Global Trends and Hotspots in the Association between Chronic Kidney Disease and Cardiovascular Diseases: A Bibliometric Analysis from 2010 to 2023

Chronic kidney disease (CKD) and cardiovascular diseases (CVD) are both significant health concerns globally. CKD is defined as abnormalities in renal structure or function, present over 3 months, and is often linked with significant morbidity and mortality, impacting around 8–16% population worldwide [1, 2]. Concurrently, CVD are a group of disorders of the heart and blood vessels and continue to be the principal cause of mortality worldwide. The interconnection between CKD and CVD is also well established. Patients with CKD are at a high risk for cardiovascular events, with 50% of all patients with CKD stage 4/5 experiencing a cardiovascular event [3]. Meanwhile, approximately 40–50% of patients with heart failure have coexisting chronic renal insufficiency [4]. The coexistence of CKD and CVD has significantly reduced the quality of life of patients and increased the medical and economic burden worldwide, which has attracted considerable attention from doctors.

Current research on the intersection of CKD and CVD is intensively focused on elucidating the pathophysiological mechanisms that link the two conditions and identifying new therapeutic targets. And we found that the period from 2010 to 2023 has witnessed a significant upsurge in research exploring this intersection. Some studies have revealed the role of novel biomarkers such as fibroblast growth factor-23 (FGF-23), a phosphatonin that increases with the progression of CKD and is associated with cardiovascular events. Another key area of investigation is the effect of CKD on cardiac structure and function, including the development of left ventricular hypertrophy, which is a common cardiac alteration in CKD and a well-known predictor of cardiovascular outcomes. Furthermore, the potential benefits of new glucose-lowering agents, like sodium-glucose cotransporter 2 (SGLT2) inhibitors [5], have gained attention not only for their protective effects on kidney function but also for their cardiovascular benefits in individuals with CKD.

However, the increasing number of publications makes it difficult for researchers to keep up with the trends and frontiers in this field. What is the volume of publications in this field in the last decade? Which countries and institutions have played an important role in this field? How has the understanding of the pathophysiological mechanisms linking CKD and CVD advanced over time? What are the most significant trends and patterns in the current research on the interconnection between CKD and CVD? Which references are key and valuable in this field? Therefore, there is an urgent need to give a comprehensive overview of this field. Compared with systemic reviews and meta-analysis, bibliometrics was established as an independent discipline in 1969 and provided a quantitative and long-term method for evaluating research advancement [6], which enables the readers to quickly grasp the trends and patterns of a specialty. Hitherto, there has been an extreme lack of bibliometric reporting on the association between CKD and CVD [7]. Our study aimed to provide a bibliometric analysis and knowledge map visualization in this field from 2010 to 2023, shedding light on the global trends, key research hotspots, and the evolution of this vital area of medical research.

Data were obtained from the Web of Science Core Collection (WOSCC), which covers a wide range of publications from various disciplines. In particular, the edition “Science Citation Index Expanded” was used. The rationale for selecting the WOSCC for bibliometric analyses has been thoroughly expounded upon in our previous studies [8‒13]. In essence, WOSCC stands out as an exceptionally comprehensive and authoritative database renowned for its citation reports and cited reference information. Moreover, the data obtained directly from WOSCC can be readily employed for bibliometric analyses, circumventing any potential issues of data corruption that may arise during format conversion. Additionally, WOSCC diligently adheres to the principles of Bradford’s law and Garfield’s law in bibliometrics, facilitating the efficient extraction of core literature.

In this study, we defined CKD as all categories (based on estimated glomerular filtration rate and urinary albumin:creatinine ratio) established in the KDIGO 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease [14]. At the same time, we defined CVD as all major cardiovascular events, especially those related to CKD, which include coronary heart disease, stroke, heart failure, atrial fibrillation (AF), and peripheral artery disease [15]. Table 1 shows our search strategy.

We systematically searched the WOSCC database, setting the search timeframe from January 1, 2010, to December 31, 2023. A total of 22,633 articles were retrieved, and the selection process was completed in a single week (from August 26, 2024, to September 1, 2024) to avoid bias from database updating. Only articles and reviews written in English were included. All retrieved publications were evaluated by two independent authors via titles, abstract, and full text to exclude the studies not related to CKD and CVD. The detailed inclusion and exclusion criteria are shown in Table 2. If disagreement persisted after consultation between two reviewers, the judgment of a third author was considered final. In the end, 2,936 documents remained. Figure 1 and Table 3 show how the process went.

