International Urology and Nephrology (2024) 56:1983–1986

https://doi.org/10.1007/s11255-024-03949-2

NEPHROLOGY - REVIEW

Alactic base excess (ABE): a novel internal milieu parameter—its

concept and clinical importance
Md Hoque1 · Jason Nagourney1 · Thomas Pawlowski1 · Joaquin Cantos2 · Gustavo Aroca‑Martinez3 · Ivan Huespe2,4 ·
Carlos G. Musso3,4

Received: 11 October 2023 / Accepted: 3 January 2024 / Published online: 10 February 2024
© The Author(s), under exclusive licence to Springer Nature B.V. 2024

Abstract
Inspired by the Stewart-Figge acid–base approach, Gattinoni et al. recently introduced a new internal milieu parameter known
as alactic base excess (ABE). The authors defined ABE as the sum of lactate and standard base excess. In the context of
sepsis, ABE has been proposed as a valuable marker to discern between metabolic acidosis resulting from the accumulation
of lactate and the retention of fixed acids, which can occur in cases of renal failure. Multiple studies have demonstrated that a
negative ABE value (<−3 mmol/L) represents an early marker of renal dysfunction, and significantly correlates with higher
mortality rates in septic patients. In conclusion, ABE is a simple and useful parameter that can be used to better interpret a
patient’s acid–base status, assess renal function, and general prognosis in sepsis. By incorporating ABE into clinical practice,
healthcare professionals can enhance their understanding of the complex acid–base imbalances in their patients and tailor
more individualized, effective treatment plans.

Keywords Alactic base excess · Strong ion difference · Sepsis · Biomarker · Acute kidney injury

Introduction (SIDa). It can be calculated using the following equation (all

concentrations in mmol/L) [1, 2]:
The Stewart-Figge acid–base approach is founded on the
SIDa = (Na + K + Ca + Mg) − [Cl + strong acids(e.g. ∶ lactate)]
idea that there are three primary factors that determine the
acid–base status: carbon dioxide partial pressure ­(pCO2), However, to account for the influence of weak acids in
strong ion difference (SID), and the total concentration of maintaining electrical charge balance in plasma water, the
weak acids and plasma proteins, such as albumin and phos- effective SID (SIDe) should be determined using the follow-
phates. The SID represents the net charge balance of fully or ing formula [3–5]:
nearly fully dissociated ions, also known as the apparent SID
SIDe = 2.46 × 10−8 × pCO2 (mmHg)∕10 − pH
+ (albumin(g∕l)) × (0.123 × pH − 0.631)
+ (phosphate (mg∕dl)) × (0.309 × pH − 0.469)
Md Hoque, Jason Nagourney, and Thomas Pawlowski are co-first
authors.
The difference between SIDa and SIDe, designated as
* Carlos G. Musso strong ion gap (SIG), can be quantified using the equation:
[email protected]
SIG = SIDa − SIDe
1
University of Rochester School of Medicine and Dentistry,
Rochester, NY, USA Normally, the value of SIG should fall within the range of
2
0–2 mmol/L, adhering to the principle of plasma electroneu-
Intensive Care Division, Hospital Italiano de Buenos Aires,
Buenos Aires, Argentina trality. Deviations from this range may indicate the presence
3
of unexplained charges, which can be identified as a SIG.
Facultad de Ciencias de La Salud, Universidad Simon
Bolivar, Barranquilla, Colombia
4
Research Department, Hospital Italiano de Buenos Aires,
Buenos Aires, Argentina

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1984 International Urology and Nephrology (2024) 56:1983–1986

