Urinary Klotho Excretion: A Key Regulator of Sodium Homeostasis in Chronic Kidney Disease Stage 2-4.

BACKGROUND Soluble alpha-klotho (klotho) is considered an important regulator of mineral homeostasis in patients with chronic kidney disease (CKD). Since the mineral transport proteins are located on the apical membrane of renal tubular cells, we hypothesized that urine klotho may also be involved in their homeostasis. We aimed to investigate the associations between serum and urine klotho and their impacts on mineral homeostasis in patients with stage 2 to 4 CKD. MATERIAL AND METHODS Serum, spot urine, and 24-h urine of klotho were measured by using enzyme-linked immunosorbent assay. Fractional excretion of sodium, potassium, calcium, phosphate, magnesium, and klotho were calculated. RESULTS A total of 53 patients with CKD stages 2 to 4 were enrolled in this cross-sectional study. The mean age was 71.1±10.5 years, and 68% were men. Linear regression analysis showed that serum log-transformed klotho was negatively associated with log-transformed fractional excretion of klotho (log-FEKlotho) (ß=-0.085, P=0.02), showing that urinary klotho excretion could negatively regulate serum klotho levels. Moreover, our multivariate stepwise regression showed log-fractional excretion of sodium was positively associated with log-FEKlotho (ß=0.138, P=0.032). This implied urinary klotho excretion positively regulated urinary sodium excretion. CONCLUSIONS Our study showed that urine klotho excretion resulted in decreased serum klotho levels and enhanced urinary sodium excretion in patients with CKD stages 2 to 4. In addition to serum klotho, we found, for the first time, that urine klotho also played a significant role in sodium homeostasis.

The Association between Serum Adiponectin Levels and Endothelial Function in Non-Dialysis-Dependent Chronic Kidney Disease Patients.

Adiponectin is the richest human circulating adipokine with anti-inflammatory, antioxidant, and insulin-sensitizing effects. We evaluated the association between serum adiponectin levels and endothelial function in chronic kidney disease (CKD) patients, obtaining fasting blood samples from 130 non-dialysis CKD subjects. We measured the endothelial function-represented by the vascular reactivity index (VRI)-via non-invasive digital thermal monitoring, and serum adiponectin concentrations by enzyme immunoassay kits. A total of 22 (16.9%), 39 (30.0%), and 69 (53.1%) patients had poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), and good (VRI ≥ 2.0) vascular reactivity. Elevated serum blood urea nitrogen (BUN) level was negatively correlated with VRI values, but serum adiponectin and estimated glomerular filtration rate were positively associated with VRI values by univariate linear regression analysis. After applying multivariate stepwise linear regression analysis adjustment, the significantly positive association of adiponectin (p < 0.001), and the significantly negative association of log-BUN (p = 0.021) with VRI values in CKD subjects remained. In an animal study using in vitro blood-vessel myography, treatment with adiponectin enhancing acetylcholine-mediated vasorelaxation in 5/6 nephrectomy CKD mice. Our study results indicated that adiponectin concentration was positively associated with VRI values and modulated endothelial function in non-dialysis CKD patients.

Empagliflozin Attenuates Vascular Calcification in Mice with Chronic Kidney Disease by Regulating the NFR2/HO-1 Anti-Inflammatory Pathway through AMPK Activation.

Vascular calcification (VC) is associated with increased cardiovascular risks in patients with chronic kidney disease (CKD). Sodium-glucose cotransporter 2 inhibitors, such as empagliflozin, can improve cardiovascular and renal outcomes. We assessed the expression of Runt-related transcription factor 2 (Runx2), interleukin (IL)-1ß, IL-6, AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor (Nrf2), and heme oxygenase 1 (HO-1) in inorganic phosphate-induced VC in mouse vascular smooth muscle cells (VSMCs) to investigate the mechanisms underlying empagliflozin's therapeutic effects. We evaluated biochemical parameters, mean artery pressure (MAP), pulse wave velocity (PWV), transcutaneous glomerular filtration rate (GFR), and histology in an in vivo mouse model with VC induced by an oral high-phosphorus diet following a 5/6 nephrectomy in ApoE-/- mice. Compared to the control group, empagliflozin-treated mice showed significant reductions in blood glucose, MAP, PWV, and calcification, as well as increased calcium and GFR levels. Empagliflozin inhibited osteogenic trans-differentiation by decreasing inflammatory cytokine expression and increasing AMPK, Nrf2, and HO-1 levels. Empagliflozin mitigates high phosphate-induced calcification in mouse VSMCs through the Nrf2/HO-1 anti-inflammatory pathway by activating AMPK. Animal experiments suggested that empagliflozin reduces VC in CKD ApoE-/- mice on a high-phosphate diet.

