Introduction: Critical care nephrology is a subspecialty that merges critical care and nephrology in response to shared pathobiology, clinical care, and technological innovations. To date, there has been no description of the highest impact articles. Accordingly, we systematically identified high impact articles in critical care nephrology. Methods: This was a bibliometric analysis. The search was developed by a research librarian. Web of Science was searched for articles published between January 1, 2000 and December 31, 2020. Articles required a minimum of 30 citations, publication in English language, and reporting of primary (or secondary) original data. Articles were screened by two reviewers for eligibility and further adjudicated by three experts. The “Top 100” articles were hierarchically ranked by adjudication, citations in the 2 years following publication and journal impact factor (IF). For each article, we extracted detailed bibliometric data. Risk of bias was assessed for randomized trials by the Cochrane Risk of Bias tool. Analyses were descriptive. Results: The search yielded 2,805 articles. Following initial screening, 307 articles were selected for full review and adjudication. The Top 100 articles were published across 20 journals (median [IQR] IF 10.6 [8.9–56.3]), 38% were published in the 5 years ending in 2020 and 62% were open access. The agreement between adjudicators was excellent (intraclass correlation, 0.96; 95% CI, 0.84–0.99). Of the Top 100, 44% were randomized trials, 35% were observational, 14% were systematic reviews, 6% were nonrandomized interventional studies and one article was a consensus document. The risk of bias among randomized trials was low. Common subgroup themes were RRT (42%), AKI (30%), fluids/resuscitation (14%), pediatrics (10%), interventions (8%), and perioperative care (6%). The citations for the Top 100 articles were 175 (95–393) and 9 were cited >1,000 times. Conclusion: Critical care nephrology has matured as an important subspecialty of critical care and nephrology. These high impact papers have focused largely on original studies, mostly clinical trials, within a few core themes. This list can be leveraged for curricula development, to stimulate research, and for quality assurance.

Critical care nephrology is a maturing subspecialty that has merged the disciplines of critical care and nephrology in response to shared pathophysiology, disease states, patient populations, clinical course, and technological innovations [1]. The critical care nephrology community has grown to be a comprehensive, multidisciplinary, and multidimensional subspecialty.

Advances in the field have evolved through the initial and subsequent consensus collaboration led by the Acute Disease Quality Initiative (ADQI) [2, 3]. The ADQI has made substantial contributions, particularly in the identification of knowledge gaps and guidance of future research [3]. This work has certainly paved opportunity for the development and publication of rigorous and evidence-informed clinical practice guidelines (CPG) for acute kidney injury (AKI) and acute renal-replacement therapy (RRT) [4], including those produced by the Kidney Disease Improving Global Outcomes (KDIGO) organization [5] and by the National Institute for Health and Care Excellence (NICE) [6]. In the acknowledgment of the growing contributions of critical care nephrology to the literature in both critical care and nephrology, KDIGO recently hosted a controversies conference as a prelude to updating existing CPG [7].

Despite the growth and maturation of this subspecialty, there has been no objective or systematic identification of those articles with the greatest impact. These high-impact articles are likely to represent landmark and foundational publications that have had a substantial impact on the field (e.g., care processes, patient prognosis, diagnostics, therapeutics). The catalog of these articles can inform revised and updated CPG, can identify knowledge gaps, can serve as inspiration for additional research, and can represent the core for the development of educational curricula. Accordingly, we sought to systematically identify and describe the highest impact articles published in the subspecialty of critical care nephrology.

Research ethics board approval was not required, as all data included in this evaluation were already published and did not directly involve human participants.

Search Strategy

In consultation with a research librarian, we searched the Web of Science Core Collection on March 7, 2022 for critical care nephrology papers from January 1, 2000 to December 31, 2020 inclusive. The search strategy was peer-reviewed by an experienced research librarian (TC).

The following search strategy was used: TS = (“critical care” OR “critical* ill*” OR “intensive care” OR ICU) AND TS = (nephrolog* OR “acute kidney injur*” OR “acute kidney failure” OR “acute kidney insufficien*” OR “acute renal injur*” OR “acute renal failure” OR “acute renal insufficien*” OR dialysis) NOT TI = (“narrative review” OR “case series” OR “case report” OR editorial OR commentary).

The final search was filtered to include articles that were English-language only and that had been cited a minimum of 30 times (arbitrarily selected by consensus among the investigators based on screening feasibility and likely impact). In addition, we further considered papers that were flagged as “Highly Cited Papers” and “Hot Papers.” Highly Cited Papers is a Web of Science filter that identifies papers in the top 1% over the past 10 years. Hot Papers is another filter that recognizes papers published in the last 2 years receiving above average citations. Both are indicators of research excellence that were worthy of consideration for inclusion even if they obtained less than 30 citations. Based on these criteria, our initial search yielded a total of 2,805 unique references for this analysis.

Of these 2,805 included papers, we collected citation data within Web of Science itself, journal impact factors (IFs) from Journal Citation Report (JCR), and 2020 CiteScores from Scopus, where available. Only journals with the latest IF from 2020 were included in the dataset. The IF is a metric that calculates “the average number of times articles from a journal published in the past 2 years have been cited in the JCR” (Clarivate, 2021). The CiteScore is a similar metric to the IF, but it takes into consideration a 4-year citation window instead of two (Elsevier, 2021).

Article Selection

Articles selected for inclusion, in order of importance, were: (1) randomized clinical trials or evidence syntheses (e.g., meta-analyses); (2) nonrandomized clinical trials; and (3) observational cohort studies. Included articles had to describe the primary (or secondary) reporting of original data. Beyond these design-specific criteria, consensus or CPG were given consideration. Narrative reviews, case series or case reports, experimental studies, and editorials or commentaries were excluded.

The initial screening of titles and abstracts of retrieved articles was independently performed by two reviewers (JP and SMB) to verify the suitability to the field of critical care nephrology. Conflicts were resolved by consensus or adjudication by a third reviewer (ASR). The second screening of articles selected from the first screen involved title, abstract, and full-text review by the same reviewers to verify eligibility. Conflicts were again resolved by consensus or adjudication by a third reviewer.

We further undertook a process of external adjudication by three recognized experts in the field of critical care nephrology (MO, NP, RW). External reviewers independently evaluated each article selected from the second screening and provided a response for each of the following questions using a 5-point Likert scale (1 = none/not likely; 2 = minor/some; 3 = neutral/uncertain; 4 = modest/moderate; 5 = significant/high):

  • 1.

    What has been the impact of this paper on the field of critical care nephrology?

  • 2.

    How likely is it that this paper influenced and changed clinical practice?

  • 3.

    How likely is it that this paper will be (or has been) cited in CPG?

For each paper, responses (equally weighted) were summated to give a maximum score of 15 and averaged across the three independent adjudicators. The list of articles was then ranked, using a hierarchal strategy to remove articles: (1) average adjudication score; (2) total citations in the 2 years after publication; and (3) Journal IF. From this list, the “Top 100” ranked articles were included as the highest impact papers in critical care nephrology.

We also specified subgroups within the “Top 100” papers across the following themes within critical care nephrology: (1) AKI (e.g., epidemiology, diagnostics, biomarkers, prognosis, therapeutics); (2) RRT (e.g., timing, modality, mode, anticoagulation, access/catheter, dose/ultrafiltration, pharmacology); (3) resuscitation/fluids (e.g., fluid therapy, vasoactive therapy, resuscitation strategies); (4) pediatrics; (5) perioperative; and (6) interventions. We recognize that articles within these themes may not be mutually exclusive.

Measures of Impact

For each article, we extracted several measures of impact, where available, including: (1) citations – as duration from publication permits older articles greater opportunity to accrue citations, we evaluated citations as: (i) total number of citations since publication, (ii) total citations in the first 2 years after publication, (iii) average annual citations since publication, (iv) total citations in the last 5 years, and (v) total citations in the last 2 years; (2) journal IF – we evaluated the IF of the journal in which the article was published, using the latest journal IF available in JCR from the year 2020; (3) CiteScore – we evaluated the CiteScore (Scopus) of the journal in which the article was published, where available; (4) Altmetric Attention Score – (Bookmarklet – Altmetric) – we downloaded the “Altmetric it” function from Altrimetic.com website and analyzed the Top 20 articles by searching for their unique digital object identifiers (DOIs), if available. These were not available for older published articles or for articles published in journals not supporting Altmetric; and (5) PlumX metrics – we downloaded the parameters from this score and analyzed the Top 20 articles using their unique DOIs, if available.

We performed further sensitivity analyses of the list of highest impact papers giving priority to other retrieved metrics of impact, including total citations (Web of Science and across all databases), citations in the past 2 and 5 years, Altmetric Attention Score, and PlumX metrics.

Data Extraction

For each included article, we extracted the authors, the sponsor institution, country, funding organization, journal type (e.g., general medical, critical care, nephrology), journal name, the DOI, the year of publication, the full title, and the topic/theme. We extracted details of the study design, registration, published protocols/statistical analysis plans, listed keywords, and MeSH terms.

Quality of Reporting

The quality and risk of bias of extracted articles were assessed using the Cochrane Risk of Bias (2.0) tool for randomized trials (RCTs) (Risk of bias tools – RoB 2 tool) [8] for the Top 100 articles, as applicable [9]. This was only performed for RCTs. The RoB 2 tool assesses bias across five domains: (1) randomization process, (2) deviation(s) from the intended intervention(s), (3) missing outcome data, (4) measurement of the outcome, and (5) selection of the reported result. The overall assessment of bias is based on the cumulative bias identified in each of these domains and is qualified as low risk, some concerns, or high risk.

Analysis

Descriptive statistical methods were used to describe the Top 100 articles in critical care nephrology. We used one-way random-effects intraclass correlation to assess the level of agreement between the three independent reviewers.

Search and Article Selection

Our search strategy identified 2,805 unique articles. After initial screening, 2,498 were excluded, leaving 307 articles for full-text screening. These 307 articles were further ranked by independent external adjudication by three content experts to arrive at the Top 100 highest impact articles (Table 1; Fig. 1). Of these, content experts agreed on perfect scores (average aggregate score of 15 for the three questions) for three articles [10‒12]. The overall reliability and agreement between the content experts for the Top 100 articles was excellent (intraclass correlation 0.96; 95% CI, 0.84–0.99, p < 0.001).

Table 1.

