Sun 

et al. BMC Nephrology (2022) 23:83

https://doi.org/10.1186/s12882-022-02715-9

RESEARCH Open Access

Central venous pressure and acute kidney

injury in critically ill patients with multiple
comorbidities: a large retrospective cohort
study
Runlu Sun1,2†, Qi Guo1,2†, Junjie Wang1,2, Yaoyao Zou3, Zhiteng Chen1,2, Jingfeng Wang1,2* and Yuling Zhang1,2* 

Abstract 
Background:  Given the traditional acceptance of higher central venous pressure (CVP) levels, clinicians ignore the
incidence of acute kidney injury (AKI). The objective of this study was to assess whether elevated CVP is associated
with increased AKI in critically ill patients with multiple comorbidities.
Methods:  This was a retrospective observational cohort study using data collected from the Medical Information
Mart for Intensive Care (MIMIC)-III open-source clinical database (version 1.4). Critically ill adult patients with CVP and
serum creatinine measurement records were included. Linear and multivariable logistic regression were performed to
determine the association between elevated CVP and AKI.
Results:  A total of 11,135 patients were enrolled in our study. Critically ill patients in higher quartiles of mean CVP
presented greater KDIGO AKI severity stages at 2 and 7 days. Linear regression showed that the CVP quartile was posi-
tively correlated with the incidence of AKI within 2 (R2 = 0.991, P = 0.004) and 7 days (R2 = 0.990, P = 0.005). Further-
more, patients in the highest quartile of mean CVP exhibited an increased risk of AKI at 7 days than those in the lowest
quartile of mean CVP with an odds ratio of 2.80 (95% confidence interval: 2.32–3.37) after adjusting for demographics,
treatments and comorbidities. The adjusted odds of AKI were 1.10 (95% confidence interval: 1.08–1.12) per 1 mmHg
increase in mean CVP.
Conclusions:  Elevated CVP is associated with an increased risk of AKI in critically ill patients with multiple comorbidi-
ties. The optimal CVP should be personalized and maintained at a low level to avoid AKI in critical care settings.
Keywords:  Central venous pressure, Acute kidney injury, KDIGO stage, Critically ill patients

Background the development of AKI. However, optimal hemody-

Acute kidney injury (AKI) is a common complication in namic indicators of the risk of AKI have not been identi-
critically ill patients and has high morbidity and mortality fied [2]. Although elevated fluid volume improves renal
[1]. Systemic and renal perfusion noticeably determines perfusion, aggressive fluid loading may lead to elevated
central venous pressure (CVP). Given the traditional
acceptance of higher CVP levels [3, 4], clinicians ignore
*Correspondence: wjingf@mail.sysu.edu.cn; zhyul@mail.sysu.edu.cn elevated CVP, and the incidence of AKI is potentially
†
Runlu Sun and Qi Guo contributed equally to this work.
1
Department of Cardiology, Sun Yat‑sen Memorial Hospital, Sun interlaced.
Yat-sen University, No. 107, the West Yanjiang Road, Yuexiu District, CVP, a local hemodynamic parameter, reflects intra-
Guangzhou 510120, China vascular volume and is determined by the interaction
Full list of author information is available at the end of the article

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Sun et al. BMC Nephrology (2022) 23:83 Page 2 of 10

