Beyond the test: patient-reported concerns and worries regarding kidney conditions and APOL1 genetic testing among Black patients

Introduction

The frequency of chronic kidney disease (CKD) in Black individuals is two to three times higher than in White Americans. A portion of this increased risk appears attributable to polymorphisms in the gene encoding apolipoprotein L1 (APOL1) (1, 2). The two renal risk variants (RRVs), G1 (two amino acid substitutions) and G2 (two amino acid deletions), evolved to confer resistance to certain subspecies of Trypanosoma parasites. Combinations of two RRVs (G1/G1, G2/G2, or G1/G2) are referred to as APOL1 high-risk genotypes and are associated with increased risk of CKD development and progression (1). Many individuals with APOL1-associated kidney disease and subnephrotic proteinuria are misclassified as having CKD of unknown etiology or hypertension-attributed CKD (2). In the United States, the estimated allelic frequency among Black Americans is 20%-22% for G1 and 13%-15% for G2, with approximately 10%-15% carrying an APOL1 high-risk genotype (1). Despite its clinical relevance for characterizing CKD etiology and risk, APOL1 genetic testing remains uncommon among Black patients with established CKD or at risk for kidney complications.

Patients with or at risk for CKD may experience concern related to uncertainty about their health and potential long-term complications, including the need for kidney replacement therapy (3, 4). In patients with or at risk for CKD, genetic diagnosis may offer several benefits, including greater understanding of disease etiology, improved genetic counseling for family planning, assessment of recurrence risk after kidney transplantation, and opportunities for presymptomatic testing among at-risk family members (5). Conversely, a genetic diagnosis may have emotional consequences, including concern about future health risks and the possibility of transmitting genetic risk to offspring (5, 6). Even among healthy individuals, such as living kidney donor candidates, APOL1 testing may evoke psychological distress and fear of kidney failure (7). Disease-specific education can mitigate anxiety and improve engagement, as knowledge may foster adaptive illness perceptions and reduce misinformation (8). In addition, APOL1 testing and disclosure of genotype results have been associated with positive self-reported behavior changes and improved medication adherence among individuals with APOL1 high-risk genotypes (9).

Despite growing recognition of the genetic and psychosocial dimensions of APOL1-associated kidney disease, data on how Black patients perceive and respond to APOL1 genetic testing remain limited. Pilot studies suggest overall openness to genetic testing (10), yet the nature and evolution of patient-reported concern and worry related to APOL1 testing have not been well characterized. Understanding these responses is important for addressing potential psychological barriers and supporting informed engagement with precision nephrology. Therefore, we investigated patterns of concern about kidney conditions and worry related to APOL1 high-risk genotypes among Black adults undergoing APOL1 genotyping in a prospective cohort study, with the goal of better understanding how genetic risk information may influence perceptions relevant to kidney health and engagement in care.

Materials and methods

Study design and participants

We conducted a single-center, prospective study of self-identified Black individuals receiving care through Nephrology and Internal Medicine services at a Midwestern academic medical center (11, 12). Eligibility criteria included self-identified Black race, age ≥18 years, and no dialysis dependence or prior kidney transplantation at enrollment. Potential participants received an explanation of APOL1 and the current understanding of the relationship between APOL1 RRVs and CKD. Written informed consent was obtained before genetic testing, and participants received an honorarium for their time at enrollment and survey completion.

Baseline enrollment included blood sample collection for APOL1 genetic testing as a research test, chart review of demographic and kidney health-related parameters [age, sex, body mass index (BMI), blood pressure, diabetes], and administration of surveys including sociodemographic information and attitudes. Sociodemographic characteristics included age, sex, educational attainment, and annual household income. Estimated glomerular filtration rate (eGFR) was calculated using the 2021 race-free CKD-EPI creatinine equation (13).

Detailed information concerning the study flow and genetic testing is provided in the Supplementary Material and Supplementary Figure 1 (11, 12). Relevant to this report, individual APOL1 genotyping results were returned to participants in person, together with a written report, by the 3-month follow-up visit. Research results were private information of the participants and were not shared directly with referring clinicians, although participants could share their results with clinicians if they chose to do so.

