Professional Documents
Culture Documents
Clinical Nutrition
journal homepage: http://www.elsevier.com/locate/clnu
Original article
a r t i c l e i n f o s u m m a r y
Article history: Background & aims: The Controlling Nutritional Status (CONUT) score was designed to assess the
Received 16 June 2019 immune-nutritional status in patients. The aim of this study was to investigate the prognostic value of
Accepted 7 November 2019 the CONUT score at the commencement of peritoneal dialysis (PD) for all-cause mortality, cardiovascular
disease (CVD), and technique failure.
Keywords: Methods: This is a STROBE-compliant, retrospective, observational, single center study. A total of 252
Cardiovascular disease
patients with end stage renal disease initially undergoing PD were enrolled in the study. Baseline data
Immunity
were collected from The Third Affiliated Hospital of Soochow University Peritoneal Dialysis database. The
Malnutrition
Mortality
primary outcome during follow-up was all-cause mortality. The secondary outcomes were CVD and
Peritoneal dialysis technique failure. Univariate and multivariate Cox regression analyses were performed to estimate the
association between confounding factors and outcomes. The area under the curve represented the test
discriminative power of CONUT score and relevant clinical parameters. The KaplaneMeier curve was
used to compare the outcomes of the patients according to the cut-off CONUT score.
Results: During a median follow-up period of 1.9 years, 35 patients (13.9%) died, 38 (15.1%) experienced
CVD events, 58 (23.0%) experienced technique failure. The high CONUT group (CONUT score > 3) had
significantly higher all-cause mortality (p ¼ 0.02), CVD prevalence (p < 0.01), and technique failure rates
(p < 0.01) than the low CONUT group (CONUT score 3). The CONUT score was an independent predictor
of all-cause mortality (hazard ratio [HR]: 1.565; 95% CI: 1.305e1.876; p < 0.001), CVD (HR: 1.346; 95% CI:
1.136e1.594; p ¼ 0.001), and technique failure (HR: 1.144; 95% CI: 1.006e1.302; p ¼ 0.041).
Conclusion: The CONUT score is a straightforward and inexpensive indicator to evaluate the immune-
nutritional status; it could be a reliable prognostic marker of all-cause mortality, CVD, and technique
failure risk in patients undergoing PD.
© 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
https://doi.org/10.1016/j.clnu.2019.11.018
0261-5614/© 2019 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Please cite this article as: Zhou H et al., Controlling Nutritional Status (CONUT) score as immune-nutritional predictor of outcomes in patients
undergoing peritoneal dialysis, Clinical Nutrition, https://doi.org/10.1016/j.clnu.2019.11.018
2 H. Zhou et al. / Clinical Nutrition xxx (xxxx) xxx
and immunological risk in patients undergoing gastrointestinal cause, including inadequate dialysis, ultrafiltration failure, re-
surgery [13]. Recently, the prognostic value of the CONUT score has fractory peritonitis, fungal peritonitis, exit-site and/or tunnel
been validated in a variety of malignant tumors [14,15]. Serum al- infection, catheter malfunction, mechanical problems, and other
bumin concentration is a major indicator of nutritional status. reasons, such as patient preference. The end of PD was defined as
Hypoalbuminemia has been reported to be associated with poor death, a switch to HD, kidney transplantation, and recovered renal
outcome in patients undergoing PD [16]. The total cholesterol level function. Patient status was recorded at the end of the study
has also been revealed to correlate with mortality in patients un- (December 31, 2018).
dergoing PD [17]. In addition, lymphocytes play a key role in cell-
mediated immunity and are associated with prevalent atheroscle- 2.5. Statistical analysis
rotic cardiovascular disease in end-stage renal disease (ESRD) [18].
The combination of these three components in the CONUT score Analyses were conducted using SPSS (version 19.0). All data
may better reflect the balance of immune-nutritional status and were first checked for normality of distribution using the
enhance the ability to accurately predict outcomes than single- KolmogoroveSmirnov test. Normally distributed data are pre-
factor markers. However, the prognostic role of the CONUT score sented as the mean ± standard deviation. Non-normally distributed
has not been investigated in patients undergoing PD. data are represented as the median (inter-quartile range).
