Contrast-Enhanced Sonography in Early Kidney Graft Dysfunction

Objectives

The aim of this study was a comparison of contrast-enhanced sonography (CEUS) and power Doppler ultrasound (US) findings in renal grafts within 30 days posttransplantation.

Methods

A total of 39 kidney recipients underwent CEUS (SonoVue bolus injection) and US examinations at 5 (T0), 15 (T1), and 30 (T2) days after grafting. The results were correlated with clinical findings and functional evolution. Fourteen patients displayed early acute kidney dysfunction: 10 had acute tubular necrosis (acute tubular necrosis [ATN] group); four acute rejection episodes (ARE group); 25 with normal evolution (as control, C group). Renal biopsies were performed to obtain a diagnosis in the four ATN cases and in all ARE patients. Creatinine and estimated glomerular filtration rate were used as kidney function parameters. CEUS analysis was performed both on cortical and medullary regions while US resistivity indexes (RI) were obtained on main, infrarenal, and arcuate arteries. From an analysis of CEUS time-intensity curves, we computed peak enhancement (PEAK), time to peak (TTP), mean transit time (MTT), regional blood flow (RBF) and volume (RBV), and cortical to medullary ratio of these indies (RATIO).

Results

An increased RI was present in the ATN and ARE groups as well as a reduced PEAK and RBF. RATIO-RBV and RATIO-MTT were lower than C among ATN cases, while TTP was higher compared to C in ARE. No statistical difference was evidence for RI between ATN and ARE groups. MTT (T0) was significantly related to creatinine at follow-up (T2).

Conclusions

US and CEUS identified grafts with early dysfunction, but only some CEUS-derived parameters distinguished ATN from ARE, adding prognostic information.     

Rescue Immunosuppression With Mammalian Target of Rapamycin Inhibitor Drugs in Liver Transplantation

Background

Mammalian target of rapamycin (mTOR) inhibitors behave as potent immunosuppressants, which have the advantages, with respect to calcineurin inhibitors (CNI; cyclosporine or tacrolimus), of no nephrotoxicity but inhibition of cell proliferation. They are particularly suitable for patients with renal insufficiency or neoplasias.

Materials and Methods

Twenty-eight liver transplant patients were immunosuppressed with everolimus or sirolimus as rescue therapy after CNI treatment: 8 hepatocellular carcinomas; 7 de novo malignancies; 6 renal insufficiencies; 3 chronic rejections; 3 acute rejection episodes; and 1 epilepsy.

Results

There were 0% tumor recurrences, 50% improvements in 33% no change, and 17% worsening of renal function among cases of renal insufficiency; 0% improvement in cases of chronic rejection, and 33% improvement in acute rejection episodes. There was a 7% incidence of acute rejection episodes, but no kidney failure, gastrointestinal intolerance, hydrocarbon intolerance, hypertension, or arterial or venous thrombosis. Diarrhea occurred in 7%; hypercholesterolemi in 46% hypertriglyceridemia in 50% thrombocytopenia in 14%, leukopenia in 14%, and anemia in 39%. The 12% intercurrent infection rate included oral thrush in 11%. Lower limb edema occurred in 21%; 1 case displayed facial edema and 1, alopecia.

Conclusions

mTOR inhibitors were safe immunosuppressive drugs whose side effects were controlled and easily managed. They have advantages with respect to CNI due to their slight effects on kidney function and lack of promotion of diabetes mellitus. Although their long-term effectiveness for control of neoplastic diseases is yet to be seen, they can be used safely in these patients with a low incidence of rejection. Their effectiveness to control steroid-resistant acute rejection episodes or renal insufficiency seems significant, but they are of doubtful benefit for chronic rejection.     

Relationship of Renal Resistive Index and Cardiovascular Disease in Renal Transplant Recipients

Background

Cardiovascular disease is the primary cause of death in renal transplant recipients, and elevated renal allograft resistive index (RI) has been associated with patient survival.

Objective

To evaluate the predictive value of intrarenal RI on atherosclerotic disease.

Patients and Methods

Ninety-seven patients who had undergone renal transplantation between 1999 and 2001 and had stable renal function were included in the study. Patients with renal artery stenosis, urinary tract obstruction, clinical symptoms of acute rejection, or chronic allograft nephropathy were excluded. Clinical and laboratory information was obtained from the medical records and included demographic data, medications used, body mass index, blood pressure, and laboratory values. Intrarenal RI and carotid intima-media thickness (IMT) were determined using Doppler ultrasonography.

