Citation classics: ranking of the top 100 most cited articles in nephrology.

BACKGROUND: The number of citations of a scientific article is considered a weight of that work in the field of interest. Bibliometric analysis of the most cited articles conducted in some medical disciplines has identified the most relevant scientific contributions that pushed forward knowledge and clinical practice of that discipline.
METHODS: We conducted a bibliometric analysis of the most cited articles in nephrology, by extracting relevant words that identify issues of nephrological interest and querying the Google Scholar database. A rank with the 100 most cited articles was obtained, based on the absolute number of citations. Articles were clustered in different areas of interest.
RESULTS: Word(s) extracted from the Google Scholar database that restituted at least 100 000 hits were 50. The extracted 100 most cited articles collected cumulatively >285 000 citations. Nine subcategories were identified and the most populated one was 'Renal function assessment' (16 articles and 68 000 citations, 24% of total). The other relevant group of articles (16, with 46 652 citations) belonged to the category 'Randomized trials and pharmacology'. Almost 70% of the articles in the top 100 were published by eight major international journals. The top 100 list included 62 articles generated from USA scientists and the author with higher number of articles was A.S. Levey (10).
CONCLUSIONS: The top 100 list of articles in nephrology helps delineate the major interests of this medical discipline. Assessment of renal functions, probably for its multidisciplinary relevance, is the heaviest topic, based on number of citations.

INTRODUCTION

Nephrology is a medical discipline that gained autonomy in the mid-1950s, when the eminent clinician Jean Hamburger in Paris proposed this term to define the branch of internal medicine that would study kidney diseases [1, 2]. In the preceding decades, mainly experimental studies and clinical observations had enriched the knowledge on specific physiological aspects of renal function [3], while at the time of Hamburger, a spectrum of glomerulonephritides and renal diseases with a defined pathogenesis were identified [4, 5]. Also, the introduction of the Kolff artificial kidney occurred a decade before, and laid the foundations for this novel branch of medicine. In recognition of the rapidly growing new discipline, prominent specialists worldwide founded the International Society of Nephrology in 1960 [1]. The development of areas of interest in nephrology and its specific clinical and research topics can be analysed from the research contributions summing up about 795 000 items in the PubMed database under the heading ‘kidney’. We were interested in assessing the most relevant scientific articles that influenced the nephrological practice and shaped the discipline, by focusing on specific topics of the research in kidney diseases.

In recent years, efforts have been made to define relevant articles in some medical specialty areas (anaesthesiology, dermatology, general surgery, urology, chronobiology and neurosciences) by identifying the 100 most cited articles [6-11], and some journals have analysed the ‘classic’ articles published by impact on readership [12, 13]. No such investigation has been conducted in nephrology. We therefore employed a bibliometric analysis aimed at identifying the top 100 most cited scientific articles on specific nephrological issues.

MATERIALS AND METHODS

The Google Scholar tool, which restitutes for each article the number of citations, was used to search for the most cited articles of nephrological interest. Compared with other instruments (such as Scopus, and Web of Science by Thomson Reuters), Google Scholar is able to capture a broader spectrum of citing sources, including books, conference publications, other citations, etc. The search was conducted by introducing in the field ‘with at least one of the words’, general terms that could capture all relevant articles dealing with kidney function, pathology, renal pathophysiology, renal diseases, principal drugs used for kidney diseases, common comorbidities of kidney diseases, principal metabolites handled by the kidney, dialysis and transplantation. We selected all index word(s) that restituted at least 100 000 items in Google Scholar. Also, a combination of terms was used to probe the search engine and to make sure that all relevant publications could be identified.

Selected articles were original articles, meta-analyses, consensus articles and guidelines. Narrative reviews were not considered. The top most cited 100 articles were identified. A preliminary analysis of number of citations allowed us to set a cut-off of 1000 citations, so all articles that received a higher number of citations were extracted and listed to generate a rank based on absolute number of citations received by each article as of 7 February 2018. Concerning the country origin of the articles, individual countries have been listed if the authors derived from up to three countries, otherwise, the origin was deemed as global, if the countries of author origin were four or more.

Since most recent articles have a lifespan shorter than older articles, the number of citations per year was also calculated. Articles were categorized according to the topic in one of nine subfields.

RESULTS

In Table 1, all terms used for searching the Google Scholar database are listed. A total of 50 terms were identified that produced more than 100 000 hits in Google Scholar search. The database was then probed with each individual term listed and all publications with at least 1000 citations were extracted. Top most cited 100 articles collected cumulatively >285 000 citations. The nine subcategories of the top 100 articles are indicated in Table 2. The most populated category was ‘Renal function assessment’, which included 16 articles that collectively accumulated nearly 68 000 citations (almost 24% of all citations). The second most abundant group of articles belonged to the subcategory ‘Randomized trials and pharmacology’ (16 articles, 46 652 citations, 16.4% of all citations). Subcategories ‘Dialysis/Transplantation’, ‘Epidemiological studies’, ‘Pathophysiology’ and ‘Acute Kidney Injury’ individually accounted for about 10% of all citations and each category contained between 9 and 14 articles (Table 2).

Table 1.

