Key Topics and New Trends in Podocyte Injury Research from 1994 to 2021: A Data-Driven Overview

We conducted a literature search on the Web of Science Core Collection (WoSCC) on podocyte injury in the past 30 years (from 1990 to 2021). The search formula was as follows: TS = (“podocyte pyroptosis” OR “podocyte apoptosis” OR “podocytopathy” OR “podocytopathies” OR “podocyte injury” OR “podocyte damage”, and OR “podocyte dysfunction”). The article language was set to English. In order to avoid deviations from data updates, all the above operations were performed within 1 day, and on July 4, 2021.

The document types included in the study were only articles and reviews. Meeting abstracts, editorial materials, and proceedings papers, among others, and were excluded. Duplicate studies were also removed artificially. All the information, including the number of papers and citations, titles, authors, affiliations, countries, keywords, journal, publication year, and references, were collected for bibliometric analysis.

In this study, HistCite (version 12.03.17), VOSviewer (version 1.6.16), CiteSpace (version 5.7.R5), and the Bibliometrix 4.1.0 Package (https://www.bibliometrix.org↗) based on the R language were used to perform the bibliometric analysis.

HistCite (Garfield et al., 2006) was used to calculate the total number of publication records, total global citation score (TGCS), and total local citation score (TLCS) for each publication year, active countries, top institutions, core journals, and authors. More importantly, it was used to identify the representative citation paths of important references.

VOSviewer (van Eck and Waltman, 2010) was used to visualize complex co-citation networks, such as the cooperation and time trends among countries, institutions, and individuals. The size of the nodes represents the number of publications; the thickness of the line represents the strength of the link; and the colors of the nodes represent different clusters or times.

CiteSpace was used to aid visual analysis of the knowledge domain and emerging trends (Chen, 2004), including cluster analysis, dual-map overlay of citations, timeline or time zone views, references, and keywords citation bursts (Chen and Leydesdorff, 2014; Chen and Song, 2019). Cluster analysis can classify references and keywords and identify important research areas on podocyte injury. The modularity Q and mean silhouette are two important evaluation indicators in cluster analysis. Q > 0.3 indicates that the clustering structure is significant enough. Mean silhouette >0.5 indicates that the clustering results are convincing. The bursts of keywords and references are often used to detect new research trends in the field.

The Bibliometrix Package is an established tool based on the R language that is used for bibliometric analysis (Aria and Cuccurullo, 2017). We conducted a thematic evolution analysis using the Bibliometrix Package to categorize the changes in podocyte injury research into different periods.

A total of 2,669 publications related to podocyte injury were retrieved from WoSCC, including 2,311 articles, and 358 reviews (Supplementary Table S1; Supplementary Figure S1). Curve fitting analysis showed that the annual number of publications on podocyte injury has undergone an overall increasing trend since 1994 (R² = 0.9329; p < 0.001). We artificially divide this period into three stages according to the annual output and growth rate: Initial stage (1994–2004), growing stage (2005–2010), and mature stage (2011–2021). In the initial stage, the total number of publications on podocyte injury was less than 20 per year, and in 1994–1996, only two articles were published in each year, and the only two articles in 1994 were written by Pascua M and Kretzler M, who investigated podocyte injury earlier than researchers in other parts of the world. Pascual et al. (1994) found that complement receptor 1 (CR1) can be used as a marker for podocyte injury (cited 68 times). Over the same period, Kretzler et al. (1994) proposed for the first time that in the uninephrectomized-desoxycorticosterone hypertensive rat model, and glomerulosclerosis may be due to podocyte injury (cited 143 times). In the growing stage, the number of total publications on podocyte injury was less than 100 per year, but increased at an average rate of 9.6 articles per year, and with an average annual growth rate of 25.23%. In the mature stage, the total number of publications on podocyte injury was more than 100 per year and increased at an average rate of 23.1 articles per year, with an average annual growth rate of 14.76% (Figure 1A). The highest number of articles was published in 2020 (n = 311), which was more than the total number of articles published in the previous 15 years (1994–2008, n = 289).

So far, these articles have been cited 72,836 times, with an average of 27.29 times per article. Since the field of research was then still immature, the TGCS and TLCS of articles published in the initial stage were low. However, the TGCS increased year by year from 2005 to 2008. Since 2009, the TGCS has been relatively stable, indicating that the research on podocyte injury has entered a relatively mature stage (Figure 1B).

From 1994 to 2021, 69 countries published research articles on podocyte injury. The global article productivity is presented in Figure 2A. The top 10 countries with the highest number of publications have generated about 84.57% of the articles in the world (Figure 2B; Table 1). China showed the highest output, publishing a total of 1,065 (39.46%) articles related to podocyte injury, followed by the United States (n = 872; 32.31%), and Japan (n = 341; 12.63%) (Figure 2C). The most cited country for published articles is the United States (cited 36,896 times), followed by China (cited 18,077 times), and Germany (cited 12,008 times) (Figure 2D). In addition, German publications have the highest average number of citations (average cited 49.83 times), followed by Italy (average cited 48.02 times), and Canada (average cited 42.79 times) (Figure 2E). The visualized international collaboration network showed that the cooperation between countries is relatively close. The United States and China showed the closest cooperation, and the United States has been in cooperation with almost all the other countries (Figure 2F). Since 1994, research in this field has increased in Germany, Italy, and the United Kingdom, whereas the research on podocyte injury in China, Spain, and Egypt has increased since 2005 (Figure 2G).

