barrier to optimal kidney care and outcomes. The interventions and trial designs were heavily informed by feedback from community partners, including people with CKD, caregivers, community leaders, policymakers, advocates, and clinicians. Four of the trials will intervene in stage 4–5 CKD to reduce disparities in access to kidney transplantation or optimal KRT, and one trial seeks to reduce unplanned health care utilization in earlier CKD. The interventions range from high-intensity patient-level interventions to low-intensity systems-based interventions, incorporating elements of effective approaches previously identified in an NIDDK workshop.²

Central principles of the ERASE-KD consortium include (1) application of an antiracist lens to all study phases; (2) race and language concordance as one approach to strengthen alliances between patients and clinical teams; (3) assessment of social risks; (4) rigor in trial design and analysis; and (5) equitable and sustainable implementation and dissemination. Community-engaged research methodologies underscore the need to continuously partner with affected populations in all aspects of these studies, including dissemination of findings.³

Before finalizing the trial designs, the consortium designed a conceptual framework that demonstrates structural racism as a root cause of kidney health disparities and identifies the targets of each trial intervention (Figure 1). Multiple contributing mechanisms were recognized, including but not limited to residential segregation, systemic biases in health care, rurality, lack of high-quality language interpretation and translation of materials for people with limited English proficiency, and lack of safeguards, including universal health care coverage. This framework informed the antiracist lens that was used to finalize the interventions.

Figure 1.

ERASE-KD conceptual framework. *Community health workers, kidney health coaches, and navigators are roles that are often used interchangeably. However, for the ERASE-KD interventions, these team members vary based on their activities, engagement with participants, and integration within their respective health systems or communities. **Although each of the listed structural racism indicators may affect kidney outcomes, only those with asterisks are a target of one or more ERASE-KD interventions. ERASE-KD, Eliminating RAcism and Structural inEquities in Kidney Disease.

Trusted multidisciplinary teams may help to effectively dismantle and repair inequitable systems and patient-level barriers to optimal care. Three of the ERASE-KD interventions focus on patient interactions with race-concordant and language-concordant teams, including two trials with community health workers (CHW)⁴ or kidney health coaches and one trial including a racially concordant transplant team composed of a social worker, transplant nephrologist, and transplant surgeon. The study teams and consortium steering committee carefully considered the implications of intervening in only one racial or ethnic group at the exclusion of other populations. In the end, the consortium felt that trust-building and rapport-building were critical to the success of these interventions, which are tailored to the sociocultural context and thus most appropriately delivered to a specific population. Given this community-specific strategy, adaptation and validation of these interventions for use in other populations will be important if the phase 2 trials demonstrate efficacy.

Adverse kidney outcomes disproportionately affect individuals with high social needs and lower socioeconomic status. Two trials in ERASE-KD will enroll people with CKD regardless of race or ethnicity. Because enrollment is focused in low-income and structurally disadvantaged communities, it is anticipated that most of the participants will have a high burden of unmet health-related social needs, defined as “social and economic needs that individuals experience that affect their ability to maintain their health and well-being.”⁵ Investigators considered the possibility that interventions addressing social needs may improve overall population outcomes while exacerbating specific racial, ethnic, or socioeconomic disparities. This consideration is particularly relevant to structural or system-wide interventions that might be more successfully leveraged by some groups or individuals, e.g., those with higher health literacy, better transportation, or greater trust in the health care system. These trials require robust statistical analysis plans to test for interactions between sociodemographic categories and treatment effect, recognizing that subgroup analyses are limited by sample size. All ERASE-KD trials will screen for health-related social risks including food insecurity, housing instability, and transportation challenges using the Accountable Health Communities screening tool, as well as social risk factors including socioeconomic status and residential and community context.⁶ Several ERASE-KD trials will connect participants with unmet social needs to community-based organizations through closed-loop referral systems.

