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The optimal target blood pressure for kidney transplant (KT) patients remains unclear. We included 808 KT patients from the KNOW-KT as a discovery set, and 1,294 KT patients from the KOTRY as a validation set. The main exposures were baseline systolic blood pressure (SBP) at 1 year after KT and time-varying SBP. Patients were classified into five groups: SBP

Abstract Cardiovascular disease remains a leading cause of morbidity and mortality after kidney transplantation (KT). Although statins reduce cardiovascular risk and have renal benefits in the general population, their effects on KT recipients are not well-established. We studied the effects of early statin use (within 1-year post-transplantation) on long-term outcomes in 714 KT recipients from the Korean cohort study for outcome in patients with KT. Compared with the control group, statin group recipients were significantly older, had a higher body mass index, and had a higher prevalence of diabetes mellitus. During a median follow-up of 85 months, 74 graft losses occurred (54 death-censored graft losses and 20 deaths). Early statin use was independently associated with lower mortality (hazard ratio, 0.280; 95% confidence interval 0.111–0.703) and lower death-censored graft loss (hazard ratio, 0.350; 95% confidence interval 0.198–0.616). Statin therapy significantly reduced low-density lipoprotein cholesterol levels but did not decrease the risk of major adverse cardiovascular events. Biopsy-proven rejection and graft renal function were not significantly different between statin and control groups. Our findings suggest that early statin use is an effective strategy for reducing low-density lipoprotein cholesterol and improving patient and graft survival after KT.

Background T50 is a novel serum-based marker that assesses the propensity for calcification in serum. A shorter T50 indicates a greater propensity to calcify and has been associated with cardiovascular disease and mortality among patients with chronic kidney disease. The factors associated with T50 and the correlation between T50 and bone mineral density (BMD) are unknown in hemodialysis (HD) patients. Methods This cross-sectional study included 184 patients undergoing HD. Individuals were grouped into tertiles of T50 to compare the demographic and disease indicators of the tertiles. Linear regression was used to evaluate the association between T50 and hip and spinal BMD in a multivariate model. Results Mineral and inflammatory parameters, including serum phosphate (r = –0.156, p = 0.04), albumin (r = 0.289, p < 0.001), and high-sensitivity C-reactive protein (r = –0.224, p = 0.003) levels, were associated with T50. We found a weak association between T50 and BMD in the total hip area in the unadjusted model (β = 0.030, p = 0.04) but did not find a statistically significant association with the total hip (β = 0.017, p = 0.12), femoral neck (β = –0.001, p = 0.96), or spinal BMD (β = 0.019, p = 0.33) in multivariable-adjusted models. Conclusion T50 was moderately associated with mineral and inflammatory parameters but did not conclusively establish an association with BMD in HD patients. Broad-scale future studies should determine whether T50 can provide insights into BMD beyond traditional risk factors in this population.

Introduction: Coronary artery calcification score (CACS) and abdominal aortic calcification score (AACS) are both well-established markers of vascular stiffness, and previous studies have shown that a higher CACS is a risk factor for chronic kidney disease (CKD) progression. However, the impact of pretransplant CACS and AACS on cardiovascular and renal outcomes in kidney transplant patients has not been established. Methods: We included 944 kidney transplant recipients from the KoreaN cohort study for Outcome in patients With Kidney Transplantation (KNOW-KT) cohort and categorized them into three groups (low, medium, and high) according to baseline CACS (0, 0 < and ≤100, >100) and AACS (0, 1–4, >4). The low (0), medium (0 < and ≤ 100), and high (>100) CACS groups each consisted of 462, 213, and 225 patients, respectively. Similarly, the low (0), medium (1–4), and high (>4) AACS groups included 638, 159, and 147 patients, respectively. The primary outcome was the occurrence of cardiovascular events. The secondary outcomes were all-cause mortality and composite kidney outcomes, which comprised of >50% decline in the estimated glomerular filtration rate and graft loss. Cox regression analysis was used to investigate the association between baseline CACS/AACS and outcomes. Results: The high CACS group (N = 462) faced a significantly higher risk for cardiovascular outcomes (adjusted hazard ratio [aHR], 5.97; 95% confidence interval [CI], 2.01–17.7) and all-cause mortality (aHR, 2.74; 95% CI, 1.27–5.92) compared to the low CACS group (N = 225). Similarly, the high AACS group (N = 638) had an elevated risk for cardiovascular outcomes (aHR, 2.38; 95% CI, 1.16–4.88). Furthermore, the addition of CACS to prediction models improved prediction indices for cardiovascular outcomes. However, the risk of renal outcomes did not differ among CACS or AACS groups. Conclusion: Pretransplant arterial calcification, characterized by high CACS or AACS, is an independent risk factor for cardiovascular outcomes and mortality in kidney transplant patients.