Traditional acid–base (Henderson– Table 1  Causes of lactic acidosis

Hasselbach) approach Tissue oxygenation reduction Hypoxemia
Shock status
Traditional acid–base diagnostic method is based on the Organ ischemia
conception that the protons in the medium come from the Oxidative metabolism reduction Ketosis diabetic
acids dissociation. This method is based on the assess- Malignancy
ment of the two components of the Henderson–Hasselbach Toxicities
equation [pH = pKa + log(A−)∕(HA)]: the metabolic com- Lactate clearance reduction Liver failure
ponent, represented by the plasma level of bicarbonate and Excessive energy waste Seizures
base excess, and the respiratory component, represented Hyperthermia
by the plasma level of carbon dioxide. The analysis of the Extreme exercise
metabolic component is complemented by the calculation Other causes d-lactic acidosis
of the anion gap [natremia − (chloremia + bicarbonatemia)],
which allows differentiation of metabolic acidosis due to
bicarbonate loss (normal anion gap) from bicarbonate Hyperlactatemia can arise from various causes (Table 1)
reconversion (high anion gap) [6]. [8]. While it was previously suggested that increased lac-
It is worth pointing out that even though both acid–base tate levels are primarily due to tissue hypoxia resulting
approaches have similar diagnostic utility, the Stew- from impaired oxygen delivery, this theory fails to account
art–Figge acid–base approach offers the advantage of for other factors such as fluid imbalance, anion gap, SID,
detecting the impact of weak acids, most importantly oxygen extraction, venous oxygen saturation, and meta-
albumin in patients with hypoalbuminemia. On a patient’s bolic acidosis. Gattinoni et al. [7] proposed a new perspec-
acid–base status, which is frequently observed in critical tive, suggesting that increased lactate serum levels, known
care units (CCUs) [5]. as hyperlactatemia, are often the result of impaired tissue
oxygen utilization or extraction rather than impaired oxy-
gen delivery. Moreover, lactate levels have been proposed
as a predictive factor for mortality, particularly in cases
Hyperlactatemia and acidosis of sepsis, making it a highly valuable biomarker in CCU
patients. For example, lactic acidosis has shown the high-
An increase in lactate concentration can result in meta- est mortality rate in CCU settings, with 56% compared
bolic acidosis, characterized by an excess of negative to unidentified anions (39%), or hyperchloremic acidosis
strong ions. However, it does not necessarily lead to aci- (29%). The control group without acidosis has shown a
demia, which is defined as low serum pH. This is because mortality rate of 26% [7].
other simultaneous processes may induce a compensatory
reduction in negative strong ions, causing a widening of
the SID and restoring normal pH. The kidneys play a cen-
tral role in correcting lactate excess, which is a common Alactic base excess concept
type of compensatory mechanism [2]. However, Musso
et al. [3] have shown that patients with compromised kid- Traditionally, it has been recognized that an increase in
neys, who were unable to regulate their hyperlactatemia, serum lactate (hyperlactatemia) does not necessarily result
were able to use hemoperfusion as an adequate treatment. in a decrease in serum pH (acidemia). The key determinant
Lactate levels were able to be restored to physiologically of how plasma lactate concentration affects serum pH lies in
normal conditions using machine interventions for a tem- the functionality of the kidneys. Lactate-induced acidemia
porary period of time, demonstrating that hemoperfusion is only observed in patients with impaired renal function,
is a valid treatment option when the kidneys are unable to defined by a serum creatinine level of ≥2 mg/dL. To bet-
compensate for this type of ion imbalance. ter understand the relationship between hyperlactatemia
Gunnerson et al. have classified acid–base disorders and acidemia, the concept of alactic base excess (ABE) was
based on the primary anion contributing to acidosis. introduced by Gattinoni et al. [7].
They define lactic acidosis as metabolic acidosis in which ABE is a novel parameter that aims to differentiate
lactate accounts for more than 50% of the standard base between metabolic acidosis caused by lactate accumula-
excess (SBE). On the other hand, SIG (unmeasured ions) tion and metabolic acidosis induced by the retention of
acidosis is characterized by the SIG accounting for more fixed acids (e.g.: phosphates, sulfates) due to renal failure.
than 50% of SBE [7]. It is defined as the sum of lactate and SBE. ABE has been
International Urology and Nephrology (2024) 56:1983–1986 1985

