About ph
Primary Hyperoxaluria, or PH, is a Family of Rare Genetic Disorders Causing Hepatic Oxalate Overproduction That Can Result in Life-threatening Kidney Damage1
Hyperoxaluria is a condition defined by increased urinary excretion of oxalate. Oxalate is a metabolic end product that can also be ingested through food and is of no known use to the body.2,3
In PH, Oxalate Is Produced Through Dysregulation of the Glyoxylate Metabolic Pathway, Where Hepatic Lactate Dehydrogenase, or LDH, Converts Overproduced Glyoxylate to Oxalate1,4-6
Calcium Oxalate Crystals Combine to
Form Kidney and Bladder Stones in PH3
When too much oxalate accumulates in the kidneys,
it binds with calcium to form calcium oxalate (CaOx) crystals4,7
CaOx crystals aggregate to form stones in the kidneys and urinary tract,
and also distribute throughout the kidney tissue, causing nephrocalcinosis3
As PH Advances, Progressive Nephrocalcinosis and Renal Damage May Lead to End-stage Renal Disease and Systemic Oxalosis
Systemic oxalosis occurs when glomerular filtration rate (GFR) drops below 30 to 45 mL/min and oxalate is no longer adequately filtered by the kidneys. At this point, CaOx crystals begin to deposit in tissues of other organs such as the heart, bone, eyes, and skin.1,10-13
Types of ph
There Are 3 Known Genetically Defined Subtypes of Primary Hyperoxaluria, All of Which Can Cause Recurrent Kidney Stones and Progressive Renal Damage14-18
In each of these subtypes of primary hyperoxaluria, hepatic lactate dehydrogenase, or LDH, catalyzes the conversion of glyoxylate to oxalate, converting this benign molecule to a disease-causing agent.4
Abbreviations: AGT, alanine-glyoxylate aminotransferase; GRHPR, glyoxylate reductase-hydroxypyruvate reductase; HOGA, 4-hydroxy-2-oxoglutarate aldolase.
Approximately 11% of patients with signs and symptoms consistent with a diagnosis of PH do not have 1 of the 3 known PH mutations. These patients likely have a PH mutation that has not been discovered yet.14
Kidney stones are the hallmark of
PH1, PH2, and PH3
Stone burden
- PH1: 73%-100% of patients have stones19,20
- PH2: 83%-100% of patients have stones, many before age 4 years16,21,22
- PH3: Nearly 100% of patients have stones, many before age 4 years17,23-25
PH stone appearance26-29
- Light whitish or pale yellow surface color
- Loose aggregations of different-sized crystals
- Approximately 1.6 cm in size
Primary hyperoxaluria often has an
early onset, but patients can vary in symptom
timing and kidney function
Patients are often diagnosed years after symptoms begin32
Abbreviations: CKD, chronic kidney disease; ESRD, end-stage renal disease.
*Limited data, N=4 patients.27
All subtypes of primary hyperoxaluria can have a significant impact on kidney function.14-18
Prevalence of PH
Primary Hyperoxaluria Is More Common Than Previously Thought and Significantly Underdiagnosed
Primary hyperoxaluria affects an estimated 8500 people in the United States.14,33
Estimated US prevalence from clinical studies14,33
<3:1,000,000 or
~1000 people
Expected US prevalence from genetic studies14,33
1:38,600 or
~8500 people
>80% of patients remain
undiagnosed14
*Prevalence based on PH mutant alleles found in the National Heart, Lung, and Blood Institute Exome Sequencing Project (NHLBI ESP) and calculated according to Hardy-Weinberg equilibrium for each PH type using the sum of all alternate PH1, PH2, or PH3 alleles (known and scored as pathogenic) and all wild-type alleles.14
Though PH1 is the most well known, all PH subtypes are likely underdiagnosed.14