A total of 10,328 authors from 2,172 institutions have published articles on podocyte injury. The top 10 institutions with the highest output in podocyte injury research are shown in Table 2. Southern Medical University in China (n = 68) was the leading institution in terms of output, followed by Nanjing Medical University in China (n = 64), the University of Bristol in the United Kingdom (n = 62), and the University of Michigan in the United States (n = 62). The TGCS of the University of Washington in the United States (cited 3,986 times) was the highest, followed by the University of Michigan (cited 3,280 times), and the University of Bristol (cited 2067 times). Cooperation among institutions was relatively close and was divided into four institutional clusters. The cooperation groups led by the University of Michigan showed the closest cooperation with other institutions (Figure 3A).

The top three most productive authors were Moin A Saleem of the University of Bristol (published 50 articles), John Cijiang He of the Icahn School of Medicine at Mount Sinai (published 43 articles), and Zhihong Liu of the Medical School of Nanjing University (published 40 articles) (Table 3). Kretzler M is an early researcher on podocyte injury. He published his first achievement in this field in 1994. So far, he has been engaged in research in this field for nearly 30 years (1994–2020) (Figure 3B). Youhua Liu of Southern Medical University was the most cited author (cited 3,120 times), followed by Stuart J Shankland of the University of Washington (cited 2,730 times) and Matthias Kretzler of the University of Michigan (cited 2,613 times). The degree of cooperation among authors was relatively low and characterized by cooperation within the institution (Figure 3C).

All articles on podocyte injury were published in 413 journals. The top 10 journals with the highest productivity are shown in Table 4. About 31.32% of the articles were published in these journals. The Journal of the American Society of Nephrology (JASN) (published 159 articles, cited 10,305 times) was the most prolific journal, followed by Kidney International (KI) (published 148 articles, cited 8,895 times) and American Journal of Physiology–Renal Physiology (published 142 articles, cited 4,476 times). These three journals were also the most cited. The dual-map overlay shows three main citation paths. The published articles were mainly focused on journals in the field of molecular, biology, immunology and medicine, and medical clinical, whereas most of the cited articles were published in journals in the field of molecular, biology, genencs, health, nursing, and medicine (Figure 4).

The top 15 most cited references includes 7 reviews and 8 research articles (Table 5). Most articles focused on the pathophysiology and mechanism of podocyte injury. The most cited article was written by Susztak, who reported that a high-glucose environment can cause podocyte depletion, and leading to early DKD (cited 767 times) (Susztak et al., 2006). Subsequently, Inoki K et al. found that reducing the activity of mammalian target of rapamycin complex 1 in podocytes is a potential strategy for preventing DKD (cited 355 times) (Inoki et al., 2011), which further promoted the development of this field of study. We subsequently constructed a visualization network of cited references and performed a cluster analysis. A total of 14 clusters were found, the modularity Q was 0.6587, and the mean silhouette value was 0.8617 (Supplementary Table S2). Six clusters with the highest K values were identified (Table 6; Figure 5A), which include “cytoskeleton,” “diabetic nephropathy,” and “stretch,” among others. Furthermore, we performed a visualized timeline for clusters (Figure 5B). We found that “interstitial fibrosis” is an early field in podocyte injury. However, the current hotspots of podocyte injury are on “autophagy,” “diabetic kidney disease,” and “lncRNA.” Finally, we conducted a reference burst. The top 25 references with the strongest citation bursts are shown in Supplementary Figure S2. Figure 5C shows the most representative references in terms of burst strength, burst duration, and burst time. We found that the works of Pavenstädt et al. (2003) have the highest bursts strength. In his article, he described the relationship between podocyte injury and glomerulosclerosis Pavenstädt et al. (2003), indicating that this is the current focus in podocyte injury research. In addition, Nagata M’s article has had a strong citation burst in recent years. His article introduced the correlation between autophagy and podocyte injury, indicating that this has garnered increased research interest in recent years (Nagata, 2016).

We extracted 4,080 keywords at data collection, and a cluster analysis revealed 8 clustering results (Table 7). The modularity Q of the cluster was 0.3087, and the mean silhouette value was 0.7322. The timeline of clustering showed that “diabetic nephropathy” and “proteinuria” were the most important areas of podocyte injury research, whereas “autophagy” was an emerging hotspot in podocyte injury studies (Figure 6A). We conducted a thematic evolution analysis on keywords, and found that the initial stages of research on podocyte injury was mainly focused on “diabetic nephropathy.” However, with the maturity of the research field, the main research hotspot of podocyte injury has gradually evolved toward “homocysteine,” “apoptosis,” and “obesity,” among others. In the past 3 years, “mitochondrial dysfunctions,” “exosome,” among others, and has gradually attracted the attention of scholars (Figure 6B). A total of 102 keywords were extracted by keyword burst analysis, the top 25 of which are shown in Supplementary Figure S3. We found that “autophagy” and “diabetic kidney disease” had the highest burst strength. In addition, we also found that “inflammation,” “protect,”, and “microRNA” were the latest keywords that emerged in the last 2 years (Figure 6C).

In addition, we followed the practice of (Kumar and Goel, 2021; Kumar et al., 2021) to explore the research gaps in the field of podocyte injury. We found that studies on podocyte injury were less exposed in acute kidney injury and IgA nephropathy, which may be related to the pathophysiological characteristics of podocytes. Notably, our study also found that the protective effect of traditional Chinese medicine monomer on podocyte injury is a promising blank field, and such as astragaloside iv (occurrences: 12), triptolide (occurrences: 10), berberine (occurrences: 7), etc. (Figure 6D). Xing et al. (2021) found that astragaloside iv can inhibit oxidative stress and alleviate podocyte damage. Coincidentally, Wan et al. (2021) found that triptolide can reverse the epithelial-mesenchymal transition of podocytes and improve podocyte-associated glomerular diseases. Therefore, the protective effect of traditional Chinese medicine monomer on podocyte injury needs more research to fill this gap.