A 6-Month clinical practice pilot study of sucroferric oxyhydroxide on nutritional status in patients on peritoneal dialysis.

BACKGROUND: Hyperphosphatemia is common in patients on peritoneal dialysis (PD). Restricting dietary phosphorus often leads to a decrease in protein intake, which may result in hypoalbuminemia. The high pill burden of phosphate binders may also contribute to compromised appetite and dietary intake. Hypoalbuminemia is associated with an increased risk of morbidity and mortality in PD patients. The goal of this study was to determine if sucroferric oxyhydroxide improves albumin and self-reported measures of appetite in PD patients. METHODS: We performed a prospective, open-label, 6-month, pilot study of 17 adult PD patients from the Denver Metro Area. Patients had to use automated peritoneal dialysis for ≥ 3 months, have a serum albumin ≤ 3.8 g/dL, and have serum phosphate ≥ 5.5 mg/dL or ≤ 5.5 mg/dL on a binder other than SO. SO was titrated to a goal serum phosphate of < 5.5 mg/dL. The primary outcome was change in serum phosphate, albumin, and phosphorus-attuned albumin (defined as albumin divided by phosphorus) over 6 months. RESULTS: The mean (SD) age and dialysis vintage was 55 ± 13 years and 3.8 ± 2.7 years, respectively. Participants' serum phosphate significantly decreased with fewer phosphate binder pills/day after switching to SO. There was no change in serum albumin, appetite, or dietary intake. However, participants had significant improvements in phosphorus-attuned albumin. CONCLUSION: The transition to SO improved phosphorus control, phosphorus-attuned albumin, and pill burden. There were no significant changes in self-reported appetite or dietary intake during the study. These findings suggest that PD patients maintained nutritional status with SO therapy. TRIAL REGISTRATION: First registered at ClinicalTrials.gov ( NCT04046263 ) on 06/08/2019.

A Pilot Study of the Safety and Efficacy of Alkali Therapy on Vascular Function in Kidney Transplant Recipients.

INTRODUCTION: Metabolic acidosis is associated with cardiovascular events, graft function, and mortality in kidney transplant recipients (KTRs). We examined the effect of alkali therapy on vascular endothelial function in KTRs. METHODS: We performed an 18-week, randomized, double-blind, placebo-controlled crossover pilot study examining the effect of sodium bicarbonate therapy versus placebo on vascular function in 20 adult KTRs at least 1 year from transplant with an estimated glomerular filtration rate (eGFR) ≥45 ml/min per 1.73 m2 and a serum bicarbonate level of 20 to 26 mEq/L. Each treatment period was 8 weeks in duration with a 2-week washout period between treatments. The primary outcome was change in brachial artery flow-mediated dilation (FMD) between sodium bicarbonate treatment and placebo. RESULTS: Twenty patients completed the study and were included in the primary analysis. The mean (SD) baseline eGFR of participants was 75 (22) ml/min per 1.73 m2, respectively. Serum bicarbonate levels did not increase significantly with treatment (0.3 [1.5] mEq/L, P = 0.37). Sodium bicarbonate therapy was not associated with worsening blood pressure, weight gain, or hypokalemia. There was no significant increase in FMD after 8 weeks of sodium bicarbonate therapy compared to placebo (mean change in FMD 2.2%, 95% CI -0.1 to 4.6, P = 0.06). There were no significant changes in high-sensitivity C-reactive protein, interleukin-6, eGFR, or urinary albumin-to-creatinine ratio during treatment. Urinary ammonium excretion decreased by 9 mmol/d (P=0.003), with sodium bicarbonate. CONCLUSIONS: Sodium bicarbonate therapy is safe and feasible in KTRs, and our results strengthen the need for a larger randomized controlled trial.

Descripción de una cohorte de pacientes de artritis idiopática juvenil en el estado de Sonora, México / Description of a cohort of patients with Juvenile Idiopathic Arthritis in the state of Sonora Mexico

IINTRODUCCIÓN: La artritis idiopática juvenil (AIJ) es una de las enfermedades crónicas degenerativas más frecuentes en la infancia, ocasionando secuelas importantes tal como la discapacidad, ceguera con un curso evolutivo, pronóstico y tratamiento distinto para todos los fenotipos. OBJETIVO: Conocer los subtipos clínicos más frecuentes de AIJ en el Servicio de Reumatología de un hospital, de segundo nivel de atención, del noroeste de México. MATERIALES Y MÉTODOS: Bajo un diseño tipo cohorte se estudiaron pacientes con AIJ del Servicio de Reumatología. La clasificación en subtipos de la enfermedad se realizó mediante los criterios clínicos y de laboratorio emitidos por la ILAR. Se midió la frecuencia de los subtipos de AIJ, así como la asociación de estos con variables sociodemográficas como edad y género. RESULTADOS: Se estudiaron 35 pacientes con AIJ dentro de los cuales predominó el género femenino con el 74% de los casos. El grupo de edad más afectado se observó en los pacientes entre 10 y 12 arios. Los subtipos de AIJ más frecuentes son la artritis asociada a entesitis (40%) y la AIJ poliarticular con factor reumatoide positivo (20%). Se encontró asociación significativa entre edad y género de los casos y género subtipo de AIJ. CONCLUSIONES: Los casos de AIJ se presentan a más temprana edad en el género masculino, al contrario los femeninos se presentan en mayores de 9 años, esto nos podría orientar en el abordaje diagnóstico de pacientes con patología articular.

