tap_659 220..
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Therapeutic Apheresis and Dialysis 13(3):220–224
doi: 10.1111/j.1744-9987.2009.00659.x
© 2009 The Authors
Journal compilation © 2009 International Society for Apheresis
Ionized Alkaline Water: New Strategy for Management of
Metabolic Acidosis in Experimental Animals
Hassan Abol-Enein, Osama A Gheith, Nashwa Barakat, Eman Nour,
and Abd-Elhameed Sharaf
Department of Urology, El Mansoura Urology and Nephrology Center (MUNC), Mansoura University,
Mansoura, Egypt
Abstract: Metabolic acidosis can occur as a result of either
the accumulation of endogenous acids or loss of bicarbon-
ate from the gastrointestinal tract or the kidney, which
represent common causes of metabolic acidosis. The appro-
priate treatment of acute metabolic acidosis has been very
controversial. Ionized alkaline water was not evaluated in
such groups of patients in spite of its safety and reported
benefits. So, we aimed to assess its efficacy in the manage-
ment of metabolic acidosis in animal models.Two models of
metabolic acidosis were created in dogs and rats. The first
model of renal failure was induced by ligation of both
ureters; and the second model was induced by urinary
diversion to gut (gastrointestinal bicarbonate loss model).
Both models were subjected to ionized alkaline water
(orally and by hemodialysis). Dogs with renal failure were
assigned to two groups according to the type of dialysate
utilized during hemodialysis sessions, the first was utilizing
Metabolic acidosis can occur as a result of either the
accumulation of endogenous acids that consume
bicarbonate (high anion gap metabolic acidosis) or
loss of bicarbonate from the gastrointestinal tract or
the kidney (hyperchloremic or normal anion gap
metabolic acidosis).The cause of high anion gap meta-
bolic acidosis includes lactic acidosis, ketoacidosis,
renal failure and intoxication with ethylene glycol,
methanol or salicylate. The most common causes of
hyperchloremic metabolic acidosis are gastrointesti-
nal bicarbonate loss, renal tubular acidosis, drug-
induced hyperkalemia, early renal failure and
administration of acids (1).
Received May 2008; revised August 2008.
Address correspondence and reprint requests to Dr Osama A
Gheith, Urology and Nephrology Center, Mansoura University, 72
Gomhoria Street, Mansoura 35516, Egypt. Email: ogheith@
yahoo.com
220
alkaline water and the second was utilizing conventional
water. Another two groups of animals with urinary diver-
sion were arranged to receive oral alkaline water and tap
water. In renal failure animal models, acid-base parameters
improved significantly after hemodialysis with ionized
alkaline water compared with the conventional water
treated with reverse osmosis (RO). Similar results were
observed in urinary diversion models as there was signifi-
cant improvement of both the partial pressure of carbon
dioxide and serum bicarbonate (P = 0.007 and 0.001
respectively) after utilizing alkaline water orally. Alkaline
ionized water can be considered as a major safe strategy in
the management of metabolic acidosis secondary to renal
failure or dialysis or urinary diversion. Human studies
are indicated in the near future to confirm this issue in
humans. Key Words: Acidosis, Alkaline ionized water,
Hemodialysis.
The use of intestinal segments in the urinary tract
can cause metabolic changes that depend on the
intestinal segment utilized. The severity of these
changes basically depends on the area of the intesti-
nal mucosa in contact with urine, the duration of
exposure to urine and renal function. The length of
time the intestinal mucosa is in contact with urine
largely depends on the surgical technique employed.
Mild chronic acidosis is neutralized via the respira-
tory system and by the bone buffers, which leads
to bone remodelling manifested by the significant
increase of serum alkaline phosphatase levels and
increased calciuria (2,3).
Metabolic acidosis is the most common metabolic
abnormality seen. The rates and severity of these
complications vary, though they may have a profound
impact on a patient’s quality of life after enterocys-
toplasty. The metabolic consequences and long-term
complications associated with enterocystoplasty are
 Alkaline Water and Metabolic Acidosis
important clinical features of this intervention, and
careful consideration should be given to them before
pursuing enterocystoplasty (4).
Increased oxidative stress in end-stage renal
disease (ESRD) patients may oxidize macromol-
ecules and consequently lead to cardiovascular
events during chronic hemodialysis. Hemodialysis
with electrolyzed reduced water (ERW) administra-
