Serum cytokines and creatinine/cystatin C ratio as prognostic biomarkers in advanced cancer patients treated with anti-PD-1/PD-L1 therapy.

OBJECTIVE: Immune checkpoint inhibitors (ICIs), specifically targeting the programmed cell death protein-1 or its ligand (PD-1/PD-L1), have been extensively used in the treatment of a spectrum of malignancies, although the predictive biomarkers remain to be elucidated. This study aims to investigate the association between baseline circulating levels of cytokines and the creatinine/cystatin C ratio (CCR) with the treatment outcomes of ICIs in patients with advanced cancer. METHODS: The pre-treatment circulating levels of 10 cytokines (PD-L1, CTLA4, CXCL10, LAG3, HGF, CCL2, MIG, GRANB, IL-18, and IL-6) were measured via automated capillary-based immunoassay platform in the serum of 65 advanced cancer patients treated with anti-PD-1/PD-L1-based systemic therapy and 10 healthy volunteers. The levels of cytokines and CCR were quantified and categorized into high and low groups based on the median value. The associations of serum cytokines and CCR with response to treatment, survival, and immune-related adverse events were assessed. RESULTS: Elevated circulating levels of 6 cytokines (PD-L1, CXCL10, HGF, CCL2, MIG, and IL-6) were observed in cancer patients compared with that in healthy volunteers. The correlation coefficients between cytokines, CCR and nutritional risk index were also calculated. In the cancer cohort (N = 65), low circulating HGF (P = 0.023, P = 0.029), low IL-6 (P = 0.002, P < 0.001), and high CCR (P = 0.031, P = 0.008) were associated with significantly improved progression-free survival (PFS) and overall survival (OS). Multi-variable COX analyses adjusted for clinicopathological factors revealed that low HGF, low IL-6, and high CCR were independent favorable prognostic factors for PFS (P = 0.028, P = 0.010, and P = 0.015, respectively) and OS (P = 0.043, P = 0.003, and P = 0.026, respectively). Grade 2 irAEs occurred more frequently in patients with low levels of circulating CCL2 and LAG3. CONCLUSIONS: Pre-treatment circulating levels of serum IL-6, HGF, and CCR may serve as independent predictive and prognostic biomarkers in advanced cancer patients treated with ICIs-based systemic therapy. These findings might help to identify potential patients who would benefit from these therapies.

The Association between Serum Creatinine/Cystatin C Ratio and Cardiovascular Morbidity and Mortality: Insights from NHANES.

Background: The Serum creatinine/cystatin C ratio (Cr/CysC ratio) is an emerging alternative index for muscle mass loss, a risk factor for cardiovascular diseases (CVDs). However, the association between the Cr/CysC ratio and CVD morbidity and mortality remains unknown. Methods: A total of 11,150 participants of the National Health and Nutrition Examination Survey (NHANES) were included in this study. Univariable and multivariable logistic regression models were employed to assess the association between the Cr/CysC ratio and self-reported CVD morbidity. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of the Cr/CysC ratio for CVD mortality. Results: At baseline, 1181 (7.90%) participants had self-reported CVDs. Lower Cr/CysC ratios were found in participants with CVDs (1.18 ± 0.30 vs. 1.05 ± 0.23, p < 0.001). In the multivariable logistic regression model, the Cr/CysC ratio was inversely linked to CVD morbidity (odds ratio: 0.65, 95% CI: 0.52-0.81, p < 0.001, per standard deviation [SD] increase). 997 (8.94%) CVD deaths were documented during a median follow-up of 16.9 years. A higher Cr/CysC ratio was associated with a decreasing risk of CVD mortality (adjusted HR: 0.54, 95% CI: 0.46-0.65, p < 0.001, per SD increase). Conclusions: In NHANES participants, the Cr/CysC ratio had an inverse correlation with CVD morbidity and mortality.

Serum Creatinine/Cystatin C Ratio as a Predictor of In-hospital Mortality in Patients Hospitalized with Acute Exacerbation of Chronic Obstructive Pulmonary Disease.

