Serum Anion Gap Predicts All-Cause Mortality in Patients with Advanced Chronic Kidney Disease: A Retrospective Analysis of a Randomized Controlled Study

Lee, Sung Woo; Kim, Sejoong; Na, Ki Young; Hui, Ran; Kang, Shin Wook; Park, Cheol Whee; Ryong, Dae; Kim, Sung Gyun; Yoon, Sun Ae; Han, Sang Youb; Park, Jung Hwan; Chang, Jae Hyun; Lim, Chun Soo; Kim, Yon Su

doi:10.1371/journal.pone.0156381

Cited by 13 publications

(9 citation statements)

References 35 publications

(49 reference statements)

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“…In this study, we also showed that the traditional AG value was positively associated with both the leukocyte count and CRP level in patients with ESKD. The association between high AG, high CRP and a high leukocyte count and a low eGFR detected in this study may also support the increased risk of mortality by high AG, as previously reported 7 , 8 .…”

Section: Discussionsupporting

confidence: 91%

False-negative diagnosis of high anion gap in patients with end-stage kidney disease

Komatsuzaki

Ikeda

Shimizu

et al. 2021

Sci Rep

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The traditional anion gap (AG) equation is widely used, but its misdiagnosis in end-stage kidney disease (ESKD) patients has not been investigated fully. Diagnostic accuracy to detect high AG was cross-sectionally evaluated using 3 AG equations in 1733 ESKD patients with an eGFR less than 15 mL/min/1.73 m2. The prevalence of high AG was 67.9%, 92.1% and 97.4% by the traditional, albumin-adjusted AG (aAG) and full AG equations, respectively. The sensitivity, specificity, accuracy and Kappa coefficient obtained with the traditional AG vs aAG equation were 0.70 vs 0.94, 0.98 vs 0.93, 0.7 vs 0.94, and 0.103 vs 0.44, respectively. Next, we created a subcohort comprising only patients with high full AG and investigated how the traditional AG equation leads to misdiagnoses. Multivariable-adjusted regression analysis in 1688 patients revealed that independent factors associated with a false-negative AG diagnosis were ARB use, eGFR, blood leukocyte count, serum chloride, bicarbonate, ionized calcium, potassium, albumin and phosphate. 93.2% of our subcohort prescribed any of RAAS inhibitors, Loop diuretics or Alkali which could increase either serum chloride or bicarbonate. Frequent use of these possible AG-reducing medications may conceal high AG state in patients with ESKD unless they have incidental inflammation which may increase AG value.

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Section: Discussionsupporting

confidence: 91%

False-negative diagnosis of high anion gap in patients with end-stage kidney disease

Komatsuzaki

Ikeda

Shimizu

et al. 2021

Sci Rep

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“…A retrospective analysis of 440 participants data suggested that adjusted serum anion gap is an independent risk factor for all -cause mortality in advanced CKD patients, with HR (95% CI) 2.968 (1.143–7.708). 19 The relationship between serum AG and mortality has been reported not only in adults but also in children. Kim and his team 20 reported that corrected AG in children at ICU admission was associated with mortality, with odds ratio (95% CI) 1.110 (1.06–1.17).…”

Section: Discussionmentioning

confidence: 99%

The Relationship Between the Serum Anion Gap and All-Cause Mortality in Acute Pancreatitis: An Analysis of the MIMIC-III Database

