The 100 top-cited articles on chronic kidney disease–mineral and bone disorder: A bibliometric analysis

Abstract

Background:

Tremendous scientific research has been conducted on chronic kidney disease–mineral and bone disorder (CKD–MBD), while only a few bibliometric analyses have been conducted in this field. In this study, we aim to identify 100 top-cited articles on CKD–MBD and analyze their main characteristics quantitatively.

Methods:

Web of Science was used to search the 100 top-cited articles on CKD–MBD. The following data were extracted and analyzed from the selected articles: author, country of origin, institutions, article type, publication journal, publication year, citation frequency, and keywords.

Results:

Among the 100 top-cited articles, the number of citations ranged between 181 to 2157, with an average number of citations of approximately 476. These articles were published in 23 different journals, with Kidney International publishing the most articles (n = 32). The largest contributor was the United States (n = 63), which was also the country that conducted the most collaborative studies with other nations. The University of Washington contributed the largest number of articles (n = 37). Block GA was the most common first-author (n = 7). The majority of articles were clinical research articles (n = 73), followed by reviews (n = 15). Although almost half of the articles had no keywords, the most concerned research direction was CKD-associated bone disease.

Conclusion:

This is the first bibliometric study of the 100 top-cited articles on CKD–MBD. This study provides the main academic interests and research trends associated with CKD–MBD research.

1. Introduction

Chronic kidney disease (CKD) is a globally recognized public health concern with a rising incidence. CKD mortality rates have increased by 41.5% from 1990 to 2017^[1] and are projected to become a leading cause of reduced life expectancy by 2040.^[2] Chronic kidney disease–mineral and bone disorder (CKD–MBD) is a common complication of CKD, characterized by disturbances in calcium, phosphorus, parathyroid hormone, and vitamin D metabolism, as well as abnormal bone turnover, mineralization, mass, linear growth, and strength, along with vascular and soft tissue calcification.^[3] CKD–MBD has been associated with increased cardiovascular events and mortality among patients,^[4,5] making it an important area of study in CKD research.

Bibliometric analysis has emerged as a valuable research tool, particularly in scientific and applied fields.^[6] The citation count of an article reflects its academic significance and impact within the scientific community. Analyzing the most highly cited articles in a field provides insights into key areas and research trends. While bibliometric analyses have been conducted in nephrology on topics such as hemodialysis, automatic peritoneal dialysis, diabetic nephropathy, renal fibrosis, and the relationship between lifestyle changes and CKD,^[7–10] to date, no bibliometric analysis specifically focusing on CKD–MBD articles has been performed. Therefore, this study aims to conduct a comprehensive bibliometric analysis of the top-cited articles on CKD–MBD, providing valuable insights and establishing a foundation for future research.

2. Materials and methods

2.1. Search strategy

The Web of Science (https://apps.webofknowledge.com) was used to search for articles related to CKD–MBD during 1950 to 2022. A comprehensive search strategy was performed to identify the intersection of the search terms describing “CKD” and “MBD,” according to the definition of CKD–MBD, being limited to the field of “Topic.” Although there was no restriction on the type of article, the language was restricted to English. Articles that met these criteria were sorted according to the number of citations, and those after 300 were removed. Two researchers independently reviewed the abstract and the full text of the articles to eliminate unqualified articles, and differences were resolved by discussion with a third researcher.

2.2. Bibliometric analysis

The top 100 highly cited articles were selected for the bibliometric analysis. Each article was summarized according to the author, country of origin, institution, article type, publication journal, publication year, citation frequency, and keywords, and the Online Analysis Platform of Literature Metrology (http://bibliometric.com/) and the Vosviewer1.6.19 were used to conduct descriptive analysis.

3. Results

3.1. Distribution of publication year

The initial round of screening generated a total of 8481 articles, and after the second round of screening, we obtained the top 100 highly cited articles on CKD–MBD. The citations of these 100 articles were relatively high, ranging between 181 and 2152, with an average of approximately 476. Table 1 enlists the top 20 cited articles on CKD–MBD. Among the top 100 articles, the majority were published during 1998 to 2013 (n = 68), and the first article was published in 1969, while the most recent was published in 2017 (Table 1; Fig. 1).

Table 1.

The list of the top 20-cited articles on CKD–MBD.