Top 100 highest impact publications in the field of critical care nephrology based on hierarchal ranking of expert review, citations in the 2 years after publication, and journal IF (2000-2020)

RankPublished yearStudyTitleJournalIFExpert scoreTotal citations (Web of Science)Citations, last 5 yearsCitations, 2 years afterCitations, yearly averagePrimary themeDOIPubMed ID
2012 Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial [10Hydroxyethyl starch 130/0.4 versus Ringer's acetate in severe sepsis NEJM 91.253 15 1,160 605 507 115 Fluid 10.1056/NEJMoa1204242 22738085 
2006 Fluids and Catheters Treatment Trial (FACTT) [11Comparison of two fluid-management strategies in acute lung injury NEJM 91.253 15 2,169 927 20 134 Fluid  16714767 
2008 VA/NIH Acute Renal Failure Trial Network (ATN) [12Intensity of renal support in critically ill patients with acute kidney injury NEJM 91.253 15 1,065 444 76 RRT  18492867 
2018 Saline Against Lactated Ringer’s or Plasma-Lyte in the Emergency Department (SALT-ED) [13Balanced crystalloids versus saline in noncritically ill adults NEJM 91.253 14.67 254 246 174 62 Fluid 10.1056/NEJMoa1711586 29485926 
2009 Randomized Evaluation of Normal vs. Augmented Level (RENAL) [14Intensity of continuous renal-replacement therapy in critically ill patients NEJM 91.253 14.67 863 410 120 66 RRT  19846848 
2018 Bicarbonate Therapy in the Intensive Care Unit (BICAR-ICU) Trial [15Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial LANCET 79.323 14.67 108 106 78 27 Intervention 10.1016/S0140-6736(18)31080-8 29910040 
2004 Acute Disease Quality Initiative (ADQI) Workgroup [3Acute 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 9.097 14.33 4,482 1,905 90 247 AKI 10.1186/cc2872 15312219 
2012 Crystalloid vs. Hydroxyethyl Starch Trial (CHEST) [16Hydroxyethyl starch or saline for fluid resuscitation in intensive care NEJM 91.253 14.33 1,031 557 103 Fluid 10.1056/NEJMoa1209759 23075127 
2016 Artificial Kidney Initiation in Kidney Injury (AKIKI) Trial [17Initiation strategies for renal-replacement therapy in the intensive care unit NEJM 91.253 14.33 505 498 224 83 RRT 10.1056/NEJMoa1603017 27181456 
10 2020 Standard vs. Accelerated Initiation of Renal Replacement Therapy in AKI (STARRT-AKI) Trial [18Timing of initiation of renal-replacement therapy in acute kidney injury NEJM 91.253 14.33 124 117 124 59 RRT 10.1056/NEJMoa2000741 32668114 
11 2018 Isotonic Solutions and Major Adverse Renal Events Trial (SMART) [19Balanced crystalloids versus saline in critically ill adults NEJM 91.253 14 483 468 329 117 Fluid 10.1056/NEJMoa1711584 29485925 
12 2008 German Competence Network Sepsis [20Intensive insulin therapy and pentastarch resuscitation in severe sepsis NEJM 91.253 14 1,926 456 108 137 Fluid 10.1056/NEJMoa070716 18184958 
13 2006 Hemodiafe Trial [21Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial LANCET 79.323 13.67 389 120 53 24 RRT 10.1016/S0140-6736(06)69111-3 16876666 
14 2001 Kellum et al. [22Use of dopamine in acute renal failure: a meta-analysis Crit Care Med 7.598 13.67 298 52 33 14 Intervention 10.1097/00003246-200108000-00005 11505120 
15 2018 Initiation of Dialysis Early vs. Late in the ICU (IDEAL-ICU) Trial [23Timing of renal-replacement therapy in patients with acute kidney injury and sepsis NEJM 91.253 13.67 231 227 148 57 RRT 10.1056/NEJMoa1803213 30304656 
16 2020 Fluid Loading in Abdominal Surgery-Saline vs. Hydroxyethyl Starch (FLASH) Trial [24Effect of hydroxyethyl starch vs saline for volume replacement therapy on death or postoperative complications among high-risk patients Undergoing major abdominal surgery: the FLASH randomized clinical trial JAMA 56.274 13.33 55 53 55 27 Fluid 10.1001/jama.2019.20833 31961418 
17 2020 Goldstein et al. [25A prospective multi-center quality improvement initiative (NINJA) indicates a reduction in nephrotoxic acute kidney injury in hospitalized children KIDNEY INT 10.612 13.33 38 37 38 19 Pediatric 10.1016/j.kint.2019.10.015 31980139 
18 2016 Early vs. Delayed Initiation of Renal Replacement Therapy (ELAIN) Trial [26Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury: the ELAIN randomized clinical trial JAMA 56.274 13.33 527 521 235 87 RRT 10.1001/jama.2016.5828 27209269 
19 2002 Bouman et al. [27Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: a prospective, randomized trial Crit Care Med 7.598 13.33 410 114 19 21 RRT 10.1097/00003246-200210000-00005 12394945 
20 2015 Saline vs. Plasma-Lyte for ICU Fluid Therapy (SPLIT) Trial [28Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial JAMA 56.274 13 372 363 163 53 Fluid 10.1001/jama.2015.12334 26444692 
21 2020 Regional Citrate vs, Systemic Heparin Anticoagulation for CRRT (RICH) Trial [29Effect of regional citrate anticoagulation vs systemic heparin anticoagulation during continuous kidney replacement therapy on dialysis filter life span and mortality among critically ill patients with acute kidney injury: a randomized clinical trial JAMA 56.274 13 38 33 38 16.5 RRT 10.1001/jama.2020.18618 33095849 
22 2013 Zarychanski et al. [30Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis JAMA 56.274 13 396 222 53 43.66667 Fluid 10.1001/jama.2013.430 23423413 
23 2008 Cathedia Study [31Femoral vs jugular venous catheterization and risk of nosocomial events in adults requiring acute renal replacement therapy – a randomized controlled trial JAMA 56.274 13 223 82 15.78571 RRT 10.1001/jama.299.20.2413 18505951 
24 2015 Wilson et al. [32Automated, electronic alerts for acute kidney injury: a single-blind, parallel-group, randomised controlled trial LANCET 79.323 12.67 191 175 76 27.14286 AKI 10.1016/S0140-6736(15)60266-5 25726515 
25 2007 Rabindranath et al. [33Intermittent versus continuous renal replacement therapy for acute renal failure in adults CDSR 9.289 12.67 198 89 12.93333 RRT 10.1002/14651858.CD003773.pub3 17636735 
26 2020 Gaudry et al. [34Delayed versus early initiation of renal replacement therapy for severe acute kidney injury: a systematic review and individual patient data meta -analysis of randomised clinical trials LANCET 79.323 12.67 54 54 54 27 RRT 10.1016/S0140-6736(20)30531-6 32334654 
27 2017 Saline Against Lactated Ringer’s or Plasma-Lyte (SALT) Trial [35Balanced crystalloids versus saline in the intensive care unit. The SALT randomized trial AJRCCM 21.405 12.67 107 107 74 21.2 Fluid 10.1164/rccm.201607-1345OC 27749094 
28 2015 Hoste et al. [36Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study Intensive Care Med 17.44 12.33 1,029 995 201 143.4286 AKI 10.1007/s00134-015-3934-7 26162677 
29 2017 Intraoperative Norepinephrine to Control Arterial Pressure (INPRESS) Trial [24Effect of individualized vs standard blood pressure management strategies on postoperative organ dysfunction among high-risk patients undergoing major surgery: a randomized clinical trial JAMA 56.274 12.33 286 279 110 55.8 Periop 10.1001/jama.2017.14172 28973220 
30 2011 Grams et al.[37Fluid balance, diuretic use, and mortality in acute kidney injury CJASN 8.237 12.33 231 130 48 20.90909 AKI 10.2215/CJN.08781010 21393482 
31 2008 Tolwani et al. [38Standard versus high-dose CVVHDF for ICU-related acute renal failure JASN 10.121 12.33 163 41 64 11.64286 RRT 10.1681/ASN.2007111173 18337480 
32 2005 Friedrich et al. [39Meta-analysis: low-dose dopamine increases urine output but does not prevent renal dysfunction or death Ann Internal Med 25.391 12.33 272 71 36 16 AKI 10.7326/0003-4819-142-7-200504050-00010 15809463 
33 2004 Monchi et al. [40Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study Intensive Care Med 17.44 12.33 226 68 20 12.44444 RRT 10.1007/s00134-003-2047-x 14600809 
34 2015 Remote Ischemic Preconditioning for Heart Surgery (RIPHeart) Trial [41A multicenter trial of remote ischemic preconditioning for heart surgery NEJM 91.253 12 402 396 187 57.14286 AKI 10.1056/NEJMoa1413579 26436208 
35 2013 SAPPHIRE Study [42Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury Crit Care 9.097 12 667 526 98 73.11111 AKI 10.1186/cc12503 23388612 
36 2001 Schortgen et al. [43Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study LANCET 79.323 12 478 70 42 22.7619 AKI 10.1016/S0140-6736(00)04211-2 11289347 
37 2017 Assessment of Worldwide AKI, Renal Angina and Epidemiology (AWARE) Study [44Epidemiology of acute kidney injury in critically ill children and young adults NEJM 91.253 11.67 409 396 174 79.2 Pediatric 10.1056/NEJMoa1611391 27959707 
38 2018 Alobaidi et al. [45Association between fluid balance and outcomes in critically ill children: a systematic review and meta-analysis JAMA Pediatrics 16.193 11.67 111 107 67 26.75 Fluid 10.1001/jamapediatrics.2017.4540 29356810 
39 2009 Oudemans-vanStraaten et al. [46Citrate anticoagulation for continuous venovenous hemofiltration Crit Care Med 7.598 11.67 211 82 35 16.15385 RRT 10.1097/CCM.0b013e3181953c5e 19114912 
40 2010 Cathedia Study [47Catheter dysfunction and dialysis performance according to vascular access among 736 critically ill adults requiring renal replacement therapy: a randomized controlled study Crit Care Med 7.598 11.67 77 45 13 6.333333 RRT 10.1097/CCM.0b013e3181d454b3 20154599 
41 2000 Barenbrock et al. [48Effects of bicarbonate- and lactate-buffered replacement fluids on cardiovascular outcome in CVVH patients Kidney Int 10.612 11.67 70 11 3.181818 RRT 10.1046/j.1523-1755.2000.00336.x 11012909 
42 2003 Symons et al. [49Continuous renal replacement therapy in children up to 10 kg AJKD 8.86 11.67 73 29 3.842105 Pediatric 10.1016/S0272-6386(03)00195-1 12722032 
43 2012 RENAL Trial [50Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: a multicentre pharmacokinetic study Crit Care Med 7.598 11.67 143 77 14.1 RRT 10.1097/CCM.0b013e318241e553 22511133 
44 2017 Borthwicka et al. [51High-volume haemofiltration for sepsis in adults CDSR 9.289 11.33 40 38 19 7.6 RRT 10.1002/14651858.CD008075.pub3 28141912 
45 2013 Chawla et al. [52Development and standardization of a furosemide stress test to predict the severity of acute kidney injury Crit Care 9.097 11.33 158 139 16 17.22222 AKI 10.1186/cc13015 24053972 
46 2009 Program to improve care in acute renal disease (PICARD) Study [53Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury Kidney Int 10.612 11.33 638 339 75 48.69231 AKI 10.1038/ki.2009.159 19436332 
47 2014 Bove et al. [54Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial JAMA 56.274 11.33 92 71 40 11.5 AKI 10.1001/jama.2014.13573 25265449 
48 2016 SAPPHIRE Study [55Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 for risk stratification of acute kidney injury in patients with sepsis Crit Care Med 7.598 11.33 60 60 21 10 AKI 10.1097/CCM.0000000000001827 27355527 
49 2005 Kutsogiannis et al. [56Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients Kidney Int 10.612 11.33 186 53 20 10.82353 RRT 10.1111/j.1523-1755.2005.00342.x 15882280 
50 2012 Bayer et al. [57Effects of fluid resuscitation with synthetic colloids or crystalloids alone on shock reversal, fluid balance, and patient outcomes in patients with severe sepsis: a prospective sequential analysis Crit Care Med 7.598 11.33 94 36 9.4 Fluid 10.1097/CCM.0b013e318258fee7 22903091 
