Judith Racapé

Influenza A/H1N1 Vaccine in Patients Treated by Kidney Transplant or Dialysis: A Cohort Study

BACKGROUND AND OBJECTIVES In 2009, the pandemic influenza A/H1N1 accounted for worldwide recommendations about vaccination. There are few data concerning the immunogenicity or the security of the adjuvanted-A/H1N1 vaccine in transplanted and hemodialyzed patients. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Sera from 21 controls, 53 hemodialyzed (HD) patients, and 111 renal transplant recipients (RT) were sampled before (T0) and 1 month after (T1) a single dose of Pandemrix® vaccine (GSK Biologicals, AS03-adjuvanted). We measured the neutralizing antibodies against A/H1N1/2009, the geometric mean (GM) titers, the GM titer ratios (T1/T0) with 95% confidence intervals, and the seroconversion rate (responders: ≥4-fold increase in titer). The HLA and MICA immunization was determined by Luminex technology. RESULTS The GM titer ratio was 38 (19 to 78), 9 (5 to 16), and 5 (3 to 6) for controls, HD patients, and RT patients, respectively (P < 0.001). The proportion of responders was 90%, 57%, and 44%, respectively (P < 0.001). In RT patients, the prevalence of histocompatibility leukocyte antigen (HLA) class I, histocompatibility leukocyte antigen class II, and MHC class I-related chain A immunization, was, respectively, 15%, 14%, and 14% before and 14%, 14%, and 11% after vaccination (P = 1, 1, and 0.39). CONCLUSIONS The influenza A/H1N1-adjuvanted vaccine is of limited efficacy but is safe in renal disease populations. The humoral response is lower in transplanted versus hemodialyzed patients. Further studies are needed to improve the efficacy of vaccination in those populations.

Major histocompatibility complex class 1 chain-related antigen a antibodies: sensitizing events and impact on renal graft outcomes.

Background. Major histocompatibility complex class 1 chain-related antigen A (MICA) antibodies (Abs) have been associated with renal graft loss in one large cohort. The triggering factors for MICA Abs and their autologous or allogeneic specificity have not been well defined. More data on the impact of MICA on renal grafts outcome are needed. Methods. We tested sera from 494 controls and 597 patients with chronic kidney disease (CKD) for MICA using Luminex. Forty CKD MICA+ patients were genotyped for MICA alleles to determine their auto- or allospecificity. We compared MICA+ with MICA− renal transplant recipients with regard to acute rejection episodes and long-term survival. Results. Blood transfusions, previous transplantation, and more than two pregnancies were independent risk factors for the presence of MICA Abs, as were CKD stage V status and male gender. Among the 40 genotyped patients, allo-Abs alone were present in 32 patients, both auto- and allo-Abs in 4 patients, and auto-Abs alone in 4 patients. When we compared MICA+ with MICA− patients, the incidence of acute rejection episodes during the first year (10.2% vs. 12.8%), as well as 1-year creatinine and proteinuria, were similar in both groups. At 10 years, actuarial patient (97.8% vs. 87.6%) and overall graft survival (76% vs. 72%) were similar between MICA+ and MICA− patients. Conclusions. In summary, (1) sensitizing events for MICA Abs are the same as for human leukocyte antigen Abs; (2) MICA Abs did not adversely affect renal graft outcomes in our cohort.

Thrombophilic factors in Stage V chronic kidney disease patients are largely corrected by renal transplantation

