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Serum creatinine/cystatin C ratio as a surrogate marker for sarcopenia in patients with gastric cancer

BMC Gastroenterology volume 22, Article number: 26 (2022) Cite this article

Abstract

Background

Sarcopenia is an age-related syndrome that may have negative impact on surgical outcomes and long-term survival of patients with gastric cancer. Serum creatinine/cystatin C (Cr/CysC) ratio has attracted attention as a surrogate marker for sarcopenia but has not been adequately studied in patients with gastric cancer. The purpose of this study was to investigate the validity of serum Cr/CysC ratio as a predictor of sarcopenia, evaluate a statistical cut-off value, and assess the relationship between Cr/CysC ratio and prognosis of patients with gastric cancer.

Methods

We retrospectively studied 327 patients who underwent surgery for gastric cancer from June 2009 to October 2021. The skeletal muscle mass index was calculated using computed tomography (CT). We determined the relevance of serum Cr/CysC ratio as a surrogate maker for sarcopenia by comparing it with various biomarkers. The Concordance index (C-index) was calculted to measure whether the Cr/CysC ratio can prognosis of patients with gastric cancer.

Results

Serum Cr/CysC was significantly correlated with with Skeletal Muscle Index (SMI) (r = 0.221, p < 0.001) and Skeletal Muscle Area (SMA) (r = 0.258, p < 0.001). The area under the curve for sarcopenia was significantly larger for serum Cr/CysC ratio than for other biomarkers (Cr/CysC: 0.644, CysC: 0.535, Cr: 0.556). Patients in the high-Cr/CysC group have longer survival time than that in low-Cr/CysC group, defined by the cutoff value 0.67. The C-index of both Cr/CysC ratio and SMI with OS was 0.63.

Conclusions

Serum Cr/CysC ratio can be used accurately, inexpensively, and easily to evaluate sarcopenia in male patients with gastric cancer. Our study shows that patients with Cr/CysC below 0.67 had possibility of sarcopenia and would be poor prognosis.

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Background

Gastric cancer is one of the most common malignant tumors worldwide. The incidence (5.7%) and mortality (8.2%) rates were fifth and third, respectively in 2018 [1]. Although development of technology has led to progress in tumor diagnosis, surgical methods, and adjuvant treatment, the survival rate of patients with gastric cancer remains low [2].

Sarcopenia is an age-related syndrome characterized by progressive and extensive loss of skeletal muscle mass and strength [3]; this has a negative impact on surgical outcomes and long-term survival of patients with gastric cancer [4]. Studies have shown that weight loss and malnutrition are common problems in patients with gastric cancer [5, 6].

In recent years, researchers have proposed a new method to predict muscle mass. Routinely measured serum creatinine (Cr) and serum cystatin C (Cys C) were used to assess renal function. Since the concentration of serum creatinine is affected by muscle mass, patients with decreased muscle mass will decrease serum creatinine [7, 8]; while serum Cys C is not affected by muscle mass [9, 10]. Based on the characteristics of these two, the method of dividing serum creatinine by serum Cys C can be used to further predict muscle mass. This method has been confirmed in the research of many diseases [11,12,13,14]. However, there are no studies to test the effectiveness of Cr/Cys C in patients with gastric cancer. Based on the above reasons, we are thinking about whether we can explore the prediction of Cr/Cys C for muscle mass in gastric cancer patients, and determine the best cut-off value of Cr/CysC ratio for predicting sarcopenia and its impact on the survival time of gastric cancer patients.