tion may efficiently increase the H2O2- and HOCl-
dependent antioxidant defense and reduce H2O2-
and HOCl-induced oxidative stress (partly restored
total antioxidant status during 1-month treatment)
(5). Electrolyzed reduced water treatment adminis-
tration is effective in palliating HD-evoked oxidative
stress, as indicated by lipid peroxidation, hemolysis,
and overexpression of proinflammatory cytokines in
HD patients (6).
The appropriate treatment of acute metabolic aci-
dosis, in particular organic form of acidosis such as
lactic acidosis, has been very controversial. The only
effective treatment for organic acidosis is cessation of
acid production via improvement of tissue oxygen-
ation. Treatment of acute organic acidosis with
sodium bicarbonate failed to reduce the morbidity
and mortality despite improvement in acid-base
parameters. Further studies are required to deter-
mine the optimal treatment strategies for metabolic
acidosis (1).
Until now ionized alkaline water has not been
evaluated in such a group of patients despite its
safety and reported benefits such as antioxidant
effects (5,6); its beneficial effects on ionized calcium
(7), and alleviation of some symptoms related to aci-
dosis as low back ache (8).
We aimed to assess the efficacy of ionized alkaline
water in the management of metabolic acidosis con-
sumed by oral route and/or by hemodialysis among
experimental animals.
METHODS
Induction of metabolic acidosis in
experimental animals
Fifteen mongrel dogs were selected with average
weight of 20 kg and 6 dogs were subjected to
open ligation of both ureters to induce state of
irreversible renal failure while the remaining 9
dogs were subjected to urinary diversion (uretero-
sigmoidostomy) aiming at inducing metabolic
acidosis. All dogs developed metabolic acidosis
and only dogs with bilateral ureteric ligaton devel-
oped chronic renal failure and were supported with
hemodialysis. All dogs were hemodialyzed for four
© 2009 The Authors
Journal compilation © 2009 International Society for Apheresis
221
hours, three times per week, against acetate based
dialysate, under general anesthesia, using an F3
hemoflux filter with an AK10 Gambro machine
(Gambro, Lund, Sweden), at a blood pump rate of
less than 200 mL per minute and average trans-
membrane pressure of 120 mm Hg. Double lumen
catheter was inserted in the right internal jugular
vein as a second step of preparation for hemodialy-
sis. Hemodiaslysis sessions were started on the next
day after ligation of ureters. Ionized alkaline water
was used randomly in some hemodialysis sessions (9
out of 21 sessions). The hemodialysis program was
continued as long as the dog remained alive. We
classified dialysis sessions into two groups; group 1
referred to dialysis sessions (12) that utilized acetate
based solution, while group 2 referred to dialysis
sessions that utilized ionized alkaline water based
solution.
Five rats were selected with an average weight
250 grams and were subjected to augmentation ileo-
cystoplasty with the aim of induction of hyperchlo-
remic metabolic acidosis. The rats fasted for 12 h
preoperatively and then were anesthetized by intra-
peritoneal injection of ketamine HCL 75 mg/kg and
diazepam 5 mg/kg. Cystoplasty was done under
sterile conditions with the aid of a microscope/
magnifying loop of 25¥ magnification.
The technique of ileocystoplasty has been
described previously in the literature by Guan et al.
(9) A midline abdominal incision was made. Right
sided nephrectomy was done taking care of the vas-
cular pedicle. Working 5 mm away from the cecum,
according to the group the length of the distal ileal
segment was taken with the mesenteric pedicle,
making sure of good arterial pulse and adequate
vessel length. The ileal segment was opened along
its antimesenteric border and was anastomosed
to the longitudinally opened urinary bladder using
7/0 PDS.
Continuity of the bowel was restored with end to
end anastomosis using simple interrupted sutures
(7/0 vicryl/PDS). Closure was done with 5/0 silk. Post-
operatively the rats were observed for 30–45 min in
the incubator and then they were returned to their
respective cages.
All animals were evaluated twice per week for the
acid-base status using capillary blood sampling. All
animals became acidotic by the second week, and
cases with bicarbonate levels less than 18 mEq/liter
were given alkaline water per mouth daily according
their thirst sensation. They were given alkaline water
orally for one week and continued for one month
then shifted to tap water for another one month and
were followed up by blood gases.
Ther Apher Dial, Vol. 13, No. 3, 2009
222 H Abol-Enein et al.

