Primary hyperoxaluria type 1 (PH1) is a metabolic stone disease that, if left undiagnosed, can have devastating consequences, including progressive kidney decline and end-stage kidney disease (ESKD).
PH1 comprises 70%-80% of primary hyperoxaluria cases, affecting only 1 to 3 individuals per million, and can develop at any age, from birth to later in life. The true burden of PH1 is still largely unknown, with an estimated incident rate of 1 in 120,000 live births in Europe.
But its prevalence is higher in inbred populations, particularly in North Africa and the Middle East, though its real extent remains unclear. In Morocco, PH1 has a prevalence of 1 in 7,267 to 1 in 6,264 cases, while Tunisia sees 5.5 cases per million children, with PH1 accounting for 13% of pediatric ESRD, compared to 0.3% in Europe and 0.7% in North America.
In a French, nationwide, retrospective, observational study on primary hyperoxaluria, the patients' geographical origins were from Maghreb and Eastern Europe in 32% and 25% of cases respectively. Developing countries also report a significantly elevated prevalence of pediatric PH1-related ESRD, ranging from 10.4% in Kuwait to 16.7% in Jordan.
PH1 occurs when a genetic mutation causes the liver to overproduce oxalate, leading to its accumulation in the kidneys, where it causes damage, triggers inflammation, and impairs waste filtration and urine production. The rate of PH1 progression is unpredictable, with kidney function potentially declining suddenly due to dehydration from acute illness or any other causes.
As the kidneys become unable to excrete oxalate, patients risk life-threatening consequences from systemic oxalosis. Diagnosis relies on clinical suspicion and is confirmed through a 24-hour urine analysis and genetic testing. Signs and symptoms generally vary from one person to another, but early detection is essential for prompt diagnosis and treatment.
In adults, PH1 often presents with recurrent kidney stones, chronic kidney disease, nephrocalcinosis, and, in some cases, ESKD without a history of stones.
In children, signs may include haematuria, dysuria, abdominal pain, nephrocalcinosis, urinary tract infections, chronic kidney disease, stone passage, and failure to thrive in infants. Fatal PH1 often remains widely underdiagnosed in clinical practice, with up to 50% of cases going unnoticed due to its nonspecific symptoms and silent early progression.
On average, diagnosis in adults takes a median of 5.5 years from clinical onset. Alarmingly, up to 70% of cases are identified only after progression to end-stage kidney disease, and 10% are diagnosed post-transplant due to symptom recurrence or graft failure.
For this reason, prompt and consistent management is crucial in PH1, regardless of age or symptoms, due to its progressive nature. Kidney function can decline rapidly, even after a single dehydration incident, making regular monitoring essential.
Staying ahead of PH1 can help slow the progression to end-stage kidney disease (ESKD), which may require a dual liver- kidney transplant with significant morbidity and mortality risks.
Content funded by Alnylam Pharmaceuticals. PH1-ITA-00099 07/25
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