Terms used to extract relevant articles with highest citations, and number of items indexed in the Google Scholar search engine for each term

Number	Term	Number of items (approx.)	Number	Term	Number of items (approx.)
1	Clearance	3 450 000	26	Nephrology	838 000
2	Urine	3 190 000	27	ACE inhibitor	753 000
3	Urea	3 040 000	28	Haemodialysis	762 000
4	Kidney	3 000 000	29	Nephropathy	717 000
5	Renal	2 900 000	30	Renin	698 000
6	Urinary	2 770 000	31	Nephritis	467 000
7	Hypertension	2 710 000	32	Tubular secretion	458 000
8	Low-protein diet	2 690 000	33	Metabolic acidosis	401 000
9	CKD	2 670 000	34	Kidney stones	393 000
10	Chronic renal failure	2 390 000	35	Glomerulonephritis	389 000
11	End stage renal disease	2 390 000	36	Proteinuria	389 000
12	Renal insufficiency	2 060 000	37	Diuretic	373 000
13	Acid base balance	2 000 000	38	Nephron	355 000
14	Dialysis	1 990 000	39	Tubular necrosis	340 000
15	End stage kidney disease	1 800 000	40	Renal cysts	307 000
16	Kidney transplant	1 760 000	41	Eclampsia	278 000
17	Renal failure	1 740 000	42	Nephrotic	259 000
18	Renal transplant	1 740 000	43	Renal glomerulus	251 000
19	AKI	1 730 000	44	Uraemic	244 000
20	Renal tubular	1 640 000	45	Haematuria	199 000
21	Kidney transplantation	1 640 000	46	Pyelonephritis	184 000
22	Renal transplantation	1 600 000	47	Diuresis	183 000
23	Creatinine	1 330 000	48	Furosemide	176 000
24	Angiotensin	1 320 000	49	Uraemia	160 000
25	Glomerular	948 000	50	Albuminuria	123 000

Table 2.

Subcategories of the top 100 most cited articles

Number	Article group	Description	Abbreviation	Number of articles	Article number	Number of citations (total)	% total
1	Renal function assessment	Studies on modalities of renal function assessment and laboratory methods	RF	16	1, 2, 4, 17, 19, 26, 27, 31–33, 39, 52, 56, 78, 81, 95	67 938	23.8
2	Randomized trials/pharmacology	Randomized clinical trials and pharmacology of relevant kidney diseases	RT	16	6–8, 14, 35, 36, 44, 46, 51, 57, 60, 72, 73, 87, 98, 100	46 652	16.4
3	Dialysis transplantation	Studies involving uraemic patients treated by dialysis or transplantation	DT	14	24, 28, 34, 41, 45, 53, 58, 59, 62, 70, 82, 83, 88, 90	29 424	10.3
4	Epidemiological studies	Studies on prevalence of renal diseases, outcomes, guidelines	ES	9	12, 13, 15, 16, 21, 30, 37, 54, 55	27 791	9.7
5	Pathophysiology	Mechanisms of kidney diseases	PP	12	18, 23, 25, 29, 43, 48, 50, 63, 68, 71, 86, 93	27 613	9.7
6	AKI	Pathogenic factors, biomarkers, classification and interventions in AKI	A	10	9, 10, 22, 38, 66, 67, 75–77, 89	27 115	9.5
7	Kidney structure and function	Studies on structural, functional aspect, development of kidney and genetics	SF	7	5, 11, 69, 74, 84, 92, 94	20 201	7.1
8	CKD/pathology	Pathogenic and predictive factors of CKD evolution/pathology of renal diseases	CK	6	3, 20, 42, 65, 85, 99	19 469	6.9
9	Comorbidities of renal disease	Studies on mechanisms of diabetic nephropathy and hypertension	DH	10	40, 47, 49, 61, 64, 79, 80, 91, 96, 97	18 891	6.6
Total						285 094	100.0

The top 10 most cited articles include 3 articles (rank number 1, 2 and 4) on modality of estimating renal function, 3 more articles (rank number 6, 7 and 8) describing results from randomized trials on the utility of Renin-Angiotensin-Aldosterone System (RAAS) blockade in diabetic nephropathy and 2 articles that dealt with definition and classification of acute kidney injury (AKI) (rank number 9 and 10); the last two were: one article on the predictive value of chronic kidney disease (CKD) on mortality and cardiovascular disease (rank number 3) and, finally, a > 50-year-old article by Graham and Karnovsky on a new method of ultrastructural cytochemistry demonstrating the reabsorption of peroxidase by the proximal tubular cells, after glomerular filtration (rank number 5) (Table 3). Among the top 10 cited articles the most rapidly growing in citations per year is the article of Levey and the Chronic Kidney Disease - Epidemiology Collaboration (CKD-EPI) consortium on glomerular filtration rate (GFR) estimation that accumulated >1087 citations per year (Table 3).

Table 3.

