==== Front PLoS One PLoS One plos PLOS ONE 1932-6203 Public Library of Science San Francisco, CA USA 10.1371/journal.pone.0287696 PONE-D-23-04816 Research Article Medicine and Health Sciences Geriatrics Medicine and Health Sciences Nephrology Medical Dialysis Biology and Life Sciences Population Biology Population Metrics Death Rates Medicine and Health Sciences Diagnostic Medicine Prognosis Medicine and Health Sciences Epidemiology Medical Risk Factors Cancer Risk Factors Medicine and Health Sciences Oncology Cancer Risk Factors Medicine and Health Sciences Nephrology Renal Diseases Chronic Kidney Disease Medicine and Health Sciences Medical Conditions Cardiovascular Diseases Cardiovascular Disease Risk Medicine and Health Sciences Cardiology Cardiovascular Medicine Cardiovascular Diseases Cardiovascular Disease Risk Biology and Life Sciences Anatomy Body Fluids Blood Medicine and Health Sciences Anatomy Body Fluids Blood Biology and Life Sciences Physiology Body Fluids Blood Combined evaluation of Geriatric nutritional risk index and Neutrophil to lymphocyte ratio for predicting all-cause and cardiovascular mortality in hemodialysis patients Geriatric nutritional risk index and Neutrophil to lymphocyte ratio for predicting death https://orcid.org/0000-0002-4047-7941 Wang Jun Formal analysis Writing – review & editing 1 Huang Li-juan Methodology Validation 1 Li Bei Data curation Formal analysis 2 Xu Mei-chang Validation 1 Yang Lei Validation 1 Deng Xu Data curation 1 https://orcid.org/0009-0009-3035-2940 Li Xin Data curation Writing – original draft 3 * 1 Department of Nephrology, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing, 210014, Jiangsu Province, China 2 Department of Nephrology, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, 210012, Jiangsu Province, China 3 Department of Science & Education Division, Nanjing Integrated Traditional Chinese and Western Medicine Hospital, Nanjing, 210014, Jiangsu Province, China Aktas Gulali Editor Bolu Abant İzzet Baysal University: Bolu Abant Izzet Baysal Universitesi, TURKEY Competing Interests: The authors have declared that no competing interests exist. * E-mail: fsyy00058@njucm.edu.cn 29 6 2023 2023 18 6 e028769621 2 2023 10 6 2023 © 2023 Wang et al 2023 Wang et al https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Objective Malnutrition, accompanied by an inflammatory profile, is a risk factor for poor prognosis in hemodialysis patients. The purpose of this study was to investigate the predictive value of NLR combined with GNRI for all-cause and cardiovascular mortality in hemodialysis patients. Methods A total of 240 maintenance hemodialysis (MHD) patients in hemodialysis centers were enrolled in this retrospective study. The influencing factors of all-cause death in hemodialysis patients were analyzed by COX regression. The cut-off values of GNRI and NLR for predicting mortality in enrolled MHD patients were 89.01 and 4, respectively. Based on these cut-off values, the patients were divided into four groups: G1: high GNRI (≥ 89.01) + high NLR (≥ 4) group; G2: high GNRI (≥ 89.01) + low NLR (<4) group, G3: low GNRI (< 89.01) + high NLR (≥4) group; G4: low GNRI (< 89.01) + low NLR (<4). Results During the follow-up period (average: 58 months), the all-cause mortality was 20.83%(50/240) and the cardiovascular mortality was 12.08%(29/240). Both NLR and GNRI were independent risk factors for the prognosis of MHD patients (P<0.05). Survival analysis showed that patients with low GNRI had a lower survival rate than those with high GNRI, whereas patients with high NLR had a lower survival rate than those with low NLR. Kaplan-Meier curve for all-cause mortality revealed that compared to G1, G2, and G4, G3 had the lowest survival rate, while G2 had the highest survival rate among all groups (P < 0.05). Kaplan-Meier curve for cardiovascular mortality showed that G3 had lower survival than G1, G2, and G4 (P < 0.001). Conclusions Our study demonstrates that bothGNRI and NLR are associated with all-cause mortality and cardiovascular mortality in MHD patients. Combining these two factorsmay contribute to a prognostic evaluation for MHD patients. Nanjing Administration of Traditional Chinese Medicine ZYQ20053 https://orcid.org/0000-0002-4047-7941 Wang Jun This research was funded by the Nanjing Administration of Traditional Chinese Medicine, Project name: Nanjing Traditional Chinese Medicine Youth Talent Training Program,(NO.ZYQ20053). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data AvailabilityAll relevant data are within the paper and its Supporting Information files. Data Availability All relevant data are within the paper and its Supporting Information files. ==== Body pmc1. Introduction With the improvement of medical and living standards, the problem of aging population is getting worse, while the incidence of chronic kidney disease (CKD) is increasing significantly [1]. End-stage kidney disease (ESRD) is the ultimate outcome for patients with CKD. Maintenance hemodialysis (MHD) is currently an essential treatment for ESRD patients [2]. ESRD patients with underlying conditions are at a high risk of death following hemodialysis [3]. Exploring the risk factors related to the mortality of MHD patients is a long-term task. Due to the specificity of the disease itself, and the treatment for MHD patients, the incidence of protein-energy malnutrition is significantly increased, which is closely related to the poor prognosis [4]. The Geriatric Nutritional Risk Index (GNRI), a simple and effective tool for assessing nutritional status, has been validated as a simplified nutritional screening tool for hemodialysis patients, which is more easily prepared than other nutrition assessment tools [5]. It has been reported to be useful for MHD death prediction [6]. Besides, it is an excellent prognostic indicator [7]. Previous studies have shown an increase in all-cause, cardiovascular, and infectious mortality in MHD patients with malnutrition [8,9]. Early identification and intervention of malnutrition positively impact the prognosis of MHD patients. It