Abstract Proteinuria is typically quantified according to the spot urine protein–creatinine ratio (UPCR) and an association with cardiovascular events has not been thoroughly investigated in chronic kidney disease (CKD) patients. We investigated whether the severity of proteinuria assessed by spot UPCR is associated with an increased risk for cardiovascular outcomes in the CKD population, and whether the relationship is influenced by urine creatinine concentration. We analyzed 1746 patients enrolled as part of The KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Multivariable Cox proportional hazard analysis was performed to evaluate models with proteinuria as a predictor of renal events and extended major adverse cardiovascular events (eMACEs). Risk for renal events was significantly associated with proteinuria across all eGFR and UPCR categories. By contrast, risk for eMACEs increased significantly with UPCR in patients with eGFR ≥ 60 mL/min/1.73 m2 (hazard ratio [HR] 2.109; 95% confidence interval [CI] 1.375–3.235; P = 0.001), but not in patients with eGFR

Abstract Data for Asian kidney transplants are very limited. We investigated the relative importance of prognostic markers in Asian kidney transplants by using Korean Organ Transplantation Registry (KOTRY) cohort. Prediction models were developed by data-driven variable selection approach. The relative importance of the selected predictors was measured by dominance analysis. A total of 4854 kidney transplant donor-recipient pairs were analyzed. Overall patient survival rates were 99.8%, 98.8%, and 91.8% at 1, 3, and 5 years, respectively. Death-censored graft survival rates were 98.4%, 97.0%, and 95.8% at 1, 3, and 5 years. Biopsy-proven acute rejection free survival rates were 90.1%, 87.4%, and 87.03% at 1, 3, and 5 years. The top 3 dominant predictors for recipient mortality within 1 year were recipient cardiovascular disease history, deceased donor, and recipient age. The dominant predictors for death-censored graft loss within 1 year were acute rejection, deceased donor, and desensitization. The dominant predictors to acute rejection within 1 year were donor age, HLA mismatched numbers, and desensitization. We presented clinical characteristics of patients enrolled in KOTRY during the last 5 years and investigated dominant predictors for early post-transplant outcomes, which would be useful for clinical decision-making based on quantitative measures.

Background The soluble forms of suppression of tumorigenicity-2 (ST2) and galectin-3 have been proposed as novel biomarkers for cardiac fibrosis and heart failure, as well as predictors of cardiovascular events and mortality. However, there are limited data on the association between soluble ST2 and galectin-3 and clinical outcomes in patients with kidney failure on replacement therapy. To determine this, we examined the associations between soluble ST2 and galectin-3 and all-cause mortality and cardiovascular events in patients on hemodialysis. Methods This study included maintenance hemodialysis patients (over 18 years old) who consented to preserve their serum in the Biobank at our institution between March 2014 and March 2015. We used Cox proportional hazards regression analysis to evaluate the associations between soluble ST2, galectin-3 levels, and clinical outcomes. The primary outcome was all-cause mortality, the secondary outcome was cardiovascular disease, and patients were followed for both outcomes until March 2018. Results A total of 296 patients were analyzed in this study. The mean age was 57 ± 13 years, and 53.0% were male. Serum concentration of soluble ST2 was significantly associated with higher mortality, after adjustment for confounding factors, but was not associated with cardiovascular disease. Serum galectin-3 level was not independently associated with either outcome after adjustment. Conclusion Elevated soluble ST2 is independently associated with an increased risk of mortality, but not with cardiovascular disease, in patients on hemodialysis. Elevated galectin-3 was not associated with mortality or cardiovascular disease.

