Differential Glucocorticoid Responsiveness of Dialysis Patients’ Lymphocytes

Abstract

Objectives To evaluate in vitro glucocorticoid responsiveness of phytohemagglutinin (PHA)-stimulated lymphocytes from peritoneal dialysis (PO) patients compared to hemodialysis (HO) patients. Design Cross-sectional study of prevalent PO and HO patients and concurrent control subjects. Setting Urban outpatient dialysis unit. Patients 20 HO, 14 PO, and 20 control subjects. Measurements Using standard lymphocyte culture techniques, the concentration of prednisolone (P) and methylprednisolone (MP) required to cause 50% inhibition (ICso) of the proliferative response to phytohemagglutinin (PHA) was determined from dose-response curves. Results There was considerable heterogeneity in the sensitivities of individual patients’ PBMC to glucocorticoid inhibition, especially those of HO patients’ cells to P. The mean: i: SO ICso for MP was significantly (p ≤ 0.001) lower than that for P in each cohort: PO 11 ± 5 vs. 34 ± 18 ng/mL; HO 22 ± 14 vs. 89 ± 43 ng/mL; control subjects 14 ± 11 vs. 55 ± 56 ng/mL. Interestingly, the ICSO for both P and MP was significantly higher in HO than in either PO or controls (ANOVA, P: F = 6.56, p = 0.003; MP: F = 3.77, p = 0.03), indicating decreased sensitivity of HO lymphocytes to both drugs. There were no significant differences in mean ICSO values for either P or MP between PO and controls. No correlations were found between ICSO for either P or MP and patient age, gender, duration of dialysis, serum creatinine, serum albumin, or parathyroid hormone level. Conclusions In vitro glucocorticoid responsiveness of dialysis patients’ lymphocytes appears to be influenced by dialysis modality, butthefactor(s) involved remains to be determined. Thegreater sensitivity of PO lymphocytes to both P and MP might result in better immunosuppression and less severe rejection after renal transplantation. MP may be particularly advantageous following renal transplantation for any patient manifesting relative or absolute in vitro resistance to P.