Systemic oxalosis: an overview of the findings and prevalence in primary hyperoxaluria

Abstract Background and Aims Systemic oxalosis is a severe co-morbidity that may arise in patients with primary hyperoxaluria type 1 (PH1). It is caused by precipitation of calcium oxalate crystals in organs besides the kidneys, as a result of high endogenous oxalate production. In this study, we aimed to provide an overview of the prevalence, features, screening modalities and factors that play a role in developing systemic oxalosis as cohort studies are currently lacking. Method A retrospective registry study was conducted using data from the OxalEurope registry, one of the largest registries of patients with PH1. All patients with primary hyperoxaluria and data on systemic oxalosis were identified. Data was analyzed using descriptive statistics, Chi-square tests, Mann-Whitney U tests and Kaplan Meier analyses. Results A total of 159 out of 291 (55%) screened PH1 patients were diagnosed with systemic oxalosis. In addition, 110 patients were recorded having no signs of systemic oxalosis at follow-up, however screening was not performed. Sixty-two patients had already developed systemic oxalosis at moment of diagnosis and systemic oxalosis was most often found in patients with ESKD (95%). The eyes, bones and heart are most frequently affected, nevertheless deposits occurred in many organs, as shown by obduction. Fundus photography (n = 16), X-ray (n = 43), and echocardiography (n = 59) are the modalities used most often to screen respectively the eyes, bones and heart. Patients who developed systemic oxalosis had significantly higher upper plasma oxalate levels (median 22 versus 175 umol/L, p<0.001). Furthermore, patients with systemic oxalosis had a significant higher mortality rate compared to patients without systemic oxalosis (48 out of 142 versus 10 out of 212, p<0.001), which difference persisted after correcting for ESKD (p<0.001). Kaplan Meier analysis (Figure 1) showed that pediatric patients with ESKD tended to developed systemic oxalosis more frequently than adults (p<0.001). Conclusion This is the first research to systematically study and report systemic oxalosis in patients with primary hyperoxaluria type 1. Systemic oxalosis is prevalent among PH1 patients, especially when ESKD is present, and may lead to significant morbidity and mortality. Patients with systemic oxalosis have a higher mortality rate and pediatric patients may develop systemic oxalosis more frequently than adults. Given the high incidence and possible implications, we would like to make an appeal on screening all patients with systemic oxalosis. Future research should focus on reliable screening modalities for early signs of systemic oxalosis.