January 2026 Research Update

This month added early but concrete research signals that oxalate production in primary hyperoxaluria type 1 (PH1) can be reduced in more than one way. In mouse and cell experiments, one oral compound lowered urine oxalate and reduced kidney crystal buildup, while a separate lab approach aimed to rescue the activity of the missing or faulty liver enzyme that triggers PH1. [1] [2]

One research group tested an experimental oral drug (called compound 2) designed to block two liver enzymes involved in making oxalate and to lower one of those enzymes by speeding up its breakdown. In a PH1 mouse model, the study reported lower urinary oxalate and fewer calcium-oxalate crystals in the kidneys compared with a control group, with no clear liver toxicity signals reported in that short-term setting. [1]

A separate laboratory study developed very small antibody-like proteins (nanobodies) that stick to AGT, the enzyme that does not work properly in PH1. In a cell model, an engineered nanobody (NB-AGT-3) was taken up by cells and was reported to increase the activity of disease-associated AGT variants, which is a different strategy than blocking oxalate production upstream. [2]

For patients and caregivers, these studies mainly matter as early research that expands the set of possible future treatment directions for PH1. The mouse and cell results help clarify that researchers are pursuing both (1) lowering the body\'s oxalate production and (2) trying to restore function of the underlying enzyme problem in PH1, but neither approach in these papers tells us how well this would work in people. What remains uncertain includes long-term safety, how well these strategies would translate to human livers and kidneys, and whether they would meaningfully reduce stones or slow kidney damage in real-world care. [1] [2]

This month\'s clinical publication was a single case that reinforces a familiar PH1 story: stones and kidney calcium buildup can begin early and progress toward chronic kidney disease, especially when diagnosis and specialized treatment are delayed. After genetic confirmation, the report describes starting lumasiran (an RNA interference medicine designed to lower oxalate production) and notes clinical stability with no reported progression during follow-up. [3]

In this report, a 9-year-old boy with PH1 had early kidney stones and nephrocalcinosis that progressed to chronic kidney disease, including an episode of obstructive stone-related acute kidney injury with partial recovery. Genetic testing confirmed a homozygous AGXT c.33dup variant, and a trial of pyridoxine was reported as ineffective before lumasiran was initiated. The authors also reported family screening that identified two siblings as heterozygous carriers. [3]

For families living with PH1, this report mainly adds a real-world example of how genetic confirmation can connect a child\'s kidney stones and kidney calcification to an underlying cause and open the door to disease-targeted therapy. Because it is only one patient, it cannot tell us what most children will experience on lumasiran, but it does help illustrate what clinicians mean by early-onset stones, kidney calcium buildup, and kidney function decline in PH1. It also highlights that access to genetic testing and newer medicines can be a major part of the patient experience, especially in resource-limited settings. [3]