Materials and methods

Patients and study design

We obtained patient data from the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University from June 2009 to May 2021. Inclusion criteria were as follows: (a) pathological diagnosis of gastric adenocarcinoma, (b) underwent radical gastrectomy, (c) underwent computed tomography (CT) imaging within 1 month preoperatively, and measure the concentration of serum creatinine and serum cystatin C whitin 1 week preoperatively. The exclusion criteria were as follows: (a) a diagnosis of metastatic or remnant gastric cancer, (b) received preoperative chemotherapy or radiotherapy, (c) having incomplete or inaccurate medical records, and (d) renal function impairment (an estimated glomerular filtration rate of < 60 mL/min/1.73 m2). After applying these criteria, 327 patients were recruited. In this study, the treatment of gastric cancer was developed according to the 2010 Japanese Gastric Cancer Treatment Guidelines [5]. Each patient provided their written informed consent to participate in this study. The research protocol was approved by the ethics committee. This research was conducted in accordance with the principles of the Declaration of Helsinki.

Data collection

We collected the following clinical information from each patient: (1) preoperative personal information, including age, sex, height, American Society of Anesthesiologists (ASA) grade, complications, and preoperative serum creatinine and serum cystatin C; (2) postoperative conditions, including tumor location, tumor size, tumor histology type (tumor differentiation divided into high, medium, and low), pTNM staging, and chemotherapy. Tumor staging conforms to the 8th edition of the corresponding American Joint Committee on Cancer guidelines [15]. To reduce bias, all evaluations were performed by two independent, well-trained researchers and all other data were ignored.

Definition of sarcopenia

Abdominal CT scan is routinely performed before surgery. Skeletal muscle mass was estimated by calculating the area of all skeletal muscles on the cross-section of the third lumbar vertebra (L3) [16] with ImageJ software. Tissues with a specific Hounsfield unit threshold of -29–150 were considered as skeletal muscles and were standardized according to height (m2), and the skeletal muscle mass was evaluated by calculating the skeletal muscle mass index (SMI) (cm2/m2) [17].

The criteria for sarcopenia were low skeletal muscle mass, low muscle strength, and/or poor physical function according to the European Working Group on Sarcopenia in Older People (EWGSOP) [18] and the Asian Working Group for Sarcopenia (AWGS) [19]. We used the following cut-off values to define sarcopenia: (1) SMI (L3) < 40.8 cm2/m2 for men and SMI < 34.9 cm2/m2 for women, considering possible racial differences indicating low muscle mass [20]. (2) Hand grip strength < 28 kg among men and < 18 kg among women were regarded as low muscle strength [19]; and (3) 6-m usual gait speed < 1.0 m/s was regarded as low physical performance [19].

Follow-up

All patients were followed up in the outpatient department in the first month after surgery. After that, the patients were followed up by telephone or in an outpatient clinic every 36 months. The overall survival (OS) was defined as the time between surgery and death from any cause or the date of the last follow-up. We choose the patients from June 2009 to October 2017. All patients were followed up for at least 3 years. The last follow-up was in October 2020.

Laboratory measurements

Serum Cr levels were measured at our hospital laboratory. Serum Cr levels were measured using an enzymatic method. Serum cystatin C concentrations were determined by using a particle-enhanced immunoturbidimetric assay, and Cr/Cys C ratio was calculated by diving serum Cr by serum Cys C.

Statistical analysis

All continuous data in this study were non-normally distributed according to the Kolmogorov–Smirnov test. Therefore, continuous data were presented as median and interquartile range (IQR). Kaplan–Meier survival analysis were used to calculate the effects of Cr/CysC ratio on survival time. Receiver operating characteristic (ROC) curve analysis was used to evaluate the utility of the Cr/CysC ratio for identifying low SMI, based on the area under the ROC curve (AUC) and 95% confidence interval (CI). The Y ouden index (sensitivity + specificity-1) was calculated to determine the optimal cutoff points for the Cr/CysC ratio. The C-index was calculated to measure the impact of Cr/CysC ratio and SMI on prognosis. All P values were two-sided, and a P value of < 0.05 was used to denote statistical significance. All statistical analyses were performed using Statistical Package for the Social Sciences, version 26.0 (IBM Corp., Armonk, NY, USA) and R version 4.1.2 (The R Foundation, Vienna, Austria).

