Liver Graft Allocation by Means of a New, Regionally Shared "Mixed" Model: The Experience in Lazio.

INTRODUCTION: Since 2013, the regional network of transplantation centers "LAZIO TRANSPLANT" have adopted a new, mixed system for the allocation of liver grafts. METHODS: The organs from donors aged <65 are assigned to patients with higher Model for End-stage Liver Disease (MELD) scores on a common regional waiting list, whereas those from donors aged >65 are allocated to patients with higher MELD scores on a specific local waiting list (LWL) at each center, on a rotational basis. RESULTS: The new mixed allocation model grants a more rational allocation of the "standard" organs to the patients with the actual worst MELD score in the entire region, avoiding the possibility that a patient in relatively better clinical condition might be transplanted before a more severely ill patient on another center's waiting list. Nonstandard organs, presenting slightly increased transplant risks, are still allocated on a rotational basis among the different transplant centers, ensuring them the possibility to select, on the basis of a global clinical risk evaluation, those patients in their LWL whose MELD score would not grant any possibility to compete for the "standard" organ allocation. CONCLUSIONS: The application of the new model had no negative impact on the overall number of transplants performed or on the global list-satisfaction percentages, but has slightly improved the cumulative mortality of the patients in the waiting list, granting to the clinically worst patients a prompt graft allocation, independent of the local center belonging.

Polyomavirus BK infection in end-stage renal disease: analysis of viral replication in patients on hemodialysis or peritoneal dialysis.

Patients in end-stage renal disease undergoing renal replacement treatment (ESRD-RRT) are considered immunocompromised. The hemodialysis (HD) or peritoneal dialysis (PD) procedures seem to produce alterations of the immune status. Interest in immunosuppression has increased due to the poliomavirus BK (BKV) infection. Our study evaluated the prevalence of BKV infection in ESRD-RRT patients and viral replication on HD or PD. From 2006 to 2011 we selected 58 patients (34 males) in ESRD-RRT for inclusion in our study. BKV replication was evaluated by qualitative real-time polymerase chain reaction. In ESRD-RRT patients, the prevalence of BKV replication on plasma was 21%. We identified two groups of patients according to the dialysis procedure: 36 patients on HD (HD group) and 22 on PD (PD group). BKV replication in the HD group was 33% (12 of 36) versus 0% (0 of 22) in the PD group. Different age, number of months on RRT, and preserved diuresis was observed in the HD versus PD groups. With our results we can speculate that BKV infection in ESRD-RRT patients is linked to factors involved in the uremia-related immune dysfunction but also to specific mechanisms related to the different RRTs. PD is an option that could be associated with a better transplant outcome for patients undergoing kidney transplantation.

Long-term interleukin-2 assessment after conversion from a twice-daily to once-daily tacrolimus regimen in stable kidney recipients.

Conversion to tacrolimus (Tac) to once daily (Tac-O) formulation is commonly followed by a 20% reduction in Tac trough levels in the first month. It is not associated with modifications of renal function but there is the issue of its effects on inflammatory cytokines and on subclinical rejection. The aim of our study was to evaluate long-term interleukins (IL)-2 profiles in stable renal transplant patients after Tac-O conversion. We enrolled 10 stable kidney transplant patients converted to Tac-O. Tac trough levels, serum creatinine concentrations, glomerular filtration rate using the Modification of Diet in Renal Disease formula, C-reactive protein, IL-2 levels, and clinical assessments were performed monthly for 6 months before and 12 months after conversion. Despite the significant reduction in Tac trough levels, we did not observe alterations suggestive of clinical or subclinical acute rejection.

Interleukin-2 profiles shortly after tacrolimus conversion from a twice-daily to once-daily regimen.

