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Hypertension is associated with vascular injury, which contributes to end-organ damage. MicroRNAs regulating mRNAs have been shown to play a role in vascular injury in hypertensive mice. We aimed to identify differentially expressed microRNAs and their mRNA targets in small arteries of hypertensive patients with/without chronic kidney disease (CKD) to shed light on the pathophysiological molecular mechanisms of vascular remodeling.Normotensive individuals and hypertensive patients with/without CKD were recruited ( n = 15-16 per group). Differentially expressed microRNAs and mRNAs were identified uniquely associated with hypertension (microRNAs: 10, mRNAs: 68) or CKD (microRNAs: 68, mRNAs: 395), and in both groups (microRNAs: 2, mRNAs: 32) with a P less than 0.05 and a fold change less than or greater than 1.3 in subcutaneous small arteries ( n = 14-15). One of the top three differentially expressed microRNAs, miR-338-3p that was down-regulated in CKD, presented the best correlation between RNA sequencing and reverse transcription-quantitative PCR (RT-qPCR, R2 = 0.328, P 0.001). Profiling of human aortic vascular cells showed that miR-338-3p was mostly expressed in endothelial cells. Two of the selected top nine up-regulated miR-338-3p predicted targets, glutathione peroxidase 3 ( GPX3 ) and protein tyrosine phosphatase receptor type S ( PTPRS ), were validated with mimics by RT-qPCR in human aortic endothelial cells ( P 0.05) and by a luciferase assay in HEK293T cells ( P 0.05).A distinct transcriptomic profile was observed in gluteal subcutaneous small arteries of hypertensive patients with CKD. Down-regulated miR-338-3p could contribute to GPX3 and PTPRS up-regulation via the canonical microRNA targeting machinery in hypertensive patients with CKD.http://links.lww.com/HJH/C27.

Background: Hypertension (HTN) causes vascular injury identified by endothelial dysfunction, vascular stiffening, and remodeling, which contributes to kidney damage leading to chronic kidney disease (CKD). MicroRNAs (miRNAs) repress/degrade target mRNAs. Their role in vascular injury in HTN remains unclear. We aimed to identify differentially expressed (DE) miRNAs in gluteal subcutaneous arteries of patients with HTN associated or not with CKD to shed light on the pathophysiological molecular mechanisms. Methods: Normotensive subjects and patients with HTN associated or not with CKD grades 3-4 were studied (n=15-16). Small arteries were isolated from gluteal subcutaneous biopsies, RNA extracted and small and total RNA sequencing performed by Illumina HiSeq-2500. DE genes were identified with a P 1.3. Top 3 DE miRNAs ( P 2, mean read count number (MRCN) >3,000 in all groups and having predicted mRNA targets) were selected for validation by reverse transcription-quantitative PCR (RT-qPCR). The mRNA targets of the top selected miRNA were predicted by TargetScan with P 1.5 and MRCN>150 and the top 9 targets were validated by RT-qPCR using gain- and loss-of-function in human aortic endothelial cells (HAECs). Gene ontology enrichment analysis (GOEA) was done in Cytoscape. Results: DE miRNAs and mRNAs were identified uniquely associated with HTN (miRNAs: 10, mRNAs: 68), CKD (miRNAs: 68, mRNAs: 395), and in both groups (miRNAs: 2, mRNAs: 32). miR-338-3p presented the best correlation between RNA sequencing and RT-qPCR (R 2 =0.328, P PTPRS , FC: 0.80±0.08 vs 1.00±0.00) and glutathione peroxidase 3 ( GPX3 , FC: 0.88±0.04 vs 1.00±0.00) were down-regulated in HAECs transfected with miR-338-3p mimics ( P GPX3 with oxidative stress detoxification ( q PTPRS with the immune system, neuronal system and developmental process ( q Conclusion: Down-regulated miR-338-3p in gluteal subcutaneous small arteries of hypertensive patients with CKD targets PTPRS and GPX3 that may play a role in vascular injury in HTN.

