A new missense mutation of calcium sensing receptor with isoleucine replaced by serine at codon 857 leading to type V Bartter syndrome.

Several genetic defects on thick ascending limb (TAL) of Henle loop were reported to cause Bartter syndrome (BS) characterized by metabolic alkalosis, hypokalemia, and normal or low blood pressure. Among them, defective basolateral calcium sensing receptors (CaSR) on TAL could result in type V BS that not only presents typical characteristics of BS but also hypocalcemia. Herein we report a 54 years old female patient with a novel mutation of CaSR that leads to type V BS. A sequencing of CaSR gene in peripheral blood mononuclear cells and urine stem cells both disclosed a heterozygous substitution of thymine for guanine (NM_001178065.1:c.2570T > G) in exon 7 at codon 857 resulting in substitution of isoleucine for serine (p.I857S). We performed functional tests of the mutant CaSR gene in vitro using urine stem cells to determine whether this mutation is responsible for the clinical presentations. Urine stem cells expressing abundant CaSR on flow cytometry of this patient and a normal subject were obtained for in vitro functional studies, including intracellular calcium and inositol 1,4,5-trisphosphate concentrations in response to increasing concentrations of extracellular calcium. The results show all of their responses to extracellular calcium are extremely sensitive in urine stem cells of the case as compared to those of the normal subject, indicating a prominent gain-of-function mutation. A novel mutation I857S in transmembrane domain 7 of CaSR in our patient would be added to the list of mutations leading to type V BS.

Infectious complications in adult patients with idiopathic minimal change nephrotic syndrome undergoing immunosuppressive therapy.

BACKGROUND: Patients with idiopathic minimal change nephrotic syndrome (MCNS) undergoing immunosuppressive therapy are susceptible to infectious complications. Study specifically focusing on adult population's infectious complications is lacking. METHODS: We retrospectively collected 101 adult patients with biopsy-proven idiopathic MCNS and analysed for the infectious complications. Published literatures were also reviewed aiming to evaluate the feasibility of prophylactic antibiotic treatment. RESULTS: Infectious complications developed in 17 of 101 (16.8%) patients, with pneumonia (n = 4), cellulitis/fasciitis (n = 4) and urinary tract infection (UTI) (n = 4) being the dominant diseases, and Gram-negative bacilli the main cause. AKI stage ≥2 (Hazard ratio = 6.1; 95% CI: 1.2-31.9, p = 0.031) and non-remission by treatment (Hazard ratio = 4.4; 95% CI: 1.2-15.6, p = .023) were the two independent risk factors relevant to developing infectious complications. Review of 16 published literatures and our data showed that even no prophylactic antibiotic therapy, only one case of Pneumocystis jirovecii pneumonia developed among the 1787 accumulative cases of MCNS. In contrast, 16 (44%) of acute flare cases were reported among the 36 patients with positive hepatitis B surface antigen that did not receive antiviral prophylactic therapy. CONCLUSIONS: Advanced acute kidney injury and non-remission by treatment are the risk factors toward developing infectious complications in adult MCNS undergoing immunosuppressive therapy. It appears unnecessary to use prophylactic antibiotic for Pneumocystis jirovecii pneumonia or other bacterial infections, while screening and prophylactic therapy for hepatitis B and latent tuberculosis are critical for patients in prevalent area.

Psychometric properties and measurement invariance of Short-Form Life Attitude Inventory for hospital staff.

