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Background: Disseminated intravascular coagulation (DIC)-positive kidneys have historically been turned down for fear of poor outcomes. Higher severity injuries, which are prone to DIC, are typically seen in younger, otherwise healthy potential donors. The continued kidney allograft shortage has generated interest in the use of these DIC-positive grafts. There have been some reports of acceptable outcomes of renal transplantation using kidneys from donors with DIC. There are multiple clinical series demonstrating good outcomes from DIC-positive kidneys when the extent of glomeruli containing fibrin thrombi is less than 50% and donor renal function is preserved. These grafts are frequently associated with a period of delayed graft function., Methods: We report 2 transplants with kidneys from brain dead donors with known DIC., Results: Both donors had renal failure and pretransplant renal biopsies showing 100% of the glomeruli containing fibrin thrombi. The recipients experienced delayed graft function requiring hemodialysis which was discontinued on postoperative days 18 and 39 for cases 1 and 2, respectively. Both patients are now over 14 months posttransplant with stable allograft function., Conclusions: Until clearer organ selection criteria are established, caution should be exercised when considering the use of kidneys with a similar phenotype and allocation decisions made by a multidisciplinary transplant team on a case-by-case basis.

Background: Delayed graft function (DGF) and slow graft function (SGF) are ischemia-reperfusion-associated acute kidney injuries (AKI) that decrease long-term graft survival after kidney transplantation. Regulatory T (Treg) cells are protective in murine AKI, and their suppressive function predictive of AKI in kidney transplantation. The conventional Treg cell function coculture assay is however time-consuming and labor intensive. We sought a simpler alternative to measure Treg cell function and predict AKI., Methods: In this prospective observational cohort study, pretransplant recipient circulating CD4+CD25+CD127lo/- and CD4+CD127lo/- tumor necrosis factor receptor 2 (TNFR2)+ Treg cells were measured by flow cytometry in 76 deceased donor kidney transplant recipients (DGF, n = 18; SGF, n = 34; immediate graft function [IGF], n = 24). In a subset of 37 recipients, pretransplant circulating Treg cell-suppressive function was also quantified by measuring the suppression of autologous effector T-cell proliferation by Treg cell in coculture., Results: The TNFR2+ expression on CD4+CD127lo/- T cells correlated with Treg cell-suppressive function (r = 0.63, P < 0.01). In receiver operating characteristic curves, percentage and absolute number of CD4+CD127lo/-TNFR2+ Treg cell predicted DGF from non-DGF (IGF + SGF) with area under the curves of 0.75 and 0.77, respectively, and also AKI (DGF + SGF) from IGF with area under the curves of 0.76 and 0.72, respectively (P < 0.01). Prediction of AKI (DGF + SGF) from IGF remained significant in multivariate logistic regression accounting for cold ischemic time, donor age, previous transplant, and pretransplant dialysis modality., Conclusions: Pretransplant recipient circulating CD4+CD127lo/-TNFR2+ Treg cell is potentially a simpler alternative to Treg cell function as a pretransplant recipient immune marker for AKI (DGF + SGF), independent from donor and organ procurement characteristics.

Background and Objectives: Current methods for rapid detection of delayed graft function (DGF) after kidney transplantation are unreliable. Urinary clusterin is a biomarker of kidney injury but its utility for prediction of graft dysfunction is unknown., Methods: In a single-center, prospective cohort study of renal transplant recipients (N=81), urinary clusterin was measured serially between 4 hr and 7 days after transplantation. The utility of clusterin for prediction of DGF (hemodialysis within 7 days of transplantation) was compared with urinary interleukin (IL)-18, neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1, serum creatinine, and clinical variables., Results: At 4 hr after reperfusion, anuria was highly specific, but of low sensitivity for detection of DGF. At 4 hr, receiver operating characteristic analysis suggested that urinary clusterin, IL-18, kidney injury molecule-1, and NGAL concentration were predictive of DGF. After adjusting for preoperative clinical variables and anuria, clusterin and IL-18 independently enhanced the clinical model for prediction of DGF. Kidney injury molecule-1 only modestly improved the prediction of DGF, whereas NGAL, serum creatinine, and the creatinine reduction ratio did not improve on the clinical model. At 12 hr, the creatinine reduction ratio independently predicted DGF., Conclusion: Both urinary clusterin and IL-18 are useful biomarkers and may allow triaging of patients with DGF within 4 hr of transplantation. Relative performance of biomarkers for prediction of graft function is time-dependant. Early and frequent measurements of serum creatinine and calculation of the creatinine reduction ratio also predict DGF within 12 hr of reperfusion.

