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Home dialysis modalities (home hemodialysis [HD] and peritoneal dialysis [PD]) are associated with greater patient autonomy and treatment satisfaction compared with in-center modalities, yet the level of home-dialysis use worldwide is low. Reasons for limited utilization are context-dependent, informed by local resources, dialysis costs, access to healthcare, health system policies, provider bias or preferences, cultural beliefs, individual lifestyle concerns, potential care-partner time, and financial burdens. In May 2021, KDIGO (Kidney Disease: Improving Global Outcomes) convened a controversies conference on home dialysis, focusing on how modality choice and distribution are determined and strategies to expand home-dialysis use. Participants recognized that expanding use of home dialysis within a given health system requires alignment of policy, fiscal resources, organizational structure, provider incentives, and accountability. Clinical outcomes across all dialysis modalities are largely similar, but for specific clinical measures, one modality may have advantages over another. Therefore, choice among available modalities is preference-sensitive, with consideration of quality of life, life goals, clinical characteristics, family or care-partner support, and living environment. Ideally, individuals, their care-partners, and their healthcare teams will employ shared decision-making in assessing initial and subsequent kidney failure treatment options. To meet this goal, iterative, high-quality education and support for healthcare professionals, patients, and care-partners are priorities. Everyone who faces dialysis should have access to home therapy. Facilitating universal access to home dialysis and expanding utilization requires alignment of policy considerations and resources at the dialysis-center level, with clear leadership from informed and motivated clinical teams.

The optimal SARS-CoV-2 vaccination schedule in dialysis patients and the potential need for a fourth vaccine dose are debatable. We prospectively assessed the humoral responses to three and four doses of BNT162b2 among dialysis patients. The study included 106 dialysis patients; 60 (56.6%) and 46 (43.4%) received 3 and 4 vaccine doses, respectively. Anti-spike (anti-S) antibody titers significantly increased after the third vaccine dose, followed by a decline, yet still remained higher than all previous measurements. The fourth vaccine dose led to another profound rise in anti-S titers. The absolute increase following the fourth dose correlated with response to the third dose. Infection risk however was similar between patients vaccinated with three or four doses.

Peritoneal dialysis (PD) causes structural and functional changes in the peritoneal membrane, which are attributed to local inflammatory process. This study assessed the presence of galectin-3 (Gal-3), a known inflammatory modulator, in dialysate effluent and correlated its levels with markers of inflammatory process. Gal-3 levels in serum and dialysate effluent were measured in prevalent PD patients on morning visits (n = 27) or during peritoneal equilibration tests (PET, n = 16), it association with clinical and laboratory parameters, including dialysate/plasma creatinine (D/P creatinine) and interleukin-6 (IL-6) levels was analysed. Gal-3 levels in dialysate effluent correlated with D/P creatinine (0.663, p = 0.005) and dialysate effluent IL-6 levels (0.674, p = 0.002), but not with serum Gal-3 levels or dialysis vintage. Patients who were high transporters had higher Gal-3 levels in dialysate effluent, as compared to lower transporters. In multivariate regression analysis, dialysate IL-6 level was the strongest predictor of dialysate Gal-3 levels. This study found Gal-3 in dialysate effluent correlated with D/P creatinine and dialysate IL-6 levels. These findings may imply that Gal-3 has a role in the intraperitoneal inflammatory process. However, this needs to be investigated further.

Reliable vascular access is a fundamental tool for providing effective hemodialysis. Vascular access dysfunction is associated with increased morbidity and mortality among hemodialysis patients. Current vascular access guidelines strongly recommend creating an arteriovenous fistula (AVF) as the first option; however, a substantial proportion of new AVFs may not be usable.To assess possible predictors of primary and secondary failure of vascular access.This retrospective cohort study included all vascular access sites created at Meir Medical Center from 2006 through 2012. Vascular access site, primary and secondary failure rates, and relevant demographic and clinical data were recorded during 60 months of follow-up.A total of 612 vascular accesses were created and followed for a median of 32 ± 29.4 months. Of these, 490 (80%) were suitable for initiating hemodialysis. Vascular access site was the most important predictor of primary failure but did not predict secondary failure. Co-morbidities such as diabetes mellitus and congestive heart failure, as well as the use of antiplatelet agents did not predict primary or secondary failure. Preoperative vascular mapping using Doppler ultrasonography was performed in 36.4% of cases and was not associated with lower rates of primary or secondary failure.Vascular access site is an important predictor of primary failure. We did not find a benefit of pre-operative vessel mapping or chronic antiplatelet therapy in terms of decreasing primary and secondary failure rates. Physicians should carefully consider the characteristics of the patient and blood vessels before creating vascular access in patients requiring chronic hemodialysis.

