KHI Workgroup Opportunity

Endpoints for Hyperoxaluria Clinical Trials


Primary hyperoxaluria and enteric hyperoxaluria are rare disorders that cause frequent kidney stones, nephrocalcinosis, and kidney failure. Promising new treatments are emerging to manipulate oxalate biosynthesis and absorption from the gastrointestinal tract. Careful evaluation of their effectiveness is essential for successful implementation. The major goal of this KHI project is to bring together patients, families, advocacy organizations (Oxalosis and Hyperoxaluria Foundation, OHF), clinicians, scientists, pharmaceutical companies, and the US Food and Drug Administration (FDA) to evaluate potential biochemical endpoints for use to establish efficacy of agents to treat hyperoxaluria to expedite their approval. Work will culminate in the authorship of a document that summarizes the consensus assessment.




Fall 2021

Primary hyperoxaluria and enteric hyperoxaluria are rare disorders. Patients typically experience frequent kidney stones, and can develop nephrocalcinosis, oxalate nephropathy, and kidney failure. There are no approved pharmacologic therapies, and available treatment options are non-specific and of limited effectiveness. Patients with severe primary hyperoxaluria are currently treated with liver transplantation, an extreme intervention given that liver function is otherwise normal. New treatments are sorely needed.

Given the slowly progressive and unpredictable rate of decline in kidney function in most patients, decrease in kidney function or end-stage renal disease is not a feasible endpoint for clinical trials. Kidney stones are common, but the stone events are also not a practical endpoint for clinical trials as their incidence is unpredictable, and reliable identification of stone events is cumbersome, potentially unsafe (as in the case of radiation exposure with computed tomography, the gold standard), and is not standardized. Thus, it is important to identify other endpoint(s) that can be reliably measured and can demonstrate a beneficial treatment effect within a relatively short timeframe in order to expedite the approval of drugs for the treatment of both primary and secondary hyperoxaluria.

The major goal of this KHI project is to bring together the community of patients, families, advocacy organizations (OHF), clinicians, scientists, pharmaceutical companies and the FDA to evaluate potential biochemical endpoints that could be used to establish the efficacy of therapeutic agents for the treatment of primary and secondary forms of hyperoxaluria, and expedite their approval. This project will culminate in the authorship of a document that summarizes the consensus assessment.

Role Name Organization
Co-ChairJohn C. Lieske, MD, FASNMayo Clinic
Co-ChairDawn S. Milliner, MDMayo Clinic
MemberFelicity Enders, PhD, MPHMayo Clinic
MemberW. Todd Lowther, PhDWake Forest School of Medicine
Board of Directors LiaisonUptal D. Patel, MDGilead Sciences, Inc.
Staff LiaisonKim HollanderOxalosis & Hyperoxaluria Foundation
Staff LiaisonJulie BertarelliOxalosis & Hyperoxaluria Foundation
Staff LiaisonMeaghan AllainKidney Health Initiative


  1. Tang X, Bergstralh EJ, Mehta RA, Vrtiska TJ, Milliner DS, Lieske JC. Nephrocalcinosis is a risk factor for kidney failure in primary hyperoxaluria. Kidney international. 2015;87(3):623-31.
  2. Zhao F, Bergstralh EJ, Mehta RA, Vaughan LE, Olson JB, Seide BM, et al. Predictors of Incident ESRD among Patients with Primary Hyperoxaluria Presenting Prior to Kidney Failure. Clinical journal of the American Society of Nephrology : CJASN. 2016;11(1):119-26.