PURPOSE: Low serum creatinine/cystatin C ratio (CCR) is associated with unfavorable characteristics in patients with chronic obstructive pulmonary disease (COPD); however, the relationship between CCR and in-hospital mortality of patients with acute exacerbation of COPD (AECOPD) is unexplored. Our objective was to assess the value of CCR for predicting in-hospital mortality of patients hospitalized with AECOPD. METHODS: Patients with AECOPD (n = 597) were retrospectively enrolled. Patient's clinical characteristics and laboratory tests, including serum cystatin C and creatinine, were reviewed. The prediction value of CCR was evaluated using area under the receiver operating characteristic curve (AUC) values. Factors potentially impacting in-hospital mortality were investigated using univariate and multivariate logistic regression analyses. RESULTS: Mortality rate during hospitalization was 10.05%. CCR was lower in non-surviving vs. survived patients (41.67 vs. 61.52, P < 0.001). AUC value for CCR for in-hospital mortality prediction was 0.79 [95% confidence interval (CI) 0.73-0.85]. On multivariate logistic regression analysis, in-hospital mortality was strongly associated with CCR < 52.27 [odds ratio (OR) 6.23, 95% CI (3.00-12.92), P < 0.001], age ≥ 81 years [OR 2.97, 95% CI (1.20-7.37), P = 0.019], oxygenation index < 300 [OR 3.28, 95% CI (1.27-8.44), P = 0.014], CRP > 8 mg/L [OR 1.84, 95% CI (1.15-2.95), P = 0.012], and D-dimer > 500 ng/L [OR 5.19, 95% CI (1.51-17.79), P = 0.009]. CONCLUSIONS: CCR was significantly lower, and is a potential prognostic indicator, in patients with AECOPD who died during hospitalization.

Utility of serum creatinine/cystatin C ratio in diagnosis of postrenal acute kidney injury.

BACKGROUND: In obstructive uropathy, despite a severe increase in the serum creatinine (Cr) levels, only a mild cystatin C (CysC) increase was previously reported. Therefore, we aimed to determine the availability of serum Cr/CysC ratio in predicting postrenal acute kidney injury (AKI). MATERIALS AND METHODS: This was a cross-sectional study involving 61-adult patients with heterogeneous AKI cases. Patients with bilateral pelvicalyceal dilatation in renal sonography were considered as postrenal AKI group (n = 15) and others were intrinsic AKI group (n = 46). Venous blood sampling for blood urea nitrogen, Cr and CysC measurements were performed on admission. RESULTS: The mean age of study population was 66.3 ± 15.5 years; 38 (62%) of which were male. Two groups were similar regarding age, gender, and comorbidities. Cr/CysC ratio was significantly higher in postrenal AKI group (6.9 ± 3.1 vs. 4.4 ± 2.1, P = 0.007). CONCLUSION: We suggest that serum Cr/CysC ratio seems to be a useful diagnostic tool for detection of postrenal AKI cases, especially for the cases without definite hydronephrosis.

The coexistence of myosteatosis and the creatinine/cystatin C ratio are determinants of outcomes in cholangiocarcinoma patients undergoing curative surgery.

