CXCR4 overexpression in chronic lymphocytic leukemia associates with poorer prognosis: A prospective, single-center, observational study.

Controversial data have been reported on the prognostic value of C-X-C motif chemokine receptor 4 (CXCR4) in chronic lymphocytic leukemia (CLL). This prospective, single-center, observational study aimed to evaluate the role of CXCR4 in the pathophysiology of CLL and its prognostic role. A total of 158 patients of CLL were enrolled, and CXCR4 expression on CLL cells was detected by flow cytometry (FCM) at initial diagnosis. The patients were divided into 2 groups according to the CXCR4 mean fluorescence intensity (MFI) median. Also, four patient specimens from the CXCR4low and CXCR4high groups were selected for RNASeq analysis. The progression-free survival (PFS) of CLL patients in the CXCR4high group was significantly shorter than the CXCR4low group, with a median follow-up time of 27 months (log-rank P < 0.001). Moreover, CXCR4 overexpression (MFI > 3376) was an independent marker of poor PFS in CLL patients (P < 0.001). Analysis of RNASeq results revealed that CXCR4 plays an important role in the migration of CLL. Collectively, CXCR4 expression levels on leukemia cells can be detected rapidly by FCM. CXCR4 overexpression was significantly associated with poorer prognosis in CLL patients within a shorter follow-up time.

Efficacy and safety of difelikefalin in the treatment of hemodialysis patients with pruritus: A meta-analysis and systematic review.

BACKGROUND: The incidence of pruritus associated with hemodialysis (HD) patients can be as high as 70%, and ~ 40% of patients suffer from moderate to severe systemic pruritus. Difelikefalin (CR845), a peripheral restrictor κ-opioid receptor agonist, activates opioid receptors on peripheral neurons and immune cells to relieve pruritus in patients. However, the clinical effect of difelikefalin on HD-related pruritus is unclear. Therefore, the purpose of this meta-analysis and systematic review was to investigate the safety and efficacy of difelikefalin in the treatment of HD-associated pruritus. OBJECTIVE: This study explored the efficacy and safety of difelikefalin in the treatment of pruritus in HD patients by systematic review and meta-analysis. MATERIALS AND METHODS: Randomized controlled trials on difelikefalin in the treatment of pruritus in HD patients were retrieved from PubMed, Embase, Cochrane Library, and Web of Science electronic databases. The retrieval deadline was January 1, 2023. Stata 15.0 software was used for data analysis of the included studies. RESULTS: A total of 4 randomized controlled trials were included, totaling 1,268 patients (736 patients in the experimental group and 532 patients in the control group). Results of the meta-analysis showed that, compared with the control group, difelikefalin could significantly improve the Worst Itch Numeric Rating Scale score (improvement > 3; risk ratio (RR) = 1.28, 95% confidence interval (CI) (1.07, 1.53)), decrease the 5-D itch score (standardized mean difference = -0.43, 95% CI (-0.55, -0.30)), and significantly improve adverse events (RR = 1.33, 95% CI (1.13, 1.56)). CONCLUSION: Although difelikefalin can improve itching symptoms in HD patients, it can also increase adverse reactions based on the current literature. Therefore, more studies are needed to further explore the safety and efficacy of difelikefalin treatment.

Exploring symptom clusters in Chinese patients with peritoneal dialysis: a network analysis.

BACKGROUND: In recent years, the research on symptom management in peritoneal dialysis (PD) patients has shifted from a single symptom to symptom clusters and network analysis. This study collected and evaluated unpleasant symptoms in PD patients and explored groups of symptoms that may affect PD patients with a view to higher symptom management. METHODS: The symptoms of PD patients were measured using the modified Dialysis Symptom Index. The symptom network and node characteristics were assessed by network analysis, and symptom clusters were explored by factor analysis. RESULTS: In this study of 602 PD patients (mean age 47.8 ± 16.8 years, 47.34% male), most had less than 2 years of dialysis experience. Five symptom clusters were obtained from factor analysis, which were body symptom cluster, gastrointestinal symptom cluster, mood symptom cluster, sexual disorder symptom cluster, and skin-sleep symptom cluster. Itching and decreased interest in sex may be sentinel symptoms, and being tired or lack of energy and feeling anxious are core symptoms in PD patients. CONCLUSIONS: This study emphasizes the importance of recognizing symptom clusters in PD patients for better symptom management. Five clusters were identified, with key symptoms including itching, decreased interest in sex, fatigue, and anxiety. Early intervention focused on these symptom clusters in PD patients holds promise for alleviating the burden of symptoms.

