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

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.

Iohexol Plasma Clearance in Animal Models: The Clear Choice for Measuring Early Renal Dysfunctio

Glomerular filtration rate is a measure of the kidney’s ability to filter blood. In animal models of early kidney failure, there is no routine method to accurately measure GFR. The expensive gold standard of GFR measurement is exogenous inulin clearance. The commonly used method, endogenous plasma creatinine concentration, is unreliable and insensitive, especially at normal levels of renal function. This study investigates the utility of iohexol, an inexpensive radio-contrast agent as a promising exogenous marker for plasma clearance kidney function evaluation in rats. Early stages of progressive kidney failure were induced with a 0.25% adenine diet in male Sprague Dawley rats (N=8) over 5 weeks. Both plasma clearance of iohexol and inulin and creatinine concentration were evaluated following weekly venous injections and blood sampling. Plasma iohexol clearance and plasma inulin clearance strongly correlate (R2=0.95). However, plasma creatinine concentration correlated weakly with iohexol(R2=0.53) and inulin(R2=0.58). Iohexol plasma clearance accurately measures changes in kidney function, especially in in comparison to creatinine analysis. The data demonstrates creatinine is an inappropriate marker for renal function in early adenine-induced CKD rat models. Ongoing analysis of this data suggests refinement of the protocol will yield a simple method for routine measure of kidney function in murine lab animals. This tool will facilitate advancement in kidney disease onset and allow for more accurate interpretation of kidney function in the various animal models.