Elevated total serum alkaline phosphatase levels have been associated with higher mortality in the general population, CKD patients, and hemodialysis patients. However, in peritoneal dialysis ...patients, this association has received little attention. The aim of this study was to evaluate the association between alkaline phosphatase and all-cause and cardiovascular mortality in peritoneal dialysis patients.
In this single center retrospective cohort study, 1021 incident peritoneal dialysis patients from January 1, 2006, to December 31, 2010 with baseline serum alkaline phosphatase values were enrolled. Collected baseline data included demographic characteristics and clinical and laboratory measurements. All patients were followed until December 31, 2012. The associations of total serum alkaline phosphatase levels with all-cause and cardiovascular mortality were assessed using multivariable-adjusted Cox models.
Of 1021 patients, mean age was 47.5 (± 15.5) years, 59.1% of patients were men, and 22.8% of patients were diabetic. The median serum alkaline phosphatase level was 64 U/L (interquartile range=52-82 U/L). During a median 31-month (interquartile range=19-45 months) follow-up period, 203 patients died, of which 109 deaths were caused by cardiovascular disease. After adjusting for demographics, comorbid conditions, liver function, and bone metabolism parameters, the highest alkaline phosphatase quartile was significantly associated with a hazard ratio for all-cause mortality of 1.70 (95% confidence interval, 1.06 to 2.74, P=0.03) and a hazard ratio for cardiovascular mortality of 1.94 (95% confidence interval, 1.02 to 3.72, P=0.04). Each 10 U/L higher baseline alkaline phosphatase level was associated with 4% (95% confidence interval, 1.00 to 1.08, P=0.04) and 7% (95% confidence interval, 1.02 to 1.11, P=0.003) higher risk of all-cause and cardiovascular mortality, respectively.
Higher total serum alkaline phosphatase levels at the commencement of peritoneal dialysis were independently associated with all-cause and cardiovascular mortality in peritoneal dialysis patients.
The morphology- and size-controlled synthesis of branched Pt nanostructures on graphene is highly favorable for enhancing the electrocatalytic activity and stability of Pt. Herein, a facile approach ...is developed for the efficient synthesis of well-dispersed Pt nanoflowers (PtNFs) on the surface of polydopamine (PDA)-modified reduced graphene oxide (PDRGO), denoted as PtNFs/PDRGO, in high yield. The synthesis was performed by a simple heating treatment of an aqueous solution that contained K2PtCl4 and PDA-modified graphene oxide (GO) without the need for any additional reducing agent, seed, surfactant, or organic solvent. The coated PDA serves not only as a reducing agent, but also as cross-linker to anchor and stabilize PtNFs on the PDRGO support. The as-prepared PtNFs/PDRGO hybrid, with spatially and locally separated PtNFs on PDRGO, exhibits superior electrocatalytic activity and stability toward both methanol oxidation reaction (MOR) and oxygen reduction reaction (ORR) in alkaline solutions.
IgA nephropathy (IgAN) is the most common primary glomerulonephritis, characterized by glomerular deposition of IgA immune complexes, mainly produced by B cells under the regulation of CD4
+
T cells. ...However, the alterations of specific CD4
+
T cell subsets and the mechanism of B cells activation in IgAN remain unclear. Therefore, we aimed to investigate the landscape characteristics and role of CD4
+
T cells in the progression of IgAN. We identified that the proportion of Th2, Th17 and Tfh (follicular helper T) cells in patients with IgAN was significantly higher than that of healthy controls (
P
< 0.05). Single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) showed that Th cells and B cells in patients with IgAN were more activated. Correspondingly, multiplex immunohistochemistry staining of renal biopsy showed increased infiltration of CD4
+
T and B cells in the kidneys of patients with IgAN. The degree of infiltration was positively correlated with the degree of renal damage. Interestingly, the proportion of Tfh cells in peripheral blood was positively correlated with the severity of proteinuria. Moreover, the proximity position of Tfh cells and B cells suggested that cell-cell interactions between Tfh and B cells were happening
in situ
. Intercellular communication analysis also showed enhanced interaction between Tfh cells and B cells in IgAN. Our findings suggested that Tfh cells of patients possibly contributed to the progression of IgAN by activating B cells
via
cell-cell interactions and TNFSF14-TNFRSF14 may be an underlying signaling pathway.