Rank	Citation number	Title	DOI
1	2152	Coronary artery calcification in young adults with end-stage renal disease who are undergoing dialysis	10.1056/NEJM200005183422003
2	1927	Mineral Metabolism, mortality, and morbidity in maintenance hemodialysis	10.1097/01.ASN.0000133041.27682.A2
3	1867	Association of serum phosphorus and calcium × phosphate product with mortality risk in chronic hemodialysis patients: A national study	10.1053/ajkd.1998.v31.pm9531176
4	1148	Definition, evaluation, and classification of renal osteodystrophy: A position statement from kidney disease: Improving global outcomes (KDIGO)	10.1038/sj.ki.5000414
5	1141	Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients	10.1046/j.1523-1755.2002.00434.x
6	1083	Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease	10.1161/hy1001.096358
7	1041	Chronic kidney disease: effects on the cardiovascular system	10.1161/CIRCULATIONAHA.106.678342
8	1040	Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: Results of the study to evaluate early kidney disease	10.1038/sj.ki.5002009
9	881	Cardiac calcification in adult Hemodialysis patients - A link between end-stage renal disease and cardiovascular disease?	10.1016/s0735-1097(01)01781-8
10	816	Serum phosphate levels and mortality risk among people with chronic kidney disease	10.1681/ASN.2004070602
11	815	Arterial stiffening and vascular calcifications in end-stage renal disease	10.1093/ndt/15.7.1014
12	777	Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis	10.1056/NEJMoa031633
13	762	Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy	10.1056/NEJMoa022536
14	750	Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease	10.1038/ki.2011.47
15	710	The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification	10.1172/JCI17202
16	704	Survival predictability of time-varying indicators of bone disease in maintenance hemodialysis patients	10.1038/sj.ki.5001514
17	680	Marked suppression of secondary hyperparathyroidism by intravenous administration of 1,25-dihydroxy-cholecalciferol in uremic patients	10.1172/JCI111639
18	656	Human vascular smooth muscle cells undergo vesicle-mediated calcification in response to changes in extracellular calcium and phosphate concentrations: A potential mechanism for accelerated vascular calcification in ESRD	10.1097/01.ASN.0000141960.01035.28
19	655	Activated injectable vitamin D and hemodialysis survival: A historical cohort study	10.1681/ASN.2004070573
20	637	Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease	10.1681/ASN.2005010052

CKD–MBD = chronic kidney disease–mineral and bone disorder.

Figure 1.

Distribution of the top 100 highly cited articles on CKD–MBD by the publication yr. The left side of the vertical axis represents the number of articles, while the right side represents the average number of citations. CKD–MBD = chronic kidney disease–mineral and bone disorder.

3.2. Distribution of publication journals

The 100 top-cited articles were published across 23 different journals, with Kidney International (n = 32), Journal of the American Society of Nephrology (n = 15), New England Journal of Medicine (n = 8), and American Journal of Kidney Diseases (n = 8) publishing the most number of articles. Kidney International had the highest average number of citations per article (n = 1487), followed by Circulation (n = 731) and the New England Journal of Medicine (n = 731). The top 10 journals publishing highly cited articles on CKD–MBD are shown in Table 2.

Table 2.

The list of top 10 journals publishing the top 100 highly cited articles on CKD–MBD.

Journal	Number of articles	Total citation number	Average citation number	Impact factor (2021)
Kidney International	32	47568	1487	18.998
Circulation	3	2192	731	39.918
New England Journal Of Medicine	8	5797	725	176.079
Journal Of The American Society Of Nephrology	15	8306	554	14.978
Journal Of Clinical Investigation	5	2550	510	19.456
American Journal Of Kidney Diseases	8	3895	487	11.072
Nephrology, Dialysis, Transplantation	4	1676	419	7.186
Clinical Journal Of The American Society Of Nephrology	3	1179	393	10.614
Lancet	2	577	289	202.731
The Journal Of Clinical Endocrinology And Metabolism	3	863	288	6.134

CKD–MBD = chronic kidney disease–mineral and bone disorder.

3.3. Distribution characteristics of the countries

The 100 top-cited articles on CKD–MBD originated from several countries, including the United States (n = 63), Japan (n = 7), the United Kingdom (n = 7), France (n = 6), and Germany (n = 6), etc. The list of the top 10 countries with the highest publications of the top-cited CKD–MBD articles is provided in Table 3. In addition, the United States conducts the most inter-country collaborative studies, followed by Canada. However, Japan exclusively conducts intra-country collaborative studies. The cooperative relationship between the countries with the top-100 highly cited publications on CKD–MBD is presented in Figure 2.

Table 3.

The distribution of the top 10 countries with the highly cited CKD–MBD articles.

Country	Number of articles
the United States	63
Japan	7
the United Kingdom	7
Germany	6
France	6
Canada	3
Sweden	1
Spain	1
Scotland	1
New Zealand	1

CKD–MBD = chronic kidney disease–mineral and bone disorder.

Figure 2.

Network map of cooperative relations between the countries with the top 100 highly cited publications on CKD–MBD. CKD–MBD = chronic kidney disease–mineral and bone disorder.