between venous return and cardiac function [5]. There- Variables

fore, CVP is generally used for bedside assessment CVP, creatinine, and urine output records during the
of volume status and responsiveness in critically ill ICU stay were extracted. Other day 1 ICU measure-
patients [6]. Nonetheless, the validity of CVP in critical ment records were also extracted, including age, sex,
care settings has recently been challenged [7]. Based on weight, blood pressure and admission illness scores (the
the rationale provided by the Starling curves and Guy- Simplified Acute Physiology Score (SAPS) [13] and the
ton theory on cardiac function [8], elevated CVP may Sequential Organ Failure Assessment (SOFA) score) [14].
increase venous pressure and decrease renal perfusion Moreover, data on the use of vasopressors, inotropes,
pressure, which further contributes to AKI. However, sedatives, diuretics, invasive mechanical ventilation, and
in critically ill patients with multiple comorbidities, comorbidities, including sepsis, congestive heart fail-
including sepsis, heart failure, arrhythmias, hyperten- ure (CHF), arrhythmias, hypertension, diabetes, chronic
sion, diabetes or others, the association between ele- renal failure and cancer, were extracted from the data-
vated CVP and AKI remains unclear. base. In this study, vasopressors included norepinephrine,
Until recently, studies have shown inconsistent con- epinephrine, phenylephrine, vasopressin, and dopamine.
clusions about the association of CVP and AKI in Inotropes included dobutamine and milrinone. Chronic
critically ill patients [9–11]. Herein, we sought to char- renal failure was defined as abnormalities of kidney
acterize the association of elevated CVP and AKI in structure or function (estimated glomerular filtration
critical care settings using the large, public, deidentified rate (eGFR) < 60 ml/min/1.73m2), present for more than
clinical database Medical Information Mart for Inten- 3 months, with implications for health [15]. Cardiac sur-
sive Care (MIMIC)-III [12]. Specifically, we hypothe- gery recovery unit (CSRU) was used as variable to indi-
sized that elevated CVP is associated with an increased cate the ICU type one patient stayed was CSRU. The
incidence of AKI in critically ill patients with multiple comorbidities were determined from the International
comorbidities. Classification of Disease, 9th Edition, Clinical Modifica-
tion codes.

Methods Exposure
Data source The primary exposure was the mean CVP during the first
We conducted a large-scale, single-center, retrospective 7 days after ICU admission. We divided the mean CVP into
cohort study using data collected from the MIMIC-III four levels according to interquartile range as follows: quartile
open source clinical database (version 1.4), which was 1, CVP ≤ 8.29 mmHg; quartile 2, 8.29 < CVP ≤ 10.64 mmHg;
developed and maintained by the Massachusetts Insti- quartile 3, 10.64 < CVP ≤  13.20 
mmHg; and quartile 4,
tute of Technology, Philips Healthcare, and Beth Israel CVP > 13.20 mmHg.
Deaconess Medical Center [12]. One author (Qi Guo)
obtained access to the database and was responsible
Outcomes
for data extraction (certification number: 25233333).
Information derived from the 61,532 electronic medical The primary outcome was the odds of 2-day and 7-day
records of critically ill patients admitted to intensive care AKI after ICU admission. We defined AKI by serum
units (ICUs) between 2001 and 2012 was included in this creatinine based on the KDIGO criteria [16]. AKI was
free, accessible database. The database was approved for categorized as Stage 1 if there was a 1.5–1.9 times
research use by the Institutional Review Boards of the serum creatinine increase from baseline, a 0.3 mg/dL
Massachusetts Institute of Technology and Beth Israel serum creatinine increase or a urine output < 0.5 ml/
Deaconess Medical Center, and studies using the data- kg/h for 6–12 h. Stage 2 was when there was a 2.0–2.9
base were granted a waiver of informed consent. times serum creatinine increase from baseline or a urine
output < 0.5 ml/kg/h for ≥12 h, and Stage 3 was when
there was a ≥ 3 times serum creatinine increase from
baseline or a ≥ 4.0 mg/dL serum creatinine increase or
Study population
urine output < 0.3 ml/kg/h for ≥24 h. The first serum
All patients in the database were screened according to
creatinine record measured on ICU Day 1 was consid-
the following inclusion criteria for this study: (1) adults
ered the “baseline”.
(≥18 years of age at ICU admission); (2) ICU stay ≥1 day;
We calculated the CVP fluctuation within the first
and (3) for patients with multiple ICU stays, only the
2 days as follows: (mean CVP on the second day – mean
data for the first stay were considered. Patients with cen-
CVP on the first day)/mean CVP on the first day. Patients
sored age, no CVP records, or no creatinine records were
were divided into 3 CVP trend groups: decreasing trend
excluded.
 Sun et al. BMC Nephrology (2022) 23:83 Page 3 of 10