We hypothesized that the CONUT score is associated with Spearman rank correlation analysis was performed to analyze the
prognosis in patients undergoing PD. Therefore, we assessed the correlation between CONUT score and selected characteristics or
prognostic value of the CONUT score at the commencement of PD parameters. The independent relationships between CONUT score
for all-cause mortality, CVD, and technique failure. and all-cause mortality, CVD, and technique failure in the study
were investigated by univariate and multivariate Cox regression
2. Materials and methods analyses (confounding factors included all selected characteristics
and parameters). The KaplaneMeier method and the log-rank test
2.1. Study design were used to estimate the survival rate of patients. The optimal cut-
off value, based on receiver operating characteristic (ROC) analysis
The present investigation was a STROBE-compliant, retrospec- results, was 3. The area under the curve (AUC) analysis was calcu-
tive, observational, single center study. All adult (18 years) pa- lated and compared for models containing only CONUT score and
tients with ESRD initially undergoing PD at the Department of joint models containing most relevant clinical parameters in pre-
Nephrology of the Third Affiliated Hospital of Soochow University dicting outcomes. A two-sided p value of <0.05 was considered to
(Changzhou, China) from August 2010 to August 2018 were eligible indicate statistical significance.
for inclusion in the study. Patients with malignancies (e.g. breast,
lung, gastrointestinal, hematologic cancers) or missing data were 3. Results
excluded. Finally, we included a total of 252 PD patients in the
study. The mean age of 252 enrolled PD patients was 48.3 ± 14.9 years,
and 33 (13.1%) were diabetic. Most patients were men (147 cases,
2.2. Human subject protection 58.3%), 42 (16.7%) were smokers, and 34 (13.5%) had a history of
CVD. The median CONUT score was 5 (3, 6). The baseline de-
The study was approved by the Ethics Committee of the Third mographic and clinical characteristics of the study population are
Affiliated Hospital of Soochow University, China (registration listed in Table 1. During the median follow-up period of 1.9 years, 35
number: #27/2013), and written informed consent was obtained patients (13.9%) died, 38 (15.1%) experienced CVD events, 58
from all participants. (23.0%) experienced technique failure, 26 (10.3%) underwent kid-
ney transplantation, 1 (0.4%) had kidney function recovery, and 3
2.3. Data collection (1.2%) were lost to follow-up.
According to the cut-off value of 3, the enrolled patients were
The initiation of PD therapy was defined as the date of first PD divided into two groups: low CONUT group (CONUT score 3; 66
treatment. Data on baseline characteristics, comorbidities, and patients, 26.2%) and high CONUT group (CONUT score > 3; 186
laboratory test results were collected from The Third Affiliated patients, 73.8%). Among 35 all-cause deaths, 2 (5.7%) were occurred
Hospital of Soochow University Peritoneal Dialysis database. Lab- in the low CONUT group, and 33 (94.3%) were occurred in the high
oratory variables were obtained from clinic records a week before CONUT group; among 38 CVD events, 2 (5.3%) were occurred in the
the first PD treatment, included lymphocyte count, hemoglobin, low CONUT group, and 36 (94.7%) were occurred in the high CONUT
serum creatinine, blood urea nitrogen (BUN), uric acid, intact group; among 58 technique failure, 5 (8.6%) were occurred in the
parathyroid hormone (iPTH), calcium, phosphate, albumin, total low CONUT group, and 53 (91.4%) were occurred in the high CONUT
cholesterol, low-density lipoprotein (LDL) cholesterol, high-density group. The KaplaneMeier curve comparing the outcomes of the
lipoprotein (HDL) cholesterol, triglycerides, C-reactive protein patients according to the cut-off CONUT score is shown in Fig. 1aec.