Background and aims Gestational diabetes mellitus (GDM), hyperglycemia diagnosed during pregnancy, is one of the most common medical complications of pregnancy, treated primarily by diet and pharmacotherapy, if indicated. It is well-established that GDM increases the risk of adverse pregnancy outcomes and long-term complications in mothers and infants. Galectin-3 (Gal-3) is important in processes of cell growth, differentiation, inflammation, and fibrosis. We evaluated Gal-3 expression in pregnancies complicated by GDM as a parameter that might explain how GDM influences early onset of future complications. Methods and results Forty-four women with GDM and 40 with normal pregnancy (NP) were recruited during delivery admission. Blood samples were obtained from parturients and umbilical cords blood, as well as placental tissue for analysis. Gal-3 mRNA expression was increased in maternal blood samples and placental tissue of women with GDM compared to NP. In GDM, Gal-3 mRNA was decreased in cord blood compared to maternal blood and placental tissue. Gal-3 GDM placental protein expression was increased compared to NP. Immunostaining revealed that Gal-3 is upregulated in GDM placental extravillous trophoblast. ELISA of Gal-3 maternal serum levels between GDM and NP were similar. Conclusion Gal-3 is strongly expressed at molecular levels (mRNA and protein expression) in GDM maternal blood and placental tissue, and decreased in cord blood. These findings highlight the role of the placenta in protecting the fetus from potential Gal-3 damage. Gal-3 expression at mRNA and protein levels might be influenced by diabetes, even if blood glucose is balanced by medication or diet.

Background: Predicting the mortality risk of patients un­dergoing hemodialysis (HD) is challenging. Cell-free DNA (cfDNA) is released into circulation from dying cells, and its elevation is predictive of unfavorable outcome. In a pilot study, we found post-HD cfDNA level to be a predictor of all-cause mortality. Thus, the aim of this study was to confirm the prognostic power of cfDNA in a larger prospective cohort study conducted at 2 medical centers. Methods: CfDNA levels were measured by a rapid fluorometric assay on sera obtained before and after 1 HD session. One hundred fifty-three patients were followed up to 46 months for mortality during which time 47 patients died. We compared the predictive value of cfDNA to age, comorbidities, and standard blood tests. Results: Examining standard blood tests, only post-HD cfDNA levels were elevated in the non-survivor group compared to survivors (959 vs. 803 ng/mL, p = 0.04). Pre- and post-HD cfDNA levels correlated with age and diabetes. Patients with elevated cfDNA (>850 ng/mL) showed lower survival than those with normal levels. A Cox proportional hazard regression model demonstrated a significant hazard ratio of 1.92 for post-HD cfDNA levels. Logistic regression models showed that post-HD cfDNA was a significant predictor of mortality at 1–3 years with odd ratios of 4.61, 4.36, and 6.22, respectively. Conclusions: Post-HD cfDNA level was superior to standard blood tests and could serve as a biomarker to assist in decision-making for HD-treated patients.

The incidence of stroke in patients undergoing hemodialysis (HD) is eight-to-ten times greater than that of the general population. However, data on the outcome of stroke in these patients are limited. In this retrospective observational cohort study, electronic medical records of all patients undergoing HD from 1.1.2014 to 31.12.2017 at Meir Medical Center, Israel, were reviewed. Stroke was defined as a focal neurological deficit of cerebrovascular origin, and confirmed as ischemic or hemorrhagic by computed tomography. Age- and sex-matched HD patients who did not experience a stroke (HD-NS) and hospitalized stroke patients with normal kidney function (NRF-S) served as the two control groups. Baseline demographic, clinical, and laboratory data were collected. Thrombolytic therapy, duration of hospital stay, and mortality were recorded. Functional status at discharge was assessed by the Modified Rankin Scale. In the cohort study group (HD-S), 52 strokes occurred during 248.3 patient years, an incidence rate of 8.13%, and a stroke rate of 0.19% patients/month. Most strokes in HD patients were ischemic, and only four patients were administered tissue plasminogen activator. HD-S had longer hospitalization than did NRF-S (10.6 ± 9.9 vs. 5.96 ± 5.3 days, p = 0.004) and lower functional status at discharge (Rankin score 3.75 ± 1.57 vs. 2.29 ± 1.89, p

Evaluate the efficacy of retraining and catheter exit site care in reducing peritonitis rates. This interventional study included all prevalent PD patients from 1/2009 to 12/2017 from a single center. Peritonitis rates and causative organisms were assessed and compared in three periods: (1) Before intervention (01/2009–12/2014), (2) after educational intervention: assessment of training process by infection control nurse and repeat training every 3 months, after each peritonitis episode and after hospitalizations > 2 weeks (01/2015–02/2016), and (3) in addition to the measures in period 2, an exit site care protocol including postoperative care, topical antibacterial therapy and nasal Staph aureus screening and eradication was implemented (03/2016–12/2017). The study included 201 patients (149 men, 52 women), mean age was 65.1 ± 12.6 years. After both interventions, including educational and exit site care strategies, peritonitis decreased significantly from 1.05 episodes per patient-year (n = 113) to 0.67 (n = 54); P = 0.017 between periods 1 and 3. The percentage of peritonitis-free patients increased from 27.4 to 52.4 and 55.6%, respectively (P = 0.001 between period 1 vs. 2 and period 1 vs. 3.). Coagulase-negative staph was the most common pathogen, causing 7.56 peritonitis episodes per year, followed by pseudomonas at 4.33 episodes annually and staph aureus at 3.44 episodes per year. Enforcement of an educational program and strict adherence to an exit site care protocol was associated with a significant decrease in peritonitis rates.

