Assessment Of Allograft Function Research Articles

Diagnostic and Prognostic Potential of Multiparametric Renal MRI in Kidney Transplant Patients.

Multiparametric MRI provides assessment of functional and structural parameters in kidney allografts. It offers a non-invasive alternative to the current reference standard of kidney biopsy. To evaluate the diagnostic and prognostic utility of MRI parameters in the assessment of allograft function in the first 3-months post-transplantation. Prospective. 32 transplant recipients (54 ± 17 years, 20 females), divided into two groups according to estimated glomerular filtration rate (eGFR) at 3-months post-transplantation: inferior graft function (IGF; eGFR<45 mL/min/1.73 m2, n = 10) and superior graft function (SGF; eGFR ≥ 45 mL/min/1.73 m2, n = 22). Further categorization was based on the need for hemodialysis (C1) and decrease in s-creatinine (C2) at 1-week post-transplantation: delayed-graft-function (DGF: n = 4 C1, n = 10 C2) and early graft-function (EGF: n = 28 C1, n = 22 C2). 3-T, pseudo-continuous arterial spin labeling, T1-mapping, and diffusion-weighted imaging. Multiparametric MRI was evaluated at 1-week in all patients and 3-months after transplantation in 28 patients. Renal blood flow (RBF), diffusion coefficients (ADC, ΔADC, D, D, D*, flowing fraction f), T1 and T1 were calculated in cortex and medulla. The diagnostic and prognostic value of these parameters, obtained at 3-months and 1-week post-transplantation, respectively, was evaluated in the cortex to discriminate between DGF and EGF, and between SGF and IGF. Logistic regression, receiver-operating-characteristics, area-under-the-curve (AUC), confidence intervals (CIs), analysis-of-variance, t-test, Wilcoxon-Mann-Whitney test, Fisher's exact test, Pearson's correlation. P-value<0.05 was considered significant. DGF patients exhibited significantly lower cortical RBF and f and higher D*. The diagnostic value of MRI for detecting DGF was excellent (AUC = 100%). Significant differences between patients with IGF and SGF were found in RBF, ∆T1, and ∆D. Multiparametric MRI showed higher diagnostic (AUC = 95.32%; CI: 88%-100%) and prognostic (AUC = 97.47%, CI: 92%-100%) values for detecting IGF than eGFR (AUC = 89.50%, CI: 79%-100%). Multiparametric MRI may show high diagnostic and prognostic value in transplanted patients, yielding better results compared to eGFR measurements. 2 TECHNICAL EFFICACY: Stage 1.

New Strategies to Expand and Optimize Heart Donor Pool: Ex Vivo Heart Perfusion and Donation After Circulatory Death: A Review of Current Research and Future Trends.

Heart transplantation remains the definitive management for end-stage heart failure refractory to medical therapy. While heart transplantation cases are increasing annually worldwide, there remains a deficiency in organ availability with significant patient mortality while on the waiting list. Attempts have therefore been made to expand the donor pool and improve access to available organs by recruiting donors who may not satisfy the standard criteria for organ donation because of donor pathology, anticipated organ ischemic time, or donation after circulatory death. "Ex vivo" heart perfusion (EVHP) is an emerging technique for the procurement of heart allografts. This technique provides mechanically supported warm circulation to a beating heart once removed from the donor and before implantation into the recipient. EVHP can be sustained for several hours, facilitate extended travel time, and enable administration of pharmacological agents to optimize cardiac recovery and function, as well as allow assessment of allograft function before implantation. In this article, we review recent advances in expanding the donor pool for cardiac transplantation. Current limitations of conventional donor criteria are outlined, including the determinants of organ suitability and assessment, involving transplantation of donation after circulatory death hearts, extended criteria donors, and EVHP-associated assessment, optimization, and transportation. Finally, ongoing research relating to organ optimization and functional ex vivo allograft assessment are reviewed.

