Abstract
RATIONALE & OBJECTIVE: Characterize the natural history of advanced primary hyperoxaluria type 1 (PH1) in a multinational patient cohort. STUDY DESIGN: A retrospective chart review. SETTING & PARTICIPANTS: Patients, from participating medical centers in North America, Europe, and the Middle East, had ≥ 4 health care visits related to PH1 spanning ≥ 6 months (except deceased patients) on/after January 1, 2000, and ≥ 2 estimated glomerular filtration rate (eGFR) values ≤ 45 mL/min/1.73m(2) (if age < 12 months, 2 serum creatinine values elevated for age) were included. EXPOSURE: None (retrospective observational study). OUTCOMES: Kidney function, liver and/or kidney transplantation, death, plasma oxalate, systemic oxalosis, emergent clinical events, and abnormal clinical laboratory values. ANALYTICAL APPROACH: Patients were categorized as not on dialysis (Cohort A) and receiving hemodialysis (Cohort B). Patients could be in more than one cohort, but not during the same time. RESULTS: Seventy patients were analyzed (up to 21 years of data; Cohort A, n = 54; Cohort B, n = 53). The median age at entry was 11.8 years (Cohort A) and 12.2 years (Cohort B). The eGFR slope was -2.8 mL/min/1.73m(2)/year (Cohort A). Patients underwent hemodialysis a median of 6 days/week (range, 3-7; Cohort B). Forty-two patients underwent liver and/or kidney transplantation (median age at first transplant, 15.3 years). Nineteen patients died (median age at death, 3.9 years [range, 2.2-34.9]), including 8 who received liver or liver-kidney transplants. Death occurred in 11 of 28 (39.3%) patients without transplant and 8 of 42 (19.0%) patients with transplant. Improvement in skeletal oxalosis after liver-kidney transplantation generally took > 1 year. Limited plasma oxalate and cardiac oxalosis data were available. The most common emergent clinical events were nephrolithiasis (Cohort A [nondialysis]) and fracture (Cohort B [hemodialysis]). The most commonly reported abnormal clinical laboratory values were bicarbonate, creatinine, and eGFR. LIMITATIONS: Minimal follow-up in some patients; small sample for some endpoints. CONCLUSIONS: Advanced PH1 is associated with high morbidity and mortality rates.