Objectives Preeclampsia (PE) is a pregnancy-related syndrome characterized by the onset of hypertension and proteinuria that can lead to end-organ dysfunction. Galectin-3 (Gal-3) is involved in cell growth, differentiation, inflammation and fibrosis. Thioredoxin (TXN) acts as antioxidant enzyme in several cellular processes, regulating inflammation and inhibiting apoptosis. TXNIP is an endogenous inhibitor of TXN. We evaluated changes in the inflammatory response of Gal-3, TXN, and TXNIP at the level of maternal blood, placenta, and umbilical cord blood of women with PE. Study design Ten women with PE and 20 with normal pregnancy (NP) were recruited during admission for delivery. Blood samples were obtained from parturients and umbilical cords, and placental tissue for analysis. Results Gal-3 and TXNIP mRNA expression were higher in maternal plasma in PE group compared to NP and were lower in cord blood plasma and placentas in the PE group. In the PE group, TXN/TXNIP mRNA ratio was higher in cord blood plasma (2.07) compared to maternal plasma (1.09). TXN/TXNIP placental protein ratio was similar between PE (0.89) and NP (0.79). ELISA demonstrated that Gal-3 levels in maternal serum were significantly higher in the PE vs. the NP group. Conclusions Pro-inflammatory changes were expressed by high Gal-3 and TXNIP mRNA in maternal blood of PE women, but not in their placental and cord blood samples. These findings may imply that the placenta has a role in protecting the fetus from the damages of inflammatory response, which is more common in PE than in NP.

Background and Aims Peritoneal dialysis (PD) is a common used method for renal replacement therapy. Prolonged PD treatment causes structural and functional changes in the peritoneal membrane which are attributed to local inflammatory process in the peritoneal cavity. Galectin-3 (Gal-3) is a galactoside-binding lectin with pro-inflammatory and pro-fibrotic effects. The aim of this study was to assess correlation between Gal-3 serum and dialysate effluent levels with peritoneal membrane transport characteristics. Method Gal-3 levels in serum and dialysate effluent were measured simultaneously in prevalent PD patients in morning visit or during peritoneal equilibration test (PET). Gal-3 levels were correlated with clinical and laboratory parameters. Interlukin (IL) -6 levels were measured in dialysate effluent. Gal-3 mRNA and protein expression were evaluated after exposure of primary endothelial cell culture to several dialysate solutions. Results 37 PD patients were included in the study; mean age was 65.7±13.1 years, mean dialysis vintage was 17.5±13 months. Gal-3 levels in dialysate effluent correlated with peritoneal equilibration test (PET) results (0.663, p=0.005) and effluent IL-6 levels (0.674, p=0.002) but not with serum Gal-3 levels or dialysis vintage. Patients with high PET results had higher effluent Gal-3 levels as compared average low PET results. In multivariate regression analysis effluent IL-6 level was the most dominant predictor of effluent Gal-3 levels. Gal-3 mRNA and protein expression in primary endothelial cell culture were not affected by stimulation with dialysate solutions. Conclusion Our study demonstrated presence of Gal-3 within the dialysate effluent in PD patients. Gal-3 levels correlated with peritoneal membrane transport characteristics and effluent IL-6 levels suggesting a role in the inflammatory process within the peritoneal cavity.

Background and Aims Intra-cranial arterial calcification (ICAC) in hemodialysis (HD) patients has a prevalence of about 90%, and its severity is correlated with age, hemodialysis vintage and mineral bone disease. Elevated concentrations of calcium and phosphorus are not sufficient to induce medial calcification because of inhibition by pyrophosphate. Alkaline Phosphatase (ALP) promotes vascular calcification by hydrolyzing pyrophosphate. Epigenetic mechanisms regulation by Apabetalone downregulates pathways involved in vascular calcification. This study assessed the combined impact of ICAC and elevated serum ALP on mortality among chronic HD patients. Method vascular calcifications represented by ICAC were measured simultaneous with mineral bone disease parameters including serum ALP of chronic HD patients who underwent non-contrast brain computerized tomography (CT) from 2015 to 2018 in our institution. Results This retrospective study included 153 hemodialysis patients (mean age 71.3±12.1 years, 60.1% male). Of the total cohort, 12(7.8%) had no brain calcifications and 69 (45.1%) had multiple intracranial calcifications. Considering the patients with normal ALP and no calcification as the reference group yielded adjusted odds ratios for all-cause mortality of 4.6 (95%CI 1.7-12.7) among patients with brain calcifications and normal ALP, p=0.003, and odds ratios for all-cause mortality of 6.1 (95%CI 2.1-17.7) among patients with brain calcifications and increased ALP. Conclusion We founded an independent association between ICAC and the risk of death among hemodialysis patients. The combined effect of ICAC and increased ALP was significantly associated with higher odds-ratio for all-cause mortality in chronic HD patients and may contribute to the risk stratification of these patients.

