The correlation between serum growth differentiation factor 15 and malnutrition in patients with end-stage kidney disease on hemodialysis.

OBJECTIVE: Malnutrition commonly occurs in patients undergoing maintenance hemodialysis. Early detection of malnutrition could allow early interventions to prevent later complications. At present, there are not many biomarkers with high predictive value of end-stage kidney disease (ESKD)-related malnutrition, especially for early malnutrition in hemodialysis patients, which needs more in-depth research. Therefore, we performed a cross-sectional study on 97 patients to identify biomarkers for malnutrition in hemodialysis patients. RESEARCH METHODS & PROCEDURES: 7-point subjective global assessment (SGA) was applied to evaluate the nutritional status of patients on hemodialysis. Serum levels of growth differentiation factor 15 (GDF15), albumin, pre-albumin, c-reactive protein (CRP), tumor necrosis factor alpha (TNF-α), hemoglobin, low density lipoprotein-cholesterol, and high density lipoprotein-cholesterol were detected before hemodialysis. Logistic analysis and linear regression were used to analyze the association between GDF15 levels and the SGA score after adjustment for basic characteristics and laboratory findings. RESULTS: Among the 97 patients on hemodialysis, 51 had malnutrition (SGA < 6). There was no difference between the malnourished and well nourished (SGA ≥ 6) groups for dialysis duration, cholesterol, CRP, TNF-α, and hemoglobin. The malnutrition group had significantly lower grip strength (p < 0.05). GDF15 levels correlated negatively with the SGA score after adjustment for possible confounding factors [rho (male) = -0.312, rho(female)= -0.437;P(male) = 0.0181, P(female) = 0.005], and might contribute to the malnutritional status, the AUCs of GDF15 for malnutrition was 0.697 (p = 0.011) in male and 0.828 (p < 0.001) in female. CONCLUSIONS: GDF15 is associated with malnutrition according to the SGA score in patients with ESKD on hemodialysis, suggesting that GDF15 might be involved in the pathogenesis of malnutrition patients with ESKD in this setting. Furthermore, GDF15 is likely to be a potential diagnostic biomarker for malnutrition according to the SGA score.

Mediating effect of gait speed on the relationship between ankle-brachial index and mild cognitive impairment in hemodialysis patients.

BACKGROUND: Patients undergoing hemodialysis are highly predisposed to arterial disease, poor physical performance, and cognitive impairment. However, the connection between them is not yet known. We aimed to investigate the mediating effect of physical performance on the relationship between arterial stiffness and mild cognitive impairment (MCI). METHODS: We conducted a multicenter cross-sectional study. The final analyzed hemodialysis patients comprised 616 subjects (men 391, women 225) from seven dialysis units in Shanghai, China. MCI was assessed by Mini-Mental State Examination (MMSE) and the Instrumental Activities of Daily Living (IADL) scale. Arterial function was measured by ankle-brachial index (ABI) and branchial-ankle pulse-wave velocity (baPWV). Physical function was assessed by the Short Physical Performance Battery (SPPB). Logistic regression and mediation model were used to analysis. RESULTS: The mean age of the final analysis sample (n = 616) was 59.0 ± 12.0 years. Hemodialysis patients with MCI were more likely to have lower ABI (p < 0.001) and higher baPWV (p < 0.01). After adjusting for covariates, lower ABI (abnormal ≤0.9 and borderline 0.91-0.99) were positively associated with MCI (OR = 4.43, 95% CI = 1.89-10.39; OR = 4.83, 95% CI = 1.61-14.46). SPPB total score and its components standing balance, gait speed score were negatively associated with MCI. In the mediational model, gait speed played a mediating role (indirect effect ab = -0.21; 95% CI = -0.58 to -0.03) in the association of ABI (≤0.9) and MMSE, while standing balance and chair stands did not. CONCLUSIONS: Lower gait speed mediates a positive association between ABI and MCI in hemodialysis patients. Suitable interventions for physical performance, especially gait speed, may reduce the risk of MCI in hemodialysis patients.

Development and validation of a diagnostic nomogram for sarcopenia in Chinese hemodialysis patients.

