Serum Sclerostin Level Is Negatively Associated with Bone Mineral Density in Hemodialysis Patients.

Background and Objectives: Sclerostin and Dickkopf-1 (DKK1) modulate osteoblastogenesis, but their role in bone loss in hemodialysis (HD) patients is inconclusive. This study investigated relationships among lumbar bone mineral density (BMD), serum sclerostin, and DKK1 in HD patients. Materials and Methods: Blood samples were obtained from 75 HD patients. Dual-energy X-ray absorptiometry measured lumbar BMD of the lumbar vertebrae (L2−L4). Enzyme-linked immunosorbent assay revealed serum sclerostin and DKK1 concentrations. Results: There were 10 (13.3%), 20 (26.7%), and 45 (60%) patients defined as presenting with osteoporosis, osteopenia, or normal BMD, respectively. Age, alkaline phosphatase, urea reduction rate, fractional clearance index for urea, sclerostin level, and percentage of female patients are significantly negatively associated with the lumbar BMD and T-score, while the body mass index and waist circumference significantly positively associated with the lumbar BMD and T-score. Multivariate forward stepwise linear regression analysis indicated that serum sclerostin (ß = −0.546, adjusted R2 change = 0.454; p < 0.001), age (ß = −0.216, adjusted R2 change = 0.041; p = 0.007), and percentage of female HD patients (ß = −0.288, adjusted R2 change = 0.072; p = 0.0018) were significantly negatively associated with lumbar BMD in HD patients. Conclusions: Advanced age, female gender, and serum sclerostin level, but not DKK1, were negatively associated with BMD in HD patients.

Arecoline induces epithelial mesenchymal transition in HK2 cells by upregulating the ERK-mediated signaling pathway.

Arecoline, a component of betel nuts, is a known carcinogen that causes oral cancers among those who chew betel nuts. Betel nut chewing is also associated with an increased risk of chronic kidney disease (CKD), but the role of arecoline in this association is unclear. This in vitro study investigates the effects of arecoline on cultured human kidney (HK2) cells. We observed that arecoline had no effect on cell viability but increased cell migration in a dose-dependent manner. Western blot analysis showed that arecoline treatment caused a dose-dependent decrease in E-cadherin expression and dose-dependent increases in N-cadherin, vimentin, α-SMA, and collagen expression; reverse transcriptase-polymerase chain reaction analysis revealed dose-dependent increases in α-SMA and collagen mRNA. Arecoline treatment upregulated the expression of phosphorylated extracellular signal-regulated kinase through epithelial mesenchymal transition and renal fibrosis in HK2 cells. These findings demonstrate that arecoline plays a role in inducing the epithelial mesenchymal transition and fibrogenesis in renal tubule cells and suggest that arecoline promotes the progression of CKD.

Neutrophil gelatinase-associated lipocalin partly reflects the dynamic changes of renal function among chronic hepatitis C patients receiving direct-acting antivirals.

BACKGROUND: Changes in renal function in chronic hepatitis C (CHC) patients receiving direct-acting antivirals (DAAs) are controversial. The evolution of neutrophil gelatinase-associated lipocalin (NGAL) in these patients remains unclear. METHODS: A total of 232 CHC patients receiving DAA at Dalin Tzu Chi Hospital from May 2016 to February 2019, were enrolled in this retrospective study. Grade 2/3 renal function deterioration, defined as a decrease in eGFR between 10% and 50% from baseline (BL) to 12 weeks after the end of treatment (P12), was investigated for its association with BL characteristics. The changes in renal function and NGAL levels were also analyzed at the SOF-base or nonSOF-base DAA. RESULTS: Sixty-two patients (26.7%) had grade 2/3 renal function deterioration at P12 after DAA therapy. Univariate analysis showed that it was associated with age (P = 0.038). Multivariate analysis indicated that age (OR = 1.033, 95% CI: 1.004-1.064, P = 0.027), sex (male; OR = 2.039, 95% CI: 1.093-3.804, P = 0.025), ACEI/ARB use (OR = 2.493, 95% CI: 1.016-6.119, P = 0.046), and BL NGAL (OR = 1.033, 95% CI: 1.001-1.067, P = 0.046) positively correlated with grade 2/3 renal function deterioration. Furthermore, eGFR was decreased (P = 0.009) and NGAL was increased (P = 0.004) from BL to P12 in CHC patients receiving SOF-based DAA. CONCLUSIONS: Of the CHC patients receiving DAA therapy, 26.7% had grade 2/3 renal function deterioration at P12, and it was associated with older age, gender being male, ACEI/ARB use, and higher BL NGAL levels. In addition, NGAL might be a biomarker of nephrotoxicity at P12 in patients receiving SOF-based DAA.

Increased Serum Leptin Level Predicts Bone Mineral Density in Hemodialysis Patients.