Background/Aims: Metabolic syndrome (MS) has been widely proved as a predictor of cardiovascular disease, all-cause, and cardiovascular mortality in general population. But its effects on mortality ...and technique failure have not been well illustrated in peritoneal dialysis (PD) patients. We aimed to investigate the association of MS and clinical outcomes in Chinese continuous ambulatory PD (CAPD) patients. Methods: A single-center, prospective, observational cohort study was conducted in CAPD patients enrolled from September 1 to December 31, 2011, and followed up until December 31, 2016. Demographic, clinical, biochemical and anthropological data were collected. The relationships between MS and mortality and technique failure were assessed using Kaplan-Meier and Cox Regression Survival Functions. Results: A total of 511 patients were enrolled. The baseline mean age was 48.4 ± 14.4 years, 282 patients (55.2%) were male, and 130 patients (25.4%) were diabetic. In total, 213 patients (41.7%) met the diagnostic criterion of MS. During a median of 4.4 years (interquartile range 2.3–5.3 years) follow-up period, 114 patients died, of whom, 65 patients (48%) died in MS group versus 49 patients (30%) in non-MS group. Patients who died tended to be older, higher in inflammation markers and with poorer nutritional state. Kaplan-Meier Survival Functions found patients with MS had a significant rising of all-cause mortality (log-rank test = 12.811, p < 0.001) and cardiovascular mortality (log-rank test = 14.529, p < 0.001) in all patients, and a significant rising of cardiovascular mortality (log-rank test = 4.486, p = 0.034) in non-diabetic patients. After adjusting for confounders, Cox Regression showed that MS was significantly associated with higher cardiovascular mortality in all patients (hazard ratio HR 2.21, 95% CI 1.12–4.36, p = 0.022) and in non-diabetic patients (HR 2.60, 95% CI 1.07–6.35, p = 0.036), but it has no significant effect on technique failure. Conclusion: In CAPD patients, MS predicted mortality, especially cardiovascular mortality. No relationship was found between MS and technique survival.
(Pro)renin receptor (PRR) is predominantly expressed in the distal nephron where it is activated by angiotensin II (ANG II), resulting in increased renin activity in the renal medulla thereby ...amplifying the de novo generation and action of local ANG II. The goal of the present study was to test the role of cycloxygenase-2 (COX-2) in meditating ANG II-induced PRR expression in the renal medulla in vitro and in vivo. Exposure of primary rat inner medullary collecting duct cells to ANG II induced sequential increases in COX-2 and PRR protein expression. When the cells were pretreated with a COX-2 inhibitor NS-398, ANG II-induced upregulation of PRR protein expression was almost completely abolished, in parallel with the changes in medium active renin content. The inhibitory effect of NS-398 on the PRR expression was reversed by adding exogenous PGE2. A 14-day ANG II infusion elevated renal medullary PRR expression and active and total renin content in parallel with increased urinary renin, all of which were remarkably suppressed by the COX-2 inhibitor celecoxib. In contrast, plasma and renal cortical active and total renin content were suppressed by ANG II treatment, an effect that was unaffected by COX-2 inhibition. Systolic blood pressure was elevated with ANG II infusion, which was attenuated by the COX-2 inhibition. Overall, the results obtained from in vitro and in vivo studies established a crucial role of COX-2 in mediating upregulation of renal medullary PRR expression and renin content during ANG II hypertension.
Inflammation-based prognostic scores have been used as outcome predictors in patients with cancer or on hemodialysis. However, their role in patients on continuous ambulatory peritoneal dialysis ...(CAPD) remains unclear. This study aimed to examine the prognostic value of inflammation-based composite scores for mortality in CAPD patients.
This study was conducted in CAPD patients enrolled from January 1, 2006 to December 31, 2014 and followed until December 31, 2016. Three inflammation-based prognostic scores, including Glasgow prognostic score (GPS), prognostic nutritional index (PNI), and prognostic index (PI), were conducted in this study. The associations between these scores and all-cause or cardiovascular mortality were evaluated by Kaplan-Meier method and Cox proportional hazards models. The areas under the curve (AUC) of receiver-operating characteristic (ROC) analysis were used to determine the predictive values of mortality.