Top 100 most cited articles in nephrology, ranked by number of citations

Number	Year	Authors	Title	Journal	Country	Cit. n	Cit. norm	Cat.
1	1976	Cockcroft DW, Gault MH.	Prediction of creatinine clearance from serum creatinine.	Nephron 1976; 16: 31–41. PubMed PMID: 1244564.	Canada	14 499	353.6	RF
2	1999	Levey AS, Bosch JP, Lewis JB et al.	A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group.	Ann Intern Med 1999; 130: 461–470. PubMed PMID: 10075613.	USA	13 186	732.5	RF
3	2004	Go AS, Chertow GM, Fan D et al.	Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization.	N Engl J Med 2004; 351: 1296–1305. PubMed PMID: 15385656.	USA	8807	677.5	CK
4	2009	Levey AS, Stevens LA, Schmid CH et al.	A new equation to estimate glomerular filtration rate.	Ann Intern Med 2009; 150: 604–612. PubMed PMID: 19414839.	USA	8699	1087.4	RF
5	1966	Graham RC Jr, Karnovsky MJ.	The early stages of absorption of injected horseradish peroxidase in the proximal tubules of mouse kidney: ultrastructural cytochemistry by a new technique.	J Histochem Cytochem 1966; 14: 291–302. PubMed PMID: 5962951.	USA	7414	145.4	SF
6	2001	Brenner BM, Cooper ME, de Zeeuw D et al.	Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.	N Engl J Med 2001; 345: 861–869. PubMed PMID: 11565518.	Global	7219	451.2	RT
7	2001	Lewis EJ, Hunsicker LG, Clarke WR et al.	Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes.	N Engl J Med 2001; 345: 851–860.	Global	6085	380.3	RT
8	1993	Lewis EJ, Hunsicker LG, Bain RP et al.	The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy.	N Engl J Med 1993; 329: 1456–1462. PubMed PMID: 8413456.	USA	5622	234.2	RT
9	2004	Bellomo R, Ronco C, Kellum JA et al.	Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group.	Crit Care 2004; 8: R204–R212. PubMed PMID: 15312219.	Global	5523	424.8	A
10	2007	Mehta RL, Kellum JA, Shah SV et al.	Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.	Crit Care 2007; 11: R31. PubMed PMID: 17331245.	Global	5217	521.7	A
11	1990	Rigat B, Hubert C, Alhenc-Gelas F et al.	An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels.	J Clin Invest 1990; 86: 1343–1346. PubMed PMID: 1976655; PubMed Central PMCID: PMC296868.	France	4225	156.5	SF
12	2007	Coresh J, Selvin E, Stevens LA et al.	Prevalence of chronic kidney disease in the United States.	JAMA 2007; 298: 2038–2047. PubMed PMID: 17986697.	USA	4174	417.4	ES
13	2003	Levey AS, Coresh J, Balk E et al.	National Kidney Foundation practice guidelines for chronic kidney disease: evaluation, classification, and stratification.	Ann Intern Med 2003; 139: 137–147. PubMed PMID: 12859163.	USA/Canada	3980	284.3	ES
14	2001	Parving HH, Lehnert H, Bröchner-Mortensen J et al.	The effect of irbesartan on the development of diabetic nephropathy in patients with type 2 diabetes.	N Engl J Med 2001; 345: 870–878. PubMed PMID: 11565519.	Global	3712	232.0	RT
15	1999	Wolfe RA, Ashby VB, Milford EL et al.	Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant.	N Engl J Med 1999; 341: 1725–1730. PubMed PMID: 10580071.	USA	3698	205.4	ES
16	1995	Burt VL, Whelton P, Roccella EJ et al.	Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988-1991.	Hypertension 1995; 25: 305–313. PubMed PMID: 7875754.	USA	3538	160.8	ES
17	1962	Chaney AL, Marbach EP.	Modified reagents for determination of urea and ammonia.	Clin Chem 1962; 8: 130–132. PubMed PMID: 13878063.	USA	3431	62.4	RF
18	1965	Black JA, Challacombe DN, Ockenden BG.	Nephrotic syndrome associated with bacteraemia after shunt operations for hydrocephalus.	Lancet 1965; 2: 921–924. PubMed PMID: 4165274.	UK	3368	64.8	PP
19	2006	Levey AS, Coresh J, Greene T et al.	Using standardized serum creatinine values in the modification of diet in renal disease study equation for estimating glomerular filtration rate.	Ann Intern Med 2006; 145: 247–254. PubMed PMID: 16908915.	USA	3242	294.7	RF
20	1999	Racusen LC, Solez K, Colvin RB et al.	The Banff 97 working classification of renal allograft pathology.	Kidney Int 1999; 55: 713–723. PubMed PMID: 9987096.	Global	3161	175.6	CK
21	2003	Coresh J, Astor BC, Greene T et al.	Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.	Am J Kidney Dis 2003; 41: 1–12. PubMed PMID: 12500213.	USA	3151	225.1	ES
22	2005	Uchino S, Kellum JA, Bellomo R et al.	Acute renal failure in critically ill patients: a multinational, multicenter study.	JAMA 2005; 294: 813–818. PubMed PMID: 16106006.	Global	3113	259.4	A
23	2003	Maynard SE, Min JY, Merchan J et al.	Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia	J Clin Invest 2003; 111: 649–658. PubMed PMID: 12618519.	USA	3100	221.4	PP
24	2000	Goodman WG, Goldin J, Kuizon BD et al.	Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis.	N Engl J Med 2000; 342: 1478–1483. PubMed PMID: 10816185.	USA	2953	173.7	DT
25	1969	Haber E, Koerner T, Page LB et al.	Application of a radioimmunoassay for angiotensin I to the physiologic measurements of plasma renin activity in normal human subjects.	J Clin Endocrinol Metab 1969; 29: 1349–1355. PubMed PMID: 4311082.	USA	2832	59.0	PP
26	2009	Matsuo S, Imai E, Horio M et al.	Revised equations for estimated GFR from serum creatinine in Japan.	Am J Kidney Dis 2009; 53: 982–992. PubMed PMID: 19339088.	Japan	2793	349.1	RF
