A mechanistic analysis of the National Cooperative Dialysis Study (NCDS).

The purpose of the NCDS was to determine the probability of clinical failure (PF) as a function of the level of dialysis and protein catabolic rate (pcr, g/kg/day). The level of dialysis prescribed in the NCDS was mechanistically defined as Kt/V (product of dialyzer urea clearance and treatment time divided by body urea volume), which exponentially determines decrease in BUN during dialysis and is also a mathematical analogue of pcr, BUN. Mechanistic analysis (MA) showed that PF was a discontinuous function of Kt/V as it was prescribed in the NCDS and that a dependence of PF on pcr could not be assessed because of the study design. The MA results were compared to those reported with statistical analysis (SA) that used BUN and pcr. The SA predicts PF is strongly dependent on pcr with nutrition-dependent high PF for pcr less than or equal to 0.8 and low PF with high pcr and intensive dialysis. The MA suggests SA results may not be valid because a continuous outcome function is assumed and, due to study design, Kt/V was a dependent variable of pcr and these two variables cannot be clearly separated by analysis of BUN and pcr alone.