(CRP), albumin, and prealbumin levels. The CONUT score was The high CONUT group had significantly higher all-cause mortality
calculated based on 3 laboratory variables: serum albumin con- (p ¼ 0.02), CVD prevalence (p < 0.01), and technique failure rates
centration, total cholesterol concentration, and total peripheral (p < 0.01) than the low CONUT group.
lymphocyte count [19] (Table S1). The correlations between CONUT score and selected character-
istics or laboratory variables are shown in Table 2. CONUT scores
2.4. Clinical outcomes were significantly associated with gender, systolic blood pressure
(BP), hemoglobin, BUN, total cholesterol, LDL cholesterol, triglyc-
The primary outcome was all-cause mortality after PD eride, albumin, lymphocyte count, ejection fraction (EF), and left
commencement. The secondary outcomes were CVD and technique ventricular mass index (LVMI) (p < 0.05).
failure during follow-up. CVD was defined as the incidence of cor- The results of our multivariate Cox analysis showed that the
onary heart disease, heart failure, stroke, or peripheral arterial CONUT score was an independent predictor of all-cause mortality
disease. PD technique failure was defined as a switch to HD for any (hazard ratio [HR]: 1.565; 95% CI: 1.305e1.876; p < 0.001), along
Please cite this article as: Zhou H et al., Controlling Nutritional Status (CONUT) score as immune-nutritional predictor of outcomes in patients
undergoing peritoneal dialysis, Clinical Nutrition, https://doi.org/10.1016/j.clnu.2019.11.018
H. Zhou et al. / Clinical Nutrition xxx (xxxx) xxx 3
Table 1 Table 2
Demographic and baseline characteristics of peritoneal dialysis patients Spearman correlation between CONUT score and variables.
(n ¼ 252).
Variables Correlation p value
Characteristics Values
coefficient
Age (years) 48.3 ± 14.9
Age 0.118 0.061
Male gender (%) 147 (58.3%)
Gender 0.147 0.019*
BMI (kg/m2) 22.5 ± 3.0
BMI 0.053 0.400
Diabetes (%) 33 (13.1%)
Diabetes 0.113 0.073
Current smoking (%) 42 (16.7%)
Systolic BP 0.198 0.002**
ESRD cause
Diastolic BP 0.015 0.818
Glomerulonephritis (%) 135 (53.6%)
Hemoglobin 0.217 0.001**
Hypertension (%) 28 (11.1%)
RRF 0.122 0.053
Diabetes mellitus (%) 24 (9.5%)
Creatinine 0.120 0.057
Other/unknown (%) 65 (25.8%)
BUN 0.137 0.030*
CVD history (%) 34 (13.5%)
Uric acid 0.044 0.487
Systolic BP (mmHg) 155.5 ± 21.5
Corrected calcium 0.067 0.289
Diastolic BP (mmHg)a 90.0 (80.0, 99.8)
Phosphorus 0.028 0.663
Hemoglobin (g/dL) 8.3 ± 1.8
iPTH 0.016 0.795
RRF (ml/min/1.73 m2)a 5.2 (4.1, 6.6)
Total cholesterol 0.276 <0.001***
Creatinine (mg/dL)a 9.6 (7.7, 12.3)
LDL cholesterol 0.252 <0.001***
BUN (mg/dL) 89.3 ± 28.3
HDL cholesterol 0.082 0.196
Uric acid (mg/dL) 8.7 ± 2.2
Triglycerides 0.146 0.020*
Corrected calcium (mg/dL)a 9.3 (8.7, 9.7)
CRP 0.081 0.201
Phosphate (mg/dL)a 6.2 (5.1, 7.7)
Albumin 0.715 <0.001***
iPTH (pg/mL)a 237.4 (100.4, 399.3)
Prealbumin 0.110 0.080
Total cholesterol (mg/dL)a 160.1 (133.2, 184.8)
Lymphocyte count 0.455 <0.001***
LDL cholesterol (mg/dL)a 78.5 (62.3, 92.2)
EF 0.202 0.001**
HDL cholesterol (mg/dL)a 36.0 (29.5, 44.5)
LVMI 0.262 <0.001***
Triglycerides (mg/dL)a 146.6 (99.2, 204.2)
CRP (mg/dL)a 5.4 (4.0, 9.9) * ¼ p < 0.05; ** ¼ p < 0.01; *** ¼ p < 0.001.
