pH EQUILIBRATION WITH ACETATE AND LACTATE

SOLUTIONS DURING PERITONEAL DIAL YSIS

Edward T. Cullom
Harold L. Moore Karl
D. Nolph and
Rebecca S. Keller

Commercial dialysis solutions contain

acetate or lactate and have pH values
usually below 6.5. Losses of ultrafiltration
in CAPD have been more frequent with
acetate than with lactate solutions. It has
been suggested that a slower increase of pH
following intraperitoneal instillation of
acetate solutions may produce alterations in
membrane
function.
We
compared
intraperitoneal equilibration ofpH in rats
with acetate and lactate solutions. In our rat
model pH equilibration rates were similar
for acetate and lactate solutions.
Commercial peritoneal dialysis solutions
contain glucose as an osmotic agent and
acetate or lactate as a buffer (1,2). The pH is
adjusted to below 6.0 to prevent glucose
caramelization during heat sterilization (3).
Acetate and lactate are absorbed during
peritoneal dialysis and, when metabolized
generate bicarbonate (2). Bicarbonate itself
is not used in commercial solutions

From the Division of Nephrology,

Department of Medicine, University of
Missouri Health
Sciences Center, H.S. Truman VA
Hospital,
and Dalton Research Center, Columbia,
Missouri.
Supported in part by the Nephrology
Research Fund.
Key Wards: Peritoneal dialysis, pH,
Acetate, Lactate, Dialysis solutions.

METHODS
Seven male Sprague-Dawley rats with intact
kidneys weighing between 400500 grams
were divided into two groups. Four rats
were dialysed with a commercial acetate
solution (Aguettant, Lyon, France), while
three rats

were dialysed with a commercial lactate

buffered solution (Fresenius, Bad Homburg,
West Germany).
A permanent simulated Tenckhoff
catheter was inserted into the peritoneal
cavity and exited behind the head via a
subcutaneous tunnel. It had dacron cuffs that
were located near the peritoneum and near
the skin-exit site. The rats were part of an
on-going animal study of the effects of
CAPD on membrane characteristics. Both
kidneys were intact and thus the rats were
not azotemic or uremic. Exchanges were
instilled at 8:00 a.m. , 2:00 p.m. and 10:00
p.m. daily. The instilled volume was 15 ml.
When the study was undertaken, the rats had
been on this CAPD schedule for 79 days on
the same solution. Samples of dialysate
were cultured daily. In the presence of
positive cultures, Kefzol12.5 mg/day/ kg
BW and Tobramycin 0.6 mg/day/kg BW
were added to the solutions for seven days
(or longer if necessary) to achieve negative
cultures.
Table I summarizes the composition of
the two dialysis solutions. The acetate
solution contains 35 rnMol of acetate per
liter and 4% dextrose. The

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ABSTRACT

because these solutions also contain calcium

and calcium bicarbonate is unstable in
solution on storage.
Many workers (4-8) have observed that
patients
on
continuous
ambulatory
peritoneal dialysis (CAPD) with solutions
containing acetate suffer losses of
ultrafiltration over time. Also encapsulating
sclerosing peritonitis is seen more often in
association with acetate solutions (9-11).
Pedersen et al (12) fear that prolonged
exposure to a low pH may irritate the
peritoneal membrane and that, during
peritoneal dialysis cycles with acetate as the
buffer, the pH in the intraperitoneal solution
increases more slowly. These studies were
undertaken to determine whether , during
peritoneal dialysis exchanges, acetate and
lactate solutions had the same rate of change
of pH.

lactate solution contains 35 mMol per liter

of lactate and 4.25% dextrose. It also shows
multiple measurements of pH, pCO2, and
p02 in our laboratories. Samples from the
bags were studied daily in the blood-gas
analyzer to insure that there were no
changes in the gas composition (pC02 and
pO2) and pH.
To monitor daily for infection, a
dialysate aliquot was removed one hour
after the 8 a.m. instillation for culture on
blood and MacConkey's agar. Rats were
considered to be infected on a specific day
if either culture was

