Limits...
Validation of a continuous infusion of low dose Iohexol to measure glomerular filtration rate: randomised clinical trial.

Dixon JJ, Lane K, Dalton RN, Turner C, Grounds RM, MacPhee IA, Philips BJ - J Transl Med (2015)

Bottom Line: We have designed a method of continuous measurement of GFR intended as a research tool to time effects of AKI.No crossover effects occurred (p = 0.85).CILDI is now ready for testing in patients with AKI.

View Article: PubMed Central - PubMed

Affiliation: General Intensive Care Unit, St. George's Hospital, London, UK. johndixon3@nhs.net.

ABSTRACT

Introduction: There is currently no accurate method of measuring glomerular filtration rate (GFR) during acute kidney injury (AKI). Knowledge of how much GFR varies in stable subjects is necessary before changes in GFR can be attributed to AKI. We have designed a method of continuous measurement of GFR intended as a research tool to time effects of AKI. The aims of this crossover trial were to establish accuracy and precision of a continuous infusion of low dose Iohexol (CILDI) and variation in GFR in stable volunteers over a range of estimated GFR (23-138 mL/min/1.73 m(2)).

Methods: We randomised 17 volunteers to GFR measurement by plasma clearance (PC) and renal clearance (RC) of either a single bolus of Iohexol (SBI; routine method), or of a continuous infusion of low dose Iohexol (CILDI; experimental method) at 0.5 mL/h for 12 h. GFR was measured by the alternative method after a washout period (4-28 days). Iohexol concentration was measured by high performance liquid chromatography/electrospray tandem mass spectrometry and time to steady state concentration (Css) determined.

Results: Mean PC was 76.7 ± 28.5 mL/min/1.73 m(2) (SBI), and 78.9 ± 28.6 mL/min/1.73 m(2) (CILDI), p = 0.82. No crossover effects occurred (p = 0.85). Correlation (r) between the methods was 0.98 (p < 0.0001). Bias was 2.2 mL/min/1.73 m(2) (limits of agreement -8.2 to 12.6 mL/min/1.73 m(2)) for CILDI. PC overestimated RC by 7.1 ± 7.3 mL/min/1.73 m(2). Mean intra-individual variation in GFR (CILDI) was 10.3% (p < 0.003). Mean ± SD Css was 172 ± 185 min.

Conclusion: We hypothesise that changes in GFR >10.3% depict evolving AKI. If this were applicable to AKI, this is less than the 50% change in serum creatinine currently required to define AKI. CILDI is now ready for testing in patients with AKI.

Trial registration: This trial was registered with the European Union Clinical Trials Register ( https://www.clinicaltrialsregister.eu/ ), registration number: 2010-019933-89 .

No MeSH data available.


Related in: MedlinePlus

Association between plasma clearance GFR calculated by the single bolus and the experimental continuous infusion of low dose Iohexol (CILDI). Solid line = line of association, dashed lines = error margins of association line. Slope = 0.988 ± 0.048, Intercept = 3.08 ± 3.92, Pearson’s correlation, r = 0.983, p < 0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4336474&req=5

Fig2: Association between plasma clearance GFR calculated by the single bolus and the experimental continuous infusion of low dose Iohexol (CILDI). Solid line = line of association, dashed lines = error margins of association line. Slope = 0.988 ± 0.048, Intercept = 3.08 ± 3.92, Pearson’s correlation, r = 0.983, p < 0.0001.

Mentions: There was no significant difference in PC between methods A (SBI) and B (CILDI) overall or on sub-group analysis; Table 3. Association (Figure 2) and agreement (Figure 3) between the methods were good. Sub-group analysis revealed closer limits of agreement, when measured in mL/min/1.73 m2, in the CKD group, although this was not significant when measured as percentage difference in GFR. When GFR was measured by CILDI, bias in the HV group was 2.2 mL/min/1.73 m2 (2.2%), limits of agreement −10.7 to 15.1 mL/min/1.73 m2 (−12.1 to 16.6%); in patients with CKD bias was 2.2 mL/min/1.73 m2 (5.8%), with limits of agreement −1.3 to 5.7 mL/min/1.73 m2 (−5.0 to 16.6%). Intra-individual variations in GFR and precision of GFR calculations are summarised in Table 4. Time to steady state (Css) was less than 10 h in all subjects (Table 4). The difference in GFR which depicts AKI can be determined by measuring the precision of CILDI at 95% and 99% confidence intervals and at 3 standard deviations (ie 99.7% confidence intervals). A difference of greater than 10.3% (3 standard deviations) after time to Css had elapsed, depicts a true difference in GFR (p < 0.003). The Pearson correlation between time to steady state concentration and GFR is 0.82.Figure 2


Validation of a continuous infusion of low dose Iohexol to measure glomerular filtration rate: randomised clinical trial.

