What is PH?

Primary hyperoxaluria (PH) is an inherited, genetic condition in which the body produces too much oxalate. The cause of the oxalate overproduction is a defect of an specific enzyme, most often located in the liver. Oxalate is a substance that is useless for the body and normally leaves the body through urine, but in high amounts, it can form kidney stones and cause kidney damage. 

Types of PH:

There are three types of PH (PH1, PH2, and PH3), with PH1 being the most common and severe. 

Importance of Genetic Testing:

Genetic testing is crucial for diagnosing PH. It helps determine the specific type of PH, which is important for treatment and management. 

Symptoms and Signs:

Common signs include recurrent kidney stones, kidney damage (kidney tissue calcification = nephrocalcinosis seen on ultrasound), and eventually kidney failure. In case of severe kidney dysfunction, oxalate will be stored throughout the body and this may cause disease of bones, eye, nerves, vessels and the heart. This condition is called systemic oxalosis.   

Conservative Therapy:

• Drinking lots of water is essential to prevent kidney stones.
• Vitamin B6 may act as a helper enzyme in case the specific enzyme is only mildly defect, which is the case in about 30% in Western PH1 patients. High dosages of this vitamin may sometimes completely normalize the oxalate excretion.
• Citrate prevents crystal formation of Calcium and oxalate and may therefore be helpful in preventing kidney stone formation.
• The usefulness of dietary intervention in PH is uncertain. It is recommended to avoid high amounts of oxalate intake and of high dose Vitamin C as the latter is metabolized into oxalate.  

Advanced Therapies:

• New RNA interference (RNAi) therapies can significantly reduce oxalate production in patients with PH1. 

Dialysis and Transplantation:

• Liver transplantation is still the only ‘cure’ for patients with PH1 and is still recommended in case of severe kidney dysfunction and incomplete response to vitamin B6 or RNAi therapy.
• In case of severe kidney dysfunction, intensive forms of dialysis are often required as bridge to liver transplantation in case of incomplete response to Vitamin B6 or RNAi therapy    

Regular Check-Ups:

• Patients should have regular check-ups to monitor kidney function and oxalate levels.
• Monitoring helps catch any complications early and adjust treatments as needed. 

Adapted Guidelines:

Recommendations are provided for managing PH in areas with limited medical resources, emphasizing the most critical aspects of care that can be adapted to diJerent settings. 

Ongoing Research:

• There are still unanswered questions and ongoing research to improve the understanding and treatment of PH. This includes finding more effective therapies and better ways to manage the condition.
• The exact role of RNAi in advanced stages of PH1 needs to be established.