BACKGROUND The aim of our study was to evaluate the prevalence of acquired thrombophilic factors in Stage V chronic kidney disease (CKD) patients according to dialysis modality, the rate of correction of these factors 1 month after renal transplantation and their impact on cardiovascular or thromboembolic events at 1 year. METHODS Three hundred and ten patients were prospectively screened for seven thrombophilic factors at transplantation; 215 of them were also assayed 1 month after. All the patients received prophylactic acetylsalicylic acid, started before transplantation. RESULTS The prevalence of thrombophilic factors was significantly higher in patients under dialysis (n = 289) than in patients not yet on dialysis (n = 21) (74 versus 52.4%; P = 0.03) but was similar in haemodialysis and peritoneal dialysis patients (74.2 versus 73.2%). One month after transplantation, the global prevalence of thrombophilic factors had dropped from 74.4 to 44.7% (P < 0.001). Most thrombophilic factors had disappeared after transplantation: antithrombin deficiency: 13.5 versus 0.9%; P < 0.001, protein C deficiency: 12.1 versus 1.9%; P < 0.001, protein S deficiency: 3.7 versus 1.4%; P = 0.1, lupus anticoagulant: 37.7 versus 8.4%; P < 0.001 and antiphospholipid antibodies: 29.3 versus 12.6%; P < 0.001. The prevalence of activated protein C resistance, which reflects inherited factor V (FV) Leiden, was unchanged (1.9%), while the prevalence of elevated factor VIIIc increased from 20.9 to 30.7%, P < 0.001. The incidence of cardiovascular or thromboembolic events 1 year after transplantation was similar in patients with more than or equal to one thrombophilic factor at 1 month (5.2%) versus thrombophilic-free patients (6.7%). CONCLUSION Acquired thrombophilic factors are highly prevalent among Stage V CKD patients. Most thrombophilic factors are corrected 1 month after transplantation.

Delayed Graft Function in Kidney Transplants: Time Evolution, Role of Acute Rejection, Risk Factors, and Impact on Patient and Graft Outcome

Background. Although numerous risk factors for delayed graft function (DGF) have been identified, the role of ischemia-reperfusion injury and acute rejection episodes (ARE) occurring during the DGF period is ill-defined and DGF impact on patient and graft outcome remains controversial. Methods. From 1983 to 2014, 1784 kidney-only transplantations from deceased donors were studied. Classical risk factors for DGF along with two novel ones, recipients perioperative saline loading and residual diuresis, were analyzed by logistic regression and receiver operating characteristic (ROC) curves. Results. Along with other risk factors, absence of perioperative saline loading increases acute rejection incidence (OR = 1.9 [1.2–2.9]). Moreover, we observed two novel risk factors for DGF: patients residual diuresis ≤500 mL/d (OR = 2.3 [1.6–3.5]) and absence of perioperative saline loading (OR = 3.3 [2.0–5.4]). Area under the curve of the ROC curve (0.77 [0.74–0.81]) shows an excellent discriminant power of our model, irrespective of rejection. DGF does not influence patient survival (P = 0.54). However, graft survival is decreased only when rejection was associated with DGF (P < 0.001).  Conclusions. Perioperative saline loading efficiently prevents ischemia-reperfusion injury, which is the predominant factor inducing DGF. DGF per se has no influence on patient and graft outcome. Its incidence is currently close to 5% in our centre.

Are all immigrant mothers really at risk of low birth weight and perinatal mortality? The crucial role of socio-economic status

BackgroundIncreasing studies show that immigrants have different perinatal health outcomes compared to native women. Nevertheless, we lack a systematic examination of the combined effects of immigrant status and socioeconomic factors on perinatal outcomes. Our objectives were to analyse national Belgian data to determine 1) whether socioeconomic status (SES) modifies the association between maternal nationality and perinatal outcomes (low birth weight and perinatal mortality); 2) the effect of adopting the Belgian nationality on the association between maternal foreign nationality and perinatal outcomes.MethodsThis study is a population-based study using the data from linked birth and death certificates from the Belgian civil registration system. Data are related to all singleton births to mothers living in Belgium between 1998 and 2010. Perinatal mortality and low birth weight (LBW) were estimated by SES (maternal education and parental employment status) and by maternal nationality (at her own birth and at her child’s birth). We used logistic regression to estimate the odds ratios for the associations between nationality and perinatal outcomes after adjusting for and stratifying by SES.ResultsThe present study includes, for the first time, all births in Belgium; that is 1,363,621 singleton births between 1998 and 2010. Compared to Belgians, we observed an increased risk of perinatal mortality in all migrant groups (p < 0.0001), despite lower rates of LBW in some nationalities. Immigrant mothers with the Belgian nationality had similar rates of perinatal mortality to women of Belgian origin and maintained their protection against LBW (p < 0.0001). After adjustment, the excess risk of perinatal mortality among immigrant groups was mostly explained by maternal education; whereas for sub-Saharan African mothers, mortality was mainly affected by parental employment status. After stratification by SES, we have uncovered a significant protective effect of immigration against LBW and perinatal mortality for women with low SES but not for high SES.ConclusionsOur results show a protective effect of migration in relation to perinatal mortality and LBW among women of low SES. Hence, the study underlines the importance of taking into account socioeconomic status in order to understand more fully the relationship between migration and perinatal outcomes. Further studies are needed to analyse more finely the impact of socio-economic characteristics on perinatal outcomes.

