Augmented Renal Clearance. An Unnoticed Relevant Event

Augmented renal clearance (ARC) is a phenomenon that can lead to a therapeutic failure of those drugs of renal clearance. The purpose of the study was to ascertain the prevalence of ARC in the critically ill patient, to study the glomerular filtration rate (GFR) throughout the follow-up and analyze the concordance between the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) estimation formula and measured GFR. Observational, prospective, multicenter study. ARC was defined as a creatinine clearance greater than 130 ml/min/1.73 m. Eighteen hospitals were recruited. GFR measurements carried out twice weekly during a 2-month follow-up period. A total of 561 patients were included. ARC was found to have a non-negligible prevalence of 30%. More even, up to 10.7% already had ARC at intensive care unit (ICU) admission. No specific pattern of GFR was found during the follow-up. Patients in the ARC group were younger 56.5 (53.5-58.5) versus 66 (63.5-68.5) years than in the non-ARC group, < 0.001. ICU mortality was lower in the ARC group, 6.9% versus 14.5%, = 0.003. There was no concordance between the estimation of GFR by the CKD-EPI formula and GFR calculated from the 4-h urine. ARC is found in up to 30% of ICU patients, so renal removal drugs could be under dosed by up to 30%. And ARC is already detected on admission in 10%. It is a dynamic phenomenon without an established pattern that usually occurs in younger patients that can last for several weeks. And the CKD-EPI formula does not work to estimate the real creatinine clearance of these patients.

Citing Articles

Development and validation of the prediction score for augmented renal clearance in critically Ill Japanese adults.

Mikami R, Imai S, Hayakawa M, Kashiwagi H, Sato Y, Nashimoto S J Pharm Health Care Sci. 2024; 10(1):69.

PMID: 39506834 PMC: 11542376. DOI: 10.1186/s40780-024-00394-2.

Clinical implications of augmented renal clearance after unrelated single cord blood transplantation in adults.

Konuma T, Takano K, Monna-Oiwa M, Isobe M, Kato S, Takahashi S Int J Hematol. 2023; 118(6):718-725.

PMID: 37851311 PMC: 10673748. DOI: 10.1007/s12185-023-03669-w.

Onset timing and duration of augmented renal clearance in a mixed intensive care unit.

Mikami R, Hayakawa M, Imai S, Sugawara M, Takekuma Y J Intensive Care. 2023; 11(1):13.

PMID: 36959656 PMC: 10035487. DOI: 10.1186/s40560-023-00660-9.

Risk factors associated with augmented renal clearance in a mixed intensive care unit population: a retrospective study.

Bing E, Archambault K, Sananikone A, Nguyen K, Fang Y, Jabamikos C Int J Clin Pharm. 2022; 44(6):1277-1286.

PMID: 35834093 DOI: 10.1007/s11096-022-01458-9.

Measured versus estimated creatinine clearance in critically ill patients with acute kidney injury: an observational study.

Kadivarian S, Heydarpour F, Karimpour H, Shahbazi F Acute Crit Care. 2022; 37(2):185-192.

PMID: 35545239 PMC: 9184982. DOI: 10.4266/acc.2021.01256.

References

Hobbs A, Shea K, Roberts K, Daley M . Implications of Augmented Renal Clearance on Drug Dosing in Critically Ill Patients: A Focus on Antibiotics. Pharmacotherapy. 2015; 35(11):1063-75. DOI: 10.1002/phar.1653. View

Herrera-Gutierrez M, Seller-Perez G, Banderas-Bravo E, Munoz-Bono J, Lebron-Gallardo M, Fernandez-Ortega J . Replacement of 24-h creatinine clearance by 2-h creatinine clearance in intensive care unit patients: a single-center study. Intensive Care Med. 2007; 33(11):1900-6. DOI: 10.1007/s00134-007-0745-5. View

Udy A, Roberts J, Boots R, Paterson D, Lipman J . Augmented renal clearance: implications for antibacterial dosing in the critically ill. Clin Pharmacokinet. 2009; 49(1):1-16. DOI: 10.2165/11318140-000000000-00000. View

Carrie C, Petit L, dHoudain N, Sauvage N, Cottenceau V, Lafitte M . Association between augmented renal clearance, antibiotic exposure and clinical outcome in critically ill septic patients receiving high doses of β-lactams administered by continuous infusion: a prospective observational study. Int J Antimicrob Agents. 2017; 51(3):443-449. DOI: 10.1016/j.ijantimicag.2017.11.013. View

Huttner A, von Dach E, Renzoni A, Huttner B, Affaticati M, Pagani L . Augmented renal clearance, low β-lactam concentrations and clinical outcomes in the critically ill: an observational prospective cohort study. Int J Antimicrob Agents. 2015; 45(4):385-92. DOI: 10.1016/j.ijantimicag.2014.12.017. View