Comparison of bone microstructure and strength in the distal radius and tibia between the different types of primary hypertrophic osteoarthropathy: an HR-pQCT study.

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.

Pharmacokinetics and pharmacodynamics of sacubitril/valsartan in peritoneal dialysis patients.

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.

Additional antibiotic lock in peritoneal dialysis-associated refractory peritonitis: A case series study and literature survey.

BACKGROUND: Refractory peritonitis is one of the leading causes of catheter failure in peritoneal dialysis (PD) patients. However, there are no established curative therapies available, and only catheter removal should be performed. Here we present a case series study to illustrate the efficacy of antibiotic lock for PD-associated refractory peritonitis. MATERIALS AND METHODS: Patients with refractory peritonitis treated with intraperitoneal antibiotics plus antibiotic lock from September 2020 to March 2022 were retrospectively analyzed. Medical cure was identified as a success of treatment. RESULTS: We identified 11 patients, of which 7 (63.64%) had a history of PD-associated peritonitis, with the episode of continuous ambulatory peritoneal dialysis (CAPD) ranging from 1 to 158 months at a median of 36 (9.5, 50.5) months. The dialysis effluent culture showed Gram-positive, Gram-negative bacteria, and was culture-negative in 5, 2, and 4 cases, respectively. The cure rates were 85.71% for culture-positive cases and 25% for culture-negative cases, and the total cure rate was 63.64%. No relevant adverse events occurred, including sepsis. CONCLUSIONS: Treatment with the additional antibiotic lock was successful in most cases, especially in those that were culture-positive. Additional antibiotic lock deserves great attention and further investigation in treating PD-associated refractory peritonitis.

Association of intradialysis blood sodium level, blood pressure variability, and hydration status with hemodialysis-related headache: a prospective cohort study.

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.

[Catheter Replacement Methods in Hemodialysis Patients With Dysfunctional Tunneled-Cuffed Catheters With Fibrin Sheaths]. / 对形成纤维蛋白鞘的带涤纶套和隧道透析导管的更换方式探索.

Objective: Tunneled-cuffed catheters (TCCs) are frequently used for establishing hemodialysis access for maintenance hemodialysis in older patients with exhausted resources of peripheral vessels. Fibrin sheath formation around the catheter is one of the most common complications of long-term use of indwelling catheter, which may cause the malfunction of the catheter. In this study, we intend to compare the prognosis of two catheter replacement methods, in situ replacement and replacement through a fibrin sheath crevice, with both being assisted by balloon dilation, and to explore the optimal catheter replacement process. Methods: A retrospective study was conducted with 52 patients who underwent a replacement of their TCCs. Among them, 27 cases had their TCC replaced by the modified method of replacement through a fibrin sheath crevice and were referred to as the sheath crevice group, while 25 cases underwent in situ catheter replacement and were referred to as the in situ group. The primary outcome indicators included maximum blood flow in hemodialysis catheter and the urea clearance rate calculated by Kt/V values at the 1, 3, and 6-month follow-ups. The secondary outcomes included dialyzer alarms being set off and catheter-related infections during follow-up. Results: There was no significant difference between the general data of the two groups. There was no massive blood loss during the replacement procedure. Neither were there cardiac tamponade, catheter-associated infections, or other complications. Follow-ups were made 1, 3, and 6 months after the replacement procedure. The sheath crevice group had higher catheter blood flow and Kt/V values at the 6-month follow-up than the in situ group did ([241.85±9.62] mL/min vs. [234.40±11.21] mL/min, P=0.014 and 1.31±0.55 vs. 1.27±0.49, P=0.005, respectively). During the follow-up process, access alarms were reported in 5 patients (three in the in situ group and two in the sheath crevice group) during dialysis. No catheter-associated infection occurred in either group. Conclusion: The catheter replacement method of balloon dilation-assisted catheter insertion through a fibrin sheath crevice is safe and effective, resulting in better long-term catheter blood flow compared with that of in situ catheter replacement.

