Pediatric nephrologists’ perspectives and clinical practices related to genetic testing and education

Abstract

Background:

While genetic testing is now more accessible in pediatric nephrology, little is known about the views of pediatric nephrologists regarding genetic testing in clinical settings.

Methods:

An online 41-item survey was developed and distributed via professional listservs to self-identified U.S. licensed pediatric nephrologists from 1/22/21 to 5/4/2021.

Results:

Pediatric nephrologists had a high referral rate to genetic counseling and agreed on the significant impact of genetic testing on diagnosis, treatment, prognosis, counseling, and kidney transplant planning. Challenges for the utilization of genetic testing among pediatric nephrologists include the need to: 1) learn how to counsel patients on risks and benefits of genetic testing, 2) choose appropriate testing, 3) interpret genetic results, and 4) return those results to patients and families.

Conclusion:

There exists an opportunity to expand genetic testing education for pediatric nephrologists to assist incorporation of genetic testing into clinical practice.

Graphical Abstract

INTRODUCTION

More than ever before, pediatric nephrologists can utilize genetic testing to elucidate the genetic causes of chronic kidney disease (CKD) in children. Although pediatric nephrology encompasses children with diverse etiologies of CKD, the leading cause of kidney disease is congenital anomalies of the kidney and urinary tract (CAKUT) [1], followed by steroid-resistant nephrotic syndromes, glomerulonephritis, kidney cystic diseases and ciliopathies [2, 3], all of which have been shown to have relatively higher chance of identifying genetic causes compared to some adult onset of CKD [2, 4]. Identification of genetic causes of kidney diseases has been shown to offer patients and their families an opportunity to understand their disease heredity, development, prognosis and clinical management [5–7]. Genetic testing is an indispensable clinical tool that can be used in pediatric nephrology alongside kidney biopsy and serologic testing, and has been increasingly utilized [2, 3]. It expands the diagnostic capabilities for pediatric patients with CKD, offering a more precise diagnosis or the reclassification of phenotypically similar diseases [8, 9]. Yet, while pediatric nephrologists play a key role in implementing genetic medicine in clinical care, their views on relevant issues in genetic testing are understudied.

Pediatric nephrologists are at the forefront of translating genetic knowledge into clinical care and management of CKD in children. Pre-test genetic counseling and informed consent prepare families for the process and manages expectations for results [10]. However, studies have shown poor genomic literacy and comfort amongst pediatric subspecialists [11, 12]. Referrals by pediatric nephrologists to genetic counseling or testing are essential for the implementation of genetic medicine in clinical settings. The views of referring physicians on the utility of genetic testing, and their confidence in consenting patients for genetic testing, genetic results interpretation and counseling are all factors that can impact such referral [13]. Nephrologists also expressed concerns about the potential harms from genetic testing and reported these concerns as a factor that limits the utilization of genetic testing [14]. However, little is known about how pediatric nephrologists view the utility, clinical application, and relevance of genetic testing in determining underlying CKD of pediatric nephrology patients. We report findings from a study that explored the views of pediatric nephrologists regarding genetic testing in the clinical setting.

METHODS

An online 41-item survey was developed and distributed via professional listservs and national organizations related to CKD. Inclusion criteria required self-identification as a currently practicing nephrologist in the U.S. The survey was developed by an interdisciplinary team of researchers consisting of pediatric and adult nephrologists, a genetic counselor, a bioethicist, and in collaboration with the Cure Glomerulonephropathy (CureGN) Consortium [15]. Questions were based on existing literature at the time of the survey [16], validated scales [17] and practical experiences in studies involving clinical genetic testing and return results [18]. The survey was reviewed by 2 adult and 3 pediatric nephrologists and revised to address comments before being finalized and administered. Participants were asked about their understanding and experiences related to genetic testing in clinical settings, including usefulness of genetic testing for clinical management, cascade testing, and procedures for returning results. They were also asked about expected barriers and possible facilitators to genetic testing. Response choices consisted of dichotomized (yes/no) or pre-defined options. Response options for opinion-based questions were on a Likert scale (i.e., “strongly disagree”, “disagree”, “neutral”, “agree”, “strongly agree”). One open-ended question was included to capture additional comments or questions (of note: no participant added comments to this question). Participant demographic information and professional experience were collected. Participants’ consent was provided online. A $25 gift card was offered for completing the survey. The IRB at Columbia University Irving Medical Center approved the study (protocol #IRB-AAAT2423).

