Background:
Renal fibrosis is considered the pathway from almost all chronic kidney diseases (CKD) to end-stage renal diseases. The unilateral ureteral obstruction (UUO) model is a well-established experimental animal model to simulate renal fibrosis associated with obstructive nephropathy in an accelerated manner. In this study, in order to understand the development trends of research on UUO-induced renal fibrosis between 2005 and 2022 and predict prospects, we conducted a comprehensive bibliometric and visualized study using Web of Science (WoS).
Methods:
The articles regarding UUO-induced renal fibrosis were culled from the “Core Collection” of the WoS database. VOSviewer software and the R-Bibliometrix Package were used in visual analysis of countries/regions, journals, authors, keywords, institutions, and highly cited articles in this field.
Results:
The number of articles regarding UUO-induced renal fibrosis has obviously increased annually. China had the largest number of publications in this field. The most frequently used keywords were “inflammation,” “transforming growth factor-beta1,” “oxigative stress,” “smad3,” “beta-catenin,” and “autophagy.” Am J Physiol-Renal was the leading journal. The most highly influential documents were published by Higgins DF and his colleagues, with 46 local citations and 749 global citations. The leading institution was Nanjing Medical University. Furthermore, Zhang Y. was the author who contributed most to this field.
Conclusion:
Our results suggest that the molecular mechanism of UUO-induced renal fibrosis remains a research hot topic, especially on the inflammatory response and oxidative stress, and international cooperation is expected to expand and deepen in the future.
Keywords: bibliometric analysis, renal fibrosis, unilateral ureteral obstruction, Web of Science
1. Introduction
Chronic kidney diseases (CKD) is an increasingly serious public health problem, with an estimated prevalence of 8% to 16% in the general population.[1] Renal fibrosis is the final common pathway for a variety of CKD and end-stage kidney diseases.[2,3] Renal fibrosis is an excessive healing or repair process marked by significant renal cell injury and consequent abnormal accumulation of extracellular matrix (ECM) proteins, primarily collagens I and III, in renal structures.[4] The continuous synthesis of ECM reduces the glomerular filtration rate, impairs kidney function, and eventually aggravates kidney injury.[5] The unilateral ureteral obstruction (UUO) is a well-characterized model of renal fibrosis caused by obstructed urine flow. Generally, the rodent UUO model is widely used to study the mechanisms of chronic obstructive kidney disease in humans.[6,7] In animals undergoing UUO, the left ureter is ligated with silk through a left flank incision. Subsequently, the static urine flow causes an increase in hydrostatic pressure and proximal tubule pressure, resulting in a decreased glomerular filtration rate and mechanical strain on tubule epithelial cells.[8] Prolonged ureteral obstruction leads to a series of pathophysiological changes in the kidney, including fibroblast proliferation and activation, inflammation, oxidative stress, cytokine release, epithelial-mesenchymal transformation (EMT), and deposition of ECM.[9] Among these changes, EMT of tubular epithelial cells is the most important contributor of renal fibrosis. EMT mostly manifests as changes in the phenotypes of epithelial cells, such as a decrease in E-cadherin expression and an induction of fibroblast markers (vimentin and α-SMA) expression.[10]
Ureteral obstruction is one of the most common complications of clinical renal diseases and can occur at any age. Previous studies have illustrated that UUO removal can attenuate renal hemodynamic and functional impairment, decrease renal fibrosis, and induce apoptosis. Nevertheless, renal damage may continue even after UUO removal.[11] On the mechanism, Ito et al[12] found that the horizontals of transforming growth factor-beta1 (TGF-β1) increased significantly, even 1 month after the removal of obstruction. Clearance of obstruction may not be sufficient to restore renal function and its histopathology, so drug intervention may be beneficial. It was reported that vitamins, antioxidants, pharmaceuticals, plant-derived compounds, and other drugs can restrain inflammation and fibrosis by inhibiting the production of fibrosis and inflammatory proteins, such as TGF-β1, tumor necrosis factor-α, collagen and fibronectin, and heat shock protein.[11] Obviously, it is extremely important to understand the molecular mechanisms of UUO-induced renal fibrosis and identify novel therapeutic strategies.
Although there have been a lot of studies and review articles on UUO-induced renal fibrosis, few articles have systematically examined the relationships among research members, summarized the current research focus, or predicted future trends in this field.[13] Bibliometric analysis is a new method for statistical and quantitative analysis of scientific research achievements that is used to assess the contribution of a research area, including countries, institutions, authors and journals. It helps scholars accurately grasp hot topics and trends in a certain field and provides better guidance for the progress of future work.[14] To date, there are few bibliometric studies on UUO-induced renal fibrosis. In the present study, we aimed to conduct a global bibliometric and visualized analysis of the literature from 2005 to 2022 on UUO-induced renal fibrosis, containing the number of countries/regions, journals, authors, keywords, institutions, and highly cited articles. Our study may provide new insight into the status and future research trends and provide new ideas for clinical prevention and treatment in the field of UUO-induced renal fibrosis.
2. Materials and methods
2.1. Data sources and search strategy
The Web of Science (WoS) is an important multidisciplinary database that provides global academic research across the sciences, social sciences, and arts & humanities. In order to conduct a comprehensive and detailed global visual study of the articles related to UUO-induced renal fibrosis, we conducted a literature search in the WoS database. Data sources from 2005 to 2022 were retrieved from the “Core Collection” of the WoS database on May 1, 2023. The formula for the search included: topic= (“unilateral ureteral obstruction” AND “fibrosis” AND “renal”) or topic= (“unilateral ureteral obstruction” AND “fibrosis” AND “kidney” NOT “renal”) or topic= (“UUO” AND “fibrosis” AND “renal” NOT “unilateral ureteral obstruction”) or topic= (“UUO” AND “fibrosis” AND “kidney” NOT “unilateral ureteral obstruction” NOT “renal”). We only chose articles and case studies for analysis. All retrieved records were exported with the format “plain text file” and the record content “full record and cited references.” Then, all files were added to the zip file and imported into bibliometric tools for further analysis. Figure 1 illustrates the search strategy used in this study.
