Case Report: A rare AGXT pathogenic variant associated with young-adult-onset end-stage kidney disease

Primary hyperoxaluria type 1 (PH1) is a rare autosomal recessive metabolic disorder caused by pathogenic variants in AGXT, leading to hepatic oxalate overproduction, recurrent nephrolithiasis, nephrocalcinosis, progressive kidney dysfunction, and, in advanced stages, systemic oxalosis. Here, we report a family in which two brothers developed recurrent nephrolithiasis and progressed to end-stage kidney disease (ESKD) in young adulthood. The proband, a 32-year-old man, presented with bilateral kidney stones, rapidly progressive renal failure, and extensive extra-renal tissue oxalate deposition on follow-up imaging. Genetic testing identified a homozygous AGXT variant, c.740T>G, p.(Leu247Arg), in both affected siblings, while the proband's mother and daughter were heterozygous carriers, consistent with autosomal recessive inheritance. Plasma oxalate levels were markedly higher in the proband than in his brother and in non-PH ESKD controls. During follow-up, the proband received maintenance hemodialysis alone, whereas his older brother underwent combined hemodialysis, hemofiltration, and hemoperfusion, and appeared to achieve better plasma oxalate control. These findings suggest that intensified blood purification may serve as a potential bridging strategy in advanced PH1 while definitive treatment is being arranged. This report expands the genotypic and phenotypic spectrum of PH1 and underscores the importance of early genetic evaluation in patients with recurrent or early-onset nephrolithiasis, especially when accompanied by rapid renal decline or a positive family history.