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Objective: Cardiovascular disease is the leading cause of death in kidney transplant recipients (KTRs), yet incompletely accountable by traditional risk factors. Inflammation is an unconventional cardiovascular risk factor, with gut-derived endotoxemia potentially driving inflammation and endothelial disease. Comparable data are lacking in kidney transplantation. This study investigated the associations of endotoxemia with inflammation, endothelial activation, and 5-year cardiovascular events in KTRs. Determinants of endotoxemia were also explored., Design and Methods: This is a single-center cross-sectional study with prospective follow-up from a prevalent cohort of 128 KTRs., Main Outcome Measures: Demographic, nutritional and clinical predictors of inflammation (high-sensitivity C-reactive protein [hsCRP]), endothelial activation (sE-selectin), and endotoxemia (endotoxin) were assessed. Follow-up data on 5-year cardiovascular event rates were collected., Results: Endotoxemia (P = .03), reduced 25-hydroxyvitamin D (P = .04), high fructose intake (P < .001), decreased fiber intake (P < .001), and abdominal obesity (P = .002) were independently associated with elevated hsCRP. In turn, endotoxemia (P = .007) and increasing hsCRP (P = .02) were both independently associated with raised sE-selectin. Furthermore, endotoxemia predicted increased cardiovascular event rate (P = .02), independent of hsCRP and a global measure of cardiovascular risk estimated by a validated algorithm of 7-year risk for major adverse cardiac events in kidney transplantation. Determinants of endotoxemia included reduced 25-hydroxyvitamin D (P < .001), hypertriglyceridemia (P < .001), increased fructose intake (P = .01), and abdominal obesity (P = .01)., Conclusions: Endotoxemia in KTRs contributes to inflammation, endothelial activation, and increased cardiovascular events. This study highlights the clinical relevance of endotoxemia in KTRs, suggesting future interventional targets., (Copyright © 2017 National Kidney Foundation, Inc. All rights reserved.)

Background/aims: Acute kidney injury (AKI) following admission to hospital is associated with increased mortality, morbidity and length of stay. Factors that predispose patients to AKI frequently co-exist. The precise description of their representation in unselected admissions could help define mechanistic inter-relationships and optimise risk stratification strategies. Our aim was therefore to define precisely, using electronically available data, the variables that are associated with AKI., Methods: A cohort study of 112,987 emergency admissions to an urban academic medical centre between 2006 and 2010 was performed. Post-admission AKI was defined using KDIGO aligned, proportionate changes in serum creatinine, denominated by the first measured. AKI correlated with co-morbidities, medications received and the C-reactive protein concentration (CRP)., Results: The relationship between post-admission AKI and putative risk factors was defined in univariate and multivariate analyses. Inclusion of CRP in multivariate analyses significantly reduced the strength of association between some co-variables such as radiological contrast and gentamicin administration but not others., Conclusion: The effect of CRP in these analyses supports the role of systemic inflammation in susceptibility to post-admission AKI. It accounts for the greater part of univariate associations between AKI and some nephrotoxic agents, placing the risk attributable to their use in context. Quantification of the systemic inflammatory response may have utility in AKI risk stratification, integrating various determinants of susceptibility., (© 2014 S. Karger AG, Basel.)

Over 40% of kidney transplant recipients (KTRs) report severe fatigue and 25% show evidence of clinical depression. These symptoms may in part result from persistent inflammation, in which translocation of gut lipopolysaccharide (LPS) could be a contributing factor. The present study investigated if plasma LPS predicted systemic inflammation, as well as symptoms of depression and fatigue. This study enrolled 128 stable KTRs that were >24 months post-transplantation [Mean age = 50 SD ± 15; 56% male]. Symptoms of depression and fatigue were assessed using the Hospital Anxiety and Depression scale and the Multidimensional Fatigue Inventory. Fasting blood was analysed for LPS and C-reactive protein (hsCRP). Analyses were adjusted for clinical and demographic markers, including age, ethnicity, gender, BMI, and kidney function (eGFR). As expected, LPS levels predicted hsCRP ( β = .39, p < .001). In turn, both LPS and hsCRP predicted depressive symptoms ( β = .31 and beta = .24, respectively, p < .01), as well as several dimensions of fatigue ( β s > .17 and <.31, p < .01). After adjustment for inflammation, LPS remained an independent predictor of depressive symptoms ( β = .28, p < .01) as well as fatigue (‘general fatigue’, ‘physical fatigue’, ‘reduced motivation’, and ‘mental fatigue’ ( β s > .19 and <29, p < .05 and >.001). In conclusion, this study identified inflammation and circulating endotoxin as independent predictors of depressive symptoms and fatigue. Control of circulating LPS, e.g., through manipulation of gut permeability, may help to improve mood and reduce lethargy in KTRs. [ABSTRACT FROM AUTHOR]