Figure 1.
Flowchart of data search strategy.
2.2. Analysis methods and tools
All downloaded data were imported into VOSviewer (version 1.6.18), R (version 4.1.2), and Microsoft Excel 2019 for bibliometric analysis. VOSviewer is a software tool for constructing and visualizing bibliometric networks. For example, VOSviewer can be used to build networks of authors or journals based on co-citation data or keywords based on co-occurrence data.[15] In VOSviewer network visualization maps, the circle and the label form an element. The degree of the node, the quality of the link, the number of citations, etc all affect how big the element is. The element color serves as a representation of the cluster to which it belongs. Different colors are used to symbolize various groupings. In this study, VOSviewer is also used to generate bibliographic coupling maps of countries/regions and institutions. In the analysis of countries/regions, data is downloaded from VOSviewer and mapped with Scimago Graphica software. R is a free software environment for statistical computing and generating graphics. It compiles and runs on a wide variety of UNIX platforms, including Windows and MacOS. The Bibliometrix Package is an R tool for comprehensive science mapping analysis. The Bibliometrix R-package can provide a set of tools for quantitative research in bibliometrics and scientometrics.[16] We used the Bibliometrix R-package to analyze core sources, author keywords and keywords plus, institutions and co-citation maps of articles. Microsoft office Excel 2019 was used for quantitative analysis of publications, including publication type and annual number of articles.
3. Results
3.1. Document types and publication outputs
This analysis comprised 1946 papers in total, consisting solely of articles and case studies. As shown in Figure 2, the line representing the number of published articles showed an overall upward trend from 2005 to 2022. It plateaued between 2005 and 2009, indicating stagnation in the field. After 2010, it surged upward, reaching its peak in 2022.
Figure 2.
Analysis of annual publications on UUO-induced renal fibrosis between 2005 and 2022. UUO = unilateral ureteral obstruction.
3.2. Bibliometric analysis of scientific cooperation of countries/regions
A total of 49 countries/regions participated in the study of UUO-induced renal fibrosis. The top 10 countries/regions in terms of publications are shown in Table 1. China published 930 articles between 2005 and 2022, accounting for 47.79% of the total amount. The United States had the second-largest number of publications (NP) (n = 258), taking up a share of 13.26%. The NP in China was 3.6 times that in the United States. In addition, Figure 3A showed the cooperation between these countries/regions. The term “SCP” denotes that the authors belong to the same country/region, and the term “MCP” denotes that the authors belong to different countries/regions. China had the largest number of single-country publications and multi-country publications (MCP), followed by the United States and Japan. However, the ratio of MCP to total publications was lower in China (n = 0.14) than in the United States (n = 0.41). The number of citations can reflect the hot topics and trends of research on the topic. In China, the total number of citations for the publications was 19,338 and the average number of citations for each article was 20.79. The United States ranked second with 13,857 total citations (TC) and 53.71 average citations. In addition, we conducted a co-authorship analysis using full counting method of VOSviewer. As shown in Figure 3B, China had the largest number of documents. The United States had the strongest intensity of cooperation with other countries.
Table 1.
Top 10 most published countries related to UUO-induced renal fibrosis studies.
| Country | Articles | Freq | SCP | MCP | MCP_Ratio | Total citations | Average article citations |
|---|---|---|---|---|---|---|---|
| China | 930 | 0.478888 | 796 | 134 | 0.1441 | 19,338 | 20.79 |
| USA | 258 | 0.132853 | 152 | 106 | 0.4109 | 13,857 | 53.71 |
| Japan | 186 | 0.095778 | 152 | 34 | 0.1828 | 5570 | 29.95 |
| Korea | 131 | 0.067456 | 116 | 15 | 0.1145 | 3194 | 24.38 |
| Germany | 71 | 0.036560 | 36 | 35 | 0.4930 | 2612 | 36.79 |
| Australia | 49 | 0.025232 | 27 | 22 | 0.4490 | 2191 | 44.71 |
| France | 37 | 0.019053 | 20 | 17 | 0.4595 | 1904 | 51.46 |
| Spain | 34 | 0.017508 | 19 | 15 | 0.4412 | 1371 | 40.32 |
| Brazil | 28 | 0.014418 | 26 | 2 | 0.0714 | 712 | 25.43 |
| Netherlands | 28 | 0.014418 | 11 | 17 | 0.6071 | 835 | 29.82 |
MCP = multi-country publications, SCP = single-country publications, UUO = unilateral ureteral obstruction.
Figure 3.
The distribution of countries/regions in UUO-induced renal fibrosis research. (A) Analysis of publications in SCP (single country publications) and MCP (multiple country publications). (B) Collaborative network visualization maps for countries/regions based on VOSviewer. UUO = unilateral ureteral obstruction.
3.3. Bibliometric analysis of journals and co-cited journals
In this study, we also illustrated the most influential journals from the aspects of publications, citations of co-cited journals, impact factor (IF) and category of Journal Citation Reports (JCR). The JCR division divides the journals in the same discipline into 4 equal parts, with the first 25% being Q1, 25% to 50% being Q2, 50% to 75% being Q3, and 75% to 100% being Q4.[17] Table 2 lists the top 10 journals with the most publications. A total of 625 papers were published by these top journals, accounting for 32.12% of the total output. Among these journals, the top 5 were Am J Physiol-Renal, Kidney Int, J Am Soc Nephrol, PloS One, and Sci Rep. It can also be found that Kidney Int (IF = 18.998) and J Am Soc Nephrol (IF = 14.978) had a large number of citations. Figure 4 shows the growth trends in the NP in the top 5 journals from 2005 to 2022. The NP in Am J Physiol-Renal increased significantly, which appeared to be the most productive journal since 2012.
Table 2.
