Calcineurin inhibitor-free immunosuppression in dual kidney transplantation from elderly donors

BACKGROUND: Kidneys from expanded-criteria donors may be particularly susceptible to calcineurin inhibitor (CI)-mediated vasoconstriction and nephrotoxicity. In the early post-transplant phase, using CI may prolong ischemic injury and, in the long term, chronic CI nephrotoxicity is an even greater concern. To avoid the acute and chronic consequences of CI in kidneys from marginal donors, CI-free protocols have been introduced for maintenance immunosuppressive therapy. A CI-free protocol of anti-thymocyte globulin (ATG) induction, sirolimus, mycophenolate mofetil (MMF) and steroids has been adopted at our center in recipients of dual kidney transplantation (DKT) from elderly donors (EDs). METHODS: Dual kidney transplantations performed since April 2003 on CI-free immunosuppression (group 1 = 31) were compared with earlier DKTs in recipients treated with CI-based therapy (group 2 = 25), retrospectively analyzing patient and graft survival, surgical and medical complications, rejection episodes and renal function. RESULTS: No deaths occurred after a mean follow-up of 10.1 +/- 7.6 (group 1) and 48.2 +/- 17.4 months (group 2). Graft loss occurred in one patient in group 1 (bilateral renal vein thrombosis) and in three patients in group 2 (one primary non-function [PNF], one chronic rejection, one Kaposi's sarcoma). The incidence of acute rejection was 19% in group 1 and 16% in group 2. Delayed graft function (DGF) was recorded in 16% and 48%, respectively. Renal function was better in group 1, with a mean S-Cr of 135 +/- 48 vs. 210 +/- 141 micromol/L at one month and 116 +/- 30 vs. 149 +/- 49 micromol/L at six months. CONCLUSIONS: After DKT from EDs, a CI-free immunosuppressive regimen including ATG induction, sirolimus, MMF and steroids affords excellent results, with a lower DGF rate and a better renal function.     

Diagnostic tools in the preoperative evaluation of children with anomalous pulmonary venous connections

Pulmonary venous abnormalities are generally diagnosed by echocardiography and often confirmed by cardiac catheterization. Although angiography has been the gold standard for evaluation it carries certain inherent risks, especially in small and sick infants. In this study we retrospectively assessed the utility of magnetic resonance angiography (MRA) and computed tomography angiography (CTA) in the evaluation of pulmonary venous abnormalities in pediatric patients. The results were compared with operative findings. We reviewed nine patients with total APVC and four with partial APVC. Twelve patients were infant (age range: 1 day to 8 months) and the other was 16 years old. MRA and/or CTA clearly visualized the anomalous drainage of pulmonary veins in all patients. Cardiac catheterization was performed five patients with one total anomalous pulmonary venous connection and four with partial anomalous pulmonary venous connection. Ten patients were operated on. Diagnoses of patients were confirmed by operative findings. In Conclusions, MR and CT angiography allow detailed and comprehensive evaluation of the APVC and are good diagnostic modalities for use in the preoperative assessment of the anomaly in pediatric patients.     

The primary defect in experimental ileitis originates from a nonhematopoietic source

The initiating etiologic factor in Crohn's disease (CD) remains unclear. SAMP1/YitFc (SAMP) mice develop chronic ileitis similar to human CD. We used bone marrow chimeras to determine if SAMP ileitis results from a primary immunological defect or from dysregulated mucosal immunity secondary to intrinsic, nonhematopoietic (e.g., epithelial) dysfunction. SAMP mice receiving wild-type (AKR) BM developed severe ileitis, whereas SAMP BM did not confer ileitis to WT recipients. WT lymphocytes from reconstituted SAMP mice resembled native SAMP populations in regard to surface phenotype and cytokine production. Ilea from native SAMP mice and SAMP recipients of wild-type BM displayed decreased epithelial barrier resistance ex vivo and increased epithelial permeability in vivo compared to native WT mice and AKR recipients of SAMP BM. This permeability defect preceded the development of ileal inflammation, was present in the absence of commensal bacteria, and was accompanied by altered ileal mRNA expression of the tight junction proteins claudin-2 and occludin. Our results provide evidence that the primary defect conferring ileitis in SAMP mice originates from a nonhematopoietic source. Generation of pathogenic lymphocytes is a consequence of this defect and does not reflect intrinsic proinflammatory leukocyte properties. Decreased barrier function suggests that defects in the epithelium may represent the primary source of SAMP ileitis susceptibility.     

Transcatheter closure of extracardiac fontan fenestration in a cyanotic patient

Fontan operation is the connection of the systemic venous return to the pulmonary arteries, performed in patients with single ventricle physiology. The Fontan circuit is commonly fenestrated because of early postoperative risks such as high systemic venous pressure and low cardiac output. As it causes progressive cyanosis and increased risk of paradoxical embolism in the follow-up period, occlusion of these fenestrations is generally suggested. Successful closure of extracardiac Fontan fenestration with atrial septal occluder in a 10-year-old girl is reported herein. To our knowledge, this is the first such report from Turkey.