The selected documents were exported to plain text files and tab delimited files, including the full record and cited references, and named as “download_xxx.txt” format. These data records were then imported into CiteSpace 6.3.R3 advanced version for transformation and analysis. CiteSpace, a widely recognized bibliometric software developed by Dr. Chaomei Chen, is a versatile tool for bibliometric analysis and is designed to visualize and analyze trends and patterns in scientific literature that employ theories like burst detection and information foraging to explore the dissemination paths of specific literature and create visual knowledge maps [16]. In this study, CiteSpace was used to detect parameters such as countries/regions, institutions, keywords, references, and subjects for cluster visualization, timeline visualization, and burst detection. Furthermore, its proficiency in visualizing co-citation networks is complemented by its exceptional capability to assess clusters using modularity (Q-score) and silhouette (S-score) values. These scores gauge the degree of clustering and coherence within clusters, with higher Q and S scores indicating more reliable and well-defined groupings [17]. This comprehensive feature set is enhanced by its ability to visualize co-citation networks and track the evolution of key terms over time, facilitating an understanding of the interconnectedness of research works and the emergence of new trends. Additionally, the bibliometric online webpage was used to obtain chord diagrams of country/region collaborations.

The analyzed data in this study included the publication trend, country collaborations, institution collaborations, keyword co-occurrence, keyword clustering, keyword bursts, and cited reference bursts. Categorical data are expressed as frequencies and descriptive statistics to present a comprehensive bibliometric knowledge.

Figure 2a displays the annual and cumulative distribution of publications on the association between CKD and CVD from 2010 to 2023. The number of annual publications saw its lowest in 2013 with 148, and its highest in 2021 with 283. Figure 2b shows the expected trend line of cumulative publications based on relevant linear calculation (y = 212.14x – 30.253, R² = 0.9989). The high R² value (0.9989) of the regression indicates that from 2010 to 2023, the cumulative number of publications related to the association between CKD and CVD has steadily increased year by year.

A total of 94 countries/regions have contributed to the association between CKD and CVD publications, of which 87 countries/regions concentrated within the largest connected component. This suggests the presence of relatively large research topics or clusters within the network. Figure 3a shows the collaboration between different countries and regions based on the coauthorship of research papers. Each node represents a country, with the size indicating the number of publications or the intensity of research activity. And the different colors of nodes indicate their significant role across various years. Lines between nodes suggest collaboration, with thicker lines representing more intensive collaborative relationships. Centrality in the CiteSpace is a measure of the importance of network nodes [18]. A node with more than 0.1 centrality is recognized with a relatively great influence in this field and is highlighted with green in the visualizations, including USA (centrality = 0.26), Switzerland (centrality = 0.15), England (centrality = 0.12), and Canada (centrality = 0.11). The USA, with the highest centrality score among the countries listed, commands a leadership role. Figure 3b highlights a strong collaboration between USA and other countries. The top five countries in terms of publications are shown in Figure 3c and online supplementary Table S1 (for all online suppl. material, see https://doi.org/10.1159/000542441), with the top three being the USA (n = 904), China (n = 361), and Japan (n = 337).

As shown in Figure 4a, the network consists of 468 institutions, with a network density of 0.0247, which suggests that the network is substantial in size but lacks a high degree of interconnectedness. The presence of the largest connected component comprises 396 institutions and accounts for 84% of the total institutions in the network, which implies the existence of research clusters or communities within the network. Network visualization revealed that there are only two central institutions: Karolinska Institute (centrality = 0.15) and Johns Hopkins University (centrality = 0.14). The top five institutions in terms of publications are shown in Figure 4b and online supplementary Table S2. It is notable that, with the exception of the Karolinska Institute, all of the top five institutions are located in the USA. Despite its fourth-place ranking in publication volume, the Karolinska Institute stands out with the highest centrality score among the listed institutions, indicating its critical role in facilitating global research collaborations.

Keywords provide a highly summarized representation of a research paper, and their co-occurrence analysis can reveal research hotspots and trends in a specific field. Through keyword co-occurrence analysis, a total of 633 keywords were identified with no central node in the current network (Fig. 5a). The top 10 most used keywords are demonstrated in online supplementary Table S3, with the top three being CKD (n = 2,194), CVD (n = 1,188), and mortality (n = 604).