Top 10 journals and co-cited journals related to UUO-induced renal fibrosis.
| Journals | Publications | IF (2022) | JCR | Co-cited journals | Citations | IF (2022) | JCR |
|---|---|---|---|---|---|---|---|
| Am J Physiol Renal Physiol | 121 | 4.097 | Q2 | Kidney Int | 6927 | 18.998 | Q1 |
| Kidney Int | 100 | 18.998 | Q1 | J Am Soc Nephrol | 6108 | 14.978 | Q1 |
| J Am Soc Nephrol | 98 | 14.978 | Q1 | Am J Physiol Renal Physiol | 3299 | 4.097 | Q2 |
| PloS One | 74 | 3.752 | Q2 | J Clin Invest | 2234 | 19.456 | Q1 |
| Sci Rep | 55 | 4.996 | Q2 | J Biol Chem | 1979 | 5.486 | Q2 |
| FASEB J | 44 | 5.834 | Q1 | Am J Pathol | 1669 | 5.770 | Q1 |
| Am J Pathol | 41 | 5.770 | Q1 | Nat Rev Nephrol | 1294 | 42.439 | Q1 |
| Front Pharmacol | 34 | 5.988 | Q1 | Plos One | 1282 | 3.752 | Q2 |
| Int J Mol Sci | 29 | 6.208 | Q1 | Nephrol Dial Transpl | 1136 | 7.186 | Q1 |
| Life Sci | 29 | 6.780 | Q1 | P Natl Acad Sci USA | 1132 | 12.779 | Q1 |
IF = impact factor, JCR = Journal Citation Reports, UUO = unilateral ureteral obstruction.
Figure 4.
Trends in the top 5 most published journals in UUO-induced renal fibrosis research. UUO = unilateral ureteral obstruction.
3.4. Bibliometric analysis of author keywords and keywords plus
The statistical analysis of author keywords and keywords plus is an important method to explore the research trend of the study.[18] Author keywords are the keywords provided by the author, which can summarize the core information of the article. Author keywords plus are extracted from the title of the cited references. In addition to searching topics such as “renal fibrosis,” “fibrosis,” “unilateral ureteral obstruction,” “chronic kidney disease,” “renal interstitial fibrosis,” and “kidney,” the top 5 author keywords are “inflammation” (n = 146), “apoptosis” (n = 94), “oxidative stress” (n = 77), “tgf-beta 1” (n = 71) and “obstructive nephropathy” (n = 63). The top 5 author keywords plus included “expression” (n = 525), “injury” (n = 357), “activation” (n = 337), “mechanisms” (n = 335) and “tgf-beta” (n = 284) (Table 3). Among all these keywords, “inflammation,” “chronic kidney disease,” “TGF-β1,” “oxigative stress,” and “tubulointerstitial fibrosis” were found in both author keywords and keywords plus. Table 4 shows the study of author keywords and keywords plus in different time periods. For the author keywords, “inflammation” appeared 146 times from 2014 to 2020. “Chronic kidney disease” appeared 160 times from 2017 to 2021, and “apoptosis” occurred 94 times between 2011 and 2019, except for the search topics. In terms of the author keywords plus, “expression” (n = 525) appeared most frequently in 2013 to 2020. “injury” (n = 357) ranked second in 2014 to 2020, followed by “activation” (n = 337) in 2015 to 2020, except for the search topics. The analysis of the author keywords showed that the research of UUO-caused renal fibrosis in the recent 10 years mainly focused on these keywords such as “inflammation,” “chronic kidney disease,” “renal interstitial fibrosis,” “apoptosis,” “TGF-β1,” and “oxidative stress,” all of which appeared more than 60 times.
Table 3.
Author keywords and keywords plus research related to UUO-induced renal fibrosis.
| Author words | Occurrences | Keywords plus | Occurrences |
|---|---|---|---|
| Renal fibrosis | 475 | Expression | 525 |
| Unilateral ureteral obstruction | 248 | Injury | 357 |
| Fibrosis | 238 | Activation | 337 |
| Chronic kidney disease | 160 | Mechanisms | 335 |
| Inflammation | 146 | Unilateral ureteral obstruction | 321 |
| Renal interstitial fibrosis | 131 | Interstitial fibrosis | 314 |
| Kidney | 103 | tgf-beta | 284 |
| Apoptosis | 94 | Kidney | 261 |
| UUO | 87 | Cells | 253 |
| Oxidative stress | 77 | Inflammation | 245 |
| Kidney fibrosis | 74 | Nephropathy | 228 |
| tgf-beta 1 | 71 | Fibrosis | 220 |
| Ureteral obstruction | 68 | Disease | 208 |
| Obstructive nephropathy | 63 | Renal fibrosis | 205 |
| Epithelial-mesenchymal transition | 59 | Tubulointerstitial fibrosis | 188 |
| tgf-beta | 53 | Chronic kidney-disease | 182 |
| Extracellular matrix | 44 | Inhibition | 173 |
| Tubulointerstitial fibrosis | 41 | Progression | 171 |
| Macrophage | 40 | Oxidative stress | 163 |
| Fibroblast | 35 | Mice | 160 |
UUO = unilateral ureteral obstruction.
Table 4.
Research on author keywords and keywords plus in different periods from 2005 to 2022.