(fluctuation ≤ −  10%), increasing trend (fluctuation Statistical analysis

≥10%), and stable trend (− 10% < fluctuation< 10%). Normally distributed continuous variables are pre-
Among the study population, 7397 patients suffered con- sented as the mean ± standard deviation, whereas non-
tinuous CVP monitoring within the first 2 days. The asso- normally distributed data are presented as the median
ciation between this CVP trend group and AKI outcome (interquartile range). Categorical variables are presented
was then evaluated for these patients. as numbers (percentages). Baseline characteristics were
Adjusted variables included age, male sex, weight, stratified by quartiles of mean CVP during the first 7 days
CSRU, ventilation use, vasopressor use, inotropes use, after ICU admission. Baseline data were compared using
sedative use, diuretic use, SAPS score, SOFA score, sep- the analysis of variance test or rank-sum test, as appro-
sis, CHF, arrhythmias, hypertension, diabetes, chronic priate, for continuous variables, and the chi-square test
renal failure, cancer, systolic blood pressure (SBP), and was used for categorical variables. We performed linear
diastolic blood pressure. and logistic regression to compute odds ratios (ORs) for
The association between CVP and AKI was fur- the association of mean CVP with the odds of AKI.
ther evaluated in patients using mechanical venti- All statistical analyses were performed using SPSS software
lation. To evaluate whether ventilation parameter (version 23.0, IBM, New York, USA) and R software (version
influence our results, models were adjusted for age, 3.6.3, R Foundation for Statistical Computing, Vienna, Aus-
male sex, weight, CSRU, ventilation use, vasopressor tria). A P value < 0.05 was considered statistically significant.
use, inotropes use, sedative use, diuretic use, SAPS
score, SOFA score, sepsis, CHF, arrhythmias, hyper- Results
tension, diabetes, chronic renal failure, cancer, SBP, Baseline characteristics
diastolic blood pressure, and positive end-expiratory Among the 61,532 ICU admissions in the MIMIC-III
pressure. v1.4 database, 11,135 patients were enrolled in our study

Fig. 1  Flow chart of enrolled subjects. A total of 11,135 subjects were enrolled in our study. All enrolled subjects were divided into 4 groups based
on CVP quartiles. ICU, intensive care unit; CVP, central venous pressure
Sun et al. BMC Nephrology (2022) 23:83 Page 4 of 10

based on the inclusion and exclusion criteria in the was greater among patients with higher CVP, ranging
Methods section (Fig. 1). The number of patients in each from 63.6% in patients with a mean CVP ≤ 8.39 mmHg
CVP quartile was approximately 2780. The mean CVP (Quartile 1) to 88.4% in patients with a mean
in each quartile was 6.7 ± 1.3 mmHg, 9.5 ± 0.6 mmHg, CVP > 13.20 mmHg (Quartile 4). A similar trend was
11.9 ± 0.7 mmHg, and 16.0 ± 3.2 mmHg in the lowest to detected between the incidence of AKI at 7 days and the
highest quartiles, respectively. Interestingly, patients in mean CVP. Moreover, patients in the higher quartiles of
higher quartile of mean CVP had lower urine output, mean CVP presented greater KDIGO AKI severity stages
higher creatinine and lower eGFR. Also, patients in the at 2 days and 7 days (Table 2). Additionally, linear regres-
highest quartile of mean CVP presented the greatest sion showed that the CVP quartile was positively cor-
weight and highest SAPS and SOFA scores. Furthermore, related with the incidence of AKI at 2 days (R2 = 0.991,
patients with the highest quartile of mean CVP were P = 0.004) and 7 days (R2 = 0.990, P = 0.005) (Fig. 2).
likely to be treated with vasopressors and diuretics and We further performed a logistic regression analysis to
more likely to have comorbidities of sepsis, CHF, arrhyth- determine the association between quartiles of mean CVP
mia, hypertension and chronic renal failure (Table 1). and AKI outcomes in 7 days. For the crude model, patients
in higher quartiles of mean CVP had a greater incidence of
Elevated CVP and AKI outcome at 2 and 7 days AKI at 7 days than those in the lowest quartile of mean CVP,
During the first 2 days and 7 days, 8544 and 9289 patients ranging from OR = 1.63 (95% CI: 1.44–1.85) to OR = 5.18
had AKI, respectively. The incidence of AKI at 2 days (95% CI: 4.37–6.14). After adjustment, the mean CVP