Iron Deficiency is Associated With Platelet Count Elevation in Patients With Dialysis-dependent Chronic Kidney Disease.

OBJECTIVE: Iron deficiency is common in patients with end-stage renal disease (ESRD). Platelet count changes may reflect iron status, but the relationship between platelet count and iron indices is unclear in patients with ESRD. METHODS: We conducted a retrospective study in 1,167 patients with ESRD from 2012 to 2017 in West China Hospital. Baseline data were used to analyze the relationship between the platelet count and iron indices. Patients were followed up for 3 years. RESULTS: Patients with iron deficiency (both absolute and functional) had a higher platelet count than those without iron deficiency (174 ± 61 × 109/L vs. 153 ± 58 × 109/L, P < .001). Receiver operating characteristic analysis showed a weak predictive power of platelet count on absolute iron deficiency (area under curve 0.620; cutoff value > 137 × 109/L, sensitivity 76%, specificity 43%) and functional iron deficiency (area under curve 0.540; cutoff value > 124 × 109/L, sensitivity 77%, specificity 32%). Platelet count was negatively correlated with ferritin (Spearman's rho [ρ] -0.1547, P < .001), transferrin saturation (ρ = -0.1895, P < .001), and serum iron (ρ = -0.1466, P < .001). The abovementioned correlations remained significant in multivariate regression (ß -0.7285, 95% confidence interval [CI] -1.0757 to -0.3814; ß -.00347, 95% CI -0.0520 to -0.0174; ß -0.0097, 95% CI -0.0159 to -0.0035, respectively). In unadjusted and adjusted Cox regression models, neither baseline platelet count nor relative thrombocytosis was associated with 3-year mortality. CONCLUSION: There was a weak but significant platelet count elevation in patients with ESRD and with iron deficiency.

The value of urinary interleukin-18 in predicting acute kidney injury: a systematic review and meta-analysis.

AIMS: 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). METHODS: 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). RESULTS: 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). CONCLUSIONS: 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.

Visceral Fat Area Is a Better Predictor Than Coronary Artery Calcification Score for Cardiovascular Outcomes and All-Cause Death in Patients on Hemodialysis.

OBJECTIVES: The aim of this study is to compare the prognostic effects of visceral fat area (VFA) with coronary artery calcification score (CACs) in patients on maintenance hemodialysis. DESIGN AND METHODS: In the prospective study with no intervention, clinical characteristics and serum biochemical indexes at baseline for each patient were collected through the electronic medical records. Body composition assessment using bioelectrical impedance analysis, computed tomography examination with the Agatston scoring method, and echocardiographic measurements were performed at enrollment. Primary endpoints included cardiovascular events (CVEs), cardiovascular death (CVD), and all-cause death. RESULTS: A total of 97 Chinese patients aged 48 (35-62) years were enrolled from our Hemodialysis Center, of which 61.9% were male and 20.6% had diabetes. The median of VFA and CACs at baseline was 64.5 (43.5-88.7) cm2 and 0.9 (0-467.6), respectively. CVEs occurred in 20 (20.6%) patients during a median follow-up of 26.4 (13-27.7) months. The cardiovascular and all-cause mortality was 8.2% (8 patients) and 11.3% (11 patients), respectively. VFA was associated with CVEs (hazard ratio [HR] = 9.21 for VFA ≥71.3 cm2 vs. VFA <71.3 cm2, P = .017), CVD (HR = 1.11 for 1 cm2 increase, P = .035), and all-cause mortality (HR = 1.08 for 1 cm2 increase, P = .011). Also, VFA was significantly correlated with cardiac structure parameters and the development of left ventricular hypertrophy (odds ratio = 1.02 for 1 cm2 increase, P = .03). Yet, CACs were not correlated with CVEs, CVD, or all-cause mortality. CONCLUSIONS: Increased VFA can be used as an independent predictor for CVEs, CVD, and all-cause mortality. The effect VFA exerts on cardiac reconstruction might be the underlying mechanism. Further studies are warranted for the management of VFA in the hemodialysis population.