DATA ANALYSIS

Data collection was from 1/22/21–5/4/2021 and analyzed by STATA 15.1. Descriptive statistics are reported for survey responses and participant demographic characteristics. Likert scale responses were collapsed in the analysis to “Disagree” (disagree/strongly disagree), “Neutral” or “Agree” (agree/strongly agree). Chi-square testing was performed to analyze differences between participants’ demographic characteristics in practice patterns, and p-values <0.05 were considered significant.

RESULTS

Participants

The survey was sent to both pediatric and adult nephrologists, however we report on the eighty-five pediatric nephrologists who completed the survey. Of the pediatric nephrologists, 44 (52%) were female and 47 (55%) identified as White (Table 1). Most participants were more than 5 years into their nephrology practice (85%), and 75% practiced in a university-affiliated hospital, which is representative of pediatric nephrologist practice patterns. Most participants had less than 20% protected time for research (68%), 60% spent more than fifth of their time in ambulatory setting, and 47% spent 6 to 20% of their time on inpatient care (Figure 1). Although most pediatric nephrologists reported primarily clinical responsibilities, 56% reported being involved as an investigator or as referring physician in research studies that include genetic testing.

Table 1.

Demographics of pediatric nephrologist respondents (N = 85).

		N	Proportion
Gender	Male	37	44%
	Female	44	52%
	Non-binary	2	2%
	Prefer not to answer	2	2%
Race and Ethnicity	White, not Latino	47	55%
	Asian, not Latino	25	29%
	Black/African American, not Latino	4	5%
	Latino	2	2%
	Multiracial, Latino	1	1%
	Native American, not Latino	1	1%
	Preferred not to answer	2	2%
Years in Practice	< 5 years	13	15%
	6 – 15 years	30	35%
	16–25 years	18	21%
	> 25 years	24	28%
Clinical Setting	University-Affiliated Hospital	64	75%
	Group practice with hospital affiliation	1	1%
	Group practice without hospital affiliation	0	-
	Other hospital	16	19%
	Solo or two-MD practice without hospital affiliation	4	5%

Figure 1.

Respondents’ time allocation to different activities.

Regarding the clinical spectrum of kidney disease, almost all participants had seen a pediatric patient with a clinical diagnosis consistent with Alport syndrome (98%), idiopathic FSGS/nephrotic syndrome (100%), polycystic kidney disease (100%), tubular defects (100%), and tuberous sclerosis (100%). Most participants had referred more than 20 patients for genetic testing (61%) during their careers, with higher proportion among those in practice 6–15 years (70%) and 16–25 years (83%) compared to those with less than 6 years or more than 25 years clinical experience (23% and 54%, respectively). No difference was found between male and female participants’ referrals for genetic testing and amount of medical education in genetics.

Views on genetic testing and its clinical integration

The overwhelming majority of participants (86%) agreed that genetic testing fits into the processes already in use for the care of kidney patients while only 3% of participants thought their patients would not benefit from genetic testing and 6% thought that their patients’ parents/guardians would decline genetic counseling. This finding may reflect the specific contexts of respondents as 49 of the 75 university-affiliated nephrologists and 6 of the 10 non-university affiliated nephrologists indicated that genetic counselors were available in their practice.

Participants were split as to their reasons to be discouraged from referring patients for genetic testing. Key barriers to the integration of genetic testing in clinical settings were: results leading to unnecessary treatments (55%), patients’ limited understanding of genetic information (54%), the effect that genetic testing may have on biological relatives (52%), or disagreements among family members (51%).