Based on the keyword co-occurrence graph, keyword clustering analysis was performed as shown in Figure 5b. The clustering was labeled using the log-likelihood ratio algorithm, and the results are presented in online supplementary Table S4. The clustering resulted in a total of 6 clusters, with modularity Q = 0.3256 > 0.3 and weighted mean silhouette S = 0.6704 > 0.5, indicating a tight clustering structure and reasonable results. Totally, 633 keywords were distributed in 6 clusters, #0 glomerular filtration rate; #1 indoxyl sulfate; #2 heart failure; #3 vascular calcification; #4 arterial stiffness; #5 cholesterol. The keyword timeline visualization illustrates the trajectory of research evolution (Fig. 6). Cluster #0 glomerular filtration rate, cluster #1 indoxyl sulfate, cluster #2 heart failure, and cluster #3 vascular calcification span across the entire timeline, indicating their foundational role in the field from as early as 2010.

The emerging trend in the research area can be predicted using burst keywords [19]. The top 20 keywords with the strongest citation bursts are illustrated in Figure 7. The “strength” column quantifies the intensity of the citation burst. “Year Begin and End” indicates the time span of the citation burst. Red bars show the duration of each burst. The leading keyword in terms of burst strength is empagliflozin (strength = 10.52), followed by serum creatinine (strength = 9.33), and Mendelian randomization (MR) (strength = 9), highlighting their significant impact in the research of CKD and CVD. Serum creatinine, left ventricular dysfunction, and proteinuria are three keywords that come out in the early stage of the research period and burst for a relatively long period. The other keyword bursts have shorter lastingness. Notably, gut microbiome, cardiovascular outcome, empagliflozin, SGLT2 inhibitors, type 2 diabetes, MR, and management consistently burst into 2023, reflecting the most current trends in research.

Figure 8 highlights the top 10 references with the strongest citation bursts, indicating their significant impact due to frequent citations over a relatively short period, and online supplementary Table S5 adds the publication types and the primary research work for these references. We can learn that the most bursty reference is Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy (strength = 36.8). The five references whose bursting continued until recently are Canagliflozin and Cardiovascular and Renal Events in Type 2 Diabetes (strength = 28.4); Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy (strength = 36.8); Global, Regional, and National Burden of Chronic Kidney Disease, 1990–2017: A Systematic Analysis for the Global Burden of Disease Study 2017 (strength = 32.24); Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction (strength = 28.69); and Dapagliflozin in Patients with Chronic Kidney Disease (strength = 34.37).

Due to the pioneering work of Richard Bright in 1836, who introduced the association between CKD and CVD, many studies have further explored the association between renal disease and cardiovascular abnormalities [20]. Through bibliometric analysis, we can find out countries and institutions that have played an important role in this field and observe a strong correlation between them. We also find that countries in East Asia, despite the fact of late commencing in the relevant research and not initially featured in early studies, have made remarkable strides in research over the past decade. Nonetheless, the absence of these countries among the top 10 references with the strongest citation bursts indicates the imperative need for an enhancement in research quality. This paradoxical situation, characterized by a disparity between quantity and quality, may be associated with the absence of a standardized academic evaluation system and disparities in research capabilities among institutions [8].

Among the high-productivity countries and institutions, there are 2 European countries, 2 East Asian countries, 1 North American country, and institutions from the USA and Sweden. These data may suggest that European, North American, and Asian regions shoulder a significant burden of the association between CKD and CVD. From an epidemiological perspective, the prevalence hotspots of CKD and CVD correspond to some extent with their research areas and institutions [21]. North America and Europe have high incidence rates due to lifestyle-related diseases and aging populations. They are also major sources of research, hosting many internationally influential research institutions and universities in these fields. At the same time, with economic development and lifestyle changes, East Asia areas are seeing rising incidences of CKD and CVD. Research in these regions is growing rapidly but may not have reached the same scale or influence as in North America and Europe. From a genetic perspective, people of African descent, especially African Americans, are more prone to hypertension and kidney diseases due to specific genetic variations (like APOL1 gene mutations) that increase the risk of CKD and CVD [22]. Certain types of kidney diseases (like IgA nephropathy) have a higher prevalence in some East Asian countries like Japan, which might be related to genetic factors [23]. Collectively, our data are generally in line with the epidemiological and genetic characteristics of the association between CKD and CVD.