| Author keywords | Freq | Year_q1 | Year_med | Year_q3 | Keywords plus | Freq | Year_q1 | Year_med | Year_q3 |
|---|---|---|---|---|---|---|---|---|---|
| Renal fibrosis | 475 | 2016 | 2019 | 2021 | Expression | 525 | 2013 | 2016 | 2020 |
| Unilateral ureteral obstruction | 248 | 2011 | 2016 | 2019 | Injury | 357 | 2014 | 2017 | 2020 |
| Fibrosis | 238 | 2013 | 2016 | 2019 | Activation | 337 | 2015 | 2018 | 2020 |
| Chronic kidney disease | 160 | 2017 | 2020 | 2021 | Mechanisms | 335 | 2016 | 2019 | 2021 |
| Inflammation | 146 | 2014 | 2018 | 2020 | Unilateral ureteral obstruction | 321 | 2011 | 2015 | 2017 |
| Renal interstitial fibrosis | 131 | 2014 | 2018 | 2020 | Interstitial fibrosis | 314 | 2012 | 2016 | 2019 |
| Kidney | 103 | 2011 | 2015 | 2017 | tgf-beta | 284 | 2012 | 2017 | 2020 |
| Apoptosis | 94 | 2011 | 2016 | 2019 | Kidney | 261 | 2012 | 2015 | 2019 |
| UUO | 87 | 2014 | 2017 | 2020 | Cells | 253 | 2014 | 2017 | 2020 |
| Oxidative stress | 77 | 2015 | 2017 | 2020 | Inflammation | 245 | 2015 | 2018 | 2020 |
| Kidney fibrosis | 74 | 2017 | 2020 | 2021 | Nephropathy | 228 | 2010 | 2014 | 2017 |
| tgf-beta 1 | 71 | 2013 | 2017 | 2020 | Fibrosis | 220 | 2012 | 2015 | 2019 |
| Ureteral obstruction | 68 | 2010 | 2014 | 2016 | Disease | 208 | 2014 | 2017 | 2020 |
| Obstructive nephropathy | 63 | 2012 | 2015 | 2018 | Renal fibrosis | 205 | 2014 | 2017 | 2019 |
| Epithelial-mesenchymal transition | 59 | 2016 | 2018 | 2020 | Tubulointerstitial fibrosis | 188 | 2011 | 2015 | 2017 |
| tgf-beta | 53 | 2013 | 2017 | 2020 | Chronic kidney-disease | 182 | 2015 | 2018 | 2020 |
| Extracellular matrix | 44 | 2012 | 2014 | 2020 | Inhibition | 173 | 2015 | 2019 | 2020 |
| Tubulointerstitial fibrosis | 41 | 2009 | 2014 | 2018 | Mice | 160 | 2013 | 2016 | 2018 |
| Macrophage | 40 | 2012 | 2018 | 2019 | Growth-factor-beta | 153 | 2010 | 2012 | 2017 |
| Fibroblast | 35 | 2014 | 2018 | 2019 | Ureteral obstruction | 140 | 2012 | 2016 | 2019 |
| Transforming growth factor-beta 1 | 31 | 2011 | 2015 | 2017 | Diabetic-nephropathy | 120 | 2013 | 2016 | 2018 |
| Autophagy | 31 | 2017 | 2019 | 2021 | Fibroblasts | 96 | 2012 | 2015 | 2019 |
| Interstitial fibrosis | 29 | 2009 | 2014 | 2017 | Pathway | 94 | 2015 | 2018 | 2021 |
| Myofibroblast | 28 | 2011 | 2016 | 2019 | Proliferation | 89 | 2014 | 2018 | 2021 |
| Epithelial-to-mesenchymal transition | 27 | 2014 | 2016 | 2019 | Angiotensin-ii | 84 | 2008 | 2012 | 2015 |
| Macrophages | 26 | 2009 | 2015 | 2019 | Obstructive nephropathy | 83 | 2010 | 2012 | 2016 |
| Mitochondria | 24 | 2014 | 2021 | 2021 | Cancer | 60 | 2016 | 2019 | 2021 |
| Angiotensin ii | 23 | 2010 | 2013 | 2016 | Damage | 59 | 2014 | 2019 | 2020 |
| Unilateral ureteral obstruction (UUO) | 23 | 2014 | 2019 | 2021 | Myofibroblasts | 50 | 2016 | 2019 | 2021 |
| smad3 | 22 | 2019 | 2021 | 2022 | Up-regulation | 46 | 2009 | 2014 | 2019 |
| Hydronephrosis | 19 | 2008 | 2012 | 2016 | Extracellular-matrix | 37 | 2010 | 2014 | 2018 |
| Proliferation | 18 | 2011 | 2015 | 2019 | Nitric-oxide | 35 | 2010 | 2012 | 2017 |
| Microrna | 18 | 2014 | 2017 | 2020 | Rat | 35 | 2008 | 2012 | 2017 |
| Acute kidney injury | 18 | 2018 | 2020 | 2021 | Dysfunction | 35 | 2017 | 2020 | 2022 |
| stat3 | 18 | 2015 | 2020 | 2021 | Messenger-rna | 34 | 2007 | 2011 | 2016 |
| Transforming growth factor-beta | 17 | 2011 | 2014 | 2016 | Contributes | 33 | 2018 | 2020 | 2022 |
| Beta-catenin | 15 | 2018 | 2020 | 2020 | Tissue growth-factor | 31 | 2011 | 2013 | 2016 |
| Nitric oxide | 14 | 2009 | 2012 | 2017 | Autophagy | 25 | 2018 | 2020 | 2021 |
| Collagen | 11 | 2006 | 2010 | 2018 | Origin | 23 | 2018 | 2020 | 2021 |
| Tubular epithelial cells | 10 | 2014 | 2019 | 2019 | EMT | 22 | 2018 | 2020 | 2021 |
EMT = epithelial-mesenchymal transformation, UUO = unilateral ureteral obstruction.
3.5. Bibliometric analysis of authors and co-cited authors
Furthermore, we estimated the influence of authors in this field using author index analysis (h_index, g_index), TC, NP, publication year (PY_start), and co-citations. The h-index, defined as the number of papers with citation number ≥ “high citation counts,” is a useful index to characterize the scientific output of a researcher.[19] The g_index is calculated for a given set of articles, and the ranking of these articles is in descending order by the number of citations they received.[20] As shown in Table 5, Z.Y. had the largest number of published papers (n = 45), followed by W.Y. (n = 39) and Z.J. (n = 35). Among the top 20 authors, we found that L.H.Y. was the author with the highest TC (n = 2994), h_index (n = 21) and g_index (n = 33), indicating that the author had great influence in this field. Additionally, Figure 5A describes a plot of the top 20 high-yield authors in the study of UUO-induced renal fibrosis between 2005 and 2022. In the figure, the size of the dot represents the publications of the author, and the intensity level of the color represents the total number of citations each year. Co-cited authors refer to 2 or more authors simultaneously cited by another or more papers, and these 2 or more authors constitute a co-cited relationship.[21] As shown in Table 5, C.R.L. had the most co-citations (n = 811), followed by L.Y.H. (n = 690), Z.M. (n = 561) and M.X.M. (n = 499). The co-citation network of the authors is shown in Figure 5B. L.Y.H. had an active co-citation relationship with Z.M., Y.J.W., S.F., I.M., K.R., L.Y.J., and other authors.