High intact fibroblast growth factor 23 levels associated with low hemoglobin levels in patients on chronic hemodialysis.

Introduction: A negative association between C-terminal fibroblast growth factor 23 (cFGF23) and hemoglobin (Hb) levels has been reported in patients with predialysis chronic kidney disease. In dialysis patients, the dominant form of serum FGF23 is intact FGF23 (iFGF23); however, its association with the Hb level remains unclear. Therefore, simultaneously monitoring iFGF23 and cFGF23 levels is crucial. In this study, we investigated the associations between both forms of FGF23 (iFGF23 and cFGF23) and renal anemia in chronic hemodialysis (CHD) patients. Methods: We included 166 CHD patients from two hospitals in this cross-sectional, observational study. The primary predictors were serum iFGF23, cFGF23, and iFGF23/cFGF23 levels. The main outcome was the Hb level. Results: Among the CHD patients included, 60.8% were men with a mean age of 59.4 ± 12.7 years. In the crude analysis, iFGF23 and iFGF23/cFGF23 levels showed a significant negative association (-0.27, p = 0.004 and -0.22, p = 0.034, respectively) with the Hb level. Even after adjusting for multiple variables (a parsimonious model), every increment of natural log transformation by 1 for (ln)iFGF23 and ln(iFGF23/cFGF23) levels showed a negative correlation with the Hb level (estimate: -0.27 [95%CI: -0.44, -0.10, p = 0.001]; -0.19 [95%CI: -0.37, -0.01, p = 0.042], respectively), whereas both were positively associated with erythropoietin-stimulating agent (ESA) hyporesponsiveness (odds ratio [OR]: [95%CI: 2.30, 1.26-4.17], p = 0.006; 1.95 [95%CI: 1.08-3.50], p = 0.025). Moreover, these abovementioned associations were more dominant in patients with diabetes who used angiotensin receptor blockers. Discussion: In conclusion, a negative association between serum iFGF23 or iFGF23/cFGF23 level and the Hb level was observed in our CHD patients. Meanwhile, a higher iFGF23 or iFGF23/cFGF23 level may predispose patients to ESA hyporesponsiveness.

Serum Intact Fibroblast Growth Factor 23 Levels Are Negatively Associated with Bone Mineral Density in Chronic Hemodialysis Patients.

(1) Background: Fibroblast growth factor 23 (FGF23) is predominantly secreted from bone and plays an important role in mineral balance in chronic kidney disease. However, the relationship between FGF23 and bone mineral density (BMD) in chronic hemodialysis (CHD) patients remains unclear. (2) Methods: This was a cross-sectional observational study that involved 43 stable outpatients on CHD. A linear regression model was used to determine risk factors for BMD. Measurements included serum hemoglobin, intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23), sclerostin, Dickkopf-1, α-klotho, 1,25-hydroxyvitamin D, intact parathyroid hormone levels and dialysis profiles. (3) Results: Study participants had a mean age of 59.4 ± 12.3 years, and 65% were male. In the multivariable analysis, cFGF23 levels showed no significant associations with the BMD of the lumbar spine (p = 0.387) nor that of the femoral head (p = 0.430). However, iFGF23 levels showed a significant negative association with the BMD of the lumbar spine (p = 0.015) and that of the femoral neck (p = 0.037). (4) Conclusions: Among patients on CHD, higher serum iFGF23 levels, but not serum cFGF23 levels, were associated with lower BMD values of the lumbar spine and femoral neck. However, further research is required to validate our findings.

Juniperus communis extract ameliorates lipopolysaccharide-induced acute kidney injury through the adenosine monophosphate-activated protein kinase pathway.