BACKGROUND: The life attitude of health care workers can deeply influence the quality of care. Examining the performance of the Short-Form Life Attitude Inventory (SF-LAI), this study analyzes the factorial structure, reliability, and invariance of the revised SF-LAI across genders and professions among the staff of a teaching medical center. METHODS: The SF-LAI was developed for university students in Taiwan. From January to February 2019, we administered a cross-sectional survey of life attitudes by distributing the SF-LAI to all staff members of a medical center in Taiwan. The construct validity was evaluated using a confirmatory factor analysis (CFA). Model fit was assessed in terms of the comparative fit index (CFI), Tucker-Lewis index (TFI), standardized root mean square residual (SRMR), and root mean square of error of approximation (RMSEA). Internal consistency was calculated using Cronbach's alpha and McDonald's omega. We also performed the CFA invariance analysis for the SF-LAI-R across genders and professions (physician, nurse and other hospital staff). RESULTS: Of 884 (24.62%) responses, 835 were valid. The participants had a mean age of 47.8 years, and 20.12% were male. In a comparison of multiple CFAs, a second-order model with six factors outperformed other models. The goodness of fit indices revealed the CFI was 0.955, TFI was 0.952, RMSEA was 0.071, and SRMR was 0.038. The Cronbach's alphas, McDonald's omega coefficients for internal consistency were all greater than 0.8. The first and second-order model had metric and scalar invariance across genders and professions. CONCLUSIONS: As health care demands evolve, humanities are becoming more important in medical education. Life attitude of hospital care worker is a crucial indicator of whether one embodies the ideals of a humanistic education. The revised SF-LAI has acceptable structural validity, internal consistency, and invariance across genders and professions among staff members of a teaching medical center.

Prophylactic hemodialysis following coronary angiography and one-year outcomes in non-dialysis patients with chronic kidney disease: A propensity-matched study.

BACKGROUND/PURPOSE: Prophylactic hemodialysis after coronary angiography in patients with chronic kidney disease (CKD) prevents contrast nephropathy; however, the one-year outcomes are unclear. This study aimed to investigate the one-year outcomes of prophylactic hemodialysis against standard treatment in patients with CKD who underwent coronary angiography. METHODS: A cohort study of 359 patients with CKD, coronary artery disease (CAD), and serum creatinine levels of 176.8-530.4 µmol/L, who were referred for elective coronary angiography was conducted. Propensity score matching identified 118 patient pairs for outcome comparisons. The hemodialysis group underwent prophylactic hemodialysis after coronary angiography, whereas the control group received standard treatment. The study's primary outcome was free from dialysis was considered the primary outcome, whereas the secondary outcome was overall survival. Unadjusted estimates of the probability of free from dialysis and overall survival were computed using Kaplan-Meier survival curves and log-rank tests. Cox proportional-hazards regression models were used in determining the risk factors associated with ESRD and mortality. RESULTS: During a mean 9.3 months follow-up duration, the hemodialysis group had significantly better free from dialysis (85.6% vs. 64.4%; P = 0.002) and overall survival (85.4% vs. 78.5%; P = 0.008) rates than the control group. Cox proportional-hazards regression analyses of the propensity score-matched patients showed that the hemodialysis group had reduced risks for ESRD and mortality (hazard ratios, 0.32 and 0.48, respectively). CONCLUSION: Prophylactic Hemodialysis following coronary angiography was associated with reduced ESRD and mortality risks in CKD patients with CAD, who did not routinely undergo dialysis.

Clinical risk factors and outcomes of massive ascites accumulation after discontinuation of peritoneal dialysis.

Background: Encapsulating peritoneal sclerosis (EPS) is a serious complication of peritoneal dialysis (PD), with high morbidity and mortality that requires an early diagnosis for effective treatment. PD withdrawal and bacterial peritonitis are important triggers for the onset of EPS. However, few studies have focused on cases of PD withdrawal without a clinical diagnosis of peritonitis, cirrhosis, or carcinomatosis. We aimed to compare the clinical characteristics and computed tomography (CT) images of patients with or without ascites in such situations and assess clinical outcomes in terms of mortality.Methods: Our retrospective review included 78 patients who withdraw PD between January 2000 and December 2017.Results: Ten patients had ascites, and 68 did not have a significant intra-abdominal collection. The ascites group had a significantly longer PD duration (months; 134.41 [range, 35.43-181.80] vs. 32.42 [733-183.47], p < 0.001) and higher peritoneal membrane transport status based on the dialysate-to-plasma ratios of creatinine (0.78 ± 0.08 vs. 0.68 ± 0.11, p = 0.009) and glucose (0.27 ± 0.07 vs. 0.636 ± 0.08, p = 0.001) than the control group. CT parameters, including peritoneal calcification, thickness, bowel tethering, or bowel dilatation, were not all present in each patient with ascites and EPS. During the 12-month study period, the ascites group had a higher risk for developing EPS (70% vs. 0%, p < 0.001) and a higher 12-month all-cause mortality (30% vs. 0%, p = 0.002).Conclusions: Ascites accumulation was not rare after PD discontinuation. A longer PD duration and high peritoneal membrane transport status could predict subsequent ascites accumulation. Furthermore, patients with ascites were at a higher risk of EPS.

