Predictors of postoperative cardiovascular complications up to 3 months after kidney transplantation.

BACKGROUND: Renal transplant patients have a high peri-operative risk for cardiovascular events. Pre-operative screening for cardiac ischaemia might lower this risk, but there are no specific guidelines. METHODS: We conducted a chart review for all renal transplants performed between January 2010 and December 2013. We collected data about patient characteristics, pre-operative cardiac evaluation before referral, diagnostic tests and interventions. Logistic regression analyses were then applied to relate these factors to the composite endpoint of cardiac death, myocardial infarction, coronary revascularisation or admission for heart failure within 3 months after transplantation. RESULTS: A total of 770 kidney transplants were performed in 751 patients. In 750 cases (97%) a referral to the cardiologist was made. Non-invasive ischaemia detection by myocardial perfusion scintigraphy, exercise stress test or dobutamine stress echocardiography was carried out in 631 cases (82%). Coronary angiography was performed in 85 cases, which revealed significant coronary artery disease in 19 cases. Prophylactic revascularisation was done in 7 cases. The incidence of the study endpoint was 8.6%. In multivariable regression analysis, age at transplantation, pre-transplant myocardial infarction or heart failure, post-operative decrease in haemoglobin and positive non-invasive ischaemia testing were significantly associated with the study endpoint. However, when analysed separately, none of the different non-invasive ischaemia detection modalities were related to the study endpoint. CONCLUSION: Especially those renal transplant candidates with a cardiac history carry a high risk for a cardiovascular event post-transplantation. Uniformity in cardiac screening of renal transplant candidates and better pre-operative preparation might lower this post-operative risk. Besides, post-transplant anaemia should be prevented.

Regulatory T cell features in chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in any of the genes encoding the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, responsible for the production of reactive oxygen species (ROS). CGD is marked by invasive bacterial and fungal infections and by autoinflammation/autoimmunity, of which the exact pathophysiology remains elusive. Contributing factors include decreased neutrophil apoptosis, impaired apoptotic neutrophil clearance, increased proinflammatory protein expression and reduced ROS-mediated inflammasome dampening. We have explored a fundamentally different potential mechanism: it has been reported that macrophage-mediated induction of regulatory T cells (Tregs ) depends on ROS production. We have investigated whether numerical or functional deficiencies exist in Tregs of CGD patients. As the prevalence of autoinflammation/autoimmunity differs between CGD subtypes, we have also investigated Tregs from gp91phox -, p47phox - and p40phox -deficient CGD patients separately. Results show that Treg numbers and suppressive capacities are not different in CGD patients compared to healthy controls, with the exception that in gp91phox -deficiency effector Treg (eTreg ) numbers are decreased. Expression of Treg markers CD25, inducible T cell co-stimulator (ICOS), Helios, cytotoxic T lymphocyte antigen 4 (CTLA-4) and glucocorticoid-induced tumor necrosis factor receptor (GITR) did not provide any clue for differences in Treg functionality or activation state. No correlation was seen between eTreg numbers and patients' clinical phenotype. To conclude, the only difference between Tregs from CGD patients and healthy controls is a decrease in circulating eTregs in gp91phox -deficiency. In terms of autoinflammation/autoimmunity, this group is the most affected. However, upon culture, patient-derived Tregs showed a normal phenotype and normal functional suppressor activity. No other findings pointed towards a role for Tregs in CGD-related autoinflammation/autoimmunity.

Processing cord blood from premature infants into autologous red-blood-cell products for transfusion.

BACKGROUND AND OBJECTIVES: The use of umbilical cord blood (UCB) for transfusion purposes has gained interest the past years. UCB transfusion could serve premature infants, who often need transfusions early in life. MATERIAL AND METHODS: We investigated the suitability of different storage media. UCB was collected after 25 0/7--35 6/7 gestational weeks and centrifuged to concentrate red cells subsequently stored in saline-adenine-glucose-mannitol (SAGM), or in additive solution-3 (AS-3), or stored as whole blood in citrate-phosphate-dextrose-adenine-1. Quality parameters were measured at 7 day intervals during 35 days and compared to the standard RBC product. RESULTS: White-blood-cell- and platelet counts were higher in the UCB products. In the fractionated units, haemolysis remained below 1·0% in 64% after 14 days, and in 30% after 21 days. Storage in SAGM or AS-3 showed similar quality. Whole blood UCB showed better pH and haemolysis rates after 21 days. CONCLUSION: UCB can be processed into autologous products for premature infants. Shelf-life is limited to 14-21 days and compares unfavourably to stored whole blood. Considering the early transfusion needs in these infants, a short shelf-life would not be a practical objection.