The collaboration network shows a strong concentration of research within certain high-productivity countries and institutions. While this indicates a robust and active research community, it also suggests that many countries and institutions may be conducting research in silos, which could lead to duplicated efforts or a lack of sharing of valuable insights. To address these issues, it is essential to enhance multi-institutional collaborations, particularly by engaging lower output regions and institutions. High-level institutions should leverage their leadership to extend their scientific impact, facilitating knowledge transfer and capacity building. At the same time, establishing more formal partnerships and collaborative frameworks can encourage the sharing of data, resources, and expertise, leading to a more cohesive and comprehensive research approach across the globe.

The combination of keyword burst graph, keyword clustering graph, and keyword clustering timeline graph can effectively highlight the research hotspots at specific time periods, providing valuable insights for future research directions. The research hotspots regarding the association between CKD and CVD primarily focus on the following four aspects: cardiovascular-kidney-metabolic (CKM) syndrome, innovative therapies and drug impact, gut microbiome, and MR analysis.

Combining the timeline graph of keyword clustering and the keyword emergence graph reveals strong focus on #5 cholesterol and their relation to CKD and CVD, and keyword burst figure highlights the “metabolic syndrome,” “body mass index,” “LDL cholesterol,” and “type 2 diabetes.” In addition, “type 2 diabetes” emerges as new focus with a burst extending into 2023. Synthesis of this information suggests that “metabolic disorders and cardio-renal interaction” is one of the current research hotspots in this field. Based on this, the American Heart Association (AHA) [24] recently has introduced a more comprehensive concept, CKM syndrome, which is defined as a systemic disorder characterized by pathophysiological interactions among metabolic risk factors, CKD, and the cardiovascular system, highlighting the importance of a unified approach to understanding and treating these interrelated conditions.

(1) Why Is the Concept of CKM Syndrome Being Proposed? First, though CKD, CVD, and metabolic disorders are diseases that occur in different systems, they are intricately linked through a complex web of physiological interactions. By proposing CKM syndrome, we can enhance the medical community’s awareness of complex interplay between cardiovascular health, kidney function, and metabolic processes, thereby fostering a deeper understanding of these conditions. In addition, it may pave the way for earlier detection. For example, CKD is often diagnosed at a relatively advanced stage of the condition. However, the new CKM staging system advocates for the assessment of both estimated glomerular filtration rate and urinary albumin-to-creatinine ratio from early stages [24]. So, if widely adopted, it has the potential to facilitate earlier detection of CKD in patients who are at risk due to hypertension, CVD, metabolic syndrome, and diabetes. Furthermore, after recognizing these connections, healthcare providers can develop more integrated treatment strategies that target multiple risk factors simultaneously, potentially improving patient outcomes. The management of these interconnected conditions could be revolutionized, by employing innovative therapies that target cardiac, renal, and metabolic disorders, such as SGLT2 inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, finerenone, and so on [25].

(2) The Pathophysiology and Mechanisms of CKM Syndrome. CKM syndrome typically arises from excess or dysfunctional adipose tissue, which releases pro-inflammatory and pro-oxidative products that can harm arteries, the heart, and kidneys. Upon entering the systemic circulation, these pro-inflammatory and pro-oxidative mediators will intensify numerous pathophysiological processes, including disturbances of endothelial function, thrombosis, and so on, which can contribute to atherosclerosis and myocardial injury. They also aggravate conditions such as glomerulosclerosis, kidney tubular inflammation, and renal fibrosis, while simultaneously promoting the emergence of metabolic disorders, including abdominal obesity, dysglycemia, dyslipidemia, and hypertension [26]. Additionally, ectopic fat may be a local source of mediators and can also lead to compressive organ damage. For example, when this fat is deposited in the epicardium and pericardium, it can initiate arrhythmogenesis, impair myocardial function, and exacerbate coronary atherosclerosis [27, 28]; when this fat accumulates within and around the kidney, it can contribute to hypertension and abnormal blood pressure variability [29]. Moreover, the pathophysiological interplay between metabolic disease, the kidneys, and the heart forms a vicious cycle of CKM syndrome. The development of metabolic dysfunction-associated steatotic liver disease will amplify systemic inflammation and insulin resistance. Type 2 diabetes can lead to diabetic cardiomyopathy, vascular endothelial dysfunction, coronary artery disease, increased glomerular filtration, and structural changes in the glomerulus and tubulointerstitial fibrosis. CKD is a major amplifier of cardiovascular risk, which can result in anemia, mineral and bone disorder, vascular calcification, hypertension, dyslipidemia, atherosclerosis, and uremic cardiomyopathy. In turn, heart failure can give rise to renal hypoperfusion, venous congestion, reduced exercise tolerance, and further metabolic dysfunction [30].