51 2020 65 Trial [58Effect of reduced exposure to vasopressors on 90-day mortality in older critically ill patients with vasodilatory hypotension: a randomized clinical trial JAMA 56.274 11 66 64 66 32 AKI 10.1001/jama.2020.0930 32049269 
52 2016 Protocolized Care for Early Septic Shock (ProCESS) & ProGReSS-AKI Trial [59The effects of alternative resuscitation strategies on acute kidney injury in patients with septic shock AJRCCM 21.405 11 102 101 44 16.83333 AKI 10.1164/rccm.201505-0995OC 26398704 
53 2016 Liu et al. [60Regional citrate versus heparin anticoagulation for continuous renal replacement therapy in critically ill patients: a meta-analysis with trial sequential analysis of randomized controlled trials Crit Care 9.097 11 84 83 32 13.83333 RRT 10.1186/s13054-016-1299-0 27176622 
54 2014 Citrate Anticoagulation vs Systemic Heparinisation (CASH) Trial [61Citrate anticoagulation versus systemic heparinisation in continuous venovenous hemofiltration in critically ill patients with acute kidney injury: a multi-center randomized clinical trial Crit Care 9.097 11 79 64 29 9.875 RRT 10.1186/s13054-014-0472-6 25128022 
55 2017 Kwiatkowski et al. [62Peritoneal dialysis vs furosemide for prevention of fluid overload in infants after cardiac Surgery: a randomized clinical trial JAMA Pediatrics 16.193 11 49 49 28 9.8 Pediatric 10.1001/jamapediatrics.2016.4538 28241247 
56 2004 Augustine et al. [63A randomized controlled trial comparing intermittent with continuous dialysis in patients with ARF AJKD 8.86 11 232 58 20 12.88889 RRT 10.1053/j.ajkd.2004.08.022 15558520 
57 2016 Fayad et al. [64Intensity of continuous renal replacement therapy for acute kidney injury CDSR 9.289 11 30 30 RRT 10.1002/14651858.CD010613.pub2  
58 2007 Bell et al. [65Continuous renal replacement therapy is associated with less chronic renal failure than intermittent haemodialysis after acute renal failure Intensive Care Med 17.44 11 145 34 9.666667 RRT 10.1007/s00134-007-0590-6 17364165 
59 2012 Yunos et al. [66Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults JAMA 56.274 10.67 718 465 40 71.5 Fluid 10.1001/jama.2012.13356 23073953 
60 2009 Stuivenberg Hospital Acute Renal Failure (SHARF) Trial [67Intermittent versus continuous renal replacement therapy for acute kidney injury patients admitted to the intensive care unit: results of a randomized clinical trial NDT 5.992 10.67 161 71 39 12.30769 RRT 10.1093/ndt/gfn560 18854418 
61 2012 Wu et al. [68Regional citrate versus heparin anticoagulation for continuous renal replacement therapy: a meta-analysis of randomized controlled trials AJKD 8.86 10.67 116 71 103 11.6 RRT 10.1053/j.ajkd.2011.11.030 22226564 
62 2010 Sutherland et al. [69Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry AJKD 8.86 10.67 369 208 77 30.75 Pediatric 10.1053/j.ajkd.2009.10.048 20042260 
63 2014 Wald et al. [70The association between renal replacement therapy modality and long-term outcomes among critically ill adults with acute kidney injury: a retrospective cohort study Crit Care Med 7.598 10.67 123 94 50 15.375 RRT 10.1097/CCM.0000000000000042 24275513 
64 2014 Chawla et al. [71Association between AKI and long-term renal and cardiovascular outcomes in United States veterans CJASN 8.237 10.67 187 160 49 23.125 AKI 10.2215/CJN.02440213 24311708 
65 2015 Beijing AKI Trial [72Fluid balance and mortality in critically ill patients with acute kidney injury: a multicenter prospective epidemiological study Crit Care 9.097 10.67 129 126 37 18.14286 AKI 10.1186/s13054-015-1085-4 26494153 
66 2018 AWARE Study [73Assessment of a renal angina index for prediction of severe acute kidney injury in critically ill children: a multicentre, multinational, prospective observational study LANCET Child & Adol Health 11.288 10.67 48 43 26 10.75 Pediatric 10.1016/S2352-4642(17)30181-5 30035208 
67 2009 Begging and Ending Supportive Therapy of the Kidney (BEST) Study [74Discontinuation of continuous renal replacement therapy: a post hoc analysis of a prospective multicenter observational study Crit Care Med 7.598 10.67 129 84 17 9.846154 RRT 10.1097/CCM.0b013e3181a38241 19623048 
68 2017 Selewski et al. [75The impact of fluid overload on outcomes in children treated with extracorporeal membrane oxygenation: a multicenter retrospective cohort study* Ped Crit Care Med 3.624 10.67 35 35 16 Pediatric 10.1097/PCC.0000000000001349 28937504 
69 2012 Selby et al. [76Use of electronic results reporting to diagnose and monitor AKI in hospitalized patients CJASN 8.237 10.67 161 109 12 16.1 AKI 10.2215/CJN.08970911 22362062 
70 2012 Friedrich et al.[77Hemofiltration compared to hemodialysis for acute kidney injury: systematic review and meta-analysis Crit Care 9.097 10.33 67 49 161 6.6 RRT 10.1186/cc11458 22867021 
71 2009 Coca et al. [78Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis AJKD 8.86 10.33 712 410 76 54.07692 AKI 10.1053/j.ajkd.2008.11.034 19346042 
72 2018 Lewis et al. [79Colloids versus crystalloids for fluid resuscitation in critically ill people CDSR 9.289 10.33 65 64 39 16 Fluid 10.1002/14651858.CD000567.pub7 30073665 
73 2014 Ronco et al. [80Continuous renal replacement therapy in neonates and small infants: development and first-in-human use of a miniaturised machine (CARPEDIEM) LANCET 79.323 10.33 92 81 31 11.25 Pediatric 10.1016/S0140-6736(14)60799-6 24856026 
74 2014 Selewski et al. [81Validation of the KDIGO acute kidney injury criteria in a pediatric critical care population Intensive Care Med 17.44 10.33 123 114 23 15.125 Pediatric 10.1007/s00134-014-3391-8 25079008 
75 2017 Ehrmann et al. [82Contrast-associated acute kidney injury in the critically ill: systematic review and Bayesian meta-analysis Intensive Care Med 17.44 10.33 37 36 17 7.2 AKI 10.1007/s00134-017-4700-9 28197679 
76 2006 Saudan et al. [83Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure Kidney Int 10.612 10.33 249 42 15.5625 RRT 10.1038/sj.ki.5001705 16850022 
77 2019 Murugan et al. [84Association of net ultrafiltration rate with mortality among critically ill adults with acute kidney injury receiving continuous venovenous hemodiafiltration: a secondary analysis of the RENAL trial JAMA Network Open 8.485 10.33 51 49 49 16.33333 RRT 10.1001/jamanetworkopen.2019.5418 31173127 
78 2017 Alberta Kidney Disease Network [85Health care costs associated with AKI CJASN 8.237 10.33 46 44 17 8.8 AKI 10.2215/CJN.00950117 29051143 
79 2013 IVOIRE Trial [86High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial Intensive Care Med 17.44 10.33 208 156 23 22.66667 RRT 10.1007/s00134-013-2967-z 23740278 
80 2003 Uchino et al. [87Continuous is not continuous: the incidence and impact of circuit "down-time" on uraemic control during continuous veno-venous haemofiltration Intensive Care Med 17.44 10.33 120 30 11 RRT 10.1007/s00134-003-1672-8 12577144 
81 2018 BigpAK Trial [88Biomarker-guided intervention to prevent acute kidney injury after major surgery: the prospective randomized BigpAK study Ann Surg 12.969 10 152 149 94 37 AKI 10.1097/SLA.0000000000002485 28857811 
82 2016 Mehta et al. [89Recognition and management of acute kidney injury in the International Society of Nephrology 0by25 Global Snapshot: a multinational cross-sectional study LANCET 79.323 10 178 177 65 29.5 AKI 10.1016/S0140-6736(16)30240-9 27086173 
83 2017 Kellum et al. [90Recovery after acute kidney injury AJRCCM 21.405 10 155 149 62 29.8 AKI 10.1164/rccm.201604-0799OC 27635668 
84 2011 Translational Research in Biomarker Endpoints and Applications in Acute Kidney Disease (TRIBE-AKD) Study [91Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery JASN 10.121 10 176 80 53 15.63636 AKI 10.1681/ASN.2010121302 21836143 
85 2006 Berbece et al. [92Sustained low-efficiency dialysis in the ICU: cost, anticoagulation, and solute removal Kidney Int 10.612 10 106 40 6.5 RRT 10.1038/sj.ki.5001700 16850023 
86 2012 REnal replacement therapy Study in intensive Care Unit patiEnts (RESCUE) trial [93Sustained low efficiency dialysis using a single-pass batch system in acute kidney injury – a randomized interventional trial Crit Care 9.097 10 87 53 42 8.4 RRT 10.1186/cc11445 22839577 
87 2009 Dose Response Multicentre International Collaborative Initiative (DO-RE-MI) Study [94Delivered dose of renal replacement therapy and mortality in critically ill patients with acute kidney injury Crit Care 9.097 10 148 53 41 11.38462 RRT 10.1186/cc7784 19368724 
88 2005 Uehlinger et al. [95Comparison of continuous and intermittent renal replacement therapy for acute renal failure NDT 5.992 10 194 47 40 11.41176 RRT 10.1093/ndt/gfh880 15886217 
89 2004 BEST Kidney Study [96Diuretics and mortality in acute renal failure Crit Care Med 7.598 10 212 40 39 11.77778 AKI 10.1097/01.CCM.0000132892.51063.2F 15286542 
90 2017 McDonald et al. [97Post-contrast acute kidney injury in intensive care unit patients: a propensity score-adjusted study Intensive Care Med 17.44 10 59 58 34 11.6 AKI 10.1007/s00134-017-4699-y 28213620 
91 2010 Gordon et al. [98The effects of vasopressin on acute kidney injury in septic shock Intensive Care Med 17.44 10 140 75 33 11.66667 AKI 10.1007/s00134-009-1687-x 19841897 
92 2013 Fiaccadori et al. [99Efficacy and safety of a citrate-based protocol for sustained low-efficiency dialysis in AKI using standard dialysis equipment CJASN 8.237 10 39 34 42 4.333333 RRT 10.2215/CJN.00510113 23990164 
93 2000 Lassnigg et al. [100Lack of renoprotective effects of dopamine and furosemide during cardiac surgery JASN 10.121 10 278 73 20 12.63636 Periop  10616845 
94 2015 Stucker et al. [101Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled trial Crit Care 9.097 10 57 53 20 8.142857 RRT 10.1186/s13054-015-0822-z 25881975 
95 2012 Colpaert et al. [102Impact of real-time electronic alerting of acute kidney injury on therapeutic intervention and progression of RIFLE class Crit Care Med 7.598 10 155 88 26 15.5 AKI 10.1097/CCM.0b013e3182387a6b 22067631 
96 2003 Manns et al. [103Cost of acute renal failure requiring dialysis in the intensive care unit: clinical and resource implications of renal recovery Crit Care Med 7.598 10 165 36 14 8.684211 RRT 10.1097/01.CCM.0000045182.90302.B3 12576950 
97 2005 Van Biesen et al. [104Relationship between fluid status and its management on acute renal failure (ARF) in intensive care unit (ICU) patients with sepsis: a prospective analysis J Nephrol 3.902 10 95 16 13 5.588235 AKI  15772923 
98 2012 Mammen et al. [105Long-term risk of CKD in children surviving episodes of acute kidney injury in the intensive care unit: a prospective cohort study AJKD 8.86 10 299 221 78 29.5 Pediatric 10.1053/j.ajkd.2011.10.048 22206744 
99 2000 Ronco C et al. [106Effects of different doses in continuous veno-venous haemofiltration on outcomes in acute renal failure: a prospective randomised trial LANCET 79.323 9.67 1,169 145 36 47 RRT 10.1016/S0140-6736(00)02430-2 10892761 
100 2005 BEST Kidney Study [107Acute renal failure in critically ill patients – a multinational, multicenter study JAMA 56.274 9.67 2,688 1,155 163 157.0588 AKI 10.1001/jama.294.7.813 16106006 
RankPublished yearStudyTitleJournalIFExpert scoreTotal citations (Web of Science)Citations, last 5 yearsCitations, 2 years afterCitations, yearly averagePrimary themeDOIPubMed ID