BACKGROUND: Leptin acts through the adipose-bone axis to regulate bone mineral density (BMD). This study evaluated the relationship between BMD and serum leptin levels in patients on hemodialysis. METHODS: In this cross-sectional study including 98 hemodialysis patients, BMD was measured using dual energy X-ray absorptiometry of the lumbar vertebrae (L2-L4), and serum leptin levels were determined using an enzyme immunoassay. RESULTS: There were 25 (25.5%), 13 (13.3%), and 60 (61.2%) patients with osteopenia, osteoporosis, and normal BMD, respectively. Advanced age (P=0.017); decreased body mass index (BMI, P < 0.001); body height (P < 0.001); prehemodialysis body weight (BW, P < 0.001); post-hemodialysis BW (P < 0.001); waist circumference (P < 0.001); and triglyceride (P=0.015), albumin (P=0.004), and leptin levels (P=0.017) were associated with lower lumbar T scores, whereas increased urea reduction rate (URR, P=0.004) and fractional clearance index for urea (Kt/V, P=0.004) were associated with lower lumbar T scores. The multivariable forward stepwise linear regression analysis with adjustment for sex; age; body height; prehemodialysis BW; BMI; waist circumference; logarithmically transformed triglycerides (log-triglycerides), albumin, creatinine, and leptin (log-leptin) levels; URR; and Kt/V indicated that high serum level of log-leptin (R 2 change = 0.184; P < 0.001), increased prehemodialysis BW (R 2 change = 0.325; P=0.008), male sex (R 2 change = 0.048; P=0.001), young age (R 2 change = 0.044; P=0.012), and increased serum albumin level (R 2 change = 0.017; P=0.044) were significantly and independently associated with lumbar BMD. CONCLUSIONS: Advanced age and female sex were associated with poor BMD, whereas increased BW, serum albumin, and leptin levels were positively associated with BMD in patients on hemodialysis.

Negative correlation between leptin serum levels and sarcopenia in hemodialysis patients.

Leptin is an adipokine secreted from adipocytes that mediate lipid metabolism and inflammation. This cross-sectional study evaluated association between serum leptin level and sarcopenia in chronic hemodialysis (HD) patients. Blood samples and measurement of muscle mass, handgrip strength, and gait speed were obtained from 76 chronic HD patients. We grouped participants into sarcopenia and non-sarcopenia groups according to the Asian Working Group for Sarcopenia. Eight (10.5%) of the total participants were in the sarcopenia group. Compared to the non-sarcopenia group, patients in the sarcopenia group were lower in height (P = 0.014), weighed less (P < 0.001), had lower waist circumference (P < 0.001), body mass index (BMI, P < 0.001), body fat mass (P = 0.048), serum triglyceride (P = 0.032), creatinine (P = 0.017), phosphorus (P = 0.015), leptin level (P = 0.001), appendicular skeletal muscle mass (P < 0.001), and handgrip strength (P = 0.043). However, urea reduction rate (URR, P < 0.001) and Kt/V (P < 0.001) were higher. After multivariate stepwise linear regression, lower logarithmically transformed leptin (log-leptin, ß: -0.392, adjusted R2 change = 0.130, P < 0.001), lower URR (ß: -2.491, adjusted R2 change = 0.054, P < 0.001)), lower handgrip strength (ß: -0.243, adjusted R2 change = 0.030, P = 0.013), lower serum phosphorus level (ß: -0.176, adjusted R2 change = 0.023, P = 0.036), and higher Kt/V (ß: 2.878, adjusted R2 change = 0.319, P < 0.001) were the independent predictors of sarcopenia in chronic HD patients. We conclude that low serum leptin level is independently associated with sarcopenia in chronic HD patients. Further studies are needed to establish the casual relationship between circulating leptin levels and uremic sarcopenia.

High serum leptin levels are associated with central arterial stiffness in geriatric patients on hemodialysis.

OBJECTIVE: Central arterial stiffness predicts cardiovascular (CV) mortality in hemodialysis (HD) patients. The aging process transforms lipid distribution and thus alters adipokine secretion. The harmful effects of leptin on CV events may change in the elderly. The purpose of this study was to investigate the relationship between leptin and central arterial stiffness markers through carotid-femoral pulse wave velocity (cfPWV) in geriatric HD patients. MATERIALS AND METHODS: Patients over 65 years old on chronic HD were recruited. Blood samples were collected, and the cfPWV was measured with the SphygmoCor system. The patients with cfPWV values >10 m/s were defined as the high arterial stiffness group. RESULTS: In total, 30 (51.7%) of the 58 geriatric patients on chronic HD in this study were in the high arterial stiffness group. The high arterial stiffness group had higher rates of diabetes mellitus (P = 0.019), hypertension (P = 0.019), and higher systolic blood pressure (P = 0.018), pulse pressure (P = 0.019), body mass index (P = 0.018), serum leptin levels (P = 0.008), and hemoglobin levels (P = 0.040) than those in the low arterial stiffness group. Multivariable forward stepwise linear regression analysis showed logarithmically transformed leptin (log-leptin, ß =0.408, adjusted R 2 change = 0.164; P = 0.001) and diabetes (ß =0.312, adjusted R 2 change = 0.085; P = 0.009) were associated with cfPWV values in geriatric HD patients. Moreover, an increased serum leptin level (odds ratio: 1.053; 95% confidence interval: 1.007-1.100; P = 0.023) was an independent factor for central arterial stiffness among geriatric HD patients after multivariate logistic regression analysis. CONCLUSION: In this study, a higher serum leptin level was correlated with central arterial stiffness in geriatric HD patients.