Secretome of Hypoxic Endothelial Cells Stimulates Bone Marrow-Derived Mesenchymal Stem Cells to Enhance Alternative Activation of Macrophages.

We intended to explore the cellular interaction between mesenchymal stem cells (MSCs) and injured endothelial cells leading to macrophage alternative polarization in healing kidney ischemic reperfusion injury. In vivo, the amounts of recruited macrophages were significantly mitigated by MSCs in the injured tissues, especially in the group using hematopoietic cell E- and L-selectin ligand (HCELL)-positive MSCs. Compared to controls, MSCs also enhanced expression of CD206 and CD163, which was further enhanced by HCELL expression. In vitro, analysis of cytokines involving macrophage polarization showed IL-13 rather than IL-4 from MSCs agreed with expression of macrophage CD206 in the presence of hypoxic endothelial cells. Among them, HCELL-positive MSCs in contact with hypoxic endothelial cells produced the greatest response, which were reduced without HCELL or using a transwell to prevent cell contact. With blockade of the respective cytokine, downregulated MSCs secretion of IL-13 and CD206 expression were observed using inhibitors of IFN-γ and TNF-α, but not using those of TGF-ß and NO. With IFN-γ and TNF-α, MSCs IL-13 secretion and CD206 expression were upregulated. In conclusion, hypoxia induces endothelial cells producing multiple cytokines. Among them, IFN-γ and TNF-α that stimulate MSCs to secrete IL-13 but not IL-4, leading to alternative polarization.

Evaluation of the association of Wnt signaling with coronary artery calcification in patients on dialysis with severe secondary hyperparathyroidism.

BACKGROUND: Patients with end-stage renal disease have a higher risk of death from cardiovascular events, which can be mainly attributed to coronary artery calcification (CAC). Wnt signaling is involved in vascular development and may play a role in vascular calcification. This study aimed to evaluate CAC prevalence in patients on dialysis with severe secondary hyperparathyroidism (SHPT) and identify CAC risk factors. METHODS: The study is a retrospective analysis of the severe hyperparathyroidism registration study that prospectively recruited patients on dialysis with severe SHPT who were candidates for parathyroidectomy, from October 2013 to May 2015. CAC and bone mineral density (BMD) were measured. Demographic and clinical data including calcium, phosphorus, alkaline phosphatase, intact parathyroid hormone, Dickkopf-related protein 1 (DKK1), and sclerostin levels were analyzed. CAC scores were reported in Agatston units (AU). RESULTS: A total of 61 patients were included in this study. No CAC, mild CAC (<100 AU), moderate CAC (>100 AU), and severe CAC (>400 AU) were observed in 4.9%, 11.4%, 14.8%, and 68.9% of patients, respectively. DKK1 and sclerostin were not associated with CAC. In univariate analysis, CAC was significantly correlated with age, sex (male), total cholesterol, and intravenous pulse calcitriol (p<0.05). CAC was not inversely correlated with the BMD, T scores, or Z scores of the femoral neck (p>0.05). In multivariate analysis, the stepwise forward multiple linear regression revealed that CAC was associated with age, male sex and intravenous pulse calcitriol (p<0.05). Furthermore, serum sclerostin was positively correlated with the BMD of the femoral neck but negatively associated with intact parathyroid hormone (p<0.05). Serum sclerostin was significantly associated with severely low bone mass with Z-scores<-2.5 of the femoral neck, even when adjusted for serum intact parathyroid hormone, vitamin D status, dialysis pattern, sex, and DKK-1 (p<0.05). CONCLUSIONS: The patients on dialysis with severe SHPT have a high prevalence of vascular calcification. Although the Wnt signaling pathway could play a role in hyperparathyroid bone disease, CAC may be mainly due to the treatment modality rather than the Wnt signaling pathway associated bone metabolism in patients on dialysis with severe SHPT.

