Kidney Week

Abstract: SA-PO0177

Diagnostic Challenges in a Young Patient with Kidney Stone Disease

Session Information

• Tubular, Metabolic, and Systemic Noncystic Genetic Kidney Diseases
  October 24, 2026 | Location: Exhibit Hall A, Convention Center
  Abstract Time: 10:00 AM - 12:00 PM

Category: Genetic Diseases of the Kidneys

• 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)

Authors

• Cuiban, Elena, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Elena Cuiban, MD

• Cana Ruiu, Daniela, Clinical County Hospital, Craiova, Romania

Daniela Cana Ruiu, MD

• Lica, Andrei Daniel, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Andrei Daniel Lica

• Stepan, Elena, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Elena Stepan, MD

• Serban Feier, Larisa, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Larisa Serban Feier

• Vacaroiu, Ileana Adeala, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania

Ileana Adeala Vacaroiu, MD, PhD

Introduction

Primary hyperoxaluria type 1 is a rare inherited metabolic disorder caused by mutations in one of the three genes: AGXT, GRHPR or HOGA1. The clinical presentation is highly variable and may overlap with other tubular disorders, making diagnosis challenging, particularly in patients with atypical genetic findings. We present the case of a young patient with high stone burden and a challenging differential diagnosis.

Case Description

A 20-year-old female with no previously known medical history presented to the ER with abdominal and loin pain. Laboratory and imaging work-up revealed severe anemia (Hb 4.8 g/dL), stage 3 AKI (creatinine 20.10 mg/dL, urea 303 mg/dL), HAGMA with a hyperchloremic component, severe hyperkalemia, and a CT scan showing obstructive bilateral staghorn kidney stones and severe hydronephrosis.
After partial recovery of kidney function, an extensive metabolic work-up was performed, revealing persistent mild hyperchloremic metabolic acidosis, hypocitraturia, hyperoxaluria, and low urinary K and Mg, suggesting either primary hyperoxaluria or RTA. A positive furosemide-fludrocortisone test guided the differential diagnosis toward distal renal tubular acidosis. Systemic immunological causes of dRTA were ruled out, and considering the severe anemia at presentation, a differential diagnosis involving SLC4A1 gene mutations was discussed. Therefore, whole-exome sequencing was performed.
Extended genetic testing detected an AGXT gene mutation (NM_000030.3:c.595+37C>T) in the heterozygous state, an intronic variant previously classified as a VUS. The in silico predictor Human Splicing Finder suggests that the genetic variant c.595+37C>T could interfere with normal exon splicing. In addition, two genetic variants of the same gene, c.32C>T, p.(Pro11Leu), and c.1020A>G, p.(Ile340Met) were identified in the homozygous state; these polymorphisms may lead to partial intracellular mistargeting of the protein encoded by the AGXT gene. Based on the genotype–phenotype correlation, the diagnosis of type 1 primary hyperoxaluria was confirmed, and treatment with Lumasiran was initiated.

Discussion

Metabolic and genetic testing are cornerstones in the evaluation of young patients with kidney stone disease, and genotype-phenotype correlations could be critical in the light of numerous newly described mutations.