title: The incident patient cohort study design with uncontrolled dose. Substantial over-estimation of mortality as a function of peritoneal dialysis dose?
abstract: In the Canada-USA (CANUSA) Study, the dialysis dose was neither randomized nor held constant, was measured at 6 month intervals, and the relative risk of mortality (R) was found to correlate linearly to mean values of weekly peritoneal plus renal urea clearance normalized to volume, (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 criteria for dose equivalency in hemodialysis (HD) and peritoneal dialysis (PD) and the HD R/D function. This PD R/D function was nonlinear with 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 measured 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 months decrements in KrT/V, and the population mortality risk at each (KprT/V)m dose level reported in CANUSA was computed from summation of the product of the R/D curve and fractional distribution of (KprT/V)ud values. From these calculations, 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.
authors.affiliation: Davies Medical Center, San Francisco, California, USA.
authors.forename: F A
authors.initials: FA
authors.lastname: Gotch
authors.forename: D E
authors.initials: DE
authors.lastname: Gentile
authors.forename: M L
authors.initials: ML
authors.lastname: Keen
authors.forename: R
authors.initials: R
authors.lastname: Amerling
authors.forename: V W
authors.initials: VW
authors.lastname: Folkert
authors.forename: A S
authors.initials: AS
authors.lastname: Kliger
authors.forename: W B
authors.initials: WB
authors.lastname: Shapiro
mesh_terms: D000704:Analysis of Variance; D001834:Body Water / Q000378:metabolism; D002170:Canada / Q000453:epidemiology; D002985:Clinical Protocols; D015331:Cohort Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000401:mortality* / Q000503:physiopathology / Q000628:therapy*; D010530:Peritoneal Dialysis; D010531:Peritoneal Dialysis, Continuous Ambulatory; D006435:Renal Dialysis; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D014508:Urea / Q000378:metabolism
chemical_list: D014508:Urea