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A Mass Spectrometry-Based Approach to Identify Phosphoprotein Phosphatases and their Interactors
Published on: April 29, 2022
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On the relationship between proteinuria and plasma phosphate
Sophie de Seigneux1, Alexandra Wilhelm-Bals2, Marie Courbebaisse3
1Service and laboratory of Nephrology, Department of Internal Medicine Specialties and Department of Physiology and Metabolism, University Hospital and University of Geneva, Switzerland.
Swiss Medical Weekly
|October 25, 2017
Summary
Albuminuria, or protein in urine, is linked to kidney and heart issues. This study shows it alters kidney phosphate handling, potentially via Klotho and FGF23 pathways, contributing to cardiovascular disease.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Biochemistry
Background:
- Albuminuria is a marker for kidney and cardiovascular disease.
- Phosphate retention is implicated in cardiovascular events in chronic kidney disease (CKD).
- The link between albuminuria and phosphate metabolism is not fully understood.
Purpose of the Study:
- To investigate if albuminuria affects tubular phosphate handling.
- To explore the molecular mechanisms linking albuminuria to phosphate dysregulation.
- To determine the role of Fibroblast Growth Factor 23 (FGF23) and Klotho in this process.
Main Methods:
- Association study between albuminuria and phosphataemia in pediatric nephrotic syndrome and adult CKD patients.
- Animal models of nephrotic proteinuria to study tubular phosphate transporter expression.
- Analysis of FGF23 and Klotho protein levels and signaling pathways in proteinuric animals.
Main Results:
- Higher albuminuria correlated with higher serum phosphate levels, independent of glomerular filtration rate (GFR).
- Albuminuric animals showed increased renal sodium-phosphate co-transporter expression.
- FGF23 pathway was inhibited, and Klotho expression was reduced in proteinuric models.
- Albumin had no direct effect on cellular phosphate transport.
Conclusions:
- Albuminuria alters kidney tubular phosphate handling independently of GFR.
- Mechanisms involve Klotho down-regulation and FGF23 resistance.
- This finding may explain the link between albuminuria and cardiovascular disease through altered phosphate handling.
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