Background: Hypertension (HTN) is associated with subclinical target organ damage including cardiac, vascular and kidney injury. The immune system plays a role in hypertension and target organ damage. Activation of T cells has been reported among peripheral blood mononuclear cells (PBMCs) of patients with HTN. MicroRNAs (miRNAs) are crucial post-transcriptional regulators of immune cells. Whether miRNAs play a role in the activation of immune cells in hypertension complicated by target organ damage in humans remains unknown. We aimed to address this question by identifying differentially expressed (DE) miRNAs and their mRNA targets in PBMCs of patients with hypertension complicated or not with metabolic syndrome (MetS) or chronic kidney disease (CKD). Methods: Normotensive subjects and patients with hypertension (HTN) associated or not with at least 2 other features of MetS or CKD were studied (n=15-16). PBMCs were isolated from blood, RNA extracted for small and total RNA sequencing (RNA-seq) using Illumina HiSeq-2500 and data were analyzed using a systems biology approach. MiRDeep2 was used for novel miRNAs prediction, miRNA annotation and counting. TargetScan 7.07 was used to predict DE miRNA targets with weighted context score percentile >50%. DE genes miRNAs and mRNAs were identified with fold change (FC) >1.5 and P 2 and mean read count number (MRCM) >500, and with predicted targets with MRCM>300 were validated by reverse transcription-quantitative PCR (RT-qPCR). Results: DE miRNAs, mRNAs and non-coding RNAs were identified in HTN (22, 19 and 0), MetS (57, 401 and 11) and CKD (6, 26 and 2) compared to NTN. TargetScan predicted that 7 miRNAs target 3 mRNAs in NTN, 57 miRNAs target 55 mRNAs in MetS and 3 miRNAs target 2 mRNAs in CKD. DE miR-409-5p (FC: 0.54±0.10 vs 1.00±0.09, P P P 2 =0.40, P 2 =0.55, P 2 =0.37, P Conclusion: This study showed that DE miR-409-5p, miR-411-5p and miR-pl-86 may play a role in HTN associated with MetS.

Background: Between 20–50% of patients undergoing maintenance dialysis for end-stage kidney disease experience symptoms of depression and/or anxiety, associated with increased mortality, greater health care utilization, and decreased quality of life. It is unknown whether mindfulness-based interventions can improve depression and anxiety symptoms in patients receiving this treatment. Methods: We conducted an 8-week multicenter randomized controlled trial comparing a brief mindfulness intervention (BMI) vs. an active control (Health Enhancement Program [HEP]) in 55 patients receiving dialysis with symptoms of depression and/or anxiety. The primary outcome was change in Patient Health Questionnaire-9 (PHQ-9) depression scores, with a primary analysis in participants with baseline PHQ-9 ≥ 10, and a secondary analysis including all participants. The secondary outcome was change in Generalized Anxiety Disorder-7 (GAD-7) anxiety scores with corresponding primary and secondary analyses. Results: Both BMI and HEP reduced depressive symptoms, with no difference between trial arms (PHQ-9 change = −7.0 vs. −6.1, p = 0.62). BMI was more effective than HEP in reducing anxiety (GAD-7 change = −8.7 vs. −1.4, p = 0.01). Secondary analyses revealed no differences between arms. Conclusions: For patients undergoing dialysis, both BMI and HEP may be helpful interventions for depression symptoms, and BMI may be superior to HEP for anxiety symptoms. Mindfulness-based and other psychosocial interventions may be further evaluated in those undergoing dialysis as treatment options for symptoms of depression and anxiety.