Results

At linear regression analysis, RI was significantly correlated with recipient age, C-reactive protein concentration, systolic blood pressure, pulse pressure, body mass index, smoking, and carotid IMT. At multivariate linear regression analysis, only pulse pressure was an independent predictor of intrarenal RI.

Conclusion

Intrarenal RI is associated with traditional cardiovascular risk factors and carotid IMT. Elevated intrarenal graft RI may be predictive of cardiovascular disease in renal transplant recipients without complications.     

Serial Soluble CD30 Measurements as a Predictor of Kidney Graft Outcome

Background

High levels of soluble CD30 (sCD30), a marker for T-helper 2-type cytokine-producing T cells, pre or post-renal transplantation serves as a useful predictor of acute rejection episodes. Over the course of 1-year, we evaluated the accuracy of serial sCD30 tests to predict acute rejection episodes versus other pathologies that affect graft outcomes.

Patients and methods

Fifty renal transplant recipients were randomly selected to examine sCD30 on days 0, 3, 5, 7, 14, and 21 followed by 1, 3, 6, and 12 months. The results were analyzed for development of an acute rejection episode, acute tubular necrosis (ATN), or other pathology as well as the graft outcome at 1 year.

Results

Compared with pretransplantation sCD30, there was a significant reduction in the average sCD30 immediately posttransplantation from day 3 onward (P < .0001). Patients were divided into four groups: (1) uncomplicated courses (56%); (2) acute rejection episodes (18%); (3) ATN (16%); and (4) other diagnoses (10%). There was a significant reduction in sCD30 immediately posttransplantation for groups 1, 2, and 3 (P < .0001, .004, and .002 respectively) unlike group 4 (P = .387). Patients who developed an acute rejection episode after 1 month showed higher pretransplantation sCD30 values than these who displayed rejection before 1 month (P = .019). All groups experienced significant improvement in graft function over 1-year follow-up without any significant differences.

Conclusion

Though a significant drop of sCD30 posttransplantation was recorded, serial measurements of sCD30 did not show a difference among subjects who displayed acute rejection episodes, ATN, or other diagnoses.     

Investigation of Antibody-Mediated Rejection in Composite Tissue Allotransplantation in a Rat Limb Transplant Model

Background

Despite the widely accepted implication of antidonor antibodies and complement in solid organ transplantation, their role in reconstructive allotransplantation is not clear. The aim of this study was to analyze the humoral immune response using a rat orthotopic limb transplantation model.

Methods

We used the Brown Norway to Lewis rat orthotopic hind-limb transplant model: Group 1, isografts; group 2, allografts with daily continuous cyclosporine treatment to prevent acute rejection; and group 3, allografts undergoing multiple episodes of acute rejection. Samples were taken at 30, 60, and 90 days. Serum was analyzed by FACS for antidonor antibodies. Tissue deposition of antibodies and complement was investigated by immunofluorescence.

Results

By day 90, animals in group 3 had undergone 19 (±3.2) acute rejection episodes. There was no difference in the occurrence of serum antidonor antibodies between the three groups at any time point. However, at 90 days, anti-third-party antibodies were significantly greater among group 3. There was no difference in antibody or complement deposition in muscles between the 3 groups.

Conclusion

Despite the increased antibody against a third party after multiple rejection episodes in this animal model, there was no clear evidence of an antibody-mediated alloresponse in limb transplantation.     

Prospective Clinical Trial Comparing Two Immunosuppressive Regimens, Tacrolimus and Mycophenolate Mofetil Versus Everolimus and Low-Dose Cyclosporine, in De Novo Renal Transplant Recipients: Results at 6 Months Follow-up

Objective

The aim of this study in renal transplant recipients was to compare a tacrolimus plus mycophenolate mofetil (MMF) immunosuppressive regimen with a combination of low dose of cyclosporine and everolimus.

Patients and Methods

Sixty consecutive patients were prospectively assigned to receive tacrolimus and MMF (TAC; n = 30) or everolimus and low-dose cyclosporine (EVL; n = 30). Tacrolimus was dosed seeking a trough blood level of 8 to 10 ng/mL by month 3 and 5 to 8 ng/mL thereafter. Everolimus was dosed seeking a trough blood level of 3 to 8 ng/mL by day 7. Cyclosporine was dosed aiming at a C2 blood level of 350 to 700 ng/mL in the first week and 150 to 400 ng/mL thereafter. All patients received induction with basiliximab and maintenance treatment with corticosteroids.

