ACKD

Management of the Metabolic Acidosis of Chronic

Kidney Disease
Nimrit Goraya and Donald E. Wesson

Subjects with CKD and reduced glomerular filtration rate are at risk for chronic metabolic acidosis, and CKD is its most common
cause. Untreated metabolic acidosis, even in its mildest forms, is associated with increased mortality and morbidity and should
therefore be treated. If reduced glomerular filtration rate or the tubule abnormality causing chronic metabolic acidosis cannot be
corrected, it is typically treated with dietary acid (H1) reduction using Na1-based alkali, usually NaHCO3. Dietary H1 reduction can
also be accomplished with the addition of base-producing foods such as fruits and vegetables and limiting intake of H1-producing
foods like animal-sourced protein. The optimal dose of Na1-based alkali that prevents the untoward effects of metabolic acidosis
while minimizing adverse effects and the appropriate combination of this traditional therapy with dietary strategies remain to be
determined by ongoing studies. Recent emerging evidence supports a phenomenon of H1 retention, which precedes the
development of metabolic acidosis by plasma acid-base parameters, but further studies will be needed to determine how best
to identify patients with this phenomenon and whether they too should be treated with dietary H1 reduction.
Q 2017 by the National Kidney Foundation, Inc. All rights reserved.
Key Words: Acid, Alkali, Bicarbonate, Chronic kidney disease, Diet

acidosis was prevalent in 7% of stage 2, 13% of stage 3,

INTRODUCTION
Acidosis is a process defined by a net gain of hydrogen ion
(H1) and/or loss of base (usually HCO3). Its metabolic va-
riety is characterized by an initial decrease in plasma bicar-
bonate concentration ([HCO3]) in a setting of a history and
physical examination supportive of this diagnosis. As a
single (as opposed to being a component of a mixed)
acid-base disorder, it is additionally characterized by a
decrease in plasma pH (equivalent to an increase in plasma
[H1]) and by a physiological response of increased ventila-
tion reflected by decreased partial pressure of carbon diox-
ide (PCO2). Prevalence of metabolic acidosis in CKD
increases with decreasing glomerular filtration rate
(GFR).1,2 Despite the daily acid (H1) challenge from diet
and metabolic processes, body buffer systems and the
increased per nephron acidification, which occurs in
response to a chronic (as opposed to an acute) decline in
GFR, can prevent or mitigate the decrease in plasma
[HCO3] that heralds the onset of metabolic acidosis. As
GFR chronically declines, some subjects ingesting a high
H1 diet might experience H1 retention before its
manifestation by decreased plasma [HCO3].3-5 It follows
that over the course of progressive GFR decline,
metabolic acidosis is a comparatively late complication
of CKD. When defined as plasma [HCO3] , 22 mEq/L,
the level at which current Kidney Disease: Improving
Global Outcomes (KDIGO) guidelines recommend
treatment of metabolic acidosis in CKD,6 metabolic
From the Baylor Scott and White Health Department of Internal Medicine,
Temple, TX; Texas A&M Health Science Center College of Medicine, Temple,
TX; Baylor Scott and White Health Department of Internal Medicine, Dallas,
TX; and Texas A&M Health Science Center College of Medicine, Dallas, TX.
Financial Disclosure: See Acknowledgment on page 303.
Address correspondence to Donald E. Wesson, MD, MBA, Baylor Scott and
White Health and Wellness Center, Texas A&M Health Sciences Center College
of Medicine, 4500 Spring Avenue, Dallas, TX 75219. E-mail: donald.wesson@
BSWHealth.org
Ó 2017 by the National Kidney Foundation, Inc. All rights reserved.
