Comparison of inulin clearance with 2-h creatinine clearance in Japanese pediatric patients with renal disease: open-label phase 3 study of inulin

Abstract

Background: There is no approved dosage and administration of inulin for children. Therefore, we measured inulin clearance (Cin) in pediatric patients with renal disease using the pediatric dosage and administration formulated by the Japanese Society for Pediatric Nephrology, and compared Cin with creatinine clearance (Ccr) measured at the same time. We examined to what degree Ccr overestimates Cin, using the clearance ratio (Ccr/Cin), and confirmed the safety of inulin in pediatric patients.

Methods: Pediatric renal disease patients aged 18 years or younger were enrolled. Inulin (1.0 g/dL) was administered intravenously at a priming rate of 8 mL/kg/hr (max 300 mL/hr) for 30 min. Next, patients received inulin at a maintenance rate of 0.7 × eGFR mL/min/1.73 m2 × body surface area (max 100 mL/hr) for 120 min. With the time the maintenance rate was initiated as a starting point, blood was collected at 30 and 90 min, while urine was collected twice at 60-min intervals. The primary endpoint was the ratio of Ccr to Cin (Ccr/Cin).

Results: Inulin was administered to 60 pediatric patients with renal disease; 1 patient was discontinued and 59 completed. The primary endpoint, Ccr/Cin, was 1.78 ± 0.52 (mean ± standard deviation). Regarding safety, five adverse events were observed in four patients (6.7%); all were non-serious. No adverse reactions were observed in this study.

Conclusions: The results in this study on the dosage and administration of inulin showed that inulin can safely and accurately determine GFR in pediatric patients with renal disease. CLINICALTRIALS.

Gov identifier: NCT03345316.

Keywords: Children; Chronic kidney disease; Creatinine clearance; Glomerular Filtration Rate; Inulin clearance.

Conflict of interest statement

OU has received consultant fees from Fuji Yakuhin Co., Ltd., the manufacturer of inulin. The other authors have declared that no conflict of interest exists.

© 2021. The Author(s).

Figures

Fig. 1

Study schema. *Patients who had been treated with drugs that may affect serum inulin, sCre, sCys-C, and sBMG underwent a wash-out period

Fig. 2

Dosage and administration of inulin. *Calculated using sCre for patients aged 2 years or older and sCys-C for those younger than 2 years. **Calculated using the Haycock method. ***If urination was not observed, the administration duration could be extended to 150 min

Fig. 3

Flow diagram of study protocol

Fig. 4

Scatter plot of Ccr and Cin