Abstract The benefits and risks of aspirin therapy for patients with chronic kidney disease (CKD) who have a high burden of cardiovascular events (CVE) are controversial. To examine the effects of low-dose aspirin on major clinical outcomes in patients with CKD. As a prospective observational cohort study, using propensity score matching, 531 aspirin recipients and non-recipients were paired for analysis from 2070 patients and fulfilled the inclusion criteria among 2238 patients with CKD. The primary outcome was the first occurrence of major CVE. The secondary outcomes were kidney events defined as a > 50% reduction of estimated glomerular filtration rate from baseline, doubling of serum creatinine, or onset of kidney failure with replacement therapy, the all-cause mortality, and bleeding event. The incidence of CVE was significantly greater in low-dose aspirin users than in non-users (HR 1.798; P = 0.011). A significant association between aspirin use and an increased risk of CVE was observed only in the lowest quartile of body weight (HR 4.014; P = 0.019) (Q1

Abstract Recently, waist to hip ratio (WHR) has been reported to be a better indicator of predicting cardiovascular outcomes than body mass index (BMI). We evaluated the effects of pre or post-transplant changes of WHR or BMI on the new onset cardiovascular diseases (CVD) in recipients of kidney transplantation (KT). A total of 572 patients were enrolled from a multicenter observational cohort (KNOW-KT). Measurement of WHR and BMI was done at pre-KT, first and last visit year after KT, and the changes of these parameters and their effect on the incident CVD were analyzed. During the median follow up period of 32.73 ± 15.26 months, the new onset CVD developed in 31 out of 572 patients. The older age, diabetes mellitus and increase of WHR from pre KT or previous follow up year were found to be independent factors predicting the new onset CVD in these patients. However, baseline BMI, WHR prior to KT did not predict the incident CVD. The new metabolic burden, presented as increase of WHR in KT patients has a critical impact on the development of new onset CVD. Strategies to prevent the metabolic burden after KT might improve cardiovascular outcomes and patient’s survival.

Objective:Among the various risk factors associated with contrast-induced acute kidney injury (CI-AKI), the importance of osmolality and viscosity is emerging among the characteristics of contrast media (CM) itself. High osmolality CM (HOCM) is deprecated and low osmotic pressure (LOCM) and iso-osmotic pressure (IOCM) are mainly used in clinical situations where the results of studies on their effect on the development of CI-AKI are contradictory. We evaluated the association between the type of CM and the risk of CI-AKI.Materials and MethodsA retrospective observational cohort study to analyze the effect of the type of CM on the development of CI-AKI. Using propensity score (PS) matching, 2,263 LOCM and IOCM groups were paired for analysis from 5,267 patients and fulfilled the inclusion criteria among 12,742 patients who underwent CAG between 1 January 2007, and 31 December 2016. LOCM included iopromide and iopamidol, IOCM was iodixanol. CI-AKI, which was the primary endpoint, was defined based on the Kidney Disease Improving Global Outcomes criteria within 48 h after exposure to the CM. A multivariable logistic regression analysis was used in the unmatched and matched cohorts, respectively. In addition, a stratified model on clinically important variables, including a high Mehran score (≥ 6), was also used in the matched cohort.ResultsLOCM users showed an increased incidence of CI-AKI (11.7% vs. 9.3%; p = 0.006), but it lost statistical significance after PS matching (9.9% vs. 9.5%, p = 0.725). In multivariable analyses, the adjusted odds ratio for CI-AKI in the LOCM group were 1.059 [95% confidence interval (CI) = 0.875–1.282; p = 0.555] in unmatched cohort and 0.987 (95% CI = 0.803–1.214; p = 0.901) in matched cohort. These results were also consistent with the high-risk (high Mehran score) group.ConclusionsAlthough the role of CM types in the development of CI-AKI has been debated, our observation shows that the selection between LOCM and IOCM during CAG has no influence on the incidence of CI-AKI.