PREPARATION OF IONIZED WATER FOR RESULTS

DIALYSIS AND FOR DRINKING
Water electrostatic ionizer (ITen Company, Cairo,
Egypt) was used to generate the required amount of
water used for both drinking and hemodialysis. When
alkaline water was used in dialysis we connected the
ionizer distal to a tank full of water previously
treated with a reverse osmosis (RO) unit. Total dis-
solved solids (TDS) of the RO water were adjusted
between 200 to 250 ppm, and the ionizer was allowed
to work for 24 h prior the first session of dialysis with
a target pH between 8 and 9.
Clinical evaluation of each dog before each dialysis
session was performed with special focus on hemo-
dynamic stability, drinking, feeding, activities, gait
and clotting of lines.
At the start of the study before induction of renal
failure, laboratory evaluation included assessment of
kidney function (creatinine and blood urea nitrogen
[BUN]); liver function (bilirubin, albumin, alanine
aminotransferase) and complete blood count (CBC).
Before each dialysis session we performed CBC,
creatinine, blood urea nitrogen, blood gases and
plasma electrolytes and post-dialysis the same
parameters were repeated. Of course assessment of
dialysis efficacy using urea kinetic modeling (single
pool) was performed.
Statistical analysis
Statistical analysis was carried out using IBM-
compatible SPSS for windows version 11.5 (SPSS
Inc., Chicago, IL, USA). All values were expressed as
means ⫾ SD for continuous parametric data, median
for continuous nonparametric data, and frequencies
for categorical data. Values of P < 0.05 were consid-
ered significant.
Table 1 showed the demographic features of both
groups at the start of the study. We observed that the
two groups were comparable regarding pre-and post-
dialysis creatinine and serum potassium (P > 0.05).
The pre-dialysis acid-base parameters suggested
higher degree of metabolic acidosis in the sessions
utilized ionized alkaline water: significantly higher
pH, and lower partial pressure of carbon dioxide,
P = 0.032 and 0.024 respectively. The mean respira-
tory rate in both groups was comparable and also the
oxygen saturation in blood gases analyses. However,
these parameters improved significantly after dialysis
with ionized water compared with the usual water
treated with RO. Not only did the post-dialysis bicar-
bonate improved significantly after dialysis from 13.6
to 17.18 vs. 13.2 to 13.4 in the other group (P = 0.048),
but also partial pressure of carbon dioxide improved
from 27.2 to 34.3 vs. 31.6 to 32.7 (Table 2).
The daily evaluation of the dialyzed dogs after
recovery from anesthesia induced during dialysis, and
the dialysis free days were recorded and recoded and
summarized in Table 3. We could not detect any sig-
nificant difference between both groups regarding
drinking, feeding, daily activities, gait (P > 0.05).Also,
the frequency of clotting of blood in the extracorpo-
real circuit was higher than that observed in humans,
so we were obliged to use a higher dose of heparin
during dialysis. However, the two groups of dialysis
sessions were comparable regarding clotting of blood
(P = 0.15).
We observed that cases of both groups were com-
parable regarding basal acid-bases status (P > 0.05)
as all of them developed metabolic acidosis after the
urinary diversion by average 2 weeks duration. On
drinking ionized alkaline water there was no signifi-

