Natural History of Advanced Primary Hyperoxaluria Type 1: A Retrospective Study.

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/1.73m2 (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/1.73m2/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.