27	2000	Levey AS, Greene T, Kusek JW et al.	A simplified equation to predict glomerular filtration rate from serum creatinine.	J Am Soc Nephrol 2000; 11: 155A. abstract.	USA	2681	157.7	RF
28	1998	Block GA, Hulbert-Shearon TE, Levin NW et al.	Association of serum phosphorus and calcium x phosphate product with mortality risk in chronic hemodialysis patients: a national study.	Am J Kidney Dis 1998; 31: 607–617. PubMed PMID: 9531176.	USA	2632	138.5	DT
29	1934	Goldblatt H, Lynch J, Hanzal RF et al.	Studies on experimental hypertension: I. The production of persistent elevation of systolic blood pressure by means of renal ischemia.	J Exp Med 1934; 59: 347–379. PubMed PMID: 19870251; PubMed Central PMCID: PMC2132360.	USA	2632	31.7	PP
30	2005	Levey AS, Eckardt KU, Tsukamoto Y et al.	Definition and classification of chronic kidney disease: a position statement from Kidney Disease: Improving Global Outcomes (KDIGO).	Kidney Int 2005; 67: 2089–2100. PubMed PMID: 15882252.	Global	2625	218.7	ES
31	2007	Choi HS, Liu W, Misra P et al.	Renal clearance of quantum dots.	Nat Biotechnol 2007; 25: 1165–1170. PubMed PMID: 17891134.	USA	2607	260.7	RF
32	1986	Pace CN.	Determination and analysis of urea and guanidine hydrochloride denaturation curves.	Methods Enzymol 1986; 131: 266–280 PubMed PMID: 3773761.	USA	2589	83.5	RF
33	1945	Bonsnes RW, Taussky HH.	On the colorimetric determination of creatinine by the Jaffé reaction.	J Biol Chem 1945; 158: 581–591.	USA	2583	35.9	RF
34	2004	Block GA, Klassen PS, Lazarus JM et al.	Mineral metabolism, mortality and morbidity in maintenance hemodialysis.	J Am Soc Nephrol 2004; 15: 2208–2218. PubMed PMID: 15284307.	USA	2512	193.2	DT
35	2006	Singh AK, Szczech L, Tang KL et al.	Correction of anemia with epoetin alfa in chronic kidney disease.	N Engl J Med 2006; 355: 2085–2098. PubMed PMID: 17108343.	USA	2473	224.8	RT
36	1987	Eschbach JW, Egrie JC, Downing MR et al.	Correction of the anemia of end-stage renal disease with recombinant human erythropoietin. Results of a combined phase I and II clinical trial.	N Engl J Med 1987; 316: 73–78. PubMed PMID: 3537801.	USA	2426	80.9	RT
37	2001	Gerstein HC, Mann JF, Yi Q et al.	Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and Nondiabetic individuals.	JAMA 2001; 286: 421–426. PubMed PMID: 11466120.	USA	2392	149.5	ES
38	2005	Chertow GM, Burdick E, Honour M et al.	Acute kidney injury, mortality, length of stay, and costs in hospitalized patients.	J Am Soc Nephrol 2005; 16: 3365–3370. PubMed PMID: 16177006.	USA	2391	199.2	A
39	1960	Fawcett JK, Scott J.	A rapid and precise method for the determination of urea.	J Clin Pathol 1960; 13: 156–159. PubMed PMID: 13821779.	UK	2340	41.0	RF
40	1984	Mogensen CE.	Microalbuminuria predicts clinical proteinuria and early mortality in maturity-onset diabetes	N Engl J Med 1984; 310: 356–360. PubMed PMID: 6690964.	Denmark	2333	70.7	DH
41	1999	Blacher J, Guerin AP, Pannier B et al.	Impact of aortic stiffness on survival in end-stage renal disease.	Circulation 1999; 99: 2434–2439. PubMed PMID: 10318666.	France	2329	129.4	DT
42	2004	Weening JJ, D’Agati VD, Schwartz MM et al.	The classification of glomerulonephritis in systemic lupus erythematosus revisited.	Kidney Int 2004; 65: 521–530. PubMed PMID: 14717922.	Global	2324	178.8	CK
43	1992	Leone A, Moncada S, Vallance P et al.	Accumulation of an endogenous inhibitor of nitric oxide synthesis in chronic renal failure.	Lancet 1992; 339: 572–575. PubMed PMID: 1347093.	UK	2312	92.5	PP
44	1994	Klahr S, Levey AS, Beck GJ et al.	The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group.	N Engl J Med 1994; 330: 877–884. PubMed PMID: 8114857.	USA	2245	97.6	RT
45	1990	Lowrie EG, Lew NL.	Death risk in hemodialysis patients: the predictive value of commonly measured variables and an evaluation of death rate differences between facilities.	Am J Kidney Dis 1990; 15: 458–482. PubMed PMID: 2333868.	USA	2231	82.6	DT
46	2005	Wanner C, Krane V, März W et al.	Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis.	N Engl J Med 2005; 353: 238–248. PubMed PMID: 16034009.	Germany	2229	185.7	RT
47	2009	Krum H, Schlaich M, Whitbourn R et al.	Catheter-based renal sympathetic denervation for resistant hypertension: a multicentre safety and proof-of-principle cohort study.	Lancet 2009; 373: 1275–1281. PubMed PMID: 19332353.	Australia	2205	275.6	DH
48	2005	Mishra J, Dent C, Tarabishi R et al.	Neutrophil gelatinase-associated lipocalin (NGAL) as a biomarker for acute renal injury after cardiac surgery.	Lancet 2005; 365: 1231–1238. PubMed PMID: 15811456.	USA	2185	182.1	PP
49	2010	Simplicity HTN-2 Investigators, Esler MD, Krum H et al.	Renal sympathetic denervation in patients with treatment-resistant hypertension (The Simplicity HTN-2 Trial): a randomized controlled trial.	Lancet 2010; 376: 1903–1909. PubMed PMID: 21093036.	Global	2176	310.8	DH
50	2001	Park CH, Valore EV, Waring AJ et al.	Hepcidin, a urinary antimicrobial peptide synthesized in the liver.	J Biol Chem 2001; 276: 7806–7810. PubMed PMID: 11113131.	USA	2166	135.3	PP
51	1977	Ondetti MA, Rubin B, Cushman DW.	Design of specific inhibitors of angiotensin-converting enzyme: new class of orally active antihypertensive agents.	Science 1977; 196: 441–444. PubMed PMID: 191908.	USA	2155	53.9	RT