Table 5.
Top 20 authors and co-cited authors related to UUO-induced renal fibrosis.
| First author | h_index | g_index | TC | NP | PY_start | Co-cited author | Citations |
|---|---|---|---|---|---|---|---|
| Zhang Y. | 16 | 29 | 927 | 45 | 2010 | Chevalier R.L. | 811 |
| Wang Y. | 21 | 36 | 1347 | 39 | 2009 | Liu Y.H. | 690 |
| Zhang J. | 16 | 24 | 677 | 35 | 2010 | Zeisberg M. | 561 |
| Lan H.Y. | 21 | 33 | 2994 | 33 | 2006 | Meng X.M. | 499 |
| Liu Y.H. | 25 | 30 | 2212 | 30 | 2005 | Klahr S. | 414 |
| Zhuang S.G. | 20 | 29 | 1593 | 29 | 2009 | Eddy A.A. | 401 |
| Li Y. | 10 | 26 | 709 | 27 | 2010 | Lan H.Y. | 267 |
| Zhang L. | 14 | 24 | 593 | 27 | 2012 | Yang J.W. | 265 |
| Huang X.R. | 18 | 25 | 2314 | 25 | 2006 | Humphreys B.D. | 257 |
| Wang L. | 16 | 25 | 952 | 25 | 2008 | Boor P. | 248 |
| Zhou Y. | 14 | 25 | 850 | 25 | 2010 | Iwano M. | 233 |
| Chevalier R.L. | 17 | 21 | 784 | 21 | 2005 | Grande M.T. | 227 |
| Liu Y. | 11 | 20 | 403 | 21 | 2012 | Strutz F. | 214 |
| Wang J. | 11 | 20 | 478 | 20 | 2012 | Wynn T.A. | 195 |
| Boor P. | 15 | 19 | 884 | 19 | 2007 | Sato M. | 191 |
| Chen J. | 12 | 19 | 416 | 19 | 2005 | Duffield J.S. | 183 |
| Chen L. | 10 | 19 | 569 | 19 | 2017 | Lin S.L. | 183 |
| Chen X. | 12 | 18 | 336 | 19 | 2013 | Bottinger E.P. | 150 |
| Li L. | 11 | 19 | 414 | 19 | 2010 | Kalluri R. | 148 |
| Liu N. | 14 | 18 | 719 | 18 | 2011 | Miyajima A. | 148 |
NP = number of publications, PY_start = publication year, TC = total citations, UUO = unilateral ureteral obstruction.
Figure 5.
Analysis of authors’ published papers in different times and the co-citation relationship between the authors in UUO-induced renal fibrosis research. (A) The top 20 most prolific authors’ productions in different periods. (B) Author co-citation network map. UUO = unilateral ureteral obstruction.
3.6. Bibliometric analysis of institutions
Figure 6A presents the bibliographic coupling analysis result of VOSviewer in evaluating the contribution of different institutions. Table 6 shows the top 10 productive institutions, with a total of 458 articles published, accounting for 23.54% of the total publications. Nanjing Medical University had the largest NP (n = 61), followed by China Medical University (n = 53), Fudan University (n = 46) and Southern Medical University (n = 46). Furthermore, the institution with the most citations was also Nanjing Medical University (n = 2216), followed by Central South University (n = 1428). In terms of cooperation intensity, Nanjing Medical University topped the list with 25,504 total link strengths, followed by Southern Medical University (n = 25,403). Subsequently, we summarized the relationship among authors, institutions, and countries using a 3-field plot on a Sankey diagram (Fig. 6B). In the figure, the height of the rectangular node is proportional to the occurrence frequency of a certain author, institution, or country in the cooperative network. The width of the lines between the nodes is proportional to the number of connections.[22] As shown in the figure, Central South University is the largest contributor to UUO-induced renal fibrosis in China, followed by Central South University.
Figure 6.
Analysis of inter-institutional cooperation and the relationship among institutions, authors and countries in UUO-induced renal fibrosis research. (A) Collaborative network visualization maps for institutions based on VOSviewer. (B) A 3-field plot showing the network between authors (left), institutions (middle), and countries (right). UUO = unilateral ureteral obstruction.
Table 6.
Top 10 institutions related to UUO-induced renal fibrosis.
| Institution | Documents | Total link strength | Citations | Country |
|---|---|---|---|---|
| Nanjing Med Univ | 61 | 25,504 | 2216 | China |
| China Med Univ | 53 | 22,466 | 980 | China |
| Fudan Univ | 46 | 18,489 | 1152 | China |
| Southern Med Univ | 46 | 25,403 | 1197 | China |
| Sun Yat Sen Univ | 45 | 19,110 | 1397 | China |
| Wuhan Univ | 45 | 20,780 | 810 | China |
| Cent s Univ | 44 | 16,946 | 1428 | China |
| Huazhong Univ Sci & Technol | 43 | 19,728 | 710 | China |
| Shanghai Jiao Tong Univ | 39 | 14,861 | 939 | China |
| Cent South Univ | 36 | 11,210 | 335 | China |
UUO = unilateral ureteral obstruction.
