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Aim: Vascular calcification (VC) is a common complication in chronic kidney disease (CKD) and has been shown to be associated with increased cardiovascular events and mortality. This study was to explore the role of Wnt‐signaling pathway in CKD VC, and the association between VC and blood pressure variability (BPV) which is a risk factor of cardiovascular events. Methods: Adult male Sprague‐Dawley rats were divided into adenine‐induced CKD group (n = 5), 5/6 nephrectomy CKD group (n = 5), sham group (n = 5) and control group (n = 5). Low‐calcium‐high‐phosphate diets were introduced to induce vascular calcification. Both daytime (hour‐to‐hour during the day) and mid‐term (day‐to‐day for 9 days) blood pressure (BP) were collected and analyzed for BPV metrics. At sacrifice, kidney, heart and aorta samples were taken for histological analyses. Calcium deposition in aorta was identified with Alizarin Red stain and graded. Immunohistochemistry stain and western blot were performed for Wnt3a, Wnt5a, β‐catenin, sclerostin, osteopontin, and α‐SMA. Results: Compared with control rats, CKD rats suffered from markedly severer VC (Grade 2.6 ± 0.2 and 1.8 ± 0.8 vs 0.0 ± 0.0 and 0.2 ± 0.4, P =.0010). VC was positively correlated with vascular Wnt3a and β‐catenin expression (P =.0032 and.0000), but not significantly associated with Wnta5a or sclerostin. Besides, CKD rats showed increased BPV (P <.001), which was also positively correlated with VC. Conclusion: We confirmed that CKD rats had enhanced Wnt‐signaling in vascular tissue and severer aorta calcification together with increased BPV. Wnt pathway may be a potential target in future VC and BPV management in CKD. SUMMARY AT A GLANCE: Vascular calcification was positively correlated with Wnt‐signaling and blood pressure variability (BPV) based on two experimental CKD models. These findings provide a new potential target for BPV management. [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: 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]

Objective: To identify primary factors contributing to hemodialysis-related headache (HRH) in maintenance hemodialysis (MHD) patients. Methods: Adult outpatients receiving MHD were prospectively enrolled from a hemodialysis (HD) center of a tertiary hospital in China. Twelve dialysis sessions were successively monitored for each patient. HRH is defined as having at least three headache episodes that begin during HD and resolve within 72 h of HD session completion. Blood gas analysis during headache episodes and body composition analysis after dialysis were conducted. Hour-to-hour vital sign variability during dialysis was assessed using the metric of average real variability (ARV). Multivariable logistic regression analysis was conducted to explore the factors triggering HRH. Results: A total of 95 Chinese MHD patients were enrolled, with 92 patients (60.9% were males) included in the final analysis. The mean age of the 92 patients was 59.3 ± 17.5 years, and the median dialysis vintage was 27.1 (12–46.2) months. Among them, 12 patients (13%) complained of 42 headache attacks, and eight (8.7%) were diagnosed with HRH. For eight patients with HRH, headache occurred 100.3 ± 69.5 min after the start of dialysis, with a mean VAS score of 4.3 ± 1 points. The quality of headaches was dull (six patients), pulsating (one patient), or stabbing pain (one patient); all the headaches were bilateral, with one having concomitant vomiting. The intradialysis headache duration and the whole headache duration were 98.8 ± 68.1 and 120 (65–217.5) minutes, respectively. Younger age (OR = 0.844, 95% CI 0.719–0.991, p = 0.039), decreased blood sodium level (OR = 0.309 in the range of 133–142 mmol/L, 95% CI 0.111–0.856, p = 0.024), increased ARV of intradialysis systolic blood pressure (OR = 3.067, 95% CI 1.006–9.348, p = 0.049) and ratio of overhydration to dry weight (OR = 1.990, 95% CI 1.033–3.832, p = 0.040) were found to be independent risk factors for HRH. Conclusions: This study suggested a significant attribution of blood sodium, hydration status and blood pressure variability to HRH. [ABSTRACT FROM AUTHOR]

