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

Area of Science:

• Nephrology
• Genetics
• Rare Diseases

Background:

• Primary hyperoxaluria type 1 (PH1) is a rare genetic disorder.
• PH1 leads to excessive oxalate production and deposition in kidneys and other organs.
• Advanced PH1 is associated with significant kidney damage and systemic complications.

Purpose of the Study:

• To characterize the natural history of advanced primary hyperoxaluria type 1 (PH1).
• To analyze outcomes in a multinational cohort of PH1 patients.
• To identify key clinical events and factors influencing morbidity and mortality in PH1.

Main Methods:

• Retrospective chart review of patients with advanced PH1.
• Inclusion criteria: ≥ 4 PH1-related visits, ≥ 6 months follow-up (or deceased), and impaired kidney function (eGFR ≤ 45 mL/min/1.73m² or elevated creatinine).
• Patients categorized into non-dialysis (Cohort A) and hemodialysis (Cohort B) groups.

Main Results:

• Seventy patients were analyzed with up to 21 years of data.
• The estimated glomerular filtration rate (eGFR) slope was -2.8 mL/min/1.73m²/year in non-dialysis patients.
• Forty-two patients underwent transplantation, and 19 patients died, with a higher mortality rate in non-transplanted individuals (39.3% vs. 19.0%).

Conclusions:

• Advanced PH1 is characterized by high rates of morbidity and mortality.
• Transplantation offers a survival benefit, but recovery from systemic oxalosis can be prolonged.
• Emergent clinical events like nephrolithiasis and fractures are common, underscoring the systemic impact of PH1.