Expanded Criteria Donor Kidney Transplantation: Comparative Outcome Evaluation Between Single Versus Double Kidney Transplantation at 8 Years: A Single Center Experience.

Transplantation of kidneys retrieved from expanded criteria donors is one of the options to expand the pool of available grafts, shorten the waiting time and increase the number of kidney transplant recipients. This study was a retrospective assessment of 99 patients who underwent renal transplantation during the period 2007-2015 with kidneys harvested from expanded criteria donors (ECD) as defined by the United Network for Organ Sharing (UNOS) following routine biopsy of all kidneys obtained by Karpinsky Score. They formed two groups: SKT (67 recipients that received a single kidney) and DKT (32 patients that received dual kidney transplant). An analysis of differences of two groups between graft and patient survival and graft function were performed after 8 years of observation. We observed between two groups the following statistical differences: Donor age (P < .001), basal high risk of recipients (P < .05), wait time before transplant (P < .05), recipient age (P < .001) delayed graft function (P < .005) while we observe similar values of donor renal function, outcome in graft and patient survival and graft function in recipients. The transplantation of kidneys obtained from expanded criteria donor, allows increase in the number of kidney transplants and in the respect of values of biopsy score and the donor renal function, showed in single or dual kidney transplantation with similar graft and patient survival.

"Immuknow" to measurement of cell-mediated immunity in renal transplant recipients undergoing short-term evaluation.

The aim of this preliminary, observational study was to evaluate the value of ImmuKnow (IK), a new tool to measure the net state of immunefunction among renal transplant recipients, in correlation with clinical and laboratory data among unselected renal transplant recipients. Forty-nine recipients of mean age of 51 years were enrolled and followed for 1 year after transplantation. All subjects received the same immunosuppressive strategy with basiliximab induction and tacrolimus, mycophenolate mofetil and steroid maintenance therapy. Samples for IK were collected before transplantation as well as at 7, 14, 21 and 42 days and after 3, 6, and 12 months. There were 54 samples with IK <225 ng/mL, 201 samples with normal IK values, and 135 samples with >525 ng/mL. We divided recipients into 3 groups with respect to their basal IK values: Group 1 (Gr1; IK <225 ng/mL); Group 2 (Gr2; normal values of IK between 226 and 524 ng/mL); and Group 3 (Gr3; IK >525 ng/mL). At 1 year, we observed a significant difference among IK values at the start and the end of the study: Gr1 vs Gr2, P<.0001; Gr2 vs Gr3, P<.06 and Gr 1 vs Gr 3, P<.01). We observed reduced IK values to predict an increased risk of infection, particularly with cytomegalovirus (CMV) replication while higher IK value did not correlate with an increased risk of acute rejection episodes. Reduction of serum creatine levels occurred within 1 year in all groups (P<.005), but there was a significant difference between Gr 2 versus Grs 1 and 3 (P<.0001 and P<.0005, respectively). There findings suggested that more stable IK values were associated with clinical quiescence and laboratory stability. In conclusion, our preliminary analysis showed a beneficial capacity of this assay to represent the global depression of the immune system. We noted that reduced IK values, as a sign of excessive immunosuppressive therapy, were associated with an increased risk of infection. We did not confirm the predictive value of higher IK values for an increased risk of an acute rejection episode.

Medial artery calcification of uremic patients: a histological, histochemical and ultrastructural study.

Recent findings suggest that vascular calcification (VC) is an active process similar to bone mineralization, the vascular smooth muscle cells (VSMCs) undergoing phenotypic differentiation into osteoblastic cells and synthesizing calcification-regulating proteins found in bone. This study has investigated the VC process of uremic patients, with a morphologic approach. Epigastric artery samples from 49 uremic, non-diabetic patients were taken during kidney transplantation. Sections from paraffin-embedded samples were stained with hematoxylin/eosin and von Kossa. CD68 was immunohistochemically detected, and sections from frozen samples were stained with Oil Red O. Deeply calcified samples were stained with Picrosirius Red, PAS, and Alcian blue. Specimens from one patient with moderate and one with severe VC were examined under the electron microscope. None of the samples had atherosclerosis. Calcifications were found in the media of 38 patients. In 23, dot-like calcifications were irregularly scattered near the adventitia (light VC); in 11, granular calcifications formed concentric rings near the adventitia (moderate-advanced VC); in 4, zones of consolidated calcifications were found (severe VC). These zones were poor in collagen, glycoproteins and proteoglycans. In cases with moderate or severe VC, VSCMs showed necrotic changes. Matrix vesicles could be recognized in the extracellular spaces. In cases with severe VC, uncalcified or partially calcified membranous bodies were found, together with Liesegang rings. Patches of fibrin were also found. These findings point to a mainly degenerative mechanism of VC, which proceeds from the outer portion of the media. An active mechanism, however, cannot be excluded. A unifying hypothesis is suggested.