1548-5595/$36.00
http://dx.doi.org/10.1053/j.ackd.2017.06.006
and 37% of stage 4 CKD patients.2
THE DAILY ACID CHALLENGE
The body defends against acid challenges to acid-base bal-
ance by excreting volatile acid (CO2 gas) through the lungs
(about 15,000 mEq/d), by liver metabolism of base-
producing food components (like plant-sourced protein)
and some organic products of metabolism (eg, lactic acid)
to yield HCO3, and by urine excretion of “fixed” acid
(about 50-100 mEq/d) with regeneration of new HCO3 by
the kidney. Diets typical of most developed societies on bal-
ance yield net production of H1 when metabolized7
because of the greater proportion of animal-sourced
protein compared with plant-sourced protein. Net endoge-
nous H1 production of such diets averages about
1 mEq/kg/body weight/d.8 Food components that yield
H1 when metabolized are animal protein including dairy
products, most grains, and lentils.9 Dietary sodium
chloride (NaCl) also increases net acid production.10 In
contrast, food components that yield base when metabo-
lized include most fruits and vegetables.9
Dietary H1 challenges cause increases in plasma [H1]
with decreases in plasma [HCO3] but even quantitatively
large changes in dietary H1 yield quantitatively small
changes in plasma [H1]/[HCO3].11 In addition, even large
changes in dietary H1 elicit plasma [H1]/[HCO3] changes
that typically fall within the normal range for each11 such
that plasma [H1]/[HCO3] levels often provide little insight
as to the magnitude of dietary H1 or base. These data attest
to the effectiveness of body buffers and kidney excretory
capacity to maintain plasma [H1]/[HCO3] but also high-
light the clinician’s challenge to gauge dietary H1 by
plasma acid-base parameters. On the other hand, patients
with CKD with reduced GFR can have greater increases in
[H1] and greater decreases in [HCO3] in response to die-
tary H1, even developing metabolic acidosis, at levels of
dietary H1 that do not cause metabolic acidosis in patients
with higher GFR.12 Consequently, clinicians are more
likely to recognize metabolic acidosis in patients with
lower GFR compared with higher GFR.

298 Adv Chronic Kidney Dis. 2017;24(5):298-304

 Managing Metabolic Acidosis 299

When dietary H1 is increased, the increment of kidney
H1 excretion is often less than the increment in dietary
H1,13,14 even in individuals with normal GFR, consistent
with retention of some of the ingested H1.15 Because this
apparent H1 retention is typically accompanied by only
minor changes in plasma levels of [H1] and [HCO3],11
much of this retained H1 apparently titrates non-HCO3
body buffers13,14,15 and/or appears in non–plasma fluid
compartments,16 possibly in interstitial fluid.17 Animal
studies support that this purported H1 retention is greater
with reduced GFR compared with normal GFR18 and
some patients with reduced GFR appear to have H1 reten-
tion.3-5 These data support the existence of a continuum of
H1 stress in which H1 retention is an earlier and metabolic
acidosis is a later manifestation. Even so, early H1 stress
manifest by H1 retention appears to cause tissue injury,
particularly in the setting of reduced GFR.18
have H1 retention without metabolic acidosis24-27 can
each achieve steady-state H1 excretion sufficient to
avoid progressive metabolic acidosis or progressive H1
retention. This augmented acidification is accomplished
in part by increased distal nephron acidification and
increased urine NH41 excretion. Augmented distal
nephron acidification in these experimental CKD models
is mediated by increased kidney levels of angiotensin II,
endothelin, and aldosterone,23,25,26 substances that also
contribute to progressive GFR decline.25,27 These data
suggest that increased kidney levels of angiotensin II,
endothelin, and aldosterone mediate the physiological,
short-term benefit of increased urine H1 excretion in
response to an H1 challenge yet, when the acid challenged
is sustained, these substances also mediate the pathophys-
iological, long-term detriment of enhanced stages of
kidney disease progression.

KIDNEY RESPONSE TO AN ACID CHALLENGE KIDNEY-RELATED CAUSES OF CHRONIC METABOLIC

Subjects with normal nephron mass given a dietary H1 chal- ACIDOSES FOR WHICH TREATMENT SHOULD BE
lenge increase urine net acid excretion (NAE) predominantly CONSIDERED
through an increment in urine ammonium (NH41) excretion Because of its untoward consequences including disturbed
with smaller quantitative contributions from increased titrat- bone14 and muscle28 metabolism, possible exacerbation of
19
able acidity and decreased urine excretion of HCO3. stages of kidney disease progression29-31 and increased
Similarly, animals challenged with dietary H1 mortality,32 chronic metabolic acidosis, even when mild,
increase urine NAE predominantly through increased urine should be treated.
