Impact of treatment modality, biochemical parameters and apoptosis on polymorphonuclear cell (PMN) function in patients with renal failure

It has been suggested that PMN apoptosis is increased in dialysis patients and may contribute to cellular dysfunction. We investigated the effect of treatment modality and biochemical parameters on PMN apoptosis and function. Blood was drawn from 17 controls, 17 patients with chronic renal failure (CRF; creatinine clearance 28 ± 14 ml/min/1.73 m²), 10 hemodialysis (HD) and 11 CAPD patients. Upon collection, whole blood aliquots were incubated in RPMI-1640 with propidium iodide (PI)-labeled Saureus (SA), PMA, fMLP or LPS for 30 min. Cells were then stained with DCFH-DA and analyzed by flow cytometry, in order to quantify phagocytosis and H₂O₂ release by PMN. After separation by gradient centrifugation, PMN were stained with Annexin-V and PI in order to quantify apoptosis by flow cytometry. The results were correlated with blood levels of urea, creatinine, bicarbonate, albumin and PTH. Results are presented as means ± SD.

Among CRF and HD patients, there was an inverse correlation between apoptosis and SA- (r = 0.62, P = 0.01 and r = 0.89, P = 0.02, respectively) and LPS-stimulated H₂O₂ release (r = 0.68, P = 0.005 and r = 0.61, P = 0.058, respectively). No biochemical parameters correlated with apoptosis or cellular functions. In summary, PMN apoptosis contributes to cellular malfunction in uremia, but does not account for all the dysfunction. Hence, it is possible that other uremic toxins affect cell performance independently of apoptosis.

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