How to recognize a suitable pancreas donor: a Eurotransplant study of preprocurement factors.

INTRODUCTION: Because of the increasing demand for pancreas transplantation, more marginal donors are offered to Eurotransplant. The aim of this study was to validate a donor quality score that would facilitate recognition of a suitable pancreas donor among all reported donors. MATERIALS AND METHODS: We analyzed all 3180 consecutively reported pancreas donors for the period between January 1, 2002 and June 30, 2005 and determined the influence of the preprocurement pancreas suitability score (P-PASS) on the acceptance of a pancreas. We defined a range and point weight for each variable based on clinical expertise and known literature. RESULTS: Multiple regression analysis using pancreas acceptance as an outcome variable identified P-PASS > or = 17 as a significant cutoff point (P < .001). Pancreata from donors with P-PASS > or = 17 were three times more likely to be refused. CONCLUSION: The donor score can help in screening for potential pancreas donors, where an ideal donor has a P-PASS < 17. Our data demonstrate that consideration of a combination of preprocurement factors can help identify a suitable pancreas donor. Therefore, we recommend that a pancreas donor score be calculated for each potential pancreas donor, and all donors with a P-PASS < 17 should be considered for pancreas donation.

Anti-oxidized low-density lipoprotein antibodies in myeloperoxidase-positive vasculitis patients preferentially recognize hypochlorite-modified low density lipoproteins.

Many patients surviving vasculitis are prone to accelerated atherosclerosis and often have enhanced levels of antibodies to oxidized low-density lipoprotein (oxLDL). To measure anti-oxLDL antibodies, oxidation of LDL is achieved with copper (Cu) or malondialdehyde (MDA). Because, in vivo, LDL may be oxidized with myeloperoxidase (MPO) or its product hypochlorite, we measured anti-hypochlorite LDL antibodies in patients with vasculitis, haemodialysis patients and healthy controls. A newly developed enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies to oxLDL as modified by hypochlorite. Results are compared with data obtained by standard LDL oxidation using MDA-LDL or Cu-LDL as substrate. Results were compared between anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients (n = 93), haemodialysis (HD) patients (n = 59) and healthy controls (HC; n = 43). Furthermore, patients with MPO-ANCA-associated vasculitis (n = 47) were compared with patients with proteinase 3 (PR3)-ANCA associated vasculitis (n = 46). Optimal cut-off points were determined by receiver operator characteristic (ROC) curve analysis. Anti-oxLDL antibodies are enhanced in AAV patients (MDA-LDL and hypochlorite-LDL) and in HD patients (hypochlorite-LDL), when compared to HC. Furthermore, patients with MPO-ANCA-associated vasculitis had higher levels of antibodies to hypochlorite-LDL than patients with PR3-ANCA-associated vasculitis. Our newly developed assay, in which hypochlorite-LDL is used as substrate, seems a more sensitive assay than traditional assays to measure oxLDL antibodies. Furthermore, our results suggest that enhanced MPO-mediated LDL oxidation occurs in patients with MPO-ANCA.

Antibodies against human 60 kDa heat shock protein are not associated with cardiovascular disease in patients with rheumatoid arthritis.

BACKGROUND: Rheumatoid arthritis is associated with an unexplained increased risk of cardiovascular disease (CVD). Antibodies against human 60 kDa heat shock protein (anti-HSP60) are associated with the presence and severity of CVD. OBJECTIVES: To investigate whether anti-HSP60 antibodies are associated with prevalent CVD in patients with rheumatoid arthritis. METHODS: In a nested case-control design, anti-HSP60 antibody levels were measured in the serum samples of 192 rheumatoid patients. In a regression analysis the association between prevalent CVD and anti-HSP60 antibodies was examined, along with the possible influence on this association of several demographic, rheumatoid arthritis, and CVD related variables. RESULTS: In a random sample of 326 patients with rheumatoid arthritis, 48 cases were identified who also suffered from CVD. Three controls per case with rheumatoid arthritis but without CVD (n = 144) were matched for sex, age, disease duration, and smoking habits. A regression analysis showed no significant association between prevalent CVD and anti-HSP60 antibodies (odds ratio = 1.00 (95% confidence interval, 0.997 to 1.004)). After correcting for possible confounding variables, still no association was found. CONCLUSIONS: In contrast to the general population, anti-HSP60 antibody titres are not associated with prevalent CVD in patients with rheumatoid arthritis. These findings could be the result of an altered immune response to HSP60 in rheumatoid arthritis.