Introduction: The hemodialysis population is aging, worldwide. In Israel, more than half of the dialysis population is older than 68 years. The policy for vascular access among this population is still a matter of debate, with several studies demonstrating conflicting results. This study compared vascular access outcomes across age groups (75 years) in a single hemodialysis center in Israel. Methods: This was a retrospective, single center analysis of all vascular accesses created in adult hemodialysis patients in our institution, from January 1, 2006, through December 31, 2012. Patient characteristics, primary and secondary access failure, and complications were collected from electronic medical records. Follow-up was until death or up to 5 years. Results: A total of 612 vascular accesses created among maintenance hemodialysis patients were included, of which 196 were in patients >75 years, 184 in patients 65–75 years, and 232 in patients 75 years group was 80.5 ± 4.3 years and 60.7% were men. Vascular access site was the most important predicator for primary access failure (odds ratio for primary failure of radiocephalic arteriovenous fistula was 3.5 (95% CI 2.1–6), whereas age did not affect the primary failure rate (odds ratio 1.5, p = 0.648). Radiocephalic fistulas were more prone to secondary failure than other vascular access sites were. Complications were slightly more common in the oldest group. Eight percent of the patients >75 years died before access was used. Conclusions: In our cohort, age did not affect vascular outcomes, whereas VA site seemed to be the most important parameter in primary and secondary VA failures. Our results support considering VA on an individual basis and supply valuable information regarding complication and failure rates of VA among patients >75 years.

Objectives:Nontuberculous mycobacteria (NTM) infections pose a diagnostic challenge in peritoneal dialysis (PD) patients. In this study, we sought to identify findings that are suggestive of NTM infection in PD adult patients.Methods:All patients with NTM exit-site infection (ESI) with/without tunnel infection and peritonitis identified during the last decade in eight medical centers in Israel were included. Clinical, microbiological, and outcome data were collected and analyzed.Results:Thirty patients were identified; 16 had ESI (53%) and 14 had peritonitis (47%). Median age was 65 years (interquartile range 52–76). Abdominal pain and cloudy PD fluid were reported in all patients with peritonitis, whereas exit-site discharge and granulation tissue were common in patients with ESI. Fourteen patients (47%) had negative cultures prior NTM diagnosis, and isolation of diphtheroids or Corynebacterium spp. was reported in 9 of 30 patients (30%). Antimicrobial treatment prior to diagnosis was documented in 13 of 30 patients (43%). Delayed diagnosis was frequent. Treatment regimens and duration of therapy varied widely. In 26 of 30 (87%) patients, catheter was removed and 19 of 30 patients (63%) required permanent transition to hemodialysis. Two patients with peritonitis (2 of 14, 14%) and seven with ESI (7 of 16, 44%) were eligible for continuation of PD.Conclusions:Culture negative peritonitis, isolation of diphtheroids or Corynebacterium spp., previous exposure to antibiotics, and/or a refractory infection should all prompt consideration of PD-related NTM infection and timely workup. Catheter removal is recommended aside prolonged antimicrobial therapy. In select patients with ESI, continuation of PD may be feasible.

BACKGROUND The third-generation bio-intact parathyroid hormone (PTH) (1-84) assay was designed to overcome problems associated with the detection of C-terminal fragments by the second-generation intact PTH assay. The two assays have been compared primarily among dialysis populations. The present study evaluated the correlations and differences between these two PTH assays among patients with chronic kidney disease (CKD) stages 3 to 5 not yet on dialysis. METHODS Blood samples were collected from 98 patients with CKD stages 3 to 5. PTH concentrations were measured simultaneously by using the second-generation - PTH intact-STAT and third-generation bio-intact 1-84 PTH assays. Other serum biomarkers of bone mineral disorders were also assessed. CKD stage was calculated by using the CKD-Epidemiology Collaboration (EPI) formula. RESULTS Serum bio-intact PTH concentrations were strongly correlated but significantly lower than the intact PTH concentrations (r=0.963, P

Von Willebrand factor (vWF) is a glycoprotein with a crucial role in the formation of platelet thrombi, and ADAMTS13 is the main enzyme responsible for vWF cleavage. Both are important in the relationship between diabetic nephropathy, hypercoagulability, and cardiovascular disease. This study evaluated a potential relationship between vitamin D (vitD) levels, vWF, ADAMTS13 activity, and inflammation in diabetic patients on chronic hemodialysis (HD). Blood samples from 52 diabetic patients on chronic HD were obtained to determine vitD levels, vWF, and ADAMTS13 activity, and inflammatory markers. HD patients were grouped according to 25-hydroxyvitamin D [25(OH) VitD]25 nmol/L (n=36). vWF antigen and vWF activity were elevated in both groups, with an average of 214.3±82.6% and 175.8±72.6%, respectively. Average ADAMTS13 activity was within the normal range in both groups. Blood samples from the vitD

