Udy et al, 2014: Augmented Renal Clearance

Journal Club 011

Author: Rohit Samuel
Reviewer: Chris Nickson

Udy AA, Baptista JP, Lim NL, Joynt GM, Jarrett P, Wockner L, Boots RJ, Lipman J. Augmented renal clearance in the ICU: results of a multicenter observational study of renal function in critically ill patients with normal plasma creatinine
concentrations*. Crit Care Med. 2014 Mar;42(3):520-7. doi:10.1097/CCM.0000000000000029. PubMed PMID: 24201175.

THE QUESTION

  • What is the prevalence and natural history of augmented renal clearance (ARC) in intensive care patients?

STUDY DESIGN

TYPE OF STUDY

  • Multi-centre, prospective cohort study

POPULATION

  • n = 281 patients were recruited, out of 932 patients admitted to the study centres during the study period
  • the study centers were four tertiary-level, university-affiliated ICUs in Australia, Singapore, Hong Kong and Portugal

Inclusion criteria

  • Expected ICU length of stay >24 hours
  • No evidence of absolute renal impairment (admission plasma creatinine <120 μmol/L)
  • No history or prior renal replacement therapy
  • No history of chronic kidney disease

Exclusion criteria

  • Invasive haemodynamic monitoring or indwelling urinary catheter not used in management
  • Age <18 years
  • Pregnancy
  • Rhabdomyolysis suspected clinically or biochemically (CK >5000 IU/L)
  • ‘Risk’ category or greater of the RIFLE criteria for acute kidney injury (AKI)

INTERVENTIONS/ COMPARISONS

  • Creatinine clearance (CRCL) was assessed through eight hour urine collection from midnight to 0800 and compared with plasma creatinine
    • ARC was defined as an eight hour CRCL ⋝ 130 mL/min/1.73m2
  • Demographic data, admission diagnosis, illness severity, use of vasopressors/inotropes/antibiotics, ICU and hospital length of stay were recorded prospectively
  • Groups defined as ARC and non-ARC were compared

OUTCOMES

Prevalence

  • 65.1% of patients had evidence of ARC on at least one occasion during the first seven study days
  • The majority of new cases occurred on day 2 in ICU
  • Of patients manifesting ARC, 74% did so on 50% or more of their CRCL measurements

Characteristics

  • Patient demonstrating ARC were more likely to be:
    • Young (49.1 vs 64.4, p<0.001)
    • Male (p=0.036)
    • Multitrauma victims (p=0.014)
    • On mechanical ventilation (p<0.001)
  • Median length of ICU stay was increased in ARC patients (5 vs 3, p<0.001)
  • There was no difference in ICU mortality (p=0.465)
  • Sustained increases in CRCL mainly occur during trauma and surgical emergency admissions

Natural history

  • Statistically significant rise in CRCL seen in overall cohort on study day 2 in ICU (p=0.001)
  • Mixed effects modelling shows that this elevation is sustained up to the end of study period at day 7 of ICU

The presence of ARC on day 1 of ICU stay is a significant predictor of CRCL until day 7 (p=0.019)

COMMENTARY AND CRITICISMS

Commentary

  • ARC appears to be common in ICU patients, at least in certain groups, and it may be important to dosing strategies of renally excreted medications
  • Other research has demonstrated the contribution of renal function to altered plasma levels of beta-lactams (Udy et al, 2010), glycopeptides (del Mar Fernandez de Gatta Garcia et al, 2007) and aminoglycosides (Rea et al, 2008)
  • The study emphasises the significance of renal function as opposed to solely focussing on renal injury

Limitations

  • Generalizability is a concern given the selected study cohort:
    • patients with abnormal renal function on admission were excluded
    • only 39.5% of patients were on vasopressors
    • patient population was relatively young
    • patient population had relatively low APACHE II and modified SOFA scores
  • Only 30% of ICU admissions in the study period were eligible for inclusion
  • CLCR is not a gold standard as a marker for renal function, however the authors suggest that this method provided the best balance between feasibility and accuracy

FINAL WORDS

  • Augmented renal clearance (ARC) was a common finding in this intensive care patient population.
  • ARC is more common in young, ventilated males admitted for multitrauma; which potentially identifies an at risk group that requires specific monitoring.
  • It may be important to consider renal function, as opposed to the absence of renal injury, when dosing renally excreted medications.

References and Links

  • del Mar Fernández de Gatta Garcia M, Revilla N, Calvo MV, Domínguez-Gil A, Sánchez Navarro A. Pharmacokinetic/pharmacodynamic analysis of vancomycin in ICU patients. Intensive Care Med. 2007 Feb;33(2):279-85. Epub 2006 Dec 13. PubMed PMID: 17165021.
  • Rea RS, Capitano B, Bies R, Bigos KL, Smith R, Lee H. Suboptimal aminoglycoside dosing in critically ill patients. Ther Drug Monit. 2008 Dec;30(6):674-81. doi: 10.1097/FTD.0b013e31818b6b2f. PubMed PMID: 19057371.
  • Udy AA, Roberts JA, Boots RJ, Paterson DL, Lipman J. Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet. 2010;49(1):1-16. doi: 10.2165/11318140-000000000-00000. Review. PubMed PMID: 20000886.

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