2012 Scandinavian Starch for Severe Sepsis/Septic Shock (6S) Trial [10Hydroxyethyl starch 130/0.4 versus Ringer's acetate in severe sepsis NEJM 91.253 15 1,160 605 507 115 Fluid 10.1056/NEJMoa1204242 22738085 
2006 Fluids and Catheters Treatment Trial (FACTT) [11Comparison of two fluid-management strategies in acute lung injury NEJM 91.253 15 2,169 927 20 134 Fluid  16714767 
2008 VA/NIH Acute Renal Failure Trial Network (ATN) [12Intensity of renal support in critically ill patients with acute kidney injury NEJM 91.253 15 1,065 444 76 RRT  18492867 
2018 Saline Against Lactated Ringer’s or Plasma-Lyte in the Emergency Department (SALT-ED) [13Balanced crystalloids versus saline in noncritically ill adults NEJM 91.253 14.67 254 246 174 62 Fluid 10.1056/NEJMoa1711586 29485926 
2009 Randomized Evaluation of Normal vs. Augmented Level (RENAL) [14Intensity of continuous renal-replacement therapy in critically ill patients NEJM 91.253 14.67 863 410 120 66 RRT  19846848 
2018 Bicarbonate Therapy in the Intensive Care Unit (BICAR-ICU) Trial [15Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial LANCET 79.323 14.67 108 106 78 27 Intervention 10.1016/S0140-6736(18)31080-8 29910040 
2004 Acute Disease Quality Initiative (ADQI) Workgroup [3Acute 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 9.097 14.33 4,482 1,905 90 247 AKI 10.1186/cc2872 15312219 
2012 Crystalloid vs. Hydroxyethyl Starch Trial (CHEST) [16Hydroxyethyl starch or saline for fluid resuscitation in intensive care NEJM 91.253 14.33 1,031 557 103 Fluid 10.1056/NEJMoa1209759 23075127 
2016 Artificial Kidney Initiation in Kidney Injury (AKIKI) Trial [17Initiation strategies for renal-replacement therapy in the intensive care unit NEJM 91.253 14.33 505 498 224 83 RRT 10.1056/NEJMoa1603017 27181456 
10 2020 Standard vs. Accelerated Initiation of Renal Replacement Therapy in AKI (STARRT-AKI) Trial [18Timing of initiation of renal-replacement therapy in acute kidney injury NEJM 91.253 14.33 124 117 124 59 RRT 10.1056/NEJMoa2000741 32668114 
11 2018 Isotonic Solutions and Major Adverse Renal Events Trial (SMART) [19Balanced crystalloids versus saline in critically ill adults NEJM 91.253 14 483 468 329 117 Fluid 10.1056/NEJMoa1711584 29485925 
12 2008 German Competence Network Sepsis [20Intensive insulin therapy and pentastarch resuscitation in severe sepsis NEJM 91.253 14 1,926 456 108 137 Fluid 10.1056/NEJMoa070716 18184958 
13 2006 Hemodiafe Trial [21Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial LANCET 79.323 13.67 389 120 53 24 RRT 10.1016/S0140-6736(06)69111-3 16876666 
14 2001 Kellum et al. [22Use of dopamine in acute renal failure: a meta-analysis Crit Care Med 7.598 13.67 298 52 33 14 Intervention 10.1097/00003246-200108000-00005 11505120 
15 2018 Initiation of Dialysis Early vs. Late in the ICU (IDEAL-ICU) Trial [23Timing of renal-replacement therapy in patients with acute kidney injury and sepsis NEJM 91.253 13.67 231 227 148 57 RRT 10.1056/NEJMoa1803213 30304656 
16 2020 Fluid Loading in Abdominal Surgery-Saline vs. Hydroxyethyl Starch (FLASH) Trial [24Effect of hydroxyethyl starch vs saline for volume replacement therapy on death or postoperative complications among high-risk patients Undergoing major abdominal surgery: the FLASH randomized clinical trial JAMA 56.274 13.33 55 53 55 27 Fluid 10.1001/jama.2019.20833 31961418 
17 2020 Goldstein et al. [25A prospective multi-center quality improvement initiative (NINJA) indicates a reduction in nephrotoxic acute kidney injury in hospitalized children KIDNEY INT 10.612 13.33 38 37 38 19 Pediatric 10.1016/j.kint.2019.10.015 31980139 
18 2016 Early vs. Delayed Initiation of Renal Replacement Therapy (ELAIN) Trial [26Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury: the ELAIN randomized clinical trial JAMA 56.274 13.33 527 521 235 87 RRT 10.1001/jama.2016.5828 27209269 
19 2002 Bouman et al. [27Effects of early high-volume continuous venovenous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: a prospective, randomized trial Crit Care Med 7.598 13.33 410 114 19 21 RRT 10.1097/00003246-200210000-00005 12394945 
20 2015 Saline vs. Plasma-Lyte for ICU Fluid Therapy (SPLIT) Trial [28Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial JAMA 56.274 13 372 363 163 53 Fluid 10.1001/jama.2015.12334 26444692 
21 2020 Regional Citrate vs, Systemic Heparin Anticoagulation for CRRT (RICH) Trial [29Effect of regional citrate anticoagulation vs systemic heparin anticoagulation during continuous kidney replacement therapy on dialysis filter life span and mortality among critically ill patients with acute kidney injury: a randomized clinical trial JAMA 56.274 13 38 33 38 16.5 RRT 10.1001/jama.2020.18618 33095849 
22 2013 Zarychanski et al. [30Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis JAMA 56.274 13 396 222 53 43.66667 Fluid 10.1001/jama.2013.430 23423413 
23 2008 Cathedia Study [31Femoral vs jugular venous catheterization and risk of nosocomial events in adults requiring acute renal replacement therapy – a randomized controlled trial JAMA 56.274 13 223 82 15.78571 RRT 10.1001/jama.299.20.2413 18505951 
24 2015 Wilson et al. [32Automated, electronic alerts for acute kidney injury: a single-blind, parallel-group, randomised controlled trial LANCET 79.323 12.67 191 175 76 27.14286 AKI 10.1016/S0140-6736(15)60266-5 25726515 
25 2007 Rabindranath et al. [33Intermittent versus continuous renal replacement therapy for acute renal failure in adults CDSR 9.289 12.67 198 89 12.93333 RRT 10.1002/14651858.CD003773.pub3 17636735 
26 2020 Gaudry et al. [34Delayed versus early initiation of renal replacement therapy for severe acute kidney injury: a systematic review and individual patient data meta -analysis of randomised clinical trials LANCET 79.323 12.67 54 54 54 27 RRT 10.1016/S0140-6736(20)30531-6 32334654 
27 2017 Saline Against Lactated Ringer’s or Plasma-Lyte (SALT) Trial [35Balanced crystalloids versus saline in the intensive care unit. The SALT randomized trial AJRCCM 21.405 12.67 107 107 74 21.2 Fluid 10.1164/rccm.201607-1345OC 27749094 
28 2015 Hoste et al. [36Epidemiology of acute kidney injury in critically ill patients: the multinational AKI-EPI study Intensive Care Med 17.44 12.33 1,029 995 201 143.4286 AKI 10.1007/s00134-015-3934-7 26162677 
29 2017 Intraoperative Norepinephrine to Control Arterial Pressure (INPRESS) Trial [24Effect of individualized vs standard blood pressure management strategies on postoperative organ dysfunction among high-risk patients undergoing major surgery: a randomized clinical trial JAMA 56.274 12.33 286 279 110 55.8 Periop 10.1001/jama.2017.14172 28973220 
30 2011 Grams et al.[37Fluid balance, diuretic use, and mortality in acute kidney injury CJASN 8.237 12.33 231 130 48 20.90909 AKI 10.2215/CJN.08781010 21393482 
31 2008 Tolwani et al. [38Standard versus high-dose CVVHDF for ICU-related acute renal failure JASN 10.121 12.33 163 41 64 11.64286 RRT 10.1681/ASN.2007111173 18337480 
32 2005 Friedrich et al. [39Meta-analysis: low-dose dopamine increases urine output but does not prevent renal dysfunction or death Ann Internal Med 25.391 12.33 272 71 36 16 AKI 10.7326/0003-4819-142-7-200504050-00010 15809463 
33 2004 Monchi et al. [40Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study Intensive Care Med 17.44 12.33 226 68 20 12.44444 RRT 10.1007/s00134-003-2047-x 14600809 
34 2015 Remote Ischemic Preconditioning for Heart Surgery (RIPHeart) Trial [41A multicenter trial of remote ischemic preconditioning for heart surgery NEJM 91.253 12 402 396 187 57.14286 AKI 10.1056/NEJMoa1413579 26436208 
35 2013 SAPPHIRE Study [42Discovery and validation of cell cycle arrest biomarkers in human acute kidney injury Crit Care 9.097 12 667 526 98 73.11111 AKI 10.1186/cc12503 23388612 
36 2001 Schortgen et al. [43Effects of hydroxyethylstarch and gelatin on renal function in severe sepsis: a multicentre randomised study LANCET 79.323 12 478 70 42 22.7619 AKI 10.1016/S0140-6736(00)04211-2 11289347 
37 2017 Assessment of Worldwide AKI, Renal Angina and Epidemiology (AWARE) Study [44Epidemiology of acute kidney injury in critically ill children and young adults NEJM 91.253 11.67 409 396 174 79.2 Pediatric 10.1056/NEJMoa1611391 27959707 
38 2018 Alobaidi et al. [45Association between fluid balance and outcomes in critically ill children: a systematic review and meta-analysis JAMA Pediatrics 16.193 11.67 111 107 67 26.75 Fluid 10.1001/jamapediatrics.2017.4540 29356810 
39 2009 Oudemans-vanStraaten et al. [46Citrate anticoagulation for continuous venovenous hemofiltration Crit Care Med 7.598 11.67 211 82 35 16.15385 RRT 10.1097/CCM.0b013e3181953c5e 19114912 
40 2010 Cathedia Study [47Catheter dysfunction and dialysis performance according to vascular access among 736 critically ill adults requiring renal replacement therapy: a randomized controlled study Crit Care Med 7.598 11.67 77 45 13 6.333333 RRT 10.1097/CCM.0b013e3181d454b3 20154599 
41 2000 Barenbrock et al. [48Effects of bicarbonate- and lactate-buffered replacement fluids on cardiovascular outcome in CVVH patients Kidney Int 10.612 11.67 70 11 3.181818 RRT 10.1046/j.1523-1755.2000.00336.x 11012909 
42 2003 Symons et al. [49Continuous renal replacement therapy in children up to 10 kg AJKD 8.86 11.67 73 29 3.842105 Pediatric 10.1016/S0272-6386(03)00195-1 12722032 
43 2012 RENAL Trial [50Variability of antibiotic concentrations in critically ill patients receiving continuous renal replacement therapy: a multicentre pharmacokinetic study Crit Care Med 7.598 11.67 143 77 14.1 RRT 10.1097/CCM.0b013e318241e553 22511133 
44 2017 Borthwicka et al. [51High-volume haemofiltration for sepsis in adults CDSR 9.289 11.33 40 38 19 7.6 RRT 10.1002/14651858.CD008075.pub3 28141912 
45 2013 Chawla et al. [52Development and standardization of a furosemide stress test to predict the severity of acute kidney injury Crit Care 9.097 11.33 158 139 16 17.22222 AKI 10.1186/cc13015 24053972 
46 2009 Program to improve care in acute renal disease (PICARD) Study [53Fluid accumulation, survival and recovery of kidney function in critically ill patients with acute kidney injury Kidney Int 10.612 11.33 638 339 75 48.69231 AKI 10.1038/ki.2009.159 19436332 
47 2014 Bove et al. [54Effect of fenoldopam on use of renal replacement therapy among patients with acute kidney injury after cardiac surgery: a randomized clinical trial JAMA 56.274 11.33 92 71 40 11.5 AKI 10.1001/jama.2014.13573 25265449 
48 2016 SAPPHIRE Study [55Urinary tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7 for risk stratification of acute kidney injury in patients with sepsis Crit Care Med 7.598 11.33 60 60 21 10 AKI 10.1097/CCM.0000000000001827 27355527 
49 2005 Kutsogiannis et al. [56Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients Kidney Int 10.612 11.33 186 53 20 10.82353 RRT 10.1111/j.1523-1755.2005.00342.x 15882280 
50 2012 Bayer et al. [57Effects of fluid resuscitation with synthetic colloids or crystalloids alone on shock reversal, fluid balance, and patient outcomes in patients with severe sepsis: a prospective sequential analysis Crit Care Med 7.598 11.33 94 36 9.4 Fluid 10.1097/CCM.0b013e318258fee7 22903091 