Impact of preemptive reduction of immunosuppression with serial monitoring for BK virus replication in renal transplant recipients undergoing short-term evaluation.

The aim of this preliminary, prospective, longitudinal study was to evaluate the effects on graft function and viral loads of modulation of immunosuppressive therapy based upon serial noninvasive monitoring of urine and serum viral loads with real-time polymerase chain reaction among unselected renal transplant recipients. Thirty-nine renal transplant recipients with follow-up times of 7.8 +/- 4.3 months were monitored monthly with urine and serum samples to measure BK viral load. Interventions such as gradual reductions of mycophenolate mofetil and/or tacrolimus were performed when repeated urine and serum viral loads were >10(5) and >10(3) copies/mL, respectively. Among 271 samples, the patients were divided into 6 groups: negative urine (group = 1; n = 10) and negative serum (group 2; n = 25) versus BK viral loads that were intermittent (urine: group 3; n = 24 and serum: group 4; n = 11) versus persistent (urine: group 5; n = 5 and serum: group 6; n = 3). In groups 3-4 we observed the higher viral loads in the urine than in the serum (10(3): 21; 10(4): 1; 10(5): 1; 10(6): 1 vs 10(2): 8; 10(3): 2; 10(4): 1). The timing of resolution of viremia was more rapid than viruria. In groups 5-6 we observed the greatest viral load and greater number in urine. The overall incidences of viruria and viremia were 74.3% and 35.9%, respectively. The overall rates of clearance of viruria were 26/29 recipients (89%) and viremia, 11/14 recipients (78%). Only 10 patients (25.6%) needed extensive reduction of immunosuppression. No modifications of serum creatinine levels and no rejection episodes were observed. In conclusion this preliminary analysis suggested that serial, noninvasive monitoring of viral load allows gradual premptive reduction of immunosuppression with consequent strong reduction in viral load.

[Cytomegalovirus and BK polyomavirus infection after renal transplantation]. / Infezione da citomegalovirus (CMV) e da polioma BK virus (BKV) dopo trapianto di rene.

Cytomegalovirus (CMV) and BK polyomavirus (BKV) infections have been described in a high percentage of renal transplant patients and are known to cause various complications in renal transplantation. They are closely related to immunosuppressive therapy and implicated in the progression of graft failure. This review focuses on the clinical aspects of CMV and BKV infection after renal transplantation, optimal monitoring, and recent preventive measures and interventions to improve graft function and recipient survival.

Outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is considered an optimal indication for liver transplantation (LT) because it may eliminate both the tumor and the underlying liver disease. The present study sought to compare cumulative survival, rate of HCC recurrence, and causes of death among patients with cirrhosis and HCC before and after the adoption of more restrictive criteria (Milan selection criteria) at the time of patient listing. Among 226 adult patients who received an elective liver transplantation between 1999 and 2005, 58 (27%) had a diagnosis of HCC at the time. The 38 patients who underwent transplantation for HCC in the period 1989 to 1998 were considered the "historical group." After LT (mean follow-up, 34 + 28 months), the cumulative survival rate was better among HCC versus non-HCC recipients (93% vs 71% at 1 year and 81% vs 67% at 3 years, respectively; P < .046), although the difference tended to attenuate after 5 years (66% vs 67%, respectively). Tumor recurrence (evaluated in patients surviving at least 3 months after LT) was observed in 10/31 in the historical group versus 4/53 among those who underwent transplantation after 1999. Among the causes of death, recurrence represented 50% in the old series and 23% in patients who underwent transplantation after 1999. Cumulative survival significantly improved among HCC patients who underwent transplantation after 1999 (93% vs 66% at 1 year and 81% vs 50% at 3 years; P < .00001). The 58 patients who underwent transplantation with a diagnosis of cirrhosis and concomitant HCC after 1999 showed even better survival than patients who underwent transplantation for end-stage liver disease without malignancy.

Fertility following solid organ transplantation.