Albumin (g/dL) 3.3 ± 0.5
Prealbumin (mg/dL) 25.9 ± 6.2
CONUTa 5 (3, 6)
with age (p < 0.001), body mass index (BMI) (p ¼ 0.005), diabetes
EF (%)a 61.0 (58.0, 63.8)
LVMI (g/m2.7)a 55.4 (46.1, 68.7)
(p < 0.001), and systolic BP (p ¼ 0.022) (Table 3). Furthermore, after
adjustment for confounding factors, age (p < 0.001), diabetes
Characteristics are independent of each other.
a (p ¼ 0.019), LVMI (p ¼ 0.004), and CONUT score (HR: 1.346; 95% CI:
Median with inter-quartile range.
1.136e1.594; p ¼ 0.001) were significantly and independently
associated with new-onset CVD (Table 4).
Fig. 1. KaplaneMeier curves for outcomes in patients undergoing PD. a. all-cause mortality; b. cardiovascular disease; c. technique failure.
Please cite this article as: Zhou H et al., Controlling Nutritional Status (CONUT) score as immune-nutritional predictor of outcomes in patients
undergoing peritoneal dialysis, Clinical Nutrition, https://doi.org/10.1016/j.clnu.2019.11.018
4 H. Zhou et al. / Clinical Nutrition xxx (xxxx) xxx
Table 3
Univariate and multivariate Cox analysis of patient survival in peritoneal dialysis patients (n ¼ 252).
Table 4
Univariate and multivariate Cox analysis of patient with cardiovascular disease undergoing peritoneal dialysis (n ¼ 252).
Please cite this article as: Zhou H et al., Controlling Nutritional Status (CONUT) score as immune-nutritional predictor of outcomes in patients
undergoing peritoneal dialysis, Clinical Nutrition, https://doi.org/10.1016/j.clnu.2019.11.018
H. Zhou et al. / Clinical Nutrition xxx (xxxx) xxx 5
Table 5
Univariate and multivariate Cox analysis of technique failure in peritoneal dialysis patients (n ¼ 252).
Fig. 2. ROC curves of the joint probability of CONUT, age and diabetes in predicting Fig. 3. ROC curves of the joint probability of CONUT, age and diabetes in predicting
mortality. cardiovascular disease.
high CONUT score and low CONUT score, respectively. Although our cause of deaths in dialysis patients [24,25], and malnutrition is an
patients had higher prevalence of malnutrition based on the established non-traditional cardiovascular risk factor in HD patients
CONUT score, the mean age and the prevalence of co-morbid dis- [26]. Precise evaluation of a patient's nutrition status may provide a
ease such as diabetes or CVD history were lower than Chung et al.‘s valid assessment of the risk for CVD [27]. The mechanism regarding
study [21]. Serum prealbumin is a more sensitive marker of nutri- the association between the CONUT score and CVD has not been fully
tional status than albumin, and it is a predictor of mortality for HD investigated. However, each component of the CONUT score has been
and PD patients [22,23]. Although serum prealbumin was a sig- reported to be related to CVD in dialysis patients. First, dyslipidemia
nificant mortality predictor in patients undergoing PD as a is a well-established traditional risk factor for CVD in the general
continuous variable in the univariate Cox model in our study, the population, but this relationship is much more complex and even
addition of other confounding factors in the multivariate analysis paradoxical in patients undergoing PD [28]. In our study, a lower total
adjusted the mortality risk of prealbumin. Thus, the CONUT score, cholesterol level means a higher CONUT score, and a higher CONUT
an immune-nutritional index, may be a better predictor of mor- score is related to a higher prevalence in CVD. This result supports
tality than prealbumin in patients undergoing PD. Routine pre- the concept of “reverse epidemiology” of dyslipidemia in dialysis
dialysis assessment of CONUT may help to improve survival patients [29,30]. Secondly, a lower count of lymphocyte indicates a
outcome in patients undergoing PD. However, a further compara- higher CONUT score. Lymphocyte count is a novel inflammatory
tive study is needed to make this conclusion. marker in renal and cardiac disorders. Chronic inflammation is found
Our observation that a high CONUT score was related to high to be correlated with coronary and thoracic periaortic calcification in
prevalence of CVD during the course of PD. CVD is the most common ESRD patients [31]. The neutrophil-to-lymphocyte ratio (NLR) can
Please cite this article as: Zhou H et al., Controlling Nutritional Status (CONUT) score as immune-nutritional predictor of outcomes in patients
undergoing peritoneal dialysis, Clinical Nutrition, https://doi.org/10.1016/j.clnu.2019.11.018
6 H. Zhou et al. / Clinical Nutrition xxx (xxxx) xxx
6. Conclusion
Funding
The datasets used and analyzed during the current study are
Fig. 4. ROC curves of the joint probability of CONUT and BMI in predicting technique available from the corresponding author on reasonable request.
failure.