A total of 1501 patients were included. During a median follow-up of 38.7 (range, 21.6-62.3) months, 346 (23.1%) patients died, of which 168 (48.6%) were due to cardiovascular diseases (CVD). After adjustment for confounders, the results showed that elevated GPS, PNI, and PI scores were all independently associated with all-cause GPS: Score 1: hazard ratio(HR) 3.94, 95% confidence interval(CI) 2.90-5.35; Score 2: HR 7.56, 95% CI 5.35-10.67; PNI: HR 1.82, 95% CI 1.36-2.43; PI: Score 1: HR 2.08, 95% CI 1.63-2.65; Score 2: HR 3.03, 95% CI 2.00-4.60) and CVD mortality(GPS: Score 1: HR 4.41, 95% CI 2.76-7.03; Score 2: HR 9.64, 95% CI 5.72-16.26; PNI: HR 1.63, 95% CI 1.06-2.51; PI: Score 1: HR 2.57, 95% CI 1.81-3.66, Score 2: HR 3.85, 95% CI 1.99-7.46).The AUC values of GPS score were 0.798 (95% CI0.770-0.826) for all-cause mortality and 0.781 (95% CI 0.744-0.817) for CVD mortality, both of which significantly higher than those of PNI and PI scores (P < 0.001, respectively).
All elevated GPS, PNI, and PI scores were independently associated with all-cause and CVD mortality. The GPS score showed better predictive value than PNI and PI scores in CAPD patients.
Prior studies have shown that the levels of some platelet (PLT) indices were associated with mortality in patients undergoing hemodialysis. We aimed to investigate whether the changes in PLT indices ...associated with mortality in patients on peritoneal dialysis (PD). A single-center, retrospective observational cohort study was conducted in incident PD patients from 1 January 2006 to 31 December 2012, and followed up until 31 December 2014. Cox proportional hazard models were used to examine the relationships between the levels of PLT indices including PLT, plateletcrit (PCT), mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (PLCR), and mortality. Of 1324 patients, 276 (20.8%) died during follow-up (median, 37; IQR, 3-107.4 months), among which 134 were due to cardiovascular diseases (CVD). The highest tertile of PLT levels at baseline was associated with increased risk for cardiovascular mortality after adjustment for demographic, clinical characteristics, and laboratory variables (hazard ratio HR:1.93; 95% confidence interval CI: 1.16-3.20). The similar treads were also observed in the middle and the highest tertile of the PCT level (HR: 1.68, 95%CI: 1.00-2.81 and HR: 1.89, 95%CI: 1.14-3.14, respectively). In addition, the highest tertile of PCT was associated with increased all-cause mortality (HR: 1.41, 95%CI: 1.01-1.96). However, none of the associations in MPV, PDW, and PLCR analyses reached statistical significance (HR: 0.71, 95%CI: 0.43-1.16; HR: 0.72, 95%CI: 0.45-1.18 and HR: 0.74, 95%CI: 0.46-1.19, respectively). These results suggest that higher PLT and PCT may be associated with higher risk for cardiovascular mortality in incident PD patients. Additional studies are needed to investigate whether correction of these two PLT indices reduces the risk.
Gasdermin D (GSDMD) is emerging as an important player in autoimmune diseases, but its exact role in lupus nephritis (LN) remains controversial. Here, we identified markedly elevated GSDMD in human ...and mouse LN kidneys, predominantly in CD11b.sup.+ myeloid cells. Global or myeloid-conditional deletion of GSDMD was shown to exacerbate systemic autoimmunity and renal injury in lupus mice with both chronic graft-versus-host (cGVH) disease and nephrotoxic serum (NTS) nephritis. Interestingly, RNA sequencing and flow cytometry revealed that myeloid GSDMD deficiency enhanced granulopoiesis at the hematopoietic sites in LN mice, exhibiting remarkable enrichment of neutrophil-related genes, significant increases in total and immature neutrophils as well as granulocyte/macrophage progenitors (GMPs). GSDMD-deficient GMPs and all-trans-retinoic acid (ATRA)-stimulated human promyelocytes NB4 were further demonstrated to possess enhanced clonogenic and differentiation abilities compared with controls. Mechanistically, GSDMD knockdown promoted self-renewal and granulocyte differentiation by restricting calcium influx, contributing to granulopoiesis. Functionally, GSDMD deficiency led to increased pathogenic neutrophil extracellular traps (NETs) in lupus peripheral blood and bone marrow-derived neutrophils. Taken together, our data establish that GSDMD deletion accelerates LN development by promoting granulopoiesis in a calcium influx-regulated manner, unraveling its unrecognized critical role in LN pathogenesis.
