Iohexol clearance in unstable critically ill patients: a tool to assess glomerular filtration rate

Gandonnière, Charlotte Salmon; Bretagne, Isabelle Benz-de; Mercier, Emmanuelle; Joret, Aurélie; Ehrmann, Stéphan; Guellec, Chantal Barin‐Le

doi:10.1515/cclm-2015-1202

Cited by 16 publications

(17 citation statements)

References 26 publications

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“…However, seven studies in critically ill adults (n = 18-66) investigated the performance of several eGFR equations. Similar to our results, multiple SCr-based eGFR equations displayed high biases and low accuracy (23-60%, dependent on equation used) when compared with mGFR values [11,13,28,[37][38][39][40].…”

Section: Interpretation Of Performance Of Egfr Methodssupporting

confidence: 88%

Glomerular filtration rate in critically ill neonates and children: creatinine-based estimations versus iohexol-based measurements

Smeets

Teunissen²,

Velden³

et al. 2022

Pediatr Nephrol

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Background Acute kidney injury (AKI) and augmented renal clearance (ARC), both alterations of the glomerular filtration rate (GFR), are prevalent in critically ill children and neonates. AKI and ARC prevalence estimates are based on estimation of GFR (eGFR) using serum creatinine (SCr), which is known to be inaccurate. We aimed to test our hypothesis that AKI prevalence will be higher and ARC prevalence will be lower in critically ill children when using iohexol-based measured GFR (mGFR), rather than using eGFR. Additionally, we aimed to investigate the performance of different SCr-based eGFR methods. Methods In this single-center prospective study, critically ill term-born neonates and children were included. mGFR was calculated using a plasma disappearance curve after parenteral administration of iohexol. AKI diagnosis was based on the KDIGO criteria, SCr-based eGFR, and creatinine clearance (CrCL). Differences between eGFR and mGFR were determined using Wilcoxon signed-rank tests and by calculating bias and accuracy (percentage of eGFR values within 30% of mGFR values). Results One hundred five children, including 43 neonates, were included. AKI prevalence was higher based on mGFR (48%), than with KDIGO or eGFR (11–40%). ARC prevalence was lower with mGFR (24%) compared to eGFR (38–51%). eGFR equations significantly overestimated mGFR (60–71 versus 41 ml/min/1.73 m2, p < 0.001–0.002). Accuracy was highest with eGFR equations based on age- and sex-dependent equations (up to 59%). Conclusion Iohexol-based AKI prevalence was higher and ARC prevalence lower compared to standard SCr-based eGFR methods. Age- and sex-dependent equations for eGFR (eGFR-Smeets for neonates and eGFR-Pierce for children) best approached measured GFR and should preferably be used to optimize diagnosis of AKI and ARC in this population. Graphical Abstract A higher resolution version of the Graphical abstract is available as Supplementary information

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Section: Interpretation Of Performance Of Egfr Methodssupporting

confidence: 88%

Glomerular filtration rate in critically ill neonates and children: creatinine-based estimations versus iohexol-based measurements

Smeets

Teunissen²,

Velden³

et al. 2022

Pediatr Nephrol

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“…In our patients, iohexol clearance was measured using a 24‐hour sampling schedule, delivering the mean GFR over 24 hours, encompassing all GFR variations (whether physiological, pathological—in unstable patients—or therapeutic) during this period. Nevertheless, in a previous work, Salmon‐Gandonnière et al demonstrated that the plasma iohexol concentration decay was steady within 24 hours in most patients and the fluid infusion volume or the use of catecholamines did not influence the iohexol pharmacokinetic parameters 18 . They also compared iohexol clearance calculated over 24 hours and over 6 hours and found that the variability of iohexol clearance over 24 hours was moderate (from 5 to 55%), suggesting that aggressive therapeutic interventions in the early period of ICU hospitalisation were not accompanied by parallel and rapid fluctuations of GFR.…”

Section: Discussionmentioning

confidence: 90%

“…Nevertheless, in a previous work, Salmon-Gandonnière et al demonstrated that the plasma iohexol concentration decay was steady within 24 hours in most patients and the fluid infusion volume or the use of catecholamines did not influence the iohexol pharmacokinetic parameters. 18 They also compared iohexol clearance calculated over 24 hours and over 6 hours and found that the variability of iohexol clearance over 24 hours was moderate (from 5 to 55%), suggesting that aggressive therapeutic interventions in the early period of ICU hospitalisation were not accompanied by parallel and rapid fluctuations of GFR. As a comparison, the coefficient of variation of creatinine clearance in healthy individuals can be as high as 35-45%, due to variability in both creatinine production and creatinine excretion.…”