The mechanisms of CKM syndrome are characterized by a complex interplay of hemodynamic and neurohormone, including sympathetic overactivity, the renin-angiotensin-aldosterone system, various chemical mediators (nitric oxide, prostaglandins, endothelins, and so on), and oxidative stress. Specific mechanisms include insulin resistance, heightened activity of the renin-angiotensin-aldosterone system, the generation of advanced glycation end-products, oxidative stress, lipotoxicity, endoplasmic reticulum stress, abnormalities in calcium handling, malfunctioning of mitochondria and impaired energy production, persistent chronic inflammation, and potentially uremic toxins [31]. In conclusion, CKM syndrome embodies a complex and interwoven pathophysiology leading to increased morbidity and mortality that goes beyond the simple sum of its components.

(3) The Future Research Trends of CKM Syndrome. Since the concept of CKM syndrome was introduced in 2023, a variety of research has been stimulated, aimed at understanding the epidemiology, intricate mechanisms, and integrated approaches to managing this complex condition. In terms of epidemiology, Minhas et al. [32] and Aggarwal et al. [33] assessed the prevalence and temporal evolution of CKM syndrome stages and demonstrated that almost 90% of American adults met criteria for CKM syndrome (stage 1 or higher), indicating an urgent need for population-wide risk-reduction measures. As for mechanisms, Kanbay et al. [34] evaluated the association between kidney diseases and CKM syndrome. D’Elia et al. [35] summed up mechanisms of lipid toxicity in the CKM syndrome. With respect to personalized clinical management, Guldan et al. [36] clarified the intricate relationship between sex hormones, gender disparities, and the progression of CVD within CKM syndrome. Li et al. [37] pointed out that higher social risk profile burden was associated with higher odds of CKM multimorbidity, independent of demographic and lifestyle factors. Ding et al. [38] noted that low education was associated with adverse CKM health for both sexes but was especially detrimental to women. Regarding to risk prediction, Li et al. [39] evaluated the association between different stages of CKM syndrome and risk of all-cause mortality. Li et al. [40] suggested that enhanced assessment of the triglyceride glucose-body mass index may provide a more convenient and effective tool for individuals at risk for CVD in CKM syndrome stage 0–3. Gao et al. [41] indicated that elevated systemic immune-inflammation index levels serve as an effective tool for screening and identifying individuals at high risk for CKM syndrome. Khan et al. [42] summarized the background, rationale, and clinical implications for the newly developed sex-specific, race-free risk equations: AHA Predicting Risk of CVD Events (PREVENT). Concerning new intervention measures, Fowler et al. [43] proposed that enhancing lymphatic function pharmacologically may be a novel and effective way to improve quality of life in patients with CKM syndrome by engaging multiple pathologies at once throughout the body, and Tain et al. [44] presented an overview of innovative reprogramming strategies targeting the renin-angiotensin system to prevent CKM syndrome.

Although the scientific understanding of CKM syndrome is increasing, there are still some important areas where our understanding is insufficient. The exact mechanisms of CKM syndrome remain incompletely understood. For example, we still do not know determinants of disease progression from subclinical to overt CVD [26]. Therefore, in-depth exploration of the key pathophysiological mechanisms and how they interact to cause disease progression are needed. Moreover, the heterogeneity of CKM syndrome should be noted, with the development of tailored prevention and treatment strategies based on individual genetic profiles, environmental factors, and lifestyle choices. Besides, comprehensive treatment strategies that address the CKM syndrome, including lifestyle modifications, pharmacological treatments, and potentially new therapeutic approaches like cell or gene therapies, should be explored. In summary, further research is required to achieve a more profound comprehension of the CKM syndrome, elucidate the benefits from an integrated management of concurrent metabolic disorders, CVD, and CKD, and guide individualized treatment choices in clinical practice.