Genome-wide association study of acute renal graft rejection.

Acute renal rejection is a major risk factor for chronic allograft dysfunction and long‐term graft loss. We performed a genome‐wide association study to detect loci associated with biopsy‐proven acute T cell–mediated rejection occurring in the first year after renal transplantation. In a discovery cohort of 4127 European renal allograft recipients transplanted in eight European centers, we used a DNA pooling approach to compare 275 cases and 503 controls. In an independent replication cohort of 2765 patients transplanted in two European countries, we identified 313 cases and 531 controls, in whom we genotyped individually the most significant single nucleotide polymorphisms (SNPs) from the discovery cohort. In the discovery cohort, we found five candidate loci tagged by a number of contiguous SNPs (more than five) that was never reached in iterative in silico permutations of our experimental data. In the replication cohort, two loci remained significantly associated with acute rejection in both univariate and multivariate analysis. One locus encompasses PTPRO, coding for a receptor‐type tyrosine kinase essential for B cell receptor signaling. The other locus involves ciliary gene CCDC67, in line with the emerging concept of a shared building design between the immune synapse and the primary cilium.

Acute Kidney Injury in Elderly Patients With Chronic Kidney Disease: Do Angiotensin-Converting Enzyme Inhibitors Carry a Risk?

In contrast to angiotensin receptor blockers (ARBs), mainly excreted by the liver, the dosage of angiotensin‐converting enzyme (ACE) inhibitors, cleared by the kidney, must be adapted to account for renal clearance in patients with chronic kidney disease (CKD) to avoid acute kidney injury (AKI). Community‐acquired AKI and the use of ACE inhibitors or ARBs in the emergency department were retrospectively assessed in 324 patients with baseline stage 3 or higher CKD. After stepwise regression analysis, the use of ACE inhibitors (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.1–3.1; P=.02) and the presence of dehydration (OR, 30.8; 95% CI, 3.9–239.1) were associated with AKI. A total of 45% of patients using ACE inhibitors experienced overdosing, which causes most of the excess risk of AKI. These results suggest that dosage adjustment of ACE inhibitors to renal function or substitution of ACE inhibitors with ARBs could reduce the incidence of AKI. Moreover, ACE inhibitors and ARBs should be stopped in cases of dehydration.

Combined introduction of anti-IL2 receptor antibodies, mycophenolic acid and tacrolimus: effect on malignancies after renal transplantation in a single-centre retrospective cohort study

BACKGROUND Several studies suggest that the introduction of tacrolimus (TRL), mycophenolic acid (MPA) and interleukin 2 receptor antibodies (IL2Ra) as single drugs more than a decade ago has not increased the risk of malignancy after renal transplantation. However, only limited data are available on their carcinogenic effects when used in combination as a potent immunosuppressive regimen. METHODS A retrospective single-centre cohort study on 929 adult renal transplant recipients. Investigation of the effect of two consecutive immunosuppressive regimens [1993-98, N = 405, anti-lymphocyte antibodies, cyclosporine and azathioprine (AZA); 1999-2007, N = 524, predominantly IL2Ra, TRL and MPA] on the incidence rate of skin cancer, solid tumours and post-transplant lymphoproliferative disease (PTLD). RESULTS In total, 365 malignancies developed among 113 patients. As compared to the previous cyclosporine and AZA-based immunosuppression, the introduction of the new immunosuppressive regimen did not increase the incidence rate of skin cancer [rate ratio 0.84; 95% confidence interval (CI) 0.48-1.46], solid tumours (0.89; 95% CI 0.46-1.67) and PTLD (0.82; 95% CI 0.28-2.21). Patients treated with the more recent regimens less frequently developed multiple skin cancers and invasive squamous cell cancer. Skin cancer after transplantation was strongly associated with the development of solid tumours (odds ratio 5.2; P < 0.0001). The introduction of the new immunosuppressive drugs reduced the incidence of first year acute rejection from 34.8 to 13.2% (P < 0.0001). CONCLUSION Although significantly more efficient in the prevention of acute rejection, the introduction of TRL, MPA and IL2Ra-based immunosuppression after kidney transplantation was not associated with an increased incidence of skin cancer, solid tumours or PTLD.