Background. Sodium glucose cotransport (SGLT)-2 inhibitors are the newest class of antihyperglycemic agents used as second- or third-line treatment in the management of type 2 diabetes. Although the use of SGLT-2 inhibitors has not been shown to cause nephrotoxicity, there have been case reports of SGLT-2 inhibitor use being associated with acute kidney injury. Case Presentation. A 72-year-old woman with a history of type 2 diabetes and no known chronic renal insufficiency presented to the emergency room with a 3-day history of nausea, vomiting, and increased somnolence. She was found to have potassium level of 7.4 (normal: 3.5-5.5) mmol/L and a markedly elevated creatinine level at 1154 (normal: 45-95) μmol/L. Imaging of the abdomen and pelvis did not reveal any findings of obstruction. Urine microscopy showed many granular casts. In the absence of other causes for her clinical presentation, the patient was diagnosed with acute kidney injury secondary to ischemic acute tubular necrosis, with canagliflozin use likely an important contributing factor. Conclusions. Physicians should inform patients to stop the use of SGLT-2 inhibitors when patients are unable to maintain hydration or during acute illness. Use of SGLT-2 inhibitors in managing type 2 diabetes should be done with caution among more vulnerable populations, including individuals with cognitive impairment and the elderly.

BACKGROUND Hypertension (HTN) is associated with target organ damage such as cardiac, vascular, and kidney injury. Several studies have investigated circulating microRNAs (miRNAs) as biomarkers of cardiovascular disease, but few have examined them as biomarker of target organ damage in HTN. We aimed to identify circulating miRNAs that could serve as biomarkers of HTN-induced target organ damage using an unbiased approach. METHODS AND RESULTS Fifteen normotensive subjects, 16 patients with HTN, 15 with HTN associated with other features of the metabolic syndrome (MetS), and 16 with HTN or chronic kidney disease (CKD) were studied. Circulating RNA extracted from platelet-poor plasma was used for small RNA sequencing. Differentially expressed (DE) genes were identified with a threshold of false discovery rate CONCLUSIONS We identified decreased circulating let-7g-5p and miR-191-5p as independent biomarkers of CKD among patients with HTN, which could have pathophysiological and therapeutic implications.

Background: Hypertension (HTN) and chronic kidney disease (CKD) are associated with vascular damage characterized by vascular remodeling and stiffening and endothelial dysfunction. miRNAs are small non-coding RNA that regulate gene expression by binding to their target messenger RNAs (mRNAs), leading to mRNA degradation or translational repression. Their implication in vascular injury remains unclear. We aimed to identify differentially expressed (DE) miRs in small arteries of HTN and CKD human subjects to gain insight into pathophysiological molecular mechanisms in these conditions. Methods: Normotensive, HTN [systolic blood pressure (BP) >135 mmHg or diastolic BP of 85-115 mmHg with BpTRU] and CKD subjects (estimated glomerular filtration rate 2 ) (n=15-16) were studied. Small arteries were isolated from subcutaneous gluteal biopsies and RNA extracted for small and total RNA sequencing using Illumina HiSeq-2500 and further studied using a systems biology approach. Differentially expressed (DE) genes were identified with fold change >1.5 and fold discovery rate Results: DE miRs were identified ( P r =0.91, P -16 ), uniquely associated with CKD, was studied further. miR-338-3p and some of its predicted targets were highly expressed in human aortic endothelial cells (HAECs). Two of them, alkaline ceramidase 2 ( ACER2 ) and glutathione peroxidase 3 (GPX3), were up-regulated by ~36% and ~60% in HAECs transfected with anti-miR-338-3p, respectively ( P ACER2 or GPX3 3’ untranslated transcribed region miR-338-3p-5p binding sites ( P Conclusion: miR-338-3p was down-regulated in small arteries, which was uniquely associated with CKD. ACER2 and GPX3 , identified as miR-338-3p targets, may play a role in vascular injury in CKD.