Objective To report short-term functional outcomes of patients incident to dialysis undergoing inpatient rehabilitation within 3 months of dialysis initiation. Design Retrospective observation study using prospectively collected data. Setting Single-center, hospital-based geriatric dialysis rehabilitation unit. All patients incident to hemodialysis admitted to the geriatric dialysis rehabilitation unit between May 2002 and April 2016 were identified using a retrospective observational design. Clinical and demographic data were collected prospectively and linked, using the unique hospital number and dates of admission and discharge, to FIM scores (used to assess functional recovery) at admission and discharge. Participants Patients (N=449; mean age ± SD, 74±9y) newly started on hemodialysis (within 3mo). Interventions Inpatient rehabilitation care, short daily dialysis therapy with nephrologist support, and geriatrician assessment. Main Outcomes Change in FIM score; discharge location. Results Patients were admitted within 3 months of hemodialysis initiation. The median length of stay in the rehabilitation program was 43 days (25th and 75th quartile, 33-55 days). Of those with complete data (n=370), 95% had improvement in FIM scores (median changes in total FIM score 25 [quartiles, 16, 33]; in motor FIM 23 [quartiles, 15, 32]; and in cognitive FIM 1 [quartiles, 0, 3], respectively). Most improvement was seen in transfer abilities, grooming, and mobility. A total of 324 patients (72%; 95% CI, 68%-76%) were discharged to a private home. An additional 11 were discharged to a seniors’ residence. Conclusion The data suggest that older patients incident to dialysis with functional decline respond well to specialized rehabilitation care and suggest this may be a novel approach to dialysis initiation.

Background Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone that stimulates insulin secretion and may affect the inflammatory pathways involved in diabetes mellitus. Calcitriol, an active form of vitamin D, plays an important role in renal, endothelial and cardiovascular protection. We evaluated the anti-inflammatory and histologic effects of a GLP-1 analogue (liraglutide) and of calcitriol in a db/db mouse diabetes model and in endothelial cells exposed to a diabetes-like environment. Methods Diabetic db/db mice were treated with liraglutide and calcitriol for 14 weeks, after which the kidneys were perfused and removed for mRNA and protein analysis and histology. Endothelial cells were stimulated with advanced glycation end products (AGEs), glucose, liraglutide and calcitriol. Total RNA and protein were extracted and analysed for the expression of selected inflammatory markers. Results Typical histological changes, glomerular enlargement and mesangial expansion were seen in db/db mice compared with control mice. Glomerular hypertrophy was ameliorated with liraglutide, compared with db/db controls. Liraglutide up-regulated endothelial nitric oxide synthase protein expression compared with the db/db control group and down-regulated p65 protein expression. Calcitriol did not further improve the beneficial effect observed on protein expression. In endothelial cells, liraglutide treatment exhibited a dose-dependent ability to prevent an inflammatory response in the selected markers: thioredoxin-interacting protein, p65, IL6 and IL8. In most gene and protein expressions, addition of calcitriol did not enhance the effect of liraglutide. Conclusions The GLP-1 analogue liraglutide prevented the inflammatory response observed in endothelial cells exposed to a diabetes-like environment and in db/db mice at the level of protein expression and significantly ameliorated the glomerular hypertrophy seen in the diabetic control group. Copyright © 2016 John Wiley & Sons, Ltd.

Aims: Class A2 gestational diabetes mellitus (GDMA2) has short- and long-term effects on the mother and child. These may include abnormalities of placentation, damage to endothelial cells and cardiovascular disease. This research investigated the function and composition of high-density lipoproteins (HDL) among women with GDMA2 and their fetuses. Methods: Thirty pregnant women were recruited during admission for delivery. The function and expression of HDL, paraoxonase1 (PON1) and apolipoprotein A1 (APOA1) in the blood samples and the placental tissue were evaluated. The effect of HDL on migration of endothelial cells was measured in vitro. Results: Compared to normal pregnancy (NP), APOA1 in the maternal plasma of women with GDMA2 was decreased. More APOA1 and PON1 were released from HDL of women with GDMA2, compared to NP. Placental APOA1 and PON1 were decreased in GDMA2. For endothelial cells stimulated with TNF&alpha, HDL cell migration was decreased when cells were evaluated with NP-HDL, as compared to GDMA2-HDL. Conclusions: GDMA2 affects the composition and function of HDL in plasma. Changes in HDL commonly seen in GDMA2 were observed in maternal and placental samples, but not in cord samples. These results might indicate a placental role in protecting the fetus by preserving the components and functions of HDL and require further investigation.