Table 1  Characteristics of the enrolled subjects based on CVP quartiles

CVP
Variables Quartile 1 Quartile 2 Quartile 3 Quartile 4 P

n 2781 2788 2782 2784

CVP, mmHg 6.7 ± 1.3 9.5 ± 0.6 11.9 ± 0.7 16.0 ± 3.2 < 0.001a,b,c,d,e,f
Urine output, ml 2080.0(1340.0–2980.0) 1961.0(1320.0–2768.0) 1850.0(1195.8–2665.0) 1535.0 (870.0–2365.0) < 0.001a,b,c,d,e,f
Creatinine, mg/dl 0.8 (0.6–1.1) 0.9 (0.7–1.2) 0.9 (0.7–1.3) 1.0 (0.8–1.6) < 0.001a,b,c,d,e,f
2
eGFR, ml/min/1.73m 87.7(63.1–101.2) 83.7(56.7–97.4) 80.8(52.1–96.6) 69.0 (39.1–91.7) < 0.001a,b,c,d,e,f
Age, years 65.0 ± 15.1 65.8 ± 14.1 65.4 ± 14.1 64.1 ± 14.1 < 0.001a,c,e,f
Male 1729 (62.2) 1773 (63.6) 1691 (60.8) 1650 (59.3) 0.007e
Weight, kg 76.0 ± 21.6 81.4 ± 18.8 85.3 ± 21.1 90.9 ± 25.0 < 0.001a,b,c,d,e,f
SBP, mmHg 116.5 ± 14.2 113.9 ± 12.5 113.0 ± 12.6 110.3 ± 12.3 < 0.001a,b,c,d,e,f
DBP, mmHg 57.7 ± 8.6 57.5 ± 7.9 57.9 ± 8.1 57.9 ± 8.3 0.268
SAPS 20.0 (17.0–22.0) 20.0 (17.0–23.0) 20.0 (18.0–23.0) 21.0 (18.0–24.0) < 0.001a,b,c,e,f
SOFA 4.0 (3.0–6.0) 5.0 (3.0–7.0) 5.0 (4.0–8.0) 7.0 (5.0–9.0) < 0.001a,b,c,d,e,f
CSRU 1354 (48.7) 1563 (56.1) 1582 (56.9) 1374 (49.4) < 0.001a,b,e,f
Treatment
 Vasopressor 1551 (55.8) 1872 (67.1) 1970 (70.8) 2054 (73.8) < 0.001a,b,c,d,e,f
 Inotropes 102 (3.7) 157 (5.6) 267 (9.6) 465 (16.7) < 0.001a,b,c,d,e,f
 Sedative 2003 (72.0) 2218 (79.6) 2291 (82.4) 2263 (81.3) < 0.001a,b,c,d
 Ventilation 2123 (76.3) 2336 (83.8) 2430 (87.3) 2406 (86.4) < 0.001a,b,c,d,e
 Diuretic 209 (7.5) 295 (10.6) 330 (11.9) 432 (15.5) < 0.001a,b,c,e,f
Comorbidities
 Sepsis 714 (25.7) 805 (28.9) 843 (30.3) 1207 (43.4) < 0.001a,b,c,e,f
 CHF 258 (9.3) 266 (9.5) 304 (10.9) 394 (14.2) < 0.001c,e,f
 Arrhythmias 268 (9.6) 267 (9.6) 299 (10.7) 411 (14.8) < 0.001c,e,f
 Hypertension 163 (5.9) 200 (7.2) 215 (7.7) 284 (10.2) < 0.001b,c,e,f
 Diabetes 682 (24.5) 819 (29.4) 868 (31.2) 883 (31.7) < 0.001a,b,c
  Chronic renal failure 210 (7.6) 247 (8.9) 256 (9.2) 380 (13.6) < 0.001c,e,f
 Cancer 137 (4.9) 92 (3.3) 72 (2.6) 68 (2.4) < 0.001a,b,c
Quartile 1, CVP ≤ 8.39 mmHg; Quartile 2, 8.39 < CVP ≤ 10.64 mmHg; Quartile 3, 10.64 < CVP ≤ 13.20 mmHg; Quartile 4, CVP > 13.20 mmHg. CVP central venous pressure;
eGFR estimated glomerular filtration rate; CSRU cardiac surgery recovery unit; SAPS simplified acute physiology score; SOFA Sequential Organ Failure Assessment; CHF
congestive heart failure; SBP systolic blood pressure; DBP diastolic blood pressure. Superscripts: a indicates a significant difference in the comparison of quartile 1 vs.
quartile 2, b for quartile 1 vs. quartile 3, c for quartile 1 vs. quartile 4, d for quartile 2 vs. quartile 3, e for quartile 2 vs. quartile 4, and f for quartile 3 vs. quartile 4
 Sun et al. BMC Nephrology (2022) 23:83 Page 5 of 10