In addition to education provided by the study team, following the sharing of APOL1 genotype results, participants were offered genetic counseling with the same certified genetic counselor affiliated with the institution. Counseling was conducted as a separate counseling visit and included education regarding APOL1-associated kidney disease risk, interpretation of test results, and discussion of participant questions. Counseling emphasized that an APOL1 high-risk genotype is a risk factor rather than a diagnosis and that kidney disease is not inevitable. Discussions also highlighted the importance of kidney monitoring and management of other risk factors. Counseling costs were covered by the protocol, and all participants had access to genetic counseling regardless of genotype result.

Participant surveys and chart review of health history and laboratory data were performed at baseline and approximately 3 and 12 months after enrollment, in coordination with standard-of-care follow-up. Enrolled participants who did not return for follow-up at the medical center had the opportunity to complete surveys by email or telephone. The study was approved by the Saint Louis University Institutional Review Board (Protocol ID 29188) and is registered at ClinicalTrials.gov (NCT05656261). Enrollment began on January 24, 2019, and this analysis includes participants who completed 3-month follow-up as of January 1, 2025.

Concerns and worrying attitudes

The survey was developed by the study team to assess APOL1-related perceptions, attitudes, and anticipated behavioral responses and was informed by established behavioral frameworks, including the Health Belief Model, and prior APOL1-related literature (14–16). Participants were asked about their degree of concerns regarding kidney conditions and worry about having an APOL1 high-risk genotype using a survey completed at baseline and 3 months after enrollment. Degree of concern was assessed on a Likert scale ranging from 1 (“not at all”) to 5 (“extremely”). For selected analyses, responses were dichotomized as “very much or extremely concerned” (Likert score 4 or 5) versus all other responses. Worry was assessed as a binary indicator. We examined changes in kidney-related concerns and worry from baseline to 3 months.

Statistical analysis

Demographic and clinical parameters were summarized according to APOL1 genotype and presented as percentages for categorical variables and median ± interquartile range (IQR) for continuous variables. Categorical variables were compared using the chi-square test, and continuous variables were compared using the Wilcoxon rank-sum test. APOL1 RRV distributions were examined according to baseline clinical characteristics. For follow-up analyses, changes in concern and worry from baseline to 3 months were categorized as “decreased,” “unchanged,” or “increased.” APOL1 RRV distributions were then examined across these response patterns. Differences were considered statistically significant at a two-tailed p-value <0.05. However, statistical significance was not generally anticipated given the sample size.

Results

Among the 200 participants in this study sample, 17.5% (35/200) had an APOL1 high-risk genotype (2 RRVs) and 82.5% (165/200) had an APOL1 low-risk genotype (0 or 1 RRV). The median age was 59 years, and 53% (106/200) were women. At baseline, 39% reported being extremely concerned about kidney conditions, 34% very concerned, 12% somewhat concerned, 10% a little concerned, and 6% not concerned at all. Across levels of kidney concern, no differences reached statistical significance, although several trends were observed (Table 1). Women comprised 38% of those reporting little or no concern, compared with 52% of those reporting “very much” concern and 62% of those reporting extreme concern, whereas men showed the inverse pattern (Figure 1A). A modest gradient was also observed according to APOL1 genotype, with individuals carrying 2 RRVs representing 6% of the lowest concern group versus approximately 18% to 22% of the moderate- to high-concern groups. Participants reporting extreme concern were slightly younger (median 57 years) than those with moderate concern (62 to 63 years), while body mass index (median 33 kg/m²), blood pressure, and diabetes prevalence (average 20%) were similar across concern categories. A combined family history of hypertension and kidney disease was more common among those with extreme concern (56%) compared with those with low concern (38%) (Figure 1B).

Table 1. Sociodemographic characteristics and clinical data of the study cohort grouped by baseline concern about kidney conditions.

Data are presented as column percentage (%).

IQR; interquartile range, GED; general educational development.

At 3 months, the proportion of participants who were very much or extremely concerned about kidney conditions declined from 73% (145/200) to 63% (126/200), with a redistribution toward lower and moderate levels of concern (Figure 2). The proportion reporting “very much” concern decreased slightly from 34% to 32%, while the proportion reporting extreme concern declined from 39% to 31%. In contrast, lower concern categories (“not at all” or “a little bit”) increased modestly over time.