Results

Patient characteristics

We included 339 adults to participate in this study from June 2009 to October 2021. Some participants were excluded because of an estimated glomerular filtration rate of < 60 mL/min/1.73 m2 (n = 12). A total of 327 participants (median age: 64 years old, range 20–89 years old) were considered eligible for the analysis, including 234 men and 93 women, whose characteristics are shown in Table 1. There were 26 sarcopenia patients (11.1%) out of 234 men, and 16 sarcopenia patients (17.2%) out of 93 women among the patients. We conducted a correlation analysis on the basic characteristics of the sample. As shown in the heat map (Fig. 1), the serum CysC/Cr ratio is positively correlated with SMA, SMI, weight, height, and BMI, and negatively correlated with age and sarcopenia, but there is no strong correlation.

Table 1 Clinical characteristics of the male and female groups
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Fig. 1
figure 1

Correlation heat map analysis between factors which are basic characteristics of the population

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Correlation between clinical factors for sarcopenia

We performed Logistic regression analysis to evaluate whether Cr/Cys C is related to sarcopenia. Univariate analysis showed that Cr/Cys C, age, lower BMI, preoperative anemia, tumor size, and pTNM stage are predictors of sarcopenia. And Cr/Cys C (p = 0.01) is still an independent predictor of sarcopenia in multivariate analysis (Table 2). In addition, other markers including age ≥ 75 years, lower BMI have also been shown to be associated with increased risk of sarcopenia (all p < 0.05).

Table 2 Univariate and multivariate analyses the risk of sarcopenia
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Association between various biomarkers and sarcopenia

Serum Cr/CysC ratio was positively correlated with SMI (r = 0.221, p < 0.001) and SMA (r = 0.258, p < 0.001). Serum Cr was positively correlated with SMI (r = 0.201, p = 0.002) and SMA (r = 0.249, p < 0.001), while serum CysC had no significant correlation with SMI and SMA (p > 0.05) (Fig. 2). We calculated the AUC of each biomarker using the ROC curve (Fig. 3), and used the DeLong test to check the effectiveness of each biomarker as a predictor of sarcopenia. We divided the patients into two groups according to whether to measure hand grip strength and 6-m usual gait speed, a standard group that measured muscle mass and a low skeletal muscle mass group that only measured muscle area. Serum Cr/CysC ratio, CysC, Cr AUC were 0.664 (95% CI 0.511–0.816), 0.630 (95% CI 0.452–0.808), 0.543 (95% CI 0.367–0.719) in standard group. And Serum Cr/CysC ratio, CysC, Cr AUC were 0.644 (95% CI 0.532–0.757), 0.535 (95% CI 0.418–0.652), 0.556 (95% CI 0.432–0.681) in low skeletal muscle mass group. The AUC of the Cr/CysC ratio in two group were both significantly greater than the AUC of all other biomarkers (p = 0.034 and p = 0.016).

Fig. 2
figure 2

Linear correlation between the skeletal muscle mass index (SMI), skeletal muscle area (SMA) and cystatin C, creatinine and creatinine/cystatin C ratio in the group

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Fig. 3
figure 3

Receiver operator characteristic curves presenting sarcopenia and low skeletal muscle mass according to serum creatinine (Cr)/cystatin C (CysC) ratio, serum CysC and serum Cr levels

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Cutoff value of serum Cr/CysC on sarcopenia

We calculated the serum Cr/CysC cutoff to be 0.67, using Youden-Index that maximizes the value of “sensitivity þ specificity-1”. Based on the calculated cut-off value, in the Low skeletal muscle mass group, the sensitivity, specificity, positive predictive value, and negative predictive value were 0.26, 0.87, 0.25 and 0.88, respectively. And the sensitivity, specificity, positive predictive value, and negative predictive value were 0.44, 0.84, 0.26 and 0.92 in the standard group (Fig. 4).

