

Managing PH1
Disease-mitigating strategies can lessen damage by reducing stone formation and renal deposition of calcium oxalate crystals, underscoring the importance of early diagnosis and intervention.1-3
medical management options
PH1 medical management options aim to delay progressive renal function decline by mitigating calcium oxalate crystal deposition and stone formation.2,4,5
- Hyperhydration2
- Recommended daily fluid intake: more than 2-3 liters/square meter of body surface area2
- Gastronomy tube may be necessary to ensure constant urine dilution in infants2
- High dose pyridoxine therapy and calcium oxalate crystallization inhibitors such as alkali citrate4-6
- Very few PH1 patients are complete responders to vitamin B6 and a subset of patients show a partial response, although data are limited, with only one prospective trial published to date (n=12)4-6
- Intensive dialysis strategies beyond conventional methods4
- Dialysis either serves as a bridge to transplantation or as an adjunct therapy after liver‐kidney transplantation4
- To reduce plasma oxalate levels, PH1 patients with compromised renal function require up to 6 hemodialysis sessions per week, which may need to be combined with continuous peritoneal dialysis4,5,7,8
Most of the above medical management options are inadequate at reducing oxalate overproduction, and even intensive dialysis will not consistently lower plasma oxalate. Currently, there are no approved medications for the treatment of PH1.3,9
managing PH1 can be burdensome2,4,10
The Skinner family is an example of that. The PH1 management tactics they use to manage the condition in their family present challenges to their everyday routines.

Watch the medical management journey Claire had to undergo to manage her PH1 prior to her liver transplant.
ONLY LIVER TRANSPLANTATION RESOLVES THE UNDERLYING METABOLIC DEFECT5
Liver transplant addresses the defect that causes glyoxylate—an organic compound generated by the liver enzyme GO—to convert into oxalate.5 This procedure carries significant morbidity and mortality.2,4,5
As kidney function declines, a kidney transplant may be required along with a liver transplant.4,5 Although effective at halting oxalate overproduction, there are clinically significant complications associated with transplant, including renal vein thrombosis, delayed graft function, and graft rejection.11
A 5-year survival rate of 67% was reported for PH1 patients who had undergone a dual liver-kidney transplant and 45% was reported for those who have poor conditions with systemic oxalosis.12,13 Children with PH1 receiving a dual liver-kidney transplant have a 1-year survival rate of 89%.14 The 5-year survival for children with PH1 is estimated at 75% after liver-kidney transplantation.15
Following dual liver/kidney transplant, oxalate stores will eventually decrease.4,12
There is an urgent need for ADDITIONAL treatment options9,16
An urgent need exists for additional treatment options that reduce liver oxalate in PH1.9,16 Lower urinary oxalate (UOx) excretion predicted improved renal survival in a retrospective study that included 192 patients with PH1 from the Rare Kidney Stone Consortium Registry.16
Higher urinary oxalate levels are associated with faster progression to ESRD16

HR=3.4 (95% CI 1.4-7.9)
P=0.005

Among patients who did not have ESRD at diagnosis, renal survival estimates were lowest for patients with UOx excretion ≥2.4 mmol/1.73 m2/24 hours (HR=3.4 [95% CI: 1.4-7.9]; P=0.005).16
Figure adapted from Zhao F, et al. Clin J Am Soc Nephrol. 2016;11(1):119-126.
Given the progressive nature of the disease, early diagnosis and disease management are critical in PH1.4,17
RESEARCH IS ONGOING
There are a number of investigational therapies in development for PH19,18-20
- Oxalate synthesis pathway inhibitors: Prevent expression or activity of enzymes involved in oxalate production9,18,21
- RNA interference (RNAi) therapeutics bind to messenger RNA of target enzymes, preventing their expression via the RNAi pathway9,21
- Enzyme inhibitors suppress enzymatic activity18
- Oxalate degraders: Live biotherapeutic products and crystalline formulations degrade oxalate in the gastrointestinal tract19,20