Health Services and Clinical Characteristics that Precede Diagnosis of Primary Hyperoxaluria Type 1
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Abstract
Study to determine the clinical features and health services utilization of individuals with primary hyperoxaluria type 1 (PH1) that precede the diagnosis of PH1. Conclusion of the study resulted in the identification of a set of characteristics that precede diagnosis of PH1 and differentiate children from PH1 children with early onset idiopathic kidney stone disease.
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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. For patients with PH1, ESRD is present in 50% by the age of 15 years and 80% by the third decade. 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. 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. 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. This study uses a nested matched case-control study with the PEDSnet database.
Study Aims
- To identify the clinical characteristics and health services utilization of individuals with primary hyperoxaluria type 1. A parsiminous set of characteristics that precede diagnosis of PH1 and differentiate children with PH1 from children with early onset idiopathic kidney stone disease are identified.
Cohort Description
Patients 21 years-old and under with early onset kidney stone disease, including cases (patients with PH1) and controls (patients with kidney stones not due to PH1) from January 2009 to November 2021. The rationale for this design and control population is to differentiate patients with PH1 from children with kidney stones, which is the most common condition caused by PH1.
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