Results

At 6-months follow-up, patient survival rates (TAC 100% vs EVL 100%) and graft survival rates (TAC 96.7% vs EVL 93.3%) were not significantly different between the groups. Patients in the EVL group showed more acute rejection episodes, but serum creatinine concentrations and creatinine clearances were not significantly different from the TAC group. Among the observed side effects, hypercholesterolemia was significantly higher in the EVL group (total cholesterol: TAC 206 ± 38 vs EVL 250 ± 55 mg/dL; P < .003).

Conclusions

This study showed that the immunosuppressive association of tacrolimus and MMF produced similar acute rejection episodes, graft survivals, and renal function at 6 months after renal transplantation compared with an immunosuppressive combination of everolimus and low-dose cyclosporine. Dyslipidemia was significantly greater among patients who received everolimus.     

Use of simulect can reduce the incidence of acute rejection and demonstrates with superior 3-year patient and graft survival rates in renal transplantation

Background

Acute rejection is a major cause of graft loss in renal transplantation. Because the highest risk for acute rejection is in the first month posttransplantation, improved prophylaxis could be most beneficial in this period. Simulect administration provides 30 to 45 days of immunoprophylaxis against acute rejection during the critical period after transplantation.

Objectives

We sought to assess the incidence of acute rejection episodes and the safety and tolerability of Simulect plus Neoral immunosuppression. Patient and graft survival rates up to 3 years posttransplantation were evaluated.

Method

Forty-one transplant recipients received Simulect by intravenous infusion of an initial 20-mg dose on the day of renal transplantation and a second 20-mg dose on day 4 posttransplant. All renal recipients received immunosuppression with Neoral and steroid.

Results

There were eight cases (19.5%) of acute rejection within 1 year. The rejection episodes were easily reversed with steroid pulse therapy in seven patients except for graft loss. The 1-, 2-, and 3-year graft survival rates were 95%, 93%, and 88%, respectively. Overall, the 3-year patient survival rate was 100%.

Conclusions

Simulect in combination with Neoral and steroid-reduced the incidence of acute rejection without an increase in adverse events. The low incidence and severity of acute rejection may have led to the superior 3-year patient and graft survival rates in renal transplantation.     

Relationship Between Platelet Activation and Acute Rejection After Renal Transplantation

Objective

To provide an earlier diagnosis and efficiently treat acute rejection episodes (ARE) after renal transplantation, we studied its relationship to platelet activation.

Patients and Methods

The peripheral blood levels of platelet surface glycoprotein (CD61), platelet activation-dependent granule membrane protein (CD62p), lysosomal enzyme glycoprotein (CD63), macula densa granule membrane glycoprotein (CD42a), and fibrinogen receptor monoclonal antibody (PAC-1) among 203 patients with uremia in various stages before and after transplantation were assayed by flow cytometry. The patients with ARE were prospectively and randomly assigned to either a treatment group with an antiplatelet activation agent or a control group.

Results

The incidence of ARE was remarkably increased among patients with greater expression levels of platelet activation markers in peripheral blood preoperatively. The values of platelet activation markers were significantly higher among patients with ARE compared with those showing either normal graft function or acute tubular necrosis. The greater the increase in CD63, the worse the ARE. The expression levels of platelet activation markers decreased remarkably among the group treated with a platelet activation inhibitor in addition to antirejection therapy: the rejection reversal time shortened and the dose of antihuman thymocyte globulin (ATG) was lower. The sensitivity of platelet activation markers was better than its specificity.

Conclusions

Our studies demonstrated an association between platelet activation and ARE after renal transplantation. Platelet activation before transplantation can predict the occurrence of ARE. Platelet activation inhibitor therapy after transplantation improved ARE reversal.     

Efficacy, Tolerance, and Safety of Mammalian Target of Rapamycin Inhibitors as Rescue Immunosuppressants in Liver Transplantation

Background

Mammalian target of rapamycin (mTOR) inhibitors behave as potent immunosuppressants which have the advantages, with respect to calcineurin inhibitors (CNI: cyclosporine or tacrolimus), of no nephrotoxicity and inhibition of cell proliferation. They are particularly suitable for patients with renal insufficiency or neoplasias.

Materials and Methods

Twenty-two liver transplant patients were immunosuppressed with everolimus or sirolimus as rescue therapy after CNI treatment: 7 hepatocellular carcinomas; 5 de novo malignancies; 4 renal insufficiencies; 4 chronic rejections; and 2 acute rejection episodes.