TABLE 1. Demographic features of dogs at the start of the study

Acetate dialysis Ionized alkaline
sessions (N = 12) water sessions (N = 9)
Group 1 Group 2 P value
Basal Hb 14.96 ⫾ 1.6 14.07 ⫾ 1.9 0.549
HCT 39 ⫾ 5 39.7 ⫾ 4.7 0.848
WBCs 12.6 ⫾ 4.1 19.6 ⫾ 4.6 0.093
Platelets 307 ⫾ 88 368 ⫾ 261 0.719
Basal weight (kgm) 20.9 ⫾ 7 18.5 ⫾ 4.2 0.702
Basal creatinine (mg/dL) 1.0 ⫾ 0.25 1.1 ⫾ 0.3 0.783
Basal bicarbonate(mEq/L) 18.2 ⫾ 2.3 18.7 ⫾ 1.4 0.756
Basal sodium (mmol/L) 146 ⫾ 5.5 147 ⫾ 4.5 0.951
Basal potassium (mmol/L) 4.6 ⫾ 1.2 4.8 ⫾ 0.0 0.786
Basal calcium (mg/dL) 9.7 ⫾ 0.0 11.7 ⫾ 0.7 0.212
Basal phosphorus (mg/dL) 4.9 ⫾ 0.0 6.9 ⫾ 0.4 0.162
Basal pH 7.36 ⫾ 0.056 7.23 ⫾ 0.02 0.101
Basal pCO2 32 ⫾ 0.0 41.3 ⫾ 4 0.053

Hb, hemoglobin; HCT, hematocrit; pCO2, partial pressure of carbon dioxide; WBCs,
white blood cells.

© 2009 The Authors

Ther Apher Dial, Vol. 13, No. 3, 2009 Journal compilation © 2009 International Society for Apheresis
 Alkaline Water and Metabolic Acidosis 223

TABLE 2. Laboratory evaluation of the studied dogs (pre- and post-dialysis)

Acetate dialysis sessions Ionized alkaline water
(N = 12) sessions (N = 9)
Group 1 Group 2 P value
Serum creatinine
Predialysis 11.09 ⫾ 3.4 11.48 ⫾ 4.59 0.827
Post-dialysis 4.5 ⫾ 1.1 4.8 ⫾ 2.4 0.643
Mean Kt/V 1.14 1.15 0.24
Serum potasium
Predialysis 5.1 ⫾ 0.96 4.90 ⫾ 1.0 0.757
Post-dialysis 2.75 ⫾ 0.56 2.8 ⫾ 0.6 0.701
Serum pH
Predialysis 7.245 ⫾ 0.036 7.2947 ⫾ 0.042 0.032
Post-dialysis 7.283 ⫾ 0.096 7.27 ⫾ 0.066 0.778
Serum pCO2
Predialysis 31.6 ⫾ 2.5 27.2 ⫾ 3.5 0.024
Post-dialysis 32.7 ⫾ 4.7 34.3 ⫾ 5.9 0.613
Serum bicarbonate
Predialysis 13.20 ⫾ 1.9 13.60 ⫾ 1.8 0.660
Post-dialysis 13.44 ⫾ 4.1 17.18 ⫾ 3.3 0.048

pCO2, partial pressure of carbon dioxide.