NH41 excretion,16 which is associated with augmented
20
distal nephron acidification. RENAL TUBULAR
Consequently, augmented ACIDOSES
CLINICAL SUMMARY
distal nephron acidification
1 Proximal Renal Tubular
with increased urine NH4
excretion contributes impor-  Metabolic acidosis, even when mild, should be treated with Acidosis
dietary acid reduction to reduce its untoward Patients with proximal
tantly to the kidney response
consequences.
to dietary H1. renal tubular acidosis
Although metabolic aci-  Dietary acid reduction might be accomplished by: (PRTA) have defective
dosis is uncommon in early prescribing sodium-based alkali, adding base-producing proximal tubular HCO3 re-
stage CKD, individuals with food components, limiting acid-producing food absorption with excess ter-
reduced GFR might never- components, or though a combination of these strategies. minal nephron HCO3
theless have H1 retention delivery that overwhelms
when eating the high H1- capacity of the distal
producing diets of developed societies.3-5 With further nephron to completely reabsorb the high HCO3 delivered
GFR decline, patients with CKD typically develop a non– load. Because urine NAE ¼ urine NH41 1 urine titratable
anion gap metabolic acidosis, which transitions to the acidity 2 urine HCO3, excess urine HCO3 excretion re-
anion gap variety as GFR nears levels at which kidney duces urine NAE. These patients reach a steady state of
replacement therapy must be considered.21 Even so, most chronically low plasma [HCO3] at which the defective
patients with CKD with reduced GFR can effect steady- proximal tubule more completely reabsorbs the lower
state H1 excretion sufficient to avoid progressive meta- HCO3 filtered load into the nephron (because of lower
bolic acidosis while eating diets typical of developed soci- plasma [HCO3]). This lower HCO3 delivery to the terminal
eties.13,22 More advanced GFR reduction in patients with nephron allows the functionally intact distal nephron to
CKD, however, is associated with reduced urine NH41 effectively excrete NH41 and titratable acidity without
5
excretion, which likely contributes to their underlying excess urine HCO3 excretion. This steady-state scenario al-
H1 retention and/or metabolic acidosis. These data suggest lows the kidney to maintain net acid balance, that is, match
the need for further studies to better determine whether dietary H1 intake with H1 excretion. The steady-state
some patients with reduced GFR but without metabolic price paid is that these patients have chronic metabolic
acidosis are nevertheless candidates for dietary H1 reduc- acidosis manifest by low serum [HCO3] with a physiolog-
tion. ical response to decrease PCO2.
Experimental CKD models with GFR reduction low The most concerning consequence of the chronic meta-
enough to be associated with metabolic acidosis23 and bolic acidosis of PRTA is the inhibited bone growth in chil-
those with less severe GFR reduction such that animals dren.33 Chronic metabolic acidosis is also associated with

Adv Chronic Kidney Dis. 2017;24(5):298-304

300 Goraya and Wesson
low bone mineral content as rickets in children and osteo-
malacia in adults and nephrolithiasis in both.34 Treatment
of metabolic acidosis in PRTA with large volumes of
NaHCO3, typically 10 to 15 mEq/kg body weight/d,33,34
is needed to maintain plasma [HCO3] at a high enough
level to avoid or ameliorate these untoward
consequences. Such treatment leads to large urine HCO3
losses that obligate potassium and phosphate losses that
also require replacement.33 Although reducing intake of
H1-producing food components and addition of base-
producing food components can be considered, the large
alkali requirements of patients with PRTA cannot be met
with these dietary strategies alone.
Distal Renal Tubular Acidosis
Patients with distal renal tubular acidosis (DRTA) have
intact proximal tubular function and so do not deliver
large HCO3 loads to the terminal nephron. In contrast to
PRTA, these patients have defective distal nephron acidifi-
cation such that they have lower excretion of NH41 and/or
titratable acidity.35,36 Consequently, patients with DRTA
are typically unable to completely excrete the high
dietary H1 load typical of developed society diets and so
are in steady-state net H1 retention without treatment.36
The H1 retained lowers plasma [HCO3] (with a physiolog-
ical PCO2 decrease) and so these patients have chronic
metabolic acidosis. The net acid retention causes bone dis-
ease34 and nephrolithiasis.37
Because patients with DRTA have intact proximal
tubular function, they do not have the large urine HCO3
losses of PRTA and so do not have the large alkali require-
ments of PRTA patients. Instead, DRTA patients require al-
kali sufficient to treat the described net H1 retention.