3.7. Bibliometric analysis of highly cited articles and co-citation network
Table 7 lists the top 10 globally cited articles in the research on UUO-induced renal fibrosis during 2005 to 2022. The ranking is based on total global citations (TGC). The table also shows the total local citations (TLC) and the list of journals that published the most influential articles. The most cited article was published by Higgins DF in 2007 in the journal “J Clin Invest.” The second most cited article was published in the journal “Nat Med” by Grande MT. Interestingly, 6 of the top 10 most cited articles were published in J Am Soc Nephrol. We also carried out a bibliometric analysis of the co-citation network. Co-citation means that a published article is simultaneously cited by 2 later articles. Therefore, some highly cited articles may be frequently co-cited when the articles are recognized as core articles, which reflects the scientific impact of the articles.[23] As shown in Figure 7, the co-citation network of articles showed the co-citation relationship between C.R.L. and other authors.
Table 7.
Top 10 most-cited articles in the world related to UUO-induced renal fibrosis.
| Title | First author | Yr | Source | DOI | TGC | TLC |
|---|---|---|---|---|---|---|
| Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition | Higgins D.F. | 2007 | J Clin Invest | 10.1172/JCI30487 | 749 | 46 |
| Snail1-induced partial epithelial-to-mesenchymal transition drives renal fibrosis in mice and can be targeted to reverse established disease | Grande M.T. | 2015 | Nat Med | 10.1038/nm.3901 | 472 | 76 |
| TGF-β/Smad3 signaling promotes renal fibrosis by inhibiting miR-29 | Qin W. | 2011 | J Am Soc Nephrol | 10.1681/ASN.2010121308 | 452 | 40 |
| Wnt/β-catenin signaling promotes renal interstitial fibrosis | He W.C. | 2009 | J Am Soc Nephrol | 10.1681/ASN.2008060566 | 439 | 55 |
| Klotho inhibits transforming growth factor-β1 (TGF-β1) signaling and suppresses renal fibrosis and cancer metastasis in mice | DOI S. | 2011 | J Biol Chem | 10.1074/jbc.M110.174037 | 397 | 0 |
| Galectin-3 expression and secretion links macrophages to the promotion of renal fibrosis | Henderson N.C. | 2008 | Am J Pathol | 10.2353/ajpath.2008.070726 | 395 | 31 |
| The NLRP3 inflammasome promotes renal inflammation and contributes to CKD | Vilaysane A. | 2010 | J Am Soc Nephrol | 10.1681/ASN.2010020143 | 392 | 35 |
| Smad3-mediated upregulation of miR-21 promotes renal fibrosis | Zhong X. | 2011 | J Am Soc Nephrol | 10.1681/ASN.2010111168 | 334 | 32 |
| miR-192 mediates TGF-β/Smad3-driven renal fibrosis | Chung A.C.K. | 2010 | J Am Soc Nephrol | 10.1681/ASN.2010020134 | 299 | 24 |
| Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes | Sabbisetti V.S. | 2014 | J Am Soc Nephrol | 10.1681/ASN.2013070758 | 277 | 2 |
CKD = chronic kidney disease, ESRD = end-stage kidney disease, TGC = total global citations, TLC = total local citations, TGF-β1 = transforming growth factor-beta1, UUO = unilateral ureteral obstruction.
Figure 7.
Article co-citation network map in UUO-induced renal fibrosis research. UUO = unilateral ureteral obstruction.
4. Discussion
Bibliometric research can provide a valuable relationship between articles, citations, co-citations, and keywords and help readers easily and clearly identify research interests and overall trends in a specific field.[24] The number and trend of publications can reflect the long-term development speed and research situation, and can also indicate the central trend of research in this field.[21] In this study, we performed a comprehensive bibliometric analysis of the literature on UUO-induced renal fibrosis. From 2005 to 2022, a total of 1946 articles were published. In the past 15 years, the NP related to UUO-induced renal fibrosis has generally increased. It is predicted that CKD will become the fifth leading cause of death in the world by 2024. Fibrosis is the final pathophysiological pathway of most CKD, and the established experimental model is the UUO model. This may be the reason why the research on renal fibrosis induced by UUO continues to grow around the world, and there is a trend of continuous growth.
Our research showed that China and the United States have been 2 major contributors to the study. China ranked first with 930 articles, accounting for 47.80% of the total articles, followed by the United States. This may suggest that China and the United States are the leaders in the study of UUO-induced renal fibrosis. In addition, there was no significant difference in the TC of articles published in China and the United States. However, the average number of citations in China was significantly lower than that in the United States, indicating that the articles in the United States had a greater impact or higher utility in the specific field. International cooperation between different academic research groups and institutions is becoming increasingly frequent. From 2005 to 2022, many countries and regions have developed extensive international communication and cooperation in the study of UUO-induced renal fibrosis. We found that the United States had the highest “total intensity of cooperation” and the most extensive cooperation with other countries. Although China had the largest publication, cooperation between China and other countries/regions was mainly limited to Singapore, Sweden, Germany, and the United States. These results may suggest that China should strengthen global cooperation and search for more partners within its global scope.
Meanwhile, Nanjing Medical University was considered the most productive institution, followed by China Medical University and Fudan University. Surprisingly, the top 10 institutions on UUO-induced renal fibrosis were all from China, indicating that China has had in-depth research and development in this field.
Bibliometric analysis of journals can provide reliable references for scientific researchers to retrieve literature or submit papers.[25] Our results also showed that the top 3 prolific journals were Am J Physiol Renal Physiol (IF = 4.097), Kidney Int (IF = 18.998), and J Am Soc Nephrol (IF = 14.978). It can be found that the IF of Am J Physiol Renal Physiol is <5, but it has the largest NP among all journals. This may suggest that the outcomes of research were mainly published in journals with moderate academic impact. In addition, Kidney Int had the greatest number of citations, followed by J Am Soc Nephrol and Am J Physiol Renal Physiol. The publications of Am J Physiol Renal Physiol showed an obvious increasing tendency from 2005 to 2022, which has maintained the first place since 2012. In contrast, the total number of citations in Am J Physiol Renal Physiol didn’t keep the increasing trend as expected. Kidney Int and J Am Soc Nephrol were both journals with high publications and TC, which indicated that the articles published by these 2 journals were of high academic value. Our results also indicated that the article with the highest global citation (LGC) was published in J Clin Invest in 2007. This article, titled Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition, was written by Higgins DF and his colleagues. It mainly discussed how the activation of hypoxia-inducible factor-1 (HIF-1) signaling in renal epithelial cells is associated with the development of CKD.[26] It is a milestone, with great clinical significance, in the development of UUO-induced renal fibrosis research.
