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Primed Peripheral Polymorphonuclear Leukocyte: A Culprit Underlying Chronic Low-Grade Inflammation and Systemic Oxidative Stress in Chronic Kidney Disease

Shifra Sela^*,, Revital Shurtz-Swirski^*, Meital Cohen-Mazor^*,, Rafi Mazor^*,, Judith Chezar, Galina Shapiro^*, Kamal Hassan^,, Galina Shkolnik, Ronit Geron and Batya Kristal^*,,

^* Eliachar Research Laboratory; Department of Nephrology; Department of Hematology, Western Galilee Hospital, Nahariya; and Bruce Rappaport Faculty of Medicine, Technion, Haifa, Israel

Address correspondence to: Dr. Batya Kristal, Head of Nephrology and Hypertension Department, Western Galilee Hospital, Nahariya 22100, Israel. Phone: 972-4-9107603; Fax: 972-4-9107482, 972-4-9107469; E-mail: batya.kristal{at}naharia.health.gov.il

Received for publication November 11, 2004. Accepted for publication April 28, 2005.

This study characterizes the causal relationship between peripheral polymorphonuclear leukocyte (PMNL) priming, systemic oxidative stress (OS), and inflammation in patients with varying degrees of renal insufficiency (chronic kidney disease [CKD] not on renal replacement therapy [RRT]: continuous ambulatory peritoneal dialysis or hemodialysis [HD]) and healthy control subjects. Rate of superoxide release was measured after stimulation of PMNL with phorbol 12-myristate 13-acetate or zymosan. Priming was estimated by the rate of superoxide release after phorbol 12-myristate 13-acetate stimulation. Systemic OS was related to PMNL priming and intracellular myeloperoxidase activity. Inflammation was linked to peripheral white blood cells and PMNL counts, PMNL apoptosis, and PMNL ex vivo survival in autologous and heterologous sera. PMNL priming and counts were related to the severity of renal failure in CKD not on RRT. Compared with control subjects, PMNL from all CKD patients showed increased priming, highest in HD, with a significant decrease in their response to zymosan. PMNL myeloperoxidase activity and apoptosis were increased in all renal failure patients. Decreased ex vivo cell survival and elevated leukocyte counts were found in all patients, highest in HD. Both PMNL priming and counts correlated negatively with the GFR. A positive significant correlation was shown between PMNL counts and their priming in all groups, suggesting that the increased PMNL count in peripheral blood is an adaptive response to PMNL priming. Hence, PMNL priming is a key mediator of low-grade inflammation and OS associated with renal failure, occurring before the onset of RRT and further augmented in chronic HD.

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