Trials and guidelines in critical care nephrology

This collection of trials and guidelines about critical care nephrology and dialysis techniques is intended to act as a quick review resource for the end-stage exam candidate, as the preparation for the CICM Second Part exam should involve some reading beyond the past paper questions, to be ready for the possibility that something interesting and original might be asked. For this sort of reading, Critical Care Nephrology would have to be the canonical textbook, buit cannot be recommended to the time-poor exam candidate, owing to to its tremendous mass. One could get trapped under it. It is probably better to read it after the fellowship. If one were after some good free overview articles to cover much of the ground, one could do worse than the free PDFs from a 2005 special edition of Critical Care Clinics, edited by John A. Kellum. It is a whole issue dedicated to critical care nephrology.

Definitions and practical nomenclature

Definitions and classification models of acute kidney injury

Definitions of CRRT terminology

Trials in critical care nephrology

Trials in AKI prevention

  • Bellomo - 2000 - what about renal dose dopamine? n=328, mostly in Australia. No difference in survival (67% vs 66%), peak creatinine ( 245 vs 249 µmol/L) or arrhythmias (33% vs 33%). 
  •  VANISH2016 - What about vasopressin? n=409. No difference in the number of renal failure free days (12 vs 14); more patients in the vasopressin group did not require CRRT, but also these patients did not survive, so... Subsequently this study was rebranded to support the use of vasopressin as a noradrenaline sparing agent.
  • SPARK2017 - what if frusemide infusion? n=73 in Canada and Australia. No increased worsening of AKI (43.2% vs 7.1%); frusemide group ended up about 1L negative.

Trials in CRRT timing

  • IDEAL - 2010 - early (within about a month) vs late (7-8 months later) dialysis for outpatients with end-stage chronic renal failure? n=828 in Australia/NZ. No difference in mortality at 4 years follow up (37.6% vs 36.6%).  May as well wait until they really need it.
  • AKIKI2016 - CRRT immediately, or only when you really need it? n=620 in France. No difference in mortality (48.5%  vs. 49.7%). Bonus: half of the patients who waited never ended up needing any RRT.
  • ELAIN2016 - CRRT immediately, or only when you really need it? n=231 in Germany. Much better mortality in the early group (39.3% vs  54.7%) as well as many secondary outcomes, sustained at long-term follow up.
  • IDEAL-ICU2018 - CRRT immediately, or after 48hrs, in septic shock? n=864 in France. No difference in mortality (58% vs. 54%), less RRT dependence at 90 days (2% vs 3%)
  • STARRT-AKI2020 - CRRT immediately, or just wait and see? n=3021 all over the world. No difference in mortality (43.9% vs 43.7%) but less RRT dependence at 90 days (10.4% vs 6%) and slightly shorter ICU stay (9 vs 10 days).
  • AKIKI-2 - 2021 - if you just "wait and see" to start CRRT, what are you waiting for? n=278 in France.  Oliguria for > 72 hrs or urea over 40mmol/L is where you draw the line; waiting longer conferred no advantage (and had a HR of 1.65 for death at 60 days).

Contrast induced nephropathy studies

  • ACT - 2011 - N-acetylcysteine for prevention of CIN? n=2308 in Brazil. Didnt work: incidence of CIN was exactly the same (12.7%) in both groups. 
  • AMACING2017 - what if we pre-hydrate them with saline? n=660 in the Netherlands. No difference in incidence of CIN (2.7%  vs 2.6%).
  • PRESERVE2018 - why not N-Ac and bicarbonate to prevent contrast nephropathy? n=4993 all over the world. No difference in composite endpoint (4.4% vs 4.7%).

Trials in CRRT modality

  • Vinsonneau - 2006 - IHD vs CRRT in ICU? n=360 in France. No difference in mortality (32% vs 33%)
  • Ye et al - 2021 - meta-analysis of 30 trials (n=3,774) comparing CRRT to SLED. No difference in mortality; SLED may be slightly better for renal recovery and was associated with the shortest hospital stay.

Trials of different dose of dialysis

  • VA/NIH - 2008 - dialysis dose 35ml/kg/hr vs. 20ml/kg/hr. n=1124 in the US. No difference in mortality (53.6% vs 51.5%). 
  • RENAL2009 - dialysis dose 40ml/kg/hr vs. 25ml/kg/hr. n=1508 in Australia/NZ. Mortality exactly the same in both groups (44.7%). 
  • IVOIRE - 2013 - yes but what if we really dialyse the crap out of them? 70ml/kg/hr vs. 30ml/kg/hr. n=140 in Europe. No difference in mortality (37.9% vs. 40.8%).
  • HEROICS - 2015 - ok, but what if we only dialyse the crap out of severely shocked post-op cardiac surgical patients? 80ml/kg/hr × 48 hrs, vs. standard care. No difference in mortality (36% in both groups). Bonus: only 56% of the standard care group got dialysed.
  • HICORES - 2016 - or maybe in sepsis? 80ml/kg/hr vs. 40ml/kg/hr. n=212 in Korea. No difference in 90-day mortality (74.8% vs 78.1%).
  • Atan et al2018 - what if we use a high-porosity filter to remove those evil proinflammatory "middle molecules"? n=76 in Australia. Noradrenaline-free time was different between groups, just slightly outside the limits of significance (p = 0.052), and was worse with the high-porosity filter (32 vs 56 hrs).

Heparin vs citrate

  • Gattas et al2015 - which is better, heparin or citrate?  n=212 in Australia and NZ. Circuit life was much longer with citrate (39.2 hours vs 22.8 hours).
  • RICH - 2020 - just to really drive the point home, citrate is much better than heparin. n=596 in Germany. Circuit life better (47 vs 26 hrs), mortality same (51.3% vs 53.6%).