52	1976	Schwartz GJ, Haycock GB, Edelmann CM Jr et al.	A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine.	Pediatrics 1976; 58: 259–263. PubMed PMID: 951142.	USA	2152	52.5	RF
53	1974	Lindner A, Charra B, Sherrard DJ et al.	Accelerated atherosclerosis in prolonged maintenance hemodialysis.	N Engl J Med 1974; 290: 697–701. PubMed PMID: 4813742.	USA	2139	49.7	DT
54	2008	Collins AJ, Foley R, Herzog C et al.	Excerpts from the United States Renal Data System 2007 annual data report.	Am J Kidney Dis 2008; 51 (1 Suppl 1): S1–S320 PubMed PMID: 18086389.	USA	2125	236.1	ES
55	2010	Chronic Kidney Disease Prognosis Consortium.	Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis	Lancet 2010; 375: 2073–2081 PubMed PMID: 20483451; PubMed Central PMCID: PMC3993088.	Global	2108	301.1	ES
56	1945	Smith HW, Finkelstein N, Aliminosa L et al.	The renal clearances of substituted hippuric acid derivatives and other aromatic acids in dog and man.	J Clin Invest 1945; 24: 388–404. PubMed PMID: 16695228; PubMed Central PMCID: PMC435470.	USA	2059	28.6	RF
57	1998	Besarab A, Bolton WK, Browne JK et al.	The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin.	N Engl J Med 1998; 339: 584–590. PubMed PMID: 9718377.	USA/ Canada/ UK	2058	108.3	RT
58	1976	Alfrey AC, LeGendre GR, Kaehny WD.	The dialysis encephalopathy syndrome. Possible aluminum intoxication.	N Engl J Med 1976; 294: 184–188. PubMed PMID: 1244532.	USA	2045	49.9	DT
59	2000	Hariharan S, Johnson CP, Bresnahan BA et al.	Improved graft survival after renal transplantation in the United States, 1988 to 1996.	N Engl J Med 2000; 342: 605–612. PubMed PMID: 10699159.	USA	2018	118.7	DT
60	2006	Drüeke TB, Locatelli F, Clyne N et al.	Normalization of hemoglobin level in patients with chronic kidney disease and anemia.	N Engl J Med 2006; 355: 2071–2084. PubMed PMID: 17108342.	Global	2011	182.8	RT
61	1982	Viberti GC, Hill RD, Jarrett RJ et al.	Microalbuminuria as a predictor of clinical nephropathy in insulin-dependent diabetes mellitus.	Lancet 1982; 1: 1430–1432. PubMed PMID: 6123720.	UK	2005	57.3	DH
62	1966	Brescia MJ, Cimino JE, Appel K et al.	Chronic hemodialysis using venipuncture and a surgically created arteriovenous fistula.	N Engl J Med 1966; 275: 1089–1092. PubMed PMID: 5923023.	USA	2004	39.3	DT
63	1981	Hostetter TH, Olson JL, Rennke HG et al.	Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation.	Am J Physiol 1981; 241: F85–F93. PubMed PMID: 7246778.	USA	1999	55.5	PP
64	1984	Mogensen CE, Christensen CK.	Predicting diabetic nephropathy in insulin- dependent patients.	N Engl J Med 1984; 311: 89–93. PubMed PMID: 6738599.	Denmark	1959	59.4	DH
65	1999	Stenvinkel P, Heimbürger O, Paultre F et al.	Strong association between malnutrition, inflammation, and atherosclerosis in chronic renal failure.	Kidney Int 1999; 55: 1899–1911. PubMed PMID: 10231453.	Sweden/ USA	1953	108.5	CK
66	2002	Nash K, Hafeez A, Hou S.	Hospital-acquired renal insufficiency.	Am J Kidney Dis 2002; 39: 930–936. PubMed PMID: 11979336.	USA	1926	128.4	A
67	2000	Ronco C, Bellomo R, Homel P et al.	Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial.	Lancet 2000; 356: 26–30. PubMed PMID: 10892761.	Italy/ Australia	1912	112.5	A
68	2004	Anavekar NS, McMurray JJ, Velazquez EJ et al.	Relation between renal dysfunction and cardiovascular outcomes after myocardial infarction.	N Engl J Med 2004; 351: 1285–1295. PubMed PMID: 15385655.	USA	1881	144.7	PP
69	1993	Kreidberg JA, Sariola H, Loring JM et al.	WT-1 is required for early kidney development.	Cell 1993; 74: 679–691. PubMed PMID: 8395349.	USA	1877	74.2	SF
70	2003	Nankivell BJ, Borrows RJ, Fung CL et al.	The natural history of chronic allograft nephropathy.	N Engl J Med 2003; 349: 2326–2333. PubMed PMID: 14668458.	Australia	1873	133.8	DT
71	2002	Li YC, Kong J, Wei M et al.	1,25-Dihydroxyvitamin D(3) is a negative endocrine regulator of the renin-angiotensin system.	J Clin Invest 2002; 110: 229–238. PubMed PMID: 12122115; PubMed Central PMCID: PMC151055.	USA	1847	123.1	PP
72	2000	Tepel M, van der Giet M, Schwarzfeld C et al.	Prevention of radiographic-contrast-agent- induced reductions in renal function by acetylcysteine.	N Engl J Med 2000; 343: 180–184. PubMed PMID: 10900277.	Germany	1842	108.3	RT
73	1996	Maschio G, Alberti D, Janin G et al.	Effect of the angiotensin-converting-enzyme inhibitor benazepril on the progression of chronic renal insufficiency. The Angiotensin-Converting-Enzyme Inhibition in Progressive Renal Insufficiency Study Group.	N Engl J Med 1996; 334: 939–945. PubMed PMID: 8596594.	Italy	1817	86.5	RT
74	1998	Kestilä M, Lenkkeri U, Männikkö M et al.	Positionally cloned gene for a novel glomerular protein—nephrin is mutated in congenital nephrotic syndrome.	Mol Cell 1998; 1: 575–582. PubMed PMID: 9660941.	Finland	1814	95.5	SF
75	2002	Rihal CS, Textor SC, Grill DE et al.	Incidence and prognostic importance of acute renal failure after percutaneous coronary intervention.	Circulation 2002; 105: 2259–2264. PubMed PMID: 12010907.	USA	1808	120.5	A
76	2004	Mehran R, Aymong ED, Nikolsky E et al.	A simple risk score for prediction of contrast-induced nephropathy after percutaneous coronary intervention: development and initial validation.	J Am Coll Cardiol 2004; 44: 1393–1399. PubMed PMID: 15464318.	USA	1803	138.7	A
