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Endothelial Dysfunction and 6-Year Risk of Mortality in Kidney Transplant Recipients.

ABSTRACT: Background:Endothelial dysfunction is an early and potentially reversible stage in the atherosclerotic process. We assessed endothelial dysfunction noninvasively in kidney transplant recipients (KTRs) and evaluated the association with mortality and graft outcomes. Methods:Flow-mediated dilation (FMD) was measured in arteria brachialis by ultrasound, with baseline diameters obtained at rest and maximal diameters obtained during reactive hyperemia occurring after 5 min of forearm occlusion. FMD% is the percentage difference of flow-mediated dilation relative to baseline. Endpoints on mortality and graft outcomes were collected from The Norwegian Renal Registry. The distribution of risk according to FMD levels was assessed in Cox regression using a restricted cubic spline function. FMD was dichotomized using receiver operating characteristic analysis to identify optimal cut points at maximal sensitivity and specificity. Results:From a total of 269 KTRs in 2012, 152 (56.5%) were eligible and examined 10 wk after transplantation, and 145 had successful FMD measurements. During a mean follow-up of 6.5 y, 26 patients died, 11 lost their graft, and 34 experienced either graft loss or death. Mortality increased with lower FMD levels until about 5% dilation and did not change with further reduction in FMD% (P for nonlinearity <0.01). An optimal cut point of FMD ≤5.36% defined impaired endothelial function and FMD% below this level, was associated with fatal outcome, hazard ratio (HR), 9.80 (1.29-74.62), P = 0.03, uncensored graft loss, HR, 7.80 (1.83-33.30), P = 0.01, but an association with death-censored graft loss was lost after adjusting for pulse pressure, HR, 4.58 (0.55-37.92), P = 0.16. Conclusions:We found that impaired FMD is strongly associated with mortality in KTRs.

SUBMITTER: Langberg NE

PROVIDER: S-EPMC8670577 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundIt is unknown whether meat intake is beneficial for long-term patient and graft survival in kidney transplant recipients (KTR).ObjectivesWe first investigated the association of the previously described meat intake biomarkers 1-methylhistidine and 3-methylhistidine with intake of white and red meat as estimated from a validated food frequency questionnaire (FFQ). Second, we investigated the association of the meat intake biomarkers with long-term outcomes in KTR.MethodsWe measured 24-h urinary excretion of 1-methylhistidine and 3-methylhistidine by validated assays in a cohort of 678 clinically stable KTR. Cross-sectional associations were assessed by linear regression. We used Cox regression analyses to prospectively study associations of log2-transformed biomarkers with mortality and graft failure.ResultsUrinary 1-methylhistidine and 3-methylhistidine excretion values were median: 282; interquartile range (IQR): 132-598 µmol/24 h and median: 231; IQR: 175-306 µmol/24 h, respectively. Urinary 1-methylhistidine was associated with white meat intake [standardized β (st β): 0.20; 95% CI: 0.12, 0.28; P < 0.001], whereas urinary 3-methylhistidine was associated with red meat intake (st β: 0.30; 95% CI: 0.23, 0.38; P < 0.001). During median follow-up for 5.4 (IQR: 4.9-6.1) y, 145 (21%) died and 83 (12%) developed graft failure. Urinary 3-methylhistidine was inversely associated with mortality independently of potential confounders (HR per doubling: 0.55; 95% CI: 0.42, 0.72; P < 0.001). Both urinary 1-methylhistidine and urinary 3-methylhistidine were inversely associated with graft failure independent of potential confounders (HR per doubling: 0.84; 95% CI: 0.73, 0.96; P = 0.01; and 0.59; 95% CI: 0.41, 0.85; P = 0.004, respectively).ConclusionsHigh urinary 3-methylhistidine, reflecting higher red meat intake, is independently associated with lower risk of mortality. High urinary concentrations of both 1- and 3-methylhistidine, of which the former reflects higher white meat intake, are independently associated with lower risk of graft failure in KTR. Future intervention studies are warranted to study the effect of high meat intake on mortality and graft failure in KTR, using these biomarkers.