Background There is conflicting evidence of benefit versus harm for warfarin anticoagulation in hemodialysis patients with atrial fibrillation. This equipoise may be explained by suboptimal Time in Therapeutic Range (TTR), which correlates well with thromboembolic and bleeding complications. This study aimed to compare nephrologist-led management of warfarin therapy versus that led by specialized anticoagulation clinic. Methods In a retrospective cohort of chronic hemodialysis patients from two institutions (Institution A: Nephrologist-led warfarin management, Institution B: Anticoagulation clinic-led warfarin management), we identified patients with atrial fibrillation who were receiving warfarin for thromboembolic prophylaxis. Mean TTRs, proportion of patients achieving TTR ≥ 60%, and frequency of INR testing were compared using a logistic regression model. Results In Institution A, 16.7% of hemodialysis patients had atrial fibrillation, of whom 36.8% were on warfarin. In Institution B, 18% of hemodialysis patients had atrial fibrillation, and 55.5% were on warfarin. The mean TTR was 61.8% (SD 14.5) in Institution A, and 60.5% (SD 15.8) in Institution B (p-value 0.95). However, the proportion of patients achieving TTR ≥ 60% was 65% versus 43.3% (Adjusted OR 2.22, CI 0.65–7.63) and mean frequency of INR testing was every 6 days versus every 13.9 days in Institutions A and B respectively. Conclusions There was no statistical difference in mean TTR between nephrologist-led management of warfarin and that of clinic-led management. However, the former achieved a trend toward a higher proportion of patients with optimal TTR. This improved therapeutic results was associated with more frequent INR monitoring.

Background: Chronic kidney disease (CKD) is a global health burden with a worldwide prevalence of 13.4% for stage 5 and 10.6% for stage 3-5. There is an epidemiological association between hypertension (HTN) and CKD. The prevalence of high blood pressure (BP) has been reported to be over 85% in stage 3 and over 90% in stage 4-5 CKD patients. Circulating cell-free small non-coding RNAs called microRNA (miRNA) have been shown to associate with different pathologies including cancer and cardiovascular disease, and accordingly possesses potential to serve as biomarkers with clinical application. We aimed to identify differentially expressed (DE) miRNAs that may be related to CKD. Methods and Results: Normotensive, HTN (systolic BP > 135 mmHg or diastolic BP of 85-115 mmHg with BPtru) and CKD (estimated glomerular filtration rate (eGFR) < 60mL/min/m 2 ) subjects (n=15-16 per group) were studied. Platelet-free plasma was isolated by a 2-step centrifugation (1000xg followed by 10,000xg) from 6 ml total blood. Plasma miRNAs were extracted using the QIAamp Circulating Nucleic Acid Kit. The quantity and quality of RNA were assessed using an Agilent 2100 Bioanalyzer. cDNA libraries were prepared using the TruSeq Small RNA Library Prep Kit, and sequenced with the HiSeq 2500 platform. FastQC was used for quality control. Sequences were mapped by STAR to the hg38 genome and annotated by miRDeep2. DE miRNAs were identified using EdgeR, which found 6 up-regulated and 3 down-regulated miRNAs uniquely associated with the HTN group, 2 up-regulated and 12 down-regulated miRNAs uniquely associated with the CKD group and 3 down-regulated miRNAs in both groups ( P P P P Conclusions and Perspectives: DE platelet-free plasma miRNAs were identified in HTN and CKD patients. Some miRNAs may have the potential to serve as biomarkers in CKD.

Cardiovascular disease is the principal cause of morbidity and mortality in patients with diabetes mellitus. The incidence or progression of kidney disease is also common in these patients. Several clinical trials have established the efficacy of angiotensin receptor blockers for the prevention of adverse cardiovascular and renal outcomes in this population and are summarized in this review article. Head-to-head comparison of angiotensin receptor blockers with angiotensin-converting enzyme inhibitors has shown similar cardioprotective and renoprotective properties of both medication classes. However, angiotensin receptor blockers have an improved safety profile with fewer episodes of cough and angioedema and may be the agent of choice in patients with diabetes and hypertension. Novel therapeutic strategies, such as those that include a mineralocorticoid receptor blocker or a selective sodium-glucose cotransporter type 2 inhibitor, may further protect patients with diabetes from cardiovascular and renal complications.

