Managing
Primary Hyperoxaluria

Current treatments

Currently, There Is No FDA-Approved Medication That Addresses All Subtypes of Primary Hyperoxaluria

Current treatment options fall under 5 categories:

Oxalate Reduction
Oxalate Reduction

Ribonucleic acid interference (RNAi) therapy1

  • Approved in PH1 patients only
  • Works by silencing the HAO1 gene encoding the glycolate oxidase (GO) enzyme that is responsible for the conversion of glycolate to glyoxylate in PH1
  • Approved by the US Food and Drug Administration (FDA) in November 2020
Oxalate Reduction

Pyridoxine (vitamin B6)2-7

  • In patients with PH1 and specific AGXT mutations, ie, in patients with p.G170R (~30% of AGXT mutant alleles), and in some patients with p.I244T (~6% of AGXT mutant alleles) or p.F152I (~3.5% of AGXT mutant alleles)
  • Two-thirds of patients with PH1 are completely unresponsive to pyridoxine
  • Trial recommended – if no response, discontinue
Oxalate Reduction

Dietary changes2

  • Avoidance of oxalate-rich foods is recommended
Crystal Inhibition
Crystal Inhibition

Aggressive hydration2

  • Adults/older adolescents: 4 liters water/day
  • School-age children: 2-3 liters water/day
  • Infants/small children: 1-1.5 liters water/day
  • Gastrostomy tube for infants or adults struggling with water intake
Crystal Inhibition

Crystallization inhibitors2

  • Oral potassium citrate or orthophosphate when glomerular filtration rate (GFR) is well preserved
  • Sodium citrate for lower GFR rates at risk for hyperkalemia
Kidney Stone Management2,8
Kidney Stone Management2,8
  • Percutaneous nephrolithotomy (PCNL), or ureteroscopy when PCNL is not indicated
    - While PCNL confers the highest “stone-free” rate, it also carries a higher rate of complications and recovery time
  • Not recommended: extracorporeal shock wave lithotripsy (ESWL), which can contribute to renal injury and renal failure in patients with PH
    - Patients with PH overwhelmingly form stones composed of calcium oxalate, which can be resistant to fragmentation by ESWL
    - Additionally, patients with PH often have concomitant nephrocalcinosis, which can be misinterpreted in imaging, leading to unnecessary shock wave application to nephrocalcinosis spots instead of stones
Renal Replacement Therapy
Renal Replacement Therapy
  • Intermittent hemodialysis (HD), with additional peritoneal dialysis (PD) in some patients2
  • Recommended for patients with oxalate levels >30-45 μmol/L2
  • No type of dialysis is able to sufficiently remove all endogenously overproduced oxalate. Even with a combination of daily HD and PD, a weekly elimination of less than half of endogenously produced oxalate can be achieved9
  • Often serves as a temporary therapy; the goal is to keep plasma oxalate levels below plasma calcium oxalate supersaturation (30-45 μmol/L) to prevent systemic oxalosis in patients awaiting organ transplant2,10,11
Organ Transplant
Organ Transplant
  • Simultaneous liver-kidney transplant recommended at chronic kidney disease (CKD) stage 3b2
  • 34% to 46% of patients with PH1 and 11% of patients with PH2 will require an organ transplant4,7,12
  • 22% to 36% of transplanted organs may fail within 5 years of transplant13
  • Kidney and liver transplant recipients require lifelong immunosuppression14

Current treatment burden

Most Patients With Primary Hyperoxaluria Live With the Fear of Recurring Kidney Stones and Progressive Renal Failure

All subtypes of primary hyperoxaluria are linked to kidney stones and burdensome stone removal procedures.7,12,15-23

70% of patients with PH require one or more urologic procedures during their lifetime15

Information about stone burden and number of stone removal procedures in people with PH1, PH2, and PH3 Information about stone burden and number of stone removal procedures in people with PH1, PH2, and PH3

*Invasive stone removal posed a great burden to patients, including potential adverse effects such as bleeding, scarring, infections, and internal organ damage, as well as days in inpatient care.7

The burden of many current treatments is high. Hyperhydration can have a significant impact on a patient’s quality of life, causing interruptions at school, work, and social events, as well as a loss of sleep. An unlimited bathroom pass can help children take more frequent breaks at school.2,26,27

  • Adults/Older Adolescents2

    4 Liters of Water/Day (135 ounces)

  • School-age Children2

    2-3 Liters of Water/Day (68-101 ounces)

  • Infants/Small Children2

    1-1.5 Liters of Water/Day (34-51 ounces)

    Infants and others struggling with water intake may require a gastrostomy tube (G-tube)2,11

Primary hyperoxaluria creates significant burdens for patients and caregivers as they try to manage their disease; despite their efforts, most remain fearful of developing stones and continued renal damage. A survey showed that 94% of patients hope for new therapies that would prevent dialysis, organ transplant, and oxalosis, and/or improve chances of a normal life span.26,28

Graphic addressing the burden of primary hyperoxaluria for patients and caregivers.

53% of patients with PH and 36% of caregivers are concerned about kidney stones, procedures, and therapies26

Graphic addressing the burden of primary hyperoxaluria for patients and caregivers.

65% of patients with PH and 24% of caregivers are worried about kidney failure26

Graphic addressing the burden of primary hyperoxaluria for patients and caregivers.

71% of patients with PH and 52% of caregivers are fearful of organ transplant26

Future treatments

Treatments Are in Development That Are Intended to Target the Underlying Cause of the 3 Known Subtypes of Primary Hyperoxaluria (PH1, PH2, and PH3)

A treatment that targets hepatic lactate dehydrogenase (LDH) can address all 3 PH subtypes by intervening in the final common step of the glyoxylate metabolic pathway that converts glyoxylate into excess oxalate.29-31

There are LDH-targeting therapies currently in varying stages of development for PH. An RNAi therapy designed to silence the LDHA gene encoding the hepatic LDH enzyme is the furthest in development and is in late-stage clinical trials.31

Hepatic LDH: One target for all 3 PH subtypes29,30,32

Graphic explaining how targeting of hepatic LDH can reduce oxalate in all known genetically defined subtypes of primary hyperoxaluria Graphic explaining how targeting of hepatic LDH can reduce oxalate in all known genetically defined subtypes of primary hyperoxaluria
Touch image for larger view

For more information on clinical trials in primary hyperoxaluria, please click below:

Future Treatments

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