Anh Dung Hoang

Cold ischemia is a major determinant of acute rejection and renal graft survival in the modern era of immunosuppression.

Background. The aim of our study was to examine, in a recent cohort of kidney transplant recipients who have received modern immunosuppressive therapy, the respective role of cold ischemia time (CIT) and delayed graft function (DGF) on acute rejection (AR) rates and long-term graft survival. Methods. We retrospectively reviewed the charts of 611 renal transplantations between 1996 and 2005. Most patients received a calcineurin inhibitor as maintenance therapy, either cyclosporine (43%) or tacrolimus (52%) and 76% of the patients received an antilymphocyte induction therapy. Study endpoints were DGF, first-year AR, and long-term graft survival. Uni- and multivariate analyses were performed to determine factors that may have influenced the study outcomes. Results. DGF was observed in 16.2% of patients. Both older donor age and longer CIT were significant risk factors for DGF. DGF rates were similar whether patients received a calcineurin inhibitor before transplantation or not. AR occurred in 16.5% of grafts during the first year. Independent predictors of AR by multivariate analysis were duration of dialysis, CIT, current panel-reactive lymphocytotoxic antibody more than 5%, and the number of human leukocyte antigen-A, B, and DR mismatches. Each hour of cold ischemia increases the risk of rejection by 4%. With respect to death-censored graft survival, three pretransplant parameters emerged as independent predictors of graft loss: younger recipient age, peak panel-reactive lymphocytotoxic antibody more than 5% and longer CIT. The detrimental effect of CIT on graft survival was entirely because of its propensity to trigger AR. When AR was added to the multivariate Cox model, CIT was no longer significant whereas first-year AR became the most important predictor of graft loss (Hazards ratio, 4.6). Conclusion. Shortening CIT will help to decrease not only DGF rates but also AR incidence and hence graft loss. Patients with prolonged CIT should receive adequate immunosuppression, possibly with antilymphocyte preparations, to prevent AR occurrence.

Regression of Left Ventricular Hypertrophy After Arteriovenous Fistula Closure in Renal Transplant Recipients: A Long-Term Follow-Up

The long‐term effects of hemodialysis arteriovenous fistula (AVF) closure on left ventricular (LV) morphology are unknown. Using echocardiography, we prospectively studied 17 kidney transplant recipients before, 1, and, 21 months after AVF closure (mean fistula flow 1371 ± 727 mL/min). Eight kidney transplant recipients with a patent AVF, matched for age, time after AVF creation, and time after transplantation, served as controls. LV mass index (LVMI) decreased from 139 ± 44 g/m2 before AVF closure to 127 ± 45 g/m2 and 117 ± 40 g/m2 at 1 and 21 months post‐closure, respectively (p < 0.001), but remained unchanged in controls. LV hypertrophy prevalence (LVMI > 125 g/m2) decreased from 65% before, to 41% early, and 18%, late, after surgery (p = 0.008), mostly from a decrease in LV end‐diastolic diameter. Consequently, the prevalence of LV concentric remodeling (relative wall thickness > 0.45 without hypertrophy) increased from 12% before, to 35% early, and 65% late, after surgery (p = 0.003). Diastolic arterial blood pressure increased from 78 ± 15 mmHg before, to 85 ± 13 mmHg early, and 85 ± 10 mmHg late, after surgery (p < 0.015).In conclusion, closure of large and/or symptomatic AVF induces long‐term regression of LV hypertrophy. However, residual concentric remodeling geometry as well as diastolic blood pressure increase may blunt the expected beneficial cardiac effects of the procedure.

Conversion from tacrolimus to cyclosporine A for new-onset diabetes after transplantation: a single-centre experience in renal transplanted patients and review of the literature

Tacrolimus (TRL) increases the incidence of new‐onset diabetes mellitus after transplantation (NODAT). Little is known about whether conversion from TRL to cyclosporine A (CsA) improves glucose metabolism in patients with NODAT. We retrospectively analysed glucose metabolism parameters in 54 TRL‐treated renal transplant patients who developed NODAT. Thirty‐four were converted to CsA whereas 20 patients continued TRL. After conversion, fasting plasma glucose decreased from 146 ± 64 to 104 ± 20 mg/dl (P < 0.0001) and HbA1c levels decreased from 6.8 ± 0.8% to 6.0 ± 0.6% (P < 0.0001) after 1 year of follow‐up. The remission rate of NODAT reached 42% (95% confidence interval 24–59%) 1 year after conversion versus 0% in the control group (P = 0.001). Blood pressure and lipid levels were stable after conversion although the use of statins significantly increased (P < 0.01). The conversion was safe in terms of graft function and acute rejection episodes. The 1‐year patient survival and graft survival rate were 100%. In conclusion, our results suggest a significant improvement of glucose metabolism after conversion to CsA in renal transplant patients with NODAT.