Renal functional deterioration is associated with physical and mental burdens for kidney transplant (KT) and chronic kidney disease (CKD) patients. However, the change in health-related quality of life (HRQOL) over time in KT patients compared to that of native CKD patients has not been evaluated. We addressed this issue using KT patients registered in the KNOW-KT cohort study and patients at CKD stage 1-3 registered in the KNOW-CKD cohort study. HRQOL scores were assessed using the Kidney Disease Quality of Life Short Form at baseline, 2-, and 4-years follow-up in 842 KT patients and at baseline and 5-year follow-up in 1,355 CKD patients. SF-36 scores declined at the 4-year follow-up, whereas CKD-targeted scores showed no change in the KT group. In contrast, CKD-targeted scores as well as SF-36 scores were decreased at the 5-year follow-up in CKD patients. When prognostic factors were analyzed for longitudinal HRQOL data over time, renal functions, diabetes, cardiovascular and cerebrovascular diseases, hemoglobin level, marital status, income, employment, and health care were significant prognostic factors. Furthermore, KT was an independent prognostic factor for better HRQOL. These results highlight that KT can offer a better HRQOL than that of CKD patients, even when renal function is similar.

Proteinuria and hyperphosphatemia are risk factors for cardiovascular disease in patients with chronic kidney disease (CKD). Although the interaction between proteinuria and the serum phosphate level is well established, the mechanistic link between the two, particularly the extent to which this interaction is mediated by phosphate-regulating factors, remains poorly understood. In this study, we examined the association between proteinuria and the serum phosphate level, as well as potential mediators, including circulating fibroblast growth factor (FGF23)/klotho, the 24-h urinary phosphate excretion rate to glomerular filtration rate ratio (EP/GFR), and the 24-h tubular phosphate reabsorption rate to GFR ratio (TRP/GFR). The analyses were performed with data from 1793 patients in whom 24-h urine protein and phosphate, serum phosphate, FGF23, and klotho levels were measured simultaneously, obtained from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Multivariable linear regression and mediation analyses were performed. Total, direct, and indirect effects were also estimated. Patients with high serum phosphate levels were found to be more likely to exhibit greater proteinuria, higher FGF23 levels, and lower klotho levels. The 24-h EP/GFR increased and the 24-h TRP/GFR decreased with increasing proteinuria and CKD progression. Simple mediation analyses showed that 15.4% and 67.9% of the relationship between proteinuria and the serum phosphate level were mediated by the FGF23/klotho ratio and 24-h EP/GFR, respectively. Together, these two factors accounted for 73.1% of the relationship between serum markers. These findings suggest that proteinuria increases the 24-h EP/GFR via the FGF23/klotho axis as a compensatory mechanism for the increased phosphate burden well before the reduction in renal function is first seen.