Evaluation of a new fluorescent-enzyme immuno-assay for diagnosis and follow-up of ANCA-associated vasculitis.

In this study we have evaluated a new, fully automated fluorescent-enzyme immuno-assay (FEIA) for detection and quantification of anti-PR3 and anti-MPO ANCA in diagnosis and follow-up of ANCA-associated small vessel vasculitis (AAV). PR3- and MPO-ANCA were determined by FEIA technology in (1) sera of 87 consecutive patients with biopsy-proven, pauci-immune necrotizing crescentic glomerulonephritis (NCGN) and 72 controls; (2) 120 sera (60 patients with Wegener's granulomatosis and 60 controls) that were previously used in a multicentre comparison of direct and capture ELISAs for PR3-ANCA; (3) in samples preceding relapse in 23 PR3-AAV patients with and 23 matched PR3-AAV patients without relapse for prediction of relapses. PR3- and/or MPO-ANCA detection in pauci-immune NCGN by FEIA revealed an overall sensitivity of 82.8%. The FEIA specificity was 96% and 100% for PR3- and MPO-ANCA, respectively. The overall sensitivity of MPO- and PR3-ANCA could be increased to 88.5% by lowering the cut-off values without affecting the specificity (ROC-curve analysis), which is similar to a multistep ANCA procedure that combines indirect immunofluorescence with direct and capture ELISAs. The sensitivity for Wegener's granulomatosis (WG) of the PR3-ANCA FEIA (60%) was more comparable to direct ELISAs (64%) than to capture ELISAs (74%). A rise of 100% in ANCA level as measured by FEIA appeared optimal (ROC-curve) for prediction of relapses and such a rise was observed in 26 patients. In 18 of these 26 patients the rise was followed by a relapse (PPV 69%), whereas in 15 of the 20 patients without a rise no relapse was observed (NPV 75%). In conclusion, detection of PR3- and MPO-ANCA by FEIA has excellent performance in terms of diagnosis of AAV patients. Furthermore, detection of rises in PR3-ANCA by FEIA for prediction of relapses gives results comparable to other techniques.

Evaluation of antineutrophil cytoplasmic antibody seroconversion induced by minocycline, sulfasalazine, or penicillamine.

OBJECTIVE: Case reports have suggested that minocycline, sulfasalazine, and penicillamine are associated with antineutrophil cytoplasmic antibody (ANCA)-positive vasculitis. This study evaluated ANCA seroconversion due to these agents in serum samples prospectively collected in randomized, double-blind, controlled trials. METHODS: The sources of study sera were 3 clinical trials: 1) a 48-week trial of minocycline for early rheumatoid arthritis, with 64 patients receiving minocycline compared with 68 receiving placebo; 2) a 37-week trial of sulfasalazine for rheumatoid arthritis, with 51 receiving sulfasalazine compared with 38 receiving placebo; and 3) a 104-week trial of penicillamine for early systemic sclerosis, with 15 undergoing high-dose penicillamine treatment versus 12 receiving low-dose penicillamine. ANCA were measured in the baseline and study-end serum samples by indirect immunofluorescence (IIF) for perinuclear ANCA (pANCA) and cytoplasmic ANCA (cANCA) patterns, and by antigen-specific enzyme-linked immunosorbent assay (ELISA) for antibodies to myeloperoxidase (anti-MPO) and proteinase 3 (anti-PR3). Laboratory personnel were blinded to the group identity of the samples. ANCA results were interpreted using an ANCA scoring system that combines the results of IIF and ELISA testing. RESULTS: No patient in any of the active study drug groups demonstrated ANCA seroconversion according to the final interpretation of the combined IIF and ELISA results. Twelve of the 248 patients (5%) were positive for anti-MPO with pANCA at baseline. No subject was positive for anti-PR3 with cANCA. There were no findings suggestive of vasculitis in any of these patients. CONCLUSION: From our study results, there was no suggestion of ANCA seroconversion induced by minocycline, sulfasalazine, or penicillamine. However, these findings do not rule out the possibility of rare, sporadic cases of either ANCA seroconversion or true drug-induced vasculitis with these drugs.