THE INCIDENT PATIENT COHORT STUDY DESIGN WITH UNCONTROLLED DOSE - SUBSTANTIAL OVER-ESTIMATION OF MORTALITY AS A FUNCTION OF PERITONEAL-DIALYSIS DOSE

In the Canada-USA (CANUSA) Study, the dialysis dose was neither random ized nor held constant, was measured at 6 month intervals, and the rel ative risk of mortality (R) was found to correlate linearly to mean va lues of weekly peritoneal plus renal urea clearance normalized to volu me, (KprT/V)m, ranging from 1.5 to 2.3. A risk/dose (R/D) function was derived for continuous ambulatory peritoneal dialysis from kinetic cr iteria for dose equivalency in hemodialysis (HD) and peritoneal dialys is (PD) and the HD R/D function. This PD R/D function was nonlinear wi th breakpoint from steep to shallow slope at (KprT/V)ud = 2.00, where ud refers to uniform single doses in contrast to mean doses with wide variances on the mean. The predicted decrease in renal urea clearance KrT/V per 6 months of CANUSA follow-up was computed from serial measur ed KrT/V in the Randomized Dialysis Prescription and Clinical Outcomes Study and showed it to be 0.21 +/- 0.34. The CANUSA (KprT/V)m values were corrected for the distributed values of 3 month decrements in KrT /V, and the population mortality risk at each (KprT/V)m dose level rep orted in CANUSA was computed from summation of the product of the R/D curve and fractional distribution of (KprT/V)ud values. From these cal culations, the authors conclude that maximum (KprT/V)ud level achieved in CANUSA was 2.00, and the study does not define R/D response above this level.