Associations between EBV serostatus and organ transplant type in PTLD risk: an analysis of the SRTR National Registry Data in the United States

In a prior multiorgan transplant database study, recipient Epstein-Barr virus (EBV) seronegativity was not associated with increased risk for posttransplant lymphoproliferative disorders (PTLD) in liver transplants (LTX), at variance with prior single center reports and with data from kidney and heart transplants (KTX and HTX). The Scientific Registry of Transplant Recipients (SRTR) in the United States is the only other registry with data on the required variables for comparison.Our study set comprised 112 756 KTX (580 PTLDs; 0.51%), 13 937 HTX (140 PTLDs; 1.0%) and 40 437 LTX (383 PTLDs; 0.95%) performed January 2003 onward. The unadjusted hazard ratio (HR) for PTLD if recipient EBV seronegative was 5.005 for KTX, 6.528 for HTX and 2.615 for LTX (p < 0.001 for all). In models adjusted for multiple covariates, the adjusted HR was 3.583 (p < 0.001) for KTX, 4.037 (p < 0.001) for HTX, 1.479 (p = 0.03) for LTX. Interaction models using EBV seropositive KTX as reference group showed significantly higher risk for all other EBV seronegative organ transplant groups and also for EBV seropositive LTX (AHR 2.053, p < 0.0001).Recipient EBV seronegativity is still significantly associated with risk for PTLD in LTX, though less so because of higher baseline risk in the EBV seropositive LTX group.     

Effect of Sirolimus Withdrawal in Patients with Deteriorating Renal Function

Sirolimus has been an important addition to immunosuppressive regimens utilized in kidney transplantation. However, sirolimus can potentiate calcineurin inhibitor (CNI) nephrotoxicity by some still uncertain mechanisms. Studies have demonstrated that withdrawal of a CNI under sirolimus immunosuppression can improve renal function. However, it has yet to be demonstrated that withdrawal of sirolimus from such a regimen can also improve renal function and reverse progressive functional deterioration. We studied 17 patients who developed deterioration of renal function while on a CNI and sirolimus. Once an established deterioration in renal function was noted, sirolimus was withdrawn from the regimen and replaced with mycophenolate mofetil. Out of 17 patients with a negative slope in 1/cr, 15 demonstrated a positive treatment effect (change to a positive slope). On aggregate, renal function improved by 18% (creatinine 2.75-2.24 mg/dL), LDL cholesterol improved, as did hematocrit values after withdrawal. The majority of patients on a CNI and sirolimus regimen who experience deterioration in renal function demonstrate improvement in renal function after withdrawal of sirolimus. This strategy may be particularly useful in those patients where CNI withdrawal is considered to be of high immunologic or metabolic risk.     

Kidney Transplantation Halts Cardiovascular Disease Progression in Patients with End-Stage Renal Disease

Morbidity and mortality from cardiovascular disease have a devastating impact on patients with chronic kidney disease (CKD) and end-stage renal disease. Renal function decline in itself is thought to be a strong risk factor for cardiovascular disease (CVD). In this study, we investigated the hypothesis that the elevated CV mortality in kidney transplant patients is due to the preexisting CVD burden and that restoring renal function by a kidney transplant might over time lower the risk for CVD. We analyzed 60,141 first-kidney-transplant patients registered in the USRDS from 1995 to 2000 for the primary endpoint of cardiac death by transplant vintage and compared these rates to all 66813 adult kidney wait listed patients by wait listing vintage, covering the same time period. The CVD rates peaked during the first 3 months following transplantation and decreased subsequently by transplant vintage when censoring for transplant loss. This trend could be shown in living and deceased donor transplants and even in patients with end-stage renal disease secondary to diabetes. In contrast, the CVD rates on the transplant waiting list increased sharply and progressively by wait listing vintage. Despite the many mechanisms that may be in play, the enduring theme underlying rapid progression of atherosclerosis and cardiovascular disease in renal failure is the loss of renal function. The data presented in this paper thus suggest that the development or progression of these lesions could be ameliorated by restoring renal function with a transplant.     

Steroid profile in an adrenocortical carcinoma producing aldosterone.

We report a rare case of primary aldosteronism due to an adrenocortical carcinoma. A 61-year-old woman with a history of hypertension and hypokalemia was referred for evaluation of a 4.2 cm measuring adrenal mass without secondary signs of malignancy. Endocrinological testing was consistent with primary aldosteronism. The patient underwent surgical resection of the adrenal mass; histology revealed an adrenocortical carcinoma. Postoperatively blood pressure, serum potassium, and aldosterone returned to normal. Four months after adrenalectomy, the patient presented again with hypokalemic hypertension and was found to have metastatic disease. Endocrinological investigation revealed primary aldosteronism and subclinical autonomous glucocorticoid hypersecretion. Careful hormonal investigation should be obtained in patients with adrenal masses causing excessive aldosterone secretion. In uncertain cases of primary aldosteronism, we would suggest to measure 18-hydroxycortisol levels, as excessive amounts may indicate adrenocortical carcinoma.     

Plasma homocysteine concentrations in young individuals at increased risk of type 2 diabetes are associated with subtle differences in glomerular filtration rate but not with insulin resistance.