Analysis of the keyword emergence graph reveals that “Innovative Therapies and Drug Impact” is another current research hotspot in the field. “Empagliflozin” and “SGLT2 inhibitors” in the keyword burst graph have become prominent since around 2020. SGLT2 inhibitors, by improving insulin sensitivity and reducing blood glucose levels, can alleviate the burden on the heart and kidneys, especially in comorbid conditions of CKD and CVD. In addition, other innovative drugs have also emerged in the treatment of CKD and CVD in recent years. For instance, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are also commonly used in the treatment of CKD and CVD, as they can lower blood pressure, slow down kidney damage, and improve cardiovascular health; β-blockers and calcium channel blockers are particularly important for CKD patients in controlling hypertension and preventing cardiovascular events; GLP-1 receptor agonists can stimulate insulin secretion, inhibit glucagon release, and slow gastric emptying [45], presenting a promising avenue for addressing the complex CKM health [24]; finerenone is a novel, selective, nonsteroidal mineralocorticoid receptor antagonist that blocks mineralocorticoid receptor overactivation and mineralocorticoid receptor-mediated sodium reabsorption, and has demonstrated anti-inflammatory and anti-fibrotic effects in preclinical kidney and CVD models [46]. Additionally, growth differentiation factor 15 might be an effective drug target in cardiometabolic disease [47]. Furthermore, the development of gene and cell therapies, as well as digital health interventions, is offering new possibilities for personalized medicine. These indicate that “Innovative Therapies and Drug Impact” has become an indispensable aspect in the study of the relationship between CKD and CVD.

In current research, SGLT2 inhibitors are garnering attention for their effectiveness in improving blood sugar control and reducing the risk of cardiovascular events. In the DAPA-CKD trial, Heerspink et al. [48] documented the cardio-renal protection achieved by dapagliflozin (an SGLT2 inhibitor) for patients with CKD. Over a median of 2.4 years, dapagliflozin reduced the risk of the primary outcome (hazard ratio, 0.61 [95% CI, 0.51–0.72]), composite of key renal outcomes (hazard ratio, 0.56 [95% CI, 0.45–0.68]), and composite death from cardiovascular causes or hospitalization for heart failure (hazard ratio, 0.71 [95% CI, 0.55–0.92]). Studies by Scheen [49] and Li et al. [50] also highlighted the positive impact of SGLT2 inhibitors on cardiovascular and renal health. Nyström [51] underscored the cardio-renal benefits of SGLT2 inhibitors across various patient populations by examining a range of real-world evidence studies. Chang et al. [52] showed that considerable medical care cost offsets may result through attenuated incidence of clinical events in CKD, type 2 diabetes, and heart failure populations if treated with dapagliflozin in addition to historical standard of care over a 4-year time horizon. Scholars have also explored the specific mechanisms of action of SGLT2 inhibitors. Zelniker and Braunwald [53] delved into how these drugs improve cardiovascular and renal health pathways, offering key insights into their therapeutic potential. Salvatore et al. [54] provided a comprehensive overview of the mechanisms of SGLT2 inhibitors in cardio-renal protection, emphasizing their importance in improving cardio-renal metabolism and hemodynamics. Girardi et al. [55] provided an analysis of the multifaceted mechanisms underlying the cardio-renal benefits of SGLT2 inhibitors in heart failure and CKD outside of the type 2 diabetes context. Additionally, ertugliflozin and empagliflozin, as newer SGLT2 inhibitors, have been investigated for cardio-renal protection effects. Cherney et al. [56] reported that ertugliflozin in patients with type 2 diabetes and atherosclerotic CVDs was noninferior to placebo groups with respect to major adverse cardiovascular events. Herrington et al. [57] found empagliflozin could decrease the risk of progression of renal disease or death from cardiovascular causes in CKD population (hazard ratio, 0.72 [95% CI, 0.64–0.82]). Beyond SGLT2 inhibitors, finerenone has also shown significant effects in the treatment of cardio-renal diseases. Bakris et al. [58] demonstrated that finerenone significantly reduces the risk of key renal outcomes (hazard ratio, 0.82 [95% CI, 0.73–0.93]) and cardiovascular outcomes (hazard ratio, 0.86 [95% CI, 0.75–0.99]) in patients with type 2 diabetes and CKD. The study by Agarwal et al. [59] further confirmed the cardiovascular and renal benefits of finerenone, offering a new drug option for the treatment of cardio-renal diseases. Vaduganathan et al. [60] summarized three prospective randomized clinical trials of patients with CKM syndrome and indicated that while the reduction in cardiovascular death was not statistically significant, finerenone reduced the risks for deaths of any cause, cardiovascular events, and kidney outcomes. Also, the effectiveness and safety of finerenone in diabetic kidney disease patients have been proven in a real-world observational study from China [61].