Table 2  Association of CVP quartiles and AKI at 2 days or 7 days Subgroup analysis by demographics, treatments
CVP
and comorbidities
Next, we determined the association between mean CVP
Quartile 1 Quartile 2 Quartile 3 Quartile 4 P
and AKI in subgroups of patients with an older age, low SBP
AKI in 2 days and a history of cardiac surgery, patients treated with vaso-
AKI 1768 (63.6) 2063 (74.0) 2251 (80.9) 2462 (88.4) < 0.001a,b,c,d,e,f pressors, diuretics and ventilation, and patients with CHF
  Stage 1 652 (23.4) 662 (23.7) 600 (21.6) 504 (18.1) < 0.001c,e,f and sepsis as comorbidities. Our data showed that CVP in all
< 0.001a,b,c,d
  Stage 2 890 (32.0) 1099 (39.4) 1257 (45.2) 1184 (42.5)
11,135 subjects was positively correlated with AKI (Fig. 4a).
  Stage 3 226 (8.1) 302 (10.8) 394 (14.2) 774 (27.8) < 0.001a,b,c,d,e,f
Additionally, among 6079 elderly patients (age ≥ 65 years),
AKI in 7 days
patients with a mean CVP of greater than 11 mmHg had
 AKI 2022 (72.7) 2267 (81.3) 2404 (86.4) 2596 (93.2) < 0.001a,b,c,d,e,f
  Stage 1 715 (25.7) 691 (24.8) 574 (20.6) 437 (15.7) < 0.001b,c,d,e,f
higher odds of AKI than those with a mean CVP of 5 mmHg
  Stage 2 1013 (36.4) 1188 (42.6) 1318 (47.4) 1205 (43.3) < 0.001a,b,c,d,e,f
(Fig. 4b). Moreover, 5008 subjects with SBP ≤ 110 mmHg and
  Stage 3 294 (10.6) 388 (13.9) 512 (18.4) 954 (34.3) < 0.001a,b,c,d,e,f higher mean CVPs had higher odds of AKI (Fig. 4c). Addi-
tionally, a higher mean CVP (approximately CVP > 10 mmHg
KDIGO stage represents the severity of AKI according to the baseline
measurement and the increase in serum creatinine or urine output. KDIGO Stage for diuretics and CVP > 8 mmHg for vasopressors) suggested
1 was defined as a low severity of AKI, Stage 2 was defined as medium severity an increased incidence of AKI in patients with use of diuret-
AKI, and Stage 3 was defined as high severity AKI. CVP central venous pressure;
AKI acute kidney injury ics, sepsis, use of ventilation, use of vasopressors (Fig. 4d & e
& f & g). However, in subjects with use of inotropes, with no
quartile remained a significant predictor of AKI at 7 days use of vasopressors or inotropes, with CHF, the mean CVP
(Fig. 3). Furthermore, the odds of AKI were 1.18-fold (95% from 5 mmHg to 10 mmHg did not show significant corre-
CI: 1.16–1.20) higher per 1 mmHg increase in mean CVP. lation with AKI (Fig. 4h & i & j). Nevertheless, an elevated
After adjusting for demographics, treatments and comor- mean CVP was positively correlated with the incidence of
bidities, the odds of AKI was 1.10 (95% CI: 1.08–1.12). AKI for patients in the CSRU (Fig. 4k).