51 2020 65 Trial [58Effect of reduced exposure to vasopressors on 90-day mortality in older critically ill patients with vasodilatory hypotension: a randomized clinical trial JAMA 56.274 11 66 64 66 32 AKI 10.1001/jama.2020.0930 32049269 
52 2016 Protocolized Care for Early Septic Shock (ProCESS) & ProGReSS-AKI Trial [59The effects of alternative resuscitation strategies on acute kidney injury in patients with septic shock AJRCCM 21.405 11 102 101 44 16.83333 AKI 10.1164/rccm.201505-0995OC 26398704 
53 2016 Liu et al. [60Regional citrate versus heparin anticoagulation for continuous renal replacement therapy in critically ill patients: a meta-analysis with trial sequential analysis of randomized controlled trials Crit Care 9.097 11 84 83 32 13.83333 RRT 10.1186/s13054-016-1299-0 27176622 
54 2014 Citrate Anticoagulation vs Systemic Heparinisation (CASH) Trial [61Citrate anticoagulation versus systemic heparinisation in continuous venovenous hemofiltration in critically ill patients with acute kidney injury: a multi-center randomized clinical trial Crit Care 9.097 11 79 64 29 9.875 RRT 10.1186/s13054-014-0472-6 25128022 
55 2017 Kwiatkowski et al. [62Peritoneal dialysis vs furosemide for prevention of fluid overload in infants after cardiac Surgery: a randomized clinical trial JAMA Pediatrics 16.193 11 49 49 28 9.8 Pediatric 10.1001/jamapediatrics.2016.4538 28241247 
56 2004 Augustine et al. [63A randomized controlled trial comparing intermittent with continuous dialysis in patients with ARF AJKD 8.86 11 232 58 20 12.88889 RRT 10.1053/j.ajkd.2004.08.022 15558520 
57 2016 Fayad et al. [64Intensity of continuous renal replacement therapy for acute kidney injury CDSR 9.289 11 30 30 RRT 10.1002/14651858.CD010613.pub2  
58 2007 Bell et al. [65Continuous renal replacement therapy is associated with less chronic renal failure than intermittent haemodialysis after acute renal failure Intensive Care Med 17.44 11 145 34 9.666667 RRT 10.1007/s00134-007-0590-6 17364165 
59 2012 Yunos et al. [66Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults JAMA 56.274 10.67 718 465 40 71.5 Fluid 10.1001/jama.2012.13356 23073953 
60 2009 Stuivenberg Hospital Acute Renal Failure (SHARF) Trial [67Intermittent versus continuous renal replacement therapy for acute kidney injury patients admitted to the intensive care unit: results of a randomized clinical trial NDT 5.992 10.67 161 71 39 12.30769 RRT 10.1093/ndt/gfn560 18854418 
61 2012 Wu et al. [68Regional citrate versus heparin anticoagulation for continuous renal replacement therapy: a meta-analysis of randomized controlled trials AJKD 8.86 10.67 116 71 103 11.6 RRT 10.1053/j.ajkd.2011.11.030 22226564 
62 2010 Sutherland et al. [69Fluid overload and mortality in children receiving continuous renal replacement therapy: the prospective pediatric continuous renal replacement therapy registry AJKD 8.86 10.67 369 208 77 30.75 Pediatric 10.1053/j.ajkd.2009.10.048 20042260 
63 2014 Wald et al. [70The association between renal replacement therapy modality and long-term outcomes among critically ill adults with acute kidney injury: a retrospective cohort study Crit Care Med 7.598 10.67 123 94 50 15.375 RRT 10.1097/CCM.0000000000000042 24275513 
64 2014 Chawla et al. [71Association between AKI and long-term renal and cardiovascular outcomes in United States veterans CJASN 8.237 10.67 187 160 49 23.125 AKI 10.2215/CJN.02440213 24311708 
65 2015 Beijing AKI Trial [72Fluid balance and mortality in critically ill patients with acute kidney injury: a multicenter prospective epidemiological study Crit Care 9.097 10.67 129 126 37 18.14286 AKI 10.1186/s13054-015-1085-4 26494153 
66 2018 AWARE Study [73Assessment of a renal angina index for prediction of severe acute kidney injury in critically ill children: a multicentre, multinational, prospective observational study LANCET Child & Adol Health 11.288 10.67 48 43 26 10.75 Pediatric 10.1016/S2352-4642(17)30181-5 30035208 
67 2009 Begging and Ending Supportive Therapy of the Kidney (BEST) Study [74Discontinuation of continuous renal replacement therapy: a post hoc analysis of a prospective multicenter observational study Crit Care Med 7.598 10.67 129 84 17 9.846154 RRT 10.1097/CCM.0b013e3181a38241 19623048 
68 2017 Selewski et al. [75The impact of fluid overload on outcomes in children treated with extracorporeal membrane oxygenation: a multicenter retrospective cohort study* Ped Crit Care Med 3.624 10.67 35 35 16 Pediatric 10.1097/PCC.0000000000001349 28937504 
69 2012 Selby et al. [76Use of electronic results reporting to diagnose and monitor AKI in hospitalized patients CJASN 8.237 10.67 161 109 12 16.1 AKI 10.2215/CJN.08970911 22362062 
70 2012 Friedrich et al.[77Hemofiltration compared to hemodialysis for acute kidney injury: systematic review and meta-analysis Crit Care 9.097 10.33 67 49 161 6.6 RRT 10.1186/cc11458 22867021 
71 2009 Coca et al. [78Long-term risk of mortality and other adverse outcomes after acute kidney injury: a systematic review and meta-analysis AJKD 8.86 10.33 712 410 76 54.07692 AKI 10.1053/j.ajkd.2008.11.034 19346042 
72 2018 Lewis et al. [79Colloids versus crystalloids for fluid resuscitation in critically ill people CDSR 9.289 10.33 65 64 39 16 Fluid 10.1002/14651858.CD000567.pub7 30073665 
73 2014 Ronco et al. [80Continuous renal replacement therapy in neonates and small infants: development and first-in-human use of a miniaturised machine (CARPEDIEM) LANCET 79.323 10.33 92 81 31 11.25 Pediatric 10.1016/S0140-6736(14)60799-6 24856026 
74 2014 Selewski et al. [81Validation of the KDIGO acute kidney injury criteria in a pediatric critical care population Intensive Care Med 17.44 10.33 123 114 23 15.125 Pediatric 10.1007/s00134-014-3391-8 25079008 
75 2017 Ehrmann et al. [82Contrast-associated acute kidney injury in the critically ill: systematic review and Bayesian meta-analysis Intensive Care Med 17.44 10.33 37 36 17 7.2 AKI 10.1007/s00134-017-4700-9 28197679 
76 2006 Saudan et al. [83Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure Kidney Int 10.612 10.33 249 42 15.5625 RRT 10.1038/sj.ki.5001705 16850022 
77 2019 Murugan et al. [84Association of net ultrafiltration rate with mortality among critically ill adults with acute kidney injury receiving continuous venovenous hemodiafiltration: a secondary analysis of the RENAL trial JAMA Network Open 8.485 10.33 51 49 49 16.33333 RRT 10.1001/jamanetworkopen.2019.5418 31173127 
78 2017 Alberta Kidney Disease Network [85Health care costs associated with AKI CJASN 8.237 10.33 46 44 17 8.8 AKI 10.2215/CJN.00950117 29051143 
79 2013 IVOIRE Trial [86High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial Intensive Care Med 17.44 10.33 208 156 23 22.66667 RRT 10.1007/s00134-013-2967-z 23740278 
80 2003 Uchino et al. [87Continuous is not continuous: the incidence and impact of circuit "down-time" on uraemic control during continuous veno-venous haemofiltration Intensive Care Med 17.44 10.33 120 30 11 RRT 10.1007/s00134-003-1672-8 12577144 
81 2018 BigpAK Trial [88Biomarker-guided intervention to prevent acute kidney injury after major surgery: the prospective randomized BigpAK study Ann Surg 12.969 10 152 149 94 37 AKI 10.1097/SLA.0000000000002485 28857811 
82 2016 Mehta et al. [89Recognition and management of acute kidney injury in the International Society of Nephrology 0by25 Global Snapshot: a multinational cross-sectional study LANCET 79.323 10 178 177 65 29.5 AKI 10.1016/S0140-6736(16)30240-9 27086173 
83 2017 Kellum et al. [90Recovery after acute kidney injury AJRCCM 21.405 10 155 149 62 29.8 AKI 10.1164/rccm.201604-0799OC 27635668 
84 2011 Translational Research in Biomarker Endpoints and Applications in Acute Kidney Disease (TRIBE-AKD) Study [91Postoperative biomarkers predict acute kidney injury and poor outcomes after adult cardiac surgery JASN 10.121 10 176 80 53 15.63636 AKI 10.1681/ASN.2010121302 21836143 
85 2006 Berbece et al. [92Sustained low-efficiency dialysis in the ICU: cost, anticoagulation, and solute removal Kidney Int 10.612 10 106 40 6.5 RRT 10.1038/sj.ki.5001700 16850023 
86 2012 REnal replacement therapy Study in intensive Care Unit patiEnts (RESCUE) trial [93Sustained low efficiency dialysis using a single-pass batch system in acute kidney injury – a randomized interventional trial Crit Care 9.097 10 87 53 42 8.4 RRT 10.1186/cc11445 22839577 
87 2009 Dose Response Multicentre International Collaborative Initiative (DO-RE-MI) Study [94Delivered dose of renal replacement therapy and mortality in critically ill patients with acute kidney injury Crit Care 9.097 10 148 53 41 11.38462 RRT 10.1186/cc7784 19368724 
88 2005 Uehlinger et al. [95Comparison of continuous and intermittent renal replacement therapy for acute renal failure NDT 5.992 10 194 47 40 11.41176 RRT 10.1093/ndt/gfh880 15886217 
89 2004 BEST Kidney Study [96Diuretics and mortality in acute renal failure Crit Care Med 7.598 10 212 40 39 11.77778 AKI 10.1097/01.CCM.0000132892.51063.2F 15286542 
90 2017 McDonald et al. [97Post-contrast acute kidney injury in intensive care unit patients: a propensity score-adjusted study Intensive Care Med 17.44 10 59 58 34 11.6 AKI 10.1007/s00134-017-4699-y 28213620 
91 2010 Gordon et al. [98The effects of vasopressin on acute kidney injury in septic shock Intensive Care Med 17.44 10 140 75 33 11.66667 AKI 10.1007/s00134-009-1687-x 19841897 
92 2013 Fiaccadori et al. [99Efficacy and safety of a citrate-based protocol for sustained low-efficiency dialysis in AKI using standard dialysis equipment CJASN 8.237 10 39 34 42 4.333333 RRT 10.2215/CJN.00510113 23990164 
93 2000 Lassnigg et al. [100Lack of renoprotective effects of dopamine and furosemide during cardiac surgery JASN 10.121 10 278 73 20 12.63636 Periop  10616845 
94 2015 Stucker et al. [101Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled trial Crit Care 9.097 10 57 53 20 8.142857 RRT 10.1186/s13054-015-0822-z 25881975 
95 2012 Colpaert et al. [102Impact of real-time electronic alerting of acute kidney injury on therapeutic intervention and progression of RIFLE class Crit Care Med 7.598 10 155 88 26 15.5 AKI 10.1097/CCM.0b013e3182387a6b 22067631 
96 2003 Manns et al. [103Cost of acute renal failure requiring dialysis in the intensive care unit: clinical and resource implications of renal recovery Crit Care Med 7.598 10 165 36 14 8.684211 RRT 10.1097/01.CCM.0000045182.90302.B3 12576950 
97 2005 Van Biesen et al. [104Relationship between fluid status and its management on acute renal failure (ARF) in intensive care unit (ICU) patients with sepsis: a prospective analysis J Nephrol 3.902 10 95 16 13 5.588235 AKI  15772923 
98 2012 Mammen et al. [105Long-term risk of CKD in children surviving episodes of acute kidney injury in the intensive care unit: a prospective cohort study AJKD 8.86 10 299 221 78 29.5 Pediatric 10.1053/j.ajkd.2011.10.048 22206744 
99 2000 Ronco C et al. [106Effects of different doses in continuous veno-venous haemofiltration on outcomes in acute renal failure: a prospective randomised trial LANCET 79.323 9.67 1,169 145 36 47 RRT 10.1016/S0140-6736(00)02430-2 10892761 
100 2005 BEST Kidney Study [107Acute renal failure in critically ill patients – a multinational, multicenter study JAMA 56.274 9.67 2,688 1,155 163 157.0588 AKI 10.1001/jama.294.7.813 16106006 
Fig. 1.