Ethics approval and consent to participate
predict CVD and cardiovascular mortality in ESRD patients [32,33]. In
one study, high NLR is independently associated with arterial stiff- The study was approved by the Ethics Committee of the Third
ness and predicted cardiovascular mortality in patients undergoing Affiliated Hospital of Soochow University, China (registration
PD [34], suggesting that a low lymphocyte count may contribute to number: #27/2013), and written informed consent was obtained
CVD. Finally, serum albumin levels, which are twice the weight of from all participants.
other indicators in CONUT score, can predict CVD mortality in pa-
tients at the initiation of HD therapy [35]. Thus, the CONUT score, an Consent for publication
efficient tool to evaluate protein metabolism, lipid metabolism,
inflammation and immune status, is a reliable biomarker for iden- Not required.
tifying patients with high risk of CVD, which may help clinicians to
improve the clinical management. Moreover, our data suggest that Authors' contributions
the combination of CONUT score, diabetes, and age may provide a
novel tool to facilitate the prediction of mortality and CVD in the MY contributed to the conception and design of the study. WYC
future. and HZ recruited the subjects. LC and HZ analyzed the data and
In our study, the CONUT score was also significantly associated wrote the initial draft of the paper. ML participated in its design and
with technique failure, and CONUT score combined with BMI was a supervised the study. YZ as a professional statistician checked the
better predictor of technique failure according to the AUC analysis. statistical methods and results. All authors contributed to the
One of the major reasons for the low prevalence of PD is the high writing, reviewing, and revising of the manuscript.
withdrawal rate from PD programs because of technique failure
[36]. Inadequate dialysis, ultrafiltration failure and peritonitis were Conflict of interest
the three leading causes of technique failure in our center. Tech-
nique failure shortens the time patients undergo PD and leads to The authors declare that they have no competing interests.
transfer to HD unplanned. In previous studies, the risk of peritonitis
is found to increase with poor nutrition [37,38]. It has been reported Abbreviations
that the initial serum albumin level is a significant predictor of
peritonitis [39], and a higher BMI is associated with a higher risk of AUC area under the curve
technique failure [40]. CONUT score or combined with BMI may BMI body mass index
help to stratify the risk for PD technique failure, and make it BP blood pressure
imperative to implement interventions and strategies that safely BUN blood urea nitrogen
prolong the duration of PD therapy among high CONUT score and CONUT controlling nutritional status
high BMI patients. CRP C-reactive protein
CVD cardiovascular disease
5. Limitations EF ejection fraction
ESRD end stage renal disease
There are several limitations to this study. First, our study did HD hemodialysis
not include information on socioeconomic status and educational HDL high-density lipoprotein
background. Second, it was an observational, retrospective, single- HR hazard ratio
center study with a relatively small sample size. The data were iPTH intact parathyroid hormone
obtained from a single center in China, with a possible selection IQR inter-quartile range
bias and a center-specific effect. The follow-up time was long. LDL low-density lipoprotein
Please cite this article as: Zhou H et al., Controlling Nutritional Status (CONUT) score as immune-nutritional predictor of outcomes in patients
undergoing peritoneal dialysis, Clinical Nutrition, https://doi.org/10.1016/j.clnu.2019.11.018
H. Zhou et al. / Clinical Nutrition xxx (xxxx) xxx 7
Please cite this article as: Zhou H et al., Controlling Nutritional Status (CONUT) score as immune-nutritional predictor of outcomes in patients
undergoing peritoneal dialysis, Clinical Nutrition, https://doi.org/10.1016/j.clnu.2019.11.018