is recommended that patients’ nutritional status should be evaluated every 1–3 months to allow timely nutritional interventions [10]. Subjective global assessment and malnutrition inflammation score are prevalent in nutrition assessment [11,12]. However, the outcomes are prone to being affected by subjective factors in both methods. The GNRI, used to assess nutrition objectively based on height, weight and albumin levels, is easier to apply clinically [5]. In patients with multiple sclerosis, malnutrition is closely associated with the immune inflammatory response [13]. Neutrophils/lymphocytes ratio (NLR) is a novel marker of inflammation derived from routine blood count test. Studies have shown that the blood NLR in ulcerative colitis (UC) patients is associated with active diseases. The NLR can be used as the activity parameter of UC [14]. Another study showed that NLR could be used as a marker of diabetes control [15]. Studies have shown that NLR can also predict the prognosis of cancer patients [16]. Our previous studies have revealed that NLR and serum albumin indices are risk factors of mortality in MHD patients. NLR has been reported as an independent risk factor of mortality in MHD patients [17]. NLR levels in CKD3-5 patients gradually increase as kidney function declines, serving as an independent predictor of cardiovascular events [18]. The first prospective study in China that included CKD1-4 showed an association between NLR and ESRD progression risk in CKD4 patients; while no association was found between NLR and all-cause mortality in CKD1-3 patients [19].A prospective cohort study in Japan showed a significant increase in NLR in patients with end-stage renal disease receiving renal replacement therapy [20]. Previous studies have demonstrated that elevated NLR can increase the risk of cardiovascular disease in hemodialysis patients [21], NLR is an effective predictor of CVD death and all-cause death in hemodialysis patients [22], Previous studies have indicated that an NLR of 5.0 may be the threshold for the risk of patients with acute coronary syndrome [23]. Results of a meta-analysis suggest that NLR is a predictor of hospitalization and long-term outcome in patients with acute ST segment elevation myocardial infarction after percutaneous coronary intervention [24]. At present, the association between all-cause mortality in NLR and MHD patients is still being explored and requires further investigation. GNRI and NLR are clinically relevant indicators of mortality in MHD patients and contribute to early diagnosis and intervention. No studies have used GNRI and NLR combinations to predict prognosis in MHD patients. The study was based on data from two hemodialysis centers, focusing on the impact of GNRI and NLR on all-cause mortality in MHD patients.This study observed the prognostic value of combined application of GNRI and NLR in MHD patients, providing clinical basis for early clinical identification of MHD patients with poor prognosis. 2. Materials and methods The study was based on data from two hemodialysis centers.From January 2014 to December 2017, 240 patients with initial hemodialysis were registered in the Chinese National Renal Data System (CNRDS) by Nanjing Integrated Traditional Chinese and Western Medicine Hospital and Nanjing Hospital of Chinese Medicine. The relevant Information and living status of patients were collected, and the relevant clinical indicators folloeing initial hemodialysis were queried in HIS (Hospital Information System). The patients were aged 26–96 years old with an average age of 63.4 ± 13.7 years old. The study was approved by the Ethics Committee of Nanjing Integrated Traditional Chinese and Western Medicine Hospital and Nanjing Hospital of Chinese Medicine (Ethics Approval Number 2022043). 2.1 Eligibility criteria Inclusion criteria: (1) Meeting the criteria for ESRD [2]; (2) More than six months on dialysis; (3) Age 26–96 years old (4) Regular hemodialysis treatment; (5) Included in traditional Chinese medicine physical assessment. Exclusion criteria: (1) Incomplete clinical data; (2)I Intermittent hemodialysis; (4) Treated with hemodialysis for acute renal injury.(5) Hemodialysis (HD) treatment for acute renal failure; (6) Irregular MHD treatment due to economic or family reasons; 2.2 Methods Clinical Data and survival status of 240 patients with initial hemodialysis were found in the Chinese National Renal Data System (CNRDS) for retrospective study. Data were collected including sex, age, dialysis duration, education years,dialysis adequacy,vascular access types, primary disease,serum albumin,hemoglobin,pre-dialysis blood urea nitrogen,pre-dialysis serum creatinine,uric acid,triglyceride,total cholesterol,high-density lipoprotein, low-density lipoprotein, blood potassium,blood calcium,blood phosphorus,NLR,PLR,GNRI,body mass index.GNRI = 1.489 × rho (albumin) + 41.7 × (actual body mass / ideal body mass). The actual body mass is based on the dialysis dry weight. If the actual body mass / ideal body mass > 1, it was regarded as 1 [5]. NLR and PLR were calculated based on the blood routine indexes of the included patients. NLR represents the platelet/lymphocyte ratio, andPLR represents the neutrophil/lymphocyte ratio [17]. 2.3 Study endpoint and follow-up All-cause of death referred to death from any cause indicated study endpoint [25]. Cardiocerebrovascular death covered heart failure, myocardial infarction, cerebral hemorrhage, cerebral infarction, and peripheral vascular disease [25]. Follow-ups were conducted by outpatient, telephone, and home visits. The follow-up would be available before patients met the end point or until December 31, 2021. 2.4 Grouping Based on these cut-off values, the patients were divided into four groups: G1: high GNRI (≥ 89.01) + high NLR (≥ 4) group; G2: high GNRI (≥ 89.01) + low NLR (<4) group, G3: low GNRI (< 89.01) + high NLR (≥4) group; G4: low GNRI (< 89.01) + low NLR (<4). 