Perspectives in Managing Kidney Disease and Atherosclerotic Cardiovascular Disease

Chronic kidney disease (CKD) is increasingly recognized as a global public health problem [1, 2]. There is an exponential increase in absolute risk for all-cause and cardiovascular mortality with decreasing kidney function [3]. The relationship between CKD and cardiovascular disease (CVD) is complex and bidirectional, with each contributing to increases in the incidence and progression of the other [2, 3]. Indeed, the heart and kidney are inextricably linked, as exemplified by the cardiorenal syndrome whereby dysfunction of one organ induces and advances dysfunction in the other [4‒7]. The myocardium and vasculature in CKD are exposed to metabolic stressors including inflammation, oxidative stress and activated renin-angiotensin-aldosterone system. Restitution of kidney function by transplant has been shown to improve cardiovascular functional reserve as measured by cardiopulmonary exercise testing [8].

Lowering lipid levels and reaching normal blood pressure targets are two frequent risk-reduction strategies for patients with CKD and atherosclerotic cardiovascular disease (ASCVD), consistent with approaches for adults with a history of any cardiovascular-related or other high-risk conditions [6, 9]. The modification of traditional risk factors such as hypertension, obesity and diabetes is a common approach to risk reduction in patients with CKD and ASCVD; however, additional interventions may be required to target those at very high risk, when standard treatment strategies alone may not be sufficient [6, 10]. The co-existance of multiple cardiometabolic health factors in these patients pose significant challenge for healthcare providers (HCPs), because these patients see multiple specialists and care may either overlap or present gaps in management, emphasizing the need for communication and coordination of care [11, 12]. Further, as the complexity of patient conditions increases, so too does the need for time, resources and communication to care for these individuals [13]. Nephrologists, in particular, typically see patients with a high number of comorbidities that require intervention and management [12, 13].

To better understand the experiences of patients with CKD and ASCVD and the role that various HCPs play in the diagnosis, treatment, and management of patients with CKD and ASCVD, we conducted a study to assess patient and HCP attitudes and perceptions about CKD and ASCVD risk, approaches to referral and diagnosis, and responsibility for care coordination and treatment of CKD and ASCVD.

Between May 18, 2021, and June 17, 2021, we conducted a cross-sectional study involving 239 HCPs who treat patients with CKD and ASCVD and 195 patients who self-reported having CKD and ASCVD. The study included an online survey that was emailed to participants from online research panel companies to which participants had agreed to be contacted for research purposes. Quantitative surveys were created for HCPs (shown in online supplement 1; for all online suppl. material, see https://doi.org/10.1159/000539804) and for patients (online shown in suppl. 2) with CKD and ASCVD in order to capture their experience and perspective regarding diagnosis, referral, treatment, and management of CKD and ASCVD.

The online surveys consisted of a variety of yes/no, multiple choice, and Likert scale questions. All responses were self-reported and voluntary, and respondents provided consent to participate. Respondents remained anonymous and were blinded to the study sponsor. This survey material was not validated or pilot tested. The WCG Institutional Review Board provided an exemption for the study since the data were deidentified and sufficient protections were in place to ensure the privacy of participants. The study and its collection of data were in conformity with all country, federal, or state laws, and the study was in adherence to the tenets of the Declaration of Helsinki.

To be included in the study, patients were required to be US residents between the ages of 40–79, diagnosed with CKD and ASCVD, and in CKD stages 2, 3, or 4 based on self-reported knowledge of their condition. Individuals who did not know the severity of their CKD were excluded from the study. We also excluded those with advanced CKD because the care becomes more nephrology-centric in these patients. HCPs included in the study were required to be board-certified in their specialty (if a physician), practicing in the USA for 3–35 years, primarily in a private practice or hospital setting, and actively seeing patients with both CKD and ASCVD. Those in Maine and Vermont were excluded to comply with Sunshine Act reporting requirements. Demographic variables were collected as part of baseline characteristics for both patients and HCPs.

HCP respondents included physicians practicing in primary care (family practice, internal medicine, and general practice), cardiology, nephrology, and endocrinology. Nurse practitioners and physician assistants practicing in cardiology were included as well.

Descriptive statistical analyses of the aggregated data were performed using Q Research Software for Windows (A Division of Displayr, Inc., New South Wales, Australia). Tests of differences (χ², t tests) within respondent types were also performed using Q Research Software. Additional analyses were performed using Stata/IC 14.1 and R (A Language and Environment for Statistical Computing) to examine factors such as the ages at which patients were diagnosed and the order in which they experienced similar medical milestones. Statistical significance was set at p < 0.05 using 2-tailed tests. Categorical data are expressed as counts and percentages.

