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Glomerular Hyper- and Hypofiltration During Acute Circulatory Failure: Iohexol-Based Gold-Standard Descriptive Study

Salmon Gandonnière, Charlotte PhD1,2; Helms, Julie PhD3,4; Le Tilly, Olivier PharmD5; Benz-de Bretagne, Isabelle PhD5; Bretagnol, Anne MD6; Bodet-Contentin, Laetitia PhD1; Mercier, Emmanuelle PhD1; Halimi, Jean-Michel PhD2,7; Benzékri-Lefèvre, Dalila MD6; Meziani, Ferhat PhD3,4; Barin-Le Guellec, Chantal PhD5,8; Ehrmann, Stephan PhD1,9; on behalf of the Clinical Research in Intensive Care and Sepsis - TRIal Group for Global Evaluation and Research in SEPsis (CRICS-TriggerSep) Network

doi: 10.1097/CCM.0000000000003804
Online Clinical Investigations

Objective: To assess glomerular filtration rate in the early phase of acute circulatory failure by measuring iohexol plasma clearance.

Design: Interventional prospective multicentric study.

Setting: Three French ICUs in tertiary teaching hospitals.

Patients: Patients with acute circulatory failure within 12 hours after ICU admission.

Interventions: IV administration of a nontoxic 5-mL dose of iohexol. Collection of nine arterial blood samples over 24 hours for iohexol plasma concentration measurements. Iohexol clearance calculation with a population pharmacokinetic model. Iohexol clearance was an estimation of the mean glomerular filtration rate over 24 hours.

Measurements and Main Results: Among 99 included patients, we could calculate iohexol clearance for 85. The median iohexol clearance was 31 mL/min (interquartile range, 16–44). According to iohexol clearance, 41 patients (48%) had severe hypofiltration (clearance, < 30 mL/min), 29 (34%) had moderate hypofiltration, and 10 (12%) had mild hypofiltration (clearance, 30–60 and 60–90 mL/min, respectively). Four patients (5%) had normal glomerular filtration rate, and only one (1%) showed hyperfiltration (clearance, > 130 mL/min). Urinary creatinine clearance underestimated renal impairment in one patient out of two; the bias of iohexol clearance toward 24-hour urinary creatinine clearance over the same period was –18.1 mL/min (limits of agreement, –73.5 to 37.4).

Conclusions: We demonstrated the feasibility of iohexol clearance measurement in unstable critically ill patients. Normal kidney function is exceptional during the early phase of acute circulatory failure. Glomerular filtration rate estimation by urinary creatinine clearance frequently fails to detect renal impairment. Hyperfiltration is very infrequent.

1Médecine Intensive Réanimation, INSERM CIC 1415, CHRU de Tours, Tours, France.

2EA4245, Cellules dendritiques, immunomodulation et greffes, Université de Tours, Tours, France.

3Université de Strasbourg (UNISTRA), Faculté de Médecine, Hôpitaux universitaires de Strasbourg, Service de réanimation, Nouvel Hôpital Civil, Strasbourg, France.

4ImmunoRhumatologie Moléculaire, INSERM UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d’Immunologie et d’Hématologie, Faculté de Médecine, Fédération Hospitalo-Universitaire (FHU) OMICARE, Fédération de Médecine Translationnelle de Strasbourg (FMTS), Université de Strasbourg, Strasbourg, France.

5Laboratoire de Biochimie et Biologie Moléculaire, CHRU de Tours, Tours, France.

6Médecine Intensive Réanimation, Hôpital de la Source, CHR Orléans, Orléans, France.

7Néphrologie et Immunologie Clinique, CHRU de Tours, Tours, France.

8INSERM (French National Institute of Health and Medical Research), UMR-1248, IPPRITT, Individual Profiling and Prevention of Risks with Immunosuppressive Therapies and Transplantation, Limoges, France.

9Faculté de médecine, Université de Tours, Tours, France.

This work was performed at Centre Hospitalier Régional et Universitaire de Tours, 2 bd Tonnellé, F37044 Tours cedex, France; Hôpitaux universitaires de Strasbourg, 1 quai Louis Pasteur, 67091 Strasbourg, France; and Centre Hospitalier Régional d’Orléans, 14 avenue de l’hôpital, 45067 Orléans, France.

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Supported, in part, by a research grant from the French Intensive Care Society and from the Firalis SAS and the “Association pour la promotion à Tours de la réanimation médicale.”

Dr. Salmon Gandonnière’s institution received funding from French Intensive Care Society and Firalis SAS; Firalis SAS was not involved in the study design, patients’ recruitment, or data analysis. Dr. Ehrmann’s institution received funding from Firalis, Hamilton, and Fisher & Paykel, and he received funding from Baxter, Aerogen, and a French Intensive Care Society Grant. He received consultancy fees from Baxter and Aerogen. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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