At the individual participant level, patient-reported kidney concern decreased in 36% (72/200), remained unchanged in 45% (90/200), and increased in 19% (38/200) at 3 months. An APOL1 high-risk genotype was more common among participants whose concern increased compared with those whose concern decreased (29% vs 11%; P = 0.02) (Figure 3). Changes in kidney concern were not strongly associated with age or sex, which were similarly distributed across groups (Table 2). In contrast, higher albuminuria was more common among participants whose concern increased, with 36% having UACR >300 mg/g compared with 14% among those whose concern decreased. Participants with declining concern were more likely to have low albuminuria (<30 mg/g; 58%) (Table 2).

Table 2. The characteristics of the patients distributed by the change in the degree of concern about kidney condition from baseline to 3 months.

*UACR was available for 119 participants.

SD, standard deviation; eGFR, estimated glomerular filtration rate; UACR, Urine albumin/creatinine ratio.

Among the overall cohort, the proportion reporting that an APOL1 high-risk genotype would be worrying decreased from 14% (28/200) at baseline to 8% (16/200) at 3 months. Among the 16 participants who reported that a high-risk genotype would be worrying at 3 months, 75% (12/16) were women, 75% (12/16) had completed high school or higher education, and 38% (6/16) were in the low-income group. These participants had mild-to-moderately reduced kidney function (median eGFR 48 mL/min/1.73 m²) and macro albuminuria (median UACR 633 mg/g). Only 2 (13%) of participants who reported that a high-risk genotype would be worrying at 3 months had an APOL1 high-risk genotype, whereas 63% (10/16) had 1 RRV and 25% (4/16) had 0 RRVs.

Discussion

In this prospective cohort of Black adults undergoing APOL1 genetic testing at an academic medical center, we evaluated changes in patient-reported kidney-related concerns and worry about genetic risk over 3 months. At baseline, nearly three-quarters of participants reported being very much or extremely concerned about having a kidney problem, underscoring the high prevalence of kidney-related concern among individuals engaged in nephrology and internal medicine care. Although the proportion reporting very much or extreme concerns about kidney conditions declined modestly to 63% at 3 months, concerns remained dynamic at the individual level, with more than one-third of participants experiencing a decrease, nearly half remaining unchanged, and approximately one-fifth reporting increased concerns. Participants whose concerns increased were more likely to carry an APOL1 high-risk genotype and to have higher levels of albuminuria, suggesting that both genetic and clinical risk factors may influence perceived vulnerability. In parallel, the proportion of participants who reported that an APOL1 high-risk genotype would be worrying declined from 14% at baseline to 8% at 3 months.

Women represented a larger proportion of participants reporting higher levels of kidney concern and were overrepresented among those who continued to report worry about an APOL1 high-risk genotype at 3 months. Prior studies across chronic disease populations, including CKD, have shown that women more frequently report health-related concerns, perceived vulnerability, and illness-related distress, which may reflect differences in health awareness, caregiving responsibilities, or willingness to acknowledge and report emotional symptoms (17, 18). Participants with a combined family history of hypertension and kidney disease were also more likely to report extreme levels of kidney concern, consistent with prior work demonstrating that family experience with serious illness heightens perceived susceptibility and threat appraisal (19). Together, these findings underscore the importance of incorporating social context and family experience into patient-centered counseling strategies related to kidney disease risk and APOL1 genetic testing.

To date, there are limited data regarding concerns about kidney conditions and perceptions of APOL1 genetic testing among Black Americans. Prior studies have shown that genetic testing can reclassify a prior diagnosis in 11% to 54% of patients with CKD and establish an etiology in 12% to 56% of patients with CKD or end-stage kidney disease without a primary renal diagnosis (20). In 2013, a survey of Black and White first-degree relatives of dialysis patients reported substantial interest in obtaining, using, and sharing genetic test results related to kidney disease (21). Our study extends this work by moving beyond hypothetical interest among relatives to examining concern and worry among individuals who underwent APOL1 genetic testing as part of a study protocol.