3.4. Distribution characteristics of research institutions

The top 100 highly cited articles on CKD–MBD originated from different universities or laboratories, and there were multiple cooperative relationships between them (Fig. 3). The top 3 institutions were the University of Washington (n = 37), Harvard University (n = 23), and University of California Los Angeles (n = 20). The organization with the most number of first-author articles was the University of Washington (n = 10), followed by Indiana University (n = 5), and Harvard University (n = 4). The distribution of the top 10 institutions with the top 100 highly cited publications on CKD–MBD is shown in Table 4.

Figure 3.

Network of institutional cooperation for the publication of the top 100 highly cited articles on CKD–MBD (n > 3). CKD–MBD = chronic kidney disease–mineral and bone disorder.

Table 4.

The list of top 10 institutions with the top 100 highly cited publications on CKD–MBD

Institution	Number of all articles	Number of first-author articles
Washington Univ	37	10
Harvard Univ	23	4
Calif Los Angeles Univ	20	3
Vet Adm Med Ctr	12	2
Calif San Francisco Univ	8	2
Indiana Univ	8	5
Amgen Inc	8	1
Michigan Univ	7	1
Colorado Univ	7	0
Massachusetts Gen Hosp	7	0

CKD–MBD = chronic kidney disease–mineral and bone disorder.

3.5. Distribution of authors

We identified 563 authors who contributed to the 100 top-cited articles on CKD–MBD. The top 10 authors with the most number of publications are shown in Table 5. Block GA from the United States contributed 9 articles, with an average of 836 citations. Additionally, he also published the most number of articles as a first-author, with an average of 943 citations per article, followed by Moe SM from the United States, with 4 first-author articles, with an average of 549 citations per article. A total of 7 articles were co-published by Moe SM and other authors, with an average of 556 citations per article. We found that 9 of the top 10 authors were from the United States and only 1 author was from France. The cooperative relationship between the authors is shown in Figure 4.

Table 5.

List of the top 10 authors with the most number of articles as the first-author.

Author	Number of first-author articles	Total citations	Average citations	Total number of all articles	Total citations	Average citations	Country
Block, GA	7	6602	943	9	7524	836	USA
Moe, SM	4	2198	549	7	3897	556	USA
Chertow, GM	2	1708	854	7	5441	777	USA
Teng, M	2	1417	708	2	1417	708	USA
HODSMAN, AB	2	507	253	2	507	253	USA
QUARLES, LD	2	535	267	2	535	267	USA
SHERRARD, DJ	1	609	609	8	2948	368	USA
Wolf, M	1	617	617	7	4376	625	USA
Raggi, P	1	881	881	5	3760	752	USA
London, GM	1	431	431	4	724	181	France

Figure 4.

Network of author cooperative relationship in CKD–MBD publications. CKD–MBD = chronic kidney disease–mineral and bone disorder.

3.6. Research types, keywords, and key points

The types of articles primarily included clinical research articles (n = 73), reviews (n = 15), guidelines (n = 4), basic research articles (n = 6), and meta-analysis (n = 2). Clinical studies mainly focused on hemodialysis patients; however, there were a few studies on early CKD and peritoneal dialysis patients. Among the 100 articles, nearly half (n = 54) had no keywords, and according to the analysis of the remaining articles, the most frequent keywords were renal osteodystrophy and dialysis, followed by vascular calcification, calcium, phosphate, and parathyroid hormone (Fig. 5). Further review of the abstract and the full text of these 100 articles revealed that CKD-related bone diseases, including bone turnover patterns in different states, fractures, noninvasive diagnosis, and the effect of drugs on bone diseases, were the topics of interest in the CKD–MBD research. Other research directions included secondary hyperparathyroidism, vascular calcification, risk of cardiovascular death, molecular mechanism studies (especially FGF-23), and epidemiological investigation, etc. Additionally, we have identified another research trend. Before 2000, the majority of research was focused on renal osteodystrophy. However, clinical studies published in the year 2000 regarding coronary artery calcification in hemodialysis patients have gained widespread attention. Subsequent research has shifted its emphasis to cardiovascular risks in CKD patients.In 2005, the definition of renal osteodystrophy was updated, introducing a more comprehensive concept known as CKD–MBD. In comparison to previous research, subsequent studies have since embarked on comprehensive management and mechanistic research in CKD patients.

Figure 5.

Network of keywords in the top-100 highly cited articles on CKD–MBD (n > 3). CKD–MBD = chronic kidney disease–mineral and bone disorder.