BackgroundLittle is known regarding optimal tacrolimus (TAC) trough levels after 1 year post-transplant in stable kidney transplant recipients (KTRs) who have not experienced renal or cardiovascular outcomes. This study aimed to investigate the effect of 1-year post-transplant TAC trough levels on long-term renal and cardiovascular outcomes and opportunistic infections in stable KTRs.MethodsKTRs receiving TAC with mycophenolate-based immunosuppression who did not experience renal or cardiovascular outcomes within 1 year post-transplant were enrolled from a multicenter observational cohort study. Renal outcome was defined as a composite of biopsy-proven acute rejection, interstitial fibrosis and tubular atrophy, and death-censored graft loss. Cardiovascular outcome was defined as a composite of de novo cardiomegaly, left ventricular hypertrophy, and cardiovascular events. Opportunistic infections were defined as the occurrence of BK virus or cytomegalovirus infections.ResultsA total of 603 eligible KTRs were divided into the low-level TAC (LL-TAC) and high-level TAC (HL-TAC) groups based on a median TAC level of 5.9 ng/mL (range 1.3-14.3) at 1 year post-transplant. The HL-TAC group had significantly higher TAC trough levels at 2, 3, 4, and 5 years compared with the levels of the LL-TAC group. During the mean follow-up of 63.7 ± 13.0 months, there were 121 renal outcomes and 224 cardiovascular outcomes. In multivariate Cox regression analysis, LL-TAC and HL-TAC were not independent risk factors for renal and cardiovascular outcomes, respectively. No significant differences in the development of opportunistic infections and de novo donor-specific anti-human leukocyte antigen antibodies and renal allograft function were observed between the two groups.ConclusionsTAC trough levels after 1 year post-transplant remained at a similar level until the fifth year after kidney transplantation and were not directly associated with long-term outcomes in stable Korean KTRs who did not experience renal or cardiovascular outcomes. Therefore, in Asian KTRs with a stable clinical course, TAC trough levels higher than approximately 6 ng/mL might not be required after a year of kidney transplantation.

Renin-angiotensin-system (RAS) blockade is thought to slow renal progression in patients with chronic kidney disease (CKD). However, it remains uncertain if the habitual use of RAS inhibitors affects renal progression and outcomes in pre-dialysis patients with advanced CKD. In this multicenter retrospective cohort study, we identified 2,076 pre-dialysis patients with advanced CKD (stage 4 or 5) from a total of 33,722 CKD patients. RAS blockade users were paired with non-users for analyses using inverse probability of treatment-weighted (IPTW) and propensity score (PS) matching. The outcomes were renal death, all-cause mortality, hospitalization for hyperkalemia, and interactive factors as composite outcomes. RAS blockade users showed an increased risk of renal death in PS-matched analysis (hazard ratio [HR], 1.381; 95% CI, 1.071-1.781; P = 0.013), which was in agreement with the results of IPTW analysis (HR, 1.298; 95% CI, 1.123-1.500; P < 0.001). The risk of composite outcomes was higher in RAS blockade users in IPTW (HR, 1.154; 95% CI, 1.016-1.310; P = 0.027), but was marginal significance in PS matched analysis (HR, 1.243; 95% CI, 0.996-1.550; P = 0.054). The habitual use of RAS blockades in pre-dialysis patients with advanced CKD may have a detrimental effect on renal outcome without improving all-cause mortality. Further studies are warranted to determine whether withholding RAS blockade may lead to better outcomes in these patients.

Chronic kidney disease (CKD) represents a major medical challenge and frequently coexists with cardiovascular disease (CVD), which can be treated by statin trerapy. However, whether statin treatment affects renal progression and outcomes in CKD patients remains unclear. We retrospectively reviewed CKD patients at Gachon University Gil Medical Center from 2003-2013. From a total of 14,497 CKD patients, 858 statin users were paired with non-users and analyze with propensity score matching was performed. The outcomes of this study were creatinine doubling, renal death, all-cause mortality, and interactive factors for composite outcomes. Statins were prescribed to 13.5% of the study subjects. Hazard ratios (HRs) [95% confidence intervals (CIs)] for statin treatment for the doubling of serum creatinine levels were significant only in CKD patients with an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2, and were 0.744 (0.635-0.873) in the unmatched cohort and 0.767 (0.596-0.986) in the matched cohort. In analyses of secondary outcomes, the HRs (95% CIs) for all-cause mortality were 0.655 (0.502-0.855) in the unmatched cohort and 0.537 (0.297-0.973) in the matched cohort. The HRs (95% CIs) for statin therapy for composite outcomes among patients with and without an eGFR ≥30 mL/min/1.73 m2 were 0.764 (0.613-0.952) and 1.232 (0.894-1.697), respectively (P for interaction, 0.017). Thus, statin treatment may have beneficial effects on renal progression and all-cause mortality only for the patients with early- stage CKD.