Background: Myosteatosis is a well-established predictor of poor prognosis in many types of cancer, and a decreased Creatinine/Cystatin C ratio (CCR) is a known indicator of unfavorable outcomes in patients with metabolic disorders and cancer. Despite this knowledge, the significance of concurrent CCR and myosteatosis in predicting the prognosis of patients with cholangiocarcinoma (CCA) who undergo radical surgery remains uncertain. Method: Data from 757 patients with cholangiocarcinoma who underwent the first radical resection in the Affiliated Hospital of Qingdao University from January 2017 to March 2022 were collected. According to the inclusion and exclusion criteria, 149 patients were finally included in the retrospective study cohort. Various clinicopathological, serological, and radiological data were collected at admission. Myosteatosis was evaluated using sliceOmatic software on computed tomography (CT) images. The study used receiver operating characteristic (ROC) curve analysis to determine the critical value of CCR, which predicts overall survival (OS) based on the Kaplan-Meier method. Univariate and multivariate Cox regression analyses were employed to identify the risk factors associated with OS and RFS confidently. Results: The group identified as the myosteatosis cohort consisted of 79 patients with an average age of 64.3 ± 7.8 years. The ROC curve analysis revealed an optimal critical CCR value of 10.834. A low CCR ≤ 10.834 and myosteatosis were found to be associated with poor OS and RFS outcomes (P = 0.022; P = 0.017; P = 0.038; P = 0.030 respectively). Moreover, patients with myosteatosis and a CCR ≤ 10.834 had the worst OS and RFS outcomes (P = 0.035; P = 0.027). Conclusion: After radical excision in CCA patients, the presence of myosteatosis and CCR had a negative correlation with prognosis. A more accurate prediction of OS and RFS was possible by combining CCR and myosteatosis, compared to CCR alone.

Multidimensional Assessment of Sarcopenia and Sarcopenic Obesity in Geriatric Patients: Creatinine/Cystatin C Ratio Performs Better than Sarcopenia Index.

The serum creatinine/cystatin C ratio (CCR) and the sarcopenia index (SI) are novel indicators for sarcopenia, but their accuracy may depend on various confounders. To assess CCR and SI diagnostic accuracy, we studied the clinical and biophysical parameters associated with sarcopenia or sarcopenic obesity. A total of 79 elderly patients (65-99 yrs, 33 females) underwent clinical, anthropometric, body composition, geriatric performance, and blood chemistry evaluation. The CCR and SI accuracy were assessed to identify sarcopenia. Sarcopenia was confirmed in 40.5%, and sarcopenic obesity in 8.9% of the subjects. Sarcopenic patients showed an increased Charlson comorbidity index, cardiovascular disease (CVD) rates and frailty, and decreased physical performance than non-sarcopenic subjects. Patients with sarcopenic obesity had increased body fat and inflammatory markers compared to obese subjects without sarcopenia. Sarcopenia was associated with a decreased CCR and SI. However, when the logistic regression models were adjusted for possible confounders (i.e., age, gender, Charlson comorbidity index, presence of CVD, and frailty score), a significant OR was confirmed for the CCR (OR 0.021, 95% CI 0.00055-0.83) but not for the SI. The AUC for the CCR for sarcopenia discrimination was 0.72. A higher performance was observed in patients without chronic kidney diseases (CKD, AUC 0.83). CCR, more than the SI, is a useful, non-invasive, and cost-effective tool to predict sarcopenia, irrespective of the potential confounders, particularly in subjects without CKD.

Usefulness of the serum creatinine/cystatin C ratio as a blood biomarker for sarcopenia components among age groups in community-dwelling older people: The SONIC study.

AIM: The serum creatinine/cystatin C ratio (CCR) or sarcopenia index is considered a useful marker of muscle mass. However, its usefulness in late-stage older adults remains unclear. We aimed to determine the usefulness of CCR as an indicator of sarcopenia in community-dwelling Japanese adults aged >75 years. METHODS: Our study recruited participants aged 70, 80, and 90 ± 1 years during the baseline years, and included a 3-year follow-up in the Septuagenarians, Octogenarians, Nonagenarians, Investigation with Centenarians study. From 2015 to 2018, 955 participants were eligible: 367 in their 70s, 304 in their 80s, and 284 in their 90s. The diagnostic components of sarcopenia, including "low muscle mass, plus low muscle strength, and/or low physical performance," were evaluated using the bioelectrical impedance analysis-measured skeletal muscle mass index (SMI), handgrip strength, and short physical performance battery (SPPB) score, respectively, in accordance with the Asia Working Group for Sarcopenia 2019 criteria. Separate analyses were performed between each component and CCR, adjusting for sex, body mass index, and other blood biomarkers in each group. RESULTS: The relationship between CCR and sarcopenia components was significant for handgrip strength (ß = 0.21, 0.13, 0.19, and P < 0.0001, =0.0088, <0.0001, for the 70s, 80s, and 90s age groups, respectively); however, it was limited for SMI (ß = 0.14; P = 0.0022, only for the 90s) and not significant for the SPPB score. CONCLUSION: CCR is a limited indicator of sarcopenia in late-stage older adults. Although its association with muscle strength was significant, its relationship with muscle mass and physical performance was less pronounced. Geriatr Gerontol Int 2024; 24: 529-536.