Summary: Primary hypertrophic osteoarthropathy (PHO) is a hereditary bone disease that is grouped into PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2) due to different causative genes. Data comparing bone microstructure between the two subtypes are scarce. This is the first study to find that PHOAR1 patients had inferior bone microstructure compared with PHOAR2 patients. Purpose: The primary goal of this study was to assess bone microarchitecture and strength in PHOAR1 and PHOAR2 patients and to compare them with age- and sex-matched healthy controls (HCs). The secondary goal was to assess the differences between PHOAR1 and PHOAR2 patients. Methods: Twenty-seven male Chinese PHO patients (PHOAR1 = 7; PHOAR2 = 20) were recruited from Peking Union Medical College Hospital. The areal bone mineral density (aBMD) was assessed by dual-energy X-ray absorptiometry (DXA). Peripheral bone microarchitecture at the distal radius and tibia were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Biochemical markers of PGE2, bone turnover, and Dickkopf-1 (DKK1) were investigated. Results: Compared with HCs, PHOAR1 and PHOAR2 patients had distinctively larger bone geometry, substantially lower vBMD at the radius and tibia, and compromised cortical microstructure at the radius. For trabecular bone, PHOAR1 and PHOAR2 patients showed different changes at the tibia. PHOAR1 patients had significant deficits in the trabecular compartment, resulting in lower estimated bone strength. Conversely, PHOAR2 patients showed a higher trabecular number, narrower trabecular separation, and lower trabecular network inhomogeneity than HCs, translating into preserved or slightly high estimated bone strength. Conclusion: PHOAR1 patients had inferior bone microstructure and strength compared with PHOAR2 patients and HCs. Additionally, this study was the first to find differences in the bone microstructure between PHOAR1 and PHOAR2 patients. [ABSTRACT FROM AUTHOR]

(1) Background: Inflammation plays an important role in the onset and progression of acute kidney injury (AKI). Despite this, evidence regarding the prognostic effect of the monocyte-to-lymphocyte ratio (MLR), a novel systemic inflammation marker, among patients with AKI is scarce. This study sets out to investigate the prognostic potential of both baseline and early changes in MLR for short-term mortality among critically ill patients with AKI. (2) Method: Eligible patients with AKI from the Medical Information Mart for Intensive Care IV database were retrospectively analyzed. MLR cutoff values were determined using maximally selected rank statistics and tertiles. The clinical outcomes were 30-day and 90-day mortality in the intensive care unit. A restricted cubic splines model and Cox proportional hazards models were utilized to evaluate the association between the baseline MLR and short-term mortality. Then, the trends in MLR over time were compared between the 30-day survivors and non-survivors using a generalized additive mixed model (GAMM). (3) Result: A total of 15,986 patients were enrolled. Multivariable Cox regression analysis identified baseline MLR ≥ 0.48 as an independent risk factor predicting 30-day mortality (HR 1.33, 95%CI 1.24, 1.45, p < 0.001) and 90-day mortality (HR 1.34, 95%CI 1.23, 1.52, p < 0.001) after adjusting for potential confounders. Similar trends were observed for 30-day and 90-day mortality when tertiles were used to group patients. The restricted cubic splines model revealed a non-linear association between MLR and 30-day and 90-day mortality (both p for non-linear < 0.001, both p for overall < 0.001). The area under the curve of 0.64 for MLR was higher than that of monocytes (0.55) and lymphocytes (0.61). In the subgroup analyses, despite the noted significant interactions, the direction of the observed association between MLR and 30-day mortality was consistent across most prespecified subgroups, except for shock and black ethnicity. The GAMM results highlighted that, as time went on, MLR in the 30-day survival group consistently declined, whereas MLR in the non-survival group rose within 15 days post-ICU admission. The difference between the two groups persisted significantly even after adjusting for confounders (p = 0.006). (4) Conclusion: A higher baseline MLR was identified as an independent risk factor predicting 30-day and 90-day mortality. The early increase in MLR was associated with high 30-day mortality, suggesting that dynamic monitoring of MLR could potentially better predict survival in critically ill patients with AKI. [ABSTRACT FROM AUTHOR]

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]