BACKGROUND: Sarcopenia is a clinical condition that is common in patients with chronic kidney disease (CKD), especially in those on dialysis. However, the relatively complicated diagnostic procedure limits its use in clinical situations. In this study we aimed to establish a simplified tool for the diagnosis of sarcopenia in patients on hemodialysis (HD). METHODS: Overall, 757 eligible patients from seven HD centers in Shanghai and Suzhou, China, were recruited from 2020 to 2021. The cross-sectional data were analyzed. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 criteria. Among them, 511 consecutive patients (77 with and 434 without sarcopenia) from five centers were included in the training set for the establishment of a diagnostic nomogram. Ten investigative parameters including clinical characteristics, body measurements and physical performance were used to derive the diagnostic nomogram. A total of 246 consecutive patients (47 with and 199 without sarcopenia) were included for validation of the diagnostic model. RESULTS: The average age of the enrolled patients was 60.4 ± 12.1 years, 59.8% were males and 90.5% received dialysis using an arteriovenous fistula. Overall, the sarcopenia rate was 16.4%. The training and validation sets showed no significant differences in sarcopenia rate (15.1% and 19.1%, respectively; P = .160). The nomogram derived from the training set for sarcopenia, which was based on only four features-age, sex, body weight and grip strength-achieved high C-indexes of 0.929 [95% confidence interval (CI) 0.904-0.953] and 0.955 (95% CI 0.931-0.979) in the training and external sets, respectively, and had a well-fitted calibration curve. The cut-off value was 0.725, with a sensitivity of 0.909 and a specificity of 0.816. The nomogram accurately diagnosed sarcopenia with fewer variables and more simplified diagnostic procedures. CONCLUSIONS: The nomogram had a good diagnostic capability for sarcopenia in patients on HD and may be a convenient tool for clinical use.

Relationship between chronic periodontitis and inflammatory cytokines in patients undergoing maintenance hemodialysis.

OBJECTIVES: To investigate the correlation between serum and gingival crevicular fluid (GCF) levels of inflammatory cytokines and the association with periodontal parameters in patients with maintenance hemodialysis (MHD) and healthy control. MATERIALS AND METHODS: Patients who were undergoing MHD were enrolled as the MHD group. Healthy individuals who underwent oral examination were selected as the control group after matching for the MHD group. All participants underwent a full-mouth periodontal evaluation, and the levels of eight inflammatory cytokines, including IL-1ß, IL-17, IL-6, IL-8, and tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase-8 (MMP-8), and C-reactive protein (CRP), in the GCF and serum were measured. RESULTS: A total of 63 MHD patients and 75 healthy persons were included. The prevalence of moderate/severe periodontitis was significantly higher in the MHD group than in the control group (88.9 vs. 66.7%, P < 0.05). The GCF levels of CRP, TNF-α, MCP-1, and MMP-8 were higher in patients in the MHD group with moderate/severe periodontitis than in the control group (P < 0.05). Serum CRP, MCP-1, TNF-α, and MMP-8 levels were positively correlated with the GCF CRP levels (P < 0.05). The GCF and serum CRP levels were positively correlated with the periodontal clinical parameters (P < 0.05). CONCLUSIONS: Serum CRP, MCP-1, TNF-α, and MMP-8 may relate with the GCF CRP levels. The GCF and serum CRP levels correlated positively with the periodontal clinical parameters, including the VPI, PPD, and CAL, indicating that CRP may play an important role between periodontitis and ESRD. CLINICAL RELEVANCE: The present study indicated that GCF and serum CRP levels correlated positively with the periodontal clinical parameters, and the CRP levels may be selected as an indicator to evaluate the severity of inflammation and the effectiveness, prognosis of periodontal treatment in ESRD patients.

Periodontal health related-inflammatory and metabolic profiles of patients with end-stage renal disease: potential strategy for predictive, preventive, and personalized medicine.

OBJECTIVES: To compare the periodontal health related-inflammatory and metabolic differences between patients with end-stage renal disease (ESRD) and healthy controls (HC), and to identify potential biomarkers in gingival crevicular fluid (GCF) and serum of ESRD patients for predictive, preventive, and personalized medicine (PPPM). METHODS: Patients with ESRD (ESRD group; n = 52) and healthy controls (HC group; n = 44) were recruited. Clinical periodontal parameters were recorded. The differential metabolites in the GCF and serum were identified by liquid chromatography/mass spectrometry (LC/MS). Inflammatory markers including interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL-8), and C-reactive protein (CRP) were also assessed. RESULTS: In the ESRD group, IL-8 and CRP were significantly higher in GCF, whereas IL-6 and CRP were significantly higher in serum, compared with HC group (all P < 0.05). In the case of GCF, taurine levels were positively correlated with IL-8 levels in both groups (all P < 0.05). In the case of serum, l-phenylalanine and p-hydroxyphenylacetic acid levels were positively correlated with CRP levels in both groups (all P < 0.05). Significant positive correlations were observed between metabolites (including pseudouridine, l-phenylalanine, and p-hydroxyphenylacetic acid) and IL-6 levels only in ESRD group. CONCLUSIONS: IL-8 and CRP are potential inflammatory makers that reflect the periodontal health of ESRD individual, which may be considered the valuable predictive diagnostics in the agreement with PPPM philosophy. Besides, metabolites of taurine in GCF as well as l-phenylalanine and p-hydroxyphenylacetic acid in serum are possible biomarkers correlated with inflammatory markers. All these biomarkers may also be highly recommended as a novel predictive/diagnostic tool for the assessment of inflammatory status from the perspectives of PPPM in view of susceptible population and individual screening.

