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Ana C Krieger,1 Heekoung Youn,2 Frank Modersitzki,2 Ya-Lin Chiu,1 Linda M Gerber,1 Elizabeth Weinshel,2 Christine R Fielding21Weill Cornell Medical College and New York Presbyterian Hospital, 2New York University School of Medicine and NYU Langone Medical Center, New York, NYBackground: Obstructive sleep apnea is commonly associated with metabolic changes and obesity, and changes in body weight by either medical or surgical approaches have been considered to affect the severity of sleep apnea and appetite-controlling hormones. This prospective study evaluated the effect of weight loss induced by laparoscopic adjustable gastric banding (LAGB) surgery on respiratory disturbance during sleep, oxygen saturation levels, sleep architecture, and leptin and ghrelin levels.Methods: Participants were patients at a university-based medical center surgical weight loss program. All participants with a body mass index > 30 kg/m2 undergoing LAGB surgery for weight reduction were offered the opportunity to participate in the study. Procedures included overnight polysomnography followed by fasting hormone levels at baseline and 12 months postoperatively.Results: Thirty subjects (10 men, 20 women) of mean age 44.0 ± 12.5 years were recruited. At 12 months postoperatively, mean excess weight loss was 44.4% ± 14%. The apnea-hypopnea index decreased from 34.2 ± 35 to 19.0 ± 21.7 events per hour (P < 0.0001), while leptin levels decreased from 24.5 ± 17.42 pg/mL to 11.6 ± 10.6 pg/mL (P = 0.02). Ghrelin levels did not change substantially. Nadir oxygen saturation levels increased from 81% to 84% at 12 months (P = 0.03). Mean oxygen saturation improved and was positively correlated with ghrelin levels at both time points (r = 0.39, P = 0.07, and r = 0.60, P = 0.01).Conclusion: LAGB surgery was associated with 44.4% excess weight loss at 12 months, accompanied by a 33.7% improvement in apnea-hypopnea index as well as a reduction in leptin levels by 31.7% in this group. An association between ghrelin and mean oxygen saturation was seen and deserves further investigation.Keywords: sleep apnea, obesity, bariatric surgery, weight loss, metabolism, leptin, ghrelin, sleep