Cardiac Allograft Vasculopathy: A Review of Risk Factors and Pathogenesis

Heart transplant remains the gold standard therapy for patients with end stage heart disease and offers improved survival and quality of life. Significant progress has been achieved in improving one year mortality after heart transplantation. Nonetheless, long-term graft survival has not changed significantly over the past few decades. Long term survival of heart transplant recipients is limited by chronic rejection, cardiac allograft vasculopathy (CAV), and malignancy. CAV is a major contributor for graft failure and mortality after the first year of in heart transplant recipients. CAV is a proliferative vasculopathy characterized by diffuse myointimal hyperplasia and progressive narrowing of the graft vessels. Both immune dependent and independent factors have been shown to contribute to the pathogenesis of CAV. Understanding these risk factors is essential in developing preventative and therapeutic strategies. Angiography with Intravascular ultrasound (IVUS) has become the key diagnostic tool in the early detection of CAV as well as prognostication. Echocardiographic assessment of allograft function in conjunction with coronary angiographic findings are used in assessing the severity of CAV. Adjustment of immunosuppression and statins remain the initial steps in the management of CAV. Retransplantation is the definitive treatment for severe CAV, however, the paucity of organs along with increased mortality associated with retransplantation makes it a less desirable option. Although significant progress has been achieved in the understanding of pathogenesis, risk factors for CAV and plaque morphology, knowledge gaps still persists and further research is warranted. Progress is still needed in developing diagnostic modalities that could detect early CAV, as well as preventative and therapeutic strategies that will facilitate graft tolerance and immune modulation. This review focuses on summarizing the pathogenesis and risk factors for CAV.

Serum cystatin C versus creatinine in the assessment of allograft function in early periods of kidney transplantation

Introduction: Serum cystatin C is not routinely used in the evaluation of renal function and this may be due to its high cost, lack of adequate studies to approve the use of cystatin C and lack of accessibility and reliability. Many kidney transplanted patients encounter with decreased performance before creatinine rising and go toward rejection without certain actions. Certainly, the early detection of renal function reduction can prevent spiritual and physical damage among patients. Objectives: This study was aimed to determine the predictive value of serum cystatin C and creatinine in the assessment of allograft function in the early period after kidney transplantation in Urmia city, Iran. Patients and Methods: In this prospective study, serum creatinine, cystatin C and glomerular filtration rate (GFR) of 49 kidney transplanted patients in the 3rd, 8th and 14th day were measured and compared together. The correlation of creatinine and cystatin C was examined using Spearman’s correlation. ROC curves were used to investigate sensitivity and specificity. Results: In this study, there was a statistically significant relationship between serum levels of creatinine and serum levels of cystatin C in 3rd, 8th and 14th day. The sensitivity and specificity of cystatin C in 14th day were 76% and 91.2%, respectively and for creatinine were 72% and 75% respectively, indicating cystatin C is a more sensitive indicator compared to creatinine on the 14th day in the presence of loss of GFR below 60 mL/cc. Conclusion: Serum cystatin C as a valuable marker can be an effective predictor marker of renal function reduction beside creatinine. Due to high cost of measuring kits of serum cystatin C, it is not possible to use this marker in all transplanted patients in the world. Therefore, we can use this marker in high-risk patients with probability of transplantation rejection.

567 Longitudinal Assessment of Allograft Function Using Tissue Doppler Echocardiography after Heart Transplantation

567 Longitudinal Assessment of Allograft Function Using Tissue Doppler Echocardiography after Heart Transplantation

Clinical Utilities of Peripheral Blood Gene Expression Profiling in the Management of Cardiac Transplant Patients

Cardiac allografts induce host immune responses that lead to endomyocardial tissue injury and progressive graft dysfunction. Inflammatory cell infiltration and myocyte damage characterize acute cellular rejection (ACR) that presents episodically in either a subclinical or symptom-associated manner. Sampling of the endomyocardium by transvenous biopsy enables pathologic grading using light microscopic criteria to distinguish severity based on the focality or diffuseness of inflammation and associated myocyte injury. Monitoring for ACR utilizes endomyocardial biopsy in conjunction with history and physical examination and assessment of allograft function by echocardiography. However, procedural and interpretive issues limit the diagnostic certainty provided by endomyocardial biopsy. The dynamic profiling of genes expressed by peripheral blood mononuclear cells (PBMCs) enables quantitative assessments of intracellular mRNA whose levels fluctuate during systemic alloimmune responses. Gene expression profiling of PBMCs using a multi-gene ACR classifier enables the AlloMap® molecular expression test to distinguish moderate to severe ACR (p = 0.0018) in heart transplant patients. The AlloMap test provides molecular insights into a patient's risk for ACR by distilling the aggregate expression levels of its informative genes into a single score on a scale of 0 to 40. The selection of a score as a threshold value for clinical decision-making is based on its associated negative predictive value (NPV), which ranges from 98 to 99% for values in three post-transplant periods: > 2 to ≤6 months, > 6 to ≤ 12 months, and > 12 months. Scores below the threshold value rule out ACR, while those above suggest increased ACR risk. Incorporating the AlloMap test into immunomonitoring protocols provides an opportunity for clinicians to enhance patient care and to define its role in immunodiagnostic strategies to optimize the clinical outcomes of heart transplant recipients. This summary highlights the concepts presented in an invited presentation at a conference focused on Immunodiagnostics and Immunomonitoring: From Research to Clinic, in San Diego, CA on November 7, 2006.