Early detection and accurate differentiation of the cause of AKI may improve the prognosis of the patient. However, to date, there are few reliable biomarkers that can discriminate between pre-renal and intrinsic AKI. In this study, we determined whether AKI is associated with altered serum and urinary levels of Klotho, S100A8/A9 (an endogenous ligand of toll-like receptor 4), and neutrophil gelatinase-associated lipocalin (NGAL), which may allow differentiation between pre-renal and intrinsic AKI. A volume-depleted pre-renal AKI model was induced in male Sprague Dawley rats fed a low-salt diet (0.03%) without water 96 h before two intraperitoneal (IP) injections of furosemide (20 mg/kg) at a 24 h interval. In contrast, in the cisplatin-induced intrinsic AKI model, animals were given a single IP injection of cisplatin (5 mg/kg). All of the animals were euthanized 72 h after the first IP injection. Serum and urinary levels of Klotho, S100A8/A9, and NGAL were measured using an enzyme-linked immunosorbent assay. We also performed a proof-of-concept cross-sectional study to measure serum and urinary biomarkers in 61 hospitalized patients with established AKI. Compared to the intrinsic AKI group, the pre-renal AKI group showed a marked depression in urinary Klotho levels (13.21 ± 17.32 vs. 72.97 ± 17.96 pg/mL; P = 0.002). In addition, the intrinsic AKI group showed marked elevation of S100A8/A9 levels compared to the pre-renal AKI group (2629.97 ± 598.05 ng/mL vs. 685.09 ± 111.65 ng/mL; P = 0.002 in serum; 3361.11 ± 250.86 ng/mL vs. 741.72 ± 101.96 ng/mL; P = 0.003 in urine). There was no difference in serum and urinary NGAL levels between the pre-renal and intrinsic AKI groups. The proof-of-concept study with the hospitalized AKI patients also demonstrated decreased urinary Klotho in pre-renal AKI patients and increased urinary S100A8/A9 concentrations in intrinsic AKI patients. The attenuation of urinary Klotho and increase in urinary S100A8/A9 may allow differentiation between pre-renal and intrinsic AKI.

Vascular calcification is an important factor associated with mortality in dialysis patients. Recently, soluble receptor for advanced glycation end product (sRAGE) and extracellular RAGE binding protein S100A12 (EN-RAGE) have been reported to be involved in the process of vascular calcification. Therefore, we investigated whether sRAGE and S100A12 are useful indicators of progression of abdominal aortic calcification in hemodialysis (HD) patients. We analyzed annual changes in vascular calcification score (VCS) for up to 4 years, compared to clinical and biological parameters in 149 HD patients. VCS was assessed annually using plain X-ray images of the lateral lumbar spine. The progression group was defined as patients with an increase in VCS more than 1 point each year on average during the observation period. Time-averaged concentrations were also evaluated to examine the association between biological parameters and changes in VCS. The patients had a mean age of 58.59 ± 12.93 years; 53.7% were male, and 45% were diabetic. The VCS increased in 55 patients; the mean increase was 1.60 ± 2.91 points. In a stepwise multivariate logistic analysis, we found that higher levels of S100A12 were significantly associated with progression of VCS (odds ratio [OR], 2.622; 95% confidence interval [CI], 1.371-5.016; P = 0.004). The relationship between sRAGE and VCS was not statistically significant (OR, 0.644; 95% CI, 0.302-1.374; P = 0.255). Our findings suggest that serum levels of S100A12 are associated with progression of abdominal aortic calcification in HD patients, independent of sRAGE level.