Fig. 4
figure 4

Frequency of sarcopenia and low skeletal muscle mass in patients with low and high serum creatine (Cre)/ cystatin C (Cys C) ratio. Cr/CysC < 0.67 was defined as low Cr/CysC, and Cr/CysC S 0.67 was defined as high Cr/CysC

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Survival outcomes

We used the calculated optimal cut-off value to draw the KM curve of serum Cr/CysC and survival time after excluding 2 patients who died within 1 month after surgery in order to reduce the impact of postoperative acute complications on survival time. As shown in the Fig. 5, serum Cr/CysC is highly correlated with OS. The OS of the high serum Cr/CysC group was significantly longer than that of the low serum Cr/CysC group (p = 0.02). We used age, BMI, pTNM stage and tumor size to perform COX regression to perform survival multivariate analysis (Table 3). And Cr/Cys C (HR = 0.565 (95% CI 0.311–1.025); p = 0.060) is marginal significant, which needs expand the sample size and eliminate confounding factors for further analysis (Table 3). In the R software, we calculated the height-calibrated Cr/CysC ratio, SMI and survival C-index value. The C-index of SMI and OS was 0.62. And after calibrationed by height, the C-index of Cr/CysC ratio and OS was 0.56. When they both as variables, we calcualted the C-index as 0.63, which higher than that of SMI.

Fig. 5
figure 5

Kaplan–Meier survival analyses of patients in low and high serum creatine (Cre)/ cystatin C (Cys C) ratio. Cr/CysC < 0.67 was defined as low Cr/CysC, and Cr/CysC S 0.67 was defined as high Cr/CysC

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Table 3 Univariate and multivariate analyses of factors in relation to overall survival
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Discussion

Baumgartner et al. first proposed the concept of "sarcopenia" [21] to describe the decrease in muscle mass of the elderly with age in 1998. The occurrence of sarcopenia is closely related to age and special physiological conditions which has received extensive attention from scientists in recent years. Many studies have shown that sarcopenia is associated with an increased risk of recurrence [22], shortened survival time [23, 24] and increased other causes of death [25] after gastric cancer resection. Weight loss and malnutrition are issues that are very worthy of our attention in all stages of gastric cancer treatment. More than half of patients with gastric cancer have some degree of weight loss due to the potential impact of the tumor at the time of diagnosis [26]. The inability to maintain weight is considered to be a poor prognostic factor that affects long-term survival during neoadjuvant therapy or chemotherapy [27, 28].

The relationship between Cr/CysC ratio and sarcopenia in different populations has been discussed. Tetsuka et al. found for the first time that the Cr/CysC ratio of patients with amyotrophic lateral sclerosis was lower than that of healthy people [29]. In the Japanese elderly without severe renal impairment, the Cr/CysC ratio is positively correlated with muscle mass and physical function [13]. The reduction of Cr/CysC ratio is considered to be a predictor of sarcopenia in patients with type 2 diabetes and COPD [11, 30]. Recent studies have found that the Cr/CysC ratio can also predict malnutrition, weakness and poor clinical outcomes in ICU patients [31,32,33]. Studies have also confirmed that this indicator can be used as an effective surrogate indicator for evaluating sarcopenia in patients after colorectal cancer surgery [34]. However, there is no report confirming the association between Cr/CysC ratio and sarcopenia in patients with gastric cancer.

This study shows that the serum Cr/CysC ratio is a useful predictor of sarcopenia compared with other biomarkers (such as serum Cr, CysC). In addition, the best cut-off value of serum Cr/CysC ratio is 0.67. Patients with Cr/CysC ≥ 0.67 can basically rule out sarcopenia.