A number of studies have indicated that kidney recipients can be safely converted from the twice-daily formulation (Tac-T) to the same dose of a once-daily tacrolimus (TAC) regimen (Tac-O) based upon monitoring of renal function. Conversion from Tac-T to Tac-O is commonly followed by a reduction in Tac trough levels, estimated by some authors to be about 20%. These alterations seem to not be associated with a modification of graft function, but study of inflammatory cytokines would be useful. The aims of our study were to monitor Tac, C-reactive protein (CRP), and interleukin (IL)-2 levels as well as to evaluate renal function among stable renal transplant patients converted from a Tac-T to a Tac-O regimen. We enrolled 10 consecutive stable kidney transplanted patients. Tac trough levels, serum creatinine concentrations, glomerular filtration rates using the Modification of Diet in Renal Disease formula (MDRD), CRP, and clinical assessment were performed monthly for 6 months before and 3 months after the conversion. After conversion we observed a slight but not significant reduction in Tac trough level. Renal function evaluated by serum creatinine and MDRD as well as CRP were not significantly different after conversion. IL-2 levels remained stable after conversion. We identified a group of patients showing reduced Tac trough levels below the therapeutic range and a group with stable Tac levels. No significant differences were observed among the two groups before versus after the conversion. Our results did not show a modification of IL-2, CRP and renal function levels, at 3 months after conversion despite the lower Tac trough concentrations. The clinical meaning of Tac trough alterations is not clear. They might reflect inter- and intraindividual differences in the clearance of Tac as recently described. They did not seem to be associated with activation of an inflammatory pathway.

Tacrolimus trough levels and level-to-dose ratio in stable renal transplant patients converted to a once-daily regimen.

Numerous evidence has been reported to support a safe 1:1 conversion from the twice-daily tacrolimus (Tac-T) to the once-daily tacrolimus regimen (Tac-O), but frequently there is a reduction in drug trough levels, which has been estimated by some authors to be about 20%. The relationship between Tac-O dosage and trough levels after conversion is not clear. The tacrolimus trough levels-to-dose ratio has been applied to better define the wide variability in doses and blood levels of tacrolimus. The aim of this study was to evaluate tacrolimus trough levels, tacrolimus daily dosage, and tacrolimus level-to-dose ratio during 1 year pre-postconversion follow-up in 31 stable kidney transplant patients who had received Tac-T therapy for over 6 months with stable renal function. They were converted to the same dosage of Tac-O. Patients before and after conversion were their own controls. The trough levels of tacrolimus showed a slight albeit significant reduction after conversion, remaining in the therapeutic range. Nineteen percent underwent an adjustment in total daily dosage after conversion versus 39% before conversion with no significant difference. No significant differences were detected in the total daily dose administered either by tacrolimus level-to-dose ratio before or after conversion. Kidney transplant recipients under Tac-O therapy were safely maintained using the same therapeutic monitoring as when receiving Tac-T.

Polyomavirus BK replication in adult polycystic kidney disease post-renal transplant patients and possible role of cellular permissivity.

Cell division and differentiation but not proliferation seem to be necessary for BK virus (BKV) replication and reactivation of persistent infection. Only terminal differentiating cells are permissive to BKV replication. Renal tubular epithelial cells in human adult polycystic kidney disease (ADPKD) are characterized by increased proliferative activity leading to cyst growth with less cellular differentiation. The aim of this study was to evaluate the possibility of different BKV replication patterns in patients with polycystic kidney disease versus non-ADPKD patients. From May 2006 to April 2008, we performed renal transplantations in 47. Eleven patients were affected by ADPKD (Pc group) and 36 patients, non ADPKD (n-Pc group). BKV replication was evaluated by quantitative real-time polymerase chain reactions (PCR) on plasma and urine samples at 12 hours (T0/early) as well as 3 (T3) and 6 (T6) months after transplantation. BKV viremia occurred in 9%, 12.5%, and 20% among the Pc group versus 33.3%, 42.4%, and 50% among the n-Pc group at 12 hours as well as 3 and 6 months posttransplantation, respectively. A higher discordance (BKV-PCR blood -/urine +) was observed in plasma and urine BKV replication among Pc versus n-Pc groups. We hypothesized that the lower number of patients with active BKV plasma replication in the Pc group may be related to a lower cellular permissivity of the renal tubular epithelial cells in ADPKD.

Improvement of graft function after conversion to once daily tacrolimus of stable kidney transplant patients.