Fig. 2  Proportion of AKI patients in different CVP quartiles and correlation between CVP quartile and AKI. The proportion of patients with different
AKI severity stages is shown in each group with different CVP quartiles. AKI, acute kidney injury; CVP, central venous pressure
Sun et al. BMC Nephrology (2022) 23:83 Page 6 of 10

Fig. 3  Odds ratios for AKI within 7 days associated with CVP in critically ill patients. For categorical variables, all odds ratios (95% CI) and P values
were calculated compared with the lowest quartile. For continuous variables, odds ratios (95% CI) corresponded to a 1 mmHg increase in CVP. CVP,
central venous pressure; AKI, acute kidney injury; CI, confidence interval

To address the effect of the ventilation properties on Elevated mean CVP is associated with an increased risk
the results, subgroup analyses in patients using invasive of AKI in critically ill patients; (2) A 1 mmHg increase in
mechanical ventilation were performed. After adjust- CVP increases the odds of AKI in critically adult patients;
ment for a series of variables, the CVP quartile 4 group (3) For critically ill patients with an older age, low SBP,
showed a significantly higher risk of AKI than the CVP a history of treatment with diuretics, vasopressors and
quartile 1 group (OR: 3.02, 95% CI: 2.41–3.79). The odds ventilation, comorbidities of sepsis, or in the CSRU, the
of AKI were 1.11 (95% CI: 1.09–1.14) times higher per mean CVP level remained a significant predictor of AKI.
1 mmHg increase in mean CVP in this ventilation sub- Clinicians use CVP as a measure of venous congestion
group (Fig. 5). in critically ill patients. Indeed, CVP has been censured
as an unusable measurement of venous congestion due
Association between CVP trend and AKI to other variables that can alter its value, including the
Given that CVP was a dynamic parameter, we also inves- relative height of the intravenous catheter to that of the
tigated the association between CVP trend and AKI. In barometer, artificial ventilation patterns, and changes
the crude model, both the decreasing trend group and in cardiac performance [17]. Despite the valid criticism,
increasing trend group showed significantly lower AKI CVP is a potentially useful measure of venous congestion
risk than the stable trend group (P < 0.001). These associ- when we recognize its fluctuations due to the above vari-
ations were diminished after further adjustment (P > 0.05) ables [18].
(Table 3). The association between CVP and AKI has been deter-
mined previously [19], and a higher CVP is associated
Discussion with poorer kidney function [9, 11, 20]. However, these
To our knowledge, this study is the first to evaluate the findings were restricted to patients receiving diuretics,
association between elevated CVP and AKI in critically ill undergoing cardiac surgery and experiencing heart fail-
patients with multiple comorbidities from a large-scale, ure. Therefore, the association between elevated CVP
public, deidentified clinical database (MIMIC-III). The and AKI remains unclear in critically ill patients over-
three principal findings are summarized as follows: (1) all after adjustment for demographics, treatments and
 Sun et al. BMC Nephrology (2022) 23:83 Page 7 of 10

Fig. 4  Odds ratios and 95% CI for AKI within 7 days associated with CVP in subgroups. Odds ratios (solid line) and 95% CI (gray area) for AKI
associated with CVP in (a) all subjects, (b) subgroup with age > 65 years, (c) subgroup with SBP < 110 mmHg, (d) subgroup with use of diuretics, (e)
subgroup with sepsis, (f) subgroup with use of ventilation, (g) subgroup with use of vasopressors, (h) subgroup with use of inotropes, (i) subgroup
without use of any vasopressors or inotropes, (j) subgroup with CHF, and (k) subgroup in CSRU. The results were calculated using an adjusted
restricted cubic spline model with a reference CVP of 5 mmHg (dotted line). CVP, central venous pressure; AKI, acute kidney injury; CSRU, cardiac
surgery recovery unit; CHF, congestive heart failure; SBP, systolic blood pressure; CI, confidence interval

comorbidities. Legrand et  al. found a linear relationship which is consistent with the findings of our study. In par-
between CVP and the incidence of AKI [21], and a meta- ticular, in subgroups of patients with older age, low SBP
analysis demonstrated that a 1 mmHg increase in CVP and cardiac surgery, those undergoing treatment with
increases the odds of AKI in critically adult patients [10], vasopressors, diuretics and ventilation and those with
Sun et al. BMC Nephrology (2022) 23:83 Page 8 of 10