We found that the Cr/CysC ratio is the most predictive of sarcopenia in patients with gastric cancer which is positively correlated with SMI and SMA among the three biomarkers of serum Cr, serum CysC and serum Cr/CysC ratio in this study. Previous studies have shown that serum Cr is related to muscle mass [35, 36]. In our study, serum Cr is positively correlated with SMI and SMA which is consistent with the results of previous studies. Serum CysC does not show any correlation with muscle mass. As an indicator of renal function, serum CysC has received more and more attention in recent years. It is a low molecular weight protein with a stable production rate and can be freely filtered by the glomerulus [19]. Therefore, the Cr/CysC ratio obtained by calibrating Cr with CysC, that is not affected by muscle mass, can predict sarcopenia.

We found that the best cut-off value of the optimal serum Cr/CysC ratio for predicting sarcopenia in patients with gastric cancer is 0.67. A study found that the optimal cut-off value of Cr/CysC ratio in diabetic patients for predicting sarcopenia was 0.9 [11], while another study found that the optimal cut-off value of Cr/CysC ratio was 0.71 in COPD patients [30]. However, there is no study to detect the optimal cut-off value of Cr/CysC ratio for sarcopenia in gastric cancer patients as we know.

The OS of the high serum Cr/CysC group defined by the optimal cut-off value was significantly higher than that of the low serum Cr/CysC group. And sarcopenia shorted the survival time of patients as an independent factor affecting the prognosis of gastric cancer patients which result is consistent with that of Cr/CysC ratio. We also constructed height-calibrated Cr/CysC ratio and SMI and survival models. Studies have shown that although the Cr/CysC ratio is related to OS, the correlation is not as good as SMI. But its correlation is greater than SMI when it is used together with SMI as an indicator to measure the prognosis of patients with gastric cancer. This means that the prognosis of gastric cancer patients can be predicted by using the Cr/CysC ratio and SMI as a combined index.

In this study, we used the area of all skeletal muscle on the CT scan at the L3 level as the standard for estimating the patient's skeletal muscle mass. Many studies have confirmed that CT scans are an effective way to assess body composition and can predict sarcopenia in the population. It has been widely used in oncology as a highly feasible method. However, it is still subject to many limitations in actual clinical applications as a method of evaluating body composition, such as its high radioactivity and high cost. In addition, the measurement of grip strength and pace is often used to assess sarcopenia. But this method is very dependent on patient compliance and is often difficult to implement in clinical operations. However, early diagnosis and intervention are very important since sarcopenia can significantly affect the prognosis of patients with gastric cancer. Serum Cr/CysC ratio is a simple, easy and low-cost method that can initially screen patients for sarcopenia and assist subsequent treatment and intervention. If the Cr/CysC ratio is lower than 0.67, detailed examinations must be carried out by BIA, DEXA, CT or MRI.

This study also has certain limitations. First of all, it is a retrospective study and sometimes there are certain deficiencies when collecting follow-up information. Second, the sample size is insufficient because this study only included data from a tertiary center for statistical analysis. The detection of serum Cr and serum CysC will also be affected by reagents and instruments. In follow-up studies, prospective studies can be carried out around this point of view and verified in other centers. Third, this study only referred to the Chinese population. Due to the different criteria for sarcopenia, this limits the applicability of the conclusions, especially for Western populations. In follow-up research, how to determine the appropriate standards according to different groups of people to verify our conclusions is very important.

Availability of data and materials

The data that support the fndings of this study are available from the corresponding author upon reasonable request. Emails could be sent to the address below to obtain the shared data: shenxian@wmu.edu.cn.

Abbreviations

Cr/CysC:

Serum creatinine/cystatin C

CT:

Computed tomography

ASA:

American Society of Anesthesiologists

SMI:

Skeletal muscle mass index

EWGSOP:

European Working Group on Sarcopenia in Older People

AWGS:

Asian Working Group for Sarcopenia

OS:

Overall survival

IQR:

Interquartile range

ROC:

Receiver operating characteristic

AUC:

Area under the ROC curve

CI:

Confidence interval

COPD:

Chronic obstructive pulmonary disease

ICU:

Intensive care unit

MRI:

Magnetic resonance imaging

References

  1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68(6):394–424.