CD44 fucosylation on mesenchymal stem cell enhances homing and macrophage polarization in ischemic kidney injury.

The lack of homing ability possibly reduces the healing potential of bone-marrow-derived mesenchymal stem cells (MSCs). Therefore, transforming native CD44 on MSCs into a hematopoietic cell E-/L-selectin ligand (HCELL) that possesses potent E-selectin affinity might enhance the homing and regenerative abilities of MSCs. Through fucosyltransferase VI (FTVI) transfection, MSCs were fucosylated on N-glycans of CD44 to become HCELL positive, thus interacting with E-selectin on injured endothelial cells. HCELL expression facilitated MSC homing in kidneys within 24h after injury and reduced lung stasis. An in vitro adhesion assay revealed that transfection enhanced the association between MSCs and hypoxic endothelial cells. In mice treated with HCELL-positive MSCs, the injured kidneys exhibited clusters of homing MSCs, whereas MSCs were rarely observed in mouse kidneys treated with HCELL-negative MSCs. Most MSCs were initially localized at the renal capsule, and some MSCs later migrated inward between tubules. Most homing MSCs were in close contact with inflammatory cells without tubular transdifferentiation. Furthermore, HCELL-positive MSCs substantially alleviated renal injury, partly by enhancing the polarization of infiltrating macrophages. In conclusion, engineering the glycan of CD44 on MSCs through FTVI transfection might enhance renotropism and the regenerating ability of MSCs in ischemic kidney injury.

Pelvic drainage during removal of dialysis catheter decreases the risk of subsequent intra-abdominal complications in refractory peritoneal dialysis-related peritonitis.

AIM: Some patients with refractory peritoneal dialysis-related peritonitis continue to develop intra-abdominal complications despite removal of the peritoneal catheter. Repeated percutaneous drainage or open laparotomy is often required, and mortality is not uncommon. The benefits of pelvic drainage placement during catheter removal in decreasing these complications and interventions remain unproven. METHODS: Forty-six patients with refractory peritonitis who underwent removal of a Tenckhoff catheter between 1991 and 2013 were reviewed retrospectively. Twelve patients had pelvic drainage using closed active suction devices during catheter removal (drainage group). The remaining 34 patients underwent catheter removal without drainage (non-drainage group). The outcomes measured were the development of intra-abdominal complications and the requirement for repeated percutaneous drainage or open laparotomy within 90 days after the catheter removal. RESULTS: Baseline characteristics were similar with the exception of a higher median number of previous peritonitis episodes in the drainage group compared with the non-drainage group (2 vs 0, P = 0.02). During the follow-up period, intra-abdominal complications occurred in 15 (44%) of 34 patients in the non-drainage group, compared with one (8%) of 12 patients in the drainage group (P = 0.03). Twelve (35%) patients in the non-drainage group required repeated percutaneous drainage or open laparotomy for management, compared with zero (0%) patients in the drainage group (P = 0.02). Drain tubes were removed at a median of 6 days (inter-quartile range: 5-10) without complications. CONCLUSIONS: In the management of refractory peritonitis, pelvic drainage during removal of dialysis catheter decreases the risk of subsequent intra-abdominal complications and invasive interventions.

Parathyroidectomy improves cardiovascular outcome in nondiabetic dialysis patients with secondary hyperparathyroidism.