Is Brain Natriuretic Peptide Clinically Useful After Cardiac Transplantation?

The clinical use of brain natriuretic peptide (BNP) in patients after cardiac transplantation remains to be defined. Over the last decade, a series of small studies have been performed to determine any potential use of this assay in the assessment of allograft function and prognosis. From the available evidence, it appears that a low BNP level in transplant recipients has a high negative predictive value for death. Why patients with higher BNP levels should be disadvantaged appears to be multifactorial. BNP titer may be influenced by severe rejection episodes and diastolic dysfunction, and possibly intracardiac pressure derangement. Although the concept of using a simple blood test to assess these patients sounds very attractive, further work is needed to define the exact role of this assay. Presently, it cannot be confirmed whether BNP can replace any of the current methods of assessing allograft performance and prognosis after transplantation.

Impaired circulating dendritic cell reconstitution identifies rejecting recipients after clinical heart transplantation independent of rejection therapy☆

Dendritic cell (DC) mediated allo-antigen presentation to host antigen specific T-lymphocytes initiates acute allograft rejection. We investigated peripheral blood DC (PBDC) incidence and DC subset reconstitution in relation to histological diagnosis of acute cellular rejection (AR) and administration of rejection therapy after clinical heart transplantation (post-HTx). Venous blood from 20 HTx recipients under standard immunosuppression was collected during serial endomyocardial biopsy (EMB) prior to administration of rejection therapy in a 9-month follow-up post-HTx. Echocardiographic assessment of allograft function during EMB was performed to distinguish clinical necessity for rejection therapy within histologically rejecting patients (R). Myeloid (mDC) and plasmacytoid (pDC) subsets identified by flow-cytometry were analysed for different ISHLT rejection grades. Circulating PBDC incidence and mDC/pDC ratio were compared sequentially between non-rejecting (NR) recipients and R patients treated (3A(+)) or not-treated (3A(-)) with rejection therapy during follow-up. Eleven samples from biopsy-proven AR episodes (AR(+): ISHLT>or=3) were compared to 89 samples from non-rejection episodes (AR(-): ISHLT grade 0, n=52; grade 1, n=29; grade 2, n=8). We observed an inverse correlation of mDCs (P<0.05) but not pDCs with increasing rejection grade. PBDC incidence and mDC/pDC ratio were low in blood samples obtained during AR (P<0.05 and P<0.01, respectively). Both PBDCs and mDC/pDC ratio decreased during each AR episode (P<0.05). Comparison of 3A(+) and 3A(-) rejectors with NR patients after 12 weeks post-HTx revealed lower PBDC incidence (P<0.01) and mDC/pDC ratio (P<0.05) for R patients, independent of rejection therapy. Defective DC subset reconstitution by dendritic cell profiling identifies patients at risk for AR after 3 months post-HTx. This finding may contribute to further optimization of immunosuppressive treatment strategies after clinical heart transplantation.

LOW CHOLESTEROL AND IMPAIRED CARDIAC FUNCTION FOLLOWING HEART TRANSPLANTATION

1. During follow-up of 59 cardiac transplant recipients over 2 or more years, a small group of subjects was observed who displayed an unpredictable, relatively marked, reduction in plasma cholesterol. 2. A significant proportion of these subjects were subsequently observed as having experienced a marked decline in left ventricular function at the time of routine radionuclide ventriculography. 3. While the mechanism for this fall in cholesterol is unclear, the observation of such an unexpected reduction in total cholesterol, late after heart transplantation should be considered significant and prompt further investigation including an assessment of allograft function.