cant effect on pH (P = 0.575). However, there was ligation of both ureters (6 dogs) to induce state
significant improvement of both pCO2 and serum of irreversible renal failure; or urinary diversion
bicarbonate (P = 0.007 and 0.001 respectively) irre- using uretero-sigmoidostomy (9 dogs) aiming at
spective to the cause of metabolic acidosis (Table 4). inducing metabolic acidosis in all dogs. Five rats
were subjected to augmentation ileo-cystoplasty
DISCUSSION with the aim of induction of hyperchloremic meta-
bolic acidosis.
In this study we aimed to evaluate the efficacy of All dogs with renal failure were supported—from
ionized alkaline water in the management of meta- the second day—by hemodialysis. So, we create two
bolic acidosis resulted from two important groups of groups of hemodialysis sessions, the first utilized
disorders that we are confronted with in our center. conventional water and the second utilized alkaline
We induced metabolic acidosis in 15 dogs and water. The two groups were comparable regarding
5 rats. Fifteen dogs were subjected to either open demographic features at the start of the hemodialysis
program shown in Table 1.
We observed that the two groups were comparable
TABLE 3. Clinical features of the studied dogs during
and in between dialysis sessions regarding pre-and post-dialysis creatinine and serum
potassium (P > 0.05). The pre-dialysis acid-base
Score of clinical features parameters suggested higher degree of metabolic
Good Moderate Poor P value acidosis in the sessions utilizing ionized alkaline
Drinking
water (pH was significantly higher and pCO2 was
Group I† 5 3 1 0.10 significantly lower). However, these parameters
Group II‡ 5 2 5 improved significantly after dialysis with ionized
Feeding water compared with the usual water treated with
Group I 3 1 5 0.93
Group II 3 1 8
RO.
Activities
The dialyzed dogs were recorded, recoded and
Group I 6 2 1 0.72 summarized in Table 3. We could not detect any sig-
Group II 7 4 2 nificant difference between both groups regarding
Gait drinking, feeding, daily activities, gait (P > 0.05).Also,
Group I 7 1 1 0.30
Group II 8 3 1
the frequency of clotting of blood in the extracorpo-
Clotting of lines
real circuit was higher than that observed in humans,
Group I 7 1 1 0.15 so we were obliged to use higher dose of heparin
Group II 6 2 4 during dialysis. However, the two groups of dialysis
†
Acetate dialysis sessions (N = 12) Group 1. ‡Ionized alkaline sessions were comparable regarding clotting of blood
water sessions (N = 9) Group 2. (P = 0.15).

© 2009 The Authors

Journal compilation © 2009 International Society for Apheresis Ther Apher Dial, Vol. 13, No. 3, 2009
224 H Abol-Enein et al.

TABLE 4. Effect of drinking ionized alkaline water for one week on acid-base
status of dogs with metabolic acidosis due to urinary diversion or induced renal
failure
Phase I Phase II
Drinking Ionized Drinking tap water after
alkaline water 2 weeks wash out period
Number of dogs (n = 15) Number of dogs (n = 9)
Mean SD Mean SD P value
pH: basal 7.26 0.06 7.28 0.03 0.57
After 1 week 7.28 0.03 7.24 0.04 0.14
pCO2: basal 33.84 6.9 35.5 6.9 0.62
After 1 week 44.25 8.8 32 0.3 0.007
Serum bicarbonate
Basal 14.66 3.8 16.2 3.2 0.29
After 1 week 21.12 3.7 13.9 1.6 0.001

Number of rats (n = 5) Number of rats (n = 5)

Mean SD Mean SD P value
pH: basal 7.24 0.04 7.23 0.03 0.66
After 1 week 7.27 0.02 7.26 0.04 0.22
pCO2: basal 33.85 6.9 35.5 6.9 0.62
After 1 week 45.25 8.8 31 0.3 0.006
Serum bicarbonate
Basal 14.66 3.8 15.2 3.2 0.39
After 1 week 25.12 3.7 14.9 1.6 0.001

pCO2, partial pressure of carbon dioxide.

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Alkaline ionized water can be considered as a
major safe strategy in the management of metabolic
acidosis encountered among animals with either
dialysis or urinary diversion. Further studies are indi-
cated in the near future to confirm this issue in
humans.
Acknowledgments: Abd-Elhameed Sharaf provided
the ionizer, which is licensed and available in Egypt.
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© 2009 The Authors

Ther Apher Dial, Vol. 13, No. 3, 2009 Journal compilation © 2009 International Society for Apheresis