Vascular calcification is associated with Wnt-signaling pathway and blood pressure variability in chronic kidney disease rats.

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, ß-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 ß-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.

Association of mineral content outside of bone with coronary artery calcium and 1-year cardiovascular prognosis in maintenance hemodialysis patients.

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.

The Association between Long- and Intra-Dialytic Blood Pressure Variability with All-Cause Mortality in Hemodialysis Patients.

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.

Association of Peridialysis Blood Pressure and Its Variability with Cardiovascular Events in Hemodialysis Patients.

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.

Short- and long-term outcomes with renin-angiotensin-aldosterone inhibitors in renal transplant recipients: A meta-analysis of randomized controlled trials.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor type 1 blockers (ARBs) are often prescribed for renal transplant recipients (RTRs), but the outcomes of these medications in RTRs remain controversial. METHODS: The PubMed, Embase, and Cochrane Library databases were systematically searched. Randomized controlled trials investigating the outcomes of ACEI/ARBs in RTRs were included for meta-analysis. RESULTS: Twenty-two trials with 2242 patients were identified. After treatment for at least 12 months, ACEI/ARBs were associated with a decline in glomerular filtration rate (GFR) (weighed mean differences [WMD] -5.76 mL/min; 95% confidence intervals [CI]: -9.31 to -2.20) and a decrease in hemoglobin (WMD -9.81 g/L; 95% CI: -14.98 to -4.64). There were no significant differences in mortality between ACEI/ARB and non-ACEI/ARB groups (risk ratio [RR] 0.98, 95% CI: 0.58 to 1.76), nor in graft failure (RR 0.68, 95% CI: 0.38 to 1.32). After short-term treatment (less than 1 year), significant differences were found in changes of 24-hour proteinuria (WMD-0.57 g/d; 95% CI: -0.72 to -0.42) and serum potassium (WMD 0.25 mEq/L; 95% CI: 0.14 to 0.37) in ACEI/ARB groups compared to control arm, while these differences were not confirmed in the long run. CONCLUSION: This meta-analysis indicates ACEI/ARBs may be prescribed to RTRs with GFR and hemoglobin being carefully monitored.

A Common Mutation and a Novel Mutation in the HPGD Gene in Nine Patients with Primary Hypertrophic Osteoarthropathy.

Primary hypertrophic osteoarthropathy (PHO) is a hereditary bone disease characterized by digital clubbing, periostosis, and pachydermia. The HPGD gene encoding 15-prostaglandin dehydrogenase and SLCO2A1 encoding one type of prostaglandin transporter were found to be responsible for PHO. Mutations of either gene would lead to increased level of prostaglandin E2 (PGE2), which might contribute to the constellation of the symptoms. The aim of the study was to analyze the HPGD gene and the clinical characteristics in nine patients with the diagnosis of PHO. Nine patients, (eight males and one female) including two siblings and seven sporadic cases, were enrolled in the study. Clinical features were summarized, and blood and urine samples were collected. Sanger method was used to sequence the HPGD gene to detect mutations. Urinary PGE2 and prostaglandin metabolite (PGE-M) levels for each patient were measured and compared to the healthy controls. A recurrent c.310_311delCT mutation was identified in all patients, of which six were homozygous, two were heterozygous, and one was compound heterozygous with this mutation and a novel heterozygous missense mutation c.488G>A (p.R163H). The levels of PGE2 in urine were much higher than normal in all patients, along with lower PGE-M levels. In conclusion, nine PHO patients were characterized by typical clinical manifestations including digital clubbing, periostosis, and pachydermia. A common mutation and a novel mutation in HPGD gene were identified to be responsible for the disease, and c.310_311delCT mutation is likely to be a hot-spot mutation site for Asian PHO patients.