INTRODUCTION: Juvenile idiopathic arthritis (JIA) is one of the most common childhood chronic degenerative diseases causing serious sequelae such as disability and blindness with clinical course, prognosis and treatment for all different phenotypes. OBJECTIVE: To determine the most common clinical subtypes of JIA in the rheumatology of a second level hospital care in northwestern Mexico. MATERIAL AND METHODS: Under a cohort design were studied patients with JIA in rheumatology service. The classification into subtypes of the disease was performed by clinical and laboratory criteria issued by the ILAR. The frequency of the subtypes of JIA, as well as the latter's association with sociodemographic variables such as age and gender was measured. RESULTS: From 35 patients with JIA predominance of female gender was 74% of the cases studied. The most affected age group was observed in patients between 10 and 12, most frequent subtypes was arthritis associated with enthesitis (40%) and poly articular JIA with positive rheumatoid factor (20%). Significant association between age and gender and gen-der cases and subtype of JIA found. CONCLUSIONS: JIA cases presented at an earlier age in the male gender, unlike girls in wich age presentation comes between 10 and 12 years.

Btk Inhibitor RN983 Delivered by Dry Powder Nose-only Aerosol Inhalation Inhibits Bronchoconstriction and Pulmonary Inflammation in the Ovalbumin Allergic Mouse Model of Asthma.

BACKGROUND: In allergen-induced asthma, activated mast cells start the lung inflammatory process with degranulation, cytokine synthesis, and mediator release. Bruton's tyrosine kinase (Btk) activity is required for the mast cell activation during IgE-mediated secretion. METHODS: This study characterized a novel inhaled Btk inhibitor RN983 in vitro and in ovalbumin allergic mouse models of the early (EAR) and late (LAR) asthmatic response. RESULTS: RN983 potently, selectively, and reversibly inhibited the Btk enzyme. RN983 displayed functional activities in human cell-based assays in multiple cell types, inhibiting IgG production in B-cells with an IC50 of 2.5 ± 0.7 nM and PGD2 production from mast cells with an IC50 of 8.3 ± 1.1 nM. RN983 displayed similar functional activities in the allergic mouse model of asthma when delivered as a dry powder aerosol by nose-only inhalation. RN983 was less potent at inhibiting bronchoconstriction (IC50(RN983) = 59 µg/kg) than the ß-agonist salbutamol (IC50(salbutamol) = 15 µg/kg) in the mouse model of the EAR. RN983 was more potent at inhibiting the antigen induced increase in pulmonary inflammation (IC50(RN983) = <3 µg/kg) than the inhaled corticosteroid budesonide (IC50(budesonide) = 27 µg/kg) in the mouse model of the LAR. CONCLUSIONS: Inhalation of aerosolized RN983 may be effective as a stand-alone asthma therapy or used in combination with inhaled steroids and ß-agonists in severe asthmatics due to its potent inhibition of mast cell activation.

Bleomycin induces molecular changes directly relevant to idiopathic pulmonary fibrosis: a model for "active" disease.

The preclinical model of bleomycin-induced lung fibrosis, used to investigate mechanisms related to idiopathic pulmonary fibrosis (IPF), has incorrectly predicted efficacy for several candidate compounds suggesting that it may be of limited value. As an attempt to improve the predictive nature of this model, integrative bioinformatic approaches were used to compare molecular alterations in the lungs of bleomycin-treated mice and patients with IPF. Using gene set enrichment analysis we show for the first time that genes differentially expressed during the fibrotic phase of the single challenge bleomycin model were significantly enriched in the expression profiles of IPF patients. The genes that contributed most to the enrichment were largely involved in mitosis, growth factor, and matrix signaling. Interestingly, these same mitotic processes were increased in the expression profiles of fibroblasts isolated from rapidly progressing, but not slowly progressing, IPF patients relative to control subjects. The data also indicated that TGFß was not the sole mediator responsible for the changes observed in this model since the ALK-5 inhibitor SB525334 effectively attenuated some but not all of the fibrosis associated with this model. Although some would suggest that repetitive bleomycin injuries may more effectively model IPF-like changes, our data do not support this conclusion. Together, these data highlight that a single bleomycin instillation effectively replicates several of the specific pathogenic molecular changes associated with IPF, and may be best used as a model for patients with active disease.