2.5 Outcome measures To compare the clinical data of death and survival MHD patients, COX regression was used to analyze the risk factors for mortality in different groups. Predictive value of GNRI combined with NLR in MHD patients was assessed. The correlation between GNRI and NLR was analyzed. The effects of different levels of GNRI and NLR on MHD survival time were observed in groups according to the GNRI and NLR cut-off values of the included patients. Patients were grouped according to GNRI and NLR cutoff values to compare all-cause mortality and cardiovascular event mortality among different groups. 2.6 Statistical processing Statistical processing was performed using IBM SPSS 24.0 and GraphPad Prism 7.0 software. Continuous variables were analyzed by independent samples t-test and expressed as mean ± standard deviation. Count data was processed with Pearson’s chi square test. Classified variables were analyzed in two groups using the Kruskal-Wallis test or one-way variance analysis. Cox regression analysis was conducted for the risk factors of death in MHD patients. Factors included in this study were dialysis duration, years of education, the spKt/V, hemoglobin, blood phosphorus, platelet-lymphocyte ratio(PLR), GNRI, and NLR. Serum albumin and body mass index were excluded because they were used to establish GNRI indicators. The cut-off values of GNRI and NLR for death prediction in MHD patients were obtained according to ROC diagnostic curve. Based on GNRI and NLR cutoffs, survival analysis was performed using the Kaplan-Meier method, and inter-group differences were compared using the log-rank test. Person test was used to analyze the correlation between two variables;P < 0.05 was considered statistically significant. 3 Results 3.1 Comparison of general data The study involved 161 male participants, with a mean age of 63.4 ± 13.7 years and an average dialysis duration of 64.8 ± 26.6 months. Vascular access types comprised arteriovenous fistula (183;76.25%), central venous catheters (21;8.75%), and artificial arteriovenous grafts (36;15.00%), Comorbid conditions included hypertension (225, 93.75%), diabetes (45; 18.75%), and heart disease (30; 12.50%). See Table 1. 10.1371/journal.pone.0287696.t001 Table 1 Comparison of related influencing factors of death in patients with MHD. Categories Death group(n = 50) Survival group (n = 190) χ2/t/Z value P Male [n (%)] 37(74.00) 125(65.79) 1.216 0.270 Age (years) 63.3±13.6 64.1±14.1 0.405 0.686 Dialysis duration (months) 69.5±24.3 46.9±27.5 5.303 <0.001 Education years 6.90±2.22 9.22±2.52 4.573 <0.001 Dialysis adequacy 1.62±0.25 1.56±0.29 1.427 0.155 Primary diseases - - - - Chronic glomerulonephritis 22(44.00) 88(46.32) 0.438 0.932 Diabetic nephropathy 10(20.00) 40(21.05) Hypertensive nephropathy 7(14.00) 28(14.74) Other 11(22.00) 34(17.89) Vascular access types - - - - Arteriovenous fistula [n (%)] 33(66.00) 150(78.95) 3.912 0.141 Central venous catheters [n (%)] 7(14.00) 14(7.37) Arteriovenous grafts [n (%)] 10(20.00) 26(13.68) SA(g/L) 37.28±4.86 39.79±3.40 3.430 0.001 Hemoglobin (g/L) 98.20±21.54 113.34±14.78 4.689 <0.001 Pre-dialysis blood urea nitrogen (mmol/L) 26.85±6.51 26.06±7.69 0.733 0.465 Pre-dialysis serum creatinine (umol/L) 627.44±242.90 613.78±262.05 0.338 0.735 Uric acid (umol/L) 457.28±65.75 448.69±76.09 0.794 0.429 Triglyceride (mmol/L) 1.96±0.46 1.91±0.55 0.552 0.582 Total cholesterol (mmol/L) 3.94±0.66 3.85±0.79 0.777 0.439 High-density lipoprotein (mmol/L) 1.08±0.31 1.04±0.37 0.623 0.534 Low-density lipoprotein (mmol/L) 3.46±0.64 3.36±0.75 0.762 0.448 Blood potassium (mmol/L) 4.65±0.69 4.55±0.79 0.809 0.421 Blood calcium (mmol/L) 2.07±0.20 2.05±0.23 0.696 0.488 Blood phosphorus (mmol/L) 1.55±0.58 1.97±0.43 4.743 <0.001 NLR 3.69±1.58 2.94±1.09 3.154 0.003 PLR 125.97±17.18 117.19±13.94 3.336 0.001 GNRI 85.82±10.75 93.53±6.67 4.837 <0.001 Body mass index (kg/m2) 18.89±3.34 21.15±2.38 4.497 <0.001 Note: SA, serum albumin; NLR, neutrophil/lymphocyte ratio; PLR, platelet/lymphocyte ratio; GNRI: Geriatric nutritional risk index; MHD, maintenance hemodialysis. 3.2 COX regression analysis for all-cause death in MHD patients During follow-up, 50 patients experienced all-cause death, including death from cardiovascular events (29/50), infections (13/50), malignancies (5/50), and other causes (3/50). Univariate COX regression analysis was used to identify GNRI and NLR levels as risk factors for all-cause mortality. COX Multifactor Regression Analysis incorporating dialysis duration, years of education, hemoglobin, blood phosphorus, PLR, indicated that GNRI and NLR were all risk factors for MHD-related death. Serum albumin and body mass index were excluded because they were used to establish GNRI indicators (Table 2). 10.1371/journal.pone.0287696.t002 Table 2 COX Multifactor analysis of prognosis in MHD patients. Variables β SE Wald value OR value (95%CI) P NLR 0.563 0.139 16.532 1.757(1.339–2.305) <0.001 GNRI -0.138 0.027 26.342 0.871(0.827–0.918) <0.001 Note: NLR, neutrophil/lymphocyte ratio; GNRI: Geriatric nutritional risk index. 3.3 Predictive value of GNRI and NLR for mortality in MHD patients The area under the ROC curve for GNRI’s prediction for mortality in MHD patients was 0.742. At the GNRI threshold of 89.01, its Jordon index was 0.506, with a specificity of 0.680 and a sensitivity of 0.826. The area under the ROC curve for the combined GNRI and NLR’s prediction for mortality in MHD patients was 0.652. At the NLR threshold of 4.0, its Jordon index was 0.404, with a specificity of 0.784 and a sensitivity of 0.620. The equation of GNRI combined with NLR = Log(7.623 = 0.307*NLR-0.111*GNRI). The area under the ROC curve for the combined GNRI and NLR’s prediction for mortality in MHD patients was 0.780, with a Jordon index of 0.509, a specificity of 0.620 and a sensitivity of 0.889. See Fig 1. 10.1371/journal.pone.0287696.g001 Fig 1 Predictive value of GNRI and NLR for mortality in MHD patients. Abbreviations: GNRI: Geriatric nutritional risk index, NLR: Neutrophils / lymphocytes ratio. 3.4 GNRI correlates with NLR GNRI was negatively correlated with NLR (r = -0.229), as shown in Fig 2. 10.1371/journal.pone.0287696.g002 Fig 2 GNRI correlates with NLR. Abbreviations: GNRI: Geriatric nutritional risk index, NLR: Neutrophils / lymphocytes ratio. 