Results

There were 16.7% tumor recurrences, and 25% improvements in renal function, 75% in chronic rejection, and 50% in acute rejection. There was no incidence of rejection, kidney failure, gastrointestinal intolerance, hydrocarbon intolerance, hypertension, or arterial or venous thrombosis. We observed incidences of 50% for hypercholesterolemia, 31.8% for hypertriglyceridemia, 22.7% for thrombocytopenia, 18.2% for leukopenia, and 9.1% for anemia. The intercurrent infection rate was 13.6%, including oral thrush in 13.6%. Lower limb edema occurred in 13.6%, with 1 case of facial edema and 1 of alopecia.

Conclusions

mTOR inhibitors were safe immunosuppressive drugs whose side effects were controlled and easily managed. They have advantages with respect to CNI due to their slight effects on kidney function and lack of promotion of diabetes mellitus. Although their long-term effectiveness for control of neoplastic diseases is yet to be seen, they can be used safely in these patients with no incidence of rejection. Their effectiveness to control chronic rejection seems significant, but it is doubtful for steroid-resistant acute rejection episodes.     

Disturbances of kidney graft perfusion as indicators of acute renal vein thrombosis in contrast-enhanced ultrasonography

Introduction

The aim of this study was to evaluate the usefulness of contrast-enhanced ultrasound (US-CE) to diagnose acute renal vein thrombosis (ARVT), acute rejection episodes (ARE), or acute tubular necrosis (ATN) in kidney grafts.

Materials and methods

We analyzed 171 US-CE among kidney transplantation patients in the early postoperative period. Patients underwent US-CE following a standard diagnostic protocol including real-time ultrasound (B-mode) and color Doppler ultrasound with spectral flow analysis. Tissue perfusion was analyzed based upon time-intensity curves for two regions: the renal cortex and the renal pyramids.

Results

Of 14 patients, in whom standard ultrasound showed high resistance parameters in the renal artery, three showed ARVT and 11 had ATN or ARE, which were confirmed by biopsy. Among patients with ARVT, the US-CE showed a lack of contrast perfusion into the cortex and renal pyramids. Patients with ARE/ATN showed slower contrast inflow into the parenchyma with reduced but still present perfusion. The differences in mean signal intensity values were significant for both the cortex and the renal pyramids: cortex: −53.8 ± 5.4 dB versus −35.0 ± 3.5 dB (P < .05) and pyramids: −54.8 ± 5.4 dB versus −37.0 ± 3.5 dB (P < .05).

Conclusion

US-CE is a noninvasive method that provides easy, reliable differentiation of ARVT from ARE/ATN.     

Tacrolimus Versus Cyclosporine for Adult Lung Transplant Recipients: A Meta-Analysis

Background

Tacrolimus and cyclosporine are the 2 major immunosuppressants for lung transplantation. Several studies have compared these 2 drugs, but the outcomes were not consistent. The aim of this meta-analysis of randomized controlled trials (RCTs) was to compare the beneficial and harmful effects of tacrolimus and cyclosporine as the primary immunosuppressant for lung transplant recipients.

Methods

We conducted searches of electronic databases and manual bibliographies. We performed a meta-analysis of all RCTs comparing tacrolimus with cyclosporine as primary immunosuppression for lung transplant recipients. Extracted, pooled data for mortality, acute rejection, withdrawals, and adverse events were analyzed using Mantel-Haenszel tests with a random effects model.

Results

Three RCTs including 297 patients were assessed in this study. Mortality at 1 year or more was comparable between lung recipients treated with tacrolimus and cyclosporine (odds ratio [OR], 0.94; 95% confidence interval [CI], 0.42-2.10; P = .88). Tacrolimus-treated patients experienced fewer incidences of acute rejection (MD = −0.14; 95% CI, −0.28 to −0.01; P = .04). Pooled analysis showed a trend toward a lower risk of bronchiolitis obliterans syndrome (BOS) among tacrolimus-treated patients, although it did not reach significances (OR, 0.53; 95% CI, 0.25-1.12; P = .10). Fewer patients stopped tacrolimus than cyclosporine (OR, 0.12; 95% CI, 0.03-0.48; P = .003). The rate of new-onset diabetes was higher among the tacrolimus group (OR, 3.69; 95% CI, 1.17-11.62; P = .03). The incidence of hypertension and renal dysfunction were comparable in these 2 groups (OR, 0.24; 95% CI, 0.03-1.70; P = .15; and OR, 1.67; 95% CI, 0.70-3.96; P = .25, respectively). There was a trend toward lower risk of malignancy in tacrolimus-treated patients, although it did not reach significance either (OR, 0.19; 95% CI, 0.03-1.13; P = .07). The incidence of infection was comparable in these 2 groups (MD = −0.29, 95% CI, −0.68 to 0.11; P = .16).