OBJECTIVE: Secondary hyperparathyroidism and its associated abnormalities in mineral metabolism and haemodynamic changes increase the cardiovascular risk in patients with end-stage renal disease (ESRD). Our objective was to determine the association of parathyroidectomy (PTX) with major cardiovascular events in nondiabetic dialysis patients with severe secondary hyperparathyroidism (SHPTH). DESIGN AND PATIENTS: We performed a cohort study with fifty-three nondiabetic ESRD patients who were treated with maintenance haemodialysis and who had intact parathyroid hormone (PTH) levels > 800 pg/ml. Participants received either only medical therapy or medical therapy and total PTX with autotransplantation for SHPTH. MEASUREMENTS: We evaluated the associations between PTX and major cardiovascular events including death, cerebrovascular accident and myocardial infarction. The biochemical and haemodynamic changes associated with PTX were measured. RESULTS: During the mean follow-up of 72 months, twenty-three patients received only medical treatment (medical group) while thirty patients underwent PTX in addition to medical treatment (PTX group). The two groups were comparable in respect of baseline characteristics. PTX group was found to be associated with a reduced incidence of major cardiovascular events (P = 0·021). A multiple Cox regression analysis showed that the variable significantly associated with major cardiovascular events was treatment modality (medical therapy vs medical therapy and parathyroidectomy, hazard ratio = 26·12, 95% CI = 1·30-526·27, P = 0·033). Blood pressure, haemoglobin, alkaline phosphatase, calcium, phosphate and calcium × phosphate product significantly improved after PTX. CONCLUSIONS: PTX was associated with better cardiovascular outcome in nondiabetic dialysis patients with severe SHPTH.

The relation of location-specific epicardial adipose tissue thickness and obstructive coronary artery disease: systemic review and meta-analysis of observational studies.

BACKGROUND: There is growing evidence about the importance of epicardial adiposity on cardiometabolic risk. However, the relation of location-specific epicardial adipose tissue (EAT) thickness to coronary atherosclerotic burden is still unclear. METHODS: This meta-analysis was used to study the relations between location-specific EAT thickness and obstructive coronary artery disease (CAD). A systemic literature search to identify eligible studies that met the inclusion criteria from the beginning until January 2014 was made. We conducted the meta-analysis of all included 10 published studies. Pre-specified subgroup analyses were performed according to ethnicity, body mass index, diagnostic tools for CAD, and measurement tool if presence of high heterogeneity between studies. Potential publication bias was also assessed. RESULTS: We identified ten observed studies with a total of 1625 subjects for planned comparison. With regard to the association between obstructive CAD and location-specific EAT thickness at the right ventricular free wall, caution is warranted. The pooled estimate showed that location-specific EAT thickness at the right ventricular free wall was significantly higher in the CAD group than non-CAD group (standardized mean difference (SMD): 0.70 mm, 95% CI: 0.26-1.13, P = 0.002), although heterogeneity was high (I2 = 93%). It should be clear that only the result of echocardiography-based studies showed a significant association (SMD: 0.98 mm, 95% CI: 0.43-1.53, P = 0.0005), and the result of all included CT-based studies showed a non-significant association (SMD: 0.06 mm, 95% CI: -0.12-0.25, P = 0.50). In the subgroup analysis, the "diagnostic tools for CAD" or "measurement tool of EAT thickness" are potential major sources of heterogeneity between studies. With regard to location-specific EAT thickness at the left atrioventricular (AV) groove, it was significantly higher in the CAD group than non-CAD group (SMD: 0.74 mm, 95% CI: 0.55-0.92, P <0.00001; I2 = 0%). CONCLUSION: Our meta-analysis suggests that significantly elevated location-specific EAT thickness at the left AV groove is associated with obstructive CAD. Based on the current evidence, the location-specific EAT thickness at the left AV groove appears to be a good predictor in obstructive CAD, especially in Asian populations. Furthermore well-designed studies are warranted because of the current limited number of studies.

Retrospective evaluation of standard diagnostic procedures in identification of the causes of new-onset syndrome of inappropriate antidiuresis.