There appears to be a broad consensus among professional health organizations that a blood pressure (BP) of 130/80 mm Hg or less is the recommended therapeutic BP target for subjects with diabetes mellitus. This review focuses on key studies that have examined the relationship between BP reduction and its impact on diabetic complications. An attempt is being made to identify the BP level at which maximum protection against diabetic complications is conferred, and below which further reduction no longer delivers a benefit that exceeds risk. Specific attention has been accorded to data contributing to establishing ideal BP goals in diabetic patients with nephropathy. On the basis of recent studies, it would appear that a BP below 140/90 mm Hg should be recommended for all diabetic individuals, and around 135/85 mm Hg for most. BP should be closer to, but not below, 130/80 mm Hg for those subjects at the highest cardiovascular risk. For those diabetic subjects at highest risk for stroke, lower BP may provide greater protection against stroke as shown in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. In younger individuals with diabetes and hypertension of shorter duration, it may be possible to lower BP below 130/80 mm Hg without untoward side effects and in fact with cardiovascular benefit, but this remains to be demonstrated. The ideal BP goal in diabetic patients with nephropathy remains questionable, and for now, the recommended target must be considered the same as that for the general diabetic population.

A 71-year-old man presented to the emergency department with a 2-week history of worsening cough and shortness of breath. The patient had a history of end-stage renal disease secondary to diabetic nephropathy, and he had received a deceased donor renal transplant 3 years before presentation. His baseline estimated glomerular filtration rate was approximately 50 ml/min. He was also known to have hypertension, type 2 diabetes mellitus, hyperlipidemia, coronary artery disease, and active hepatitis B. His medications included extended-release tacrolimus 16 mg daily, mycophenolic acid 720 mg twice daily, prednisone 5 mg daily, lamivudine, valsartan, metoprolol, doxazocin, atorvastatin, pantoprazole, and insulin. On examination, the patient was hemodynamically stable but tachypneic, with an oxygen saturation of 87% while breathing ambient air. His jugular venous pressure was not elevated, and there was no peripheral edema. His cardiac and respiratory examination was otherwise unremarkable. On laboratory investigations, the patient was noted to have hypercalcemia (total corrected calcium 3.09 mmol/l) which was not present during routine lab testing 2 weeks earlier. His parathyroid hormone level was suppressed. Renal function was unchanged from his previous values. Pertinent laboratory data are presented in Table 1. Chest radiograph on presentation showed diffuse increased markings over the left lung field with relative oligemia of the right lung. Further investigations included a negative ventilation perfusion scan and a normal transthoracic echocardiogram. Computed tomography (CT) of the chest revealed diffuse ground-glass opacities, involving the posterior portions of both lungs and the apices bilaterally. In the context of the hypercalcemia, CT scan of the abdomen and pelvis was performed, and there was no evidence of an underlying malignancy.

A 67-year-old man known for metastatic colon cancer received treatment with oxaliplatin and developed severe acute kidney injury requiring dialysis. Renal biopsy revealed severe acute tubular necrosis. Acute kidney injury is a rare but severe adverse effect of oxaliplatin administration.

Background Recent studies have raised concern about the safety of erythropoiesis‐stimulating agents because of evidence of increased risk of hypertension and cardiovascular morbidity and mortality in chronic kidney disease ( CKD ) patients. In the present study, we investigated the effects of recombinant human erythropoietin ( EPO ) on endothelial function of gluteal subcutaneous resistance arteries isolated from 17 stage 4 patients (estimated glomerular filtration rate 21.9±7.4 mL/min per 1.73 m 2 ) aged 63±13 years. Methods and Results Arteries were mounted on a pressurized myograph. EPO impaired endothelium‐dependent relaxation in a concentration‐dependent manner. The maximal response to acetylcholine with EPO at 1, 10, and 20 IU/mL was reduced by 12%, 34%, and 43%, respectively, compared with the absence of EPO ( P EPO ‐induced endothelial dysfunction was significantly associated with carotid stiffness and history of cardiovascular events. EPO had no effect on norepinephrine‐induced vasoconstriction or sodium nitroprusside–induced relaxation. ABT ‐627, an endothelin type A receptor antagonist, and tempol, a superoxide dismutase mimetic, partially reversed the altered endothelial function in the presence of EPO ( P EPO . Conclusions EPO alters endothelial function of resistance arteries in CKD patients via a mechanism involving in part oxidative stress and signaling through an endothelin type A receptor. EPO ‐induced endothelial dysfunction could contribute to deleterious effects of EPO described in large interventional trials.