Clinical implications and predictive value of the creatinine­cystatin C ratio in patients with multiple myeloma and renal impairment.

The creatinine (Cr)-cystatin C ratio (CCR) at the time of cancer diagnosis is associated with survival; however, to the best of our knowledge, the association between this ratio and mortality in patients with multiple myeloma and renal impairment (RI) is unclear. Therefore, the present study aimed to assess this association, as well as disease prognosis and the clinical significance of the CCR in patients with multiple myeloma and RI. The present retrospective study included 191 patients diagnosed with multiple myeloma and RI between 2012 and 2022. The predictive value of the CCR was evaluated using area under the receiver operating characteristic curve (AUC) values. The factors affecting overall survival (OS) were assessed using uni- and multivariate logistic regression analyses. The effect of the CCR on survival was evaluated using a Cox regression model and the Kaplan-Meier method. There was a significant association between low CCR and poor progression-free survival (PFS) and overall survival (OS). The 1-, 2- and 3-year PFS and OS rates in patients with a low CCR were significantly lower than those in patients with a high CCR. The 1-, 2- and 3-year AUC values of the CCR were 0.712, 0.764 and 0.746 respectively. Multivariate analysis revealed sex, age, Cr levels, CCR and C-reactive protein levels as independent prognostic factors affecting OS rates. The CCR is a potential prognostic indicator in patients with multiple myeloma with RI and is associated with clinical stages.

Muscle-origin creatinine-cystatin C ratio is an osteoporosis marker in individuals with normal renal function: evidence from observational and Mendelian randomization analysis.

Background: Creatinine-cystatin C ratio (CCR) has been demonstrated as an objective marker of sarcopenia in clinical conditions but has not been evaluated as an osteoporosis marker in individuals with normal renal function. Methods: We selected 271,831 participants with normal renal function from UK Biobank cohort. Multivariable linear/logistic regression and Cox proportional hazards model were used to investigate the phenotypic relationship between CCR and osteoporosis in total subjects and gender-stratified subjects. Based on the genome-wide association study (GWAS) data, linkage disequilibrium regression (LDSC) and Mendelian randomization (MR) analysis were performed to reveal the shared genetic correlations and infer the causal effects, respectively. Results: Amongst total subjects and gender-stratified subjects, serum CCR was positively associated with eBMD after adjusting for potential risk factors (all P<0.05). The multivariable logistic regression model showed that the decrease in CCR was associated with a higher risk of osteoporosis/fracture in all models (all P<0.05). In the multivariable Cox regression analysis with adjustment for potential confounders, reduced CCR is associated with the incidence of osteoporosis and fracture in both total subjects and gender-stratified subjects (all P<0.05). A significant non-linear dose-response was observed between CCR and osteoporosis/fracture risk (P non-linearity < 0.05). LDSC found no significant shared genetic effects by them, but PLACO identified 42 pleiotropic SNPs shared by CCR and fracture (P<5×10-8). MR analyses indicated the causal effect from CCR to osteoporosis/fracture. Conclusions: Reduced CCR predicted increased risks of osteoporosis/fracture, and significant causal effects support their associations. These findings indicated that the muscle-origin serum CCR was a potential biomarker to assess the risks of osteoporosis and fracture.