Rationale for referral to genetic testing

All participants answered that it is their job to recommend genetic evaluation and that they are qualified to recommend genetic evaluation to their patients. Genetic testing was considered clinically important for disease diagnosis (92%), understanding (85%), prognosis (86%), treatment (84%), family counseling (88%), and kidney transplant planning (93%, Figure 2). The majority (70%) of participants would recommend genetic testing for family members, especially in the presence of a tailored lab report (91%).

Figure 2.

Perceived impact of genetic testing on kidney-related clinical care.

Barriers and challenges to genetic testing

Factors that would discourage referral of patients were concerns that genetic testing would lead to the diagnosis of untreatable kidney disease in asymptomatic children (41%) and challenges related to testing teenagers (43%; Figure 3).

Figure 3.

Pediatric nephrologists’ views on barriers to referral of patients for genetic testing.

Participants identified their top three challenges to genetic testing to be interpretation of results (63%), selection of the appropriate genetic test (55%) and providing genetic counseling for the family (53%, Table 3). Other major challenges that were indicated to limit referrals for genetic evaluation included navigating the cost of genetic testing for patients (38%) and unaffordability of genetic testing to their patients (19%) (Table 4).

Table 3.

Pediatric nephrologists rank their top 3 most challenging issues in genetic testing in clinical practice.

Which aspect of genetic testing do you find (or think will be) most challenging? Select a number to rank the top 3 choices, with 1 being the most challenging.	RANK (N)			N (%)
	1	2	3
Interpreting genetic results	22	21	11	54 (63.5%)
Selecting the right test	14	23	10	47 (55.3%)
Follow-up genetic counseling of family	11	17	17	45 (52.9%)
Integrating result into clinical care	8	14	18	40 (47.1%)
Identifying which patient to test	12	3	21	36 (42.4%)
Discussing results with patients and family	9	17	10	36 (42.4%)
Ordering the Test	18	10	7	35 (41.2%)
Consenting for Genetic Testing	11	6	9	28 (32.9%)

Table 4.

Pediatric nephrologists’ perceived barriers to genetic testing in clinical practice.

What are the factors that limit your referral of patients for genetic evaluation?	Total N (%)
I don’t know how to navigate the cost of genetic testing for my patients	32 (37.6%)
My patients cannot afford genetic testing.	16 (18.6%)
My patients decline genetic counseling	5 (5.9%)
My patients would not benefit from genetic testing	3 (3.5%)
I have never suspected a genetic disorder in one of my patients.	2 (2.4%)
I don’t know how to refer patients for a genetic evaluation.	2 (2.4%)
It is difficult for me to refer to medical geneticists and/or genetic counselors	1 (1.2%)
I don’t know how to interpret genetic test results.	1 (1.2%)
I don’t know which genetic testing panel is best to order	1 (1.2%)
It is not my job to recommend genetic evaluation.	0
I am not qualified to recommend genetic evaluation to my patients.	0
None of the above	22 (25.9%)

Factors that strongly discouraged referral to clinical genetic testing were out-of-pocket cost for patients (63%), and concern for denial of life insurance (43%), disability insurance (41%), or health insurance (41%) (Figure 3). In addition, participants were somewhat discouraged by administrative logistics (43%), causing stigma for the patient (38%), issues of privacy and confidentiality (35%), unique challenges surrounding family counseling (44%), the lack of treatment options (33%), and the identification of unexpected secondary/incidental genetic findings (45%).

Factors important to incorporating genetic testing into clinical practice

Most participants (69%) reported that they can find or have reliable information to care for their patients with genetic results, though only 56% of those surveyed stated that they have enough time to integrate genetic testing into their clinic workflow (Table 2). Further, only 36% of participants have a designated person/team to lead the effort to incorporate genetic testing into clinical practice.

Table 2.

Pediatric nephrologists use of genetic testing in daily clinical practice.