Despite improving immunosuppressive protocols in renal transplantation, chronic allograft nephropathy (CAN) remains a major impediment to long-term graft survival. The optimal immunosuppressive regimen for a patient with CAN is unknown. The aim of this study is to evaluate the various immunosuppressive management strategies of biopsy-proven CAN and of chronic allograft dysfunction (CAD) (no biopsy). A systematic review of randomized trials (n = 12 trials with 635 patients) was conducted. Studies included patients who were >6 mo post-transplant. All patients were on a calcineurin inhibitor (CNI), most often cyclosporine, and were randomized to convert to mycophenolate mofetil (MMF), tacrolimus, or sirolimus (Rapa) or to add azathioprine, MMF or Rapa to their current regimen. Follow-up time was 6 to 36 mo. The outcome measures evaluated were renal function in 11 of 12 studies and repeat renal biopsy results in one study. The methodological quality scores of the trials were generally low, using the Jadad scale (median value 2/5). Results varied between studies but suggested that CNI withdrawal is safe and that conversion to MMF or Rapa may be beneficial. The incidence of adverse effects ranged from 0% to 68% between the studies, and medication withdrawal occurred in 0% to 24% of patients. The review did not result in a consensus regarding the management of CAN and CAD. Further studies are required to determine the best therapeutic option for patients with CAD and CAN.

Accelerated cardiovascular disease is a frequent complication of renal disease. Chronic kidney disease promotes hypertension and dyslipidemia, which in turn can contribute to the progression of renal failure. Furthermore, diabetic nephropathy is the leading cause of renal failure in developed countries. Together, hypertension, dyslipidemia, and diabetes are major risk factors for the development of endothelial dysfunction and progression of atherosclerosis. Inflammatory mediators are often elevated and the renin-angiotensin system is frequently activated in chronic kidney disease, which likely contributes through enhanced production of reactive oxygen species to the accelerated atherosclerosis observed in chronic kidney disease. Promoters of calcification are increased and inhibitors of calcification are reduced, which favors metastatic vascular calcification, an important participant in vascular injury associated with end-stage renal disease. Accelerated atherosclerosis will then lead to increased prevalence of coronary artery disease, heart failure, stroke, and peripheral arterial disease. Consequently, subjects with chronic renal failure are exposed to increased morbidity and mortality as a result of cardiovascular events. Prevention and treatment of cardiovascular disease are major considerations in the management of individuals with chronic kidney disease.

Two cases of atypical anaphylactoid reactions to intravenous iron dextran in hemodialysis patients are described. Anaphylactic reactions to iron dextran in dialysis patients are not uncommon. Pulmonary edema is not generally seen in anaphylaxis. Our patients both developed significant pulmonary edema following intravenous infusion of iron dextran, which responded promptly to treatment of anaphylaxis. Potential mechanisms are discussed.

Although apparently phenotypically normal at birth, mice heterozygous for inactivation of the gene encoding parathyroid hormone-related peptide (PTHrP) develop haplotype insufficiency by 3 months of age. In addition to histologic and morphologic abnormalities similar to those seen in homozygous mutants, heterozygous animals demonstrated alterations in trabecular bone and bone marrow. These included metaphyseal bone spicules which were diminished in volume, irregularly distributed, and less well developed than those seen in age-matched controls as well as bone marrow, which contained an inordinate number of adipocytes. A substantial reduction in PTHrP mRNA was detected in heterozygous tissue, while circulating parathyroid hormone (PTH) and calcium concentrations were normal. Thus, while a physiologic concentration of PTH was capable of maintaining calcium homeostasis, it was incapable of compensating for PTHrP haploinsufficiency in developing bone. In normal animals, both PTHrP and the PTH/PTHrP receptor were expressed predominantly in chondrocytes situated throughout the proliferative zone of the tibial growth plate. In the metaphysis, the PTH/PTHrP receptor was identified on osteoblasts and preosteoblastic cells situated in the bone marrow, while PTHrP was expressed only by osteoblasts. These observations indicate that postnatal bone development involves susceptible pathways that display exquisite sensitivity to critical levels of PTHrP and imply that the skeletal effects of PTH are influenced by locally produced PTHrP. Moreover, identification of both the ligand and its N-terminal receptor in metaphyseal osteoblasts and their progenitors suggests an autocrine/paracrine role for the protein in osteoblast differentiation and/or function. Impairment in this function as a consequence of PTHrP haploinsufficiency may critically influence the course of bone formation, resulting in altered trabecular architecture and perhaps low bone mass and increased bone fragility.