Fertility is usually restored in women after solid organ transplantation, and successful pregnancies have been reported in female recipients of kidney, liver, heart, pancreas-liver, and lung transplants. However, women with solid organ allografts have higher incidence of pregnancy complications like hypertension, preeclampsia, preterm delivery. Hypertension appears to be dependent on the type of immunosuppressive agents. The influence of pregnancy on the risk of rejection is poorly known on the basis of available data. Rejection rate appears to be at least similar to the nonpregnant population. In some cases, such as in liver transplant pregnant women, even higher as compared to the nonpregnant population. Maintaining appropriate blood levels of immunosuppressive drugs is currently recommended. Malformation rate in the offsprings of transplanted women appears to not be increased; long-term follow- up of children born to allograft recipients is necessary to investigate possible developmental, immunological, or oncological disorders. We followed 70 pregnancies after kidney transplantation and nine after liver transplantation. All recipients were maintained on immunosuppressive therapy during pregnancy, except one mother who refused immunosuppression and experienced transplant rejection. Hypertension was the most frequent complication during pregnancy: in 23% of kidney transplantated mothers and in one out of nine liver transplant recipients. The only malformation observed in the newborns was the dislocation of the hip in the child of a kidney transplant recipient.

Intractable pruritus in patients with hepatitis C virus.

Intractable pruritus is one of the most common symptoms of chronic liver disease, especially experienced by patients with prolonged cholestasis. It can become the most distressing symptom in patients affected by chronic liver disease, causing a reduction in quality of life, interfering with daily activities, and leading to sleep deprivation or contributing to psychological disturbances up to suicide ideation. Therefore, pruritus that does not respond to medical therapy is an indication for liver transplantation. We treated nine patients with hepatitis C virus affected by intractable pruritus with the molecular adsorbent recirculating system. In each patient, liver function, renal function, and hemodynamic variables were evaluated before and after the treatment. Before undergoing the treatment each patient underwent abdominal ultrasound or computed tomography scan to exclude organic causes for pruritus. We observed a decrease in total bilirubin, creatinine, and bile acids together with a significant improvement in Visual Analog Scale for staging of pruritus in all the patients. Due to the small number of patients the results were not significant.

Giant hemangiomas of the liver: surgical strategies and technical aspects.

The incidence of hemangiomas is 2-7% in the general population. We evaluated more than 300 patients with hepatic hemangiomas. Surgical removal of hepatic hemangiomas was performed in 48 cases due to uncertain diagnosis (2 cases), intractable symptoms (26 cases), size increase (18 cases), and liver failure in 2 cases that were treated by hepatic transplantation. In all, 26 patients underwent enucleation of hemangiomas or segmentectomies, while the remaining 20 patients underwent right lobectomies or left lateral segmentectomies. Blood transfusions were required in four cases (including two liver transplants); mean post-resection hospital stay was 6.3 days. We observed no perioperative mortality and only two cases of major morbidity (bile leaks not requiring reoperation). Our experience confirms that, after adequate patient selection, surgical treatment of hepatic hemangiomas is a very effective therapeutic choice with no mortality and low morbidity.

Predictive factors of outcome after liver transplantation in patients with cirrhosis and hepatocellular carcinoma.

Studies to define the optimal upper limits of tumor size and number as predictors of outcome after orthotopic liver transplantation (OLT) have yielded conflicting results. We analyzed 72 patients with cirrhosis and hepatocellular carcinoma (HCC) who underwent OLT over a 12-year period in a single center. Predictive factors for survival and tumor recurrence, according to the Milan criteria, were also examined. Our cohort included 60 men and 12 women of mean age 54 +/- 8 years and mean follow-up of 40 +/- 39 months. Origin of cirrhosis was postviral in 70% and Child class B or C in two thirds of patients. HCC was multifocal in 61%; about one fifth of patients had micro- or macrovascular involvement or positive nodes upon histologic examination. The cumulative size of the lesions was <3 cm in 17 patients; >3 to < or =5 cm in 28 patients; >5 to < or =8 cm in 14 patients; and >8 cm in 13 patients. According to the number and size of tumor nodules, 49 patients met the Milan criteria. During follow-up 25 patients died, 13 due to tumor recurrence. The 1- and 2-year survivals were 90% and 85% for patients who met the Milan criteria versus 57% and 51% for patients exceeding those limits (P = .006). A cumulative tumor size >8 cm was predictive of survival and tumor recurrence upon multivariate analysis. The adoption of Milan criteria for selection of cirrhotic patients has improved survival and reduced the rate of tumor recurrence. The evaluation of cumulative tumor size might further improve patient selection.