Characteristics of patient and HCP survey respondents are shown in Tables 1 and 2, respectively. Of the 195 patients surveyed, 65% (n = 127) were in CKD Stage 3 and 37% (n = 72) had type 2 diabetes (T2D). Of the 239 HCPs surveyed, 58 were nephrologists and 74 were cardiologists. Information regarding primary care providers has been previously published [14]. An infographic summarizing the results of this study is shown in online supplement 3.

Nephrologists reported that 63% of the patients they diagnosed with CKD were on referral from other providers, with the largest percentage (83%) of referrals coming from PCPs. Nephrologists who personally diagnosed patients with CKD (n = 54) most commonly diagnosed them at an appointment made specifically to discuss symptoms (31%), although 22% of the time it was made at an appointment that served as a follow-up to an acute event (such as a heart attack or kidney stones) or at an appointment made for another condition (21%). More than half of patients (n = 100, 51%) reported that they were diagnosed with CKD first, then ASCVD, and 44% (n = 85) were diagnosed with ASCVD prior to CKD. Ten patients reported there was no clear diagnosis received first. Patients who were diagnosed with ASCVD first reported waiting a longer period of time between diagnoses (shown in Fig. 1).

Nearly two thirds (61%) of nephrologists said they review a patient’s history of an inflammatory condition or disease (such as diabetes or obesity). However, only about a third of nephrologists measured or tested for inflammation directly and consider it in decision-making when determining treatment and management of CKD (28%) and ASCVD (31%). Among patients who state that their nephrologist is actively involved in their care (defined as diagnosing them, treating them, or not treating them but still being involved in their management) (n = 127), 80% say their nephrologist is their coordinator of care, especially those who are in stage 3 (82%) or stage 4 (83%). This is fairly congruent with the percentage of nephrologists who also view themselves or another nephrologist as the coordinator of a patient’s CKD care (86%). The remaining 20% of CKD patients who report their nephrologist is actively involved in their care identify another HCP as their coordinator of CKD care; 6% say it is their PCP while 9% say it could be another specialty. Five percent of patients say they do not consider any provider to be their coordinator of care for CKD.

Most nephrologists agreed that the presence of cardiometabolic comorbidities increased patients’ risk of developing CKD (shown in Fig. 2). Patients did not have a similar perception, though; less than half believed CKD increases the risk of developing ASCVD and that ASCVD increases the risk of developing CKD (shown in Fig. 2). However, patients with T2D were more likely to report they understood the connection between T2D and the risk of developing CKD (74%) and ASCVD (70%).

Slightly more than half of nephrologists (52%) reported they typically discuss the risk of developing CKD with patients prior to their diagnosis of CKD (shown in Fig. 3). About 78% of nephrologists, however, report discussing with patients how CKD is related to or impacts other health conditions upon patients’ diagnosis of CKD.

Patients with T2D were significantly more likely to report that they had a discussion with their diagnosing provider at the time of CKD diagnosis about how CKD impacts or relates to other conditions (51% as compared to 33% of those without T2D). Only 37% of patients with T2D reported that they had a similar discussion about ASCVD’s impact on or relation to other conditions. Less than half (39%, n = 77) of patients recall their HCP discussing how CKD is related to or impacts other conditions (shown in Fig. 4). Sixty-two percent of the surveyed patients agreed that CKD increases their risk of having a serious cardiovascular event such as a heart attack, stroke, or death.

When compared to cardiologists, nephrologists rated higher levels of agreement (rated as a 6 or 7 on a 7-point scale where “1” meant “do not agree at all” and “7” meant “completely agree”) that inflammation has some degree of impact on CKD and ASCVD; 81% agreed with the statement, “inflammation has an impact on ASCVD development,” (vs. 70% of cardiologists), and 74% agreed with the statement, “inflammation has an impact on CKD development” (vs. 62% of cardiologists). Additionally, 81% of nephrologists agreed that “inflammation impacts CKD progression and severity,” while only 66% of cardiologists agreed with the statement. Slightly more than half (57%) of nephrologists who test for inflammation (n = 28) reported that they order a test specifically for high-sensitivity C-reactive protein (hs-CRP).

