A 65-year-old man with CKD stage 4 (GFR 22 mL/min) develops peripheral neuropathy and recurrent nephrolithiasis. Serum oxalic acid is elevated. Which transport abnormality at the proximal tubule BEST explains primary oxaluria type 1, the inherited form that mimics this presentation?

• A Overexpression of SLC26A6 oxalate transporter in the proximal tubule, secreting excess oxalate into the tubular lumen
• B Impaired ABCG2 transporter on apical membrane causing accumulation of oxalate in proximal tubule cells
• C Mutation in the NaPi-IIa phosphate cotransporter causing phosphate wasting and secondary hyperoxaluria
• D Deficiency of alanine-glyoxylate aminotransferase (AGXT) in peroxisomes, causing glyoxylate to be metabolized to oxalate instead of glycine, with subsequent oxalate accumulation and renal deposition ✓

Explanation

Primary hyperoxaluria type 1 (PH1) is caused by deficiency of alanine-glyoxylate aminotransferase (AGXT), a peroxisomal enzyme that normally converts glyoxylate to glycine. Without AGXT, glyoxylate is shunted to the cytosol where lactate dehydrogenase converts it to oxalate. Massive oxalate production exceeds renal excretory capacity, leading to calcium oxalate deposition in kidneys (nephrocalcinosis, stones), peripheral nerves (oxalate neuropathy), and eventually systemic oxalosis. Pyridoxine (B6) acts as AGXT cofactor and reduces oxalate in responsive cases. Options B, C, and D describe incorrect molecular mechanisms not responsible for primary hyperoxaluria.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.