BACKGROUND: Many diagnostic procedures are conducted in patients with syndrome of inappropriate antidiuresis (SIAD). However, the contribution in identification of the cause of SIAD remains unknown. METHODS: The study was conducted at Kaohsiung Veterans General Hospital in southern Taiwan. From January 2000 to December 2009, medical records of 439 adult patients hospitalized for new-onset SIAD at a single center were retrospectively collected. All diagnostic procedures during hospitalization were divided into four groups: chest/lung, central nervous system, abdomen, and bone marrow to evaluate their positive rate leading to the cause of SIAD. Factors associated with "procedures leading to the cause" were also analyzed to improve efficacy of survey. RESULTS: Cause of SIAD was identified in 267 (60.8%). Of them, 150 were pulmonary disorders, 44 were drugs, 37 were central nervous system disorders, 32 were malignancy and 4 were post-surgery. Survey for chest/lung, central nervous system, abdomen, and bone marrow were performed in 96.6%, 29.2%, 38.0% and 3.6% of patients, respectively; positive findings leading to the cause of SIAD were 39.6%, 12.5%, 5.3% and 6.3%, respectively. Among the diagnostic procedures, chest x-ray (424/439, 96.6%) was most frequently performed with the highest identification rate of 34.7% (147 cases). Major significant independent factors that associated with "procedure leading to a cause" were: absence of SIAD-associated drug history, presence of fever/chills, and presence of respiratory symptoms. Cause of SIAD became evident later during the follow-up period in 10 of 172 (5.8%) patients who were initially thought to be cause-unknown. Malignancy was the cause for 5 cases and pulmonary tuberculosis was for the other five. Eight of these causes became evident within one year after the diagnosis of SIAD. CONCLUSIONS: SIAD with unidentified causes were prevalent. Current diagnostic procedures remain not satisfying in determining the cause of SIAD, but chest radiograph did demonstrate higher diagnostic rate, especially in patients presented with fever, chills, respiratory symptoms, and without SIAD-associated drug history. Patients with unidentified cause should be followed for at least one year when most hidden causes (e.g. malignancy and tuberculosis) become obvious.

A novel poly-naphthol compound ST104P suppresses angiogenesis by attenuating matrix metalloproteinase-2 expression in endothelial cells.

Angiogenesis, the process of neovascularization, plays an important role in physiological and pathological conditions. ST104P is a soluble polysulfated-cyclo-tetrachromotropylene compound with anti-viral and anti-thrombotic activities. However, the functions of ST104P in angiogenesis have never been explored. In this study, we investigated the effects of ST104P in angiogenesis in vitro and in vivo. Application of ST104P potently suppressed the microvessels sprouting in aortic rings ex vivo. Furthermore, ST104P treatment significantly disrupted the vessels' development in transgenic zebrafish in vivo. Above all, repeated administration of ST104P resulted in delayed tumor growth and prolonged the life span of mice bearing Lewis lung carcinoma. Mechanistic studies revealed that ST104P potently inhibited the migration, tube formation and wound closure of human umbilical endothelial cells (HUVECs). Moreover, ST104P treatment inhibited the secretion and expression of matrix metalloproteinase-2 (MMP-2) in a dose-dependent manner. Together, these results suggest that ST104P is a potent angiogenesis inhibitor and may hold potential for treatment of diseases due to excessive angiogenesis including cancer.

Trends in the incidence of urothelial carcinoma in Taiwan after the ban on aristolochic acid-containing Chinese herbal preparations, 2001-2018: a national population-based cohort study.

PURPOSE: Urothelial carcinoma (UC) of the bladder (BUC) and the upper urinary tract (UTUC) are the two most common UCs. The incidence of UTUC in Taiwan is the highest worldwide. Aristolochic acid (AA) was identified as the main cause of UTUC in Taiwan. To explore trends in the incidence of UC in Taiwan after the ban on Chinese herbal preparations containing AA in 2003. METHODS: We used data from the Taiwanese National Health Insurance Research Database-linked Taiwanese National Cancer Registry for 2001-2018. UC was defined in accordance with the International Classification of Disease for Oncology. The age-standardized incidence was calculated on the basis of the World Health Organization standard population. Trends in the incidence were calculated as the annual percent change (APC) by using the Joinpoint regression program. RESULTS: Over the investigated period, the incidence of UC decreased at an average annual percent change (AAPC) of - 1.19% (95% CI - 1.47 ~ - 0.91, P < 0.001). However, the incidence in UTUC significantly increased, with the AAPC being 1.47% (95% CI 1.03 ~ 1.90, P < 0.001). In contrast, the incidence of BUC significantly decreased, with the overall AAPC being - 1.92% (95% CI - 2.3 ~ - 1.54, P < 0. 001). From 2001 to 2018, the overall incidence of UCs and BUC decreased in Taiwan, but the incidence of UTUC significantly increased. CONCLUSION: We suggest to apply the same review standards of new drug development process to herbal preparations and incorporate them into the adverse drug reaction or poison surveillance system. Most importantly, raise public awareness of the potential toxicity of phytotherapy.