While 83% of nephrologists reported that they recommended lifestyle modification to patients for CKD and 70% for ASCVD, just slightly more than half of patients reported that they were currently using lifestyle modification to treat CKD and ASCVD (53% and 56%, respectively). Nephrologists reported prescribing or recommending angiotensin-converting enzyme inhibitors the most frequently (93% of the time for CKD, 95% for ASCVD) of any treatment for CKD and ASCVD, followed by angiotensin-II receptor blockers (88% for CKD, 79% for ASCVD), diuretics (86% for CKD, 72% for ASCVD), and statins (74% for CKD, 81% for ASCVD).

Thirteen percent of patients reported they were not currently using any treatment for CKD, and 5% reported not currently treating ASCVD. Patients generally reported that making changes to their lifestyle was the biggest challenge in managing CKD (32%) and ASCVD (41%). The numbers were even higher among those with T2D (40% and 52%, respectively).

CKD and ASCVD are well-documented conditions that have a dependent interplay with each other and other cardiometabolic diseases [11]. The presence of these and other comorbidities poses a challenge for HCPs in managing cardiorenal progression and working to prevent or reduce complications, particularly since care may be spread among other specialists and not overseen by any single provider [15, 16]. Patients face a similar challenge in managing multiple cardiometabolic conditions and having a clear understanding of which HCPs to discuss symptoms with and identify methods of lowering their risk for the development or progression of their diseases.

Our study examined the perceptions of CKD and ASCVD among patients and certain HCPs to better understand patterns of diagnosis, discussions of risk, and coordination of treatment. Although PCPs maintain overall coordination of care for most patients [14], our study demonstrated important distinctions in specialist oversight for CKD and ASCVD. Nephrologists, specifically, oversee care for the vast majority of patients with CKD and recognize the impact of cardiometabolic conditions on CKD but reported discussing the risk of developing CKD less frequently than all other specialists surveyed. Our study also found that a subset of patients exists who do not view their nephrologist as their coordinator of CKD care, even when they report that they are seeing a nephrologist in an active way (diagnosing, treating, or otherwise involved in managing their care). This suggests a gap may exist between patients and HCPs in understanding who ultimately has responsibility for CKD care.

Monitoring various biometrics, particularly markers that indicate increased inflammation, can help identify patients at high risk of cardiorenal events [17, 18]. Elevated hemoglobin A1C, for instance, may indicate the presence of micro- or macro-vascular complications [11, 12]. By targeting lower HbA1C levels (<6.5–<8.0%, as recommended by the 2022 Kidney Disease Improving Global Outcomes [19] Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease [16]), patients can effectively reduce progressive albuminuria and complications resulting from diabetes, such as retinopathy [12]. Similarly, identifying elevated lipid levels – those of very low-density lipoprotein (VLDL), in particular – and initiating treatment can help moderate risk, not just for cardiovascular events but also for CKD [5, 6, 20]. Inflammatory responses marked by enhanced circulating plasma levels (interleukin-6 [IL-6], in particular) are associated with increased cardiovascular risk and progression of CKD, particularly in those with T2D [21, 22]. The presence of hs-CRP, a marker of systemic inflammation that is correlated with a decline in estimated glomerular filtration rate, also represents an increased risk of atherothrombotic events, particularly among those with renal disease [23]. Nephrologists who closely monitor patients with cardiometabolic comorbidities, which may include evaluating biometrics that indicate signs of increased inflammation, may be able to help prevent disease progression through appropriate risk modification.

Although nephrologists in our study indicated significantly high levels of agreement with statements that inflammation has an impact on CKD and ASCVD development, progression and severity, fewer nephrologists reported even reviewing a patient’s history of inflammation. Even less said they measure or test for inflammation as part of their clinical decision-making when treating a patient with CKD. While clinical practice guidelines offer recommendations for diagnosing CKD and ASCVD and monitoring their progression, particularly in the presence of T2D, there are no inflammatory biomarkers that can be followed over time to monitor and predict clinical outcomes within the context of CKD and ASCVD [17, 22‒24].

Patients with multiple cardiometabolic conditions benefit from physical activity because it improves cellular function, lowers inflammatory markers, and improves insulin sensitivity [25]. Such benefits are similarly associated with decreased cardiovascular risk and improved kidney function [16, 25]. Our study revealed that only about half of patients were currently using some type of lifestyle modification to treat their CKD and ASCVD, however, and many reported it was their biggest challenge. Nephrologists can educate patients on the benefits of physical activity to mitigate both cardiovascular and kidney risk, particularly if they become engaged in patient care coordination at earlier stages of patients’ diseases. Furthermore, nephrologists who engage with other HCPs managing patients with cardiometabolic conditions have an opportunity to coordinate care and reinforce appropriate behavior modification strategies.