Flow diagram of paper selection.

Fig. 1.

Flow diagram of paper selection.

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The Top 100 Highest Impact Articles

The Top 100 articles were published across 20 journals. The most common general medical journals were the New England Journal of Medicine (NEJM) (n = 13), the Journal of the American Medical Association (JAMA) (n = 11), and the Lancet (n = 8). The most common critical care subspecialty journals were Critical Care Medicine (CCM) (n = 12), Critical Care (n = 10), and Intensive Care Medicine (n = 9). The most common nephrology subspecialty journals were Kidney International (n = 6), the American Journal of Kidney Diseases (n = 6), and Clinical Journal of the American Society of Nephrology (n = 5). Of the Top 100 articles, 38 were published in the last 5 years of the citation window (2015–2020). In total, 62 of the Top 100 articles are open access.

Of the Top 100 articles, 44% were randomized trials, of which 4 [9%] were international, 24 [55%] were multicenter, and 18 [41%] were single-center, and 14% were systematic reviews. Six articles were nonrandomized interventional studies, 35 were observational studies (12 prospective; 23 retrospective), and one article was a consensus paper [3].

Quality and Risk of Bias of RCTs in the Top 100 Articles

The overall risk of bias for RCTs was low, with 83% of the studies falling into the low-risk category (Fig. 2). The remainder fell within the “some concerns” category, due to differences in baseline characteristics of study groups, bringing the effectiveness of randomization into question. No RCT was assessed as high risk in any domain (Fig. 2).

Fig. 2.

Summary graph of the Cochrane Risk of Bias 2.0 (RoB2) assessments of the randomized clinical trials within the Top 100 papers (n = 43). Bias was assessed in five specific domains: (1) randomization process; (2) deviation(s) from the intended intervention(s); (3) missing outcome data; (4) measurement of the outcome; and (5) selection of the reported result. Risk of bias was qualified as one of low risk, some concerns, or high risk. The overall assessment of bias reflects the summative risk of bias across these domains. Data are presented as a percentage of the 43 clinical trials examined.

Fig. 2.

Summary graph of the Cochrane Risk of Bias 2.0 (RoB2) assessments of the randomized clinical trials within the Top 100 papers (n = 43). Bias was assessed in five specific domains: (1) randomization process; (2) deviation(s) from the intended intervention(s); (3) missing outcome data; (4) measurement of the outcome; and (5) selection of the reported result. Risk of bias was qualified as one of low risk, some concerns, or high risk. The overall assessment of bias reflects the summative risk of bias across these domains. Data are presented as a percentage of the 43 clinical trials examined.

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Subgroups of Highest Impact Papers

The most common primary subgroup themes of the included articles were focused on RRT (42%), on AKI (30%), and on fluid therapy and resuscitation (14%). A total of 10% of articles were focused on pediatrics (AKI, n = 4; RRT, n = 2; fluid/resuscitation, n = 3; interventional, n = 1) (Table 2). Of these, 9 (90%) were published in pediatric journals. Of the Top 100 articles, 6% were focused on perioperative care and 8% on specific pharmacological or therapeutic interventions (bicarbonate, dopamine, fenoldopam, diuretics) [15, 22, 39, 41, 54, 62, 96, 100].

Table 2.

Summary of subgroup themes of Top 100 highest impact articles in critical care nephrology