In addition, our results showed that Z.Y., as a first author, owns the largest nymber of published articles, followed by W.Y., Z.J., and L.H.Y. Though, it is worth noting that L.H.Y. may be the most influential author in the field of UUO-induced renal fibrosis research since she had the largest number of citations. Moreover, L.H.Y. 2011 article, titled Smad3-mediated Upregulation of Mir-21 Promotes Renal Fibrosis, had the largest citations. This author also has many in-depth studies on the TGF-β/Smad signaling pathway, such as the effects of microRNA and angiotensin converting enzyme on the TGF-β/Smad signaling pathway.[27,28] Among all authors, Chevalier RL has a strong co-citation relationship with authors such as E.A.A. and K.S.
Keywords are important research themes and the core content of a piece of literature. Through bibliometric analysis of the author keywords and keywords plus, we accurately revealed the hot topics and overall development trend in the field of UUO-induced renal fibrosis research. Our study showed that “inflammation,” “chronic kidney disease,” “tgf-beta,” “oxidative stress,” and “tubulointerstitial fibrosis” appeared in both author keywords and keywords plus. Oxidative stress and the inflammatory response are the most prominent features of kidney injury. In the injury response, inflammation initially appears as a renal protective effect, and oxidative stress can amplify the inflammatory response to promote kidney damage.[29] Therefore, oxidative stress and the inflammatory response have received extensive attention in this field and need further study. It is worth noting that tgf-beta 1, tgf-beta in author keywords, and tgf-beta and growth-factor-beta in keywords plus belong to growth factors. At present, the most studied growth factor is TGF-β1. A large amount of evidence shows that TGF-β1 can promote the production of ECM and prevent its degradation, as well as mediate the transformation of renal tubular epithelial cells into myofibroblasts through EMT, inducing renal fibrosis.[30] This is an important research direction for UUO-induced renal fibrosis. We also summarized the frequency of occurrence of author keywords and keywords plus in different time periods. We found that inflammation, oxidative stress, tgf-beta, macrophages, and other keywords appeared frequently in the past 10 years. At the same time, smad3, beta-catenin, and autophagy have been the focus of research from 2018 to 2021. This result indicated that the molecular mechanism of UUO-induced renal fibrosis will remain a research hot topic over the next few years.
There are some limitations to our study. Firstly, our data came from the core data set of the WoS, data from other databases were excluded, which may result in incomplete data collection. Secondly, the data in the WoS database is updated quickly, and our results are limited to the analysis of specific time periods.
In conclusion, we conducted a bibliometric and visualized study using 1946 documents retrieved from the WoS database to map global research trends in UUO-induced renal fibrosis from 2005 to 2022. Through bibliometric analysis, the appropriate academic articles were analyzed to investigate the relationships among countries/regions, authors, keywords, institutions, and citations. The results indicated that the annual publication of UUO-induced renal fibrosis research increased significantly from 2005 to 2022. China remained a leader in this field, followed by the United States and Japan. The author keyword analysis showed that “inflammation,” “TGF-β1,” “oxigative stress,” “smad3,” “beta-catenin,” and “autophagy” appeared most frequently. In aspects of journal analysis, Am J Physiol-Renal published the most articles, followed by Kidney Int and J Am Soc Nephrol. The most highly influential articles were published by Higgins DF and his colleagues, with 46 total local citations and 749 total global citations. Among all the organizations, Nanjing Medical University had the largest NP and achieved a lot of important research results. In addition, several researchers, such as Z.Y., W.Y., Z.J., L.H.Y., and L.Y.H., have made great contributions to this field. These results will help researchers better understand and grasp future research hot topics and directions.
Author contributions
Data curation: Yashu Wang, Zhaohua Yang.
Formal analysis: Yashu Wang, Xinna Deng.
Investigation: Yashu Wang, Zhaohua Yang.
Software: Yashu Wang, Xinna Deng.
Validation: Yashu Wang, Xinna Deng.
Writing – original draft: Yashu Wang.
Writing – review & editing: Xinna Deng, Haijiang Wu.
Supervision: Zhaohua Yang.
Abbreviations:
- CKD
- chronic kidney disease
- ECM
- extracellular matrix
- EMT
- epithelial-mesenchymal transformation
- IF
- impact factor
- MCP
- multi-country publication
- NP
- number of publications
- TC
- total citations
- TGF-β1
- transforming growth factor-beta1
- UUO
- unilateral ureteral obstruction
- WoS
- Web of Science.
This work was supported by the Hebei Science and Technology Department Program (Nos. H2018206110 and H2020206326).
The manuscript submitted does not contain information about medical device(s)/drug(s).
The authors have no conflicts of interest to disclose.
This is a review that does not require an ethics committee review board approval and informed consent.
The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.
How to cite this article: Wang Y, Deng X, Yang Z, Wu H. Global research trends in unilateral ureteral obstruction-induced renal fibrosis: A bibliometric and visualized study. Medicine 2023;102:32(e34713).
Contributor Information
Yashu Wang, Email: medicine147@sina.com.
Xinna Deng, Email: dengxinna001@163.com.
Zhaohua Yang, Email: yzh18733155169@163.com.