77	1997	McCullough PA, Wolyn R, Rocher LL et al.	Acute renal failure after coronary intervention: incidence, risk factors, and relationship to mortality	Am J Med 1997; 103: 368–375 PubMed PMID: 9375704.	USA	1794	89.7	A
78	1988	Intersalt cooperative research group.	Intersalt: an international study on electrolyte excretion and blood pressure. Results from 24 hour urinary sodium and potassium excretion.	BMJ 1988; 297: 319–328. PubMed PMID: 3416162; PubMed Central PMCID: PMC1834069.	Global	1772	61.1	RF
79	1996	Klag MJ, Whelton PK, Randall BL et al.	Blood pressure and end-stage renal disease in men.	N Engl J Med 1996; 334: 13–18. PubMed PMID: 9375704.	USA	1753	83.5	DH
80	2002	Wright JT Jr, Bakris G, Greene T et al.	Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial.	JAMA 2002; 288: 2421–2431. PubMed PMID: 12435255.	USA	1752	116.8	DH
81	2002	Dharnidharka VR, Kwon C, Stevens G.	Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis.	Am J Kidney Dis 2002; 40: 221–226. PubMed PMID: 12148093.	USA	1747	116.5	RF
82	2002	Eknoyan G, Beck GJ, Cheung AK et al.	Effect of dialysis dose and membrane flux in maintenance hemodialysis	N Engl J Med 2002; 347: 2010–2019. PubMed PMID: 12490682.	USA	1733	115.5	DT
83	1999	Zimmermann J, Herrlinger S, Pruy A et al.	Inflammation enhances cardiovascular risk and mortality in hemodialysis patients.	Kidney Int 1999; 55: 648–658. PubMed PMID: 9987089.	Germany	1695	94.2	DT
84	2003	Nauli SM, Alenghat FJ, Luo Y et al.	Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells.	Nat Genet 2003; 33: 129–137. PubMed PMID: 12514735.	USA	1717	122.6	SF
85	2003	Ojo AO, Held PJ, Port FK et al.	Chronic renal failure after transplantation of a nonrenal organ.	N Engl J Med 2003; 349: 931–940. PubMed PMID: 12954741.	USA	1682	120.1	CK
86	1998	Furlan M, Robles R, Galbusera M et al.	von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura and the hemolytic-uremic syndrome.	N Engl J Med 1998; 339: 1578–1584. PubMed PMID: 9828245.	Global	1712	90.1	PP
87	2011	Baigent C, Landray MJ, Reith C et al.	The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial.	Lancet 2011; 377: 2181–2192. PubMed PMID: 21663949; PubMed Central PMCID: PMC3145073.	Global	1679	279.8	RT
88	2003	London GM, Guérin AP, Marchais SJ et al.	Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality.	Nephrol Dial Transplant 2003; 18: 1731–1740. PubMed PMID: 12937218.	France	1650	117.8	DT
89	1996	Levy EM, Viscoli CM, Horwitz RI.	The effect of acute renal failure on mortality. A cohort analysis.	JAMA 1996; 275: 1489–1494. PubMed PMID: 9375704.	USA	1628	77.5	A
90	2002	Chertow GM, Burke SK, Raggi P et al.	Sevelamer attenuates the progression of coronary and aortic calcification in hemodialysis patients.	Kidney Int 2002; 62: 245–252. PubMed PMID: 12081584.	USA/ Germany/ Austria	1610	107.3	DT
91	2003	Adler AI, Stevens RJ, Manley SE et al.	Development and progression of nephropathy in type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS 64).	Kidney Int 2003; 63: 225–232. PubMed PMID: 12472787.	UK	1605	114.6	DH
92	1994	Schuchardt A, D’Agati V, Larsson-Blomberg L et al.	Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret.	Nature 1994; 367: 380–383. PubMed PMID: 9375704.	USA	1583	68.8	SF
93	2003	Mishra J, Ma Q, Prada A et al.	Identification of neutrophil gelatinase-associated lipocalin as a novel early urinary biomarker for ischemic renal injury.	J Am Soc Nephrol 2003; 14: 2534–2543. PubMed PMID: 14514731.	USA	1579	112.8	PP
94	1957	Margoshes M, Vallee BL.	A cadmium protein from equine kidney cortex.	J Am Chem Soc 1957; 79: 4813–4814.	USA	1571	26.2	SF
95	1987	Schwartz GJ, Brion LP, Spitzer A.	The use of plasma creatinine concentration for estimating glomerular filtration rate in infants, children and adolescents.	Pediatr Clin North Am 1987; 34: 571–590. PubMed PMID: 3588043.	USA	1558	51.9	RF
96	2007	Bellamy L, Casas JP, Hingorani AD et al.	Pre-eclampsia and risk of cardiovascular disease and cancer in later life: systematic review and meta-analysis.	BMJ 2007; 335: 974. PubMed PMID: 17975258; PubMed Central PMCID: PMC2072042.	UK	1552	155.2	DH
97	1993	Dyck PJ, Kratz KM, Karnes JL et al.	The prevalence by staged severity of various types of diabetic neuropathy, retinopathy, and nephropathy in a population-based cohort: the Rochester Diabetic Neuropathy Study.	Neurology 1993; 43: 817–824. PubMed PMID: 8469345.	USA	1551	64.6	DH
98	2001	Mann JF, Gerstein HC, Pogue J et al.	Renal insufficiency as a predictor of cardiovascular outcomes and the impact of ramipril: the HOPE randomized trial.	Ann Intern Med 2001; 134: 629–636 PubMed PMID: 11304102.	Germany, Canada	1548	96.7	RT
99	2004	Keith DS, Nichols GA, Gullion CM et al.	Longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization.	Arch Intern Med 2004; 164: 659–663. PubMed PMID: 15037495.	USA	1542	118.6	CK
100	2008	Mann JF, Schmieder RE, McQueen M et al.	Renal outcomes with telmisartan, ramipril, or both, in people at high vascular risk (the ONTARGET study): a multicentre, randomised, double-blind, controlled trial.	Lancet 2008; 372: 547–553. PubMed PMID: 18707986.	Global	1531	170.1	RT

