Treatment Overview
Living with Primary Hyperoxaluria (PH) involves a constant awareness of kidney health. This rare genetic condition causes the liver to produce excessive amounts of oxalate, a natural chemical that the kidneys must filter out. Because the kidneys cannot handle this overload, crystals form, leading to frequent, painful kidney stones and potentially permanent kidney damage. The anxiety surrounding the next stone event or the long-term risk of kidney failure can be a heavy burden for patients and their families. Treatment is vital to lower oxalate levels, prevent crystal formation, and preserve kidney function for as long as possible.
Because PH is a genetic metabolic disorder, it affects everyone differently depending on the specific gene mutation involved. There are three main types (PH1, PH2, and PH3), with PH1 being the most common and typically the most severe. Treatment plans are highly specialized and depend on the type of PH, the level of kidney function remaining, and how well the patient responds to specific therapies (National Institute of Diabetes and Digestive and Kidney Diseases, 2019).
Overview of treatment options for Primary Hyperoxaluria
The primary goal of treatment is to reduce the amount of calcium oxalate depositing in the kidneys. The strategy focuses on two main fronts: stopping the production of oxalate in the liver and diluting the urine to prevent crystals from clumping together.
High fluid intake, known as hyperhydration, is the foundation of care. Patients must drink large amounts of water daily to flush the kidneys. However, fluids alone are rarely enough for severe cases. Medication plays a crucial role in altering the body’s chemistry to inhibit stone formation. For Type 1 PH, genetic therapies and vitamin supplementation are central to the treatment plan. In advanced cases where kidneys have already failed, dialysis and organ transplantation (liver and kidney) may be required, but early medical management aims to delay or prevent this need.
Medications used for Primary Hyperoxaluria
Doctors prescribe specific medications to manage the chemical imbalance caused by the liver’s overproduction of oxalate.
For Type 1 Primary Hyperoxaluria (PH1), high-dose Vitamin B6 (pyridoxine) is often the first treatment. Approximately one-third of PH1 patients respond, with Vitamin B6 significantly lowering urine oxalate levels, potentially preventing kidney failure.
Crystallization inhibitors, like prescription citrate (e.g., potassium citrate) or neutral phosphates, are medications used to change urine chemistry. They do not halt oxalate production but help prevent solid stone formation.
RNA interference (RNAi) therapies, the newest and most advanced medication for PH1, target the liver-based root cause. Injectable drugs like lumasiran and nedosiran substantially reduce, and sometimes normalize, urinary oxalate excretion in PH1 patients (New England Journal of Medicine, 2021).
How these medications work
The medications used for Primary Hyperoxaluria target the production line of oxalate or the environment within the kidneys.
Vitamin B6 supplements: Act as a “helper” molecule for a liver enzyme. In some PH1 patients, B6 stabilizes the misshapen, partially functional enzyme, allowing it to properly break down glyoxylate instead of converting it to harmful oxalate.
Crystallization inhibitors: Work by chemical binding. Citrate binds to calcium in the urine, preventing it from forming stones with oxalate. Citrate also decreases urine acidity, inhibiting stone growth.
RNA interference therapies: Silence specific genes. They effectively “turn off” the liver’s instructions to produce oxalate-making enzymes. Blocking this genetic production dramatically reduces oxalate in the bloodstream and kidneys.
Side effects and safety considerations
PH treatments are typically lifelong and require ongoing monitoring. Vitamin B6 is safe, but high long-term doses can cause nerve damage (neuropathy), leading to numb or tingling hands and feet.
Crystallization inhibitors like potassium citrate may cause stomach upset, nausea, or diarrhea. New RNAi therapies are usually well-tolerated, though patients might experience injection site reactions, such as redness or pain.
Regular checks of kidney function and urine oxalate levels are vital to confirm treatment efficacy. Patients must stay well-hydrated; illness or vomiting can cause dehydration, quickly raising the risk of stone formation. Severe back pain, inability to urinate, or blood in the urine necessitate immediate medical attention, as these signal a stone blockage.
Since everyone’s experience with the condition and its treatments can vary, working closely with a qualified healthcare provider helps ensure safe and effective care.
References
- Oxalosis and Hyperoxaluria Foundation. https://www.ohf.org
- National Institute of Diabetes and Digestive and Kidney Diseases. https://www.niddk.nih.gov
- Mayo Clinic. https://www.mayoclinic.org
- MedlinePlus. https://medlineplus.gov
Medications for Primary Hyperoxaluria
These are drugs that have been approved by the US Food and Drug Administration (FDA), meaning they have been determined to be safe and effective for use in Primary Hyperoxaluria.