Conversion From Prograf to Advagraf Among Kidney Transplant Recipients Results in Sustained Decrease in Tacrolimus Exposure

Background. Advagraf is a slow release form of tacrolimus with once-daily formulation. The potential advantages of Advagraf are better adherence and a safer profile by avoiding toxic peak concentrations. In this study, we evaluated the required daily doses of tacrolimus and subsequent blood levels on conversion from Prograf to Advagraf among kidney transplant recipients. Methods. We retrospectively reviewed data from 55 patients for whom a switch from Prograf to Advagraf was identified. Tacrolimus daily doses and concomitant blood levels were analyzed at several time points ranging from 3 months before to 6 months after conversion. Results. We observed a significant increase in tacrolimus daily doses, starting with a dose of 0.063 mg/kg of Prograf, increasing up to 0.081 mg/kg of Advagraf at 6 months (P<0.0001). After conversion, we observed a quick and sustained decrease in trough tacrolimus levels, decreasing from 8.05 ng/mL at day 0 to 6.30 ng/mL at day 180 (P=0.0009). At 6 months, 35% of patients experienced a decrease in trough levels of more than 30%. Creatinine values remained stable over time, and no patient experienced an acute rejection episode. Conclusions. Contrary to the manufacturer instructions, we found a significant decrease in tacrolimus exposure after switching to Advagraf. Therefore, the switch from Prograf to Advagraf should be performed under close medical supervision.

HLA mismatches remain risk factors for acute kidney allograft rejection in patients receiving quadruple immunosuppression with anti-interleukin-2 receptor antibodies.

Background. New immunosuppressive drugs such as anti-interleukin-2 receptor antibodies (aIL2R) and mycophenolate mofetil (MMF) have reduced the incidence of acute rejection after renal transplantation. Whether matching donor and recipient human leukocyte antigen (HLA) antigens is still relevant in patients receiving modern immunosuppression has been questioned. Methods. We retrospectively analyzed the incidence and risk factors of acute rejection during the first posttransplant year and the impact of acute rejection on long-term graft survival in a cohort of 208 renal transplant patients treated with aIL2R (basiliximab, n=166; daclizumab, n=42), calcineurin inhibitors (tacrolimus, n=180; cyclosporin, n=28), mycophenolate mofetil, and steroids. Graft and patient survival were calculated by the Kaplan-Meier method. Risk factors for acute rejection were analyzed by logistic regression modeling. Results. Twenty-seven patients were treated for acute rejection (26 biopsy-proven) during the first posttransplant year. The Kaplan-Meier estimate of first-year acute rejection was 13.2%. The number of HLA mismatches (odds ratio [OR] 1.65 per HLA mismatch) and long periods of dialysis before transplantation (OR 3.1 for more than 4 years of dialysis) were the only independent risk factors for first-year acute rejection. First-year acute rejection was associated with a significant reduction in overall and death-censored graft survival at 5 years after transplantation. Conclusions. Although infrequent in patients receiving modern immunosuppressive drugs, acute rejection remains an important risk factor for graft loss after renal transplantation. Our results suggest that better HLA matching and shorter periods of dialysis before transplantation could reduce acute rejection rates and further improve outcomes under current immunosuppressive regimens.

Evolution of immunoglobulin and mannose binding protein levels after renal transplantation: association with infectious complications.

