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Length/serum creatinine ratio does not predict measured creatinine clearance in critically ill children
J Fong1, S Johnston, T Valentino
1Division of Pediatric Critical Care, New York Hospital-Cornell Medical Center, NY 10021, USA.
Insights
Estimating glomerular filtration rate (GFR) in critically ill children using standard formulas is unreliable. This method may lead to significant drug overdosage due to inaccurate renal function assessment.
Area of Science:
- Pediatric Nephrology
- Critical Care Medicine
- Clinical Pharmacology
Background:
- Accurate renal function assessment is crucial for drug dosing in critically ill children.
- Existing methods for estimating glomerular filtration rate (GFR) are validated in non-critically ill children but not in critically ill populations.
- Creatinine clearance (CLCR) is a key indicator of renal function.
Purpose of the Study:
- To evaluate the accuracy of an age- and sex-based GFR estimation method compared to measured 24-hour CLCR in critically ill children.
- To determine if this estimation method is reliable for adjusting drug dosages in this vulnerable patient group.
Main Methods:
- Measured 24-hour CLCR (CLCR-measured) in 100 critically ill children admitted to a pediatric intensive care unit.
- Estimated GFR (CL-estimated) using a published formula based on serum creatinine, patient length, age, and sex.
- Calculated the percentage difference and bias between CLCR-measured and CL-estimated.
Main Results:
- A significant correlation was found between CLCR-measured and CL-estimated (r=0.68, p<0.001).
- CL-estimated was higher than CLCR-measured in 84% of patients, with a mean bias of 45.2%.
- Discrepancies greater than 50% were observed in 36% of patients; adjustments for weight percentile did not improve accuracy.
Conclusions:
- The standard age- and sex-based GFR estimation method does not accurately reflect measured 24-hour CLCR in critically ill children.
- Relying on this estimation method for drug dosage adjustments in critically ill children may lead to substantial overdosage.
- Further research is needed to develop reliable methods for assessing renal function in critically ill pediatric patients.
Objective:
Information regarding renal function is important in critically ill children to adjust the dosage of drugs that are eliminated by the kidneys. Methods for estimating glomerular filtration rate (GFR) based on age and serum creatinine level have shown good agreement with measured creatinine clearance (CLCR) in children without critical illness but have not been examined in critically ill children.
Methods:
CLCR (24 hours) was measured (CLCR-measured) in 100 individuals (aged 5.6 years [range, 0.1 to 20.8 years]) admitted to a pediatric intensive care unit. Urine was collected by indwelling bladder catheters. Serum levels were determined. CLCR was calculated (CLCR-measured) according to the standard formula. GFR was estimated (CL-estimated) according to a published method, in which GFR is based on serum creatinine levels, patient length, and a constant that varies with the age and sex of the child. For each patient, the percentage difference between methods was calculated as the difference between the methods divided by the average obtained by the two methods and expressed as a percentage. Bias was calculated as the absolute value of the percentage difference.
Results:
CLCR-measured and CL-estimated were significantly correlated (CLCR-measured = 0.57 CL-estimated + 16.8; r = 0.68; p < 0.001). However, CL-estimated was greater than CLCR-measured in 84 patients. The difference ranged from -230 to +123 ml/min/1.73 m2 (mean -25.9 ml/min/1.73 m2 [95% confidence interval, -18.1 to 33.7 ml/min/1.73 m2]). The mean percentage difference between the methods was also large (-38.1% [95% confidence interval, -47.1% to 29.2%]) and ranged from -153.2% to 102.1%. The mean bias was 45.2% (95% confidence interval, 37.7% to 52.8%). In 36 of 100 patients the discrepancy between the two methods was greater than 50%. Adjusting for weight percentile, as a proxy for abnormal muscle mass, did not improve the model.
Conclusion:
A method to estimate GFR in children that is based on age and sex, but not critical illness, does not correspond with measured 24-hour CLCR. Use of this method to adjust dosage of drugs eliminated by the kidney might result in significant overdosage in most critically ill children.