Clinical features of genetically confirmed patients with primary hyperoxaluria identified by clinical indication versus familial screening

Primary hyperoxaluria is a rare monogenic disorder characterized by excessive hepatic production of oxalate leading to recurrent nephrolithiasis, nephrocalcinosis, and progressive kidney damage. Most patients with primary hyperoxaluria are diagnosed after clinical suspicion based on symptoms. Since some patients are detected by family screening following detection of an affected family member, we compared the clinical phenotype of these two groups. Patients with primary hyperoxaluria types 1, 2, and 3 enrolled in the Rare Kidney Stone Consortium Primary Hyperoxaluria Registry were retrospectively analyzed following capture of clinical and laboratory results in the Registry. Among 495 patients with primary hyperoxaluria, 47 were detected by family screening. After excluding 150 patients with end stage kidney disease at diagnosis, 300 clinical suspicion and 45 family screening individuals remained. Compared to patients with clinical suspicion, those identified by family screening had significantly fewer stones at diagnosis (mean 1.2 vs. 3.6), although initial symptoms occurred at a similar age (median age 6.1 vs. 7.6 years). Urinary oxalate did not differ between these groups. The estimated glomerular filtration rate at diagnosis and its decline over time were similar for the two groups. Altogether, five of 45 in family screening and 67 of 300 of clinical suspicion individuals developed end stage kidney disease at last follow-up. Thus, patients with primary hyperoxaluria identified through family screening have significant disease despite no outward clinical suspicion at diagnosis. Since promising novel treatments are emerging, genetic screening of family members is warranted because they are at significant risk for disease progression.