We will report elsewhere detailed results of

the incidence of peritonitis and changes in
peritoneal transport and morphology with
each type of solution. The purpose of this
paper is to report on pH equilibration in
infected and noninfected animals with the
two different solutions.
Figures 1-3 show mass plots of pH, pC02
and pO2 as a function of dwell time in
infected and non-infected animals. Different
symbols are used for the results with acetate
and lactate buffers. Following instillation,
pH increases toward physiologic levels. The
p02 and pCO2 results are more varied, but
presumably approach values reflected in the
peritoneal interstitium and microcirculation.
Most likely the variation seen here reflects
interanimal variation because little variation
was seen in pC02 and p02 in dialysis
solution before instillation (Table I). Ranges
of p02 and pC02 values overlap with
infected and non-infected animals and with
the different solutions.
Table II shows mean pH values from the
same data at selected intervals . There were
no
significant
differences
between
solutions.
DISCUSSION
Many factors may influence the rate of
increase in dialysate pH during net
exchange. First, the net movement of
hydrogen ion and acetate (or lactate) from
dialysis solution into the peritone

al microcirculation and the net movements

of bicarbonate and other ions from blood
into dialysis solution will be influenced by
temperature, total membrane resistances
including fluid films , total pore area, mean
pore size and ultrafiltration (3). Lactate and
acetate
absorption
rates
affect
intraperitoneal
buffer
concentrations.
Lactate is a racemic mixture of L and D
isomers and these have different absorption
rates (13). Thus, the pH is influenced
markedly by the buffer environment and the
latter is influenced by multiple ions
approaching diffusion equilibrium at
different rates.
Secondly, the pKA of acetate (4.76) is
higher than that of lactate (3.86). Thus at the
same pH a higher portion of the acetate
would be in the acid form. Hydrogen-ion
diffusion from peritoneal dialysis solution
and a fall in hydrogenion concentration
would produce a shift of undissociated acid
to the base anion and free hydrogen ion. The
greater acid reserve with acetate might
provide a richer source of hydrogen ion to
blunt the rise in pH with hydrogen ion loss.
Thus, acetate with a higher pK in a pH
environment of the instilled solution should
act as a better buffer for change
of pH in either direction and slow the rise in
pH with hydrogen ion loss from the system.
However, if undissociated
acid were absorbed faster than hydrogen
ion across the peritoneum, dialysate pH
should increase more rapidly with acetate
as free hydrogen ion shifts to the
undissociated acid form.

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positive.
Following the 2:00 p.m. instillation
and after vigorous to-and-fro mixing, a 3
mi aliquot was removed for blood gases and
pH analysis using a Corning Model 158
blood gas analyzer (Corning Medical Co. ,
Corning Glass Works, Corning, N .Y .). To
minimize the effects of sampling on
intraperitoneal volume, we took only one
sample per day per rat for determination of
pH, pC02, and p02. With each succeeding
day, the sample was taken later in the dwell
time. The daily progression for sampling
following instillation, was every three
minutes for the firSt 30 minutes, every 10
minutes for the second 30 minutes and after
two and three hours. Samples were removed
with a blunt large-bore needle inserted into
the end of the catheter. Syringes were
capped
immediately
and
submitted
promptly to analysis. Mean pH values at
selected intervals were compared by nonpaired t analysis.

RESULTS

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In the physiological setting of peritoneal

dialysis, it seems necessary to do empirical
studies such as ours to establish whether
acetate and lactate solutions produce
different pH changes. Our studies in rats
show no obvious differences. It could be
that the numerous factors impacting on the
rate of pH change combine in such a way as
to minimize any differences predicted from
pK values alone.
LaGreca and co-workers could find no
differences in acetate and lactate masstransfer coefficients from peritoneal
dialysis solutions (2). Bicarbonate transfer
into dialysis solution did not differ with
lactate oracetate buffers. Bicarbonate
transfer is probably a

important and thus we might expect results

in humans to differ from those in rats and
rabbits.
We cannot comment on possible effects
of repeated transient exposures to low pH
on the peritoneal membrane. Rat studies in
our laboratories (to be reported) have
shown that CAPD with acetate solutions is
associated with prolonged infections (even
with
antibiotic
therapy),
increased
membrane permeability, and mesothelial
alterations not seen with lactate. It now
seems unlikely that differences in pH
equilibration rates explain the findings.
In summary , our rat studies lend no
support to the hypothesis that the noxious
effects of acetate solutions are due to a
relatively longer low pH than that seen
with lactate solutions.

