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Background There is little information on the pharmacokinetics and pharmacodynamics of sacubitril/valsartan (SV) in patients undergoing peritoneal dialysis (PD) complicated with hypertension or heart failure (HF). This study was designed to evaluate the pharmacokinetics and pharmacodynamics of SV in PD patients with complications of hypertension or HF. Methods This was an open-label and cross-sectional study investigating PD patients diagnosed with hypertension or New York Heart Association Class II–IV HF. The concentrations of valsartan, sacubitril and sacubitrilat (LBQ657) were measured by ultra-performance liquid chromatography tandem mass spectrometry in plasma, urine and peritoneal dialysate samples. Pharmacodynamics were evaluated by comparing changes in mean sitting systolic blood pressure (msSBP), mean sitting diastolic blood pressure (msDBP), mean sitting heart rate, N-terminal-pro B-type natriuretic peptide (NT-proBNP) and left ventricular ejection fraction (LVEF). Results Forty patients with PD were enrolled including 27 (67.5%) patients with hypertension, 4 (10%) patients with HF and 9 (22.5%) patients with both hypertension and HF. This study included three treatment cohorts: 50 mg twice daily (BID), 100 mg once daily and 100 mg BID. The plasma maximum drug concentrations in the 100 mg BID group were 1995 ± 1499 ng/mL for valsartan, 171 ± 148 ng/mL for sacubitril and 13 686 ± 7418 ng/mL for LBQ657. The 24-h recovery rate of LBQ657 was 3.77% in urine and 2.23% in peritoneal dialysate. After taking SV, msSBP and msDBP decreased by 19.25 ± 10.32 mmHg and 10.10 ± 8.00 mmHg from baseline, respectively. NT-proBNP decreased by 1436.50 (0.00–18 198.00) from baseline, while LVEF increased by 5.00 (–0.25 to 9.25) from baseline after SV treatment. Conclusions PD and residual renal function contributed only to a minor degree to the elimination of LBQ657. Additionally, a dose of 100 mg BID SV is safe and effective in patients with PD with complications of hypertension or HF. [ABSTRACT FROM AUTHOR]

Coronary artery calcifications (CACs) are common among maintenance hemodialysis (MHD) patients and associated with increased morbidity and mortality due to cardiovascular events. The insight into chronic kidney disease‐mineral and bone disorder (CKD‐MBD) established a correlation between dysregulated mineral metabolism and CACs. This study aimed to identify the association of mineral content outside of bone (MCOB) with CACs and cardiovascular events in MHD patients. In the pilot prospective study with no intervention, patients underwent body composition assessment by body composition monitor after hemodialysis and computed tomography examination using the Agatston scoring method simultaneously within a week. The primary end point included cardiovascular events and cardiovascular death. Correlations and receiver operating characteristic analysis elucidated the associations of MCOB with CACs; multivariate analysis assessed the cardiovascular risk for groups with different MCOB. One hundred three eligible patients with an average age of 48 (35‐63) years old were enrolled and followed up to 12 (11‐12.5) months, among which 52.4% had detectable CACs at baseline. MCOB showed an inverse correlation with Agatston score and significantly discriminated the patients with Agatston score > 0 (AUC = 0.737; P < 0.001) and 400 (AUC = 0.733; P < 0.001). MCOB ≤ 9.2657 mg/kg was an independent risk factor for CACs (OR = 4.853; P = 0.044) and strong predictor for cardiovascular morbidity and mortality (HR = 10.108; P = 0.042), as well as rehospitalization (HR = 2.689; P = 0.004). MCOB inversely correlated with the presence and extent of CACs, and could discriminate Agatston score > 0 and 400, which also presented as an independent indicator for CKD‐MBD and 1‐year cardiovascular prognosis in adult MHD patients. Additional studies are required for identifying this issue. [ABSTRACT FROM AUTHOR]