3.5 All-cause death survival curves of MHD patients with different levels of GNRI, NLR The diagnostic threshold of GNRI at 89.01 was regarded as a cutoff value. A total of 175 patients with high GNRI (mortality19/175) and 65 patients with low GNRI (mortality 31/ 65) were classified as statistically significant differences. Survival analysis revealed that the survival rate of patients with low GNRI was lower than those with high GNRI ((χ2 = 48.712, P<0.001)) (Fig 3A). The NLR diagnostic threshold of 4.0 was considered as a dividing line. The patients were categorized into high NLR group with 69 patients (mortality 31/ 69) and low NLR group with 171 patients (mortality 19/171). Survival analysis indicated that patients with high NLR survival has lower survival rate than those with low NLR (χ2 = 48.712, P < 0.001) (Fig 3B). 10.1371/journal.pone.0287696.g003 Fig 3 Kaplan–Meier survival curves for all-cause mortality. Comparison of different GNRI levels with all-cause mortality (A). Comparison of different NLR levels with all-cause mortality (B). Abbreviations: Ref: Reference values, GNRI: Geriatric nutritional risk index, NLR: Neutrophils / lymphocytes ratio. 3.6 Survival curve analysis of different subgroups and all causes of death and cardiovascular events In the all-cause mortality comparison, there were 45 cases in G1 (mortality 8 / 45), 128 cases in G2 (mortality 10 / 128), 27 cases in G3 (mortality 23 / 27) and 40 cases in G4 (mortality 9 / 40) (Table 3). Survival analysis revealed that G3 group had a lower survival rate than G1, G2, and G4 groups (P < 0.001), while G2 group exhibited a higher survival than G1, G3 and G4 (P < 0.05) (Fig 4A). Cardiovascular events accounted for 29 of the 50 deaths. There were 45 cases in G1 (mortality 4/ 45), 128 cases in G2 (mortality 6 / 128), 27 cases in G3 (mortality 14/ 27) and 40 cases in G4 (mortality 5/ 40) (Table 3). Survival analysis demonstrated a lower survival rate in G3 compared to G1, G2, and G4 (P < 0.001) (Fig 4B). 10.1371/journal.pone.0287696.g004 Fig 4 Survival curve analysis of different groups and all-cause death and cardiovascular mortality. Comparison of mortality rates from cause among groups (A). Comparison of mortality rates from cardiovascular events among groups (B). 10.1371/journal.pone.0287696.t003 Table 3 A comparison of mortality rates in different groups. Categories G1 (n = 45) G2 (n = 128) G3 (n = 27) G4 (n = 40) χ2 value P All-cause death [n (%)] 8(17.78) 10(7.81) 23(85.19) ***###@@@ 9(22.50)&&& 81.273 <0.001 Cardiovascular mortality [n (%)] 4(8.89) 6 (4.69) 14(60.87)***###@@@ 5(12.50)&&& 81.800 <0.001 Non-cardiovascular mortality [n (%)] 4(8.89) 4(3.13) 9(33.33)***@@@ 4(10.00)&&& Note:*Compared with G1and G3,***P<0.001;#Compared with G2 and G3,### P<0.001;@Compared with G3and G4,@@@ P<0.001;&Compared with G2and G4, &&&为P<0.001. 4 Discussion There were statistical differences in the indicators (dialysis duration, education years, hemoglobin, blood phosphorus, NLR, PLR and GNRI) among different groups. It has been reported that dialysis duration is positively correlated with the occurrence of sarcopenia in MHD patients [26]. The sarcopenia leads to a decrease in exercise capacity, resulting in an increased incidence of cardiovascular and cerebrovascular events. With the increase of dialysis duration, the patients experience more nutrient loss, acid-base imbalance, and hormonal level changes, resulting in an increased incidence of sarcopenia [27]. Patients with lower years of education are more likely to be frail due to lower incomes, which may indirectly affect their ability to receive better treatment [28]. The dialysis adequacy refers to the removal of excess water and toxins from the patient’s body through hemodialysis to achieve a comfortable state [29]. Indicators such as serum albumin, hemoglobin, and body mass index reflect the nutritional status of patients. The risk of frailty is 1.89 times higher in hemodialysis (MHD) patients with serum albumin concentrations below 32 g/L than in those with concentrations at or above 39 g/L [30]. Lower hemoglobin concentration in MHD patients,are associated with a higher likelihood of debilitation and poor prognosis [31]. MHD patients with a low body mass index (<18.5 kg/m2) have a significantly increased risk of frailty, sarcopenia, and consequently, a higher risk of death [32,33]. Grip strength, grip strength, walking speed, and upper arm circumference serve as indicators of muscle strength and mass. Studies have shown that the prevalence of sarcopenia in MHD patients ranges between 3.9% to 63.3% [34,35]. Furthermore, sarcopenia can induce an increased incidence of adverse events and affect prognosis [36,37]. In this study, patients were grouped based on the cut-off values of GNRI and NLR for MHD death prediction (89.01 and 4, respectively). The 5-year follow-up of 240 MHD patients included in this study showed 50 all-cause deaths, with a 5-year mortality rate of 20.83%. By multifactorial Cox regression analysis, NLR and GNRI were found as independent risk factors for prognosis in MHD patients. NLR is a systemic inflammation marker. Inflammatory factors easily trigger malnutrition and thereby induce a debilitating syndrome [38]. In our study, NLR and PLR levels were increased in MHD patients with the debilitating syndrome, and NLR was an independent risk factor for prognosis in MHD patients [17]. As an important indicator of systemic inflammation, NLR is an independent risk factor for predicting kidney failure in patients with stage 4 chronic kidney disease [19]. Stimulated by inflammation, it induces hyperplasia of megakaryocytes, which in turn interacts with endothelial cells and white blood cells to produce inflammatory factors in a vicious cycle. The occurrence of various diseases is associated with increased platelets [39,40]. NLR is a novel inflammatory factor that plays a great role in the development of coronary heart disease, myocardial infarction and tumors [41,42]. Mortality in MHD patients may be linked to higher NLR