This has been asked about in Question 12 from the first paper of 2010 and Question 5 from the first paper of 2003.

Specifically, " Briefly outline the relationship between dose of dialysis and outcome"

The 2010 question makes reference to the following "relevant studies":

Since then, there have been a few more:

In summary:

Higher intensity renal replacement therapy does not reduce mortality rates or improve renal recovery among patients with AKI.

There is no evidence to recommend a dose in excess of 25ml/kg/hr.

It seems beyond a certain dose, renal replacement therapy removes as many useful molecules as it does toxins, and the benefit from escalating the dose deteriorates.

The evidence

In detail:

  • Ronco (2000):
    • 425 patients, single centre RCT
    • Compared 20ml/kg/hr, 35ml/kg/hr, 45ml/kg/hr
    • Observed survival at 15 days after cessation of dialysis
    • Survival in the three groups was 41%, 57%, and 58%
    • Conclusion: "We recommend that ultrafiltration...should reach at least 35 mL/kg/hr"
  • Bouman (2002)
    • 106 patients, two-centre RCT
    • Compared 19ml/kg/hr performed later with 20ml/kg/hr performed earlier, and 48ml/kg/hr performed earlier.
    • Observed survival at 28 days
    • For the three grous, 28 day survival was 75%, 68.8% and 74.3%
    • Conclusion: "survival ... and recovery of renal function were not improved using high ultrafiltrate volumes"
  • Saudan (2006)
    • 206 patients, single centre RCT
    • CVVH (25ml/kg/hr) compared with CVVHDF (42ml/kg/hr)
    • Observed survival at 28 and 90 days
    • Survival at 90 days was 34% for CVVH and 59% for CVVHDF
    • Conclusion: "increasing the dialysis dose especially for low molecular weight solutes confers a better survival"
  • Tolwani (2008)
    • 200 patients, single-centre RCT
    • 20ml/kg/hr compared with 35ml/kg/hr
    • Observed in-ICU survival or 30 day survival, whichever happened first
    • Survival for low-dose CRRT patients was 56%, vs. 49% for the high-dose group
    • Conclusion: "a difference in patient survival or renal recovery was not detected"
  • VA/NIH (2008)
    • 1124 patients, massive multicentre RCT
    • Compared 35ml/kg/hr and 20ml/kg/hr
    • Observed 60 day survival, as well as many other parameters
    • Survival for low-dose CRRT was 51.5% and 53.6% for high-dose group
    • Conclusion:"Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure"
  • RENAL study (2009)
    • 1508 patients, massive multicentre RCT
    • Compared 25ml/kg/hr to 40ml/kg/hr
    • Observed 90 day survival
    • Survival in both groups was the same: 44.7%
    • Conclusion: " treatment with higher-intensity continuous renal-replacement therapy did not reduce mortality at 90 days"

So, though small trials occasionally found a mortality benefit, large well-designed studies were unable to detect one. At this stage, the issue could be said to have been put to rest. Subsequent investigators have made attempts to find subtle non-survival benefits, or to investigate higher dialysis doses in patients with sepsis. More negative trials ensued.