Background: Blood pressure variability (BPV) is a potential prognostic predictor for all-cause mortality. Objectives: We conducted a retrospective cohort study to compare the prognostic value of long-term BPV with intra-dialytic BPV in hemodialysis (HD) patients. Materials and Methods: We included 611 HD patients and collected their baseline blood pressure (BP) measurements for 1 year and monitored them for 40 months. Long-term BPV was assessed by pre-dialysis BP SD and pre-dialysis absolute BP residual metric. Intra-dialytic BPV was assessed by intra-dialytic BP average real variability and intra-dialytic absolute BP residual. Results: Long-term systolic BPV showed a weak correlation with mean BP, but a stronger correlation with intra-dialytic BPV. High long-term systolic blood pressure (SBP) SD and long-term SBP residual metrics were associated with high all-cause mortality (p = 0.0084 and 0.0056, respectively), while no such association was found for intra-dialytic BPV or diastolic BPV. According to receiver operating characteristic curve with mortality as dependent variable, long-term SBP residual metric showed the strongest prognostic ability (area under curve [AUC] 0.679, p = 0.0006), which was even stronger in patients with BP ≥140/90 mm Hg (AUC 0.713, p = 0.0004). After completely adjusting for confounders, long-term SBP residual metric remained significantly associated with all-cause mortality (hazard ratio 1.628 per quartile; 95% CI 1.086–2.441). Conclusions: Our results suggest long-term SBP residual metric to be a better predictor of all-cause mortality in HD patients, which could be used as an additional target for BP management. [ABSTRACT FROM AUTHOR]

Background/Aims: Blood pressure variability (BPV) is a novel cardiovascular risk factor for the population undergoing hemodialysis (HD). Methods: We conducted a retrospective cohort study of 526 HD patients. Four short-term peridialysis BPV metrics were analyzed: systolic blood pressure (SBP) change, SBP coefficient of variation (CV), SBP intradialytic average real variability (ARV), and absolute SBP residual. Multi variate analysis with Cox regression models were used to account for the potential confounders. Results: Short-term BPV is found to be affected by age, pre-dialysis SBP, antihypertensive drugs, dialysis time, and vascular access. Calcium-channel blockers (CCBs) were found to be associated with lower BPV than those on non-CCB therapy or no antihypertensive drugs. Patients dialyzed in the morning had a greater absolute SBP change than those dialyzed in the afternoon or evening. Patients using fistulas had a lower BPV than catheters. Higher BPV metrics including SBP CV (unadjusted hazard ratio [HR]: 1.37, 95% confidence interval [CI] 1.14-1.66, p=0.001), SBP intradialytic ARV (unadjusted HR: 1.46, 95% CI: 1.20-1.77, p< 0.001), and SBP residual (unadjusted HR: 1.47, 95% CI: 1.21-1.79, p< 0.001) were associated with a greater risk of cardiovascular events. After complete multivariate adjustment for other potential confounders, the HR remained statistically significant for SBP intradialytic ARV (HR 1.31, 95% CI: 1.04-1.66, p=0.024). Conclusion: Peridialytic BPV may be a potential target for improved blood pressure (BP) management in HD patients. Each short-term BPV metric has different advantages and disadvantages and should be applied according to the clinical context and purpose. [ABSTRACT FROM AUTHOR]

• Maintenance hemodialysis patients with low serum leptin have a poor prognosis. • Decreased serum leptin was associated with a higher risk of cardiovascular events and death. • Decreased serum leptin may cause left ventricular hypertrophy and peripheral vascular disease. We explored the associations between serum leptin concentration and cardiovascular prognosis in maintenance hemodialysis patients. In our prospective study with no intervention, demographics data at baseline were collected from electronic medical records. Serum leptin concentration was determined by ELISA. Patients underwent body composition assessment and echocardiographic measurements after hemodialysis. The primary endpoints were defined as cardiovascular events (CVEs), cardiovascular death (CVD) and all-cause death. A total of 165 eligible patients aged 51(43–65) y were enrolled and the mean serum leptin concentration was 35.49 (29.98) ng/ml. During a median follow-up of 18 (12–22) months, CVEs occurred in 37 (22.42%) patients and the cardiovascular and all-cause mortality was 10.91% and 21.82%. Serum leptin concentration was associated with CVEs (HR = 0.982, p = 0.003), CVD (HR = 0.934, p = 0.002) and all-cause death (HR = 0.943, p < 0.001). Decreased serum leptin concentration was an independent risk factor for the development of left ventricular hypertrophy (LVH, OR = 0.98, p = 0.007) and peripheral vascular disease (PVD, OR = 0.974, p = 0.007). Serum leptin concentration can independently predict cardiovascular outcomes and all-cause death in MHD patients. The effects that serum leptin concentration on development of LVH and PVD maybe the potential mechanism. [ABSTRACT FROM AUTHOR]