What question did this study set out to answer?

This research aims to investigate the molecular mechanisms underlying proximal tubule dysfunction associated with metabolic acidosis and Fanconi-like syndrome.

February 12, 2026Science Translational Medicine

Metabolic acidosis causes a Fanconi-like syndrome with intracellular trafficking defects and proximal tubule dysfunction

View Full Paper

Ask AI

Bookmark

This research aims to investigate the molecular mechanisms underlying proximal tubule dysfunction associated with metabolic acidosis and Fanconi-like syndrome.
Used Atp6v0a4 knockout mice to model metabolic acidosis and proximal tubule dysfunction.
Assessed alterations in endolysosomal trafficking using markers like Rab7 and Lamp1.
Examined the effects of bicarbonate therapy on correcting metabolic acidosis and associated defects.
Studied human kidney organoids to correlate findings with human data.
Atp6v0a4 KO mice displayed significant proximal tubule dysfunction with increased phosphaturia and proteinuria.
Diminished Rab7 levels and increased Ist1-labeled Lamp1-positive vesicles were observed in KO mice under metabolic acidosis.
Bicarbonate therapy corrected the proximal tubule dysfunction and trafficking defects in KO mice.
Comparable trafficking defects were noted in wild-type mice after acid challenge, mimicking KO results.
Human kidney organoids showed similar trafficking alterations correlating with findings in mouse models.

Discussion

No takes yet. Share an insight, caveat, or question.

Implication

Experimental analysis shows metabolic acidosis leads to proximal tubule dysfunction in a mouse model, suggesting pathogenic insights for kidney disease.

Cite This Study

Hennings et al. (2026) studied this question.

synapsesocial.com/papers/698d6eeb5be6419ac0d54e4a https://doi.org/10.1126/scitranslmed.ads6299

View Full Paper

Ask AI

Bookmark

Implication

Experimental analysis shows metabolic acidosis leads to proximal tubule dysfunction in a mouse model, suggesting pathogenic insights for kidney disease.

Metabolic acidosis causes a Fanconi-like syndrome with intracellular trafficking defects and proximal tubule dysfunction

Key Points

Discussion

Implication

Cite This Study

Metabolic acidosis causes a Fanconi-like syndrome with intracellular trafficking defects and proximal tubule dysfunction

Key Points

Discussion

Implication

Cite This Study

Keep reading

Keep reading