    Article  Google Scholar 

  2. Kim Y, Ejaz A, Spolverato G, et al. Conditional survival after surgical resection of gastric cancer: a multi-institutional analysis of the us gastric cancer collaborative. Ann Surg Oncol. 2015;22(2):57–64.

    Google Scholar 

  3. Morley JE, Baumgartner RN, Roubenoff R, Mayer J, Nair KS. Sarcopenia. J Lab Clin Med. 2001;137(4):231–43.

    Article  CAS  Google Scholar 

  4. Zhuang C-L, Shen X, Zou H-B, et al. EWGSOP2 versus EWGSOP1 for sarcopenia to predict prognosis in patients with gastric cancer after radical gastrectomy:analysis from a large-scale prospective study. Clin Nutr. 2019.

  5. Drissi M, Cwieluch O, Lechner P, Radziwill R, Vehling-Kaiser U, Hengst K, Masin M. Nutrition care in patients with cancer: a retrospective multicenter analysis of current practice—indications for further studies? Clin Nutr. 2014. https://doi.org/10.1016/j.clnu.2014.03.002.

    Article  PubMed  Google Scholar 

  6. James EJ, et al. Sarcopenia is associated with toxicity in patients undergoing neo-adjuvant chemotherapy for oesophago-gastric cancer. Eur J Surg Oncol. 2015.

  7. Viollet L, Gailey S, Thornton DJ, Friedman NR, Flanigan KM, Mahan JD, et al. Utility of cystatin C to monitor renal function in Duchenne muscular dystrophy. Muscle Nerve. 2009;40:438–42.

    Article  CAS  Google Scholar 

  8. Cartin-Ceba R, Afessa B, Gajic O. Low baseline serum creatinine concentration predicts mortality in critically ill patients independent of body mass index. Crit Care Med. 2007;35:2420–3.

    Article  CAS  Google Scholar 

  9. Vinge E, Lindergård B, Nilsson-Ehle P, et al. Relationships among serum cystatin C, serum creatinine, lean tissue mass and glomerular filtration rate in healthy adults. Scand J Clin Lab Invest. 1999;59:587–92.

    Article  CAS  Google Scholar 

  10. Anders G. Cystatin C is indispensable for evaluation of kidney disease. EJIFCC. 2017;28:268–76.

    Google Scholar 

  11. Kashani KB, Frazee EN, Kukrálová L, Sarvottam K, Herasevich V, Young PM, et al. Evaluating muscle mass by using markers of kidney function: development of the sarcopenia index. Crit Care Med. 2017;45:e23-9.

    Article  Google Scholar 

  12. Kashani K, Sarvottam K, Pereira NL, Barreto EF, Kennedy CC. The sarcopenia index: a novel measure of muscle mass in lung transplant candidates. Clin Transplant. 2018;32:13182.

    Article  Google Scholar 

  13. Osaka T, Hamaguchi M, Hashimoto Y, Ushigome E, Tanaka M, Yamazaki M, et al. Decreased the creatinine to cystatin C ratio is a surrogate marker of sarcopenia in patients with type 2 diabetes. Diabetes Res Clin Pract. 2018;139:52–8.

    Article  CAS  Google Scholar 

  14. Suzuki K, Furuse H, Tsuda T, Masaki Y, Okazawa S, Kambara K, et al. Utility of creatinine/cystatin C ratio as a predictive marker for adverse effects of chemotherapy in lung cancer: a retrospective study. J Int Med Res. 2015;43:573–82.

    Article  CAS  Google Scholar 

  15. Huhmann MB, Cunningham RS. Importance of nutritional screening in treatment of cancer-related weight loss. Lancet Oncol. 2005;6:334–43.

    Article  Google Scholar 

  16. Mourtzakis M, Prado CMM, Lieffers JR, Reiman T, McCargar LJ, Baracos VE. A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care. Appl Physiol Nutr Metab. 2008;33(5):997–1006.

