Reduced functional measure of cardiovascular reserve predicts admission to critical care unit following kidney transplantation

Background: There is currently no effective preoperative assessment for patients undergoing kidney transplantation that is able to identify those at high perioperative risk requiring admission to critical care unit (CCU). We sought to determine if functional measures of cardiovascular reserve, in particular the anaerobic threshold (VO2AT) could identify these patients. Methods: Adult patients were assessed within 4 weeks prior to kidney transplantation in a University hospital with a 37-bed CCU, between April 2010 and June 2012. Cardiopulmonary exercise testing (CPET), echocardiography and arterial applanation tonometry were performed. Results: There were 70 participants (age 41.7614.5 years, 60% male, 91.4% living donor kidney recipients, 23.4% were desensitized). 14 patients (20%) required escalation of care from the ward to CCU following transplantation. Reduced anaerobic threshold (VO2AT) was the most significant predictor, independently (OR = 0.43; 95% CI 0.27–0.68; p,0.001) and in the multivariate logistic regression analysis (adjusted OR = 0.26; 95% CI 0.12–0.59; p = 0.001). The area under the receiveroperating- characteristic curve was 0.93, based on a risk prediction model that incorporated VO2AT, body mass index and desensitization status. Neither echocardiographic nor measures of aortic compliance were significantly associated with CCU admission. Conclusions: To our knowledge, this is the first prospective observational study to demonstrate the usefulness of CPET as a preoperative risk stratification tool for patients undergoing kidney transplantation. The study suggests that VO2AT has the potential to predict perioperative morbidity in kidney transplant recipients

Antibodies with Dual Reactivity to Plasminogen and Complementary PR3 in PR3-ANCA Vasculitis

Patients with inflammatory vascular disease caused by anti-neutrophil cytoplasmic autoantibodies (ANCA) can harbor antibodies not only to the autoantigen proteinase 3 (PR3) but also to complementary PR3 (cPR3105–201), a recombinant protein translated from the antisense strand of PR3 cDNA. The purpose of this study was to identify potential endogenous targets of anti-cPR3105–201 antibodies. Patients’ plasmapheresis material was tested for the presence of antigens reactive with affinity-purified rabbit and chicken anti-cPR3105–201 polyclonal antibodies. Antigen-containing fractions were tested with patients’ anti-cPR3105–201 affinity-purified IgG, and putative protein targets were sequenced by mass spectrometry. Unexpectedly, plasminogen was identified as a target of anti-cPR3105–201. Reactivity of affinity-purified antibodies from two patients was lost when plasminogen was converted to plasmin, indicating restricted specificity. Antiplasminogen antibodies from five patients bound plasminogen at a surface-exposed loop structure within the protease domain. This loop contains an amino acid motif that is also found in a portion of recombinant cPR3105–201; site-directed mutagenesis of this sequence decreased antibody reactivity by 30%. Functionally, antiplasminogen antibodies delayed the conversion of plasminogen to plasmin and increased the dissolution time of fibrin clots. Serologically, antiplasminogen antibody levels were higher in PR3-ANCA patients (n = 72) than healthy control subjects (n = 63), myeloperoxidase-ANCA patients (n = 34), and patients with idiopathic thrombosis (n = 57; P = 0.001). Of the patients with PR3-ANCA, nine had documented deep venous thrombosis events, five of whom were positive for antiplasminogen antibodies. In summary, capitalizing on interactions with complementary proteins, specifically complementary PR3, this study identified plasminogen as a previously undescribed autoantigen in PR3-ANCA vasculitis

Correlation between VO₂AT and other CPET-derived indices of cardiovascular reserve (n = 70).

a<p>Logarithmic transformation applied for analysis; r, Pearson’s correlation coefficient; Fisher’s z-transformation has been used to derive CIs and p-values under the null hypothesis H_0: r = 0.3.</p>*<p>p<0.05.</p

Accuracy in Predicting CCU Admission of the Final Model using Receiver Operator Characteristics (ROC) Curves.

<p>Accuracy in Predicting CCU Admission of the Final Model using Receiver Operator Characteristics (ROC) Curves.</p

Final risk-prediction model based on 3 predictors of CCU admission.

<p>One metric unit increase in the parameters (except desensitization status) is associated with the odds of CCU admission. *Desensitization (none) = No desensitization therapy is associated with decrease odds in CCU admission. OR, odds ratio; Horizontal bars represent the 95% CI.</p

Univariate logistic regression of major echocardiographic parameters and CCU admission.

<p>LVEF, LV ejection fraction; LVMI, LV mass index corrected to body surface area; E/E’, ratio of early transmitral flow velocity to annular mitral velocity (averaged of septal and lateral); LAVI, left atrial volume index corrected to body surface area. OR, odds ratio; Horizontal bars represent the 95% CI. One metric unit increase in the parameters is associated with the odds of CCU admission.</p

Echocardiographic indices for all patients.

<p>Data are mean ± SD or frequencies (%). Analysed using independent samples t-test or χ².LVEF, LV ejection fraction; LA, left atrium; LAVI, left atrial volume index corrected to body surface area; LVMI, LV mass index corrected to body surface area; LVH, left ventricular hypertrophy; E/A, the ratio of peak early to late transmitral ventricular filling velocities; IVRT, isovolumic relaxation time; E/E’, ratio of early transmitral flow velocity to annular mitral velocity (averaged of septal and lateral).</p

Associations between preoperative anaerobic threshold, clinical variables, arterial compliance and CCU admission (n = 70).

†<p>Univariate logistic regression.</p>‡<p>Multiple (binary) logistic regression modeling.</p>*<p>p<0.05.</p