A, AKI; Cat., subcategory as indicated by abbreviations in Table 2; Cit. n, total number of citations; Cit. norm, number of citations per year, since publication; CK, chronic kidney disease/pathology; DH, comorbidities of renal disease; DT, dialysis transplantation; ES, epidemiological studies; PP, pathophysiology; RF, renal function assessment; RT, randomized trials/pharmacology; SF, kidney structure and function.

The first most cited article dealing with issues relevant to the haemodialysis field is at the 15th position, by Wolfe et al., concerning the mortality risk in patients on dialysis compared with that in transplanted patients. This article collected 3698 citations (Table 3). There are 11 other articles dealing with specific issues related to chronic dialysis (at the 24th, 28th, 34th, 45th, 46th, 53rd, 58th, 62nd, 82nd, 83rd and 90th position) and these concern risk factors for mortality, atherosclerosis, mineral metabolism, aluminium intoxication, vascular access, effects of dialysis membrane type and inflammation. All the 12 articles were globally cited 27 481 times (9.6% of the total citations of the top 100 articles).

Another relevant aspect is represented by epidemiological studies on the classification and incidence of CKD in the US population (two articles by Levey and Coresh et al., respectively, at rank number 12 and 13). Other articles of epidemiological interest are found at position 21st, 30th, 37th, 54th and 55th, and collectively have been cited 20 555 times (7.2% of the global citations).

A total of four studies on anaemia correction by erythropoiesis-stimulating agents are present in the top 100 list. The four articles allocate to the 35th, 36th, 57th and 60th position. Cumulative citations of these studies were 8968 (3.1% of total citations) (Table 3).

Basic sciences or mechanism of diseases were addressed in some articles, namely at rank 11th [genetic polymorphism at the angiotensin-converting enzyme (ACE) gene, regulating plasma levels of the enzyme], 18th (nephrotic syndrome caused by shunt operation for hydrocephalus), 23rd (tyrosine kinase and endothelial dysfunction in pre-eclampsia), 43rd (nitric oxide accumulation in renal failure), 50th (urinary antimicrobial effects of hepcidin), 69th (kidney development), 74th (mutated nephrin and nephrotic syndrome), 84th (cellular function of polycystin 1 and 2), 86th [von Willebrand factor and thrombotic thrmocytopenic purpura (TTP)] and 92nd (tyrosine kinase receptor and kidney development); the number of citations for each of these articles ranged from 4225 to 1583 (Table 3).

Epidemiology, classification and management of acute renal failure and AKI has received proper attention: besides the 9th and 10th article by the AKI Network, we find articles at 22nd, 38th, 66th, 67th, 75th, 76th, 77th and 89th rank. Cumulative citations of this subcategory are 27 115 (9.5% of total) (Table 2).

Common comorbidities of CKD, such as diabetes and hypertension, relative to their potential to cause renal diseases were topics covered in 10 out of the top 100 articles (rank number 40, 47, 49, 61, 64, 79, 80, 91, 96 and 97): half of them focused on hypertension and half on predictive factors of diabetic nephropathy in patients affected by diabetes mellitus (Table 3); all 10 articles received 6.6% of total citations (Table 2).

Among the top 100 articles there were 9 ‘classic’ articles, which were published more than 50 years ago (rank number 5, 17, 18, 29, 33, 39, 56, 62 and 94), and spanned across four categories (Kidney structure and function, Renal function assessment, Pathophysiology and Dialysis transplantation). The oldest article included in the top 100 was the 1934 article by Goldblatt in the Journal of Experimental Medicine describing the effect on systemic blood pressure consequent to renal ischaemia, that has been cited 2632 times since then, with a mean rate of 31.7 citations/year for a period of 83 years.

A total of 35 scientific journals had published the top 100 most cited articles in nephrology, of which eight included almost 70% of all contributions (The New England Journal of Medicine, The Lancet, American Journal of Kidney Diseases, Kidney International, Annals of Internal Medicine, JAMA, Journal of Clinical Investigation and Journal of the American Society of Nephrology) (Table 4).

Table 4.

Number of articles for the different scientific journals that contributed to the top 100 most cited articles in nephrology

Journal	Number of articles
N Engl J Med	27
Lancet	10
Am J Kidney Dis	7
Kidney Int	7
Ann Intern Med	5
JAMA	5
J Clin Invest	4
J Am Soc Nephrol	4
Crit Care	2
J Biol Chem	2
Circulation	2
Br Med J	2
Clin Chem	1
Hypertension	1
Nephron	1
J Histochem Cytochem	1
J Clin Endocrinol Metab	1
Nephrol Dial Transpl	1
J Exp Med	1
Nat Biotechnol	1
Methods Enzymol	1
J Clin Pathol	1
Science	1
Pediatrics	1
Am J Physiol	1
Cell	1
Mol Cell	1
J Am Coll Cardiol	1
Am J Med	1
Nat Genet	1
Nature	1
J Am Chem Soc	1
Pediatr Clin North Am	1
Neurology	1
Arch Intern Med	1
Total	100

The principal author or co-author with higher number of articles in the top 100 is AS Levey with 10 articles (rank number 2, 4, 12, 13, 19, 21, 27, 30, 44 and 82) accounting for a total of 45 716 citations (16.0% of all citations).

Concerning the country of origin of the articles included in the top 100 list, the great majority of studies were contributed by USA scientists (total 62 articles), while 16 articles were contributed by authors from four or more countries (defined as global). The UK contributed seven articles and other countries (Germany, Canada, France, Australia, Italy, Denmark, Sweden and Finland) with a lower number (Figure 1). Plotting all the 100 top cited articles in a timeline graph by number of articles published and the year of publication shows that the maximum number of articles were published in 2003 (nine articles), there is a large skewness towards the old articles going back to 1934, while the most recent article was published in 2011 (Figure 2).