BACKGROUND: Chronic renal dysfunction is present in about one quarter of kidney transplant patients at 1 year and in about 90% by 10 years. Nephrotoxicity caused by calcineurin inhibitors is among the most common factors. Elevated tacrolimus levels have been correlated with worse control of side effects including acute and/or chronic nephrotoxicity. The aim of this study was to observe the effects on graft function of conversion from the twice daily to the once daily extended release tacrolimus formulation in stable kidney transplant recipients within 5 years of grafting. METHODS: Thirty-one stable kidney transplant patients were converted at the same dosage (1 mg:1 mg). Patients served as their own controls based on results before versus after conversion. RESULTS: The trough levels of tacrolimus showed a slight albeit significant reduction after the conversion. Serum creatinine and glomerular filtration rate showed a significant improvement without an association with the tacrolimus trough levels. CONCLUSION: We suggest that the immunosuppression with once daily tacrolimus may be a good option for kidney transplant patients.

Meaning of early polyomavirus-BK replication post kidney transplant.

Polyomavirus BK (BKV) infection is ubiquitous in the human population. Under immunosuppression, BKV can undergo reactivation resulting in viral replication. What really happens in the early hours posttransplantation is not clearly defined; the meaning of early viremia and viruria is not clear. BKV viremia is considered a marker of infection. The aim of our study was to investigate the prevalence of early BKV infection in kidney transplant patients, to evaluate the relationship to infections at 3 and 6 months and the association with recipient, donor, and graft features. We enrolled 36 kidney transplanted patients from May 2006 to April 2007. BKV load was measured on plasma and urine samples by Q-PCR at 12 hours (T(0)/early) as well as 3 (T(3)) and 6 (T(6)) months thereafter. A high percentage of BKV infections were detectable in the first hours after transplantation (33.3%), which remained unchanged to month 6 post transplantation. Moreover, patients who were positive at T(0) had a high probability of remaining positive thereafter. The number of copies in plasma samples tended to increase at 3 months and to decrease thereafter, whereas the urine viral load tended to steadily increase. Among BKV-positive patients, we identified 2 groups according to viremic state at T(0): 9 patients (group A); who were already positive and remained so to T(6) 5 and 3 patients who turned positive at 3 or at 6 months, respectively (group B). Group A included 75% of positive patients at T(0) and 90% of positive patients at either T(3) or T(6) (P = .007). The most important contribution of our study was to highlight the presence of BKV infection in renal transplant recipients from the first hours posttransplantation. This condition seemed to be the most important risk factor for persistent infection in the first 6 months.

RIFLE criteria and hepatic function in the assessment of acute renal failure in liver transplantation.

Renal dysfunction in cirrhotic patients is primary related to disturbances of circulatory function, triggered by portal hypertension with chronic intrarenal vasoconstriction and hypoperfusion. Pretransplant renal function is an important factor implicated in the development of acute renal failure (ARF) after liver transplantation (OLT), but other factors mostly related to liver function seem to influence the development of ARF. The Acute Dialysis Quality Initiative workgroup developed the RIFLE classification to define ARF. We sought to evaluate the incidence of ARF among patients undergoing OLT, to evaluate the association of ARF with pre-OLT renal and hepatic functions, and to evaluate the influence of ARF on chronic kidney disease (CKD) at 1 month post-OLT. Clinical, renal, hepatic function, and donor risk index data of 24 patients who underwent deceased donor OLT were collected before transplantation, in the perioperative period and in the first month post-OLT. ARF occurred in 37.5% of patients with 56% developing the R grade and 44% the I grade; no patient showed the F grade. An association was observed between ARF and a higher Model for End-Stage Liver Disease (MELD) score and between ARF and a reduced pre-OLT serum albumin. No association was noted between ARF and other pre-OLT parameters. In cirrhotic patients serum creatinine is a bias for renal function assessment and the Modification of Diet in Renal Disease formula overestimates GFR. Post-OLT CKD was present in 6.7% of patients without ARF and in 44.4% of patients with ARF. The R grade developed more frequently among patients with viral cirrhosis. The association of ARF with MELD and hypoalbuminemia may be the result of a close relationship between renal and hepatic functions among cirrhotic patients. Post-OLT CKD may be the result of unrecognized, preexisting CKD and/or the effects of not fully resolved acute damage to an injured kidney.