COVID-19 and outcomes in Chinese peritoneal dialysis patients.

BACKGROUND: Reports on COVID-19 in peritoneal dialysis (PD) patients are scarce in China. This study aimed to describe the characteristics and outcomes of PD patients with COVID-19 after China abandoned the 'zero-COVID' policy. METHODS: This single-centre retrospective study included patients receiving PD who underwent testing for COVID-19 infections between 7 December 2022 and 7 January 2023. Outcomes of interest included factors associated with positive COVID-19 testing result and clinical outcomes including COVID-19-related hospitalisation and severe COVID-19, which were analysed using logistic regression analyses. RESULTS: A total of 349 PD patients (male 53.6%, age 49 ± 13 years old) were included, and 235 patients (67.3%) were infected. There were no significant differences between COVID-19 and non-COVID-19 patients other than higher proportion of vaccinated patients and slow transporters in the patients who tested positive for COVID-19 (44.7% vs. 28.1%, p = 0.003; 8.7% vs. 1.8%, p = 0.03, respectively). Multivariate analysis showed COVID-19 was associated with vaccination (odds ratio (OR): 1.71, 95% confidence interval (CI): 1.02-2.86) and slow transport type (compared with average transport type, OR: 4.52, 95% CI: 1.01-20.21). Among the patients with infection, 38 (16.2%) patients were hospitalised, 18 (7.7%) patients had severe disease and 9 (3.8%) patients died. In multivariate logistic analysis, both age (OR: 1.04, 95% CI: 1.01-1.07; OR: 1.06, 95% CI: 1.02-1.11) and hyponatremia (OR: 5.44, 95% CI: 1.63-18.13; OR: 6.50, 95% CI: 1.77-23.85) were independent risk factors for COVID-19-related hospitalisation and severe disease. CONCLUSIONS: Although vaccinated patients were more likely to have tested positive for COVID-19 infection, they appeared to have less severe infection and less need for hospitalisation. Patients who were older with a history of hyponatremia were more likely to experience adverse outcomes from COVID-19.

Prognostic Value of the Baseline and Early Changes in Monocyte-to-Lymphocyte Ratio for Short-Term Mortality among Critically Ill Patients with Acute Kidney Injury.

(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.

Utilization of Hydrogels in Mesenchymal Stem Cell-Based Therapy for Kidney Diseases.

Kidney diseases are major global health problems, with high prevalence and mortality. However, current treatment strategies for kidney diseases fail to achieve satisfactory efficacy. Mesenchymal stem cell (MSC)-based therapy has been a promising strategy for treating kidney diseases. Preclinical studies have proven their safety and effectiveness in treating acute kidney injury (AKI) and chronic kidney disease (CKD), but the outcomes of clinical trials have shown very limited clinical efficacy. A variety of innovative approaches have been proposed to enhance the therapeutic potential of MSCs, and hydrogels are attractive candidates. Hydrogels are three-dimensional (3D) networks formed by hydrophilic polymers of natural or synthetic origin with diverse physical and chemical properties. They have been widely applied in the field of drug delivery and regenerative medicine, including MSC-based therapy. Many studies have proven that hydrogels can improve the therapeutic efficacy of MSCs for kidney diseases, but there are still challenges limiting the widespread application of this method. In this review, we introduce the application of MSCs in kidney diseases and the factors that influence therapeutic efficiency and focus on the beneficial effects of hydrogels in MSC-based therapy for AKI and CKD.