#4551 development of an x-ray–based bone oxalosis grading scale to assess oxalate accumulation in patients with primary hyperoxaluria type 1

Abstract Background and Aims Primary hyperoxaluria type 1 (PH1) is a rare genetic disease in which hepatic oxalate overproduction can lead to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis, a condition in which calcium oxalate is deposited in various tissues, including bone [1]. Radiological signs of bone oxalosis include findings such as dense metaphyseal bands and coarse trabeculation [2]. No scale exists to grade bone oxalosis severity using X-rays. Method An X-ray grading scale to evaluate systemic oxalosis in specific bones was developed based on expert opinion. Scores on individual items ranged from 0–4, except for ribs and spine, which ranged from 0–2. Higher values represent more advanced oxalosis. To validate the scale, 85 X-ray images from 5 pediatric patients with PH1 who had developed bone oxalosis were collected from charts at Shaare Zedek Medical Center and de-identified [2]. Two blinded, independent raters evaluated each X-ray twice and assigned a grade to each applicable item on the scale. Inter-rater and intra-rater reliability analyses were conducted using the weighted Cohen's kappa with asymptotic 95% confidence intervals (CIs) of the estimate and interpreted as proposed in the literature [3]. Total weighted kappa estimates were generated by pooling all observed ratings across all items. Results Total overall inter-rater (0.83 [95% CI: 0.79, 0.87]) and intra-rater (0.95 [0.93, 0.97]) kappa estimates demonstrated almost perfect agreement. Overall inter-rater kappa estimates were >0.8 to 1.0 (almost perfect agreement) for the left hand/wrist, left hip, left knee (femur), and left humerus; >0.6 to 0.8 (substantial agreement) for the right hip, right knee (tibia), right humerus, spine, and ribs; and >0.4 to 0.6 (moderate agreement) for the right knee (femur) and right knee (fibula). The overall inter-rater kappa estimate for the left knee (fibula) demonstrated poor agreement (−0.08 [−0.27, 0.10]). Overall inter-rater kappa estimates for the right hand/wrist and left knee (tibia) were considered unreliable due to lack of variability in the data, and the standard errors were not estimable. Calculable overall intra-rater kappa estimates were >0.8 to 1.0 (almost perfect agreement) for the spine and >0.6 to 0.8 (substantial agreement) for the right knee (femur) and right knee (fibula). Most other overall intra-rater kappa estimates could not be calculated because the kappas for one or both raters lacked variability. In these instances, intra-rater kappa estimates for the first and second raters demonstrated moderate to almost perfect agreement (>0.4 to 1.0; left hand/wrist, right hip, left hip, left knee [femur], right knee [tibia], left knee [tibia], right humerus, left humerus, and ribs). For the left knee (fibula), intra-rater kappa estimates for the first and second raters were −0.14 (−0.34, 0.05) and 1.00, respectively, and for the right hand/wrist, they were 1.00 and 0.00. Conclusion We developed a novel X-ray–based bone oxalosis grading scale for patients with PH1. Total overall weighted kappa estimates for inter-rater and intra-rater reliability demonstrated almost perfect strength of agreement. Most individual items demonstrated reliable kappa estimates. The right and left knee (fibula) were removed from the scale due to poor reliability.