Serum creatinine/cystatin C ratio as a prognostic indicator for patients with colorectal cancer.

Background: This study aimed to explore the relationship between creatinine/cystatin C ratio and progression-free survival (PFS) and overall survival (OS) in colorectal cancer (CRC) patients undergoing surgical treatment. Methods: A retrospective analysis was conducted on 975 CRC patients who underwent surgical resection from January 2012 to 2015. Restricted three-sample curve to display the non-linear relationship between PFS/OS and creatinine-cystatin C ratio. Cox regression model and Kaplan-Meier method were used to evaluate the effect of the creatinine-cystatin C ratio on the survival of CRC patients. Prognostic variables with p-value ≤0.05 in multivariate analysis were used to construct prognostic nomograms. The receiver operator characteristic curve was used to compare the efficacy of prognostic nomograms and the traditional pathological stage. Results: There was a negative linear relationship between creatinine/cystatin C ratio and adverse PFS in CRC patients. Patients with low creatinine/cystatin C ratio had significantly lower PFS/OS than those with high creatinine/cystatin C ratio (PFS, 50.8% vs. 63.9%, p = 0.002; OS, 52.5% vs. 68.9%, p < 0.001). Multivariate analysis showed that low creatinine/cystatin C ratio was an independent risk factor for PFS (HR=1.286, 95%CI = 1.007-1.642, p=0.044) and OS (HR=1.410, 95%CI=1.087-1.829, p=0.010) of CRC patients. The creatinine/cystatin C ratio-based prognostic nomograms have good predictive performance, with a concordance index above 0.7, which can predict the 1-5-year prognosis. Conclusion: Creatinine/cystatin C ratio may be an effective prognostic marker for predicting PFS and OS in CRC patients, aid in pathological staging, and along with tumour markers help in-depth prognostic stratification in CRC patients.

Serum creatinine/cystatin C ratio as a muscle mass evaluating tool and prognostic indicator for hospitalized patients: A meta-analysis.

Objective: Sarcopenia is a syndrome of decreased muscle mass and deficits in muscle strength and physical function. We aimed to investigate the relationship between creatinine/cystatin C ratio (CCR) and sarcopenia and the prognostic value of CCR in hospitalized patients. Materials and methods: We searched for relevant studies in PubMed, EMBASE, and the Cochrane Database up to August 25, 2022. Meta-analyses were performed to evaluate the relationship between CCR and skeletal muscle [computed tomography-assessed skeletal muscle (CTASM), muscle strength, and physical performance], prognosis and important clinical outcomes in hospitalized adults. The pooled correlation coefficient, the area under the receiver operating characteristic (ROC) curves, and hazard ratio (HR) together with their 95% confidence intervals (CIs) were calculated. We also conducted subgroup analyses to explore the sources of heterogeneity. Results: A total of 38 studies with 20,362 patients were eligible. These studies were of moderate to high quality. Our results showed that CCR was significant correlations with all CTASM types (Fisher's Z ranged from 0.35 to 0.5; P values ranged from < 0.01 to 0.01), handgrip strength (Fisher's Z = 0.39; 95% CI, 0.32-0.45; P < 0.001) and gait speed (Fisher's Z = 0.25; 95% CI, 0.21-0.30; P < 0.001). The ROC curves suggested that CCR had good diagnostic efficacy (0.689; 95% CI, 0.632-0.746; P < 0.01) for sarcopenia. CCR can reliably predict mortality in hospitalized patients, which was confirmed by regression analysis of CCR as both continuous (HR 0.78; 95% CI, 0.72-0.84; P < 0.01) and categorical variables (HR 2.05; 95% CI, 1.58-2.66; P < 0.0001). In addition, less evidence showed that higher CCR was independently associated with a shorter duration of mechanical ventilation, reduced length of stay in the intensive care unit and hospital, less nutritional risk, and decreased complications in hospitalized patients. Conclusion: CCR could be a simple, economical, and effective screening tool for sarcopenia in hospitalized patients, and it is a helpful prognostic factor for mortality and other important clinical outcomes. Systematic review registration: https://inplasy.com/inplasy-2022-9-0097/, identifier INPLASY202290097.