Are tubular cells not only victims but also perpetrators in renal fibrosis?

Renal fibrosis plays a major role in the progression of renal failure. Determining whether the tubule or the glomerulus is the initiating factor is made difficult by the complexity of disease processes. This Commentary discusses new findings by Grgic et al., who show that acute injury to the renal tubule is sufficient to produce the full spectrum of renal fibrosis.

In vitro removal of beta-2-microglobulin from uremic blood with an immunoadsorption wall.

Dialysis-related amyloidosis (DRA), caused by the accumulation of beta-2-microglobulin (ß-2M), remains a major concern in long-term renal replacement therapies. For years, we have developed an immunoadsorption wall (iWall) for the removal of ß-2M. In this study, we employed a new approach taking advantage of the melting of a buffer ice rod to improve the conditions associated with the manufacturing of an iWall and tested its performance with uremic serum and blood. The preliminary results reveal that the present iWalls thus prepared not only possess the superior properties of affinity and specificity but also show structural stability and acceptable hemocompatibility. We believe that this breakthrough might provide a promising path to successful treatment of DRA as well as establish a useful platform for studying removal of certain pathological toxins accumulated in the blood.

Erythropoiesis-stimulating agents and incident malignancy in chronic kidney and end-stage renal disease: A population-based study.

Research investigating incident malignancy risk in erythropoiesis-stimulating agent (ESA) users with chronic kidney disease (CKD) is lacking. We aimed to compare the incident cancer risk between ESA and non-ESA users with CKD or end-stage renal disease (ESRD). In this retrospective cohort study, all adults newly diagnosed with CKD or ESRD between 2000 and 2012 were enrolled. The study population included 98,748 patients. After case-control matching, 7115 patients were included. The defined daily dose (DDD) of ESA was used as the unit for measuring the amount of ESA prescribed. The primary outcome was the risk of incident malignancy. The secondary outcomes were incident malignancy risk in different tertiles of cumulative ESA doses and the risk of different types of cancers. The risk of incident malignancy was 1.84 times higher with ESA treatment than without ESA treatment (hazard ratio, 1.84; 95% confidence interval, 1.43-2.36; p < 0.001). The malignancy risk was positively correlated with the cumulative dose of ESA (p-for-trend = 0.001) and a significant difference in the high annual cumulative DDD cohort (hazard ratio [HR], 2.39; 95% confidence interval [CI], 1.76-3.25; p < 0.001). The risk of genitourinary malignancy was 12.55 times higher with ESA treatment than without ESA treatment (HR, 12.55; 95% CI, 5.78-27.24; p < 0.001). ESA usage is associated with an increased risk of malignancy, particularly genitourinary cancers, in patients with CKD or ESRD. Clinicians should be aware of the occurrence of malignancy, and keep ESA dosage as low as possible.

Local treatment options for young women with ductal carcinoma in situ: A systematic review and meta-analysis comparing breast conserving surgery with or without adjuvant radiotherapy, and mastectomy.