Purpose: Achieving rapid protection against hepatitis B (HBV) is critical for patients with chronic renal failure (CRF). HEPLISAVTM (HBsAg-ISS) is an investigational vaccine containing hepatitis B surface antigen (HBsAg) and 1018 ISS, a Toll-like Receptor 9 agonist adjuvant. Methods: This was a single-blind, randomized study of 41 subjects, 40–70 years of age, with progressive loss of renal function (glomerular filtration rate [GFR] ≤ 45 mL/min/1.73m2). Subjects were randomized 1:1 to receive HBsAgISS either single dose or double dose, at 0, 4 and 24 weeks. AntiHBsAg concentrations were measured at weeks 4, 12, 24, 28 and 50. Immunogenicity endpoints included seroprotection rate (SPR) and serum geometric mean concentrations (GMC). Safety of HBsAgISS was assessed, including local and systemic reactogenicity and adverse events. Results: A total of 21 subjects received the single dose and 20 subjects received the double dose. Fifteen subjects were on dialysis. Forty of the 41 randomized subjects (97.6%) received the first 2 injections of study drug. Only 2 subjects (1 at each dose level) received the third injection due to premature discontinuation of the study because of an FDA-imposed clinical hold that was subsequently removed. The SPR for the combined HBsAg-ISS groups was 10% (4/40) after one dose at week 4, 58 % (23/40) after 2 doses at week 12, and 100% (11/11) after 2 doses at week 24. GMC was 3.2, 20.4 and 258.7 mIU/mL at week 4, 12 and 24, respectively. No significant differences were observed in subjects pre-dialysis or on dialysis. The most frequently reported local and systemic reactogenicity events were pain at the injection site and fatigue. Conclusion: HBsAg-ISS was immunogenic and welltolerated, and preliminary results suggest the potential of rapid protection against HBV in patients with chronic renal failure. Abstract

Background Observational data suggest that serum magnesium (Mg) concentration is inversely related to vascular calcification and hyperparathyroidism among patients with end-stage renal disease (ESRD). In recent years, there have been several case reports of hypomagnesemia due to use of proton-pump inhibitors (PPI), with the hypomagnesemia attributed to inappropriate gastrointestinal (GI) Mg loss. We hypothesized that the tendency to GI Mg loss is more common than is currently reported. Since patients with ESRD have little to no renal Mg loss to affect serum Mg concentration, dialysis patients are an interesting population in whom to study the relationship between PPI use and serum Mg levels. Methods Using a single-center cross-sectional design, we studied 155 prevalent hemodialysis (HD) patients. Serum Mg concentration for each patient was determined based on the mean of 3 consecutive serum Mg levels drawn at 6 week intervals. PPI use at the time of the blood tests was documented. The relationship between PPI use and Mg concentration was determined in unadjusted analyses, as well as after adjustment for age, gender, race, cause of ESRD, diabetes, time on HD and dialysate Mg concentration. Results 55 % of patients were on PPIs at the time of the study. The majority of patients (62 %) used a dialysate Mg (in mmol/L) of 0.5, and the remainder (38 %) used a dialysate Mg of 0.375. Serum Mg levels were significantly lower among PPI users vs. non-users (0.93 vs. 1.02 mmol/L, p