levels promoting tumor and cardiovascular disease. GNRI is one of the indicators of nutritional assessment. Its use in Asian MHD patients has some predictive value for nutritional status and prognosis [42,43]. A study involving 3,536 MHD patients points out that low levels of GNRI are associated with increased mortality from all causes [44]. Another study of 2,791 people with chronic kidney disease indicates that low GNRI levels are connected to cardiovascular and all-cause mortality [7]. Poor immune function due to malnourishment increases the incidence of inflammatory infections, leading to cardiovascular events and poor prognosis. In this study, the relationship between GNRI and NLR reveals a negative correlation between them, which may be related to nutrient loss in patients with inflammatory factors. In this study, GNRI combined with NLR markers significantly increased the predictive value of death. We subdivided MHD patients with varying degrees of GNRI and NLR, with 89.01 of GNRI and 4.0 of NLR as cutoff values for death prediction, respectively. This indicated lower survival in patients with high NLR and low GNRI. Kobayashi’s study shows chronic inflammatory levels in MHD patients with GNRI≥90 have lower all-cause mortality compared to those with GNRI<90 [45]. Another clinical study reveals a significant increase in all-cause mortality in MHD patients with GNRI below 92 [46]. Epidemiologically, GNRI predicts cardiovascular outcomes, and studies have shown a correlation between GNRI and cardiovascular events in patients with chronic heart failure [47]. It has been verified that GNRI is strongly associated with mortality from various causes and cardiovascular events in MHD patients [7]. Chronic inflammation is common in MHD patients. Inflammatory states increase muscle protein metabolism, inhibit albumin production and accelerate its breakdown [48]. Our previous study showed an increase in frailty and mortality in MHD patients with NLR above 2.98 [17]. Another study showed higher NLR levels result in more cardiovascular events in MHD patients [49]. Based on these findings, we further subdivided the GNRI and NLR levels The low GNRI + high NLR group (G3) had the worst all-cause mortality and cardiovascular mortality, while the high GNRI + low NLR group(G2) had the best all-cause mortality compared to the other three groups. Studies have revealed a negative correlation between GNRI and leptin, which predicts patient’s future nutritional status [50]. MHD patients with high GNRI indicate good nutritional status and higher lean mass index and bone mineral density [51]. It has been reported that there is a negative correlation between GNRI levels and IL-6 in MHD patients [52]. Elevated NLR levels in patients indicate an increase in neutrophils and a decrease in lymphocytes, which are pro-inflammatory cells releasing pro-inflammatory factors, activating macrophages to promote foam cell formation, and inducing cardiovascular diseases [53]. Decreased lymphocytes and a weakened immune system can trigger infection and cardiovascular events [54]. The combination of GNRI and creatinine index was used to predict all-cause mortality of MHD. Lower GNRI and Cr indices were associated with an increased risk of all-cause mortality, and GNRI was considered more suitable for predicting prognosis in hemodialysis patients because it is simpler to calculate than creatinine index [44]. In addition, MHD patients with low GNRI and low modified creatinine index had significantly higher all-cause mortality and cardiovascular event mortality [55]. Consequently, we suggest that when MHD patients are in a low GNRI and high NLR state, the body’s immunity weakens, and infections and cardiovascular events increase, leading to poor prognosis. However, there are some limitations in this study. (1) GNRI and NLR may change over time. (2) Other influencing factors weren’t considered in this retrospective study. (3) The sample size was small. Further expansion of the sample should be carried out to determine the association between GNRI and NLR for all-cause and cardiovascular mortality. In conclusion, our study shows that GNRI and NLR are associated with all-cause mortality and cardiovascular mortality in MHD patients. A combination of the two may contribute to a prognostic evaluation in MHD patients. Supporting information S1 File Original data. (XLS) Click here for additional data file. 10.1371/journal.pone.0287696.r001 Decision Letter 0 Aktas Gulali Academic Editor © 2023 Gulali Aktas 2023 Gulali Aktas https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version0 23 Mar 2023 PONE-D-23-04816Combined Evaluation of Geriatric Nutritional Risk Index and Neutrophil to lymphocyte ratio for Predicting All-cause mortality and cardiovascular mortality in Hemodialysis PatientsPLOS ONE Dear Dr. Wang, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. 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For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. 4. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.  5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information.  Additional Editor Comments: Make revisions in accordance with the reviewers, please. I invite to respond the comments of the reviewers. the paper will be reconsidered if adequately revised. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Partly ********** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ********** 3. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ********** 4. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: No ********** 5. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Introduction; I advise authors to make it clear why they studied NLR in hemodialysis patients as a risk factor for CV mortality. Chronic kidney disease is associated with low grade inflammation (). On the other hand, NLR is associated with various inflammatory conditions such as pancreatitis (Iran J Colorectal Res 2022;10(3):75-86.), diabetes mellitus type 2 (African health sciences, 19(1), 1602-1606), autoimmune disorders (Revista da Associação Médica Brasileira, 63, 1065-1068), and thyroid conditions (Ethiop. J. Health Dev. 2021; 35(3):149-153). Inflammation involve in all of these diseases similar to the chronic kidney disease. Materials&Methods; An inclusion criteria was noted as Age≥18. However, mean age was 63 years. Please revise. Results and Discussion; fair enough Reviewer #2: 1. the title is not well worded and too long ("All-cause mortality and cardiovascular mortality"?????) 