Plasma homocysteine levels are elevated in individuals with type 2 diabetes contributing to the increased cardiovascular risk of these patients. As insulin resistance is a key feature in type 2 diabetic patients, hyperhomocysteinemia might be a consequence of insulin resistance. We studied this hypothesis in 839 individuals(male: 302, female: 537, mean age: 37.5 years) with a higher prevalence of insulin resistance (positive family history of type 2 diabetes, history of gestational diabetes, overweight). Subjects with overt type 2 diabetes or known kidney disease were excluded from the study. Mean plasma homocysteine concentration was 8.9 micromol/l (95% RCI 4.8-14.9). Adjusted for age and sex we could not find a significant correlation between homocysteine levels and BMI, insulin levels, or the insulin sensitivity-index (r = 0.35; p = 0.48). Furthermore, after a successful lifestyle intervention resulting in a significant decrease in BMI, body fat content and improved insulin sensitivity (p < 0.0001 each) no differences in homocysteine concentrations could be achieved. However,in the cross-sectional analysis we found a significant and independent, negative correlation between glomerular filtration rate (GFR) and homocysteine levels (r = -0.37; p < 0.0001). In conclusion, our study did not reveal a significant association between levels of homocysteine and insulin resistance in a population with an increased risk for type 2 diabetes. However, plasma homocysteine levels were related to subtle differences in kidney function at this early stage.     

Assessment of a single-acquisition imaging sequence for oxygen-sensitive (3)He-MRI.

MRI of the lungs using hyperpolarized helium-3 ((3)He) allows the determination of intrapulmonary oxygen partial pressures (p(O2)). The need to separate competing processes of signal loss has hitherto required two different imaging series during two different breathing maneuvers. In this work, a new imaging strategy to measure p(O2) by a single series of consecutive scans is presented. The feasibility of the method is demonstrated in three healthy human volunteers. Maps and histograms of intrapulmonary p(O2) are calculated. Changes in the oxygen concentration of the inhaled gas mixture are well reproduced in the histograms. Monte Carlo (MC) simulations of the temporal evolution of (3)He hyperpolarization within the lungs were performed to evaluate the accuracy of this measurement technique, and its limitations.     

Poor Predictive Value of Serum Creatinine for Renal Allograft Loss

Both medical care and pharmaceutical development have led to an increase in expected graft and patient survival for patients who undergo renal transplantation. From a research perspective, it has become increasingly difficult to study the efficacy of new therapies using traditional 'hard' endpoints. In reaction to this dilemma, the transplant community has sought a surrogate endpoint. A natural candidate for a surrogate marker for graft loss that has been proposed is renal function (serum creatinine or calculated GFR levels). Using data from the USRDS, we conducted a retrospective evaluation of transplant data from 1988 to 1999 to quantify the predictive value of renal function for the outcomes of graft loss, death-censored graft loss, and patient death. Renal function along with the change in renal function demonstrated a high relative risk for ultimate graft survival and graft loss (odds ratio = 2.2 for an increase of 1 mg/dL). However, the predictive value as measured by the area under the receiver operating characteristic curve (AUC) for this criteria was poor (0.627). These findings held true for the slope of creatinine and formulations of GFR. While renal function is a strong risk factor and highly correlated with graft failure, the utility of renal function as a predictive tool for graft loss is limited.     

Plasma quality after whole-blood filtration depends on storage temperature and filter type

The study evaluated the quality of plasma obtained after whole-blood filtration with four different polyester filters and one polyurethane filter. The activities of coagulation factors and proteinase inhibitors were not or only negligibly affected by filtration, in all experiments. Filtration did not increase markers of clotting and fibrinolysis. Only a strong neutrophil and complement activation was observed, which depended on the type of filter and whole-blood storage conditions. However, as neutrophil elastase-specific degradation products did not increase and the complement-derived anaphylatoxin C3a was found in its inactivated form, C3a-desArg, these filtration-dependent changes apparently have little impact on the therapeutic quality of whole-blood-filtered fresh frozen plasma for transfusion.     

Extension of platelet shelf life from 4 to 5 days by implementation of a new screening strategy in Germany

Background The Paul‐Ehrlich‐Institute analysed all fatalities due to bacterial infections between 1997 and 2007. Thereafter, the platelet shelf life was reduced to a maximum of 4 days after blood donation because the majority of all cases of severe transfusion‐transmitted bacterial infections occurred with day 5 platelets. The current study compares the analytical sensitivity and the diagnostic specificity of four rapid bacterial detection procedures. Methods Nine transfusion‐relevant bacterial strains were spiked in pooled platelets or apheresis platelets at a low concentration (10 CFU/bag). Samples were collected after day 3, day 4 and day 5 and investigated by four rapid bacterial detection methods (modified BacT/ALERT, Bactiflow, FACS method and 16s DNA PCR methods). Results Seven out of nine bacterial strains were adequately detected by BacT/ALERT, Bactiflow and PCR in apheresis platelets and pooled platelets after sample collection at day 3, day 4 and day 5. For three bacterial strains, analytical sensitivity was reduced for the FACS method. Two bacterial strains did not grow under the storage conditions in either pooled or apheresis platelets. Conclusions A late sample collection on day 3, day 4 or day 5 after blood donation in combination with a rapid bacterial detection method offers a new opportunity to improve blood safety and reduce errors due to sampling., BacT/ALERT, Bactiflow or 16s ID‐NAT are feasible for late bacterial screening in platelets may provide data which support the extension of platelet shelf life in Germany to 5 days.