Changes in Mortality According to Creatinine/Cystatin C Ratio in Chronic Kidney Disease and Non-chronic Kidney Disease Patients.

Background: Serum creatinine and cystatin C are not only good indicators of renal function but have also been confirmed to be related to disease prognosis and mortality in various diseases via creatinine/cystatin C ratio (CCR). However, although they are biomarkers of renal function, there is no study regarding renal impairment as a confounding variable in the relationship between CCR and all-cause mortality. Methods: Patients who had simultaneous measurements of serum creatinine and cystatin C between 2003 and 2020 were enrolled. The patients with chronic kidney disease (CKD) were defined as having an estimated glomerular filtration rate (eGFR) CKD-EPI Cr-Cystatin C < 60 ml/min/1.73 m2. CCR was calculated by dividing the serum creatinine level by the cystatin C level measured on the same day. The main outcome assessed was all-cause mortality according to CCR in CKD or non-CKD groups. Results: Among the 8,680 patients in whom creatinine and cystatin C levels were measured simultaneously, 4,301 were included in the CKD group, and 4,379 were included in the non-CKD group, respectively. CCR was 1.4 ± 0.6 in total participants. The non-CKD group showed higher mean CCR, (1.5 ± 0.7 vs. 1.3 ± 0.5) as well as a wider distribution of CCR (p < 0.001) when compared to the CKD group. In non-CKD group, 1st, 4th and 5th quintiles of CCR significantly increased the all-cause mortality risk compared to 2nd quintile of CCR, suggesting U-shaped mortality risk according to CCR in non-CKD. On the other hand, in CKD group, the risk of all-cause mortality linearly increased and 5th quintile of CCR showed 1.82 times risk of mortality compared to 2nd quintile of CCR. In the subgroup analysis of mortality by age and sex, the mortality difference according to CCR were diminished in old age and female sex subgroups. Conclusion: We discovered a U-shaped relationship between mortality and CCR levels in normal renal function, and an increased risk of mortality in CKD with elevated CCR.

Serum creatinine to cystatin C ratio and clinical outcomes in adults with non-dialysis chronic kidney disease.

Background: Studies have suggested that the serum creatinine/cystatin C (Cr/CysC) ratio is a surrogate marker for muscle wasting is associated with adverse outcomes in several disease conditions. To clarify the utility of the Cr/CysC ratio as a prognostic marker in chronic kidney disease (CKD) we evaluated the association between the Cr/CysC ratio clinical outcomes in patients with non-dialysis CKD. Methods: This prospective observational cohort study included 1,966 participants of the KoreaN cohort study Outcomes in patients With CKD (KNOW-CKD). We evaluated associated factors with the serum Cr/CysC ratio and association between the serum Cr/CysC ratio and composite outcomes of all-cause death and cardiovascular events (CVEs). Results: The mean age was 54 ± 12 (SD) years and 61% were men. The mean serum Cr/CysC ratio was 10.97 ± 1.94 in men and 9.10 ± 1.77 in women. The Cr/CysC ratio correlated positively with urinary creatinine excretion, a marker of muscle mass. In the fully adjusted Cox proportional hazard model, the Cr/CysC ratio was associated with the occurrence of adverse outcomes through a median follow-up of 5.9 years [hazard ratio (HR) = 0.92, 95% confidence interval (CI) = 0.85-0.99 for the composite outcomes, HR = 0.87, 95% CI, 0.78 - 0.97 for all-cause death, and HR = 0.93; 95% CI, 0.84-1.04 for CVEs]. In subgroup analyses, there were interactions of the Cr/CysC ratio with age and sex for risk of the clinical outcomes, but not eGFR group. Conclusion: A higher Cr/CysC ratio is associated with a lower risk of the composite outcomes, especially all-cause mortality, even after adjusting for eGFR. These suggest that the Cr/CysC ratio is a useful prognostic marker in CKD.