Please indicate how strongly you agree or disagree with the following statements related to genetic testing for nephrology patients at your principle place of practice.	Disagree/Strongly Disagree	Neutral	Agree/StronglyAgree
	N (%)
Using genetic testing fits within the processes I already use to care for renal patients	4 (4.7%)	8 (9.4%)	73 (85.9%)
Staff have enough time to facilitate the integration of genetic testing into clinical practice	19 (22.4%)	18 (21.2%)	48 (56.5%)
I can find/use reliable sources of information I need to apply genetic while caring for patients	12 (14.1%)	15 (17.6%)	58 (68.2%)
I believe that genetic testing is relevant to my current clinical practice	6 (7%)	0	79 (92.9%)
A clearly designated person or teams lead the effort to incorporate genetic testing into clinical practice	35 (41.2%)	19 (22.4%)	31 (36.5%)
A variety of strategies are being used to enable staff to use genetic testing	18 (21.2%)	17 (20%)	50 (58.8%)

DISCUSSION

Understanding pediatric nephrologists’ perspectives and their approach to the referral to genetic testing of their patients can help in the development of tailored approaches to facilitate utilization of genetics in pediatric nephrology. Our sample of participants was representative of pediatric nephrologists in the U.S., with a majority working in academic settings and primarily seeing patients [19]. Demonstrating an overall interest in genetics in nephrology practice, more than half of the participants reported being involved in research studies that include genetic testing.

Participants overwhelmingly agreed about the potential of genetic testing to significantly impact diagnosis, treatment, prognosis, family counseling, and transplant planning. Accordingly, they reported a relatively high referral rate to genetic counseling and testing. These findings are likely because a substantial proportion of children with CKD have genetic etiologies [6] and as most of our participants indicated having access in their practice to genetic counseling and testing. These findings are promising for genetic medicine in nephrology.

Nevertheless, participants identified several challenges to the utilization of genetic testing in pediatric nephrology. These include difficulties in the clinical implementation of genetic testing: counseling patients on risks and benefits of testing, choosing appropriate testing, interpreting genetic results, and returning results to the patient/family. These barriers could be alleviated by creating Genomic Medicine Boards to help nephrologists choose the appropriate testing and interpret results as well as increasing nephrology trainees’ genomic education and continuous medical education in genomics for practicing nephrologists—both of which were recommended by the National Kidney Foundation Working Group[11]. Participants also indicated structural challenges to the clinical integration of genetic testing. Only half of the participants reported that they have enough staff to facilitate the integration of genetic testing into clinical practice and only a third reported that they have designated persons or teams leading the effort to incorporate genetic testing into their clinical practice. This barrier may be in the process of changing as multiple kidney genetic clinics that offer genetic counseling by nephrologists and genetic counselors have been created over the past years, and they can alleviate some of the challenges by providing referral options [20–23]. Yet, it is also the case that at a minimum, nephrologists should be able to refer their patients to more knowledgeable colleagues or to center of excellence [24]. Tackling these challenges in individual practices is critical to ensure that clinical settings can improve the provision of genetic testing and return of results. Moreover, there is a need to incorporate genetic referral into existing infrastructures in clinical settings, including educating the staff about how to manage the administrative burden associated with referral of patients to genetic testing or counseling. Like any other new medical intervention, investment in structural implementation is necessary to prevent exacerbation of existing genomic disparities in clinics [25, 26].

Most pediatric nephrologists stated that the possibility of revealing unexpected incidental genetic results not related to the kidney disease strongly or somewhat discouraged them from referring their patients to genetic testing. In addition, pediatric nephrologists stated that the risk of denial of life insurance, disability insurance and health insurance due to pre-existing condition strongly or somewhat discouraged them from referring their patients to genetic testing. The latter concern regarding health insurance may indicate limited knowledge of the Affordable Care Act with respect to the prohibition of health insurance discrimination based on pre-existing conditions. However, the concerns over disability and life insurance discrimination may be different. They may indicate understanding of the limitations of the legal protections under the Genetic Information Non-discrimination Act (GINA) but potentially also perception of genetic exceptionalism given that individuals with existing symptomatic disease might already experience challenges with securing life and disability insurance, regardless of the genetic etiology. These concerns highlight a need to revisit existing policies, and in the meantime: increase medical education and training opportunities to both pediatric nephrology trainees and practicing physicians.