    Article  Google Scholar 

  17. Prado CMM, Lieffers JR, McCargar LJ, et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 2008;9(7):629–35.

    Article  Google Scholar 

  18. Cruz-Jentoft AJ, Baeyens JP, Bauer JM, et al. Sarcopenia: European consensus on definition and diagnosis: report of the European working group on sarcopenia in older people. Age Ageing. 2010;39(4):412e23.

    Article  Google Scholar 

  19. Chen L-K, Woo J, Assantachai P, et al. Asian working group for sarcopenia:2019 consensus update on sarcopenia diagnosis and treatment. J Am Med Dir Assoc. 2020;21(3):300–7.

    Article  Google Scholar 

  20. Zhuang C-L, Huang D-D, Pang W-Y, et al. Sarcopenia is an independent predictor of severe postoperative complications and long-term survival after radical gastrectomy for gastric cancer: analysis from a large-scale cohort. Medicine (Baltim). 2016;95(13):e3164.

    Article  Google Scholar 

  21. Baumgartner RN, Waters DL. 80. Sarcopenia and sarcopenic-obesity. Principles and practice of geriatric medicine, Volume 2, Fourth Edition.

  22. Fukuda Y, Yamamoto K, Hirao M, Nishikawa K, Nagatsuma Y, Nakayama T, Tanikawa S, Maeda S, Uemura M, Miyake M, Hama N, Miyamoto A, Ikeda M, Nakamori S, Sekimoto M, Fujitani K, Tsujinaka T. Sarcopenia is associated with severe postoperative complications in elderly gastric cancer patients undergoing gastrectomy. Gastric Cancer. 2016;19(3):986–93. https://doi.org/10.1007/s10120-015-0546-4.

    Article  PubMed  Google Scholar 

  23. Kawamura T, Makuuchi R, Tokunaga M, Tanizawa Y, Bando E, Yasui H, Aoyama T, Inano T, Terashima M. Long-term outcomes of gastric cancer patients with preoperative sarcopenia. Ann Surg Oncol. 2018;25(6):1625–32. https://doi.org/10.1245/s10434-018-6452-3.

    Article  PubMed  Google Scholar 

  24. Kudou K, Saeki H, Nakashima Y, Edahiro K, Korehisa S, Taniguchi D, Tsutsumi R, Nishimura S, Nakaji Y, Akiyama S, Tajiri H, Nakanishi R, Kurashige J, Sugiyama M, Oki E, Maehara Y. Prognostic significance of sarcopenia in patients with esophagogastric junction cancer or upper gastric cancer. Ann Surg Oncol. 2017;24(7):1804–10. https://doi.org/10.1245/s10434-017-5811-9.

    Article  PubMed  Google Scholar 

  25. Shen Y, Hao Q, Zhou J, Dong B. The impact of frailty and sarcopenia on postoperative outcomes in older patients undergoing gastrectomy surgery: a systematic review and meta- analysis. BMC Geriatr. 2017;17(1):188. https://doi.org/10.1186/s12877-017-0569-2.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Maconi G, Manes G, Porro GB. Role of symptoms in diagnosis and outcome of gastric cancer. World J Gastroenterol. 2008;14(8):1149–55.

    Article  Google Scholar 

  27. Correia MI, Waitzberg DL. The impact of malnutrition on morbidity, mortality, length of hospital stay and costs evaluated through a multivariate model analysis. Clin Nutr. 2003;22(3):235–9.

    Article  Google Scholar 

  28. Choi WJ, Kim J. Nutritional care of gastric cancer patients with clinical outcomes and complications: a review. Clin Nutr Res. 2016;5(2):65–78.

    Article  Google Scholar 

  29. Syuichi T, Mitsuya M, Kunihiko I, Imaharu N. Creatinine/cystatin C ratio as a surrogate marker of residual muscle mass in amyotrophic lateral sclerosis. Neurol Clin Neurosci. 2013;1:32–7.