Fig. 5  Association between CVP and AKI in subjects using ventilation. For categorical variables, all odds ratios (95% CI) and P values were calculated
compared with the lowest quartile. For continuous variables, odds ratios (95% CI) corresponded to a 1 mmHg increase in CVP. CVP, central venous
pressure; AKI, acute kidney injury; CI, confidence interval

sepsis as a comorbidity, we found that elevated CVP was

still correlated with the odds of AKI. However, in sub-
jects with CHF or with use of inotropes, a trend was not
found possibly due to the limited sample size.
Table 3 Association between CVP trend and AKI at 2 days or
A more thorough understanding enables revaluation
7 days
of the interaction between CVP and AKI. As an indica-
Odds ratio 95% CI P tor of cardiac preload and renal afterload, CVP is deter-
Crude model AKI in 2 days mined by the interaction between cardiac function and
Decreasing trend 0.865 0.752–0.996 0.043 venous return [22, 23]. Decreased renal function would
Stable trend 1 (Reference) lead to more liquid retention and further increase the
Increasing trend 0.933 0.810–1.076 0.342 CVP [17]. On the other hand, based on Guyton’s theory,
AKI in 7 days cardiac output equals venous return, and venous reflux
Decreasing trend 0.808 0.682–0.958 0.014 is dependent on the mean circulatory filling pressure
Stable trend 1 (Reference) (MCFP) and CVP gradient [8]. Specifically, extra fluid
Increasing trend 0.782 0.660–0.927 0.005 only increases CVP and tissue edema but does not sig-
Adjusted model AKI in 2 days nificantly increase end-diastolic volume or stroke vol-
Decreasing trend 0.909 0.780–1.060 0.224 ume. When CVP was increased or MCFP was decreased,
Stable trend 1 (Reference)
venous reflux was decreased; in contrast, venous reflux
Increasing trend 1.083 0.928–1.265 0.312
was increased when CVP was decreased or MCFP was
AKI in 7 days
increased [24, 25]. Therefore, lower CVP is necessary to
Decreasing trend 0.842 0.701–1.012 0.067
ensure venous reflux and cardiac output when MCFP
Stable trend 1 (Reference)
is in the flat part of the Starling curve. In fact, a healthy
Increasing trend 0.887 0.739–1.066 0.202
individual has a relatively low CVP [26]. According to
this theory, it is hypothesized that a high CVP is trans-
Odds ratios (95% CI) were calculated compared with the stable trend group. CVP
central venous pressure; AKI acute kidney injury; CI confidence interval
mitted backward, increasing renal venous pressure,
 Sun et al. BMC Nephrology (2022) 23:83 Page 9 of 10