REFERENCES
I. LaGreca G, Biasoli S, Chiarmonte S et
al. Acetate, lactate and bicarbonate
kinetics in peritoneal dialysis. In:
Atkins RC etal eds. Peritoneal
Dialysis.
Edinburgh:
ChurchillLivingstone, 1981: 217.
2. LaGreca G, Biasiolo S, Chiarmonte S
et al. Acid-base balance on peritoneal
dialysis. Clin NephroI1981;16:1.
3. Nolph KD, Popovich RP , Ghods AJ et
al. Determinants of low clearances of
small solutes during peritoneal dialysis. Kidney Int 1978;13:117.
4. Faller B, Marichal JF. Loss of ultrafiltration in continuous ambulatory peritoneal dialysis: A role for acetate. Perit
Dial Bull 1984;4:10-13.
5. Nolph KD et al. Factors affecting
ultrafiltration in continuous ambulato

ry peritoneal dialysis. First report of an

International Cooperative Study. Perit
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6. Slingeneyer A, Canaud B, Mion C.
Permanent loss of ultrafiltration capacity of the peritoneum in long-term
peritoneal dialysis: An epidemiological
study. Nephron 1983;33:133.
7. Faller B, Marichal JF. Loss of ultrafiltration in CAPD: Clinical data. In:Gahl
et al eds. Advances in Peritoneal
Dialysis. Int Congr Ser no 567.
Amsterdam: Excerpta Medica, 1981 ;
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8. Verger C, Brunschvicg O, Le Charpentier Yet al. Structural and ultrastructural
peritoneal membrane changes and
permeability alterations during CAPD.
Proc Eur Dial Transplant Assoc 1981 ;
18:199.
9. Ghandi VC, Humayun HM, Ing TS et
al. Sclerotic thickening of the peritoneal
membrane in maintenance peritoneal
dialysis patients. Arch Intern Med
1980;140:1201.
10. Rottembourg J, Gahl G, Poignet JL et
al. Severe abdominal complications in
patients undergoing continuous ambulatory peritoneal dialysis. Proc Eur
Dial Transpl Assoc 1983;24:236.
II. Slingeneyer A, Mion C, Mourad G et al.
Progressive sclerosing peritonitis.
Trans ASAIO 1983;24:633.
12. Pedersen FB, Ryttov N, Deleuran P et
al. Acetate versus lactate in peritoneal
dialysis solutions. Nephron 1985:39:
55-58.
13. Rubin J, Adair C, Johnson B et al.
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peritoneal dialysis. Nephron 1982;
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14. Robson M, Pinto T, Kao E et al. The
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15. Oreopoulos DG. Personal communica
tion.

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major determinant of dialysate pH. Serum

acetate levels were higher than lactate levels
in CAPD patients using acetate and lactate
solutions respectively. Accumulating higher
serum acetate levels could slow absolute
acetate transfer rates during prolonged
exchanges, preserve intraperitoneal acetate,
and favor a more rapid rise in
intraperitoneal pH subsequent to hydrogenion absorption.
Pedersen and colleagues, who found a
prolonged lower dialysate pH in humans
with acetate as compared to lactate,
attributed this to the higher buffer value of
acetate and a possible slower decline in
acetic acid compared to lactic acid (12).
After human studies Robson and his
colleagues reported that, as bicarbonate
diffuses into the solution, pH remains lower
with acetate than with lactate solutions (14).
This is compatible with predictions from
pKA values.
In rabbits after one hour, Oreopoulos
and his colleagues had results similar to
ours (15). Differences from Robson are
not easily explained. The commercial
acetate solution we used started with a
slightly higher pH than the lactate solution
(Table I). Although all lactate points might
have been slightly higher if lactate solution
had started at the same higher pH, it seems
unlikely that this would make a major
difference in the time required for pH to
approach physiologic levels. The early
increases are very rapid with both
solutions. It is possible that species
differences are