4. Discussion

In this study, we conducted a bibliometric analysis of the top 100 highly cited articles on CKD–MBD published during 1950 to 2022. We found that Kidney International, Journal of the American Society of Nephrology, and New England Journal of Medicine are the top 3 journals to publish the largest number of highly cited articles on CKD–MBD. Furthermore, we found that Block GA authored the most articles on CKD–MBD, with 7524 citations and an average of 836 citations. The most frequently cited article was published in the Journal of the American Society of Nephrology in 2004 and pertained to the relationship between mineral metabolism disorders and mortality and morbidity in hemodialysis patients.^[11] This study showed that hyperphosphatemia, hypercalcemia, and moderate to severe secondary hyperparathyroidism are associated with all-cause mortality and that hyperphosphatemia and secondary hyperparathyroidism were also associated with the incidence of cardiovascular disease (CVD) and fracture.^[11]

The United States is the largest contributor to CKD–MBD research, with the largest number of research institutions, the largest number of articles, and the most number of citations. Japan, which ranks second in terms of article contributions, lags far behind the United States in the number of articles, while developing countries are not even on the list. In addition to the distinct advantages of the United States, such a large gap may be due to the restriction of the article language as English and that most of the top journals are from the United States. In addition, the academic gap between developed and developing countries is also caused by several factors, such as the lack of funding, lack of research capacity, language barriers, and biases of publishers and editors. The social and economic burden of CKD on developing countries continues to grow.^[12,13] The incidence of CKD in China is as high as 10.8%,^[14] and the standard rate of blood phosphorus in dialysis patients in China is far lower than that in developed countries. Therefore, we hope that developing and developed countries actively carry out academic cooperation to promote more high-quality research on CKD–MBD.

In this study, we observed that the most number of articles were published between 1999 to 2012, while fewer articles were included in the top 100 from the past 5 years due to the relatively low frequency of citations. Additionally, we found that the research hotspots changed with time. Before 2000, CKD–MBD research was primarily focused on bone diseases, including the pattern of bone turnover under different conditions, the risk of fracture in dialysis patients, the exploration of noninvasive diagnosis methods, the therapeutic effect of drugs on renal osteopathy, etc.

Although a review on vascular calcification in uremia was published in the United States in 1969, a study on coronary artery calcification in dialysis patients published in the New England Journal of Medicine in 2000 set off an upsurge in the study of cardiovascular calcification and ranks first with a frequency of 2152 citations. The study assessed coronary artery calcification in 39 patients (aged < 30 years) on dialysis with end-stage renal disease by computed tomography. It was found that patients with calcification were relatively older, spent longer time on dialysis, and had higher levels of serum calcium and phosphorus, thus indicating that young patients undergoing regular dialysis may suffer from clinically asymptomatic but possibly severe coronary artery disease that is not commensurate with their age.^[15] Many subsequent studies have focused on the risk of CVDs in patients with end-stage kidney disease, suggesting that the existence and degree of vascular calcification is a strong predictor of cardiovascular and all-cause mortality in patients with CKD, especially in patients with end-stage kidney disease.^[16–19] Among these studies, FGF-23 is the most frequently mentioned factor in the research on the CKD–MBD mechanism.

With increasing evidence that mineral and bone metabolic disorders are associated with increased risk of cardiovascular calcification, morbidity, and mortality, Kidney Disease Improving Global Outcomes organization first proposed a new definition of CKD–MBD in 2005 and redefined, evaluated, and classified “renal osteodystrophy.”^[20] In 2009, Kidney Disease Improving Global Outcomes issued the first edition of the CKD–MBD guidelines,^[21] and the latest version of the guidelines^[22] published in 2017 is also included in the top 100 articles selected in this study, indicating that it is widely recognized and accepted. However, the clinical practice in different countries is based on the population characteristics of those countries, such as Japan^[23] and China,^[24] which have their own CKD–MBD guidelines for different PTH target values, different PTH detection methods, etc.

This study also found that 70% of the top 100 articles were clinical studies, primarily focusing on hemodialysis patients, while clinical studies on early CKD patients and peritoneal dialysis patients were limited. Additionally, a few studies focused on the epidemiology, mechanism, and drug intervention strategies. Uremic toxins may cause CVDs in patients with CKD,^[25] but there is only 1 study in the top 100 articles that explores the direct correlation between serum indophenol sulfate and aortic calcification in CKD patients as a predictor of high cardiovascular mortality.^[26] Therefore, there are limited high-quality articles on the effects of uremic toxins on CKD–MBD.

5. Conclusions

In conclusion, this bibliometric analysis provides valuable insights into the highly cited articles on CKD–MBD. The findings shed light on the key research areas, publication trends, and contributors in the field. The analysis serves as a foundation for further research and collaboration in the study of CKD–MBD.

Strengths and limitations

(1) The study provides a more macroscopic understanding of the trends and focus of CKD–MBD research.

(2) There may be some selection bias in the research content; the earlier the publication date, the more the citations.

(3) The number of citations of an article, does not signify the most meaningful research or landmark research.

Author contributions

Conceptualization: Ting Kang.

Data curation: Dongmei Zhang, Dan Tang.

Visualization: Haixia Mao.

Writing – original draft: Ting Kang, Haixia Mao.

Writing – review & editing: Santao Ou.