  • Vesconi (2009)
    • 15,200 patients - prospective multicentre observational study.
    • Groups were separated by CRRT dose, according to whether they received less or more than 35ml/kg/hr.
    • Outcome measures included ICU mortality, ICU length of stay and duration of mechanical ventilation.
    • Higher CRRT dose patient mortality was 60.8% vs. 52.5% for the low-dose group
    • However, the higher CRRT dose was associated with shorter ICU stay and more rapid extubation among the survivors.
    • Conclusion: "no evidence for a survival benefit afforded by higher dose RRT"
  • Van Wert (2010) - a meta-analysis.
    • 12 trials met inclusion criteria (3999 patients).
    • Mortality was only one among numerous parameters assessed.
    • Meta-analyses found no effect of high-dose renal replacement therapy on mortality.
    • Conclusion: "High-dose renal replacement therapy in acute kidney injury does not improve patient survival or recovery of renal function overall or in important patient subgroups, including those with sepsis."
  • Zhang et al (2012)
    • 141 patients with sepsis and AKI; single centre RCT.
    • Compared super-high CRRT doses: 50ml/kg/hr vs 85ml/kg/hr.
    • Observed survival at 28, 60 and 90 days.
    • No difference between the groups was found at any timeframe.
    • Conclusion: "increasing the intensity of renal replacement therapy... had no effect on survival"
  • IVOIRE study (2013)
    • 140 patients with septic shock and AKI, multicentre RCT.
    • Compared 35ml/kg/hr vs 70ml/kg/hr (HVHF, High Volume HaemoFiltration).
    • Primary endpoint was 28 day mortality.
    • Mortality was 40.8% vs 37.9%.
    • Conclusion: "HVHF... cannot be recommended for treatment of septic shock complicated
      by AKI"
  • Clark (2014) - a meta-analysis specific for CRRT intensity in sepsis
    • 4 trials (470 patients) met inclusion criteria.
    • Comparion of standard intensity to high intensity (over 50ml/kg/hr)
    • 28 day mortality was the main outcome measure.
    • Pooled analysis did not show any meaningful difference.
    • Conclusion: "Insufficient evidence exists of a therapeutic benefit".
    • Furthermore, "further trials should focus on alternative extracorporeal therapies as an adjuvant therapy for septic AKI rather than HVHF". Essentially, the authors are saying that this is a dead end, and we should think about something else.

References

Ronco, Claudio, et al. "Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial." The Lancet 356.9223 (2000): 26-30.

Saudan, P., et al. "Adding a dialysis dose to continuous hemofiltration increases survival in patients with acute renal failure." Kidney international 70.7 (2006): 1312-1317.

Bouman, Catherine SC, et al. "Effects 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." Critical care medicine 30.10 (2002): 2205-2211.

Tolwani, Ashita J., et al. "Standard versus high-dose CVVHDF for ICU-related acute renal failure." Journal of the American Society of Nephrology 19.6 (2008): 1233-1238.

VA/NIH Acute Renal Failure Trial Network. "Intensity of renal support in critically ill patients with acute kidney injury." The New England journal of medicine359.1 (2008): 7.

Bellomo, R., et al. "Intensity of continuous renal-replacement therapy in critically ill patients." The New England journal of medicine 361.17 (2009): 1627-1638.

Jun, Min, et al. "Intensities of renal replacement therapy in acute kidney injury: a systematic review and meta-analysis." Clinical Journal of the American Society of Nephrology 5.6 (2010): 956-963.

Zhang, Ping, et al. "Effect of the intensity of continuous renal replacement therapy in patients with sepsis and acute kidney injury: a single-center randomized clinical trial." Nephrology Dialysis Transplantation 27.3 (2012): 967-973.

Vesconi, Sergio, et al. "Delivered dose of renal replacement therapy and mortality in critically ill patients with acute kidney injury." Crit Care 13.2 (2009): R57.

Van Wert, Ryan, et al. "High-dose renal replacement therapy for acute kidney injury: systematic review and meta-analysis." Critical care medicine 38.5 (2010): 1360-1369.

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 39.9 (2013): 1535-1546.

Clark, Edward, et al. "High-volume hemofiltration for septic acute kidney injury: a systematic review and meta-analysis." Critical Care 18.1 (2014): R7.

Clark, Edward G., and Sean M. Bagshaw. "Unnecessary Renal Replacement Therapy for Acute Kidney Injury is Harmful for Renal Recovery." Seminars in dialysis. Vol. 28. No. 1. 2015.

Zhang, Ping, et al. "Effect of the intensity of continuous renal replacement therapy in patients with sepsis and acute kidney injury: a single-center randomized clinical trial." Nephrology Dialysis Transplantation 27.3 (2012): 967-973.