Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study

Comparison of methods to predict equilibrated Kt/V in the HEMO Pilot Study. The ongoing HEMO Study, a National Institutes of Health (NIH) sponsored multicenter trial to test the effects of dialysis dosage and membrane flux on morbidity and mortality, was preceded by a Pilot Study (called the MMHD Pilot Study) designed to test the reliability of methods for quantifying hemodialysis. Dialysis dose was defined by the fractional urea clearance per dialysis determined by the predialysis BUN and the equilibrated postdialysis BUN after urea rebound is completed (eKt/V). In the Pilot Study the blood side standard for eKt/V was calculated from the predialysis, postdialysis, and 30-minute postdialysis BUN. Four techniques of approximating eKt/V that eliminated the requirement for the 30-minute postdialysis sample were also evaluated. The first adjusted the single compartment Kt/V using a linear equation with slope based on the relative rate of solute removal (K/V) to predict eKt/V (rate method). The second and third techniques used equations or mathematical curve fitting algorithms to fit data that included one or more samples drawn during dialysis (intradialysis methods). The fourth technique (dialysate-side) predicted eKt/V from an analysis of the time-dependent profile of dialysate urea nitrogen concentrations (BioStat method; Baxter Healthcare, Inc., Round Lake, IL, USA). The Pilot Study demonstrated the feasibility of conventional and high dose targets of about 1.0 and 1.4 for eKt/V. Based on the blood side standard method, the mean ± SD eKt/V for patients randomized to these targets was 1.14 ± 0.11 and 1.52 ± 0.15 (N = 19 and 16 patients, respectively). Single-pool Kt/Vs were about 0.2 Kt/V units higher. Results were similar when eKt/V was based on dialysate side measurements: 1.10 ± 0.11 and 1.50 ± 0.11. The approximations of eKt/V by the three blood side methods that eliminated the delayed 30-minute post-dialysis sample correlated well with eKt/V from the standard blood side method: r = 0.78 and 0.76 for the single-sample (Smye) and multiple-sample intradialysis methods (N = 295 and 229 sessions, respectively) and 0.85 for the rate method (N = 295). The median absolute difference between eKt/V computed using the standard blood side method and eKt/V from the four other methods ranged from 0.064 to 0.097, with the smallest difference (and hence best accuracy) for the rate method. The results suggest that, in a dialysis patient population selected for ability to achieve an equilibrated Kt/V of about 1.45 in less than a 4.5 hour period, use of the pre and postdialysis samples and a kinetically derived rate equation gives reasonably good prediction of equilibrated Kt/V. Addition of one or more intradialytic samples does not appear to increase accuracy of predicting the equilibrated Kt/V in the majority of patients. A method based on dialysate urea analysis and curve-fitting yields results for equilibrated Kt/V that are similar to those obtained using exclusively blood-based techniques of kinetic modeling

Abundance of Early Functional HIV-Specific CD8+ T Cells Does Not Predict AIDS-Free Survival Time

Background T-cell immunity is thought to play an important role in controlling HIV infection, and is a main target for HIV vaccine development. HIV-specific central memory CD8+ and CD4+ T cells producing IFNγ and IL-2 have been associated with control of viremia and are therefore hypothesized to be truly protective and determine subsequent clinical outcome. However, the cause-effect relationship between HIV-specific cellular immunity and disease progression is unknown. We investigated in a large prospective cohort study involving 96 individuals of the Amsterdam Cohort Studies with a known date of seroconversion whether the presence of cytokine-producing HIV-specific CD8+ T cells early in infection was associated with AIDS-free survival time. Methods and Findings The number and percentage of IFNγ and IL-2 producing CD8+ T cells was measured after in vitro stimulation with an overlapping Gag-peptide pool in T cells sampled approximately one year after seroconversion. Kaplan-Meier survival analysis and Cox proportional hazard models showed that frequencies of cytokine-producing Gag-specific CD8+ T cells (IFNγ, IL-2 or both) shortly after seroconversion were neither associated with time to AIDS nor with the rate of CD4+ T-cell decline. Conclusions These data show that high numbers of functional HIV-specific CD8+ T cells can be found early in HIV infection, irrespective of subsequent clinical outcome. The fact that both progressors and long-term non-progressors have abundant T cell immunity of the specificity associated with low viral load shortly after seroconversion suggests that the more rapid loss of T cell immunity observed in progressors may be a consequence rather than a cause of disease progression