reducing renal perfusion pressure and increasing renal Acknowledgments

We would like to thank the participants, developers and investigators
venous congestion, further leading to AKI [19, 27]. associated with the Medical Information Mart for Intensive Care (MIMIC)-III
In septic patients, CVP was reported to be associated database.
with AKI risk even after adjustment for positive end-
Authors’ contributions
expiratory pressure [21]. Likewise, our study showed R.L.S. and Q.G. had full access to all the data in the study and take responsi-
that the positive association between CVP and AKI risk bility for the integrity of the data and accuracy of the data analysis. Concept
persisted after adjustment for positive end-expiratory and design: Y.L.Z. and J.F.W. Analysis or interpretation of data: Q.G., J.J.W.,
Y.Y.Z. and Z.T.C. Drafting of the manuscript: R.L.S. and Q.G. Statistical analysis:
pressure in subgroup with use of ventilation. Both CVP All authors. Of note, Y.Y.Z. contributed to the analysis of research data, design
and positive end-expiratory pressure were shown to be and implementation of subgroup analysis, production of Fig. 4, and remark-
independently associated with worsening of renal func- able revision of the manuscript. The author(s) read and approved the final
manuscript.
tion [28]. Meanwhile, several studies demonstrated that
the increase of positive end-expiratory pressure could led Funding
an increase in CVP [29, 30]. Taken together, high positive Runlu Sun received funding from the National Natural Science Founda-
tion of China (Grant number: 81700397). Qi Guo received funding
end-expiratory pressure might involve with AKI, at least from Guangdong Basic and Applied Basic Research Foundation (Grant
partly, by increasing CVP. Nevertheless, the mediating number: 2020A1515110313) and Yat-sen Start-up Foundation (Grant
effect of CVP deserves further investigations. number: YXQH202014). Yaoyao Zou received funding from the National
Natural Science Foundation of China (Grant number: 81801605), Guang-
Our study was based on data extracted from elec- dong Natural Science Foundation (Grant number: 2018A030313690),
tronic medical records in MIMIC-III v1.4 [12], a large and Guangdong Medical Scientific Research Foundation (Grant number:
open clinical database, allowing precise research on A2018062). Yuling Zhang received funding from the National Natu-
ral Science Foundation of China (Grant number: 81970388) and the
the effects of an elevated CVP load. The use of data- Natural Science Foundation of Guangdong Province (Grant number:
base technologies and statistics played a critical role 2019A1515011682). Jingfeng Wang received funding from the National
in achieving the meaningful conclusion of the present Natural Science Foundation of China (Grant numbers: 82070237 and
81870170), Bioland Laboratory (Guangzhou Regenerative Medicine and
study. Additionally, this study has several limitations. Health Guangdong Laboratory) (Grant number: 2019GZR110406004),
First, this study is imperfect due to its retrospective and Guangzhou Science and Technology Plan Projects (Grant number:
nature and the source of the data used. Given the ret- 201803040010).
rospective cohort study design, it is impossible to iden- Availability of data and materials
tify a causal link between AKI and CVP. Hence, no valid The data that support the findings of this study are available from the Institu-
causal relationship can be established. Next, preadmis- tional Review Boards of the Massachusetts Institute of Technology and Beth
Israel Deaconess Medical Center, but restrictions apply to the availability of
sion serum creatinine determinations were unavailable, these data, which were used under license for the current study and are there-
and some patients may have already developed AKI fore not publicly available. Data are however available from the authors (Prof.
on admission. Thus, the odds of AKI may have been Yuling Zhang, E-mail: zhyul@​mail.​sysu.​edu.​cn or Prof. Jingfeng Wang, E-mail:
wjingf@​mail.​sysu.​edu.​cn, Dr. Runlu Sun, E-mail: sunrlu@​mail.​sysu.​edu.​cn or Dr.
underestimated during the ICU stay. Finally, although Qi Guo, E-mail: guoq69@​mail.​sysu.​edu.​cn) upon reasonable request and with
some predictors of disease severity were included in permission of the Institutional Review Boards of the Massachusetts Institute of
our study and adjusted analysis confirmed the associa- Technology and Beth Israel Deaconess Medical Center.
tion between elevated CVP and the incidence of AKI,
the results may be affected by other confounding fac- Declarations
tors associated with AKI. Additional prospective studies Ethics approval and consent to participate
should be conducted to evaluate these parameters and The database was approved for research use by the Institutional Review
the potential effect of elevated CVP load. Boards of the Massachusetts Institute of Technology and Beth Israel Deacon-
ess Medical Center, and studies using the database were granted a waiver
of informed consent. All methods were performed in accordance with the
Conclusions relevant guidelines and regulations.
In conclusion, this study found that elevated mean CVP
Consent for publication
is associated with an increased risk of AKI in critically Not applicable.
ill patients with multiple comorbidities. Individualizing
CVP measurements and maintaining a low CVP should Competing interests
The authors declare that they have no competing interests.
be encouraged to avoid unnecessary renal damage.
Author details
1
 Department of Cardiology, Sun Yat‑sen Memorial Hospital, Sun Yat-sen Uni-
Abbreviations versity, No. 107, the West Yanjiang Road, Yuexiu District, Guangzhou 510120,
AKI: Acute kidney injury; CHF: Congestive heart failure; CSRU: Cardiac surgery China. 2 Guangdong Province Key Laboratory of Arrhythmia and Electrophysi-
recovery unit; CVP: Central venous pressure; ICU: Intensive care unit; MIMIC: ology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou,
Medical Information Mart for Intensive Care; OR: Odds ratio; SAPS: Simplified China. 3 Department of Rheumatology, Sun Yat-Sen Memorial Hospital, Sun
Acute Physiology Score; SBP: Systolic blood pressure; SOFA: Sequential Organ Yat-Sen University, Guangzhou, China.
Failure Assessment.
Sun et al. BMC Nephrology (2022) 23:83 Page 10 of 10

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