Dixon JJ, Lane K, Dalton RN, Turner C, Grounds RM, MacPhee IA, Philips BJ - J Transl Med (2015)

Association between plasma clearance GFR calculated by the single bolus and the experimental continuous infusion of low dose Iohexol (CILDI). Solid line = line of association, dashed lines = error margins of association line. Slope = 0.988 ± 0.048, Intercept = 3.08 ± 3.92, Pearson’s correlation, r = 0.983, p < 0.0001.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4336474&req=5

Fig2: Association between plasma clearance GFR calculated by the single bolus and the experimental continuous infusion of low dose Iohexol (CILDI). Solid line = line of association, dashed lines = error margins of association line. Slope = 0.988 ± 0.048, Intercept = 3.08 ± 3.92, Pearson’s correlation, r = 0.983, p < 0.0001.
Mentions: There was no significant difference in PC between methods A (SBI) and B (CILDI) overall or on sub-group analysis; Table 3. Association (Figure 2) and agreement (Figure 3) between the methods were good. Sub-group analysis revealed closer limits of agreement, when measured in mL/min/1.73 m2, in the CKD group, although this was not significant when measured as percentage difference in GFR. When GFR was measured by CILDI, bias in the HV group was 2.2 mL/min/1.73 m2 (2.2%), limits of agreement −10.7 to 15.1 mL/min/1.73 m2 (−12.1 to 16.6%); in patients with CKD bias was 2.2 mL/min/1.73 m2 (5.8%), with limits of agreement −1.3 to 5.7 mL/min/1.73 m2 (−5.0 to 16.6%). Intra-individual variations in GFR and precision of GFR calculations are summarised in Table 4. Time to steady state (Css) was less than 10 h in all subjects (Table 4). The difference in GFR which depicts AKI can be determined by measuring the precision of CILDI at 95% and 99% confidence intervals and at 3 standard deviations (ie 99.7% confidence intervals). A difference of greater than 10.3% (3 standard deviations) after time to Css had elapsed, depicts a true difference in GFR (p < 0.003). The Pearson correlation between time to steady state concentration and GFR is 0.82.Figure 2

Bottom Line: We have designed a method of continuous measurement of GFR intended as a research tool to time effects of AKI.No crossover effects occurred (p = 0.85).CILDI is now ready for testing in patients with AKI.

View Article: PubMed Central - PubMed

Affiliation: General Intensive Care Unit, St. George's Hospital, London, UK. johndixon3@nhs.net.

ABSTRACT

Introduction: There is currently no accurate method of measuring glomerular filtration rate (GFR) during acute kidney injury (AKI). Knowledge of how much GFR varies in stable subjects is necessary before changes in GFR can be attributed to AKI. We have designed a method of continuous measurement of GFR intended as a research tool to time effects of AKI. The aims of this crossover trial were to establish accuracy and precision of a continuous infusion of low dose Iohexol (CILDI) and variation in GFR in stable volunteers over a range of estimated GFR (23-138 mL/min/1.73 m(2)).

Methods: We randomised 17 volunteers to GFR measurement by plasma clearance (PC) and renal clearance (RC) of either a single bolus of Iohexol (SBI; routine method), or of a continuous infusion of low dose Iohexol (CILDI; experimental method) at 0.5 mL/h for 12 h. GFR was measured by the alternative method after a washout period (4-28 days). Iohexol concentration was measured by high performance liquid chromatography/electrospray tandem mass spectrometry and time to steady state concentration (Css) determined.

Results: Mean PC was 76.7 ± 28.5 mL/min/1.73 m(2) (SBI), and 78.9 ± 28.6 mL/min/1.73 m(2) (CILDI), p = 0.82. No crossover effects occurred (p = 0.85). Correlation (r) between the methods was 0.98 (p < 0.0001). Bias was 2.2 mL/min/1.73 m(2) (limits of agreement -8.2 to 12.6 mL/min/1.73 m(2)) for CILDI. PC overestimated RC by 7.1 ± 7.3 mL/min/1.73 m(2). Mean intra-individual variation in GFR (CILDI) was 10.3% (p < 0.003). Mean ± SD Css was 172 ± 185 min.

Conclusion: We hypothesise that changes in GFR >10.3% depict evolving AKI. If this were applicable to AKI, this is less than the 50% change in serum creatinine currently required to define AKI. CILDI is now ready for testing in patients with AKI.

Trial registration: This trial was registered with the European Union Clinical Trials Register ( https://www.clinicaltrialsregister.eu/ ), registration number: 2010-019933-89 .

No MeSH data available.


Related in: MedlinePlus