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New insights into proteinuria/albuminuria
Wayne D Comper1, Julijana Vuchkova1, Kevin J McCarthy2
1Salaqua Diagnostics Inc, New York, NY, United States.
Frontiers in Physiology
|October 13, 2022
Summary
Nephrotic syndrome dramatically increases protein clearance due to nephron uptake, not just glomerular filtration. Proximal tubule receptors for protein retrieval and degradation explain these changes in kidney disease.
Area of Science:
- Nephrology
- Molecular Biology
- Physiology
Background:
- Proteinuria in nephrotic patients increases 10,000-100,000-fold compared to healthy subjects.
- Extracellular biophysical mechanisms at the glomerular filtration barrier do not fully explain this increase.
- The nephron's filtration and cellular uptake processes are critical for understanding fractional protein clearance changes.
Purpose of the Study:
- To explain the significant increase in fractional protein clearance observed in nephrotic patients.
- To investigate the role of the nephron, particularly proximal tubular cells, in protein handling.
- To re-evaluate existing concepts of glomerular filtration selectivity.
Main Methods:
- Analysis of fractional protein clearance in healthy and nephrotic human subjects.
- Examination of protein receptors and pathways in proximal tubular cells.
- Critique of established glomerular filtration selectivity models ('charge selectivity', 'large pores').
Main Results:
- Glomerular filtration of proteins is primarily size-selective and largely unchanged in kidney disease.
- Proximal tubular cells possess high- and low-capacity receptors for protein retrieval and degradation.
- Inhibition or saturation of these proximal tubule pathways may cause nephrotic syndrome and hypoproteinemia.
Conclusions:
- The nephron's combined filtration, retrieval, and degradation pathways quantitatively explain fractional protein clearance changes in nephrotic conditions.
- Established glomerular concepts of 'charge selectivity' and 'large pores' are flawed.
- Proximal tubular protein retrieval is a crucial physiological process, alongside water and salt retrieval.
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