Kidney and Pancreas Transplantation in the United States, 1998–2007: Access for Patients with Diabetes and End-Stage Renal Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73092/1/j.1600-6143.2009.02566.x.pd

Association of Center Volume with Outcome After Liver and Kidney Transplantation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73934/1/j.1600-6143.2004.00462.x.pd

Analytical approaches for transplant research

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73605/1/j.1600-6135.2004.00402.x.pd

Catheter‐related Infection and Septicemia: Impact of Seasonality and Modifiable Practices from the DOPPS

Hemodialysis (HD) catheter‐related infection (CRI) and septicemia contribute to adverse outcomes. The impact of seasonality and prophylactic dialysis practices during high‐risk periods remain unexplored. This multicenter study analyzed DOPPS data from 12,122 HD patients (from 442 facilities) to determine the association between seasonally related climatic variables and CRI and septicemia. Climatic variables were determined by linkage to National Climatic Data Center of National Oceanic and Atmospheric Administration data. Catheter care protocols were examined to determine if they could mitigate infection risk during high‐risk seasons. Survival models were used to estimate the adjusted hazard ratio (AHR) of septicemia by season and by facility catheter dressing protocol. The overall catheter‐related septicemia rate was 0.47 per 1000 catheter days. It varied by season, with an AHR for summer of 1.46 (95% CI: 1.19–1.80) compared with winter. Septicemia was associated with temperature (AHR = 1.07; 95% CI: 1.02–1.13; p  < 0.001). Dressing protocols using chlorhexidine (AHR of septicemia = 0.55; 95% CI: 0.39–0.78) were associated with fewest episodes of CRI or septicemia. Higher catheter‐related septicemia in summer may be due to seasonal conditions (e.g., heat, perspiration) that facilitate bacterial growth and compromise protective measures. Extra vigilance and use of chlorhexidine‐based dressing protocols may provide prophylaxis against CRI and septicemia.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102686/1/sdi12141.pd

Paradoxical patterns of sinusoidal obstruction syndrome-like liver injury in aged female CD-1 mice triggered by cannabidiol-rich cannabis extract and acetaminophen co-administration

© 2019 The Authors. Environmental Toxicology published by Wiley Periodicals, Inc. Exposure to environmental contaminants and consumption of a high, saturated fatty diet has been demonstrated to promote precursors for metabolic syndrome (hyperglycemia, hyperinsulinemia, and hypertriglyceridemia). The purpose of this study was to determine if exposure to the most prevalent environmental persistent organic pollutants (POPs) would act as causative agents to promote metabolic syndrome independent of dietary intake. We hypothesized that POPs will activate the advanced glycated end-product (AGE)-and receptor for AGE (RAGE) signaling cascade to promote downstream signaling modulators of cardiovascular remodeling and oxidative stress in the heart. At 5-weeks of age nondiabetic (WT) and diabetic (ob/ob) mice were exposed POPs mixtures by oral gavage twice a week for 6-weeks. At the end of 6-weeks, animals were sacrificed and the hearts were taken for biochemical analysis. Increased activation of the AGE-RAGE signaling cascade via POPs exposure resulted in elevated levels of fibroblast differentiation (α-smooth muscle actin) and RAGE expression indicated maladaptive cardiac remodeling. Conversely, the observed decreased superoxide dismutase-1 and -2 (SOD-1 and SOD-2) expression may exacerbate the adverse changes occurring as a result of POPs treatment to reduce innate cardioprotective mechanisms. In comparison, ventricular collagen levels were decreased in mice exposed to POPs. In conclusion, exposure to organic environmental pollutants may intensify oxidative and inflammatory stressors to overwhelm protective mechanisms allowing for adverse cardiac remodeling

Mechanisms Contributing to Adverse Cardiovascular Events in Patients with Type 2 Diabetes Mellitus and Stage 4 Chronic Kidney Disease Treated with Bardoxolone Methyl

BackgroundBardoxolone methyl, an Nrf2-activating and nuclear factor-κB-inhibiting semisynthetic oleanane triterpenoid compound, was evaluated in a phase 3 trial (BEACON) in patients with type 2 diabetes mellitus (T2DM) and stage 4 chronic kidney disease (CKD). The trial was terminated because of an increase in heart failure events in the bardoxolone methyl group, many of which appeared related to fluid retention. Thus, additional analyses were conducted to explain these serious adverse events.MethodsPatients (n = 2,185) were randomized to receive once-daily bardoxolone methyl (20 mg) or placebo. Twenty-four-hour urine collections were analyzed in a subset of the BEACON population and from a separate, open-label pharmacology study in patients with stage 3b/4 CKD and T2DM administered 20 mg bardoxolone methyl once daily for 56 consecutive days.ResultsBardoxolone-methyl-treated patients in the BEACON substudy had a clinically meaningful reduction in urine volume and sodium excretion at week 4 relative to baseline (p &lt; 0.05), and a separate study revealed that decreased sodium excretion and urine output occurred in some patients with stage 4 CKD but not those with stage 3b CKD. The clinical phenotype of fluid overload and heart failure in BEACON was similar to that observed with endothelin receptor antagonists in advanced CKD patients, and preclinical data demonstrate that bardoxolone methyl modifies endothelin signaling.ConclusionsThe totality of the evidence suggests that through modulation of the endothelin pathway, bardoxolone methyl may pharmacologically promote acute sodium and volume retention and increase blood pressure in patients with more advanced CKD

Organ donation in the United States

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72348/1/j.1600-6143.3.s4.4.x.pd

Glutathione Deficiency in Cardiac Patients Is Related to the Functional Status and Structural Cardiac Abnormalities

International audienceBACKGROUND: The tripeptide glutathione (L-gamma-glutamyl-cysteinyl-glycine) is essential to cell survival, and deficiency in cardiac and systemic glutathione relates to heart failure progression and cardiac remodelling in animal models. Accordingly, we investigated cardiac and blood glutathione levels in patients of different functional classes and with different structural heart diseases. METHODS: Glutathione was measured using standard enzymatic recycling method in venous blood samples obtained from 91 individuals, including 15 healthy volunteers and 76 patients of New York Heart Association (NYHA) functional class I to IV, undergoing cardiac surgery for coronary artery disease, aortic stenosis or terminal cardiomyopathy. Glutathione was also quantified in right atrial appendages obtained at the time of surgery. RESULTS: In atrial tissue, glutathione was severely depleted (-58%) in NYHA class IV patients compared to NYHA class I patients (P = 0.002). In patients with coronary artery disease, this depletion was related to the severity of left ventricular dysfunction (P = 0.006). Compared to healthy controls, blood glutathione was decreased by 21% in NYHA class I patients with structural cardiac disease (P<0.01), and by 40% in symptomatic patients of NYHA class II to IV (P<0.0001). According to the functional NYHA class, significant depletion in blood glutathione occurred before detectable elevation in blood sTNFR1, a marker of symptomatic heart failure severity, as shown by the exponential relationship between these two parameters in the whole cohort of patients (r = 0.88). CONCLUSIONS: This study provides evidence that cardiac and systemic glutathione deficiency is related to the functional status and structural cardiac abnormalities of patients with cardiac diseases. These data also suggest that blood glutathione test may be an interesting new biomarker to detect asymptomatic patients with structural cardiac abnormalities