These studies collectively emphasize that the field of innovative therapies and drug impact is continually progressing and evolving, playing a crucial role in improving the clinical outcomes for patients with CKD and CVD. From SGLT2 inhibitors to GLP-1 receptor agonists, and extending to finerenone, ertugliflozin, and empagliflozin, these drugs demonstrate significant potential in improving blood sugar control in diabetic patients, reducing the risk of cardiovascular events, and enhancing renal function. These findings not only provide new perspectives for the clinical treatment of cardio-renal diseases but also guide the direction for future research and drug development, but their long-term efficacy and safety still require further research and validation.

The prominence of the term “gut microbiome” in keyword burst, with a high strength (strength = 8.47), and its persistence since 2018, indicates that research on the “gut microbiome” is receiving widespread attention in the field and holds enduring research value. As understanding deepens regarding the role of the gut microbiome in cardiovascular and renal diseases, the gut microbiome plays a crucial role in maintaining a healthy physiological state and the development and progression of cardio-renal diseases. Studies suggest that changes in the gut microbiota can impact renal and cardiovascular health, particularly through metabolic byproducts and inflammatory pathways.

The study by Beker et al. [62] highlighted the importance of reducing uremic toxins produced by the gut microbiome in improving cardio-renal health. Similarly, Saadat and Niknafs [63] revealed the impact of phosphate binders on the gut microbiome, indicating that modulating the gut microbiome through phosphate level can effectively alleviate the burden of cardio-renal diseases. Further studies by Kalantar-Zadeh et al. [64], Evenepoel et al. [65], and Peters et al. [66] focused on the roles of inflammation and gut microbiota dysbiosis in cardio-renal diseases, delving deeper into the association between the gut microbiome and renal health and revealing the potential link between gut microbiome diversity and the risk of renal diseases.

In research related to gut microbial metabolites and therapeutics, Gupta et al. [67] centered their study on gut microbial metabolites, finding that reducing levels of trimethylamine N-oxide can decrease the risk of cardio-renal diseases. Li et al. [68] discovered that fructooligosaccharides can effectively alter the gut microbiome and reduce levels of harmful cardio-renal metabolites. Some scholars have also approached the subject from a broader perspective. Raj et al. [69] investigated the interactions between the liver, kidneys, and intestines, or the so-called liver-kidney-gut axis, revealing the key role of the gut microbiome in regulating this axis. Mafra et al. [70] studied the role of gut microbiome interventions in preserving residual kidney function in patients with CKD. The latest research by Nemet et al. [71] provided a comprehensive spectrum of various compounds produced by the gut microbiome, laying the groundwork for precise regulation of the gut microbiome and interventions targeting specific compounds. Tain et al. [72] pointed out that a gut-microbiota-targeted diet, which includes probiotics, prebiotics, and postbiotics, has emerged as a reprogramming strategy to avert CKM syndrome with developmental origin.

In summary, these studies collectively emphasize the significant role of the gut microbiome in cardio-renal health. An imbalance in the gut microbiota can exacerbate cardio-renal diseases, while modulating the gut microbiome can alleviate the burden of these diseases. Future research may further reveal more complex interactions between the gut microbiome and cardio-renal diseases, providing new strategies and approaches for the prevention and treatment of these conditions.

In the keyword burst, “mendelian randomization” (strength = 9) emerges as a research focus from 2021 to 2023, indicating more attention has been given in this topic. Randomized controlled trials are usually considered as the gold standard to investigate the causal relationship between risk factor and a condition. However, randomized controlled trials are not always conducted due to the cost of human and financial resources. MR is an epidemiological approach using genetic variants as instrumental variables of exposure to explore the causal effects on the disease outcomes. The genetic variants such as single-nucleotide polymorphisms are randomly assigned at conception according to the Medel’s law; hence, the MR studies are less susceptible to the confounders or reverse causations overcoming the limitations in the observational studies. Taking advantage of the available resources in the genome-wide association studies (GWAS), this approach has been popularized in the recent literature to obtain evidence about the causal relationship of disease of interest.