Chronic kidney disease (CKD) is a major risk factor for the development of cardiovascular disease (CVD). Previous trials have investigated the effects of low-dose aspirin on CVD prevention in patients with diabetes; however, patients with CKD were not examined. The role of aspirin in diabetics is controversial, and the available literature is contradictory. Therefore, we studied whether low-dose aspirin would be beneficial for patients with CKD, a group that is at high risk for CVD.From a total of 25340 patients with CKD, 1884 recipients of low-dose aspirin (100 mg/day) were paired 1∶1 with non-recipients for analysis using propensity score matching. The primary endpoint was the development of atherosclerotic CVD, including coronary arterial disease, stroke, and peripheral arterial disease. Secondary endpoints included death from any cause, bleeding events, doubling of serum creatinine, and renal death.The incidence of a primary endpoint of any atherosclerotic CVD was significantly higher in the aspirin users than in the non-users (P

Although innate immunity plays important roles in xenograft rejection, there have been few studies on the role of toll-like receptors (TLRs) in xenotransplantation. Furthermore, most studies focused on the recipient's TLRs. Therefore, we investigated whether TLRs in porcine islets can contribute to islet xenograft rejection. Adult porcine islets were isolated and stimulated by polyinosinic/polycytidylic acid (poly I:C) or lipopolysaccharide (LPS). Both poly I:C and LPS stimulation in porcine islets induced expression of chemokines (RANTES, MCP-1, IP-10, and IL-8), cytokines (IL-6 and type I interferons), and adhesion molecules (VCAM-1 and ICAM-1). Porcine islet supernatants stimulated by TLR agonists induced chemotaxis of human leukocytes. They also induced procoagulant activation (tissue factor and fgl-2). However, TLR stimulation did not influence insulin secretion. When porcine MyD88 was knocked down using shRNA lentivirus, TLR-mediated induction of proinflammatory mediators and procoagulants was attenuated. When LPS was injected to MyD88 or TLR4 knockout mice after porcine islet transplantation, LPS stimulation on donor islets interfered with islet xenograft tolerance induction by anti-CD154 antibodies. Inflammatory cell infiltration and expression of proinflammatory chemokines and cytokines in islet xenografts also increased. In conclusion, TLR activation in porcine islets induced both a proinflammatory and procoagulant response and thereby contributed to xenograft rejection.

Fluid overload has been linked to mortality in peritoneal dialysis (PD) patients. Residual renal function is important for patient survival. Therefore, the objective of this study was to analyze volume status in PD patients, and to identify associations between volume status and residual renal volume. We performed a cross-sectional, observational, single-center study. Body composition was measured using a portable multifrequency whole-body bioimpedance assessment, and residual renal volume was measured. We examined 75 patients (66.7% male), with a mean age of 50.7±13.0 years and mean body mass index of 23.5±3.5 kg/m2. Length of time on dialysis was 46.5±37.9 months. Anuria (≤100 mL/day) is associated with relative overhydration (ROH) (p=0.014) and extracellular water volume (p=0.014). In a multivariable linear regression analysis, anuria (coefficient β=0.217, p=0.025), diabetes (coefficient β=0.213, p=0.027), and serum albumin level (coefficient β=−0.533, p