Introduction: Hyperoxaluria is a risk factor for kidney stone formation and chronic kidney disease progression. The microbiome is an important protective factor against oxalate accumulation through the activity of its oxalate-degrading enzymes (ODEs). In this cross-sectional study, we leverage multiomics to characterize the microbial community of participants with primary and enteric hyperoxaluria, as well as idiopathic calcium oxalate kidney stone (CKS) formers, focusing on the relationship between oxalate degrading functions of the microbiome., Methods: Patients diagnosed with type 1 primary hyperoxaluria (PH), enteric hyperoxaluria (EH), and CKS were screened for inclusion in the study. Participants completed a food frequency questionnaire recording their dietary oxalate content while fecal oxalate levels were ascertained. DNA and RNA were extracted from stool samples and sequenced. Metagenomic (MTG) and metatranscriptomic (MTT) data were processed through our bioinformatics pipelines, and microbiome diversity, differential abundance, and networks were subject to statistical analysis in relationship with oxalate levels., Results: A total of 38 subjects were recruited, including 13 healthy participants, 12 patients with recurrent CKS, 8 with PH, and 5 with EH. Urinary and fecal oxalate were significantly higher in the PH and the EH population compared to healthy controls. At the community level, alpha-diversity and beta-diversity indices were similar across all populations. The respective contributions of single bacterial species to the total oxalate degradative potential were similar in healthy and PH subjects. MTT-based network analysis identified the most interactive bacterial network in patients with PH. Patients with EH had a decreased abundance of multiple major oxalate degraders., Conclusion: The composition and inferred activity of oxalate-degrading microbiota were differentially associated with host clinical conditions. Identifying these changes improves our understanding of the relationships between dietary constituents, microbiota, and oxalate homeostasis, and suggests new therapeutic approaches protecting against hyperoxaluria., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Background: Understanding the relationship between clinical and patient-reported outcomes (PROs) will help support clinical care and future clinical trial design of novel therapies for focal segmental glomerulosclerosis (FSGS)., Methods: FSGS patients ≥8 years of age enrolled in the Nephrotic Syndrome Study Network completed Patient-Reported Outcomes Measurement Information System PRO measures of health-related quality of life (HRQoL) (children: global health, mobility, fatigue, pain interference, depression, anxiety, stress and peer relationships; adults: physical functioning, fatigue, pain interference, sleep impairment, mental health, depression, anxiety and social satisfaction) at baseline and during longitudinal follow-up for a maximum of 5 years. Linear mixed-effects models were used to determine which demographic, clinical and laboratory features were associated with PROs for each of the eight children and eight adults studied., Results: There were 45 children and 114 adult FSGS patients enrolled that had at least one PRO assessment and 519 patient visits. Multivariable analyses among children found that edema was associated with global health (-7.6 points, P = 0.02) and mobility (-4.2, P = 0.02), the number of reported symptoms was associated with worse depression (-2.7 per symptom, P = 0.009) and anxiety (-2.3, P = 0.02) and the number of emergency room (ER) visits in the prior 6 months was associated with worse mobility (-2.8 per visit, P < 0.001) and fatigue (-2.4, P = 0.03). Multivariable analyses among adults found the number of reported symptoms was associated with worse function in all eight PROMIS measures and the number of ER visits was associated with worse fatigue, pain interference, sleep impairment, depression, anxiety and social satisfaction. Laboratory markers of disease severity (i.e. proteinuria, estimated glomerular filtration rate and serum albumin) did not predict PRO in multivariable analyses, with the single exception of complete remission and better pain interference scores among children (+9.3, P  =  0.03)., Conclusions: PROs provide important information about HRQoL for persons with FSGS that is not captured solely by the examination of laboratory-based markers of disease. However, it is critical that instruments capture the patient experience and FSGS clinical trials may benefit from a disease-specific instrument more sensitive to within-patient changes., (© The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA.)

Background: Volume overload and depletion both lead to high morbidity and mortality. Achieving euvolemia is a challenge in patients with end stage kidney disease on hemodialysis (HD). Blood volume analysis (BVA) uses radiolabeled albumin to determine intravascular blood volume (BV). The measured BV is compared to an ideal BV (validated in healthy controls). We hypothesized that BVA could be used in HD to evaluate the adequacy of the current clinically prescribed "estimated dry weight" (EDW) and to titrate EDW in order to improve overall volume status. We were also interested in the reproducibility of BVA results in end stage kidney disease., Methods: Twelve adults on chronic HD were recruited; 10 completed the study. BVA (Daxor, New York, NY, USA) was used to measure BV at baseline. EDW was kept the same if the patient was deemed to be euvolemic by BVA otherwise, the prescribed EDW was changed with the aim that measured BV would match ideal BV. A second BVA measurement was done 1-3 months later in order to measure BV again., Results: Based on BVA, 6/10 patients were euvolemic at baseline and 5/10 were euvolemic at the second measurement. When comparing patients who had their prescribed EDW changed after the initial BVA to those who did not, both groups had similar differences between measured and ideal BV (P = 0.75). BV values were unchanged at the second measurement (P = 0.34) and there was no linear correlation between BV change and weight change (r 2  = 0.08)., Conclusions: This pilot study is the first longitudinal measurement of BVA in HD patients. It revealed that changing weight did not proportionally change intravascular BV. BV remained stable for 1-3 months. BVA may not be helpful in clinically stable HD patients but studies on patients with hemodynamic instability and uncertain volume status are needed., Trial Registration: ClinicalTrials.gov (NCT02717533), first registered February 4, 2015.

