Primary hyperoxaluria (PH) encompasses 3 genetically distinct, autosomal-recessive, inborn errors of glyoxylate metabolism characterized by the over-production of oxalate, a highly insoluble metabolic endproduct that is eliminated mainly by the kidney. All 3 forms of PH exhibit some extent of overlap in the clinical manifestations, where overproduction of oxalate is a prominent observation. Renal oxalate deposition in patients with PH1 and some patients with PH2 and PH3 leads to nephrocalcinosis, tubular dysfunction, and progression to end-stage renal disease (ESRD). Systemic oxalosis occurs in patients with PH1 due to the over-production of oxalate by the liver and the impairment of the body’s ability to eliminate oxalate, producing a broad range of serious life-threatening complications. At present, no therapies are approved by regulatory authorities for the treatment of all patients with PH. The consequences of systemic deposition of calcium oxalate crystals in patients with systemic oxalosis include bone fractures, non-healing painful cutaneous ulcers, treatment-refractory anemia, retinal calcium oxalate deposition, and cardiomyopathy and arrhythmias due to deposition in the cardiac conduction system.1 For patients with PH1, ESRD is present in 50% by the age of 15 years and 80% by the third decade.2 Given the limitations of dialysis and the inability to substantially impact oxalate over-production in most patients with PH1, most clinical centers until recently considered liver transplantation approaches earlier in the disease course to minimize the risk of irreversible tissue damage. Other treatments include combined liver and kidney transplantation.3,4 However, Lumasiran, a siRNA-based therapeutic that reduces expression of glycolate oxidase, was recently approved by the FDA for treatment of PH1 based on sustained reduction of urinary oxalate with the majority of patients receiving lumasiran achieving normal urinary oxalate levels.5 Because urine oxalate is the primary mediator of the ultimate end-organ effects of PH1, there is a critical need to identify patients with PH1 early in the disease course in order to prevent the systemic effects of hyperoxaluria and oxalosis and avoid the need for liver/kidney transplant.
The purpose of this study is to determine the clinical features and health services utilization of individuals ≤21 years with PH1 that precede the diagnosis of PH1. We will conduct a nested matched case-control study using the PEDSnet database. Aim 1: To identify the clinical characteristics and health services utilization of individuals with primary hyperoxaluria type 1. We will identify a parsiminous set of characteristics that precede diagnosis of PH1 and differentiate children with PH1 from children with early onset idiopathic kidney stone disease. This study will generate new knowledge about characteristics of children with PH1 that precede the diagnosis of PH1. This information will inform strategies for the early identification of children with possible PH1 to facilitate targeted genetic testing. This analysis plan will continue to be revised based on findings from exploration and review of the data by the study team.