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Implications of The CANUSA Study PDF
Implications of The CANUSA Study PDF
Nephrology
Dialysis
Transplantation
Introduction
The CanadaUSA (CANUSA) study of peritoneal
dialysis [1] has increased awareness of the association
between increased removal of small molecular weight
solutes and improved patient survival. The data also
suggest that patients who start continuous ambulatory
peritoneal dialysis (CAPD) with little residual renal
function are less well nourished and that a poor
nutritional status is associated with decreased patient
survival [2]. There is also a suggestion that patients
with higher peritoneal transport, as defined by the
peritoneal equilibrium test (PET ) [3], have a decreased
probability of survival [4]. These CANUSA-derived
data suggest that dialysis treatment should be initiated
earlier, that the total weekly clearance of small molecular weight solutes should be considerably higher than
is current practice and that higher peritoneal transport
is not a desirable feature for CAPD treatment. These
suggestions are controversial [5,6 ]. There are concerns,
in an incident dialysis population, about the relative
value of clearance due to residual renal function and
that due to peritoneal dialysis. Others are concerned
that earlier initiation of dialysis may not be accepted
by funding agencies and that the increased economic
burden is not justifiable. Higher adequacy targets are
not considered feasible for heavier patients with little
residual function, and the increased cost of higher
dialysate volumes may discourage some providers.
The objective of this review is to present the conclusions reached in the peer-reviewed publications from
the CANUSA peritoneal dialysis study group [1,2,4]
and to consider the controversy regarding the clinical
inferences derived from those conclusions.
Methods
Subject
Publications
1. Adequacy of dialysis
2. Initiation of dialysis
3. Membrane transport
rate (GFR) defined as the average of urea and creatinine clearance. Daily clearances were converted to
weekly by multiplying the daily values by seven. These
estimates of adequacy of dialysis were determined
when CAPD or CCPD training was completed and at
6 monthly intervals thereafter.
Estimates of nutritional status were obtained at the
same intervals as for adequacy. These included the
serum albumin concentration, the subjective global
assessment (SGA) [8], protein catabolic rate (PCR)
according to Randerson et al. [9] normalized to standard body weight (0.58/V ) and percentage lean body
mass (%LBM ) from creatinine kinetics [10]. The statistical analyses are described in detail elsewhere [1].
Results
The relative risk (RR) of death was increased with
increased age, dialysis in the USA, insulin-dependent
diabetes mellitus, history of cardiovascular disease,
lower serum albumin concentration, and worse nutritional status according to SGA and %LBM. The RR
of death was decreased by 6% for a 0.1 greater weekly
Kt/V and by 7% for a 5 l/1.73 m2 greater weekly CCr.
Conclusions
Controlling for other independent variables, there is
an association of greater weekly Kt/V and greater
weekly CCr with a decreased RR of death. There was
also an association of better nutritional status with a
decreased RR of death.
Prediction
Data from the multivariate statistical analysis was used
to create a mathematical model to predict survival at
different levels of weekly Kt/V and weekly CCr. This
model assumes that peritoneal and renal clearances are
equivalent, and predicts the probability of survival, in
this population, if total weekly clearances could be
maintained at stable levels by increasing peritoneal
clearance as renal clearance is lost.
The predicted 2 year survival probabilities are shown
in Table 2. Over the range of adequacy studied, there
was a progressive increase in the probability of survival
with increased Kt/V and CCr.
Clinical inference
The theoretical constructs addressing adequacy of dialysis for CAPD [1113] were reviewed recently [14].
159
Survival %
CCr
Survival %
2.3
2.1
1.9
1.7
1.5
81
78
74
71
66
95
80
70
55
40
86
81
78
72
65
160
D. N. Churchill
Table 5. Two year survival probabilities according to nutritional
status at initiation of dialysis
Methods
The residual renal function at initiation of CCPD was
determined for the 680 patients enrolled in the
CANUSA study [1] and expressed as renal Kt/V and
as an estimate of GFR determined from the mean of
renal urea and creatinine clearance. For each of renal
Kt/V and GFR, three cohorts were created representing the upper, middle and lower thirds of residual
renal function. For each tertile of residual renal
function, nutritional status was expressed as the mean
of serum albumin concentration, SGA, %LBM and
nPCR. For several levels of each of these baseline
nutritional estimates, the association with the actual
survival probability was determined using the
KaplanMeier method [18] and compared by the
log-rank test.
Albumin
g/l
<30
3035
>35
Log-rank
LBM
%
64%
75%
85%
P<0.001
<63
6373
>73
<0.001
nPCR
g/kg
65%
81%
88%
<0.001
<0.09
0.91.02
>1.02
71%
80%
83%
Results
For weekly renal Kt/V, the mean value at initiation of
continuous peritoneal dialysis was 0.71 [1]; one-third
had values >0.89, one-third were 0.440.89 and onethird were <0.44. For weekly renal GFR, the mean
value at initiation was 39 l [1]; one-third had values
>50, one-third were 2550 and one-third were
<25 l/1.73 m2. The data for Kt/V and GFR defined
tertiles are shown in Tables 3 and 4 respectively. For
each of the estimates of nutritional status, higher initial
residual renal function is associated with better nutritional status. For patients with initial serum albumin
concentrations >35 g/l, 3035 g/l and <30 g/l, the 2
year survival probabilities were 85, 75 and 64% respectively (P<0.001; log-rank test). For those with initial
%LBM >73%, 6373% and <63%, the 2 year survival
probabilities were 88, 81 and 65% respectively
(P<0.001; log-rank test). For those with initial nPCR
Table 3. Mean values of nutritional status at initiation of dialysis
according to residual renal function estimated by weekly Kt/V
tertiles (n=680)
Kt/V
>0.89
0.440.89
<0.44
ANOVA P
Albumin
g/l
SGA
units
LBM
%
nPCR
g/kg
35.4
35.0
34.2
<0.05
5.4
5.1
5.1
<0.05
71.6
68.0
64.8
<0.001
1.12
1.03
0.98
<0.001
Albumin
g/l
SGA
units
LBM
%
nPCR
g/kg
>50
2550
<25
ANOVA P
35.8
34.8
34.1
<0.01
5.4
5.2
5.0
<0.05
73.8
68.1
58.0
<0.001
1.10
1.04
0.99
<0.001
161
transporters. This is clinically important and statistically significant. There is a trend to an increased RR of
technique failure among high transporters. Possible
mechanisms include fluid overload from ultrafiltration
failure, malnutrition from loss of proteins in the dialysate and adverse effects of increased glucose absorption.
Summary
Inference
Discussion
The three CANUSA studies reviewed [1,2,4] have
addressed adequacy of dialysis [1], the association
162
D. N. Churchill
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