Emerging evidence demonstrates the involvement of Janus tyrosine kinase/signal transducer and transcription activator (JAK/STAT) proteins in the pathophysiology of diabetic kidney disease (DKD). The JAK/STAT pathway is involved in the inflammatory response and endothelial cell dysfunction observed in DKD. The glucagon-like peptide-1 (GLP-1) analog liraglutide is an effective treatment for type 2 diabetes because it improves the inflammatory changes observed in experimental models of DKD. This study used db/db mice and endothelial cells (ECs) to determine the effect of diabetic environment on the JAK/STAT pathway and to assess the potential effect of liraglutide (200 μg/kg) in both models.Diabetic db/db mice (12 weeks old) were treated with liraglutide for 14 weeks. The kidneys were then perfused with saline and removed for mRNA, protein, and immunohistochemical analyses. Endothelial cells were stimulated advanced glycation end products (AGEs) (200 μg/μL) glucose (200 mg/dL) and liraglutide (100 nM) for 24 hours. Total RNA and protein were extracted and analyzed for expression of JAK/STAT signaling.Phosphorylated (p-) STAT3 was significantly upregulated in db/db mice compared with non-diabetic mice. Liraglutide significantly downregulated p-STAT3 protein expression in db/db mice. In db/db mice, p-STAT3 was primarily expressed in the glomeruli, whereas p-JAK2 was also expressed in kidney tubules. In ECs, liraglutide treatment prevented increased expression of p-STAT3 and p-JAK2. Liraglutide inhibited the target gene suppressor of cytokine signaling 3 (SOCS3) and sirtuin 1 (SIRT1) in db/db mice and in cultured EC.This study suggests that the GLP-1 analog liraglutide inhibits the JAK/STAT pathway, which participates in intracellular processes in experimental models of diabetes.背景: 越来越多的证据表明Janus酪氨酸激酶/信号转导与转录激活因子(Janus tyrosine kinase/signal transducer and transcription activator，JAK/STAT)蛋白参与了糖尿病肾病(diabetic kidney disease，DKD)的病理生理学过程。在DKD中观察到的炎症反应以及内皮细胞功能障碍与JAK/STAT通路有关。胰高血糖素样肽-1(glucagon-like peptide-1，GLP-1)类似物利拉鲁肽是一种有效的2型糖尿病治疗药物，因为在DKD实验模型中观察到它可以改善炎症反应。这项研究利用db/db小鼠与内皮细胞(endothelial cells，ECs)来测定糖尿病环境对JAK/STAT通路的影响，并且在这两个模型中评估了利拉鲁肽(200 μg/kg)的潜在影响。 方法: 糖尿病db/db小鼠(12周龄)使用利拉鲁肽治疗14周。然后在肾脏中灌入生理盐水，取出后进行mRNA、蛋白质以及免疫组化分析。使用晚期糖基化终产物(200 μg/μL)、葡萄糖(200 mg/dl)与利拉鲁肽(100 nM)刺激内皮细胞24小时。提取出全部的RNA与蛋白质并且分析了JAK/STAT信号的表达。 结果: 与非糖尿病小鼠相比较，在db/db小鼠中磷酸化STAT(p- STAT3)显著上调了。在db/db小鼠中利拉鲁肽可以显著下调p-STAT3蛋白的表达。在db/db小鼠中，p-STAT3主要在肾小球中表达，而p-JAK2在肾小管中也有表达。在ECs中，使用利拉鲁肽治疗后可以防止p-STAT3与p-JAK2表达增加。在db/db小鼠以及培养的EC中，利拉鲁肽可以抑制细胞因子信号3(suppressor of cytokine signaling，SOCS3)以及sirtuin 1(SIRT1)的靶基因抑制因子。 结论: 这项研究表明，GLP-1类似物利拉鲁肽可以抑制JAK/STAT通路，这个通路与糖尿病实验模型的细胞内进程有关。.

Anemia management strategies among chronic hemodialysis patients with high ferritin levels remains challenging for nephrologists.To compare anemia management in stable hemodialysis patients with high (≥ 500 ng/ml) vs. low (500 ng/ml) ferritin levels.In a single center, record review, cohort study of stable hemodialysis patients who were followed for 24 months, an anemia management policy was amended to discontinue intravenous (IV) iron therapy for stable hemodialysis patients with hemoglobin10 g/dl and ferritin ≥ 500 ng/ml. Erythropoiesis-stimulating-agents (ESA), IV iron doses, and laboratory parameters were compared among patients with high vs. low baseline ferritin levels before and after IV iron cessation.Among 87 patients, 73.6% had baseline ferritin ≥ 500 ng/ml. Weekly ESA dose was greater among patients with high vs. low ferritin (6788.8 ± 4727.8 IU/week vs. 3305.0 ± 2953.9 IU/week, P = 0.001); whereas, cumulative and monthly IV iron doses were significantly lower (1628.2 ± 1491.1 mg vs. 2557.4 ± 1398.9 mg, P = 0.011, and 82.9 ± 85 vs. 140.7 ± 63.9 mg, P = 0.004). Among patients with high ferritin, IV iron was discontinued for more than 3 months in 41 patients (64%) and completely avoided in 6 (9.5%).ESA dose and hemoglobin levels did not change significantly during this period.Iron cessation in chronic hemodialysis patients with high ferritin levels did not affect hemoglobin level or ESA dose and can be considered as a safe policy for attenuating the risk of chronic iron overload.