Section: T a B L E 1 Patient Characteristicsmentioning

confidence: 99%

A single Bayesian estimator for iohexol clearance estimation in ICU, liver failure and renal transplant patients

Destère

Gandonnière

Åsberg

et al. 2022

Brit J Clinical Pharma

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Iohexol clearance has been proposed to estimate the glomerular filtration rate (GFR). A population pharmacokinetics (popPK) model was developed from heterogeneous patients. A Bayesian estimator (MAP-BE) based on a limited sampling strategy (LSS) was derived and evaluated in external patients. Methods: Full pharmacokinetic data (7-12 samples) from 172 patients receiving iohexol for measurement of their GFR (unstable and stable ICU patients, liver failure patients and kidney transplant patients) were split into development (n = 136) and validation (n = 36) datasets. A PopPK model was developed in Monolix and was used to develop MAP-BE based on LSS. Its performance for GFR estimation was evaluated in the validation set. Results: A two-compartment model with first-order elimination best described the data. The final model included the type of patients on volume of distribution (Vd), clearance and intercompartmental constants, serum creatinine on clearance and bodyweight on Vd. The best LSS included samples at 0.1-1-9 h exhibiting a relative mean prediction error (MPE) (RMSE) = À3.7% (14.3%) and better performance than the Bröchner-Mortensen formula (À3.0%/17%). Split by type of patients, the highest interindividual variability and imprecision was observed in unstable ICU patients (MPE (RMSE) = 3.7% (18.8%)) while the best performances were obtained for renal transplant patients (MPE (RMSE) = 1.0% (5.8%)). All LSS that included samples before 9 hours for the third sample were associated with an increased imprecision. Conclusion:A single MAP-BE of iohexol based on a three-sample LSS for four heterogeneous populations was developed and allowed accurate estimation of GFR in kidney transplant patients, slightly biased in stable ICU patients and slightly imprecise in unstable ICU patients.

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“…Mostly they are still subclinical and cannot be identified through serum creatinine levels. Consequently, early identification of potential abnormalities of renal function in cardiac patients plays an important role in early targeted therapy and reducing the occurrence of postoperative AKI [ 11 ].…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Four eGFR Calculating Formulae in Predicting Postoperative Acute Kidney Injury in Adult Patients Undergoing Open‐Heart Surgery with Cardiopulmonary Bypass

Qiu

Jin

et al. 2022

Contrast Media & Molecular Imaging

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Objective. There are four widely-used formulae to calculate the perioperative glomerular filtration rate (GFR) of patients undergoing cardiac surgery. We assessed the predictive values of these formulae in the occurrence of postoperative acute kidney injury (AKI). Methods. Patients who underwent open-heart valvular surgery with cardiopulmonary bypass from January 2015 to October 2017 were enrolled in this retrospective study. Demographic data and perioperative serum creatinine levels were collected. The estimated GFR (eGFR) was calculated using four formulae: Cockcroft Gault (CG), body surface area (BSA) corrected CG, simplified modification of diet in renal disease (MDRD), and chronic kidney disease-epidemiology collaboration (CKD-EPI) formula. The incidence of post-operative AKI was calculated and the predictive capability of these formulae was evaluated. Results. A total of 290 patients were included. 136 patients (46.90%) developed AKI after surgery. The eGFR in the AKI group was significantly lower than those in the non-AKI group at all investigated time points. In addition, the eGFR in the non-AKI group increased temporarily on the day of operation, then decreased on the following days, and returned to preoperative level about one week after surgery. However, in the AKI group, the eGFR decreased from the day of operation, which still did not recover to the preoperative level by the end of the first week after surgery. The eGFR calculated by the BSA-standardized CG formula had the highest AUC ROC curves of 0.699 and 0.774 before operation and on the day of operation, respectively. While eGFR calculated by CKD-EPI formula had the highest AUC ROC of 0.874 and 0.887 at the first and second postoperative day. Conclusions. The eGFR formula is a powerful tool for perioperative renal function assessment. The BSA-corrected CG and CKD-EPI formula have better performance in predicting postoperative AKI after cardiopulmonary bypass than serum creatinine level and other formulae.

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Iohexol clearance in unstable critically ill patients: a tool to assess glomerular filtration rate

Abstract: 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.

Cited by 16 publications

References 26 publications

Glomerular filtration rate in critically ill neonates and children: creatinine-based estimations versus iohexol-based measurements

Glomerular filtration rate in critically ill neonates and children: creatinine-based estimations versus iohexol-based measurements

A single Bayesian estimator for iohexol clearance estimation in ICU, liver failure and renal transplant patients

Evaluation of Four eGFR Calculating Formulae in Predicting Postoperative Acute Kidney Injury in Adult Patients Undergoing Open‐Heart Surgery with Cardiopulmonary Bypass

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