Septic shock can aggravate organ dysfunction and even lead to death. Juniperus communis (JCo) extract has been experimentally demonstrated to have anti-inflammatory and antioxidant effects. We investigated the anti-inflammatory and antioxidant mechanism of JCo extract in vivo and in vitro. In a lipopolysaccharide (LPS)-induced acute kidney injury rat model, JCo extract improved animal survival, reduced kidney injury scores, suppressed kidney injury molecule-1, and preserved E-cadherin expression from LPS damage, as demonstrated by the immunohistochemistry examinations of the rat kidneys. In LPS-stimulated NRK-52E cells, JCo extract inhibited nuclear factor-κB (NF-κB) and increased adenosine monophosphate-activated protein kinase (AMPK) expression, prompting the activation of the antioxidant nuclear factor erythroid 2-related factor-2/heme oxygenase-1 pathway against oxidative stress. JCo extract ameliorated LPS-induced acute kidney injury by suppressing NF-κB signaling and stimulating the release of tumor necrosis factor-α and interleukin-1ß through the AMPK pathway.

Correlation between Serum 25-Hydroxyvitamin D Level and Peripheral Arterial Stiffness in Chronic Kidney Disease Stage 3-5 Patients.

Vitamin D deficiency and high brachial-ankle pulse wave velocity (baPWV) are each independently associated with higher incidence of mortality and cardiovascular (CV) disease or CV events, respectively. This study aimed to evaluate the relationship between serum 25-hydroxyvitamin D levels and baPWV in non-dialysis patients with stage 3−5 chronic kidney disease (CKD). We enrolled 180 CKD patients. A commercial enzyme-linked immunosorbent assay was used to measure 25-hydroxyvitamin D levels. BaPWV values were measured using an automatic pulse wave analyzer. Either left or right baPWV > 18.0 m/s was considered indicative of peripheral arterial stiffness (PAS). In this study, 73 (40.6%) patients were found to have PAS. Compared to those without PAS (control group), patients with PAS were older and had higher incidence of diabetes mellitus, higher systolic and diastolic blood pressure, higher levels of intact parathyroid hormone, and C-reactive protein, and lower levels of 25-hydroxyvitamin D. Multivariate logistic regression analysis found 25-hydroxyvitamin D levels (odds ratio [OR]: 0.895, 95% confidence interval [CI] 0.828−0.968, p = 0.005) and old age (OR: 1.140, 95% CI 1.088−1.194, p < 0.001) to be independently associated with PAS in patients with stage 3−5 CKD. Lower serum 25-hydroxyvitamin D levels and older age were associated with PAS in these patients.

Dapagliflozin Ameliorates Lipopolysaccharide Related Acute Kidney Injury in Mice with Streptozotocin-induced Diabetes Mellitus.

Sepsis, which is a serious medical condition induced by infection, has been the most common cause of acute kidney injury (AKI) and is associated with high mortality and morbidity. Sodium-glucose cotransporter 2 (SGLT2) inhibitor is a new oral antidiabetic drug that has greatly improved the cardiovascular and renal outcomes in patients with type 2 diabetes independent of its sugar lowering effect, possibly by attenuation of the inflammatory process. We investigated the effect of the SGLT2 inhibitor dapagliflozin on lipopolysaccharide (LPS)-induced endotoxic shock with AKI in streptozotocin-induced diabetic mice. Endotoxin shock with AKI was induced by intravenous injection of 10 mg/kg LPS in C57BL6 mice with streptozotocin-induced diabetic mellitus with or without dapagliflozin treatment. Observation was done for 48 hours thereafter. In addition, NRK-52E cells incubated with LPS or dapagliflozin were evaluated for the possible mechanism. Treatment with dapagliflozin attenuated LPS-induced endotoxic shock associated AKI and decreased the inflammatory cytokines in diabetic mice. In the in vitro study, dapagliflozin decreased the expression of inflammatory cytokines and reactive oxygen species and increased the expressions of AMP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor, and heme oxygenase 1. These results demonstrated that dapagliflozin can attenuate LPS-induced endotoxic shock associated with AKI; this was possibly mediated by activation of the AMPK pathway.

Linagliptin Protects against Endotoxin-Induced Acute Kidney Injury in Rats by Decreasing Inflammatory Cytokines and Reactive Oxygen Species.