SubgroupAuthor (Year)TrialJournal (IF)Expert review scoreTimes cited (All)Cited initial 2 yearsAverage annual citationsCited last 2 yearsDOI
AKI (rank) 
 7 Bellomo (2004) ADQI (RIFLE) Crit Care (9.1) 14.33 4,775 90 247 572 10.1186/cc2872 
 24 Wilson (2015) e-Alert Lancet (79.3) 12.67 196 76 27 58 10.1016/S0140-6736(15)60266-5 
 28 Hoste (2015) AKI-EPI ICM (17.4) 12.33 1,078 201 143 475 10.1007/s00134-015-3934-7 
 30 Grams (2011) AKI in FACCT CJASN (8.2) 12.33 247 48 21 38 10.2215/CJN.08781010 
 32 Friedrich (2005) SR/MA (Dopamine) Ann Internal Med (25.4) 12.33 291 36 16 24 10.7326/0003-4819-142-7-200504050-00010 
 34 Meybohm (2015) RIPHeart NEJM (91.3) 12.00 412 187 57 87 10.1056/NEJMoa1413579 
 35 Kashani (2013) SAPPHIRE Crit Care (9.1) 12.00 707 98 73 172 10.1186/cc12503 
 36 Schortgen (2001) HES in Sepsis Lancet (79.3) 12 509 42 23 11 10.1016/S0140-6736(00)04211-2 
 45 Chawla (2013) FST Crit Care (9.1) 11.33 169 16 17 43 10.1186/cc13015 
 46 Bouchard (2009) Fluid Overload Kidney Int (10.6) 11.33 688 75 49 114 10.1038/ki.2009.159 
RRT (rank) 
 3 Palevsky (2008) ATN NEJM (91.3) 15.00 1,129 76 131  
 5 Bellomo (2009) RENAL NEJM (91.3) 14.67 908 120 66 123  
 9 Gaudry (2016) AKIKI NEJM (91.3) 14.33 547 224 83 177 10.1056/NEJMoa1603017 
 10 Bagshaw/Wald (2020) STARRT-AKI NEJM (91.3) 14.33 135 124 59 117 10.1056/NEJMoa2000741 
 13 Vinsonneau (2006) Hemodiafe Lancet (79.3) 13.67 426 53 24 34 10.1016/S0140-6736(06)69111-3 
 15 Barbar (2018) IDEAL-ICU NEJM (91.3) 13.67 254 148 57 153 10.1056/NEJMoa1803213 
 18 Zarbock (2016) ELAIN JAMA (56.3) 13.33 570 235 87 187 10.1001/jama.2016.5828 
 19 Bouman (2002) HVHF CCM (7.6) 13.33 451 19 21 25 10.1097/00003246-200210000-00005 
 21 Zarbock (2020) RICH JAMA (56.3) 13.00 39 38 17 33  
 23 Parenti (2008) Cathedia JAMA (56.3) 13 237 16 26  
Resuscitation and fluids (rank) 
 1 Perner (2012) 6S NEJM (91.3) 15.00 1,239 507 115 156 10.1056/NEJMoa1204242 
 2 Wiedemann (2006) FACCT NEJM (91.3) 15.00 2,286 20 134 320  
 4 Self (2018) SALT-ED NEJM (91.3) 14.67 264 174 62 133 10.1056/NEJMoa1711586 
 8 Myburgh (2012) CHEST NEJM (91.3) 14.33 1,111 103 138 10.1056/NEJMoa1209759 
 11 Semler (2018) SMART NEJM (91.3) 14.00 501 329 117 256 10.1056/NEJMoa1711584 
 12 Brunkhorst (2008) VISEP NEJM (91.3) 14.00 2045 108 137 112 10.1056/NEJMoa070716 
 16 Futier (2020) FLASH JAMA (56.3) 13.33 56 55 27 53 10.1001/jama.2019.20833 
 20 Young (2015) SPLIT JAMA (56.3) 13.00 393 163 53 79 10.1001/jama.2015.12334 
 22 Zarychanski (2013) SR/MA (HES) JAMA (56.3) 13.00 433 53 44 44 10.1001/jama.2013.430 
 27 Semler (2017) SALT AJRCCM (21.4) 12.67 114 74 21 32 10.1164/rccm.201607-1345OC 
Pediatrics (rank) 
 17 Goldstein (2020) NINJA Kidney Int (10.6) 13.33 40 38 19 37 10.1016/j.kint.2019.10.015 
 37 Kaddourah (2017) AWARE NEJM (91.3) 11.67 428 38 79 37 10.1056/NEJMoa1611391 
 42 Symons (2003) CRRT < 10 kg AJKD (8.9) 11.67 80 174 222 10.1016/S0272-6386(03)00195-1 
 55 Kwiatkowski (2017) PD versus Furosemide JAMA Pediatrics (16.2) 11.00 51 10 12 10.1001/jamapediatrics.2016.4538 
 62 Sutherland (2010) Fluid Overload AJKD (8.9) 10.67 396 28 31 21 10.1053/j.ajkd.2009.10.048 
 66 Basu (2018) RAI (AWARE) Lancet Child Adol Health (11.3) 10.67 48 77 11 63 10.1016/S2352-4642(17)30181-5 
 68 Selewski (2017) Fluid Overload PCCM (3.6) 10.67 37 26 35 10.1097/PCC.0000000000001349 
 73 Ronco (2014) Carpe Diem Lancet (79.3) 10.33 97 16 11 19 10.1016/S0140-6736(14)60799-6 
 74 Selewski (2014) KDIGO in kids ICM (17.4) 10.33 126 31 15 22 10.1007/s00134-014-3391-8 
 98 Mammen (2012) LTO in AKI AJKD (8.9) 10.00 316 23 30 42 10.1053/j.ajkd.2011.10.048 
Perioperative (rank) 
 16 Futier (2020) FLASH JAMA (56.3) 13.33 56 55 27 53 10.1001/jama.2019.20833 
 29 Futier (2017) IMPRESS JAMA (56.3) 12.33 294 110 56 169 10.1001/jama.2017.14172 
 34 Meybohm (2015) RIP Heart NEJM (91.3) 12.00 412 187 57 87 10.1056/NEJMoa1413579 
 81 Gocze (2018) BigpAK Study Ann Surgery (12.9) 10.00 153 94 37 98 10.1097/SLA.0000000000002485 
 84 Parikh (2011) TRIBE-AKI JASN (10.1) 10.00 181 53 16 19 10.1681/ASN.2010121302 
 93 Lassnigg (2000) Dopamine/Furosemide JASN (10.1) 10.00 295 20 13 20  
Interventions (rank) 
 6 Jaber (2018) BICAR-ICU Lancet (79.3) 14.67 115 78 27 59 10.1016/S0140-6736(18)31080-8 
 14 Kellum (2001) Dopamine (SR) CCM (7.6) 13.67 322 33 14 10 10.1097/00003246-200108000-00005 
 32 Friedrich (2005) SR/MA (Dopamine) Ann Internal Med (25.4) 12.33 291 36 16 24 10.7326/0003-4819-142-7-200504050-00010 
 34 Meybohm (2015) RIP Heart NEJM (91.3) 12.00 412 187 57 87 10.1056/NEJMoa1413579 
 47 Bove (2014) Fenoldopam JAMA (56.3) 11.33 95 40 12 20 10.1001/jama.2014.13573 
 55 Kwiatkowski (2017) PD versus Furosemide JAMA Pediatrics (16.2) 11.00 51 10 12 10.1001/jamapediatrics.2016.4538 
 89 Uchino (2004) Diuretics in AKI CCM (7.6) 10.00 221 39 12 11 10.1097/01.CCM.0000132892.51063.2F 
 93 Lassnigg (2000) Dopamine/Furosemide JASN (10.1) 10.00 295 20 13 20  
SubgroupAuthor (Year)TrialJournal (IF)Expert review scoreTimes cited (All)Cited initial 2 yearsAverage annual citationsCited last 2 yearsDOI
AKI (rank) 
 7 Bellomo (2004) ADQI (RIFLE) Crit Care (9.1) 14.33 4,775 90 247 572 10.1186/cc2872 
 24 Wilson (2015) e-Alert Lancet (79.3) 12.67 196 76 27 58 10.1016/S0140-6736(15)60266-5 
 28 Hoste (2015) AKI-EPI ICM (17.4) 12.33 1,078 201 143 475 10.1007/s00134-015-3934-7 
 30 Grams (2011) AKI in FACCT CJASN (8.2) 12.33 247 48 21 38 10.2215/CJN.08781010 
 32 Friedrich (2005) SR/MA (Dopamine) Ann Internal Med (25.4) 12.33 291 36 16 24 10.7326/0003-4819-142-7-200504050-00010 
 34 Meybohm (2015) RIPHeart NEJM (91.3) 12.00 412 187 57 87 10.1056/NEJMoa1413579 
 35 Kashani (2013) SAPPHIRE Crit Care (9.1) 12.00 707 98 73 172 10.1186/cc12503 
 36 Schortgen (2001) HES in Sepsis Lancet (79.3) 12 509 42 23 11 10.1016/S0140-6736(00)04211-2 
 45 Chawla (2013) FST Crit Care (9.1) 11.33 169 16 17 43 10.1186/cc13015 
 46 Bouchard (2009) Fluid Overload Kidney Int (10.6) 11.33 688 75 49 114 10.1038/ki.2009.159 
RRT (rank) 
 3 Palevsky (2008) ATN NEJM (91.3) 15.00 1,129 76 131  
 5 Bellomo (2009) RENAL NEJM (91.3) 14.67 908 120 66 123  
 9 Gaudry (2016) AKIKI NEJM (91.3) 14.33 547 224 83 177 10.1056/NEJMoa1603017 
 10 Bagshaw/Wald (2020) STARRT-AKI NEJM (91.3) 14.33 135 124 59 117 10.1056/NEJMoa2000741 
 13 Vinsonneau (2006) Hemodiafe Lancet (79.3) 13.67 426 53 24 34 10.1016/S0140-6736(06)69111-3 
 15 Barbar (2018) IDEAL-ICU NEJM (91.3) 13.67 254 148 57 153 10.1056/NEJMoa1803213 
 18 Zarbock (2016) ELAIN JAMA (56.3) 13.33 570 235 87 187 10.1001/jama.2016.5828 
 19 Bouman (2002) HVHF CCM (7.6) 13.33 451 19 21 25 10.1097/00003246-200210000-00005 
 21 Zarbock (2020) RICH JAMA (56.3) 13.00 39 38 17 33  
 23 Parenti (2008) Cathedia JAMA (56.3) 13 237 16 26  
Resuscitation and fluids (rank) 
 1 Perner (2012) 6S NEJM (91.3) 15.00 1,239 507 115 156 10.1056/NEJMoa1204242 
 2 Wiedemann (2006) FACCT NEJM (91.3) 15.00 2,286 20 134 320  
 4 Self (2018) SALT-ED NEJM (91.3) 14.67 264 174 62 133 10.1056/NEJMoa1711586 
 8 Myburgh (2012) CHEST NEJM (91.3) 14.33 1,111 103 138 10.1056/NEJMoa1209759 
 11 Semler (2018) SMART NEJM (91.3) 14.00 501 329 117 256 10.1056/NEJMoa1711584 
 12 Brunkhorst (2008) VISEP NEJM (91.3) 14.00 2045 108 137 112 10.1056/NEJMoa070716 
 16 Futier (2020) FLASH JAMA (56.3) 13.33 56 55 27 53 10.1001/jama.2019.20833 
 20 Young (2015) SPLIT JAMA (56.3) 13.00 393 163 53 79 10.1001/jama.2015.12334 
 22 Zarychanski (2013) SR/MA (HES) JAMA (56.3) 13.00 433 53 44 44 10.1001/jama.2013.430 
 27 Semler (2017) SALT AJRCCM (21.4) 12.67 114 74 21 32 10.1164/rccm.201607-1345OC 
Pediatrics (rank) 
 17 Goldstein (2020) NINJA Kidney Int (10.6) 13.33 40 38 19 37 10.1016/j.kint.2019.10.015 
 37 Kaddourah (2017) AWARE NEJM (91.3) 11.67 428 38 79 37 10.1056/NEJMoa1611391 
 42 Symons (2003) CRRT < 10 kg AJKD (8.9) 11.67 80 174 222 10.1016/S0272-6386(03)00195-1 
 55 Kwiatkowski (2017) PD versus Furosemide JAMA Pediatrics (16.2) 11.00 51 10 12 10.1001/jamapediatrics.2016.4538 
 62 Sutherland (2010) Fluid Overload AJKD (8.9) 10.67 396 28 31 21 10.1053/j.ajkd.2009.10.048 
 66 Basu (2018) RAI (AWARE) Lancet Child Adol Health (11.3) 10.67 48 77 11 63 10.1016/S2352-4642(17)30181-5 
 68 Selewski (2017) Fluid Overload PCCM (3.6) 10.67 37 26 35 10.1097/PCC.0000000000001349 
 73 Ronco (2014) Carpe Diem Lancet (79.3) 10.33 97 16 11 19 10.1016/S0140-6736(14)60799-6 
 74 Selewski (2014) KDIGO in kids ICM (17.4) 10.33 126 31 15 22 10.1007/s00134-014-3391-8 
 98 Mammen (2012) LTO in AKI AJKD (8.9) 10.00 316 23 30 42 10.1053/j.ajkd.2011.10.048 
Perioperative (rank) 
 16 Futier (2020) FLASH JAMA (56.3) 13.33 56 55 27 53 10.1001/jama.2019.20833 
 29 Futier (2017) IMPRESS JAMA (56.3) 12.33 294 110 56 169 10.1001/jama.2017.14172 
 34 Meybohm (2015) RIP Heart NEJM (91.3) 12.00 412 187 57 87 10.1056/NEJMoa1413579 
 81 Gocze (2018) BigpAK Study Ann Surgery (12.9) 10.00 153 94 37 98 10.1097/SLA.0000000000002485 
 84 Parikh (2011) TRIBE-AKI JASN (10.1) 10.00 181 53 16 19 10.1681/ASN.2010121302 
 93 Lassnigg (2000) Dopamine/Furosemide JASN (10.1) 10.00 295 20 13 20  
Interventions (rank) 
 6 Jaber (2018) BICAR-ICU Lancet (79.3) 14.67 115 78 27 59 10.1016/S0140-6736(18)31080-8 
 14 Kellum (2001) Dopamine (SR) CCM (7.6) 13.67 322 33 14 10 10.1097/00003246-200108000-00005 
 32 Friedrich (2005) SR/MA (Dopamine) Ann Internal Med (25.4) 12.33 291 36 16 24 10.7326/0003-4819-142-7-200504050-00010 
 34 Meybohm (2015) RIP Heart NEJM (91.3) 12.00 412 187 57 87 10.1056/NEJMoa1413579 
 47 Bove (2014) Fenoldopam JAMA (56.3) 11.33 95 40 12 20 10.1001/jama.2014.13573 
 55 Kwiatkowski (2017) PD versus Furosemide JAMA Pediatrics (16.2) 11.00 51 10 12 10.1001/jamapediatrics.2016.4538 
 89 Uchino (2004) Diuretics in AKI CCM (7.6) 10.00 221 39 12 11 10.1097/01.CCM.0000132892.51063.2F 
 93 Lassnigg (2000) Dopamine/Furosemide JASN (10.1) 10.00 295 20 13 20  