To evaluate (a) the properties of high-density lipoproteins (HDL)/cholesterol, which include apolipoprotein A-1 (ApoA1) and paraoxonase1 (PON1), both are negative predictors of cardiovascular risk and (b) HDL function, among women with preeclampsia (PE). PE is a multi-system disorder, characterized by onset of hypertension and proteinuria or other end-organ dysfunction in the second half of pregnancy. Preeclampsia is associated with increased risk for later cardiovascular disease. The inverse association between HDL, cholesterol levels and the risk of developing atherosclerotic cardiovascular disease is well-established. Twenty-five pregnant women [19 with PE and 6 with normal pregnancy (NP)] were recruited during admission for delivery. HDL was isolated from blood samples. PON1 activity and HDL were analyzed. An in vitro model of endothelial cells was used to evaluate the effect of HDL on the transcription response of vascular cell adhesion molecule-1 (VCAM-1) and endothelial nitric oxide synthase (eNOS) mRNA expression. PON1 activity (units/ml serum) was lower in the PE group compared to normal pregnancy (NP) (6.51 ± 0.73 vs. 9.98 ± 0.54; P = 0.015). Increased ApoA1 was released from PE-HDL as compared to NP-HDL (3.54 ± 0.72 vs. 0.89 ± 0.35; P = 0.01). PE-HDL exhibited increased VCAM-1 mRNA expression and decreased eNOS mRNA expression on TNF-α stimulated endothelial cells as compared to NP-HDL. HDL from women with PE reduced PON1 activity and increased ApoA1 release from HDL particles. This process was associated with increased HDL diameter, suggesting impaired HDL anti-oxidant activity. These changes might contribute to higher long-term cardiovascular risks among women with PE.

Fitz-Hugh-Curtis syndrome (FHCS) is a condition characterized by inflammation of the liver capsule (perihepatitis) and adjacent peritoneal surfaces. We report a case of FHCS developing in a peritoneal dialysis (PD) patient in whom catheter removal due to recurrent peritonitis was complicated by post-operative wound infection. To the best of our knowledge, this is the first case description of FHCS in the context of PD.

Upper respiratory tract infection (URTI) occurs frequently in the general population and is considered a benign self-limited disease. Dialysis patients constitute a high risk population whose morbidity and mortality rate as a result of URTI is unknown.To assess the local incidence, morbidity and mortality of URTI in dialysis patients compared to the general population.In this retrospective cohort study we reviewed the charts of all chronic dialysis patients diagnosed with URTI at Meir Medical Center, Kfar Saba, Israel during the 2014-2015 winter season.Among 185 dialysis patients, 40 were found to be eligible for the study. The average age was 66.1 ± 15.7 years, and the co-morbidity index was high. Influenza A was the most common pathogen found, followed by rhinovirus, respiratory syncytial virus and para-influenza. Of the 40 patients 21 (52.5%) developed complications: pneumonia in 20%, hospitalization in 47.5%, and respiratory failure requiring mechanical ventilation in 12.5%. Overall mortality was 10%. General population data during the same seasonal period showed a peak pneumonia incidence of 4.4% compared to 20% in the study population (P0.0001).The study findings show that compared to the general population, URTI in dialysis patients is a much more severe disease and has a higher complication rate. Influenza A, the most common pathogen, is associated with a worse prognosis.

Background Since there are many disorders that can present with thrombotic microangiopathy (TMA), establishing a correct diagnosis is important to offer the most appropriate therapy. Case Report A 26-year-old woman was transferred to our hospital with fragmentation hemolytic anemia, thrombocytopenia, and acute kidney failure. History revealed that she was recently diagnosed with adult-onset Still's disease (AOSD) and received intraocular injections of bevacizumab to treat acute retinal artery occlusion. At our hospital, she underwent extensive investigations and was treated with high-dose steroids, hemodialysis, and therapeutic plasma exchange. For recurrent disease, she received a single dose of eculizumab. Results The patient's ADAMTS13 activity was normal and she had evidence of complement activation. Genetic testing identified a benign polymorphism in the C3 gene. Pathophysiology of TMA in AOSD is briefly discussed and an overview of the literature is presented. Conclusion Work-up of a new fragmentation hemolytic anemia and thrombocytopenia should include careful review of past history, including medications, as well as relevant laboratory investigations with aim to establish a correct diagnosis. Occasionally, the correct diagnosis is not the obvious one and there could be multiple contributors to the pathogenesis. Establishing diagnosis is important for counseling patient on disease prognosis and to guide treatment.

