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Molecular Pathophysiology of Acid-Base Disorders
Carsten A Wagner1, Pedro H Imenez Silva1, Soline Bourgeois1
1Institute of Physiology, University of Zurich, Zurich, Switzerland; National Center for Competence in Research Kidney, Switzerland.
Seminars in Nephrology
|July 14, 2019
Summary
Renal acid-base disorders stem from inherited or acquired kidney issues. This review details genetic mutations causing proximal and distal renal tubular acidosis, and chronic kidney disease impacts on acid-base balance.
Area of Science:
- Nephrology
- Renal Physiology
- Genetics
Background:
- Acid-base balance is vital for cellular functions and cardiovascular health.
- The kidneys play a crucial role in maintaining acid-base homeostasis through bicarbonate reabsorption, regeneration, and acid excretion.
- Disturbances in renal acid-base handling can lead to serious health consequences.
Purpose of the Study:
- To review acid-base disorders arising from inherited and acquired renal processes.
- To highlight specific genetic mutations affecting kidney tubule function and acid-base balance.
- To discuss the impact of chronic kidney disease on acid-base homeostasis.
Main Methods:
- Literature review of inherited and acquired renal acid-base disorders.
- Analysis of genetic mutations affecting proximal tubule and collecting duct function.
- Examination of the role of ammoniagenesis in chronic kidney disease.
Main Results:
- Rare inherited monogenic diseases affecting SLC4A4, CLCN5, ATP6V1, ATPV0A4, SLC4A1, and FOXI1 genes cause proximal and distal renal tubular acidosis.
- Mutations in carbonic anhydrase II lead to mixed proximal and distal phenotypes.
- Advanced chronic kidney disease impairs ammoniagenesis, contributing to renal acidosis.
Conclusions:
- Genetic defects in renal tubules are significant causes of inherited renal tubular acidosis.
- Acquired conditions, particularly chronic kidney disease, profoundly affect acid-base balance due to impaired renal function.
- Understanding these renal mechanisms is key for managing acid-base disorders.
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