Leukocyte metabolism and function in uremia.

Area of Science:

• Immunology
• Nephrology
• Cellular Metabolism

Background:

• Patients with kidney failure undergoing hemodialysis often experience increased susceptibility to infections.
• Leukocyte (white blood cell) dysfunction is a potential contributing factor to this increased infection risk.

Purpose of the Study:

• To investigate and compare leukocyte and granulocyte metabolism and function in non-diabetic hemodialysis patients, stable non-diabetic transplant recipients, and healthy controls.
• To determine if metabolic abnormalities in leukocytes correlate with impaired function and could explain increased infection vulnerability.

Main Methods:

• Measured oxygen consumption, glucose uptake, lactate production, and glucose oxidation in leukocytes from 13 hemodialysis patients, 8 transplant recipients, and 13 controls.
• Stimulated granulocyte metabolism using opsonized zymosan (Z) and phorbol myristate acetate (PMA).
• Assessed granulocyte motility in response to zymosan-activated plasma (ZAP).

Main Results:

• Granulocytes from hemodialysis patients exhibited significantly impaired stimulated oxygen consumption, resting and stimulated glucose uptake, stimulated lactate production, and ZAP-stimulated motility compared to controls.
• Transplant recipients showed metabolic responses that were often intermediate between hemodialysis patients and controls, but not significantly different from controls.
• Specific impairments included reduced oxygen consumption (Z: 2.41 vs 3.73; PMA: 2.63 vs 3.67) and glucose uptake (resting: 17.7 vs 36.5; Z: 44.2 vs 71.8; PMA: 63.7 vs 92.8).

Conclusions:

• Hemodialysis is associated with significant abnormalities in granulocyte glucose and oxygen metabolism.
• These metabolic defects likely contribute to impaired granulocyte function, increasing the risk of infection in hemodialysis patients.
• Further research is warranted to explore therapeutic strategies targeting leukocyte metabolism to mitigate infection risk.