Because individuals in industrialized societies typically
ingest diets that produce about 1.0 mEq/kg body weight/d
net of acid,8 most recommendations suggest that DRTA
patients receive 1.0 to 1.5 mEq/kg body weight/d alkali
equivalent daily, typically as NaHCO3.36,38 Oral alkali
correction of metabolic acidosis due to DRTA in children
improved bone growth, mineral density, and
histopathology.38,39 Although there are no published
studies describing DRTA treatment exclusively by
reducing H1-producing or adding base-producing dietary
constituents, the comparatively lower alkali requirements
of patients with DRTA suggest that dietary strategies
might be used at least as adjunctive treatment to Na1 or
K1-based alkali.
CHRONIC METABOLIC ACIDOSIS OF CKD
The 2013 KDIGO guidelines6 are the most structured rec-
ommendations for treatment of chronic metabolic acidosis
but it is not clear that these recommendations should be
applied unmodified to other etiologies of chronic meta-
bolic acidosis. These recommendations read as follows:
“We suggest that in people with CKD and serum [HCO3]
,22 mEq/L treatment with oral bicarbonate supplementa-
tion be given to maintain serum bicarbonate within the
normal range, unless contraindicated.6” The authors
comment that the indicated serum [HCO3] below which
to treat has not been rigorously determined with large-
scale studies but reflects opinions and experience of the au-
thors. Recommended doses range from 0.5 to 1.0 mEq
HCO3 or its equivalent per kilogram lean body weight
per day. This is similar in amount to that recommended
for DRTA because the concern with the chronic metabolic
acidosis of CKD is the failure to completely excrete meta-
bolically produced H1, mostly from dietary intake. The
treatment goal, as stated in KDIGO, is to maintain serum
HCO3 in the normal range. The guidelines recommend
Na1-based alkali therapy such as Na1 citrate or NaHCO3
as tolerated.
GENERAL MANAGEMENT STRATEGIES FOR
CHRONIC METABOLIC ACIDOSIS
Dietary H1 Reduction
Because diets of developed societies are typically acid-
producing, chronic metabolic acidosis might be treated
by adding Na1-based alkali (avoiding K1-based alkali
because of the reduced K1-excreting capacity of some pa-
tients with CKD with very low GFR) like NaHCO3 or Na1
citrate, by limiting intake of acid-producing dietary
constituents like animal-sourced protein, and/or by add-
ing base-producing plant sourced constituents like fruits
and vegetables.
Na1-Based Alkali Therapies
Sodium bicarbonate (NaHCO3) is the common alkali salt
used to treat metabolic acidosis because it is effective, rela-
tively well tolerated, widely available, and inexpensive.
Potassium bicarbonate is used less commonly, except in
patients who require substantial HCO3 replacement (like
PRTA) that is associated with large K1 losses in response
to treatment. Potassium bicarbonate should be avoided
in patients with very low GFR (,25% of normal) because
of the risk for K1 retention with hyperkalemia. Because cit-
rate is metabolized to yield HCO3, Na1 citrate is often used
in patients unable to tolerate NaHCO3. Use of Na1 citrate
is limited by its unpleasant taste, comparatively high
expense, and because it promotes gastric aluminum ab-
sorption.40 Consequently, NaHCO3 is the alkali salt on
which we will focus our discussion.
Sodium bicarbonate is water soluble and when taken
orally rapidly reacts with gastric hydrochloric acid (HCl)
to form NaCl, CO2, and H2O. Excess HCO3 that does not
neutralize gastric H1 rapidly empties into the small intes-
tine and is absorbed. Reaction of NaHCO3 with gastric
HCl increases gastric lumen pH, stimulating gastric parie-
tal cells to secrete more HCl into the gastric lumen. Secre-
tion of HCl into the gastric lumen induced by a rise in
gastric pH leads to HCO3 extrusion into perigastric capil-
laries and eventually into the systemic circulation to in-
crease extracellular [HCO3] if it is reduced. If
extracellular [HCO3] attains a level that exceeds the kidney
tubule maximum for reabsorption, the excess HCO3 is
eliminated in the urine.