Findings from this study indicate a need for further education for nephrologists who treat patients with both CKD and ASCVD on treatments appropriate for patients with multiple cardiometabolic diseases, as well as increased education for patients about effective methods of risk reduction and lifestyle modification to manage cardiorenal conditions. Certain risk factors outside of their scope of care will require nephrologists to engage in a multidisciplinary approach to patients; comprehensive treatment plans that consider clinical practice guidelines and seminal study findings will be needed to address both renal and cardiovascular issues. Because many patients consider their nephrologist to be their coordinator of CKD care, particularly as their CKD progresses, nephrologists may be in a position to direct treatment for patients’ care of other cardiometabolic conditions and prevent or mitigate complications.

Certain limitations are inherent in self-reported data. Patients who responded to our survey had to rely on knowledge of CKD and ASCVD and memory of when they experienced certain medical events related to their conditions, which may indicate recall bias and may not make their responses entirely generalizable to the broader population of those with CKD and ASCVD. Further, patients in our study were not as demographically diverse as the population of those with CKD and ASCVD, thereby limiting generalizability. Patients and HCPs did not represent matched pairs, which may reflect real differences between the populations surveyed rather than differences in perception. Additionally, patients and HCPs who completed our survey represent a limited pool of respondents and may be different from patients and HCPs who do not participate in survey research. The survey also did not follow up with patients or HCPs to assess the effectiveness of prescribed or recommended interventions in reducing CKD or ASCVD risk.

Nephrologists, perhaps more than any other specialists, have a deeper understanding of the interplay of CKD with certain cardiometabolic diseases. As care coordinators for patients in more advanced stages of CKD, nephrologists are uniquely positioned to also help patients understand their risk for developing CKD and how CKD can impact other conditions. Although nephrologists and patients in our study reported different recollections of conversations about treatments for CKD and ASCVD, nephrologists have an opportunity to continually educate patients about CKD risk, severity, and progression, particularly with patients at high risk for inflammation and multiple cardiometabolic diseases. Increased collaboration between nephrologists and other HCPs may lead to improved management of cardiometabolic risk in patients with CKD and ASCVD.

The authors thank Stephanie Burkhead, MPH, of KJT Group, Inc., Rochester, NY for providing medical writing support, which was funded by Novo Nordisk Inc., Plainsboro, NJ, in accordance with Good Publication Practice (GPP 2022) guidelines. Novo Nordisk Inc. funded the study and had a role in the study design, data collection, analysis, and interpretation of data, as well as writing support of the manuscript.

The study was submitted to the WCG Institutional Review Board, which provided an exemption since the data were deidentified and sufficient protections were in place to ensure the privacy of participants. Respondents who entered the survey were asked to consent to participate and were made aware that their participation could be discontinued at any time.

At the time of the study, T.N. was a health economics and outcomes research fellow with Novo Nordisk Inc. and Rutgers University. M.C. reports research support to his institution for studies in which he is the principal investigator from Amgen, Boehringer-Ingelheim, CSL Behring; consulting fees from Amgen, Bayer, Boehringer-Ingelheim, Medtronic, Merck, Novo Nordisk, Zoll. E.M. serves on the Speakers’ Bureau and as an Advisory Board member for Eli Lilly, BI, Novo Nordisk, Abbott, Bayer and Research Abbott. S.M. and R.O. are employees of, and shareholders in, Novo Nordisk Inc. D.R. serves in the Zeus national advisory panel (Novo Nordisk).

This work was funded by Novo Nordisk Inc. (Plainsboro, NJ, USA), which had a role in the design of the study and in the collection, analysis, and interpretation of the data. Prior Presentation and Publication. Portions of these data were presented as a poster at the American College of Cardiology (ACC) Scientific Sessions from March 4–6, 2023. The abstract from this presentation was published in J Am Coll Cardiol. 2023 Mar, 81 (8_Supplement) 539. A parallel manuscript entitled, “Cardiorenal care coordination: holistic patient care opportunities in the primary care setting for patients with chronic kidney disease and atherosclerotic cardiovascular disease,” was published in Postgrad Med 2023 Sep;135 (7):708–716, doi 10.1080/00325481.2023.2256209. Epub 2023 Sep 11. The article focuses on the patient journey of those with CKD and ASCVD in the primary care setting and how primary care providers manage patients with CKD and ASCVD.

R.O., S.M., and T.N. had a role in the study design, data collection, analysis and interpretation of data. All authors critically reviewed the manuscript and approved of the final version.

Data are available upon request from the corresponding author (D.R.).