Septic shock can increase pro-inflammatory cytokines, reactive oxygen species (ROS), and multiple organ dysfunction syndrome (MODs) and even lead to death. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been proven to exert potential antioxidant and anti-inflammatory effects. We investigated the effects of linagliptin on endotoxic shock and acute kidney injury (AKI) in animal and cell models. In the cell model, linagliptin attenuated ROS by activating the AMP-activated protein kinase (AMPK) pathway, restoring nuclear-factor-erythroid-2-related factor (Nrf2) and heme oxygenase 1 (HO-1) protein, and decreasing pro-inflammatory cytokines (tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß)). In the animal model, 14-week-old conscious Wistar-Kyoto rats were randomly divided into three groups (n = 8 in each group). Endotoxin shock with MODs was induced by the intravenous injection of Klebsiella pneumoniae lipopolysaccharide (LPS, 20 mg/kg). Linagliptin improved animal survival without affecting hemodynamic profiles. In the histopathology and immunohistochemistry examinations of the rat kidneys, linagliptin (10 mg/kg) suppressed nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and inducible nitric oxide synthase (iNOS), decreased injury scores, and preserved E-cadherin expression from LPS damage. In conclusion, linagliptin ameliorated endotoxin-shock-induced AKI by reducing ROS via AMPK pathway activation and suppressing the release of TNF-α and IL-1ß in conscious rats.

High-Serum Angiopoietin-Like Protein 3 Levels Associated with Cardiovascular Outcome in Patients with Coronary Artery Disease.

BACKGROUND: Angiopoietin-like protein 3 (ANGPTL3) plays a pivotal role in lipid metabolism and angiogenesis, and there is growing interest regarding the association between ANGPTL3 and coronary artery disease (CAD). This study aims to investigate whether ANGPTL3 levels can be used to predict the future occurrence of major adverse cardiovascular events (MACEs) in patients with CAD. METHODS: Overall, 90 patients with CAD were enrolled between January and December 2012. The study's primary endpoint was incidence of MACEs. Patient follow-up was completed on June 30, 2017. RESULTS: Following a median follow-up period of 54 months, 33 MACEs had occurred. Patients reporting MACEs had lower statin use (P=0.022) and higher serum C-reactive protein (P < 0.001) and serum ANGPTL3 (P < 0.001) levels than those without MACEs. Kaplan-Meier analysis revealed higher cumulative incidence of CV events in the high ANGPTL3 group (median ANGPTL3 level ≥ 222.37 ng/mL) than in the low ANGPTL3 group (log-rank P=0.046). Multivariable Cox regression analysis demonstrated that ANGPTL3 levels were independently associated with MACEs in patients with CAD (hazard ratio: 1.003; 95% confidence interval: 1.000-1.005; P=0.026) after adjusted for age, gender, and body mass index, classical risk factors, and potential confounders. CONCLUSIONS: Serum ANGPTL3 levels could serve as a biomarker for future occurrence of MACEs in patients with CAD.

Metabolic Syndrome With Aortic Arterial Stiffness And First Hospitalization Or Mortality In Coronary Artery Disease Patients.

PURPOSE: Metabolic syndrome (MetS) and aortic arterial stiffness (AS) are risk factors for future cardiovascular events. We evaluated their roles in first hospitalization or all-cause mortality prediction in coronary artery disease (CAD) patients. PATIENTS AND METHODS: From January to December 2012, 115 CAD patients were enrolled from a single center and followed up for 5.5 years. The composite endpoint included hospitalization for unstable angina, myocardial infarction, revascularization, or heart failure and all-cause mortality. Patients with carotid-femoral pulse wave velocity > 10 m/s (measured using applanation tonometry) constituted the high AS group. RESULTS: During a median 54-month follow-up, there were 43 (37.4%) and 11 (9.6%) hospitalization and mortality events, respectively. Overall, 41 (35.7%) and 70 (60.9%) patients were diagnosed with AS and MetS, respectively. CAD patients with high AS had higher diabetes and MetS percentages, were older, and had higher waist circumference and systolic blood pressure (SBP) but lower glomerular filtration rate than those with low AS. Multivariate logistic regression analysis revealed old age (P < 0.001), diabetes (P = 0.003), and high waist circumference (P = 0.044) and SBP (P = 0.007) as independent predictors of AS in CAD patients. Kaplan-Meier analysis showed that CAD patients with concurrent MetS and high AS had a higher risk for hospitalization (log rank test, P = 0.005) or developing all-cause mortality (log rank test, P = 0.002). Compared with CAD patients without MetS or AS, composite outcome development risk in those with both the conditions was 10.2-fold higher (P < 0.001); this risk was 6.54-fold higher in those with AS alone (P = 0.007). CONCLUSION: In CAD patients, age, diabetes, and high waist circumference and SBP are the independent predictors of AS. Additionally, CAD patients with AS with and without MetS have a high first hospitalization or all-cause mortality development risk.

Specific drug delivery efficiently induced human breast tumor regression using a lipoplex by non-covalent association with anti-tumor antibodies.

