Evidence in Intensive Care - Renal

Sysematic reviews and meta-analyses in blue
Other high impact trials in red

Atrial Natiuretic Peptide
Cochrane review 2009

ANP causes afferent vasodilatation, inhibits PG release and the rennin-angiotensin system and exerts a natiuretic effect which may minimise obstruction. Improves GFR in animal studies.
Intervention was ANP given before or immediately after development of AKI.
No mortality difference.
Lower RRT in low dose ANP
No difference in contrast nephropathy
Studies not good enough (heterogenicity) to influence practice.
Need decent study of ANP preventing AKI eg in cardiac surgery patients.


Sodium bicarbonate to prevent contrast induced nephropathy (CIN)
Neprol Dial Transplant 2010 25:747-758

rd most common cause of hospital aquired AKI (11% of cases).
Most common regimen was 3ml/kg before and 1ml/kg of 1.26% NaHCO3.
Small risk reduction in bicarb group.
Greatest benefit in coronary surgery and CRF.
Mortality and need for RRT not affected.
The individual studies were of low quality so not good enough evidence to change practice. Ensuring adequate hydration may be more important than the composition of the fluid.

RRT for prevention of contrast induced AKI: a meta-analysis.
Song et al Am J Nephrol 2010

No benefit of prophylactic RRT to prevent CI-AKI.
Contrast causes renal ischaemia and direct tubular toxicity. Defined as increase in creat of 44 or >25% baseline within 72h of contrast.

Citrate for RRT

Regional citrate versus heparin anticoagulation for continuous renal replacement therapy: a meta-analysis of randomized controlled trials.
Wu M-Y, et al. Am J Kidney Dis 2012;

No difference in circuit survival time.
Decreased risk of bleeding with citrate.
No difference in alkalosis.
More hypocalcaemia but no adverse events related to this.

Efficacy and safety of regional citrate anticoagulation in critically ill patients undergoing continuous renal replacement therapy.
Zhang Z et al. Intensive Care Med 2011

As effective and reduced risk of bleeding with citrate.
Longer circuit survival.

Conclusion of above 2 studies:
Without major bleeding risk or significant liver disease citrate is safe and causes less bleeding. Circuit survival is at least as good or better with citrate.

Regional citrate vs heparin
Nephrol Dial Trans 2011;26:232-239

No mortality difference.
Less HIT.
Less bleeding episodes.
Longer filter patency.
Hypo and hypercalcaemia both more common with citrate.

What we already know about citrate:
Can use a fixed dose in relation to blood flow or measure post filter ionised calcium and adjust dose by protocol.
Now (2011) 5 trials of citrate including this one.
3 show longer circuit survival.
4 show less bleeding.
2 show reduced transfusion requirements
1 single centre RCT showed a 90 day mortality benefit (Van Straaten) - the above RCT was multicentre.
Dutch multicentre RCT currently underway.

Timing of RRT

Only 2 randomised controlled trials with conflicting results - Bouman et al. Effects of early high-volume continuous veno-venous hemofiltration on survival and recovery of renal function in intensive care patients with acute renal failure: a prospective, randomized trial. Crit Care Med 2002;30:2205-2211. Sugahara et al. Early start on continuous hemodialysis therapy improves survival rate in patients with acute renal failure following coronary bypass surgery. Hemodial Int 2004;8:320-325).

Clinical factors associated with initiation of renal replacement therapy in critically ill patients with acute kidney injury – a prospective multicenter observational study.
Bagshaw et al. J Crit Care 2011
Clinical practice of RRT is very variable and no single parameter triggers its initiation. Optimal timing is unknown.
Mortality with RRT is about 50%.

RRT in patients with ARF. (systematic review)
JAMA 2008;299:793-805

No differences in timing of starting it
No difference in intermittent or continuous
Cellulose membranes (rather than biocompatible membranes worse)
Benefit of high dose CRRT (35mls/kg/h) (did not include RENAL trial)

Dose of RRT

Intensity of RRT - RENAL investigators.
NEJM 2009;361:1627-1638

1508 critically ill patients with AKI 40ml/kg/h vs 25
Actual doses 33 vs 22
Only difference was more hypophosphataemia in intensive group

Delivered dose of RRT in critically ill patients with AKI
Vesconi et al. Crit Care 2009;13:R57

553 patients. Observational. Looked at results and compared them with what dose RRT they had received. Intensive = >35mls/kg/h
No difference in mortality.
Shorter length of ventilation and stay in intensive group.
Patients in all trials get a significantly lower dose than that prescribed.

