RESUMEN
Objective:To investigate the relationship between serum fibroblast growth factor 21 (FGF21) and sarcopenia in hemodialysis (HD) patients, and to explore the relationship between FGF21 and signal pathways related to skeletal muscle metabolism in uremic state at the cellular level.Methods:The data of the HD patients from the blood purification center of the Third Affiliated Hospital of Soochow University were collected in this prospective observational study between January 2018 and December 2019. Serum FGF21 concentration was detected by enzyme-linked immunosorbent assay (ELISA). Meanwhile, the skeletal muscle indexes (SMI) at the fourth thoracic vertebra (T4) and the first lumbar vertebra (L1) were assessed by chest CT. According to the T4 SMI and L1 SMI, the patients were divided into sarcopenia group and non-sarcopenia group. The relationship between serum FGF21 and sarcopenia was analyzed. The C2C12 mouse myoblasts were cultured in vitro, which were intervened with healthy human serum, healthy human serum+different concentrations of FGF21, uremic serum, uremic serum+different concentrations of FGF21. The expressions of muscle ring finger protein-1 (MURF1), muscle atrophy F-box (Atrogin-1), myogenic differentiation (MyoD) and myogenin (MyoG) were detected by Western blotting. Results:A total of 118 HD patients with age of (52.64±15.29) years were enrolled in the study, including 64 males (54.2%) and 54 females (45.8%). The images at T4 and L1 level assessed by chest CT could be acquired from 118 patients and 82 patients, respectively. According to the lowest sex-specific quartile ( P25) of T4 SMI (male < 59.92 cm 2/m 2, female < 46.75 cm 2/m 2) and the lowest sex-specific quartile ( P25) of L1 SMI (male < 29.02 cm 2/m 2, female < 24.50 cm 2/m 2), patients were divided into sarcopenia group and non-sarcopenia group, and there were 29(24.58%) and 20(24.39%) patients in the sarcopenia group, respectively. When the patients were divided into two groups according to the sex-specific lowest quartile of T4 SMI, although the serum FGF21 level in the sarcopenia group was higher than that in the non-sarcopenia group, there was no statistical significance between the two groups [448.52(183.96, 1 684.08) ng/L vs. 273.65 (152.83, 535.54) ng/L, Z=-1.741, P=0.082]. When the patients were divided into two groups according to the sex-specific lowest quartile of L1 SMI, the serum FGF21 level in the sarcopenia group was significantly higher than that in the non-sarcopenia group [460.95(188.91, 1 276.38) ng/L vs. 239.10(133.25, 466.36) ng/L, Z=-2.170, P=0.030]. Binary logistic regression analysis showed that higher serum FGF21 was an independent influencing factor for sarcopenia in HD patients regardless of whether the patients were divided into two groups according to the sex-specific lowest quartile of T4 SMI or the sex-specific lowest quartile of L1 SMI (T4 SMI grouping: OR=4.085, 95% CI 1.778-9.388, P=0.001; L1 SMI grouping: OR=7.327, 95% CI 1.841-29.160, P=0.005). At T4 and L1 levels, the area under the receiver operating characteristic curve of FGF21 in predicting sarcopenia in HD patients was 0.636(95% CI 0.494-0.779, P=0.036) and 0.684(95% CI 0.535-0.833, P=0.018), respectively. Cell experiment showed that compared with the uremic serum group, the expressions of MURF1 and Atrogin-1 in myotube cells were increased, while the expressions of MyoD and MyoG were significantly decreased in uremic serum+FGF21 group (both P < 0.05). Conclusions:Higher serum FGF21 is associated with an increased risk of sarcopenia in HD patients. FGF21 may increase the expression of ubiquitin proteasome system, reduce the synthesis and differentiation of skeletal muscle protein, and promote the occurrence of muscle atrophy in uremic patients
RESUMEN
Objective:To explore the value of quantitative susceptibility mapping (QSM) in evaluating renal injury in patients with early diabetic nephropathy (DN).Methods:From October 2019 to December 2020, 32 patients with early DN were prospectively enrolled in the Third Affiliated Hospital of Soochow University. According to the estimated glomerular filtration rate (eGFR), they were divided into three groups: DN1 (eGFR≥90 ml·min -1·1.73 m -2, 11 cases), DN2 (60-<90 ml·min -1·1.73 m -2, 11 cases) and DN3 (30-<60 ml·min -1·1.73 m -2, 10 cases). At the same time, 32 normal volunteers were recruited as the control group. Both kidneys were scanned by QSM to measure the susceptibility of renal cortex and medulla. Paired samples t-test was used to compare the differences of the susceptibility between left and right kidneys and between cortex and medulla. One-way analysis of variance was performed to compare the differences of corresponding susceptibility values among different groups, and LSD- t was used for the pairwise comparison. Pearson correlation test was performed between the susceptibility value of the medulla and eGFR. The ROC curve was used to analyze the diagnostic efficacy of QSM parameters in the diagnosis of DN and different degrees of severity of DN. Results:The susceptibility values of bilateral renal medulla in normal volunteers and patients with DN were lower than those of renal cortex (all P<0.001). There was no significant difference in the susceptibility value between left and right renal cortex (all P>0.05). There was significant difference in the susceptibility value between left and right medulla (all P<0.05). There was no significant difference in the susceptibility value of bilateral renal cortex among the control group and the DN1－DN3 groups (both P>0.05). The susceptibility values of left renal medulla in control group, DN1, DN2 and DN3 groups were (-4.46±1.16)×10 -2, (-5.96±0.97)×10 -2, (-7.97±1.25)×10 -2, (-9.58±1.45)×10 -2 ppm, of right renal medulla were (-3.70±0.65)×10 -2, (-5.06±1.28)×10 -2, (-7.33±1.46)×10 -2, (-9.09±2.22)×10 -2 ppm, respectively. The overall difference of the susceptibility value of bilateral renal medulla was statistically significant (both P<0.05), and there were significant differences between each two groups (all P<0.05). The linear positive correlation were found between the susceptibility values of renal medulla and the corresponding eGFR (left kidney r=0.732, P<0.001; right kidney r=0.684, P<0.001). The areas under the ROC curve (AUC) of left and right renal medulla susceptibility value in diagnosis of normal and DN were 0.931 and 0.943, of DN1 and DN (2 and 3) were 0.952 and 0.883, of DN (1 and 2) and DN3 were 0.888 and 0.831, respectively. Conclusion:The susceptibility value of QSM quantitative parameter has a certain value in the staging and differential diagnosis of early DN, among which the susceptibility value of renal medulla has higher diagnostic efficiency.