Conclusion

Using tacrolimus as primary immunosuppressant for lung transplant recipient resulted in comparable survival and reduction in acute rejection episodes when compared with cyclosporine.     

De novo anti-HLA antibodies in renal allograft recipients: a cross-section study

Background

The occurrence of anti-HLA antibodies plays a well established role in solid organ rejection. The development of x-MAP multiple bead technology (Luminex) has enabled more accurate detection and definition of these alloantibodies.

Methods

In 267 kidney transplant patients with stable allograft function for ≥3 years, we analyzed the presence of anti-HLA antibodies by Luminex technology. These patients had no alloantibodies before transplantation, and the immunosuppression treatment was: tacrolimus, cyclosporine, mycophenolate mofetil, prednisone, everolimus, and/or sirolimus.

Results

Fifteen of the 267 patients showed anti-HLA class I antibodies and 12 showed anti-HLA class II antibodies, Seven patients had donor-specific antibodies (DSA): 1 anti-HLA class I, 5 anti-HLA class II, and 1 with both classes. No differences were found between DSA and the use or not of any specific therapy. However, in the retrospective review, we found a higher incidence of acute rejection episodes in the immediate posttransplant period among patients who developed class II DSA than those without DSA.

Conclusions

The prevalence of patients with normal renal function who develop DSA beyond 3 years after transplantation was relatively low. Steroid or withdrawal replacement of calcineurin inhibitors with inhibitors of mammalian target of rapamycin seem to not be risk factors to increase the development of DSA. The finding that patients who developed DSA showed a higher rate of previous acute rejection episodes suggested that they should be monitored more frequently for HLA antibodies.     

Infectious Complications After Deceased Kidney Donor Transplantation

Background

Despite improvements in immunosuppressive therapy, infections remain a complication of renal transplantation that is associated with increased morbidity and graft rejection. The aim of this study was to evaluate the relationship between initial renal function after deceased donor transplantation and viral infections.

Methods

We included patients 18 years and older who received a deceased donor transplantation between January 1995 and December 2004. They were divided into 2 groups: cases from 1994 to 1999, versus from 2000 to 2004. Initial renal function was classified as immediate (IGF), slow (SGF), or delayed (DGF). Infections were classified according to Centers for Disease Control and prevention standards.

Results

Among 534 patients, SGF and DGF patients who underwent immunosuppression between 2000 and 2004 show a higher infection rate than IGF patients (P = .005). SGF patients showed a higher incidence of tissue-invasive cytomegalovirus disease (P < .001). Second episodes of viral infections were more common among all patients in this period. However, DGF patients were more susceptible to second episodes of viral infection. In the first group, OKT3 use (P = .013) and donor age (P = .012) were the major risk factors associated with viral infections whereas in the second group, thymoglobulin use (P = .002), acute rejection episode (P = .003), and anemia (P = .044) were the risk factors for viral infection.

Conclusion

Initial renal function after deceased donor transplantation was correlated with viral infection. DGF patients had a higher risk for second infection episodes. SGF patients had a higher risk for tissue-invasive cytomegalovirus infection.     

Hyperuricemia after renal transplantation

Background

Hyperuricemia is a common complication after kidney transplantation, and may adversely affect graft survival.

Objective

To assess the prevalence of and predictors for development of hyperuricemia after renal transplantation.

Materials and Methods

Hyperuricemia was defined as a serum uric acid concentration of at least 7.0 mg/dL in men and 6.0 mg/dL in women. From March 2008 to May 2010, uric acid concentration was measured in 12,767 blood samples from 2961 adult renal transplant recipients (64% male and 36% female patients).

Results

Hyperuricemia was observed in 1553 patients (52.4%). The disorder frequently occurred in women (P = .003) and in patients with impaired renal graft function (P = .00). After adjustment for sex, serum creatinine concentration, diabetes mellitus, cyclosporine concentration, and dyslipidemia, only female sex (P = .03) and renal allograft dysfunction (P = .05) were associated with hyperuricemia after kidney transplantation.