Gong

Zhou

Gui

et al. 2021

IJGM

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Purpose We aimed to investigate the relationship between the serum anion gap (AG) and all-cause mortality in patients with acute pancreatitis (AP) in intensive care units (ICUs). Patients and Methods In this retrospective cohort analysis, data of patients with AP were extracted from the Medical Information Mart for Intensive Care database (version III). We collected the maximum serum AG value within the first 24 hours of ICU admission. The main outcome was 90-day all-cause mortality. A multivariate Cox proportional hazard regression model was used to examine the association between the serum AG and mortality. The restricted cubic spline curve was used to confirm a non-linear relationship between serum AG values and mortality. Results Of the 279 patients included in the study, 87 (31.18%) died. The serum AG value was positively associated with 90-day all-cause mortality (hazard ratio [HR] 1.08, 95% confidence interval [CI] 1.02–1.14), after adjusting for age, sex, alcohol consumption, congestive heart failure, diabetes mellitus, hypertension, eGFR, albumin, and the SOFA score. There was a non-linear relationship between serum AG values and mortality after adjusting for potential confounders. We used a two-piecewise regression model to obtain a threshold inflection point value of 13.8 mmol/L. The HR and the 95% CI on the left inflection point were 0. 82 (0.61–1.09; p = 0.1719), and on the right inflection point were 1.15 (1.08–1.23; p < 0.0001). Conclusion The relationship between all-cause mortality in patients with acute pancreatitis and serum AG values was non-linear. All-cause mortality and serum AG values were positively correlated when the serum AG value was >13.8 mmol/L.

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“…β2MG, which is a well-known representative marker of smaller mid-size UTs in patients undergoing maintenance dialysis, has recently been rediscovered as a novel filtration marker predicting CKD progression and mortality [ 8 ]. Additionally, an increased AG caused by retention of anionic UTs reflects the potential for progression of uremic syndrome in ESRD patients and has also been proven to be related to mortality around the commencement of dialysis [ 9 , 10 ]. Although each biomarker reflecting the accumulation of UTs has been proven to be related to poor prognosis in ESRD patients, it remains unknown whether the combination of these three biomarkers, reflecting accumulation of multiple specific UTs, shows a greater association with worsening prognosis.…”

Section: Introductionmentioning

confidence: 99%

A Novel Uremic Score Reflecting Accumulation of Specific Uremic Toxins More Precisely Predicts One-Year Mortality after Hemodialysis Commencement: A Retrospective Cohort Study

Arai

Shioji

Tanaka

et al. 2020

Toxins

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Uremic toxins (UTs) generally accumulate in patients developing end-stage renal disease (ESRD). Although some kinds of UTs cause early death after starting hemodialysis (HD), it remains unknown whether the degree of excessive accumulation of various UTs is associated with worsening of prognosis. We retrospectively conducted this cohort study consisting of adult patients developing ESRD who initiated HD at the National Center for Global Health and Medicine from 2010 to 2019. We created a new uremic score, which was defined as the aggregate score of the following variables reflecting uremic state: elevated blood urea nitrogen, β2-microglobulin, and anion gap before starting HD. The primary outcome was early mortality within 1-year after HD commencement. The hazard ratio (HR) and 95% confidence interval (CI) for a one-point increase in uremic score was calculated with Cox proportional hazard models adjusted by baseline conditions. We included 230 participants, 16 of whom experienced the primary outcome of early mortality after HD commencement. Uremic score was significantly associated with the primary outcome (crude HR: 1.91, 95% CI 1.16–3.14; adjusted HR: 4.19, 95% CI 1.79–9.78). Our novel uremic score, reflecting accumulation of specific UTs, more precisely predicts early mortality after HD commencement.

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Serum Anion Gap Predicts All-Cause Mortality in Patients with Advanced Chronic Kidney Disease: A Retrospective Analysis of a Randomized Controlled Study

Cited by 13 publications

References 35 publications

False-negative diagnosis of high anion gap in patients with end-stage kidney disease

False-negative diagnosis of high anion gap in patients with end-stage kidney disease

The Relationship Between the Serum Anion Gap and All-Cause Mortality in Acute Pancreatitis: An Analysis of the MIMIC-III Database

A Novel Uremic Score Reflecting Accumulation of Specific Uremic Toxins More Precisely Predicts One-Year Mortality after Hemodialysis Commencement: A Retrospective Cohort Study

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