Survival in kidney transplantation from living donors: a single-center experience.

BACKGROUND: Transplantation from living donors, in Italy, is still not accepted, in particular those from unrelated donors. The aim of this paper was to present the experience of one transplant center. MATERIALS AND METHODS: Since 1982, 608 transplants were performed from living donors using cyclosporine as the main component of immunosuppressive therapy. Among those, 402 transplants were from related living donors (338 one haplotype pairs and 25 zero haplotypes pairs) and 206 from unrelated living donors (171 spouses and 35 emotionally related subjects). RESULTS: Graft survival at 1, 5, and 10 years showed no statistically meaningful difference between the two groups. A group of 19 transplants performed in predialytic phase patients was compared with a contemporaneous group of 167 transplants performed in patients who were already receiving dialysis. These two groups did not show any statistically meaningful difference in graft survival at 1, 5, or 10 years. DISCUSSION AND CONCLUSIONS: We think that transplants from living donors, whether related or unrelated, must always be proposed as a therapeutic option for end-stage renal disease patients, since they show an higher graft survival than that from cadaveric donors, independent of the compatibility between donor and recipient and independent of the degree of relationship of the pair. Transplantation from living donors definitely is a complementary, not substitutive, program to that from cadaveric donors, which should always be encouraged with awareness campaigns among the population and targeted programs for healthy personnel.

Low-dose intramuscular hepatitis B immune globulin and lamivudine for long-term prophylaxis of hepatitis B recurrence after liver transplantation.

The combination of lamivudine and hepatitis B immunoglobulins (HBIg) to prevent recurrence of HBV hepatitis has significantly improved the survival of patients transplanted for HBV-related end-stage liver disease. Generally, HBIg are administered intravenously. We evaluated the efficacy, tolerability, and cost savings of long-term intramuscular HBIg and lamivudine in 28 patients (23 men and 5 women), who received liver transplants for acute or chronic HBV-related liver disease. Twelve patients started lamivudine before and 16 at the time of liver transplantation. HBIg were administered intravenously during the first week (50 to 70,000 IU) and intramuscularly thereafter (1200 IU every 3 to 6 weeks) to maintain an HbsAb titer >100 IU/L. Mean follow-up was 20 +/- 13 months. Only one patient experienced HBV recurrence (9 months after transplantation). This patient had failed to follow the scheduled prophylaxis. Cumulative survival at 3 years was 83%. Intramuscular HBIg were well tolerated in all cases. Cost analysis comparing intramuscular vs intravenous HBIg administration showed that 39,490 Euros were saved per patient per year. These preliminary results show that low-dose intramuscular HBIg and lamivudine are efficacious and cost-effective for long-term prophylaxis of hepatitis B recurrence after liver transplantation.

Measurement of oxysterols and alpha-tocopherol in plasma and tissue samples as indices of oxidant stress status.

Oxidant stress seems to play a role in several setting of human pathology, such as atherosclerosis, cancer, and aging. The study of oxidant stress in human disease should be based on the evaluation of either sensitive and specific markers of enhanced oxidant stress, such as oxysterols, or antioxidant defense, by measuring alpha-tocopherol. We have developed a rapid method to measure the oxysterols 7beta-hydroxycholesterol and 7-ketocholesterol in plasma (50 healthy subjects) and tissue as an index of oxidant stress in vivo, and from the same sample alpha-tocopherol content. The mean plasma concentration of 7beta-hydroxycholesterol and 7-ketocholesterol was 4.6+/-1.1 and 13.4+/-7.6 ng/mL, respectively. Plasma alpha-tocopherol concentration was 5.8+/-1.0 micromol/mol cholesterol. Samples from atherosclerotic plaques contained 20 times more cholesterol, about 45 times higher oxysterols levels, and 600 times more alpha-tocopherol compared to normal arteries. No significant difference in cholesterol and oxysterol content was observed between cirrhotic and normal liver. However, cirrhotic liver contained significantly smaller concentration of alpha-tocopherol compared to normal liver. In conclusion, we have developed a rapid and reliable method for the assay of cholesterol oxidation products and alpha-tocopherol in plasma and tissue useful for estimation of oxidant stress/antioxidant balance.