Project description:BackgroundSarcopenia and endothelial dysfunction are both common among kidney transplant (KT) recipients. We aimed to evaluate the association between endothelial dysfunction and sarcopenia, as well as its individual components.MethodsVascular reactivity index (VRI), skeletal muscle index (SMI = skeletal muscle mass/height2), handgrip strength (HGS), and 6-meter usual gait speed (GS) were measured in 95 KT recipients. Low SMI was defined as SMI less than 10% of the sex-specific reference values from Chinese adults; low HGS as HGS < 28 kg for men and < 18 kg for women; slow GS as GS below 1.0 m/s. Sarcopenia was diagnosed based on the presence of low SMI as an essential criterion, accompanied by either low HGS or slow GS. Vascular reactivity was classified as being indicative of poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), or good (VRI ≥ 2.0) vascular reactivity.ResultsOf the 95 patients, aged 45.2 ± 10.9 years, 11.6% had sarcopenia and 13.7% had poor vascular reactivity. Patients with sarcopenia were lower in body mass index (p = 0.001) and VRI (p = 0.041), and have a higher proportion of low muscle mass (p < 0.001), low HGS (p < 0.001), and slow GS (p = 0.001). Patients with poor vascular reactivity have a higher proportion of sarcopenia (p = 0.005), low HGS (p = 0.006), and slow GS (p = 0.029). Multivariate logistic regression analysis showed that patients in the poor VRI group were significantly associated with sarcopenia (odds ratio, OR = 6.17; 95% confidence interval [1.06-36.04]; p = 0.043), comparing to those with good VRI. We further analysed the effects of VRI on individual components of sarcopenia and found that VRI predicted slow GS significantly (OR = 0.41; 95% CI = [0.21-0.79]; p = 0.007), but not low SMI (OR = 1.15; 95% CI [0.53-2.49]; p = 0.718) and HGS (OR = 0.59; 95% CI [0.31-1.16]; p = 0.125).ConclusionsWe concluded that endothelial dysfunction is a key determinant of sarcopenia in KT recipients. Furthermore, endothelial dysfunction is more closely related to gait speed than muscle mass and strength.

Project description:Background and objectivesIn kidney transplant recipients, elevated circulating advanced glycation endproducts (AGEs) are the result of increased formation and decreased kidney clearance. AGEs trigger several intracellular mechanisms that ultimately yield excess cardiovascular disease. We hypothesized that, in stable kidney transplant recipients, circulating AGEs are associated with long-term risk of cardiovascular mortality, and that such a relationship is mediated by inflammatory, oxidative stress, and endothelial dysfunction biomarkers.Design, setting, participants, & measurementsProspective cohort study of stable kidney transplant recipients recruited between 2001 and 2003 in a university setting. We performed multivariable-adjusted Cox regression analyses to assess the association of AGEs (i.e., Nε -[Carboxymethyl]lysine (CML) and Nε -[Carboxyethyl]lysine (CEL), measured by tandem mass spectrometry) with cardiovascular mortality. Mediation analyses were performed according to Preacher and Hayes's procedure.ResultsWe included 555 kidney transplant recipients (age 51±12 years, 56% men). During a median follow-up of 6.9 years, 122 kidney transplant recipients died (52% deaths were due to cardiovascular causes). CML and CEL concentrations were directly associated with cardiovascular mortality (respectively, hazard ratio, 1.55; 95% confidence interval, 1.24 to 1.95; P<0.001; and hazard ratio, 1.53; 95% confidence interval 1.18 to 1.98; P=0.002), independent of age, diabetes, smoking status, body mass index, eGFR and proteinuria. Further adjustments, including cardiovascular history, did not materially change these findings. In mediation analyses, free thiol groups and soluble vascular cell adhesion molecule-1 consistently explained approximately 35% of the association of CML and CEL with cardiovascular mortality.ConclusionsIn stable kidney transplant recipients, circulating levels of AGEs are independently associated with long-term risk of cardiovascular mortality.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2019_09_17_CJN00540119.mp3.

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Endothelial Dysfunction and 6-Year Risk of Mortality in Kidney Transplant Recipients.

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