Background: Obstructive sleep apnea is commonly associated with metabolic changes and obesity, and changes in body weight by either medical or surgical approaches have been considered to affect the severity of sleep apnea and appetite-controlling hormones. This prospective study evaluated the effect of weight loss induced by laparoscopic adjustable gastric banding (LAGB) surgery on respiratory disturbance during sleep, oxygen saturation levels, sleep architecture, and leptin and ghrelin levels., Methods: Participants were patients at a university-based medical center surgical weight loss program. All participants with a body mass index > 30 kg/m(2) undergoing LAGB surgery for weight reduction were offered the opportunity to participate in the study. Procedures included overnight polysomnography followed by fasting hormone levels at baseline and 12 months postoperatively., Results: Thirty subjects (10 men, 20 women) of mean age 44.0 ± 12.5 years were recruited. At 12 months postoperatively, mean excess weight loss was 44.4% ± 14%. The apnea-hypopnea index decreased from 34.2 ± 35 to 19.0 ± 21.7 events per hour (P < 0.0001), while leptin levels decreased from 24.5 ± 17.42 pg/mL to 11.6 ± 10.6 pg/mL (P = 0.02). Ghrelin levels did not change substantially. Nadir oxygen saturation levels increased from 81% to 84% at 12 months (P = 0.03). Mean oxygen saturation improved and was positively correlated with ghrelin levels at both time points (r = 0.39, P = 0.07, and r = 0.60, P = 0.01)., Conclusion: LAGB surgery was associated with 44.4% excess weight loss at 12 months, accompanied by a 33.7% improvement in apnea-hypopnea index as well as a reduction in leptin levels by 31.7% in this group. An association between ghrelin and mean oxygen saturation was seen and deserves further investigation.

Background: Urinary oxalate excretion is an important contributor to calcium oxalate stone formation. Methods of reducing oxalate excretion are not wholly satisfactory, and no controlled trials using them have been performed to prevent stone recurrence. Some lactic acid bacteria can degrade oxalate in vitro. This study sought to reduce urinary oxalate excretion in calcium stone formers with idiopathic hyperoxaluria., Design, Setting, Participants, and Measurements: A randomized, double-blind, placebo-controlled trial was performed of Oxadrop, a mix of four lactic acid bacterium species. This preparation previously reduced oxalate excretion in stone formers with idiopathic and enteric hyperoxaluria. Patients were selected from two stone prevention clinics. Twenty people with calcium stones and idiopathic hyperoxaluria (>40 mg/d) were enrolled and randomly assigned 1:1 in placebo and active preparation arms. Both groups took 3.6 g of granulate each day: Either placebo or the experimental preparation. Participants performed two consecutive 24-h urine collections at baseline, at 28 d of therapy, and at 56 d, after being off the preparation for 4 wk. Diet was replicated at each point., Results: There was no effect of the study preparation: Mean 24-h urinary oxalate excretion in placebo-treated patients was 73.9 mg at baseline and 72.7 mg after treatment, whereas the Oxadrop-treated patients had 59.1 mg at baseline and 55.4 mg after treatment. The preparation was well tolerated; three participants on active treatment experienced mild constipation., Conclusions: In this randomized, placebo-controlled trial, Oxadrop did not reduce urinary oxalate excretion in participants with idiopathic hyperoxaluria.

Chronic obstructive pulmonary disease (COPD) is associated with significant morbidity and mortality. Its possible association with obstructive sleep apnea is a major cause of concern for clinicians. As the prevalence of both COPD and sleep apnea continues to rise, further investigation of this interaction is needed. In addition, COPD patients are at risk for hypoventilation during sleep due to the underlying respiratory dysfunction. In this study, 13 COPD subjects and 13 non-COPD control subjects were compared for the presence and severity of obstructive sleep apnea and nocturnal hypoventilation. All 26 subjects had presented to a sleep clinic and showed no signs of daytime hypoxemia. After matching for BMI and age, COPD subjects had a similar prevalence of sleep apnea with a lower degree of severity compared to the control subjects. However, less severe events, such as RERA, occurred at similar rates between the two groups. There was no significant difference between groups in the magnitude of oxyhemoglobin desaturation during sleep. Interestingly, severity and presence of nocturnal hypoxemia correlated with that of sleep apnea in the control group, but not in the COPD subjects. In conclusion, COPD without daytime hypoxemia was not a risk factor for sleep apnea or nocturnal hypoventilation in this study.