Renal Literature Summaries

OVERVIEW

Key issues:

• Renal-dose dopamine
• Diuretics and acute renal failure
• IHD versus CRRT
• Dose of RRT
• Timing of RRT
• Fluid balance
• Contrast nephropathy

“RENAL-DOSE DOPAMINE”

Bellomo R, Chapman M, Finfer S, Hickling K, Myburgh J. 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. 2000 Dec 23-30;356(9248):2139-43. PubMed PMID: 11191541

• MC RCT, 23 ICUs, ANZICS
• n = 328
• patients with SIRS + early acute renal dysfunction (oliguria or increase in serum creatinine concentration)
• continuous low dose dopamine infusion (2mcg/kg/min) vs placebo
  -> no difference in peak serum creatinine (primary outcome)
  -> no difference in RRT
  -> no difference in ICU or hospital LOS

DIURETICS AND ACUTE RENAL FAILURE

Bagshaw SM, Delaney A, Haase M, Ghali WA, Bellomo R. Loop diuretics in the management of acute renal failure: a systematic review and meta-analysis. Crit Care Resusc. 2007 Mar;9(1):60-8. Review. PubMed PMID: 17352669.

• Meta-analysis
• 5 small RCTs, n=555 (only 2 trials in critically ill patients)
• Loop diuretics associated with
  -> no difference in  mortality
  -> no difference in rate of independence from RRT
  -> shorter duration of RRT (1.4 days; 95% CI, 0.2 to 2.3 days; P=0.02)
  -> increased urine output (OR, 2.6; 95% CI, 1.4-4.9; P=0.004)
• Need a high quality RCT!

Ho KM, Sheridan DJ. Meta-analysis of frusemide to prevent or treat acute renal failure. BMJ. 2006 Aug 26;333(7565):420. Epub 2006 Jul 21. PMC1553510.

• Meta-analysis
• 9 small RCTs, n=849 mixed patients with, or at risk, of AKI
• Frusemide associated with
  -> no difference in hospital mortality
  -> no difference in risk of RRT or number of dialysis sessions
  -> no difference in duration of oliguria <500mL/d
  -> increased risk of temporary deafness and tinnitus (RR 3.97, 95% CI 1.00 to 15.78)
• Still need a high quality RCT!

IHD VERSUS CRRT

Pannu N, Klarenbach S, Wiebe N, Manns B, Tonelli M; Alberta Kidney Disease Network. Renal replacement therapy in patients with acute renal failure: a systematic review. JAMA. 2008 Feb 20;299(7):793-805. doi: 10.1001/jama.299.7.793. PMID: 18285591.

• meta-analysis
• 30 RCTs and 8 prospective cohort studies
• No difference in:
  ->  all-cause mortality
  ->  requirement for chronic dialysis treatment in survivors
• For CRRT patients risk of death was lower at doses of 35 mL/kg/ h compared with 20 mL/kg/h (RR 0.74; 95% CI, 0.63-0.88)
  — this finding not supported by the subsequent RENAL trial (see below)

To add: http://www.nature.com/ki/journal/v70/n7/pdf/5001705a.pdf

DOSE OF RRT

Eknoyan G, Beck GJ, Cheung AK, Daugirdas JT, Greene T, Kusek JW, Allon M, Bailey J, Delmez JA, Depner TA, Dwyer JT, Levey AS, Levin NW, Milford E, Ornt DB, Rocco MV, Schulman G, Schwab SJ, Teehan BP, Toto R; Hemodialysis (HEMO) Study Group. Effect of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med. 2002 Dec 19;347(25):2010-9. PubMed PMID: 12490682.

• RCT
• low vs high flux dialysis
• also looked at dose for patients having thrice weekly treatments
  -> no difference in mortality
  -> increase in dose of dialysis does not appear to make a difference to outcomes
  -> this may not apply in continuous RRT

Ronco C, Bellomo R, Homel P, Brendolan A, Dan M, Piccinni P, La Greca G. Effects of different doses in continuous veno-venous haemofiltration on outcomes  of acute renal failure: a prospective randomised trial. Lancet. 2000 Jul 1;356(9223):26-30. PubMed PMID: 10892761.

• RCT
• n = 425
• not blinded
• inclusion criteria: ICU patient with oliguric ARF using CVVH
• ultrafiltration rates of: 20 VS 35 VS 45mL/kg/hr
• end point was mortality at 15 days
  -> 35 and 45mL/kg/hr are more effective than 20mL/kg/hr
• Commentary:
  weaknesses = 20mL/kg/hr group had a high proportion of old patients with sepsis

Vinsonneau C, Camus C, Combes A, Costa de Beauregard MA, Klouche K, Boulain T, Pallot JL, Chiche JD, Taupin P, Landais P, Dhainaut JF; Hemodiafe Study Group. Continuous venovenous haemodiafiltration versus intermittent haemodialysis for acute renal failure in patients with multiple-organ dysfunction syndrome: a multicentre randomised trial. Lancet. 2006 Jul 29;368(9533):379-85. PubMed PMID:  16876666.