GFR Estimation Using a Panel of Filtration Markers in Shanghai and Beijing.

RATIONALE & OBJECTIVES: Estimated glomerular filtration rate (eGFR) using creatinine and cystatin C (eGFRcr-cys) may be less accurate compared to measured GFR (mGFR) in China than in North America, Europe, and Australia due to variation across regions in their non-GFR determinants. The non-GFR determinants of ß2-microglobulin (B2M) and ß-trace protein (BTP) differ from those of creatinine and cystatin C. Thus, the average eGFR using all 4 markers (eGFRavg) could be more accurate than eGFRcr-cys in China. STUDY DESIGN: Diagnostic test study. SETTING & PARTICIPANTS: 1,066 participants in Shanghai and Beijing with creatinine and cystatin C and 666 participants with all 4 filtration markers. TESTS COMPARED: Index tests were previously developed equations for eGFR using creatinine, cystatin C, B2M, and BTP and combinations. The reference test was mGFR using plasma clearance of iohexol. We compared the performance of eGFRavg to eGFRcr-cys using the proportion of participants with errors in eGFR >30% of mGFR (1 - P30) and root mean square error (RMSE) of the regression of eGFR on mGFR on the logarithmic scale. We also compared classification and reclassification of mGFR categories using eGFRavg compared to eGFRcr-cys. OUTCOMES: Accuracy was significantly better for eGFRavg (1 - P30 of 10.4% and RMSE of 0.214) compared to eGFRcr-cys (1 - P30 of 13.8% and RMSE of 0.232; P = 0.004 and P = 0.006, respectively). However, improvements in accuracy did not generally translate into significant improvement in classification or reclassification of mGFR categories. LIMITATIONS: Study population may not be generalizable to clinical settings other than large urban medical centers in China. CONCLUSIONS: A panel of endogenous filtration markers including B2M and BTP in addition to creatinine and cystatin C may improve GFR estimation in China. Further study is necessary to determine whether GFR estimation using B2M and BTP can be improved and whether these improvements lead to useful clinical applications.

A Validation Study on eGFR Equations in Chinese Patients With Diabetic or Non-diabetic CKD.

Aims: It remains controversial to choose the optimal equation to estimate glomerular filtration rate (GFR) in chronic kidney disease (CKD) patients with diabetes. Materials and Methods: Two hundred and fifteen diabetic CKD patients and 192 non-diabetic CKD patients were enrolled in this study. Iohexol GFR, serum creatinine (SCr), and Cystatin C(CysC) were measured simultaneously for each patient. SCr- and CysC-based estimated GFR (eGFR) were calculated through eight equations, including three CKD-EPI equations, Revised Lund-Malmö study equation (RLM), CAPA equation, and three Full Age Spectrum (FAS) equations. Bias, precision, and accuracy were compared among eGFR equations with iohexol-GFR serving as measured GFR (mGFR). Independent predictive factors of accuracy were explored using multivariate logistic regression analysis. Results: In the diabetic group, CKD-EPISCr-CysC showed the best performance among three CKD-EPI equations (interquartile range of 13.88 ml/min/1.73 m2 and 30% accuracy of 72.56%). Compared to CKD-EPISCr-CysC, the other five equations did not significantly improve the performance of GFR estimates. Mostly, eGFR equations were less accurate in diabetic group than in non-diabetic group. Significant differences were found in different mGFR range (P < 0.001). The multivariate logistic regression analysis identified that BMI, mGFR, and diabetic kidney disease (DKD) status were independent predictors of accuracy of three equations in diabetic group. HbA1c was a predictor of accuracy of CKD-EPISCr and CKD-EPICysC in diabetic group. Conclusions: This study showed that eGFR equations were less accurate in the diabetic group than in the non-diabetic group. CKD-EPIScr-CysC had the best performance among CKD-EPI equations in Chinese diabetic CKD patients. The other five equations did not significantly improve the performance of GFR estimates. BMI, mGFR, DKD status, and HbA1c were independent factors associated with accuracy in eGFR equations.