proposed as a measurement of renal function in cases of demonstrated that a significant number of patients with
sepsis. The calculation for ABE is as follows: a negative ABE value, even without meeting the criteria
for acute kidney injury (AKI), later develop worsening
ABE(mmol∕L) = Standard Base Excess(mmol∕L) kidney function and acidemia to the point of being diag-
+ Lactate(mmol∕L) nosed with AKI [1].
  It has been reported an increase in Urinary Strong
Standard base excess (SBE) represents the amount of acid Ion Difference (SIDu), plasmatic unmeasured anions,
or base required to restore the serum pH to 7.4, assuming and phosphate before the occurrence of AKI. This find-
a normal P­ aCO2 level. It is quantified using the following ing suggests that “subclinical AKI” can be diagnosed
equation: by detecting alterations in acid–base regulation. In this
sense, it has been documented that a negative ABE value
SBE(mmol∕L) = [HCO3 − (mmol∕L) − 24.8 mmol∕L]
in patients without AKI criteria reflects a “subclinical
+ 16.2 mmol∕L × (pH − 7.4) AKI” secondary to fixed acid retention. It is also associ-
ated with poor outcomes independent of AKI criteria.
SBE is utilized instead of actual base excess as it provides
The fixed acid retention without AKI criteria is attrib-
a better indication of the extracellular fluid buffer base sta-
uted to the kidney’s inability to acidify urine as a com-
tus. While it may seem counterintuitive that the ABE equa-
pensatory mechanism during metabolic acidosis. This
tion includes lactate, it is named as such to emphasize the
fixed acid retention can be attributed to “acute tubular
separation of lactate from the standard bases, allowing for
dysfunction,” which reduces acid tubular secretion due
individual assessment. It is important not to confuse the term
to overload or dysfunction of organic anion transporters
“alactic” with “non-lactic,” which is used in other internal
(OAT1) or reduced proton tubular secretion capability.
milieu equations to indicate the exclusion of lactate from
Therefore, dynamic ABE monitoring appears to be a
the equation components. The concept of ABE is based on
complementary tool for detecting “subclinical AKI,” as
the idea that the renal tubules compensate for increased acid
its components are widely measured and easy to calcu-
levels in the body (primarily lactic acid, which will be dis-
late [1, 9].
cussed further in this review) by releasing fixed acids to
2. Neutral ABE value (≥ 3 to < 4 mmol/L): This category
maintain serum pH and other functions.
indicates that the kidneys are compensating for a buildup
of lactic acid. In these cases, patients may have elevated
levels of lactic acid in the blood, but the blood pH
ABE categories
remains normal as the kidneys effectively concentrate
the fixed acids in the urine and maintain pH balance.
The results obtained from the ABE equation can be further
Prognostically, patients with a neutral ABE value gener-
classified into three categories to provide a proposed diag-
ally have lower mortality rates compared to those with
nosis [1, 7, 9]:
a negative ABE value. However, there are exceptions,
particularly in patients with negative ABE values and
1. Negative ABE value (<−3 mmol/L): This category
high renal function (GFR > 60 mL/min/1.73 m ­ 2), which
represents the most concerning result, as it is a strong
may suggest the possibility of a negative ABE being
indicator of mortality in patients with sepsis. Given the
an indicator of future renal dysfunction rather than a
complexity of these relationships, the use of ABE as a
present one [1, 7].
potential new biomarker to predict sepsis-related mor-
3. Positive ABE value (≥ 4 mmol/L): This category sug-
tality becomes extremely useful. Lactate, as a powerful
gests that there is no significant concentration of stand-
marker of illness severity established by the Sequential
ard bases or lactic acid in the blood, as the kidneys have
Organ Failure Assessment (SOFA), adds further signifi-
compensated for metabolic acidosis, or the body has
cance to the inclusion of ABE in this context.
employed other compensatory mechanisms to contribute
  A negative ABE value indicates that the standard
to alkalosis in response to falling blood pH. A positive
bases are not being adequately eliminated in the urine
ABE value can also provide guidance in the decision-
and are instead accumulating in the blood, along with
making process for fluid resuscitation in CCUs, as met-
lactic acid. The strain on the renal tubules to excrete
abolic alkalosis can be caused by diuretics or volume
fixed acids can eventually overwhelm their capacity,
contraction.
leading to a failure of compensation mechanisms involv-
ing organic anion transporters or the proton pump. This
Lower significant link has been found between positive
can quickly result in acidemia and a worsening glomeru-
ABE values and patient mortality in comparison to negative
lar filtration rate (GFR). Notably, research findings have
ABE values [1, 7].
1986 International Urology and Nephrology (2024) 56:1983–1986

Conclusion 4. Gucyetmez B, Atalan HK (2016) Non-lactate strong ion differ-

ence: a clearer picture. J Anesth 30(3):391–396
5. Figge J, Bellomo R, Egi M (2018) Quantitative relationships
In conclusion, capturing the physiological capabilities of among plasma lactate, inorganic phosphorus, albumin, unmeas-
the kidneys in restoring acid–base balance through ABE is ured anions and the anion gap in lactic acidosis. J Crit Care
crucial. ABE provides valuable insights into the underly- 44:101–110
6. Musso CG, Vilas MF (2019) Water, electrolyte, and acid-base dis-
ing causation factors and supports individualized therapeu- orders in the elderly. In: Musso CG, Jauregui JR, Macías-Núñez
tic approaches. By considering ABE, clinicians can more JF, Covic A (eds) Clinical nephrogeriatrics. Springer, Cham, pp
confidently assess the renal function’s impact on acid–base 43–62
status and make informed decisions tailored to each patient’s 7. Gattinoni L, Vasques F, Camporota L, Meessen J, Romitti F, Pas-
ticci I et al (2019) Understanding lactatemia in human sepsis.
needs. Potential impact for early management. Am J Respir Crit Care
Med 200(5):582–589
8. Ratnam S, Kaehny W, Schapiro J (2011) Pathogenesis and treat-
Declarations ment of metabolic acidosis and alkalosis. In: Schrier R (ed)
Renal and electrolyte disorders. Wolters Kluwer, Philadelphia,
Conflict of interest All the authors declare that they have no conflict pp 86–121
of interest. 9. Gattinoni L, Carlesso E, Cadringher P, Caironi P (2006) Strong
ion difference in urine: new perspectives in acid-base assessment.
Crit Care 10(2):137. https://​doi.​org/​10.​1186/​cc4890

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jurisdictional claims in published maps and institutional affiliations.
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