Given the increasing research focused on the relationship between the CKD and CVD, MR has been used to investigate the causal effects between these two conditions. Since the complex interplay between CKD and CVD, there are also studies performing bidirectional MR to test the causal impact between these two traits. Yu et al. [73] have found the causal effects of higher renal function on lower blood pressure, while the causal effects of blood pressure on kidney function were not statistically significant, indicating the feasibility of improving renal function in reducing the health burden of hypertension. Park et al. [74] have investigated the bidirectional relation between AF and renal function. AF has been found to be a causal risk factor for renal function impairment, while the reverse causality has not been identified. However, Geurts et al. [75] used summary statistics from the largest to date GWAS meta-analyses and supported a bidirectional causal association between kidney function and AF. Kelly et al. [76] have found the independent causal effect of impaired renal function on stroke, particularly large artery stroke, and the association remained significant even with control of systolic blood pressure. Hu et al. [77] further confirmed the causal effects of CVDs, including heart failure, strokes, ischemic strokes, on kidney function despite the insufficient evidence of causal effects of renal function on CVDs. Given the genetic variability in different races, genetic resources from different population are required to identify the different and common mechanisms underlying the crosstalk between CKD and CVD. A trans-ethnic MR study conducted by Zheng et al. [78] has identified eight cardiometabolic risk factors and showed causal effects on CKD in Europeans, and three of them showed causality in East Asians, providing insights of therapeutic intervention in different populations. Dubin et al. [79] combined large-scale proteomics and MR analyses, and revealed novel circulating protein biomarkers and potential mediators of heart failure in CKD.

To sum up, the MR-based research is a time-efficient method to identify the causal association between CKD and CVD. Further studies may identify more evidence for the disease-related risk factors on these two conditions, while the translation of these findings into effective clinical applications also remains an area requiring further exploration. Promising risk factor may need to undergo clinical studies to confirm causality and investigate underlying mechanisms.

Highly bursty references reflect to some extent the research interests of a given period. Not surprisingly, several of the top references with strong citation bursts pertain to key developments in the understanding of CKD and its association with CVD. First, these references mark significant advancements in understanding the association between CKD and CVD, providing essential frameworks for clinical practice. Faul [80] suggested that chronically elevated FGF-23 levels contribute directly to high rates of left ventricular hypertrophy and mortality in individuals with CKD. Meta-analysis conducted by Matsushita [81] further bridged the link between renal dysfunction and cardiovascular risk, reinforcing the need for integrated care. The research by Baigent [82] on lipid-lowering strategies in CKD patients has opened avenues for CVD prevention within this vulnerable population. Besides, it is notable that the papers with citations persisting until 2023 are the ones published more recently. This trend is logical, as research continuously evolves, and the academic community frequently cites the most current literature to stay abreast of the latest findings and recommendations [8]. Recent papers like McMurray et al. [83] and GBD Chronic Kidney Disease Collaboration. [84] are showing strong citation bursts up to 2023, indicating they are current influential works in the field. Bikbov B. et al. [84] pointed out that kidney disease had a major effect on global health, both as a direct cause of global morbidity and mortality and as an important risk factor for CVD, while the other four references with a burst extending into 2023 all focused on the application of SGLT2 inhibitors in metabolic disorders and cardio-renal diseases. This indicates that “Innovative Therapies and Drug Impact” is a current research hotspot in the field, which aligns with our discussion in the previous text.

Several limitations can be noticed in this study. First, we focused solely on the WOSCC database, potentially leading to the omission of relevant information from other large databases. Second, our inclusion criteria were limited to English publications, which could result in underestimating the contribution of non-English literature. Third, it is important to note that the current version of CiteSpace is limited to visualization analysis of countries, institutions, authors, etc., and cannot perform full-text analysis or assess the quality of the included literature. These limitations should be taken into consideration when interpreting the results.

We present a comprehensive overview of the global research trends concerning the association between CKD and CVD. From 2010 to 2023, there has been a consistent linear increase in publications on this topic, indicating sustained interest and research activity. The USA leads with the highest number of publications, with the University of Pennsylvania being the most prolific institution. Current research hotspots and frontiers are mainly in CKM syndrome; innovative therapies and drug impact; gut microbiome; MR analysis. Considering the notable burst intensity and duration of four keywords, it is highly likely that this research surge will persist and influence emerging research trends.

An ethics statement was not required for this study type as it is based exclusively on data from published literature. More information of the individual studies can be found in the original publication(s).

All the authors declared no competing interests.

No funding was received for the study.

B.C. and X.W.: conceptualization, software, visualization, formal analysis, and writing – original draft. D.P.: writing – review and editing. J.W.: methodology and writing – review and editing. All authors read and approved the final manuscript.

Binghao Chen and Xiangqiu Wang contributed equally to this work.

All original contributions are included in the manuscript. The data that support the findings of this study are openly available in the Web of Science Core Collection.