Xenotransplantation using transgenic pigs as an organ source is a promising strategy to overcome shortage of human organ for transplantation. Various genetic modifications have been tried to ameliorate xenograft rejection. In the present study we assessed effect of transgenic expression of human heme oxygenase-1 (hHO-1), an inducible protein capable of cytoprotection by scavenging reactive oxygen species and preventing apoptosis caused by cellular stress during inflammatory processes, in neonatal porcine islet-like cluster cells (NPCCs). Transduction of NPCCs with adenovirus containing hHO-1 gene significantly reduced apoptosis compared with the GFP-expressing adenovirus control after treatment with either hydrogen peroxide or hTNF-α and cycloheximide. These protective effects were diminished by co-treatment of hHO-1 antagonist, Zinc protoporphyrin IX. We also generated transgenic pigs expressing hHO-1 and analyzed expression and function of the transgene. Human HO-1 was expressed in most tissues, including the heart, kidney, lung, pancreas, spleen and skin, however, expression levels and patterns of the hHO-1 gene are not consistent in each organ. We isolate fibroblast from transgenic pigs to analyze protective effect of the hHO-1. As expected, fibroblasts derived from the hHO-1 transgenic pigs were significantly resistant to both hydrogen peroxide damage and hTNF-α and cycloheximide-mediated apoptosis when compared with wild-type fibroblasts. Furthermore, induction of RANTES in response to hTNF-α or LPS was significantly decreased in fibroblasts obtained from the hHO-1 transgenic pigs. These findings suggest that transgenic expression of hHO-1 can protect xenografts when exposed to oxidative stresses, especially from ischemia/reperfusion injury, and/or acute rejection mediated by cytokines. Accordingly, hHO-1 could be an important candidate molecule in a multi-transgenic pig strategy for xenotransplantation.

ObjectiveTo analyze the trends in life expectancy and cause-eliminated life expectancy of the registered residents in Qingpu District, Shanghai from 2002 to 2021, and to identify the major diseases causing life expectancy loss in the area, so as to provide a theoretical basis for strengthening disease prevention and interventions and optimizing health resources allocation.MethodsUsing the International Classification of Diseases (ICD)-10 classification of death causes, average life expectancy and cause-eliminated life expectancy were calculated with the abbreviated life table and the cause-eliminated life expectancy table. A trend forecast of life expectancy from 2022 to 2029 was made.ResultsFrom 2002 to 2021, the life expectancy of Qingpu District residents showed an increasing trend, with an average annual growth of 0.32 years (AAPC=0.39%, P

ObjectiveTo analyze the characteristics and changing trend of injury cause of mortality of residents in Qingpu District from 2002 to 2020， and to provide scientific reference for formulating regional prevention and control measures.MethodsThe injury mortality data of the registered residents in Qingpu District from 2002 to 2020 were collected. The indicators such as crude mortality rate， standardized mortality rate， and the ranking of causes of death were calculated.ResultsFrom 2002 to 2020， the average annual crude mortality rate was 50.27/ 100 000， the age-standardized mortality rate based on the world standard population（ASRW） was 30.08/100 000， and the age-standardized mortality rate based on the 2010 Chinese census（ASMRC） was 35.58/100 000. The average annual crude mortality rate of males was higher than that of females ［Z=54.402， Mantel-Hanszel χ2=1 742.509， P

Objective To explore the effect of group cognitive behavioral therapy (CBT) on the clinical outcome of patients with persistent high-risk human papillomavirus (HR-HPV) infection, and to construct a systematic psychological intervention treatment program for persistent HR-HPV infection patients with emotional disorders. Methods A total of 96 patients with persistent HR-HPV infection complicated with emotional disorder admitted in our hospital from September 2021 to March 2022 were recruited, and then randomly divided into an intervention group (n=44) and a control group (n=45) after 5 of them were excluded due to personal reason. The control group received health education and follow-up monitoring, and the intervention group received group CBT intervention additionally. Their clinical outcomes and psychological scale scores were compared between the 2 groups. Results In a follow-up for 6 and 12 months, the regression rate of HR-HPV infection was higher, and the sustained infection rate and progression rate of HR-HPV in the intervention group than the control group (P < 0.05). The intervention group also obtained lower scores of Nine-Item Patient Health Questionnaire (PHQ-9) and generalized anxiety scale (GAD-7) immediately after the intervention, and 6 and 12 months in follow-up for when compared with the control group (P < 0.05). And the scores at above time points were statistically lower than those before intervention in the intervention group (P < 0.05), but no such differences were observed in the control group (P>0.05). Conclusion Systematic psychological intervention treatment is beneficial to HR-HPV infection subside for patients with persistent HR-HPV infection. [Key words] human papillomavirus , cognitive behavioral therapy , cervix, reversion ,