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Primary hyperoxaluria type 1

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Last updated: 18th Jan 2021

Primary hyperoxaluria type 1

What is primary hyperoxaluria type 1?

Primary hyperoxaluria Type 1, or PH1, is an inherited disorder caused by a mutation in the AGTX gene. PH1 is characterised by the overproduction of oxalate and its accumulation in the kidneys and urinary tracts.

Excessive oxalate combined with calcium in the kidney manifests as kidney stones and crystals which, if persistent, can lead to complications including recurrent urolithiasis, nephrocalcinosis and progressive renal decline. In undiagnosed or unmanaged PH1 cases, these complications can ultimately lead to chronic kidney disease (CKD), end-stage kidney disease (ESKD) and death1,2.

Primary hyperoxaluria type 1 symptoms

Primary hyperoxaluria Type 1 affects both children and adults, and symptoms often arise during childhood. Kidney stones are often the first sign of hyperoxaluria, with symptoms including sudden back pain, persistent flank or abdominal pain, a frequent urge to urinate and blood or pain when urinating. In cases that have progressed to renal failure, symptoms include low urine output, fatigue, loss of appetite and anaemia. Renal failure may also be accompanied by oxalosis, whereby excess oxalate builds up in the blood vessels, bones and body organs.   

Primary hyperoxaluria type 1 diagnosis

Primary hyperoxaluria Type 1 diagnosis at an early stage is critical for optimal management and is often based on clinical suspicion3. Diagnosis of PH1 involves measuring urinary oxalate (UOx) using a 24-hour urine analysis for levels excreted within 24 hours4. A spot urine test that is less precise may also be used to measure oxalate:creatinine ratios, and a blood test may be used to measure oxalate levels in the blood (to assess oxalosis)4. Genetic testing for mutations in the AGTX gene confirms a PH1 diagnosis4.

Primary hyperoxaluria treatment

The primary aim of primary hyperoxaluria Type 1 treatment is to clear oxalate and slow down kidney function decline. PH1 treatment options therefore include hyperhydration and intensive dialysis1,5. In more severe cases of PH1, a liver transplantation can correct the faulty AGTX gene, and/or a kidney transplantation may be required1,5. Treatment burdens for PH1 are high and new treatment options such as RNA interference therapy (RNAi) and oxalate degraders are emerging or under investigation6.

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References

  1. Cochat P, Rumsby G. Primary hyperoxaluria. N Engl J Med. 2013;369:649–58.
  2. Bhasin B, Ürekli HM, Atta MG. Primary and secondary hyperoxaluria: understanding the enigma. World J Nephrol. 2015;4:235–44.
  3. Sas DJ, Harris PC, Milliner DS. Recent advances in the identification and management of inherited hyperoxalurias. Urolithiasis. 2019;47:79–89.
  4. Cochat P, Hulton SA, Acquaviva C, Danpure CJ, Daudon M, De Marchi M, et al. Primary hyperoxaluria type 1: indications for screening and guidance for diagnosis and treatment. Nephrol Dial Transplant. 2012;27(5):1729–36.
  5. Lawrence JE, Wattenberg DJ. Primary hyperoxaluria: the patient and caregiver perspective. Clin J Am Soc Nephrol. 2020;15(7):909–11.
  6. Rumsby G, Hulton SA. From pathogenesis to novel therapies in primary hyperoxaluria. Expert Opin Orphan Drugs. 2019;7(2):57–66.