Orally administered NaHCO3 has had few notable
adverse effects when given to CKD patients.29,41-44 Most
adverse effects from NaHCO3 were caused by release of
1
CO2 gas when it contacts gastric H and consists of
Adv Chronic Kidney Dis. 2017;24(5):298-304
 Managing Metabolic Acidosis
belching, gastric distension, and flatus. Higher doses
might theoretically cause volume retention and possibly
exacerbate hypertension in patients with very low GFR.
Nevertheless, studies in which NaHCO3 was
administered to patients with CKD at much higher than
the recommended KDIGO doses showed that NaHCO3
did not increase blood pressure or cause edema.45 In
more recent studies, investigators did not observe a signif-
icant difference between the NaHCO3 and control group
with regard to worsened hypertension requiring higher-
dose drug therapy and worsening edema requiring
increased loop diuresis.29 Other investigators43 analyzed
adverse effect profiles in CKD of differing etiologies (esti-
mated glomerular filtration rate [eGFR] 15-45 mL/min/
1.73 m2) who received escalating doses of NaHCO3 for
more than 6 weeks. NaHCO3 had no notable influence
on such effects like bloating, flatulence, stomach upset,
nausea, edema, and shortness of breath and no patient
was hospitalized. These authors also found that patients
with edema have larger alkali requirements to correct
acidosis.
One potential concern for exogenous NaHCO3 therapy is
that it might cause metabolic alkalosis. Such therapy rarely
causes metabolic alkalosis in patients with normal GFR and
normal extracellular fluid volume46 and did not increase
serum [HCO3] higher than normal when given for 1 year
at 1 mEq/kg body weight/d (5.9 g/d for 70 kg body weight)
to patients with stage 4 CKD with metabolic acidosis.47
Consequently, NaHCO3 at doses mostly used in patients
with CKD (2-3 g/d) is unlikely to cause this complication.
However, practitioners and patients must be mindful of
all circumstances that can cause metabolic alkalosis (eg,
vomiting, diarrhea, and hypokalemia), and in such cases,
NaHCO3 should be temporarily discontinued.
Because serum alkalization decreases ionized calcium,
HCO3 therapy or its equivalent might theoretically cause
tissue, importantly vascular, calcification. Indeed, both
calcium-containing and non–calcium-containing alkali
salts have been associated with progressive (but not de
novo) vessel calcification.48 On the other hand, NaHCO3
therapy did not change serum total calcium and inorganic
phosphorus concentrations or the calcium/phosphate
product in patients with CKD.49 Consequently, further
studies will determine if the described benefits of HCO3
therapy in patients with CKD with metabolic acidosis
are counterbalanced by untoward effects of progressive
and/or de novo vascular calcification.
The optimal daily dose of NaHCO3 that provides kidney
and other organ protection yet minimizes adverse effects
remains to be determined. The National Kidney Founda-
tion recommends 0.5 to 1.0 mEq of NaHCO3/kg body
weight/d in patients with serum [HCO3] ,22 mEq/L.6
The amount of NaHCO3 required to increase serum
[HCO3] by a given amount can be calculated according
to the following formula: [desired HCO3
level] 2 [measured HCO3 level] 3 [HCO3 space ¼ 50%
body weight (kg)].50 Because metabolic acidosis increases
the space of distribution of administered HCO3,50 patients
with CKD with metabolic acidosis might require slightly
more administered HCO3 than suggested by this formula.
Adv Chronic Kidney Dis. 2017;24(5):298-304
301
Most patients are able to take oral NaHCO3 without ma-
jor complications. Tolerance and compliance of those using
NaHCO3 depend on the galenic form of this substance.
Tablets and capsules are well tolerated and the dose can
be better controlled. Some manufacturers add flavors to
improve tablet taste. How NaHCO3 is viewed and pre-
scribed depends on local regulations. In some localities,
NaHCO3 is registered as a drug, whereas it is registered
in others as a food supplement. It can also be registered
as both a food supplement and a drug.
Although there is no chemical difference between baking
soda bought in the supermarket and NaHCO3 powder or
tablets bought in pharmacies, only in pharmacies can pa-
tients be professionally advised regarding interactions,
adverse effects, and warnings. Also, dosing with
powdered NaHCO3 is less precise than with tablets, and
its temperature sensitivity makes storage of NaHCO3 chal-
lenging. Consequently, the better recommendation for pa-
tients with CKD is NaHCO3 prescribed and purchased as
tablets or capsules from a pharmacy rather than in a super-
market.