References
- [1].Jha V, Garcia-Garcia G, Iseki K, et al. Chronic kidney disease: global dimension and perspectives. Lancet. 2013;382:260–72. [DOI] [PubMed] [Google Scholar]
- [2].Li S, Zhao Y, Wang Z, et al. Transplantation of amniotic fluid-derived stem cells preconditioned with glial cell line-derived neurotrophic factor gene alleviates renal fibrosis. Cell Transplant. 2019;28:65–78. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [3].Humphreys BD. Mechanisms of renal fibrosis. Annu Rev Physiol. 2018;80:309–26. [DOI] [PubMed] [Google Scholar]
- [4].Chen F, Gao Q, Wei A, et al. Histone deacetylase 3 aberration inhibits Klotho transcription and promotes renal fibrosis. Cell Death Differ. 2021;28:1001–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5].Zhang B, Liu P, Zhou Y, et al. Dihydroartemisinin attenuates renal fibrosis through regulation of fibroblast proliferation and differentiation. Life Sci. 2019;223:29–37. [DOI] [PubMed] [Google Scholar]
- [6].Jiménez-Uribe AP, Bellido B, Aparicio-Trejo OE, et al. Temporal characterization of mitochondrial impairment in the unilateral ureteral obstruction model in rats. Free Radic Biol Med. 2021;172:358–71. [DOI] [PubMed] [Google Scholar]
- [7].Bai Y, Wang W, Yin P, et al. Ruxolitinib alleviates renal interstitial fibrosis in UUO mice. Int J Biol Sci. 2020;16:194–203. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [8].Peng YH, Xiao J, Yan C, et al. Potential role of the resident mesenchymal stem-like cells in renal fibrogenesis after ureteral obstruction. Stem Cells Int. 2019;2019:2543171. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [9].Lu M, Li H, Liu W, et al. Curcumin attenuates renal interstitial fibrosis by regulating autophagy and retaining mitochondrial function in unilateral ureteral obstruction rats. Basic Clin Pharmacol Toxicol. 2021;128:594–604. [DOI] [PubMed] [Google Scholar]
- [10].Yang J, Antin P, Berx G, et al. Author correction: guidelines and definitions for research on epithelial-mesenchymal transition. Nat Rev Mol Cell Biol. 2021;22:834. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [11].Martínez-Klimova E, Aparicio-Trejo OE, Tapia E, et al. Unilateral ureteral obstruction as a model to investigate fibrosis-attenuating treatments. Biomolecules. 2019;9:141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [12].Ito K, Chen J, El-Chaar M, et al. Renal damage progresses despite improvement of renal function after relief of unilateral ureteral obstruction in adult rats. Am J Physiol Renal Physiol. 2004;287:F1283–93. [DOI] [PubMed] [Google Scholar]
- [13].Xiao P, Wu D, Wang J. Bibliometric analysis of global research on white rot fungi biotechnology for environmental application. Environ Sci Pollut Res Int. 2022;29:1491–507. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [14].Wang C, Jing H, Sun Z, et al. A bibliometric analysis of primary aldosteronism research from 2000 to 2020. Front Endocrinol (Lausanne). 2021;12:665912. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [15].Van-Eck NJ, Waltman L. Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics. 2010;84:523–38. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [16].Martynov I, Klima-Frysch J, Schoenberger J. A scientometric analysis of neuroblastoma research. BMC Cancer. 2020;20:486. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [17].Dong Q, Liang Q, Chen Y, et al. Bibliometric and visual analysis of vascular calcification research. Front Pharmacol. 2021;12:690392. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [18].Zhang G, Xie S, Ho YS. A bibliometric analysis of world volatile organic compounds research trends. Scientometrics. 2010;83:477–92. [Google Scholar]
- [19].Hirsch JE. An index to quantify an individual’s scientific research output. Proc Natl Acad Sci U S A. 2005;102:16569–72. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [20].Bao Y, Mehmood K, Saifullah, et al. Global research on the air quality status in response to the electrification of vehicles. Sci Total Environ. 2021;795:148861. [DOI] [PubMed] [Google Scholar]
- [21].Ma D, Yang B, Guan B, et al. A bibliometric analysis of pyroptosis from 2001 to 2021. Front Immunol. 2021;12:731933. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [22].Koo M. Systemic lupus erythematosus research: a bibliometric analysis over a 50-year period. Int J Environ Res Public Health. 2021;18:7095. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [23].Chang CY, Gau ML, Tang KY, et al. Directions of the 100 most cited nursing student education research: a bibliometric and co-citation network analysis. Nurse Educ Today. 2021;96:104645. [DOI] [PubMed] [Google Scholar]
- [24].Geng D, Feng Y, Zhu Q. Sustainable design for users: a literature review and bibliometric analysis. Environ Sci Pollut Res Int. 2020;27:29824–36. [DOI] [PubMed] [Google Scholar]
- [25].Garfield E. Journal impact factor: a brief review. CMAJ. 1999;161:979–80. [PMC free article] [PubMed] [Google Scholar]
- [26].Higgins DF, Kimura K, Bernhardt WM, et al. Hypoxia promotes fibrogenesis in vivo via HIF-1 stimulation of epithelial-to-mesenchymal transition. J Clin Invest. 2007;117:3810–20. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [27].Li R, Chung AC, Dong Y, et al. The microRNA miR-433 promotes renal fibrosis by amplifying the TGF-β/Smad3-Azin1 pathway. Kidney Int. 2013;84:1129–44. [DOI] [PubMed] [Google Scholar]
- [28].Liu Z, Huang XR, Chen HY, et al. Loss of angiotensin-converting enzyme 2 enhances TGF-β/Smad-mediated renal fibrosis and NF-κB-driven renal inflammation in a mouse model of obstructive nephropathy. Lab Invest. 2012;92:650–61. [DOI] [PubMed] [Google Scholar]
- [29].Zheng T, Tan Y, Qiu J, et al. Alternative polyadenylation trans-factor FIP1 exacerbates UUO/IRI-induced kidney injury and contributes to AKI-CKD transition via ROS-NLRP3 axis. Cell Death Dis. 2021;12:512. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [30].Zou J, Zhou X, Ma Y, et al. Losartan ameliorates renal interstitial fibrosis through metabolic pathway and Smurfs-TGF-β/Smad. Biomed Pharmacother. 2022;149:112931. [DOI] [PubMed] [Google Scholar]