Mahmoud S, Shen C . Augmented Renal Clearance in Critical Illness: An Important Consideration in Drug Dosing. Pharmaceutics. 2017; 9(3). PMC: 5620577. DOI: 10.3390/pharmaceutics9030036. View

Udy A, Dulhunty J, Roberts J, Davis J, Webb S, Bellomo R . Association between augmented renal clearance and clinical outcomes in patients receiving β-lactam antibiotic therapy by continuous or intermittent infusion: a nested cohort study of the BLING-II randomised, placebo-controlled, clinical trial. Int J Antimicrob Agents. 2017; 49(5):624-630. DOI: 10.1016/j.ijantimicag.2016.12.022. View

Lannou A, Carrie C, Rubin S, de Courson H, Biais M . Renal response after traumatic brain injury: A pathophysiological relationship between augmented renal clearance and salt wasting syndrome?. Anaesth Crit Care Pain Med. 2020; 39(2):239-241. DOI: 10.1016/j.accpm.2019.11.001. View

Tomasa-Irriguible T, Martinez-Vega S, Mor-Marco E, Herraiz-Ruiz A, Raguer-Pardo L, Cubells-Larrosa C . Low molecular weight heparins in COVID-19 patients: beware of augmented renal clearance!. Crit Care. 2020; 24(1):325. PMC: 7286205. DOI: 10.1186/s13054-020-03058-3. View

10.

Udy A, Varghese J, Altukroni M, Briscoe S, McWhinney B, Ungerer J . Subtherapeutic initial β-lactam concentrations in select critically ill patients: association between augmented renal clearance and low trough drug concentrations. Chest. 2011; 142(1):30-39. DOI: 10.1378/chest.11-1671. View

11.

Barrasa H, Soraluce A, Uson E, Sainz J, Martin A, Sanchez-Izquierdo J . Impact of augmented renal clearance on the pharmacokinetics of linezolid: Advantages of continuous infusion from a pharmacokinetic/pharmacodynamic perspective. Int J Infect Dis. 2020; 93:329-338. DOI: 10.1016/j.ijid.2020.02.044. View

12.

Bilbao-Meseguer I, Rodriguez-Gascon A, Barrasa H, Isla A, Solinis M . Augmented Renal Clearance in Critically Ill Patients: A Systematic Review. Clin Pharmacokinet. 2018; 57(9):1107-1121. DOI: 10.1007/s40262-018-0636-7. View

13.

Baptista J, Roberts J, Sousa E, Freitas R, Deveza N, Pimentel J . Decreasing the time to achieve therapeutic vancomycin concentrations in critically ill patients: developing and testing of a dosing nomogram. Crit Care. 2014; 18(6):654. PMC: 4277659. DOI: 10.1186/s13054-014-0654-2. View

14.

Udy A, Roberts J, Lipman J . Implications of augmented renal clearance in critically ill patients. Nat Rev Nephrol. 2011; 7(9):539-43. DOI: 10.1038/nrneph.2011.92. View

15.

Spyropoulos A, Ageno W, Barnathan E . Hospital-based use of thromboprophylaxis in patients with COVID-19. Lancet. 2020; 395(10234):e75. PMC: 7173816. DOI: 10.1016/S0140-6736(20)30926-0. View

16.

Tomasa Irriguible T . Augmented renal clearance: Much more is better?. Med Intensiva (Engl Ed). 2018; 42(8):500-503. DOI: 10.1016/j.medin.2018.02.004. View

17.

Atkinson Jr A . Augmented renal clearance. Transl Clin Pharmacol. 2020; 26(3):111-114. PMC: 6989233. DOI: 10.12793/tcp.2018.26.3.111. View

18.

Baptista J, Udy A, Sousa E, Pimentel J, Wang L, Roberts J . A comparison of estimates of glomerular filtration in critically ill patients with augmented renal clearance. Crit Care. 2011; 15(3):R139. PMC: 3219011. DOI: 10.1186/cc10262. View

19.

Ruiz S, Minville V, Asehnoune K, Virtos M, Georges B, Fourcade O . Screening of patients with augmented renal clearance in ICU: taking into account the CKD-EPI equation, the age, and the cause of admission. Ann Intensive Care. 2015; 5(1):49. PMC: 4681181. DOI: 10.1186/s13613-015-0090-8. View

20.

Cook A, Hatton-Kolpek J . Augmented Renal Clearance. Pharmacotherapy. 2019; 39(3):346-354. DOI: 10.1002/phar.2231. View