Background: Serum uric acid (SUA) has been revealed to be positively associated with the body composition parameters in hemodialysis patients, but few studies have investigated that in patients on ...peritoneal dialysis (PD). The aim of this study was to identify the relationship between SUA and appendicular skeletal muscle mass (ASM) and the effect of their interaction on mortality in PD patients. Methods: This was a single-center retrospective cohort study. Patients who underwent multifrequency bioelectrical impedance analysis between January 1, 2013, and December 31, 2016, and had data on SUA values were enrolled. All patients were followed up until December 31, 2019. Results: In total, 802 prevalent PD patients (57.9% male), with mean age of 46.2 ± 14.2 years were enrolled. The average SUA and ASM were 6.8 ± 1.3 mg/dL and 21.2 ± 4.9 kg. According to multiple linear regression models, SUA was positively associated with relative ASM in middle-aged and older PD patients (standardized coefficients β 0.117; 95% confidence interval CI 0.027, 0.200; p = 0.010). Further sex-stratified analysis showed that the association existed only in males (β 0.161; 95% CI 0.017, 0.227; p = 0.023). Moreover, the presence of hyperuricemia was found to predict lower risk of all-cause mortality (hazard ratio HR 0.514, 95% CI 0.272, 0.970; p = 0.040) only in patients with lower relative ASM. And, the adjusted HR of every 1 mg/dL elevated SUA level was 0.770 (95% CI 0.609, 0.972; p = 0.028) for all-cause mortality in the lower relative ASM subgroup. Conclusions: There exists a positive association between the SUA and ASM, and the ASM significantly affected the association between SUA and all-cause PD mortality.
Abstract
Background
With the rapid development of intraocular collamer lens (ICL) operation, it is foreseeable that we will encounter a large number of glaucoma patients with ICL implantation ...history. However, our current understanding of the treatment of glaucoma patients with ICL is limited. Hence we report a rare case of refractory glaucoma after intraocular collamer lens and intraocular lens implantation in a patient who underwent unsuccessful transscleral cyclophotocoagulation, which led to intraocular collamer lens displacement, angle closure and uncontrolled intraocular pressure.
Case presentation
A 39-year-old woman presented with intractably elevated intraocular pressure in the right eye. Since her intraocular collamer lens implantation surgery in 2017, her intraocular pressure had remained over 40 mmHg while using 3 types of anti-glaucoma medications. The patient had a history of phacoemulsification and posterior chamber phakic intraocular lens implantation for complicated cataracts secondary to uveitis in 2006. On gonioscope examination, there were signs of pigment dispersion, and the anterior chamber angle was open. Ultrasound biomicroscopy examination showed contact and rubbing between the intraocular collamer lens and posterior surface of the iris. And typical advanced glaucomatous optic neuropathy and visual field defects were observed. Transscleral cyclophotocoagulation was performed to control the intraocular pressure and prevent further visual field loss. However, the intraocular collamer lens was displaced after transscleral cyclophotocoagulation, which resulted in formation of a shallow anterior chamber 1 week later, angle closure and loss of intraocular pressure control 1 month later, even though the maximum dose of anti-glaucoma medication was used. Finally, an Ahmed glaucoma valve was successfully implanted in her anterior chamber, and the glaucoma was controlled, as observed at the 10-month follow-up.
Conclusions
Pigment dispersion is a common phenomenon after intraocular collamer lens implantation and may accelerate the progression of glaucoma. Transscleral cyclophotocoagulation should be carefully considered in glaucoma patients with elevated intraocular pressure after intraocular collamer lens implantation, given that transscleral cyclophotocoagulation may cause intraocular collamer lens displacement.
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