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Platelet function as an assay for uremic toxins

R M Lindsay, B N Dennis, J C Bergström

Artificial Organs

|January 1, 1981

Summary

Uremic syndrome may involve middle molecule toxins that inhibit platelet function. A new in vitro test using gel-filtered platelets can help study these toxins and their role in uremic platelet defects.

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Area of Science:

Nephrology
Hematology
Biochemistry

Background:

The specific toxins causing uremic syndrome are unknown.
Middle molecular weight (500-3000 daltons) substances and hormonal factors like parathormone are suspected toxins.
Uremic platelet dysfunction is linked to a dialyzable inhibitor, possibly in the middle molecular weight range.

Purpose of the Study:

To investigate the role of middle molecules as toxins in uremic syndrome.
To develop and validate an in vitro assay for studying platelet inhibitors.
To assess the toxicity of middle molecules in uremic serum ultrafiltrates.

Main Methods:

Developed an in vitro system using gel-filtered platelets to measure 14C-labeled serotonin release in response to collagen.
Tested the system's ability to detect reversible and irreversible platelet inhibition by exogenous factors and uremic patient plasma.
Fractionated uremic and normal serum ultrafiltrates and analyzed platelet inhibitory activity in different molecular weight fractions.

Main Results:

The gel-filtered platelet assay demonstrated a reversible platelet inhibitor in uremic patients.
Platelet toxicity was found in fractions containing middle molecular weight substances and a salt peak in uremic serum ultrafiltrates.
Normal serum ultrafiltrates showed platelet toxicity only at the salt peak, suggesting middle molecules are specifically toxic in uremia.

Conclusions:

The findings support a toxic role for middle molecules in uremic syndrome.
The developed gel-filtered platelet assay is a potentially useful tool for studying the biological effects of middle molecules.
Careful controls and understanding bioassay limitations are crucial when investigating uremic toxins.

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