2. Abstract: in Introduction add: "Aim of the study was To investigate the predictive value of the.........." 3. Abstract: methodology - this sentence do not belong here: "COX regression analysis showed that GNRI and NLR were risk factors for death in MHD patient" same one is in the Results section too. 4. Improve English ********** 6. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. 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Please note that Supporting Information files do not need this step. 10.1371/journal.pone.0287696.r002 Author response to Decision Letter 0 Submission Version1 24 Apr 2023 Response the academic editor： 1.Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf Response：We have revised the manuscript in accordance with the article format required by POLS ONE. 2.Thank you for stating the following financial disclosure:    "Funding: This research was funded by the Nanjing Administration of Traditional Chinese Medicine, Project name: Nanjing Traditional Chinese Medicine     Youth Talent Training Program,(NO.ZYQ20053).     YES - Specify the role(s) played." Please state what role the funders took in the study.  If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript." If this statement is not correct you must amend it as needed. Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf. Response：Annotations have been added to the manuscript 3. We note that you have indicated that data from this study are available upon request. PLOS only allows data to be available upon request if there are legal or ethical restrictions on sharing data publicly. For more information on unacceptable data access restrictions, please see http://journals.plos.org/plosone/s/data-availability#loc-unacceptable-data-access-restrictions. In your revised cover letter, please address the following prompts: a) If there are ethical or legal restrictions on sharing a de-identified data set, please explain them in detail (e.g., data contain potentially sensitive information, data are owned by a third-party organization, etc.) and who has imposed them (e.g., an ethics committee). Please also provide contact information for a data access committee, ethics committee, or other institutional body to which data requests may be sent. b) If there are no restrictions, please upload the minimal anonymized data set necessary to replicate your study findings as either Supporting Information files or to a stable, public repository and provide us with the relevant URLs, DOIs, or accession numbers. For a list of acceptable repositories, please see http://journals.plos.org/plosone/s/data-availability#loc-recommended-repositories. We will update your Data Availability statement on your behalf to reflect the information you provide. Response：Article data can be used publicly, the original data has been provided to the editorial department when submission, we have changed in the declaration. 4. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section. Response：We have deleted the relevant content from the article. 5. Please include captions for your Supporting Information files at the end of your manuscript, and update any in-text citations to match accordingly. Please see our Supporting Information guidelines for more information: http://journals.plos.org/plosone/s/supporting-information. Response：We have supplemented the original data used in the article and have no other supplementary information. Response Reviewer #1： ①Introduction; I advise authors to make it clear why they studied NLR in hemodialysis patients as a risk factor for CV mortality. Chronic kidney disease is associated with low grade inflammation (). On the other hand, NLR is associated with various inflammatory conditions such as pancreatitis (Iran J Colorectal Res 2022;10(3):75-86.), diabetes mellitus type 2 (African health sciences, 19(1), 1602-1606), autoimmune disorders (Revista da Associação Médica Brasileira, 63, 1065-1068), and thyroid conditions (Ethiop. J. Health Dev. 2021; 35(3):149-153). Inflammation involve in all of these diseases similar to the chronic kidney disease. Response：Thank you for your suggestion.We have added relevant content in the manuscript. Materials&Methods; An inclusion criteria was noted as Age≥18. However, mean age was 63 years. Please revise. Response：Thank you for your suggestion.We have revised it in the manuscript. Response Reviewer #2： 1.the title is not well worded and too long ("All-cause mortality and cardiovascular mortality"?????) Response：Thank you for your suggestion.We have added relevant content in the manuscript. 2. Abstract: in Introduction add: "Aim of the study was To investigate the predictive value of the.........." Response：Thank you for your suggestion.We have revised it in the manuscript. 3. Abstract: methodology - this sentence do not belong here: "COX regression analysis showed that GNRI and NLR were risk factors for death in MHD patient" same one is in the Results section too. Response：Thank you for your suggestion.We have revised it in the manuscript. 4. Improve English Response：Thank you for your suggestion.We have revised it in the manuscript. Attachment Submitted filename: Response to Reviewers.doc Click here for additional data file. 10.1371/journal.pone.0287696.r003 Decision Letter 1 Aktas Gulali Academic Editor © 2023 Gulali Aktas 2023 Gulali Aktas https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version1 1 Jun 2023 PONE-D-23-04816R1Combined Evaluation of Geriatric Nutritional Risk Index and Neutrophil to lymphocyte ratio for Predicting All-cause mortality and cardiovascular mortality in Hemodialysis PatientsPLOS ONE Dear Dr. Wang, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process. Please submit your revised manuscript by Jul 16 2023 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org. When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file. Please include the following items when submitting your revised manuscript:A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'. A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'. An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'. If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter. If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols. Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols. We look forward to receiving your revised manuscript. Kind regards, Gulali Aktas Academic Editor PLOS ONE Journal Requirements: Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [Note: HTML markup is below. Please do not edit.] Reviewers' comments: Reviewer's Responses to Questions Comments to the Author 1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation. Reviewer #1: All comments have been addressed Reviewer #2: All comments have been addressed ********** 2. Is the manuscript technically sound, and do the data support the conclusions? The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented. Reviewer #1: Yes Reviewer #2: Yes ********** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: I Don't Know ********** 4. Have the authors made all data underlying the findings in their manuscript fully available? The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified. Reviewer #1: Yes Reviewer #2: Yes ********** 5. Is the manuscript presented in an intelligible fashion and written in standard English? PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here. Reviewer #1: Yes Reviewer #2: Yes ********** 6. Review Comments to the Author Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters) Reviewer #1: Dear Author You have mentioned a very good topic in your article but background must be improved. NLR is a novel marker of inflammation derived from routine blood count test. Its association with inflammation has been reported in inflammatory bowel disease (Wiener klinische Wochenschrift (2015)127:262-265. DOI 10.1007/s00508-014-0683-5), diabetes mellitus (Afri Health Sci. 2019;19(1):1602-1606. DOI: 10.4314/ahs.v19i1.35), and gastrointestinal conditions (Iran J Colorectal Res. 2022;10(3):75-86. doi: 10.30476/ACRR.2022.97244.1160). Improve the background please. Best Regards... Reviewer #2: - In Abstract section, please write full terms for NLR and GNRI. - In Results section, for number of patients (50 and 29) except total number write values in percentages (%) - Three last sentences in Introduction should be written on better way and they should have better formulation in context of Introduction ("No studies have used GNRI and NLR combinations to predict prognosis in MHD patients. GNRI and NLR are clinically relevant indicators of mortality in MHD patients and contribute to early diagnosis and intervention. The study was based on data from two hemodialysis centers, focusing on the impact of GNRI and NLR on all-cause mortality in MHD patients." - "The study was based on data from two hemodialysis centers" - this information should be part of Materials and Methods - In Materials and Methods section write the type of the study - Inclusion and Exclusion criteria should include more information about patients - What about Inform consent of the patients? Did you provide it? - In Methods section include formula for NLR calculation - In Materials and Methods section include information about all parameters that you was analyzed in the study and explain (for example: hemoglobin, blood phosphorus, platelet-lymphocyte ratio(PLR)...) - In Statistical processing section, explain how you determined correlation between two variables (Did you use Pearson or Sperman correlation coefficient?) ********** 7. PLOS authors have the option to publish the peer review history of their article (what does this mean?). If published, this will include your full peer review and any attached files. If you choose “no”, your identity will remain anonymous but your review may still be made public. Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No ********** [NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.] While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org. Please note that Supporting Information files do not need this step. 10.1371/journal.pone.0287696.r004 Author response to Decision Letter 1 Submission Version2 7 Jun 2023 Response Reviewer #1： 1.You have mentioned a very good topic in your article but background must be improved. NLR is a novel marker of inflammation derived from routine blood count test. Its association with inflammation has been reported in inflammatory bowel disease (Wiener klinische Wochenschrift (2015)127:262-265. DOI 10.1007/s00508-014-0683-5), diabetes mellitus (Afri Health Sci. 2019;19(1):1602-1606. DOI: 10.4314/ahs.v19i1.35), and gastrointestinal conditions (Iran J Colorectal Res. 2022;10(3):75-86. doi: 10.30476/ACRR.2022.97244.1160). Improve the background please. Best Regards... Response：Thank you for your suggestion.We have added relevant content in the manuscript. Response Reviewer #2：  1.In Results section, for number of patients (50 and 29) except total number write values in percentages (%) Response：Thank you for your suggestion.We have revised it in the manuscript. 2. Three last sentences in Introduction should be written on better way and they should have better formulation in context of Introduction ("No studies have used GNRI and NLR combinations to predict prognosis in MHD patients. GNRI and NLR are clinically relevant indicators of mortality in MHD patients and contribute to early diagnosis and intervention. The study was based on data from two hemodialysis centers, focusing on the impact of GNRI and NLR on all-cause mortality in MHD patients." Response：Thank you for your suggestion.We have revised it in the manuscript. 3.  "The study was based on data from two hemodialysis centers" - this information should be part of Materials and Methods Response：Thank you for your suggestion.We have revised it in the manuscript. 