The American College of Medical Genetics and Genomics (ACMG) recommends disclosure of actionable genetic results because those can be life-saving, like the identification of increased risk for cancer or cardiovascular diseases [27]. The ACMG identified these genes with the belief that the benefits of knowing about such genetic risk factors out-weigh the risks—though left it to the individual patient’s decision as to whether they are interested in receiving such results. Although studies have shown that most patients want to know about such risks [18], returning actionable incidental results to children and their families poses additional challenges and ethical considerations that need to be considered. These include the long-term impact of these findings on children [28], as well as worries that such an action precludes children from making their own decision once they mature and infringes on their “right to open future” [29, 30].

Knowledge of etiology of kidney failure can inform about prognosis, treatment options, and the clinical course of disease, as well as screening of potential kidney donors and risk of recurrence after kidney transplant. Physicians or genetic counselors should discuss these considerations with patients and their parents when deciding whether to perform genetic testing, which test to perform (diagnostic vs screening tests), and the types of potential results that may be received. The impact of returning diagnostic and actionable incidental results to children and their families should be discussed as part of the pre-test counseling [30–34], with special legal and social considerations of the views of adolescents (ages 13–17) as they are reaching maturity. These considerations include how to engage adolescents in the decision making process given that their decision making capacity may be similar to that of adults (as growingly acknowledged by all stakeholders, including professional medical societies), and how to resolve potential disagreements between parents and adolescents [30]. In addition, there is a need to consider how to communicate results with adolescents given concerns about the negative psychosocial effects of results them, including potential impact on identity formation and family dynamics. It is important that clinicians and genetic counselors develop guidelines on how to engage with teens in genomic conversations [35].

Some facilitators to the implementation of genetic testing were identified. For example, while most nephrologists reported family counseling challenges as a major barrier to referral to genetic testing, they also stated that their comfort in returning results would increase if they had more targeted information for their patients’ family related to the returned results. In addition, some of the barriers to genetic testing can be alleviated by referral to genetic counselors who can identify the most cost-effective genetic test, interpret the results, refer to other sub-specialists in the case of secondary findings and provide family counseling. However, there is a shortage of genetic counselors in the United States [36], including those with expertise in nephrology and pediatric and adolescent patients [35]. This challenge can be partially addressed by creating multidisciplinary teams for kidney genetic clinics. This approach was recently shown to be successful with a multidisciplinary workflow the paired a pediatric nephrology clinic with genetic counselors to return genetic results to 63% of their 126 patient cohort [37]. Concurrently, education of pediatric nephrologists regarding the risks and benefits of genetic testing, the criteria utilized by genetic counselor to choose appropriate testing, the meaning of the different parts of genetic reports, and how to engage pediatric populations in genomic conversations could help nephrologists refer to genetic counseling only the more complicated cases.

The study has several limitations. First, survey response rate could not be determined due to distribution of invitations for research participation through anonymous listservs described in Methods. Second, to avoid participant fatigue, the survey did not collect details about group practices, such as their size or whether they were in rural or urban settings, which precluded more nuanced analyses. Thus, for example, while structural challenges and lack of available staff may provide some explanation as to why participants also perceived the cost and administrative logistics of genetic testing as major barriers to utilization of genetic testing, it is unclear if regional disparities exist in referral practices that may reflect socioeconomic and resource challenges. These are areas for future investigation to barriers to implementation of genetic testing in clinical practice.

CONCLUSION

There is an opportunity to expand genetic testing education for pediatric nephrologists to assist incorporation of genetic testing into clinical practice. For this promise to materialize, there is a need to strengthen the genetic infrastructures in clinical settings, including investment in staff who can manage the administrative burden. The results of this study can inform the implementation of continuing medical education in genomics for pediatric nephrologists, and of other tools to assist clinicians in counseling and returning genetic results to families.

Data Availability

Relevant survey questions and survey data will be made available upon request to the corresponding authors.