Diagnostic and prognostic value of the Creatinine/Cystatin C ratio for low muscle mass evaluation among US adults.

Background: Identifying patients with low muscle mass is crucial for the diagnosis of sarcopenia. Although the Creatinine/Cystatin C (Cr/CysC) is recommended as a simplified indicator to identify patients with low muscle mass, its ability to assess muscle mass and predict a poor prognosis has not been validated. We aimed to determine the diagnosis value of Cr/CysC for low muscle mass and examine the association of Cr/CysC with mortality. Methods: In this cohort study we analyzed data from the National Health and Nutrition Examination Survey from 1999 to 2002. Follow-up was conducted up to December, 2015. Appendicular skeletal mass was calculated based on dual-energy X-ray absorptiometry (DXA) scans. Low muscle mass was defined referring to five international diagnostic criteria. The diagnostic value of Cr/CysC as a replacement indicator of muscle mass was measured using area under the curve, positive percent agreement, negative percent agreement and kappa. Cox proportional hazards regression models were developed to examine the association between Cr/CysC and risk of mortality. Results: This cohort study of 3,741 adults comprised 1,823 females (48.73%), with a weighted mean (SE) age of 44.46 (0.43) years. The positive percent agreement of Cr/CysC for the diagnosis of low muscle mass was poor (40.23-58.74%), except for Foundation of the National Institute of Health (FNIH) criteria (80.90-58.97%). But the negative percent agreement of Cr/CysC for the diagnosis of low muscle mass was high (males: 62.15-88.17%; females: 55.26-82.30%). Moreover, the risk of death was reduced by 2% per 0.01 unit increase in Cr/CysC (aHR, 0.98; 95% CI, 0.98-0.99, P < 0.001). Conclusions: Cr/CysC performed well not only in identifying non-sarcopenia cases, especially when based on FNIH diagnostic criteria, but also in revealing a positive association with higher risk of mortality. The optimal cut-off values for Cr/CysC were <1.0 in males and <0.8 in females. Expanding the use of Cr/CysC would allow for early and targeted treatment of sarcopenia.

Relationship of creatinine cystatin C ratio with muscle mass and grip strength in memory clinic outpatients.

OBJECTIVES: The purpose of this study was to examine the relationship of the serum creatinine/cystatin C ratio (CCR) with hand grip strength (HGS), total body muscle mass, trunk muscle mass, and skeletal muscle mass index (SMI) in patients attending a memory clinic. DESIGN: This cross-sectional study enrolled outpatients of a memory clinic in Japan from October 2010 to July 2017. SETTING AND PARTICIPANTS: We enrolled 1945 participants aged 60 years or older with measured skeletal muscle mass, HGS, and serum creatinine and serum cystatin C levels. MEASURES: Linear multiple regression analysis was performed for men and women using total body muscle mass, trunk muscle mass, and SMI as objective variables. The exposure variables were selected from previous reports if they were strongly linked to muscle mass. Total body muscle mass and trunk muscle mass were corrected by dividing by body weight. Multiple regression analysis was also conducted for men and women using HGS as an objective variable. Because cognitive function and HGS are strongly related, we also conducted sensitivity analysis by excluding participants with a Mini-Mental State Examination score < 24 to alleviate any concern that we did not fully adjust for the effect of cognitive dysfunction. RESULTS: In men, CCR was significantly associated with total body muscle mass, trunk muscle mass, and SMI (P = 0.013, P = 0.008, and P < 0.001, respectively). In women, CCR was significantly associated with total body muscle mass and trunk muscle mass (P = 0.013 and P < 0.001, respectively), but not with SMI (P = 0.932). On the other hand, CCR was significantly associated with grip strength in both men and women (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: CCR was associated with both muscle mass and muscle strength. This study suggests that CCR is a useful marker not only for muscle mass but also for muscle strength.