Hypogammaglobulinemia (hypo‐Ig) and low mannose binding protein (MBP) levels might be involved in the infectious risk in renal transplantation. In 152 kidney transplant recipients treated with calcineurin inhibitors (CNI) and mycophenolate mofetil (MMF), during the first year, we prospectively recorded the incidence of hypogammaglobulinemia, and low MBP levels. Their influence on infectious complications was evaluated in 92 patients at 3 and 12 months (T3 and T12). The proportion of deficiency increased significantly: hypo‐IgG: 6% (T0), 45% (T3), and 30% (T12) (P < 0.001); hypo‐MBP: 5%, 11%, and 12% (P = 0.035). Hypo‐IgG at T3 was not associated with an increased incidence of first‐year infections. A significantly higher proportion of patients with combined hypogammaglobulinemia [IgG+ (IgA and/or IgM)] at T3 and with isolated hypo‐IgG at T0 developed infections until T3 compared with patients free of these deficits (P < 0.05). Low MBP levels at T3 were associated with more sepsis and viral infections. Hypogammaglobulinemia is frequent during the first year after renal transplantation in patients treated with a CNI and MMF. Hypo‐IgG at T0 and combined Igs deficts at T3 were associated with more infections. MBP deficiency might emerge as an important determinant of the post‐transplant infectious risk.

Pediatric En Bloc Dual Kidney‐Pancreas Transplantation Into an Adult Recipient: a Simplified Technique. Benefits of the en bloc kidney‐pancreas transplantation technique in pediatric donors

The lower age limit for pancreas donors is not well defined. Fear of inadequate islet β‐cell mass and of technical complications has hampered the use of pediatric donors. A surgical technique of ‘en bloc’ kidney‐pancreas is described.

Conversion to sirolimus for chronic renal allograft dysfunction: risk factors for graft loss and severe side effects

We retrospectively reviewed our experience with 45 kidney transplant recipients (KTR) that were switched from CNI to SRL, mainly for chronic allograft dysfunction (CAD) (41/45). The mean serum creatinine at switch was 2.5 ± 0.8 mg/dl. At 1 year, patient survival was 93%. Death-censored graft survival was 67% at 1 year and 54% at 2 years. SRL was stopped because of severe side effects in 15 patients. Among these, eight patients developed ‘de novo’ high-grade proteinuria. Univariate analysis revealed that (1) a higher SRL level at 1 month was a predictor of SRL withdrawal due to severe side effects (P = 0.006), and (2) predictors of graft failure after SRL conversion were low SRL loading dose (P = 0.03) and a higher creatinine level at conversion (P = 0.003). In conclusion, the therapeutic index of SRL in patients suffering from CAD is narrow, with high exposure triggering serious adverse events that may mandate SRL discontinuation, while too low exposure may expose patients to under-immunosuppression and graft loss.

Kidney donation after circulatory death in a country with a high number of brain dead donors: 10-year experience in Belgium

Worldwide shortage of standard brain dead donors (DBD) has revived the use of kidneys donated after circulatory death (DCD). We reviewed the Belgian DCD kidney transplant (KT) experience since its reintroduction in 2000. Risk factors for delayed graft function (DGF) were identified using multivariate analysis. Five‐year patient/graft survival was assessed using Kaplan–Meier curves. The evolution of the kidney donor type and the impact of DCDs on the total KT activity in Belgium were compared with the Netherlands. Between 2000 and 2009, 287 DCD KT were performed. Primary nonfunction occurred in 1% and DGF in 31%. Five‐year patient and death‐censored graft survival were 93% and 95%, respectively. In multivariate analysis, cold storage (versus machine perfusion), cold ischemic time, and histidine‐tryptophan‐ketoglutarate solution were independent risk factors for the development of DGF. Despite an increased number of DCD donations and transplantations, the total number of deceased KT did not increase significantly. This could suggest a shift from DBDs to DCDs. To increase KT activity, Belgium should further expand controlled DCD programs while simultaneously improve the identification of all potential DBDs and avoid their referral for donation as DCDs before brain death occurs. Furthermore, living donation remains underused.

Undiagnosed rupture of right hemidiaphragm: Hepatothorax: a case report

Abstract A case of late diagnosis of right diaphragmatic rupture due to blunt trauma is presented. Traumatic diaphragmatic rupture is an uncommon but severe problem in a patient with multiple injuries. One third of left-sided ruptures and half of right-sided ruptures have been undetected for several days. Traumatic diaphragmatic rupture should be suspected on the basis of an abnormal chest X-ray in patients with multiple injuries. Imaging studies like computed tomography, scan and magnetic resonance imaging can be helpful for differential diagnosis. Right-sided injuries occur more commonly than previously thought and often require thoracotomy.