Patient education is critical to helping patients understand their disease course and future care options. Importantly, perceptions about illnesses may also impact individual clinical and physical symptomatology (22). In the current study, more than one-third of participants experienced a decrease in concern about kidney conditions, and the proportion reporting that an APOL1 high-risk genotype would be worrying declined over the 3-month follow-up period. Participation in a research study that includes access to structured information, engagement with trained clinicians and research staff, and access to formal genetic counseling may help contextualize genetic risk. Future studies should seek to identify which components of education and counseling are most effective in addressing kidney-related concerns and responses to genetic risk information.

APOL1 RRVs originated in populations with African ancestry and, through migration, are now found among individuals throughout North, Central, and South America (23). Given the impacts of structural racism, medical mistrust, and underrepresentation of Black individuals in clinical trials, it is essential to incorporate patient perspectives and attitudes into APOL1 testing practices (11). Prior work has shown that concern about psychological distress and receiving “bad news” can serve as a barrier to genetic testing (24), while other studies have demonstrated that disclosure of APOL1 results may motivate positive lifestyle changes and improved medication adherence among individuals with high-risk genotypes (9). Our findings contribute to this growing body of literature by demonstrating that kidney-related concern is common and dynamic and may vary according to genetic and clinical risk factors.

This study has limitations that warrant consideration. The sample size was modest, and follow-up duration was relatively short, limiting the ability to draw conclusions regarding long-term psychological responses to APOL1 testing. We did not assess baseline psychiatric conditions, which may have influenced reported concern or worry and limited interpretation of individual responses. Participants were engaged in established medical care, primarily nephrology, and may not represent individuals without regular healthcare access. Information regarding the number of individuals who declined APOL1 testing and reasons for declining testing was not systematically collected as part of the study. Because the survey instrument was not formally validated, findings regarding concerns and worry should be interpreted as exploratory assessments of participant perceptions rather than validated measures of psychological outcomes. Additionally, changes in concerns and worry over time may reflect both study engagement and broader external influences, including increased awareness of APOL1-associated kidney disease and the evolving role of APOL1 testing within precision nephrology (1). The clinical significance of patient-reported concerns and worry remains uncertain. These responses may reflect adverse psychological effects, increased health awareness and engagement, or a combination of both. Ongoing work is needed in larger and more diverse populations, with longer follow-up and validated psychological, behavioral, and clinical outcome measures, to better understand how APOL1 testing affects patients over time and how counseling and education can best support informed care.

In summary, in this prospective cohort of Black adults undergoing APOL1 genotyping, patient-reported kidney-related concerns were common and generally persisted over time, while patient-reported worry related to APOL1 genetic risk declined. Participants whose kidney concerns increased over time were more likely to have an APOL1 high-risk genotype and higher levels of albuminuria. These findings highlight the nuanced psychological responses associated with APOL1 testing and underscore the importance of patient-centered education and counseling as APOL1 testing becomes increasingly integrated into clinical practice.

St. Louis APOL1 study collaborators

Orhun Aydin, PhD; Anne Buganski, RN; Ezequiel Bellorin Font, MD; Ava DeLonais-Parker, BS; Farzana Hoque, MD; Nourhan Houjeij, MD; Kevin Lee, MPA; Mary Lesko, RN; Kenan Li, PhD; Kunal Malhotra, MD; Rushda Mansuri, MD, MPH; Marilyn Maxwell, MD; Enbal Shacham, PhD; and Mowaffaq Said, MD.

Generative AI statement

The author(s) declared that generative AI was not used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

Supplementary material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fneph.2026.1815147/full#supplementary-material

Schematic presentation of study procedures. APOL1, apolipoprotein L1; CKD, chronic kidney disease; CLIA, Clinical Laboratory Improvement Amendments; DNA, deoxyribonucleic acid; RRV, renal risk variant; SNP, single nucleotide polymorphism. Created in BioRender. Lentine, K. (2026) https://BioRender.com/qtws5mi. Supplementary material at the source

Supplementary material Supplementary material at the source

Footnotes

Edited by: Fernanda Sales Luiz Vianna, Federal University of Rio Grande do Sul, Brazil

Reviewed by: Abraham Aron, MedStar Georgetown University Hospital, United States

George Vasquez Rios, Icahn School of Medicine at Mount Sinai, United States