4. In Materials and Methods section write the type of the study Response：Thank you for your suggestion.We have revised it in the manuscript. 5.Inclusion and Exclusion criteria should include more information about patients Response：Thank you for your suggestion.We have revised it in the manuscript. 6.What about Inform consent of the patients? Did you provide it? Response：Due to the retrospective nature of the study, informed conssent was waived.The study was approved by the ethic committee of our hospital. 7.In Methods section include formula for NLR calculation Response：Thank you for your suggestion.We have revised it in the manuscript. 8.In Materials and Methods section include information about all parameters that you was analyzed in the study and explain (for example: hemoglobin, blood phosphorus, platelet-lymphocyte ratio(PLR)...) Response：Thank you for your suggestion.We have revised it in the manuscript. 9.In Statistical processing section, explain how you determined correlation between two variables (Did you use Pearson or Sperman correlation coefficient?) Response：Person test was used to analyze the correlation between two variables.Modifications were made in statistical methods. Attachment Submitted filename: Response to Reviewers.doc Click here for additional data file. 10.1371/journal.pone.0287696.r005 Decision Letter 2 Aktas Gulali Academic Editor © 2023 Gulali Aktas 2023 Gulali Aktas https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Submission Version2 12 Jun 2023 Combined Evaluation of Geriatric Nutritional Risk Index and Neutrophil to lymphocyte ratio for predicting all-cause and cardiovascular mortality in hemodialysis patients PONE-D-23-04816R2 Dear Dr. Li, We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements. Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication. An invoice for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, please contact our Author Billing department directly at authorbilling@plos.org. If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org. Kind regards, Gulali Aktas Academic Editor PLOS ONE Additional Editor Comments (optional): Dear Authors You responded the editorial and reviewers' comments adequately. There is nothing more that need further revision. Thank you. Reviewers' comments: 10.1371/journal.pone.0287696.r006 Acceptance letter Aktas Gulali Academic Editor © 2023 Gulali Aktas 2023 Gulali Aktas https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 22 Jun 2023 PONE-D-23-04816R2 Combined Evaluation of Geriatric Nutritional Risk Index and Neutrophil to lymphocyte ratio for predicting all-cause and cardiovascular mortality in hemodialysis patients Dear Dr. Li: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information please contact onepress@plos.org. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Professor Gulali Aktas Academic Editor PLOS ONE ==== Refs References 1 Boris Bikbov, Caroline A Purcell, Andrew S Levey, Mari Smith, Amir Abdoli, Molla Abebe, et al. Global, regional, and national burden of chronic kidney disease, 1990–2017:a systematic analysis for the Global Burden of Disease Study 2017[J].The Lancet,2020,395(10225). doi: 10.1016/S0140-6736(20)30045-3 2 Maria Pippias , Jager Kitty J Caskey Fergus , Anna Casula , Helen Erlandsson , Patrik Finne , et al . Kidney transplant outcomes from older deceased donors: a paired kidney analysis by the European Renal Association-European Dialysis and Transplant Association Registry. [J].Transplant international: official journal of the European Society for Organ Transplantation,2018,31 (7 ). doi: 10.1111/tri.13103 29210108 3 Yajima Takahiro, Yajima Kumiko, and Arao Maiko. Combined Evaluation of Geriatric Nutritional Risk Index and Modified Creatinine Index for Predicting Mortality in Patients on Hemodialysis. Nutrients(4). doi: 10.3390/NU14040752 4 Alice Sabatino , Giovanni Piotti , Carmela Cosola , Ilaria Gandolfini , Kooman Jeroen P Fiaccadori Enrico . Dietary protein and nutritional supplements in conventional hemodialysis.[J]. Seminars in dialysis,2018,31 (6 ). doi: 10.1111/sdi.12730 29909606 5 Yamada K , Furuya R , Takita T , et al . Simplified nutritional screening tools for patients on maintenance hemodialysis. Am J Clin Nutr. 2008. 87 (1 ): 106–13. doi: 10.1093/ajcn/87.1.106 18175743 6 Ren M , Sheng Q , Xie X , Zhang X , Han F , Chen J . Geriatric nutritional risk index is associated with mortality in peritoneal dialysis patients. Intern Med J. 2020. 50 (4 ): 470–476. doi: 10.1111/imj.14680 31707748 7 Xiong J , Wang M , Wang J , et al . Geriatric nutrition risk index is associated with renal progression, cardiovascular events and all-cause mortality in chronic kidney disease. J Nephrol. 2020. 33 (4 ): 783–793. doi: 10.1007/s40620-019-00676-1 31773640 8 Mehrotra Rajnish , et al . Serum Albumin as a Predictor of Mortality in Peritoneal Dialysis: Comparisons With Hemodialysis.[J] American Journal of Kidney Diseases 58.3(2011). doi: 10.1053/j.ajkd.2011.03.018 21601335 9 Lukowsky Lilia R , Kheifets Leeka , Arah Onyebuchi A , Nissenson Allen R , Kalantar-Zadeh Kamyar . Patterns and predictors of early mortality in incident hemodialysis patients: new insights.[J].American journal of nephrology,2012,35 (6 ). doi: 10.1159/000338673 22677686 10 Marian A.E. Bokhorst de van der Schueren , Patrícia Realino Guaitoli , Elise P . Nutrition screening tools: Does one size fit all? A Jansma, Henrica C.W. de Vet. systematic review of screening tools for the hospital setting[J]. Clinical Nutrition,2014,33 (1). doi: 10.1016/j.clnu.2013.04.008 23688831 11 Chen Szu-Chia , Chung Wei-Shiuan , Wu Pei-Yu ,Huang Jiun-Chi , Chiu Yi-Wen , Chang Jer-Ming , et al . Associations among Geriatric Nutrition Risk Index, bone mineral density, body composition and handgrip strength in patients receiving hemodialysis[J]. Nutrition,2019,65 . doi: 10.1016/j.nut.2019.02.013 31029923 12 Jagadeswaran D , Indhumathi E , Hemamalini AJ , Sivakumar V , Soundararajan P , Jayakumar M . 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