• RCT
• n = 360
• patients with ARF and MODS
• CVVHDF (mean blood flow = 146mL/min) VS IHD (5 hours with mean blood flow 278mL/min)
  -> there was equivalent efficacy between groups (fluid removal and urea concentration)
  -> IHD was not associated with increased hypotension
  -> CVVHDF did cause more hypothermia
  -> no difference in duration of renal support

VA/NIH Acute Renal Failure Trial Network, Palevsky PM, Zhang JH, O’Connor TZ,  Chertow GM, Crowley ST, Choudhury D, Finkel K, Kellum JA, Paganini E, Schein RM,  Smith MW, Swanson KM, Thompson BT, Vijayan A, Watnick S, Star RA, Peduzzi P. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008 Jul 3;359(1):7-20. doi: 10.1056/NEJMoa0802639. Epub 2008 May 20. Erratum in: N Engl J Med. 2009 Dec 10;361(24):2391. PubMed PMID: 18492867; PubMed Central PMCID: PMC2574780.

• MRCT
• included both CRRT and IHD
• intensive 35mL/kg/hr or 6 times/week vs less intensive 20mL/kg/hr or 3 times per week
• n = 1124
  -> no change in 60d mortality
  -> no acceleration in renal recovery
  -> no change in non-renal organ failure

RENAL Replacement Therapy Study Investigators, Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, McArthur C, McGuinness S, Myburgh J, Norton R, Scheinkestel C, Su S. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009 Oct 22;361(17):1627-38. doi: 10.1056/NEJMoa0902413. PubMed PMID: 19846848. [Free Full Text]

• MC RCT
• n = 1508
• 25mL/kg/h vs 40mL/kg/h of effluent flow
  -> showed there is no benefit in effluent flow rates of 25 vs 40mL/kg/hr
  -> no difference in 90 day mortality
  -> no difference in patient receiving CRRT at 28 and 90 days
  -> more hypophosphatemia and more filters used in the high intensity arm
  -> lower urea and creatine concentrations in high intensity arm
• Commentary:
  — what was actually delivered was 22 mL/kg/h vs 33 mL/kg/h (filters crashed more often in high intensity arm)

FLUID BALANCE

Payen D, de Pont AC, Sakr Y, Spies C, Reinhart K, Vincent JL; Sepsis Occurrence in Acutely Ill Patients (SOAP) Investigators. A positive fluid balance is associated with a worse outcome in patients with acute renal failure. Crit Care. 2008;12(3):R74. doi: 10.1186/cc6916. Epub 2008 Jun 4. PubMed PMID: 18533029; PubMed Central PMCID: PMC2481469.

• MC observational cohort study; 198 ICUs from 24 European countries
• n= 3,147
• 1,120 (36%) had ARF at some point during their ICU stay
• Findings:
  -> Oliguric patients and RRT patientshad higher 60dmortality rates than patients with neither (41%, 52% and 32% respectively; P<0.001)
  -> positive fluid balance was one of the independent risk factors for death
• Commentary:
  — does not establish causation

To add: http://cjasn.asnjournals.org/content/6/5/966

CONTRAST NEPHROPATHY

Marenzi, G. et al (2003) “The prevention of radiocontrast-agent induced nephropathy by hemofiltration” N Engl J Med 349:1333-1340

• RCT
• n = 114
• inclusion criteria: chronic renal failure undergoing coronary angiograms
• normal saline hydration VS haemofiltration (pre and post procedure)
  -> patients do better if have haemofiltration
  -> reduction in mortality (in hospital and at 1 year)

Marenzi, G. et al (2006) – Am J Med 119:155-162

• pre and post exposure haemofiltration VS only post exposure haemofiltration
  -> pre and post exposure group did better
  -> elective planned haemofiltration should be considered in high risk patients undergoing large contrast exposure

Merten, G.J., et al (2004) “Prevention of contrast-induced nephropathy with sodium bicarbonate: a randomised controlled trial” JAMA 291:2328-2334

• RCT
• single centre
• n = 119
• pre and post infusions of normal saline VS sodium bicarbonate
  -> significant reduction in nephropathy with bicarbonate (25%)

Solomon, R. et al (1994) “Effects of saline, mannitol and furosemide to prevent acute decreases in renal function by radiocontrast agents” N Engl J Med 331:1416-1420

• RCT
• n = 78
• CRF patients undergoing coronary angiography
• 0.45% saline VS 0.45% saline + mannitol VS 0.45% saline + frusemide
• outcome in terms of increase in creatinine
  -> best = saline alone
  -> worst = saline + frusemide

Tepel, M. et al “Prevention of radiographic-contrast agent induced reductions in renal function by acetylcysteine” N Engl J Med 343:210-212

• RCT
• n = 83
• chronic renal insufficiency + N-acetylcysteine and 0.45% saline before and after contrast VS fluid alone
  -> significant reduction in creatinine in N-acetylcysteine group
  -> further studies have not been so positive
  -> on systematic review there appears a trend to benefit