FIGURE 1:

Countries of origins of the articles included in the top 100 list.

FIGURE 2:

Timeline of the articles included in the top 100 most cited.

DISCUSSION

In this study, we have evaluated the top 100 articles that had a high impact on the practice of nephrology, by assessing the number of times these articles were cited. Therefore, by analysing the topics that were covered by the set of articles, one can draw the contours of the discipline and, potentially, its evolution over time since its establishment about 60 years ago. Through this analysis, one can also obtain information on the major source of articles that contributed to the most cited and assess their country of origin.

We decided to use an approach based on Google Scholar search, which is more comprehensive of all citing sources of an article. One has to consider, however, that the cumulative number of citations in each subcategory does not reflect the global interest of the nephrology community for that specific field; instead it represents an estimation of the weight of single publications that have been produced in that specific subfield.

It is not possible to comment on each individual article included in the top 100 list; however, we can draw some considerations that help understand the major interests of the nephrological professionals worldwide.

The first two most cited articles are: (i) the 1976 article on Cockcroft–Gault formula for estimating creatinine clearance and (ii) Levey’s 1999 article on estimating GFR by the Modification of Diet in Renal Disease (MDRD) formula. Both of them accumulated >27 600 citations (9.7% of the total citations of the top 100 articles). Therefore, the highest interest of nephrologists in the last three to four decades has been related to estimating GFR in a more accurate way. As a matter of fact, at the fourth position we find the article by Levey et al. describing the new CKD-EPI formula for estimating GFR, while at the 27th position of most cited articles there is a 2000 abstract by Levey et al. on a modification of the original MDRD formula to calculate estimated GFR, which is worth of 2681 citations. Also, at the 19th rank we find the article by Levey and the CKD-EPI consortium on the expression of the MDRD formula by standardized creatinine measurement. Finally, another article by Schwartz et al. on estimating GFR in children, collected 2152 citations and ranked 52nd. In total, 10 articles concerned measurement of serum creatinine, and different formulas to estimate GFR by different methods or in different ethnic groups, and cumulatively they were cited 53 140 times (18.6% of total citations of the top 100 articles). This result can be, at least partially, explained by the interdisciplinary relevance of this topic.

Another relevant field of interest in nephrological research is the pharmacological intervention aimed at slowing the progression rate of CKD. At the 6th position we find a clinical trial from Brenner et al. about the Reduction of Endopoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study with 7219 citations. While on the 7th and 8th positions, we find two studies from Ed Lewis's group on the renoprotective effects of RAAS blockade in diabetic nephropathy, which cumulatively were cited 11 707 times. It is noteworthy that a good proportion of articles describing randomized controlled trials with drugs involve antagonists of the renin-angiotensin system that have a broader organ protection in common chronic conditions such as diabetes, hypertension and cardiovascular diseases and, therefore, have a multidisciplinary interest. Even though the pharmacological intervention and randomized controlled studies do not have the proper weight in the nephrological literature, compared with other medical specialties, since ‘only’ 13 articles among the top 100 concerned randomized controlled trials, and the paucity of controlled studies in nephrology has been emphasized in a previous report by the Cochrane investigators [14].

Among the first 10 most cited articles, 4 were published <15 years ago, and this aspect may represent a sign of acceleration of the nephrological community on specific research topics (epidemiology of CKD, exact estimation of GFR and classification of AKI).

Correction of anaemia in uraemic patients after the introduction of erythropoiesis-stimulating agents in the late 1980s has represented a classic topic of the nephrological research. Among the top 100 articles, we find four contributions describing intervention studies evaluating the effects of recombinant human erythropoietin on correction of anaemia in end-stage renal disease patients. Aside from the original pilot study in 25 haemodialysis patients by Eschbach et al., the other three studies that received significant citations in this field, addressed the issue of different targets of haemoglobin on mortality and quality of life in dialysis patients with or without cardiovascular disease, and in patients Stage 3–4 CKD.

The large prevalence of articles published in the USA among the top 100 list is not surprising, since the scientific and medical research core, starting at the beginning of the 20th century, shifted its gravitational centre from Europe to Northern America, supported by a rapid growth of public and private universities in the USA [15]. Perhaps, American authors tend to cite other articles produced in that country. Also, relevant journals that are based in the USA, tend to prefer American reviewers [7].

The number of citations cannot be considered the unique criterion to establish the absolute relevance of a scientific article. It perhaps reflects a measure of recognition or the way that specific contribution intersects with relevant, even though practical, issues; the number of citations is by no way a measure of the scientific or clinical quality of a specific study. Associated to this concept is the finding that, when the journal Nature commissioned a search from the Thomson Reuters Institute to identify the top 100 most cited scientific articles ever [16], in first position was an article of practical impact in lab experiments: that is, the method for protein microassay in fluids, described by Oliver Lowry in 1951, which accumulated 305 000 citations. On the other side, the 1953 Watson and Crick article published in Nature about the discovery of the DNA structure, was cited, at the time of the Nature article was published, ‘only’ 5307 times [16].

In conclusion, this analysis allows identification of major fields of interest in the nephrological clinical and basic research. Most relevant aspects that have been explored in the top 100 most cited articles deal with the modality of evaluation of renal function, controlled trials with pharmacologic agents useful for delaying the progression of CKDs and the epidemiological assessment of prevalence of CKDs in the general population. Specific issues pertaining to morbidity of the uraemic status and definition and management of AKI are also relevant aspects of the nephrological investigation. The relevant nephrological literature comes from English-based journals and is produced in the USA. Information from this analysis may help guide the process of scientific updating required for a proper clinical practice of the modern nephrologist.

CONFLICT OF INTEREST STATEMENT

None declared. The results presented in this article have not been published previously in whole or in part, neither in abstract format.