The aim of this study was to systematically review relevant studies to evaluate the value of urinary interleukin-18 (uIL-18) in predicting acute kidney injury (AKI). A comprehensive search of PubMed, Medline, Embase, and Cochrane Library was conducted for literature published up to 1 August 2022. Quality Assessment Tool for Diagnostic Accuracy Studies-2 (QUADAS-2) was applied to assess the literature quality. Then, relevant data were extracted from each eligible study and a random-effects regression model was utilized to pool sensitivity, specificity, and construct summary receiver operating characteristic (SROC) and area under curve (AUC). Twenty-six studies with 7183 patients were enrolled and relevant information was extracted. The estimated sensitivity and specificity of uIL-18 in the diagnosis of AKI were 0.64 (95% confidence interval (CI): 0.54–0.73) and 0.77 (95%CI: 0.71–0.83), respectively. The pooled diagnostic odds ratio (DOR) was 6.08 (95%CI: 3.63–10.18), and the AUC of uIL-18 in predicting AKI was 0.78 (95%CI: 0.74–0.81). Subgroup analysis showed that uIL-18 in pediatric patients was more effective in predicting AKI than in adults (DOR: 7.33 versus 5.75; AUC: 0.81 versus 0.77). Urinary IL-18 could be a relatively good biomarker with moderate predictive value for AKI, especially in pediatric patients. However, further research and clinical settings are still needed to validate our findings. [ABSTRACT FROM AUTHOR]

The negative effects of obesity on the cardiovascular health have drawn much attention. Weight-adjusted-waist index (WWI) has been proved to reflect weight-independent centripetal obesity. However, the association between WWI and abdominal aortic calcification (AAC) has not been reported before. Using data from National Health and Nutrition Examination Survey 2013–2014, we aimed to determine the relationship of WWI and AAC in adults aged ≥ 40 years. WWI was determined by dividing waist circumference by the square root of weight. AAC was measured by dual-energy X-ray absorptiometry and quantified by Kauppila scores. Severe AAC (SAAC) was defined as an AAC score > 6. We utilized weighed multivariable logistic regression and generalized additive model to explore the independent association between WWI and AAC. Threshold effects were further calculated by two-piecewise linear regression model. 3082 participants were enrolled in our analysis, of which 48.2% were male. WWI was positively associated with AAC scores (β = 0.34, 95% CI 0.05–0.63) and exhibited a nonlinear relationship with SAAC. On the left of the breakpoint (WWI = 11.11), WWI and SAAC were positively associated (OR = 2.86, 95% CI 1.40–5.84), while no such relationship was found on the right (OR = 1.07, 95% CI 0.77–1.48). Our findings indicated that WWI may serve as a simple biomarker of AAC in US adults aged ≥ 40 years. [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]

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]

Primary hypertrophic osteoarthropathy (PHO) is an inherited disease characterized by digital clubbing, periostosis, and pachydermia. Based on two causative genes, hydroxyprostaglandin dehydrogenase ( HPGD ) and solute carrier organic anion transporter family member 2A1 ( SLCO2A1 ), PHO is categorized into two subtypes: hypertrophic osteoarthropathy, primary, autosomal recessive 1 (PHOAR1) and hypertrophic osteoarthropathy, primary, autosomal recessive 2 (PHOAR2). In this study, we summarized the clinical manifestations and analyzed SLCO2A1 gene in 23 PHOAR2 patients in our center. As a result, 18 patients displayed complete phenotypes of PHO with digital clubbing, periostosis, and pachydermia. 29 mutations were found in total, and 22 of them were novel mutations including 13 missense, three nonsense, four deletion, one frame-shift and one splicing site mutations. Compared with nine PHOAR1 patients we previously reported, PHO patients with SLCO2A1 mutations were all male and presented with a later onset age. Peptic ulcers and myelofibrosis occurred only in PHOAR2 patients. The urinary level of prostaglandin E2 metabolite (PGEM) is significantly higher in PHOAR2 patients than that in PHOAR1 group. In conclusion, this study was the largest cohort to date to summarize PHOAR2 patients and to assess the phenotypic difference between two subtypes of PHO. The difference of urinary PGEM concentration between two subtypes is helpful for the differential diagnosis of PHO. [ABSTRACT FROM AUTHOR]