Adding Base-Producing Dietary Components
High dietary H1 contributes to metabolic acidosis in pa-
tients with reduced GFR.12 Consequently, dietary H1
reduction might be accomplished by adding or substitut-
ing base-inducing foods like fruits and vegetables to the
high H1 diet typical of industrialized societies. Acid con-
tents of many foods have been published9 and might be
used to determine how much of what foods to prescribe
to patients with CKD. Adding base-producing fruits and
vegetables reduced urine NAE in patients with CKD
with reduced eGFR but no metabolic acidosis51 and also
improved metabolic acidosis in patients with CKD whose
eGFR was low enough to be associated with metabolic
acidosis.31,47,52 Fruits and vegetables prescribed in
amounts equivalent to 50% of their calculated dietary H1
load amounted to adding 2 to 4 cups of fruits and
vegetables to their daily diets.31,47,51 Patient participants
in these studies were carefully selected to be at very low
risk to develop hyperkalemia in response to the
increased K1 load that accompanies fruits and
vegetables. Therefore, clinicians should use caution
when considering prescribing fruits and vegetables to
CKD patients, particularly those with very low GFR.
Removing/Limiting H1-Producing Dietary
Components
Dietary acid reduction might also be accomplished by
limiting intake of H1-producing food components,
including animal source protein, and limiting intake of di-
etary NaCl.10 When fresh fruits and vegetables were
added to the diets of patients with CKD with metabolic
acidosis, patients substituted these food components
given at no cost for more expensive, processed food com-
ponents that they had previously purchased, leading to
decreased NaCl intake.47 Therefore, increasing the propor-
tion of fresh plant-based foods in the diet, which are natu-
rally low in NaCl, might help reduce NaCl intake, in
addition to reducing the dietary H1 load.
302
Theoretical Stages of H+ Retention with Recommended Treatment
H+ intake Low dietary H+, High dietary H+,
Normal GFR Normal GFR
and GFR
Normal Range
Serum
[HCO3-]
H+
Retention
Na+-based No data to support
No
Alkali Rx? treatment
Alkaline No data to support
Not Necessary treatment
diet?
Considerations regarding management of metabolic
acidosis in CKD within a theoretical construct for stages
of progressive H1 retention, which eventually manifests
as metabolic acidosis (Fig. 1), are given as follows:
 Low dietary H1 intake, normal GFR: Animals ingesting a
plant protein, base-producing diet have low kidney
levels of endothelin,53 angiotensin II,26 and aldoste-
rone25 because of less need to increase H1 excretion
compared with animals eating an animal protein, acid-
producing diet. Because kidney levels of these sub-
stances are low, there is comparably little to no kidney
injury.53 The data support that no dietary alkali is
needed for analogous patients fitting this construct.
 High dietary H1 intake, normal GFR: Such animals
achieve steady-state H1 excretion, which avoids pro-
gressive H1 retention yet they have steady-state H1
retention16,18 without significant change in serum
[HCO3].18 These animals also have increased levels of
endothelin,20 angiotensin II,26 and aldosterone,25 each
of which help mediate increased H1 excretion in
response to this increment in dietary H1. Despite
increased kidney levels of these substances, 96 weeks
of these H1-producing diets in animals did not decrease
GFR but did increase kidney tubulointerstitial fibrosis,53
a feature of progressive stages of kidney disease. High
H1 diets might decrease serum [HCO3]/pH slightly
but such small decreases remain within normal limits
for clinical laboratories and so would not be evident
clinically.11 Although epidemiologic studies support
that high H1 diets increase risk for CKD54 and type 2
diabetes,55 there are no published interventional data
examining the long-term effect of high dietary H1 on
kidney or other organ function in patients with baseline
normal GFR to inform a management recommendation.
That being said, such patients would theoretically
benefit from reducing their high dietary H1 content.