    Article  Google Scholar 

  30. Kusunoki H, Tsuji S, Wada Y, Fukai M, Nagai K, Itoh M, et al. Relationship between sarcopenia and the serum creatinine/cystatin C ratio in Japanese rural community-dwelling older adults. JCSM Clin Rep. 2018;3:e00057.

    Google Scholar 

  31. Barreto EF, Poyant JO, Coville HH, Dierkhising RA, Kennedy CC, Gajic O, et al. Validation of the sarcopenia index to assess muscle mass in the critically ill: a novel application of kidney function markers. Clin Nutr. 2019;38:1362–7.

    Article  Google Scholar 

  32. Inker LA, Astor BC, Fox CH, Isakova T, Lash JP, Peralta CA, et al. KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014;63:713–35.

    Article  Google Scholar 

  33. Isoyama N, Qureshi AR, Avesani CM, Lindholm B, Bàràny P, Heimbürger O, et al. Comparative associations of muscle mass and muscle strength with mortality in dialysis patients. Clin J Am Soc Nephrol CJASN. 2014;9:1720–8.

    Article  Google Scholar 

  34. Yang J, Zhang T, Feng D, Dai X, Lv T, Wang X, Gong J, Zhu W, Li J. A new diagnostic index for sarcopenia and its association with short-term postoperative complications in patients undergoing surgery for colorectal cancer. Colorectal Dis. 2019;21(5):538–47. https://doi.org/10.1111/codi.14558.

    Article  CAS  PubMed  Google Scholar 

  35. Thongprayoon C, Cheungpasitporn W, Kashani K. Serum creatinine level, a surrogate of muscle mass, predicts mortality in critically ill patients. J Thorac Dis. 2016;8:E305e11.

    Article  Google Scholar 

  36. Udy AA, Scheinkestel C, Pilcher D, Bailey M. Australian and New Zealand Intensive Care Society Centre for Outcomes and Resource Evaluation. The association between low admission peak plasma creatinine concentration and in-hospital mortality in patients admitted to intensive care in Australia and New Zealand. Crit Care Med. 2016;44:73–82.

    Article  Google Scholar 

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Acknowledgements

We gratefully acknowledge all staff members of Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China, for their help and cooperation.

Funding

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Author notes

  1. Jing Sun, Hui Yang and Wentao Cai are co-author

Authors and Affiliations

  1. Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China

    Jing Sun, Hui Yang, Wentao Cai, Jingwei Zheng, Ningzhe Shen, Xinxin Yang, Bujian Pan, Weiteng Zhang, Xiaodong Chen & Xian Shen

  2. Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China

    Xiaodong Chen & Xian Shen

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  6. Xinxin Yang
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  7. Bujian Pan
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  8. Weiteng Zhang
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  9. Xiaodong Chen
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  10. Xian Shen
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Contributions

ZS and XS are the main authors of manuscript and have made substantial contributions to the conception and design of study. XY, TC, HY, XW, CZ, TZ, DC, ZS and JP have been involved in collection and analysis of the data, ZS and XS gave final approval and revised of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Weiteng Zhang, Xiaodong Chen or Xian Shen.

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The research was in compliance with the Declaration of Helsinki. Ethical approval was obtained from the Second Affiliated Hospital, Wenzhou Medical University (ID: 2014063) and the necessity for informed consent was waived.

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Not applicable.

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The authors declare that they have no competing interests.

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Sun, J., Yang, H., Cai, W. et al. Serum creatinine/cystatin C ratio as a surrogate marker for sarcopenia in patients with gastric cancer. BMC Gastroenterol 22, 26 (2022). https://doi.org/10.1186/s12876-022-02093-4

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  • DOI: https://doi.org/10.1186/s12876-022-02093-4

Keywords

  • Serum Cr/CysC ratio
  • Sarcopenia
  • Gastric cancer

BMC Gastroenterology

ISSN: 1471-230X

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