Measures of Impact

The median (IQR) total number of citations on Web of Science for each of the Top 100 articles was 161 (87–369) (total citations all databases 175 [95–393]). Nine articles were cited on Web of Science >1,000 times [3, 10‒12, 16, 20, 36, 106, 107]. The highest cited article was the landmark ADQI consensus conference paper on AKI [3]. The Top 100 articles were cited a median 40 times (IQR, 20–76) in the 2 years after publication, a median annual average of 16 times (IQR, 11–44), and a median 82 (IQR, 52–208) and 33 (IQR, 19–85) in the last 5 years and 2 years of the study citation window. The median (IQR) Journal IF and CiteScore for the journals where the Top 100 articles were published were 10.6 (8.9–56.3) and 14.4 (10.7–24.8), respectively. The median (IQR) Altmetric Attention Score for the Top 20 papers was 239 (56–464) (online suppl. Table 1; for all online suppl. material, see https://doi.org/10.1159/000535558). The most common domains contributing to the Altmetric score were Twitter, Facebook, mainstream media, and blogs (online suppl. Table 2). The three articles with the highest Altimetric Attention Score were published more recently [13, 18, 19]. Similarly, the PlumX metrics for the Top 20 papers were more active for more recently published papers. In total, 27 papers were designated “Highly Cited” and “Hot Paper” status in Web of Science. Online supplementary Tables 3–7 show sensitivity analyses of the highest cited articles using a spectrum of citation metric only.

Critical care nephrology is an integral aspect of care for the critically ill patient and has matured as an important subspecialty in both critical care and nephrology [108]. This rigorous bibliometric analysis has summarized and cataloged the most important and highest impact papers that have shaped the discipline over the past 25 years.

There are several notable findings from this review process. First, articles ranked in the Top 100 were nearly all original studies and were focused on critically ill patients and/or in acute care and intensive care unit (ICU) settings. The notable exception is the ADQI consensus conference article that launched the first standard definition for AKI (i.e., Risk, Injury, Failure, Loss, End-Stage [RIFLE] criteria) [3]. Second, the largest proportion of articles were represented by randomized trials, particularly focused on the primary themes of fluid therapy, acute RRT, and AKI. Indeed, among the Top 10 articles, eight were trials that focused on fluid therapy and management, and strategies for acute RRT. Third, more than half of the ranked articles were multicenter in design, though relatively few were international in scope. Fourth, across these ranked articles, agreement between expert reviewers was excellent and the quality of reporting was high. Finally, relatively few articles described novel therapeutic interventions focused specifically on AKI.

The highest cited article among the Top 100 was the report from the 3rd ADQI consensus conference published in 2004 (ranked #7 for impact) [3]. This landmark ADQI article launched the first standard definition for AKI (i.e., RIFLE criteria) and identified several knowledge gaps and themes for further investigation [3]. This was the only consensus or guideline paper in the Top 100 articles. This foundational publication cast a stronger lens on the field of critical care nephrology and provoked a series of high-quality influential articles also listed in the Top 100 articles [12, 96, 107, 109]. This also draws attention to the importance of ADQI for driving research and innovation, identification of knowledge gaps, and striving for consensus in the field of critical care nephrology over the last 25 years [110]. While initially focused on acute dialysis, specifically continuous RRT (CRRT) [111‒118], ADQI has evolved to address a wide spectrum of themes in critical care nephrology, including biomarkers of AKI, fluid therapy, organ interaction (e.g., pulmonary-renal, hepato-renal, cardio-renal), sepsis, pediatric AKI, COVID-19, perioperative care, quality improvement, clinical trial design, digital health, and several technical aspects of acute RRT (e.g., precision CRRT, blood purification, etc.) (see https://www.adqi.org/) [119‒125].

The 2012 KDIGO Clinical Practice Guideline for AKI was also a landmark publication in the field of critical care nephrology [5]. The guideline proposed harmonized criteria for the definition and classification of AKI that have since been widely adopted as the current standard. The guideline further provided rigorous recommendations on both the prevention and treatment of AKI. The guideline was not identified by our bibliometric search, likely due to the primary publication being in a journal supplement and availability maintained on the KDIGO website: https://kdigo.org/guidelines/acute-kidney-injury/). However, our initial search did identify several articles that provided commentary on the guideline [126‒129].

While 10% of the Top 100 articles were pediatric focused, this theme may be under-represented in our review. In total, 8 of the 10 papers focused on pediatric critical care nephrology were published in the last 10 years, with 5 in the last 5 years, including the landmark AWARE and AWAKEN studies [44, 130]. Only two were interventional studies [25, 62]. The first was the NINJA study, where Goldstein et al. [25] significantly reduced AKI rates among children receiving nephrotoxic medications following the implementation of a multi-center hospital-wide AKI surveillance and quality improvement initiative. The second was a single-center trial of critically ill children at risk of fluid overload following cardiac surgery, where Kwiatkowski et al. [62] found peritoneal dialysis improved outcomes compared with furosemide. This paucity of pediatric focused articles may relate to our search methodology, that fewer articles focused on pediatrics have been heavily cited, or that this theme (pediatric critical care nephrology) has more recently seen greater attention, increased innovation, and research productivity. Notably, however, several recent high-profile articles have been published in pediatrics [25, 44, 45, 62, 130] and this work has been consolidated in a dedicated pediatric ADQI consensus meeting [120].

This ranking of the Top 100 highest impact articles in critical care nephrology will certainly evolve with the publication of new research and innovations in the field, and with newer practice changing evidence. As such, the current Top 100 ranking should be viewed as iterative. An exemplar example is the landmark single-center trial published by Ronco et al. [106], showing higher dose CRRT reduced mortality in critically ill patients with AKI (ranked #99). The trial by Ronco et al. [106], along with the “low-dose dopamine” in the AKI trial by Bellomo et al. [131], both published in the year 2000, are arguably keystone studies that launched the subspecialty of critical care nephrology [106, 131]. Ronco et al. [106] unquestionably inspired the design and successful completion of two large key high-quality multicenter randomized trials focused on dose during acute RRT in critically ill patients that changed clinical practice, specifically the ATN and RENAL trials (ranked #3 and #5) [12, 14, 106]. While these three trials had comparable total citations, a higher relative priority during adjudication was given to the more recent evidence from the ATN and RENAL trials.

Several articles included in the Top 100 have generated important new knowledge that has substantially shaped clinical practice. The 6S (rank #1), CHEST (rank # 8), and VISEP (rank #12) trials found evidence of harm with the use of synthetic hydroxyethyl starches compared with crystalloid solutions for acute resuscitation in critically ill patients, with increased rates of AKI, RRT use, and mortality, particularly in those with sepsis [10, 16, 20]. This was followed by marked reductions in hydroxyethyl starch use in critically ill patients [132]. High-profile trials in the Top 100 [13, 19, 28] have further suggested that aggregated evidence may favor balanced crystalloid solutions over 0.9% saline as resuscitation fluid for most critically ill patients [133]. The BICAR-ICU trial (rank #6) found that mitigation of severe metabolic acidosis in critically ill patients with supplementary bicarbonate may improve survival and reduce RRT utilization, particularly among the subgroup of patients with stage 2–3 AKI [15]. The FACTT trial (rank #2) found a strategy of conservative fluid management after initial resuscitation in critically ill patients with acute lung injury enabled a near neutral fluid balance after 7 days and reduced duration of invasive mechanical ventilation and ICU stay, without increasing RRT use for AKI [11]. Several noteworthy trials have provided guidance on the optional application of acute RRT in critically ill patients with AKI, including timing of initiation [17, 18, 23, 26], dose [12, 14, 106], modality [21], and anticoagulation [29] that will likely serve as basis for an updated CPG.

The Top 100 articles can also be leveraged and integrated into the design and implementation of educational curricula and training programs with a focus on critical care nephrology, including dual training in both nephrology and critical care [134]. Similarly, several of the Top 100 articles can be utilized to anchor baseline and changes to evidence-informed practices following publication or in the design of quality improvement and implementation science initiatives and extend beyond critical care nephrology. For example, describing the facilitators/barriers, the temporal changes and the extent of new evidence adoption [25] and/or de-adoption [10, 16] can be important to understanding how clinical practice and patient outcomes have been impacted [132, 135, 136].

Strengths and Limitations

Our study is strengthened by the use of an a priori established protocol, a rigorous and comprehensive peer-reviewed search strategy, and the integration of numerous measures of impact. Our study is further strengthened by having all the included papers independently adjudicated using standardized questions by three context experts. We also recognize that our study has limitations. Specifically, we recognize that the citation measures used to screen for high-impact articles will evolve with time, with older papers accumulating more citations. As such, potentially high-impact publications appearing in the preceding few years may not have had sufficient time to accumulate citations to be included in our initial screening. Second, while we recruited three diverse leaders and content experts in the field critical care nephrology for adjudication, we recognize that their judgment on the importance and impact of identified articles may be different from others. Moreover, this adjudication process may result in older impactful publications receiving lower rank priority [106, 131]. While this may have influenced the order of articles, the overall list of identified high-impact articles based on conventional citation metrics remains similar (online suppl. Tables 5–7). In addition, the process of adjudication of papers was not blinded (as may be done during manuscript peer review for journals); however, this was not feasible or practical. Despite this, adjudication was performed independently and reliability and agreement in scoring was excellent. Finally, as such, we recognize the Top 100 highest impact articles listed here will be iterative and somewhat analogous to the “Billboard Hot 100” (see https://www.billboard.com/charts/hot-100/).

Critical care nephrology is an important subspecialty focus for both critical care and nephrology. The current Top 100 highest impact articles in the field have largely focused on original studies, mostly clinical trials, within a few core themes. This list can be leveraged for curriculum development and training, stimulating research innovation, benchmark evidence adoption/de-adoption, quality assurance, and implementation science.

Thane Chambers, Research Impact Librarian, peer reviewed the search strategy. Dr. Bagshaw is supported by a Canada Research Chair in Critical Care Outcomes and Systems Evaluation.

Research ethics board approval was not required, as all data included in this evaluation were already published and did not directly involve human participants.

S.M.B. has received fees from Baxter, BioPorto, Sea Star Medical, SphingoTec, and Novartis for scientific advisory and fees from I-SPY-COVID for Data Safety Monitoring. R.W. has received unrestricted research funding and speaker fees from Baxter. R.W. has received fees for scientific advisory and speaking, and unrestricted research funding from Baxter. All other authors have no declarations.

This work was supported by the Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta.

S.M.B. conceived the study. S.M.B., J.P., A.S.R., and J.K. wrote the protocol. J.K. performed the search and extracted bibliometric data. R.W., M.O., and N.P. performed external adjudication. S.M.B. and J.P. wrote the manuscript. S.M.B. supervised the project. All authors reviewed and provided critical revisions to the manuscript.

The data that support the findings of this study are not publicly available but are available from SMB upon reasonable request.

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