A New HLA Allocation Procedure of Kidneys From Deceased Donors in the Current Era of Immunosuppression

INTRODUCTION It has recently been proposed to replace the current Eurotransplant kidney allocation based primarily on mismatches (MM) at the 3 HLA loci by a simpler system based on full HLA-DR compatibility. The present study analyzes this system in the current era of immunosuppression. METHODS From 1999 to 2012, 723 renal grafts were performed on 586 patients who were treated with a calcineurin inhibitor, mycophenolate mofetil, and in most cases antilymphocyte globulins. Four groups of HLA MM were compared: (A) A+B 2-4/DR 1-2 MM (n = 397), (B) A+B 2-4 MM/DR 0 MM (n = 106), (C) A+B 0-1 MM/DR 1-2 MM (n = 138), and (D) A+B 0-1/DR 0 MM (n = 82). RESULTS Acute rejection episodes were less frequent during the first post-transplantation year in group D than in the other groups (P = .018). Patient survival was lower in group A than in the other groups (P = .008). Immunologic graft survival was higher in group D than in the other groups in univariate (P = .015) and multivariate analyses (P = .033; 96.4% vs 90.1% at 10 years). CONCLUSIONS In the current era of immunosuppression, allocation of kidneys from deceased donors could be performed primarily according to full DR compatibility then to the best A+B matching, affording excellent graft outcome to most recipients.

Prevention of Tunneled Cuffed Hemodialysis Catheter–Related Dysfunction and Bacteremia by a Neutral-Valve Closed-System Connector: A Single-Center Randomized Controlled Trial

BACKGROUND Hemodialysis (HD) tunneled cuffed catheters may be fitted with neutral-valve closed-system connectors. Such connectors, which are flushed with saline solution and used for 3 consecutive HD sessions, provide a mechanically closed positive-pressure barrier and potentially may be useful to prevent catheter-related bacteremia and dysfunction. STUDY DESIGN Single-center randomized controlled trial. SETTING & PARTICIPANTS 66 adult HD patients with a tunneled cuffed catheter. INTERVENTION Neutral-valve closed-system connector (Tego Needlefree Hemodialysis Connector) versus trisodium citrate, 46.7%, locking solution (Citra-Lock; control group). OUTCOMES Primary composite outcome was the incidence rate of catheter-related dysfunction or bacteremia. Secondary outcomes were the separate incidence rates of catheter-related dysfunction and bacteremia and the cost of both procedures. MEASUREMENTS Catheter dysfunction was defined as the requirement of urokinase and/or a mean blood flow ≤250 mL/min during 2 consecutive HD sessions. Catheter-related bacteremia was defined as ≥2 positive blood cultures. Time of catheter use was calculated and the incidence rate of complications was expressed per 100 person-years. RESULTS 66 patients were followed up for a median of 86 (IQR, 29-200) days. The composite primary outcome was not significantly reduced in the closed-system-connector intervention group versus the citrate-locking-solution control group (63.56 vs 71.51 per 100 person-years; P = 0.3). Catheter dysfunction in the intervention group was not decreased versus controls (59.59 vs 51.64 per 100-person-years; P = 0.9). Only 6 catheter-related bacteremia events were identified, one in the intervention group (3.97 vs 19.86 per 100 person-years; P = 0.06). LIMITATIONS Small size of the patient population and single-center study. CONCLUSIONS Superiority of the closed-system connector in terms of prevention of the primary efficacy end point compared to the standard locking solution was not observed. Further evaluation in a larger study is suggested.