BACKGROUND: A cationic liposome-PEG-PEI complex (LPPC) was employed as a carrier for achieving targeted delivery of drug to human epidermal growth factor receptor-2 (HER2/neu)-expressing breast cancer cells. LPPC can be easily loaded with an anti-tumor drug and non-covalently associated with an anti-tumor antibody such as Herceptin that is clinically used to rapidly form immunoparticles within 1 h. RESULTS: Drug-loaded LPPC have an average size about 250 nm and a zeta potential of about 40 mV. Herceptin was complexed onto surface of the LPPC to form the drug/LPPC/Herceptin complexes. The size of curcumin/LPPC/Herceptin complexes were 280 nm and the zeta potentials were about 23 mV. Targeting ability of this delivery system was demonstrated through specific binding on surface of cells and IVIS images in vivo, which showed specific binding in HER2-positive SKBR3 cells as compared to HER2-negative Hs578T cells. Only the drug/LPPC/Herceptin complexes displayed dramatically increased the cytotoxic activity in cancer cells. Both in vitro and in vivo results indicated that Herceptin adsorbed on LPPC directed the immunocomplex towards HER2/neu-positive cells but not HER2/neu-negative cells. The complexes with either component (curcumin or doxorubicin) used in the LPPC-delivery system provided a better therapeutic efficacy compared to the drug treatment alone and other treatment groups, including clinical dosages of Herceptin and LipoDox, in a xenografted model. CONCLUSIONS: LPPC displays important clinical implications by easily introducing a specific targeting characteristic to drugs utilized for breast cancer therapy.

Osteocalcin and carotid-femoral pulse wave velocity in patients on peritoneal dialysis.

OBJECTIVE: Vascular calcification is a cardiovascular risk factor in dialysis patients. Vascular calcification involves a complex process of biomineralization resembling osteogenesis, which leads to arterial stiffness. Osteocalcin is the most abundant noncollagenous protein in the bone matrix. It is synthesized in the bone by osteoblasts and reflects the rate of bone formation. The aim of this study was to evaluate the relationship between serum osteocalcin levels and the carotid-femoral pulse wave velocity (cfPWV) in peritoneal dialysis (PD) patients. MATERIALS AND METHODS: Serum intact osteocalcin and cfPWV were measured in 62 PD patients. Those with CfPWV values >10 m/s were defined as the high central arterial stiffness group, while those with values ≤10 m/s were regarded as the low central arterial stiffness group, according to the European Society of Hypertension and of the European Society of Cardiology guidelines. RESULTS: Seventeen of the 62 PD patients (27.4%) were in the high central arterial stiffness group. The high central arterial stiffness group were older (P = 0.002), had a longer PD vintage (P = 0.018), and had higher serum osteocalcin levels (P = 0.001) than those in the low group. Multivariate logistic regression analysis showed that the osteocalcin level (odds ratio: 1.069, 95% confidence interval (CI): 1.005-1.137, P = 0.035), PD vintage (odds ratio: 1.028, 95% CI: 1.010-1.048, P = 0.003), and age (odds ratio: 1.081, 95% CI: 1.005-1.162, P = 0.035) were independently associated with central arterial stiffness in PD patients. Among these patients, cfPWV (ß: 0.216, P = 0.001) values and log-transformed intact parathyroid hormone (ß: -'0.447, P < 0.001) levels were independently associated with the osteocalcin level in PD patients after multivariate forward stepwise linear regression analysis. CONCLUSION: Older PD patients with a longer PD vintage and higher serum osteocalcin levels had higher central arterial stiffness as measured by cfPWV. The serum osteocalcin level is an independent marker of central arterial stiffness in PD patients.

Serum levels of sclerostin as a potential biomarker in central arterial stiffness among hypertensive patients.