Once daily tacrolimus formulation: monitoring of plasma levels, graft function, and cardiovascular risk factors.

BACKGROUND: Advagraf, an extended release formulation of tacrolimus, is administered once daily during the morning fast. Tacrolimus can be safely converted from the twice daily formulation (Prograf) to the same dose (1 mg:1 mg) of once daily dosing tacrolimus (m-Tac). The adverse effects of tacrolimus play important roles in posttransplant cardiovascular risk factors (CVR): hyperglycemia, posttransplant diabetes mellitus, dyslipidemia and hypertension. It has been suggested that avoiding high tacrolimus peak levels minimizes its diabetogenic effects leading to better glycemic control. The aim of our study was to observe the effects of conversion to m-Tac therapy on graft function and CVR among stable transplant kidney recipients. METHODS: We selected 2 groups of 20 patients with stable kidney transplantation, who had been treated with Prograf for >6 months with a triple regimen. Group 1 were converted to once daily tacrolimus at the same dose (1 mg:1 mg); whereas in group 2, the therapy was maintained as a twice daily regimen. Blood pressure, creatinine and glomerular filtration rate levels evaluated by the Modification of Diet in Renal Disease formula, as well as urea, total, high- and low-density lipoprotein remained stable between the 2 groups as well as inside group 1 before and after conversion. RESULTS: After conversion, glycemia and triglyceride values showed significant reductions in group 1 and between the 2 groups. These results were significant, as they may be associated with better long-term graft and patient survivals.

A long-standing cystic lymph-node metastasis from occult thyroid carcinoma.

Here we report the case of a patient with a soft tissue mass of the neck. For more than 10 years it was thought to be a branchial cyst and was later diagnosed to be a cystic lymph node metastasis from an occult thyroid carcinoma.

Serum cytokeratins determination in differentiated thyroid carcinoma.

To assess the potential value of cytokeratins (CK) 8,18,19 as tumor markers for thyroid diseases, a study was performed comparing serum CK 8,18,19 levels in patients affected from thyroid carcinoma, adenoma, other benign thyroid diseases and healthy volunteers as controls. One hundred cases (65 patients and 35 controls) were examined. Thirty patients had thyroid carcinoma (18 papillary--PTC, 8 follicular--FTC, 4 medullary--MTC), 19 non-toxic goiter, 10 thyroid adenoma, 6 chronic thyroiditis and 35 healthy volunteers as controls. These controls were matched by age and sex. The mean value of CK in benign thyroid diseases (46.1 U/L) was significantly higher (p<0.02) than that in healthy controls (29.6 U/L). The mean value of CK in carcinomas (68.1 U/L) was significantly higher than that in healthy controls (p<0.01) and benign thyroid diseases patients (p<0.05). The positive rate of CK in thyroid carcinomas was 28.1%, while in benign thyroid diseases was 17.8%. The CK sensitivity for thyroid carcinomas was 28.1%, with a specificity of 80% and accuracy of 70.4%. In PTC patients the mean CK value was not significantly higher than in the benign diseases' group and in healthy subjects. No evident correlation between CK levels and tumor mass was found. In FTC patients the mean value was significantly higher than in the benign diseases' group and in healthy subjects. Large tumors showed the highest levels, while small tumor values were similar to the control ones. In MTC patients the mean value was significantly higher than in the benign diseases' group and in healthy subjects, with the highest peaks in large tumors and metastatic tumors. The detection of increased values in thyroid carcinomas with high metastatic potential (FTC and MTC) seems to confirm the role of these antigens in predicting the malignancy's degree of the neoplasm. These findings, if confirmed in larger series, could play an important role in assessing the CK 8,18,19 serum level as a real prognostic factor. Further repeated serum determinations after total thyroidectomy might indicate the role of CK 8,18,19 as serum markers predicting the risk of metastases.