Goraya and Wesson
High dietary H+, High dietary H+,
Modestly Severely
Reduced GFR Reduced GFR
Normal Range
Figure 1. Treatment considerations for metabolic
acidosis within a theoretical continuum of
increasing acid (H1) retention that eventually
manifests as metabolic acidosis. The top horizon-
tal line of boxes characterizes 4 progressive
stages of H1 retention according to a combination
of dietary H1 intake and remaining GFR. The next
Treat to keep 2 horizontal displays figuratively compare serum
Insufficient data serum [HCO3] in [HCO3] and tissue H1 retention among the 4
to support either normal range stages. The last 2 horizontal line of boxes de-
treatment but scribes recommendations for treating each of
further studies
needed
Possibly the 4 stages with dietary H1 reduction, done as
adjunctive to Na1-based alkali therapy or with a base-
+
Na -based alkali
producing or alkaline diet. Abbreviation: GFR,
glomerular filtration rate.
 High dietary H1 intake, modestly decreased GFR, but no
metabolic acidosis by serum acid-base parameters: Such ani-
mal CKD models have H1 retention yet no significant
decrease in serum [HCO3].18,24,25,27 They also have
increased kidney levels of endothelin,25 angiotensin
II,26,27 and aldosterone,25 and without dietary H1 reduc-
tion they have progressive GFR decline characterized by
tubulointerstitial fibrosis.25-27 Analogous patients with
CKD with modestly reduced eGFR have H1 retention
but with serum [HCO3] not different from comparable
patients with normal eGFR3,4 and have increased urine
excretion of endothelin and aldosterone.3 Small-scale in-
terventional studies show that such patients with CKD
have progressive eGFR decline without dietary H1
reduction and that dietary H1 reduction reduces urine
excretion of endothelin and aldosterone,3 reduces
indices of kidney injury,51 and slows eGFR decline.41
Larger scale studies will determine if dietary H1 reduc-
tion should be standard of care for patients with CKD
with modestly reduced GFR but no metabolic acidosis
by serum acid-base parameters.
 High dietary H1 intake, severely decreased GFR with metabolic
acidosis: Analogous animal CKD models fitting this
construct have increased kidney levels of endothelin,23
with progressive GFR decline that is slowed by dietary
H1 reduction.56 Analogous patients with CKD with
severely reduced eGFR have increased urine endothelin
excretion,30 and small-scale interventional studies show
progressive GFR decline that is ameliorated by dietary
H1 reduction.29-31 Current guidelines recommend
treatment with Na1-based oral alkali for amelioration of
the disturbed bone and muscle metabolism caused by
the metabolic acidosis of CKD6 and, as mentioned, recent
studies support that this intervention will also slow eGFR
decline. Other recent small-scale studies support the
benefit of base-producing fruits and vegetables in treating
Adv Chronic Kidney Dis. 2017;24(5):298-304
 Managing Metabolic Acidosis
metabolic acidosis in CKD,31,47 but larger scale studies
must confirm these studies before such interventions,
which carry the risk of hyperkalemia because of the high
K1 content of plant-based foods, become a standard
recommendation for treating the metabolic acidosis of
CKD. These fruit and vegetable interventions, however,
might be effective adjuncts to Na1-based alkali to improve
metabolic acidosis, particularly given that the fruit and
vegetable intervention has additional salutary effects like
better blood pressure control.31,47
CONCLUSION
Metabolic acidosis accompanying CKD increases mortality
and contributes to morbidity such as decreased bone min-
eral content, increased protein catabolism, and possibly
enhanced stages of kidney disease progression. Most of
these untoward consequences can be mitigated by treating
metabolic acidosis and so clinicians have an imperative to
do so. The most effective treatment strategy available to cli-
nicians is dietary H1 reduction that can be accomplished
with Na1-based alkali and/or with base-producing food
components like fruits and vegetables. Each of these strate-
gies to reduce dietary H1 is relatively inexpensive and
comparatively well-tolerated but Na1-based alkali is
the currently recommended treatment, and NaHCO3
therapy is recommended for patients with serum
[HCO3] , 22 mEq/L. Whether patients with CKD with
reduced GFR but no metabolic acidosis or selected patients
with normal GFR but eating diets of high H1 content are
candidates for dietary H1 reduction will be determined
by further study.
ACKNOWLEDGMENT
Financial Disclosure: Dr Goraya has no financial disclosures. Dr
Wesson is a paid consultant for Tricida.
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