Table 1.
Demographic and clinical characteristics of the study population.
Fig 1.
Correlation between d-sp ELISPOT (as number of spots) and median (i.e., median number of spots against the six B cell lines) PRT (A) and PRT+IL-15 (B) (rho = 0.18, P = 0.021 and rho = 0.19, P = 0.016, respectively). Correlation between median PRT and median PRT IL-15 (rho = 0.96, P<0.001) (C).
Fig 2.
Median PRT and median PRT+IL5 (as number of spots) for each of the 168 patients.
Dotted lines connect data belonging to the same patients. The number of spots was larger with median PRT+IL15 compared to median PRT (P<0.001 by Wilcoxon matched-pairs signed-ranks test).
Table 2.
Association between recipients’ pre-transplant characteristics and pre-transplant number of spots of each assay.
Fig 3.
Risk of BPAR (i.e. proportion of patients developing BPAR) according to the number of IFN-γ spots for d-sp ELISPOT (A), median PRT (B), and median PRT+IL15 (C). The solid line represents the risk of BPAR, the dashed lines represent the upper and lower 95% confidence intervals. The risk of BPAR significantly increased with the number of spots of d-sp ELISPOT (P = 0.042), whereas it did not increase with the number of spots of Median PRT and Median PRT+IL15 (P = 0.87 and P = 0.88, respectively). The superimposed histograms report the frequency distribution of the data values in the study population. The spread of the data values was larger with d-sp ELISPOT compared to Median PRT and Median PRT+IL15. Outside the range of the actual data distribution the risk of BPAR is not reported because it would otherwise represent an inaccurate extrapolation of the BPAR risk estimates. The plotted risk of BPAR is adjusted for recipient and donor age, living (vs deceased) donor, cold ischemia time, Thymoglobulin induction, re-transplantation, pre-transplant HLA antibodies, HLA A/B AND HLA DR mismatch, glomerulonephritis as primary renal disease, dialysis vintage, and prednisone withdrawal (i.e., Model 2 in Table 3). Every covariate was set to the mean value in the study population, the indicator variate prednisone withdrawal was set to zero (i.e., no withdrawal).
Table 3.
Crude and adjusted odds ratio of BPAR associated with d-sp ELISPOT.
Fig 4.
Fitted means of 48-months eGFR decline from multiple regression models for repeated measures (see text) in patients with positive and negative d-sp ELISPOT (A), positive and negative PRT (B), positive and negative PRT+IL15 (C), and in hypothetical patients having number of IFN-γ spots equal to the 0°, 80°, 90°, and 95° centile of the study population for d-sp ELISPOT (D), for median PRT (E), and for median PRT+IL15 (F). The 48-months eGFR decline did not differ significantly when comparing positive vs negative assays, but it did differ when examining the relation with the numerical variable number-of-spots of median PRT (E) and of median PRT+IL15 (F). According to multiple regression models, the 48-months eGFR declined by -3.4mL/min/1.73m2 (95%CI: -5.8 to -1.1; P = 0.005) and by -2.8 mL/min/1.73m2 (-5.2 to -0.3; P = 0.037) per one standard deviation unit increase in the number of IFN-γ spots of median PRT and median PRT+IL15, respectively. Panels D, E, and F report the fitted 48-months eGFR decline of hypothetical patients having number of IFN-γ spots equal to the 0°, 80°, 90°, and 95° centile of the study population to provide a visual appraisal of the fitted relation mentioned above between the number of IFN-γ spots and eGFR decline. Dots represent predicted means from the fitted multiple regression models for repeated measures, vertical bars represent 95% confidence intervals. Regression models were adjusted for 3-month eGFR, recipient and donor age, living (vs deceased) donor, cold ischemia time, Thymoglobulin induction, re-transplantation, pre-transplant HLA antibodies, HLA A/B AND HLA DR mismatch, glomerulonephritis as primary renal disease, dialysis vintage, and prednisone withdrawal.