Table 1.

Potential end points for clinical trials in enteric hyperoxaluria

Potential Trial End Point	Strengths	Limitations
Clinical outcome
Symptomatic kidney stone events	Clinical outcome that could support traditional approval	Limited available data on frequency and risk factors of symptomatic kidney stone events in patients with EH
Surrogate
Irreversible loss of kidney function	Validated surrogate for progression to kidney failure that could support traditional approval	Limited data on the rate of loss of kidney function and risk factors of more rapid loss of kidney function in patients with EH
New kidney stones or growth of kidney stones on imaging	Mechanistic rationale and observational data suggest changes on imaging could be associated with future symptomatic kidney stone events	No data available to demonstrate that treatment of asymptomatic kidney stones that are detected by imaging reduces the risk of future symptomatic kidney stones; not clear how to define this end point or the magnitude of change that would confer benefit
Urinary oxalate	Mechanistic rationale and observational data suggest magnitude of hyperoxaluria is associated with future symptomatic kidney stone events	Available observational data suggest substantial uncertainty regarding the relationship between urinary oxalate and symptomatic kidney stone events; available data inadequate to determine how an end point based on urinary oxalate should be defined, magnitude of urinary oxalate change that would confer benefit, and in what patient population(s)
Urinary calcium oxalate supersaturation	Mechanistic rationale and observational data in non-EH populations suggest an association with kidney stone formation	Limited data in EH populations to support use of calcium oxalate supersaturation as a surrogate end point
Plasma oxalate	Mechanistic rationale for use as a surrogate for the development of clinical manifestations of systemic oxalosis	Reports of systemic oxalosis are rare in patients with EH; hence, the role of plasma oxalate as an end point in EH trials is unclear

EH, enteric hyperoxaluria.