Abstract
Background:
Acute kidney injury (AKI) is associated with significant morbidity and mortality, particularly in unstable critically ill patients. In this context, serum creatinine concentration is an imperfect tool for estimating glomerular filtration rate (GFR), an index of renal function. The objective of this pilot study was to evaluate the feasibility of measuring iohexol clearance for GFR assessment in critically ill patients with acute circulatory failure at intensive care unit (ICU) admission.
Methods:
ICU patients were prospectively included within 12 h of acute circulatory failure; a non-toxic dose of iohexol (5 mL) was infused intravenously and iohexol plasma concentration decrease was measured over 24 h. Urinary iohexol concentration was measured in urine samples collected four times, every 6 h for 24 h. The Kidney Disease Improving Global Outcome score, measuring AKI, was calculated each day.
Results:
Among 18 patients with acute circulatory failure, AKI developed in 15; 14 showed decreased serum creatinine concentration during the first 24 h even though 10 presented AKI. The absolute variation in serum creatinine concentration was correlated with fluid balance over 24 h. Median [min; max] plasma clearance of iohexol was 39.4 mL/min [6.1; 154.0] and iohexol urinary clearance 32.8 mL/min [0.8–170.4]. The correlation between plasma and urinary clearance was ρ=0.97, p<0.0001.
Conclusions:
GFR may be estimated by plasma iohexol clearance in unstable critically ill patients. This method is reliable, correlates very well with urinary iohexol clearance and does not depend on input/output fluid balance and fluid infusion, as compared with serum creatinine concentration.
Acknowledgments:
We thank the study nurses of the réanimation polyvalente department of Tours university hospital center: Christine Mabilat, Véronique Siméon-Vieules and Aurélie Aubrey. We also express our gratitude to Marie Leclerc, clinical research assistant, and to the biochemistry technicians who performed the iohexol measurements. We thank Laura Smales for the English editing.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: The authors acknowledge receipt of a grant “Bourse de Recherche Clinique” from the French society of intensive care “Société de Réanimation de Langue Française” (www.srlf.org) for the conduct of this study.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Hoste EA, Clermont G, Kersten A, Venkataraman R, Angus DC, De Bacquer D, et al. RIFLE criteria for acute kidney injury are associated with hospital mortality in critically ill patients: a cohort analysis. Crit Care 2006;10:R73.10.1186/cc4915Search in Google Scholar PubMed PubMed Central
2. Kidney Disease: Improving Global Outcomes (KDIGO). Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int 2012;2:1–138.Search in Google Scholar
3. Plataki M, Kashani K, Cabello-Garza J, Maldonado F, Kashyap R, Kor DJ, et al. Predictors of acute kidney injury in septic shock patients: an observational cohort study. Clin J Am Soc Nephrol 2011;6:1744–51.10.2215/CJN.05480610Search in Google Scholar PubMed
4. Kiers HD, Griesdale DE, Litchfield A, Reynolds S, Gibney RT, Chittock D, et al. Effect of early achievement of physiologic resuscitation goals in septic patients admitted from the ward on the kidneys. J Crit Care 2010;25:563–9.10.1016/j.jcrc.2010.04.012Search in Google Scholar PubMed
5. Badin J, Boulain T, Ehrmann S, Skarzynski M, Bretagnol A, Buret J, et al. Relation between mean arterial pressure and renal function in the early phase of shock: a prospective, explorative cohort study. Crit Care 2011;15:R135.10.1186/cc10253Search in Google Scholar PubMed PubMed Central
6. Bragadottir G, Redfors B, Ricksten S-E. Assessing glomerular filtration rate (GFR) in critically ill patients with acute kidney injury – true GFR versus urinary creatinine clearance and estimating equations. Crit Care 2013;17:R108.10.1186/cc12777Search in Google Scholar PubMed PubMed Central
7. Erley CM, Bader BD, Berger ED, Vochazer A, Jorzik JJ, Dietz K, et al. Plasma clearance of iodine contrast media as a measure of glomerular filtration rate in critically ill patients. Crit Care Med 2001;29:1544–50.10.1097/00003246-200108000-00008Search in Google Scholar PubMed
8. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron 1976;16:31–41.10.1159/000180580Search in Google Scholar PubMed
9. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 1999;130:461–70.10.7326/0003-4819-130-6-199903160-00002Search in Google Scholar PubMed
10. Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF, Feldman HI, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604–12.10.7326/0003-4819-150-9-200905050-00006Search in Google Scholar PubMed PubMed Central
11. Pickering JW, Ralib AM, Endre ZH. Combining creatinine and volume kinetics identifies missed cases of acute kidney injury following cardiac arrest. Crit Care 2013;17:R7.10.1186/cc11931Search in Google Scholar PubMed PubMed Central
12. Macedo E, Bouchard J, Soroko SH, Chertow GM, Himmelfarb J, Ikizler TA, et al. Fluid accumulation, recognition and staging of acute kidney injury in critically-ill patients. Crit Care 2010;14:R82.10.1186/cc9004Search in Google Scholar
13. Andreev E, Koopman M, Arisz L. A rise in plasma creatinine that is not a sign of renal failure: which drugs can be responsible? J Intern Med 1999;246:247–52.10.1046/j.1365-2796.1999.00515.xSearch in Google Scholar
14. Leblanc M, Garred LJ, Cardinal J, Pichette V, Nolin L, Ouimet D, et al. Catabolism in critical illness: estimation from urea nitrogen appearance and creatinine production during continuous renal replacement therapy. Am J Kidney Dis 1998;32:444–53.10.1053/ajkd.1998.v32.pm9740161Search in Google Scholar
15. Nejat M, Pickering JW, Walker RJ, Endre ZH. Rapid detection of acute kidney injury by plasma cystatin C in the intensive care unit. Nephrol Dial Transplant 2010;25:3283–9.10.1093/ndt/gfq176Search in Google Scholar
16. Lipcsey M, Furebring M, Rubertsson S, Larsson A. Significant differences when using creatinine, modification of diet in renal disease, or cystatin C for estimating glomerular filtration rate in ICU patients. Ups J Med Sci 2011;116:39–46.10.3109/03009734.2010.526724Search in Google Scholar
17. Delanaye P, Cavalier E, Morel J, Mehdi M, Maillard N, Claisse G, et al. Detection of decreased glomerular filtration rate in intensive care units: serum cystatin C versus serum creatinine. BMC Nephrol 2014;15:9.10.1186/1471-2369-15-9Search in Google Scholar
18. Brondén B, Eyjolfsson A, Blomquist S, Dardashti A, Ederoth P, Bjursten H. Evaluation of cystatin C with iohexol clearance in cardiac surgery. Acta Anaesthesiol Scand 2011;55:196–202.10.1111/j.1399-6576.2010.02361.xSearch in Google Scholar
19. Mårtensson J, Martling C-R, Oldner A, Bell M. Impact of sepsis on levels of plasma cystatin C in AKI and non-AKI patients. Nephrol Dial Transplant 2012;27:576–81.10.1093/ndt/gfr358Search in Google Scholar
20. Price M. Comparison of creatinine clearance to inulin clearance in the determination of glomerular filtration rate. J Urol 1972;107:339–40.10.1016/S0022-5347(17)61021-8Search in Google Scholar
21. Bröchner-Mortensen J. A simple method for the determination of glomerular filtration rate. Scand J Clin Lab Invest 1972;30:271–4.10.3109/00365517209084290Search in Google Scholar PubMed
22. Brändström E, Grzegorczyk A, Jacobsson L, Friberg P, Lindahl A, Aurell M. GFR measurement with iohexol and 51Cr-EDTA. A comparison of the two favoured GFR markers in Europe. Nephrol Dial Transplant 1998;13:1176–82.10.1093/ndt/13.5.1176Search in Google Scholar PubMed
23. Dixon JJ, Lane K, Dalton RN, Turner C, Grounds RM, MacPhee IA, et al. Validation of a continuous infusion of low dose Iohexol to measure glomerular filtration rate: randomised clinical trial. J Transl Med 2015;13:58.10.1186/s12967-015-0414-3Search in Google Scholar PubMed PubMed Central
24. Benz-de Bretagne I, Le Guellec C, Halimi JM, Gatault P, Barbet C, Alnajjar A, et al. New sampling strategy using a Bayesian approach to assess iohexol clearance in kidney transplant recipients. Ther Drug Monit 2012;34:289–97.10.1097/FTD.0b013e31824a6534Search in Google Scholar PubMed
25. Castagnet S, Blasco H, Vourc’h P, Benz-De-Bretagne I, Veyrat-Durebex C, Barbet C, et al. Routine determination of GFR in renal transplant recipients by HPLC quantification of plasma iohexol concentrations and comparison with estimated GFR. J Clin Lab Anal 2012;26:376–83.10.1002/jcla.21537Search in Google Scholar PubMed PubMed Central
26. Cavalier E, Rozet E, Dubois N, Charlier C, Hubert P, Chapelle J-P, et al. Performance of iohexol determination in serum and urine by HPLC: validation, risk and uncertainty assessment. Clin Chim Acta 2008;396:80–5.10.1016/j.cca.2008.07.011Search in Google Scholar PubMed
27. Greenblatt DJ, Ransil BJ, Harmatz JS, Smith TW, Duhme DW, Koch-Weser J. Variability of 24-hour urinary creatinine excretion by normal subjects. J Clin Pharmacol 1976;16:321–8.10.1002/j.1552-4604.1976.tb01527.xSearch in Google Scholar PubMed
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