BACKGROUND: Sclerostin is known to be a canonical Wnt/ß-catenin signaling pathway inhibitor, while the Wnt/ß-catenin signaling pathway is proposed to be involved in the development of arterial stiffness. This study aims to investigate the relationship between serum sclerostin levels and carotid-femoral pulse wave velocity (cfPWV) among hypertensive patients. METHODS: Fasting blood samples were obtained from 105 hypertensive patients. Patients with cfPWV values of > 10 m/s were classified in the high arterial stiffness group, whereas those with cfPWV values of ≤10 m/s were assigned to the low arterial stiffness group. Serum sclerostin and Dickkopf-1 (DKK1) levels were quantified using commercially available enzyme-linked immunosorbent assays. RESULTS: Thirty-six hypertensive patients (34.3%) who belonged to the high arterial stiffness group were generally older (p < 0.001), presented with lower estimated glomerular filtration rates (eGFR, p = 0.014), higher incidence of diabetes mellitus (p = 0.030), average systolic blood pressures (SBP, p = 0.013), pulse pressure (p = 0.026), serum creatinine levels (p = 0.013), intact parathyroid hormone levels (iPTH, p = 0.003), and sclerostin levels (p < 0.001) than their counterparts in the low arterial stiffness group. A multivariable logistic regression analysis identified sclerostin as an independent predictor of arterial stiffness in hypertensive patients (odds ratio, 1.042; 95% confidence interval (CI), 1.017-1.068; p = 0.001). Multivariable forward stepwise linear regression analysis also showed that serum sclerostin level (ß = 0.255, adjusted R2 change: 0.146, p = 0.003) was positively associated with cfPWV values in patients with hypertension. CONCLUSIONS: In this study, serum sclerostin level, but not DKK1, is found to be positively correlated with cfPWV values and is identified as an independent predictor of arterial stiffness in hypertensive patients after adjusting for significant confounders.

High Levels of Serum Adipocyte Fatty Acid-binding Protein Predict Cardiovascular Events in Coronary Artery Disease Patients.

Background: Adipocyte fatty acid-binding protein (A-FABP) is a cardiometabolic predictor of cardiovascular (CV) disease in humans. We evaluated the association between serum A-FABP levels and future CV events in patients with coronary artery disease (CAD). Methods: A total of 106 CAD patients were enrolled in this study between January and December 2012 and were followed-up until June 30, 2017. The primary endpoint was the incidence of major adverse CV events. Results: During a median follow-up period of 53 months, 44 CV events occurred. Patients with CV events presented higher systolic blood pressure (p = 0.020), total serum cholesterol (p = 0.047), and serum A-FABP levels (p < 0.001) compared with patients without CV events. Kaplan-Meier analysis showed that the cumulative incidence of CV events in the high A-FABP group (median A-FABP concentration of >17.63 ng/mL) was higher than that in the low A-FABP group (log-rank p < 0.001). Multivariate Cox analysis showed that triglycerides (hazard ratio (HR): 1.008, 95% confidence interval (CI): 1.001-1.016, p = 0.026) and serum A-FABP levels (HR: 1.027, 95% CI: 1.009-1.047, p = 0.004) were independently associated with CV events. Conclusion: Serum A-FABP level is a biomarker for future CV events in patients with CAD. Further prospective studies are needed to confirm the mechanisms underlying this association.

Association between hyperleptinemia and cardiovascular outcomes in patients with coronary artery disease.

PURPOSE: Hyperleptinemia has been independently associated with human cardiovascular (CV) diseases. Accordingly, we evaluate the association between serum leptin and future CV events in patients with coronary artery disease (CAD). PATIENTS AND METHODS: This study enrolled 98 patients with CAD from January to December 2012. The primary endpoint included incidences of major adverse CV events and hospitalization. Patients follow-up had been completed on June 30, 2017. RESULTS: After a median follow-up of 52 months, 43 CV events had occurred. Patients with CV events had higher systolic blood pressure (P = 0.030), total cholesterol (P = 0.034), C-reactive protein (P = 0.018), and serum leptin levels (P = 0.001) than those without CV events. Kaplan-Meier analysis showed greater cumulative incidences of CV events in the high leptin group (median leptin concentration >6.03 ng/mL) than in the low leptin group (log-rank P = 0.012). Multivariate Cox regression analysis showed that triglyceride (HR: 1.010; 95% CI: 1.001-1.018; P = 0.022) and leptin levels (HR: 1.054; 95% CI: 1.026-1.082; P < 0.001) were independently associated with CV events in patients with CAD. CONCLUSION: Serum leptin levels could serve as a biomarker for future CV events in patients with CAD.

Hyperleptinemia is associated with the aortic augmentation index in kidney transplant recipients.