Across all five ERASE-KD trials and many other studies that address health disparities, the interventions will be administered at least in part by specific individuals, including CHWs, kidney health coaches, and clinicians. In particular when there will be significant interaction between participants and a relatively small number of individuals who administer the intervention (treatment agents), an individually randomized group treatment (IRGT) trial design should be considered. The IRGT design accounts for the possibility that the effect of an intervention varies based on who administers it, resulting in clusters defined by the treatment agent. In an IRGT, individual participants are randomized to the intervention or standard of care arm as in a conventional randomized trial, but sample size calculations and analysis plans account for natural clustering by treatment agent in the intervention arm.⁷ Failure to account for clustering or intraclass correlation in the analysis may lead to an inflated type 1 error rate, while failure to account for clustering in sample size calculations may lead to an underpowered study. IRGT principles should be considered whenever the intervention will be administered by a small number of treatment agents who cannot be considered interchangeable. The ERASE-KD trials will provide robust estimates of intraclass correlation and effect size to inform the design of phase 3 trials of similar interventions to address health disparities. The consortium will also contribute new approaches to sample size calculation for time-to-event end points in IRGT.

Equity-focused implementation science principles are another key consideration across all ERASE-KD trials. Evaluating implementation outcomes including reach, adoption, fidelity, and sustainability can support widespread uptake of evidence-based interventions. To understand best practices around implementation and contextual factors, all study protocols have incorporated an implementation evaluation, ranging from individual-level assessments (i.e., surveys and interviews) to system-level assessments leveraging electronic health record data. Ensuring that the trial results are robust and generalizable is essential to support policy change and encourage broader adoption of effective interventions. Recent Centers for Medicare & Medicaid Services policies that provide reimbursement for CHWs, patient navigators, and social work services may facilitate adoption.⁸

Study teams have developed robust dissemination plans that include dissemination of best practices for optimizing equity, such as staff and organizational antibias trainings. Several trials will also evaluate cost-effectiveness to inform implementation and future trials aimed at advancing kidney health equity.

Future Applications

The collection of common data elements, including patient-reported outcomes and assessment of social risk factors, across ERASE-KD will help to identify areas of need for future trials and ensure prioritization of interventions with greatest value and relevance for affected populations.^9,10 Curbing multidecade kidney health disparities will require careful delineation of causal pathways and theoretical frameworks to identify underlying mechanisms. The prioritization of a priori hypothesis generation regarding causal pathways will inform the design of future interventions to improve health equity.

Supplementary Material

jasn-36-970-s001.docx ^{(27.3KB, docx)}

jasn-36-970-s002.pdf ^{(1.4MB, pdf)}

Disclosures

Disclosure forms, as provided by each author, are available with the online version of the article at http://links.lww.com/JSN/F7.

Funding

C.M. Wyatt: NIDDK (U24DK137631). D. Mohottige: NIDDK (K23DK139454). J.E. Obayemi: NIDDK (T32DK077662). A.E. Johnson: NHLBI (K23HL165110). S.L. Tummalapalli: Agency for Healthcare Research and Quality (K08HS028684). L. Glover: NHLBI TransOmics for Precision Medicine Fellowship. This work was supported by NIDDK (U01DK137269, U01DK137272, U01DK137258, U01DK124645, and U01DK137262).

Author Contributions

Conceptualization: Stefany Olague.

Funding acquisition: Huiman Barnhart, Keisha Bentley-Edwards, Christina M. Wyatt.

Methodology: Huiman Barnhart, Keisha Bentley-Edwards, LáShauntá Glover, Christina M. Wyatt.

Supervision: Christina M. Wyatt.

Writing – original draft: Christina M. Wyatt.

Writing – review & editing: Huiman Barnhart, Keisha Bentley-Edwards, LáShauntá Glover, Amber E. Johnson, Dinushika Mohottige, Joy E. Obayemi, Stefany Olague, Melvin Thompson, Sri Lekha Tummalapalli, Megan Urbanski, Christina M. Wyatt.

Supplemental Material

This article contains the following supplemental material online at http://links.lww.com/JSN/F15.

Supplemental Summary 1. ERASE-Kidney Disease Consortium members.