Kidney biopsies are not routinely performed for diabetic patients with chronic kidney disease. However in some cases, a biopsy is carried out to exclude other treatable Prolonged duration of diabetes, insulin therapies and presence of diabetic retinopathy were associated with a greater likelihood of DN. The high prevalence of NDRD in our population emphasizes the judicious use of kidney biopsy in diabetic patients. e renal diseases. The prevalence and the nature of non diabetic renal disease (NDRD) among diabetic patients in Israel have not yet been evaluated.To assess pathological findings of kidney biopsies conducted in patients with diabetes mellitus.A total of 200 native kidney biopsies were performed during the study period. Patients who had a diagnosis of diabetes mellitus were included in the study. Clinical data and pathological findings were retrospectively collected and analyzed.The cohort included 34 patients, median age 61.8 years. The male to female ratio was 25:9; mean serum creatinine was 1.8 ± 1.2 mg/dl The duration of diabetes was significantly shorter in patients with NDRD (6.8 ± 7.1 years vs. 13.0 ± 9.6 years in diabetic nephropathy (DN) or combined), whereas insulin therapy was significantly more common in patients with DN (72% vs 5% in NDRD). Diabetic retinopathy was documented in 57% of patients with diabetic nephropathy but wasn't documented in any patient with NDRD. Prevalence of NDRD, DN and combined pathology was 58.8%, 32.4% and 8.8% respectively. Neither the level of proteinuria nor the rate of renal function deterioration could predict pathological findings in the biopsy. The most common NDRD disease was nephrosclerosis.Non-diabetic renal disease was common. Prolonged duration of diabetes, insulin therapies and presence of diabetic retinopathy were associated with a greater likelihood of DN. The high prevalence of NDRD in our population emphasizes the judicious use of kidney biopsy in diabetic patients.

Glucagon-like peptide-1 (GLP-1) is a gut incretin hormone that stimulates insulin secretion and may affect the inflammatory pathways involved in diabetes mellitus. Calcitriol, an active form of vitamin D, plays an important role in renal, endothelial and cardiovascular protection. We evaluated the anti-inflammatory and histologic effects of a GLP-1 analogue (liraglutide) and of calcitriol in a db/db mouse diabetes model and in endothelial cells exposed to a diabetes-like environment.Diabetic db/db mice were treated with liraglutide and calcitriol for 14 weeks, after which the kidneys were perfused and removed for mRNA and protein analysis and histology. Endothelial cells were stimulated with advanced glycation end products (AGEs), glucose, liraglutide and calcitriol. Total RNA and protein were extracted and analysed for the expression of selected inflammatory markers.Typical histological changes, glomerular enlargement and mesangial expansion were seen in db/db mice compared with control mice. Glomerular hypertrophy was ameliorated with liraglutide, compared with db/db controls. Liraglutide up-regulated endothelial nitric oxide synthase protein expression compared with the db/db control group and down-regulated p65 protein expression. Calcitriol did not further improve the beneficial effect observed on protein expression. In endothelial cells, liraglutide treatment exhibited a dose-dependent ability to prevent an inflammatory response in the selected markers: thioredoxin-interacting protein, p65, IL6 and IL8. In most gene and protein expressions, addition of calcitriol did not enhance the effect of liraglutide.The GLP-1 analogue liraglutide prevented the inflammatory response observed in endothelial cells exposed to a diabetes-like environment and in db/db mice at the level of protein expression and significantly ameliorated the glomerular hypertrophy seen in the diabetic control group. Copyright © 2016 John WileySons, Ltd.

Since there are many disorders that can present with thrombotic microangiopathy (TMA), establishing a correct diagnosis is important to offer the most appropriate therapy.A 26-year-old woman was transferred to our hospital with fragmentation hemolytic anemia, thrombocytopenia, and acute kidney failure. History revealed that she was recently diagnosed with adult-onset Still's disease (AOSD) and received intraocular injections of bevacizumab to treat acute retinal artery occlusion. At our hospital, she underwent extensive investigations and was treated with high-dose steroids, hemodialysis, and therapeutic plasma exchange. For recurrent disease, she received a single dose of eculizumab.The patient's ADAMTS13 activity was normal and she had evidence of complement activation. Genetic testing identified a benign polymorphism in the C3 gene. Pathophysiology of TMA in AOSD is briefly discussed and an overview of the literature is presented.Work-up of a new fragmentation hemolytic anemia and thrombocytopenia should include careful review of past history, including medications, as well as relevant laboratory investigations with aim to establish a correct diagnosis. Occasionally, the correct diagnosis is not the obvious one and there could be multiple contributors to the pathogenesis. Establishing diagnosis is important for counseling patient on disease prognosis and to guide treatment.