OBJECTIVE: Increased circulating leptin, a marker of leptin resistance, is common in patients with obesity and is also an independent factor in prediction of cardiovascular disease. The aim of this study was to evaluate the relationship between fasting serum leptin levels and the aortic augmentation index (AIx) in kidney transplant recipients. MATERIALS AND METHODS: Fasting blood samples were obtained from 70 kidney transplant recipients. The aortic AIx was measured using a validated tonometry system (SphygmoCor). Plasma leptin levels were measured using a commercial enzyme-linked immunosorbent assay kit. RESULTS: Simple linear analysis of the aortic AIx in kidney transplant recipients showed that body fat mass (P = 0.002), diastolic blood pressure (DBP) (P = 0.020), logarithmically transformed triglycerides (P = 0.035), and leptin (P < 0.001) were positively correlated, while height (P = 0.004) and the glomerular filtration rate (P = 0.022) were negatively correlated with the aortic AIx in kidney transplant recipients. Forward stepwise linear regression analysis of the factors significantly associated with the aortic AIx showed that leptin (P < 0.001), DBP (P = 0.014), and body height (P = 0.036) were independent predictors of the aortic AIx in kidney transplant recipients. CONCLUSION: These results suggest that the serum fasting leptin level is associated with the aortic AIx in kidney transplant recipients.

High serum leptin level is associated with peripheral artery disease in adult peritoneal dialysis patients.

OBJECTIVE: Peripheral artery disease (PAD) is associated with systemic atherosclerosis and indicates an increased risk of mortality in peritoneal dialysis (PD) patients. A high leptin level accelerates atherosclerosis in apoE-deficient mice. The purpose of this study was to examine the association of serum leptin level and PAD in adult PD patients. MATERIALS AND METHODS: The clinical characteristics of sixty PD patients recruited from June 2015 to October 2016 were obtained. Serum leptin concentrations were determined. Ankle-brachial index (ABI) values were measured and those with a left or right ABI <0.9 were defined as the low ABI group. RESULTS: Twenty of these 60 PD patients (33.3%) had diabetes mellitus and 32 patients (53.3%) had hypertension. Thirteen PD patients (21.7%) were in the low ABI group. Higher serum leptin (P = 0.002) and C-reactive protein (CRP, P < 0.001) levels were found in the low ABI group compared with those in the normal ABI group. More number of patients with diabetes (P = 0.015) and current smokers (P = 0.037) were noted in the low ABI group than in the normal ABI group. After adjustment for factors that were significantly associated with PAD in multivariate logistic regression analysis, each increase of 1 ng/mL in the serum leptin level (odds ratio [OR], 1.062; 95% confidence interval [CI], 1.014-1.114; P = 0.012) and each increase of 0.1 mg/dL in the serum CRP level (OR, 1.107; 95% CI, 1.011-1.211; P = 0.028) were found to be independent predictors of PAD in PD patients. CONCLUSION: Higher serum leptin and CRP levels correlated positively with the diagnosis of PAD in PD patients.

Positive correlation of serum leptin levels and peripheral arterial stiffness in patients with type 2 diabetes.

OBJECTIVE: Leptin plays a pathophysiologic role in the pathogenesis of aortic dysfunction and peripheral arterial stiffness (PAS). Our aim was to evaluate the risk factors for developing PAS and the association of leptin and PAS in patients with type 2 diabetes mellitus (DM). MATERIALS AND METHODS: Fasting blood samples were obtained for biochemical data and leptin determinations from 105 patients with type 2 DM. In this study, we applied an automatic pulse wave analyzer (VaSera VS-1000) to measure the brachial-ankle pulse wave velocity (baPWV); a baPWV value >14.0 m/s on either side was considered high PAS. RESULTS: Seventy-five patients (71.4%) had high PAS and they included a higher percentage of patients with hypertension (P < 0.001), older age (P < 0.001), and a higher body fat mass (P = 0.043), systolic blood pressure (P < 0.001), diastolic blood pressure (P = 0.016), serum blood urea nitrogen (P = 0.003), and leptin level (P < 0.001), and lower height (P = 0.027) and glomerular filtration rate (P < 0.001) compared with type 2 DM patients with low PAS. After adjusting for factors significantly associated with PAS in these patients by multivariate logistic regression analysis, age (ß = 0.470, adjusted R2 change = 0.279; P < 0.001), logarithmically transformed leptin (log-leptin, ß = 0.259, adjusted R2 change = 0.085; P = 0.001), and hypertension (ß = 0.197, adjusted R2 change = 0.031; P = 0.011) were significant independent predictors of PAS in type 2 DM patients. CONCLUSION: The serum leptin level could be a predictor of PAS in type 2 DM patients.