Background: Obesity is increasingly impacting the overall health status and the global costs for health care. The increase in body mass index (BMI) is also observed in kidney allograft recipients and deceased organ donors., Methods: In a retrospective single-center study, we analyzed 1132 deceased donor kidney grafts, transplanted at our institution between 2000 and 2009 for recipient and donor BMI and its correlation with delayed graft function (DGF). Recipients/donors were classified according to their BMI (<18.5, 18.5-24.9, 25-29.9, and >30 kg/m(2)). DGF was defined as requirement for one dialysis within the first week after transplantation., Results: Overall DGF rate was 32.4%, mean recipient BMI was 23.64 ± 3.75 kg/m(2), and mean donor BMI was 24.69 ± 3.44 kg/m(2). DGF rate was 25.2%, 29.8%, 40.9%, and 52.6% in recipients with BMI less than 18.5, 18.5 to 24.9, 25 to 29.9, and more than 30 kg/m, respectively (P<0.0001). Donor BMI less than 18.5, 18.5 to 24.9, 25 to 29.9, more than 30 kg/m(2) resulted in a DGF rate of 22.5%, 31.0%, 37.3%, and 51.2% (P < 0.0001). Multivariate analysis revealed recipient BMI and dialysis duration as independent risk factors for DGF. DGF results in inferior 1- and 5-year graft and patient survival., Conclusion: Recipient and donor BMI correlate with the incidence of DGF. Awareness thereof should have an impact on peri- and posttransplant measures in renal transplant recipients.

Background: Studies reporting the immediate pediatric intensive care unit (PICU) treatment after combined liver-kidney transplantation (CLKT) are scarce, although this period is pivotal for survival and long-term outcome., Methods: We retrospectively analyzed all pediatric CLKT performed in our center between 1998 and 2010., Results: Sixteen patients underwent 17 CLKT at a median age of 5.3 years (range, 1.3-15.9 years). Median body weight at CLKT was 17.7 kg (range, 9.2-55 kg). Underlying diagnosis was primary hyperoxaluria type 1 in nine patients and autosomal recessive polycystic kidney disease in seven patients. Median time on PICU was 8.5 days (range, 3-68 days); however, patients with primary hyperoxaluria type 1 had a significantly longer stay (P=0.031). Median duration of ventilation was 1 day; however, five patients required ventilation for 25 to 52 days. Continuous veno-venous hemofiltration was applied in nine patients due to delayed kidney graft function, volume overload, or high plasma oxalate. Overall, the survival rate after CLKT was 100% and long-term outcome was very good at a mean follow-up of 3.6 years (range, 0.5-12.2 years). Waiting time, donor age, and donor-to-recipient weight ratio were found to be significant risk factors for an extended PICU stay (P=0.02, 0.0031, and 0.014, respectively)., Conclusions: Immediate postoperative course after CLKT may be challenging and complex. However, excellent results can be achieved, even in small children.

Background: Activation of the renin angiotensin system may contribute to the development of delayed graft function after renal transplantation. We, therefore, examined the impact of pretransplant treatment with blockers of the renin angiotensin system on early graft function after renal transplantation., Method: The case records of all patients who received a live donor transplant between January 2001 and August 2008 were reviewed., Results: Serum creatinine measurements were recorded for the first nine posttransplant days, in 94 recipients of live donor kidneys, where there were neither surgical nor hemodynamic complications and no documented rejection or infection. Forty patients (43%) were treated with a blocker of the renin-angiotensin-aldosterone system before transplantation. Serum creatinine levels fell more slowly in these patients (P=0.02). Two patients required hemodialysis after transplantation; both were on an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker., Conclusion: Live donor renal transplant recipients who are taking a renin-angiotensin-aldosterone system blocker at the time of transplantation are more likely to have impaired graft function postoperatively in the absence of other explanations. This observation requires further exploration in live and deceased donor renal transplantation.

Background: Ischemia reperfusion injury leading to acute renal failure (ARF) and delayed graft function is an important problem in organ transplantation. CD4+ T cells, essential for transplant rejection, may mediate ischemic ARF. We have demonstrated that the caspase-1 mediated production of IL-18 is pathogenic in ischemic ARF in mice. A potential source of IL-18 in ischemic ARF is the CD4+ T cell. We therefore examined the effect CD4+ T cell depletion on the development of ischemic ARF and the activation of IL-18., Methods: Functional and histological correlates were examined in two groups of mice with ischemic ARF: 1) CD4 T-cell depleted with the antibody GK1.5, and 2) T-cell receptor alpha-chain deficient (TCRalpha -/-) mice. TCRalpha -/- mice lack the alpha chain of the T-cell receptor and therefore lack functional CD4+ and CD8+ T cells., Results: Flow cytometry of lymph nodes and immunohistochemistry of kidneys demonstrated complete depletion of CD4+ T cells in mice with ischemic ARF treated with GK 1.5. CD4+ T-cell depletion did not confer functional (serum creatinine, BUN and FITC-labeled inulin clearance) or histological protection against ischemic ARF. Likewise, TCRalpha -/- mice were not protected against ischemic ARF. Renal caspase-1 activity and IL-18 protein were similar in CD4+ T-cell depleted and wild-type postischemic reperfusion., Conclusions: Ischemic ARF can occur in the absence of classical T-cell function. The evaluation of other inflammatory mediators (e.g., macrophages or NK cells) as a source of IL-18 and mediator of ischemic ARF warrants further investigation.