Mode of RRT

Intermittent vs continuous RRT
Cochrane Review 2007

No difference in

  • Mortality
  • Need for dialysis after discharge
  • LOS
  • Haemodynamic stability, occurrence of hypotension or escalation of vasopressors
CRRT had higher MAP
Choice of modality should be tailored to individual patient and unit.
May be better to use CRRT in haemodynamically unstable patients but can still do intermittent safely.

Nephrol Dial Trans 2008;24:512-518

No difference in outcome.

RRT in patients with ARF. (systematic review)
JAMA 2008;299:793-805

No differences in timing of starting it
No difference in intermittent or continuous
Cellulose membranes (rather than biocompatible membranes worse)
Benefit of high dose CRRT (35mls/kg/h) (did not include RENAL trial)


Association between a chloride-liberal vs. chloride- restrictive intravenous fluid administration strategy and kidney injury in critically ill adults.

Yunos NM et al.
JAMA 2012; 308: 1566–1572.
Chloride restricive fluid strategy associated with significant decrease in AKI and RRT. Also less hypernatraemia and acidosis.
No long term outcome difference.

AKI may be related to chloride induced vasoconstriction and a decrease in GFR mediated by higher distal chloride delivery.
Agrees with another study (Shaw
et al. Major complications, mortality, and resource utilization after open abdominal surgery: 0.9% saline compared to Plasma-Lyte. Ann Surg 2012;255:821-829) which shoed that 0.9% saline on day of surgery associated with post op complications including AKI.

Observational fluid balance study on the RENAL trial data
CCM 2012;40:1753-1760

Positive fluid balance at initiation of RRT is associated with an increased risk of death (than neutral or negative) - adjusted for illness severity.
Positive fluid balance associated with increased RRT and ICU and hospital LOS.
Risk increased with amount of fluid overload.
Agrees with other studies:
Crit Care 2008 - +ve balance and oliguria with AKI increased mortality.
Kidney Int 2009 - significant survival difference in patients with, compared to without, fluid overload at initiation of RRT. Duration of fluid overload while on RRT correlated with risk. Mortality was lower when fluid overload was corrected with RRT than with those who who finished RRT with >10% fluid accumulation.
ARDSnet - trend to higher mortality in patients with positive fluid balance with more need for RRT.

What should we do?
Discontinue fluids (salty ones) as soon as not fluid responsive, aim for neutral or negative balance as soon as haemodynamics allow, reassess on a regular basis.

Glomerular hyperfiltration in critically ill patients
Anaesth Intensive Care 2008;36:674-680

Relatively common (post op and trauma) and means increased drug elimination with need for bigger doses.
Can be measured by creatinine clearance.

Effects of donor pre-treatment with low dose dopamine on graft function after kidney transplant
Schnuelle. JAMA 2009;302:1067-1075

Dopamine group required less dialysis
No difference in acute rejection or graft survival at 3 years
Not good enough evidence to start using dopamine for brain dead donors

The fallacy of the BUN: creatinine ratio in critically ill patients
Authors: Rachoin et al. Nephrol Dial Transplant 2012;27:2248–2254.

Urea to creatinine ration has been used to distinguish between pre renal and intrinsic AKI (in pre-renal increased ADH causes reabsorption of water and urea meaning serum urea increases more than creatinine).
This study shows it is not a useful test in critically ill patients (protein catabolism, steroids, GI bleeding) and does not imply a benign course.

Ultrafiltration in decompensated heart failure with cardiorenal syndrome.
Bart BA et al. N Engl J Med 2012;367:2296–2304.

Diuretics (frusemide infusion with oral metolazone added if necessary plus dobutamine for hypotension and ventricular failure) better than filtration for decompensated heart failure and worsening renal function.
Same weight loss, lower creat in diuretic group, more adverse events in RRT, no mortality difference.