PURPOSE: Young age is associated with poor prognosis in ductal carcinoma in situ (DCIS) of female breast and controversy exists regarding the optimal treatment modality for young patients. We aimed to compare treatment outcomes among breast conserving surgery (BCS), BCS with adjuvant radiotherapy (BCS + RT), and total mastectomy (MT) for young DCIS women. METHODS: PubMed, Cochrane, and Embase were searched for studies reporting comparative results among BCS, BCS + RT, or MT in ≤50 years old (y/o) DCIS females. Study quality was assessed and meta-analysis with subgroup analysis was performed to pool the effect sizes of the outcomes-of-interest. RESULTS: We included 3 randomized control trials and 18 observational studies. For DCIS women ≤50 y/o, RT following BCS significantly reduced the risk for ipsilateral breast tumor recurrence (IBTR) (HR = 0.66, 95% CI 0.50-0.87). However, the benefit was less robust in extremely young patients and with long follow-ups. RT revealed no statistically significant preventive effect on ipsilateral invasive recurrence (HR = 1.38, 95% CI 0.98-1.94). On the other hand, MT yielded the lowest IBTR (BCS + RT vs MT: HR = 4.4, 95% CI 2.06-9.40), both in ipsilateral DCIS recurrence and ipsilateral invasive recurrence. There was great heterogeneity and could not reach an evident conclusion concerning survival outcomes. CONCLUSION: This study highlighted the varying effect of RT for young DCIS females. The local control benefit of MT was definite without survival differences observed. Our study provided a moderate certainty of evidence to guide the treatment for young DCIS women. Further age-specific prospective trial is warranted.

Kidney bioengineering by using decellularized kidney scaffold and renal progenitor cells.

Patients with end-stage renal disease often need dialysis to maintain their lives because of donor organ shortage. The creation of a transplantable graft to permanently replace kidney function would overcome the organ shortage problem and the morbidity associated with immunosuppression. In the present study, we decellularized rat kidneys by the perfusion of detergent, yielding acellular scaffolds with the vascular, uretic, as well as cortical and medullary architecture. To regenerate the functional organ, we seeded tubular epithelial cells and mouse kidney progenitor cells from the ureter together with endothelial cells and mouse kidney progenitor cells from the renal artery. The renal constructs from seeded cells were cultured in a whole-organ bioreactor. After 3 months of organ culture, the seeded cells formed renal tubules, grew in the glomeruli, and some mouse kidney progenitor cells were also scattered in the interstitium. We tested the function of the bioengineered kidney with standardized perfusate in vitro. The bioengineered kidney not only produced urine but also reabsorbed albumin, glucose, and calcium. We conclude that seeded cell-based bioengineering of kidneys with physiological secreting and reabsorbing properties is possible and holds therapeutic promise.

Mouse kidney progenitor cells accelerate renal regeneration and prolong survival after ischemic injury.

Acute tubular necrosis is followed by regeneration of damaged renal tubular epithelial cells, and renal stem cells are supposed to contribute to this process. The purpose of our study is to test the hypothesis that renal stem cells isolated from adult mouse kidney accelerate renal regeneration via participation in the repair process. A unique population of cells exhibiting characteristics consistent with renal stem cells, mouse kidney progenitor cells (MKPC), was isolated from Myh9 targeted mutant mice. Features of these cells include (1) spindle-shaped morphology, (2) self-renewal of more than 100 passages without evidence of senescence, and (3) expression of Oct-4, Pax-2, Wnt-4, WT-1, vimentin, alpha-smooth muscle actin, CD29, and S100A4 but no SSEA-1, c-kit, or other markers of more differentiated cells. MKPC exhibit plasticity as demonstrated by the ability to differentiate into endothelial cells and osteoblasts in vitro and endothelial cells and tubular epithelial cells in vivo. The origin of the isolated MKPC was from the interstitium of medulla and papilla. Importantly, intrarenal injection of MKPC in mice with ischemic injury rescued renal damage, as manifested by decreases in peak serum urea nitrogen, the infarct zone, and the necrotic injury. Seven days after the injury, some MKPC formed vessels with red blood cells inside and some incorporated into renal tubules. In addition, MKPC treatment reduces the mortality in mice after ischemic injury. Our results indicate that MKPC represent a multipotent adult stem cell population, which may contribute to the renal repair and prolong survival after ischemic injury.