Guidelines in Critical Care Nephrology

Guidelines for dialysis

Guidelines for contrast-induced nephropathy

Guidelines for specific diseases


Mishra, Rajesh C., et al. "ISCCM Guidelines on Acute Kidney Injury and Renal Replacement Therapy." Indian Journal of Critical Care Medicine: Peer-reviewed, Official Publication of Indian Society of Critical Care Medicine 26.Suppl 2 (2022): S13.

Kodadek, Lisa, et al. "Rhabdomyolysis: an American association for the surgery of trauma critical care committee clinical consensus document.Trauma Surgery & Acute Care Open 7.1 (2022): e000836.

Bellomo, Rinaldo, 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." Critical care 8.4 (2004): R204.

Mehta, Ravindra L., et al. "Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury.Critical care 11.2 (2007): 1-8.

Ostermann, Marlies, et al. "Recommendations on acute kidney injury biomarkers from the acute disease quality initiative consensus conference: a consensus statement." JAMA network open 3.10 (2020): e2019209-e2019209.

Neri, Mauro, et al. "Nomenclature for renal replacement therapy in acute kidney injury: basic principles." Critical Care 20.1 (2016): 1-11.

Davenport, Matthew S., et al. "Use of intravenous iodinated contrast media in patients with kidney disease: consensus statements from the American College of Radiology and the National Kidney Foundation." Radiology 294.3 (2020): 660-668.

Orlacchio, Antonio, et al. "SIRM-SIN-AIOM: Appropriateness criteria for evaluation and prevention of renal damage in the patient undergoing contrast medium examinations—Consensus statements from Italian College of Radiology (SIRM), Italian College of Nephrology (SIN) and Italian Association of Medical Oncology (AIOM)." La radiologia medica 127.5 (2022): 534-542.

Latus, J., et al. "Contrast medium-induced acute kidney injury—consensus paper of the working group “Heart and Kidney” of the German Cardiac Society and the German Society of Nephrology." Der Internist 62 (2021): 111-120.


Vinsonneau, Christophe, et al. "Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial." The Lancet 368.9533 (2006): 379-385.

Cooper, Bruce A., et al. "A randomized, controlled trial of early versus late initiation of dialysis." New England Journal of Medicine 363.7 (2010): 609-619.

RENAL Replacement Therapy Study Investigators. "Intensity of continuous renal-replacement therapy in critically ill patients." New England Journal of Medicine 361.17 (2009): 1627-1638.

Gordon, Anthony C., et al. "Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic shock: the VANISH randomized clinical trial." Jama 316.5 (2016): 509-518.

Bellomo, Rinaldo, et al. "Low-dose dopamine in patients with early renal dysfunction: a placebo-controlled randomised trial. Australian and New Zealand Intensive Care Society (ANZICS) Clinical Trials Group." Lancet (London, England) 356.9248 (2000): 2139-2143.

Joannes-Boyau, Olivier, et al. "High-volume versus standard-volume haemofiltration for septic shock patients with acute kidney injury (IVOIRE study): a multicentre randomized controlled trial." Intensive care medicine 39 (2013): 1535-1546.

Combes, Alain, et al. "Early high-volume hemofiltration versus standard care for post–cardiac surgery shock. The HEROICS study." American journal of respiratory and critical care medicine 192.10 (2015): 1179-1190.

Gaudry, Stéphane, et al. "Initiation strategies for renal-replacement therapy in the intensive care unit." New England Journal of Medicine 375.2 (2016): 122-133.

Zarbock, Alexander, et al. "Effect 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 315.20 (2016): 2190-2199.

ACT Investigators*. "Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascular angiography: main results from the randomized Acetylcysteine for Contrast-induced nephropathy Trial (ACT)." Circulation 124.11 (2011): 1250-1259.

Nijssen, Estelle C., et al. "Prophylactic hydration to protect renal function from intravascular iodinated contrast material in patients at high risk of contrast-induced nephropathy (AMACING): a prospective, randomised, phase 3, controlled, open-label, non-inferiority trial." The Lancet 389.10076 (2017): 1312-1322.

Bagshaw, Sean M., et al. "The effect of low-dose furosemide in critically ill patients with early acute kidney injury: a pilot randomized blinded controlled trial (the SPARK study)." Journal of critical care 42 (2017): 138-146.

Atan, Rafidah, et al. "A double-blind randomized controlled trial of high cutoff versus standard hemofiltration in critically ill patients with acute kidney injury." Critical care medicine 46.10 (2018): e988-e994.

STARRT-AKI Investigators, et al. "Timing of initiation of renal-replacement therapy in acute kidney injury." The New England Journal of Medicine 383.3 (2020): 240-251.

Gaudry, Stéphane, et al. "Comparison of two delayed strategies for renal replacement therapy initiation for severe acute kidney injury (AKIKI 2): a multicentre, open-label, randomised, controlled trial." The Lancet 397.10281 (2021): 1293-1300.

VA/NIH Acute Renal Failure Trial Network. "Intensity of renal support in critically ill patients with acute kidney injury." New England Journal of Medicine 359.1 (2008): 7-20.

Zarbock, Alexander, et al. "Effect 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 324.16 (2020): 1629-1639.

Park, Jung Tak, et al. "High-dose versus conventional-dose continuous venovenous hemodiafiltration and patient and kidney survival and cytokine removal in sepsis-associated acute kidney injury: a randomized controlled trial." American Journal of Kidney Diseases 68.4 (2016): 599-608.

Ye, Zhikang, et al. "Comparing renal replacement therapy modalities in critically ill patients with acute kidney injury: a systematic review and network meta-analysis.Critical care explorations 3.5 (2021).