Conclusion

Hyperuricemia is a common complication after kidney transplantation, and renal allograft insufficiency predisposes to higher uric acid concentration.     

Outcome of renal transplantation in Alport's syndrome: a single-center experience

Background

Anti-glomerular basement membrane (anti-GBM) nephritis post-renal transplantation (RTx) is known to cause graft loss in Alport's syndrome (AS). We evaluated the results of RTx in AS patients vis à vis patient and graft survivals, incidence of anti-GBM nephritis, and causes of graft failure.

Materials and methods

Between 1993 and 2009 we performed 31 RTx on AS patients (28 males and three females) of overall mean age of 22 ± 7.9 years from six deceased and 27 living donors. Two patients underwent second RTx.

Results

Over a follow-up of 1, 3, 5, and 10 years, the mean serum creatinines (mg/dL) were 1.51 ± 0.52, 1.59 ± 0.26, 1.61 ± 0.30, and 1.63 ± 0.32, respectively. Patient survivals at 1, 5, and 10 years were 89.71%, 81.32% and 81.32% with graft survival for all periods of 81.2%. Twenty-one percent experienced biopsy-proven acute rejection episodes. Graft failures were due to anti-GBM nephritis in 12.2% (n = 4), chronic allograft nephropathy in 3.2% (n = 1), and acute rejection or cyclosporine toxicity 3.2% (n = 1 each). The mean duration to graft loss was 4.9 ± 2.4 months.

Conclusion

Graft and patient survivals were acceptable among transplant recipients with AS despite the risk of anti-GBM nephritis.     

Efficacy and Safety of Mycophenolate Mofetil Monotherapy in Liver Transplant Patients With Renal Failure Induced by Calcineurin Inhibitors

Objective

To assess the efficacy and safety of mycophenolate mofetil (MMF) monotherapy in liver transplant recipients with renal failure secondary to the use of calcineurin inhibitors (CNIs).

Materials and methods

Thirty-one patients on MMF monotherapy with creatinine levels >1.3 mg/dL, previously immunosuppressed with CNIs and MMF, were analyzed. Conversion was started in patients with no acute or chronic rejection episodes and stable liver chemistry. CNI doses were reduced by 25% every 2 to 3 months, or to 50% if the dose was lower than 1 mg/d of tacrolimus or 50 mg/d of cyclosporine. Different variables were recorded from the time that conversion to monotherapy was decided, on the discontinuation day of the calcineurin inhibitor, and during the follow-up.

Results

Mean times from transplant to conversion ranged from 14 to 186 months. The minimum follow-up time in monotherapy was 12 months. Renal function improved at 6 months in 70% of cases and at 12 months in 69.6%. Patients with no renal function improvement maintained stable creatinine values. There were no rejection episodes, graft losses, or deaths. No leukopenia occurred, and triglyceride and uric acid values improved.

Conclusions

MMF monotherapy is a safe alternative in patients with posttransplant renal failure secondary to the use of CNIs. Renal function improvement was achieved in almost 70% of patients at 12 months, and creatinine values were maintained in all other patients. The risk of rejection due to the slow tapering of CNIs is minimum.     

XM-ONE detection of endothelium cell antibodies identifies a subgroup of HLA-antibody negative patients undergoing acute rejection

Background

Kidney transplant recipients exhibiting antibodies (Ab) against either HLA or non-HLA antigens undergo frequent episodes of rejection and exhibit decreased long-term graft survival. The novel flow cytometry crossmatch kit XM-ONE, detects Abs to HLA antigens plus those directed to Tie-2-positive precursor endothelial cells (anti-endothelial cell antibodies, AECA). We studied the clinical importance of these lesser known antibodies.

Methods

We retrospectively analyzed 208 sera from 160 recipients of deceased donor grafts for AECA using non-donor peripheral blood endothelial progenitor cells as targets and Luminex methodology for HLA antibodies.

Results

AECA were detected in 64 patients (40%). A significantly higher proportion of patients showing a positive endothelial crossmatch experienced rejection (31 AECA-positive among 43 rejection cases, 72%) compared with those without rejection (33/117, 28.2%). Immunoglobulin M(IgM) predominated (66%) over IgG (14%) and IgG plus IgM (20%). HLA antibodies positively and significantly associated with rejection as expected. Of special interest were the 19 patients who presented with acute rejection episodes along with restricted AECA positivity. The relative-risk for an acute rejection episode with either AECA or HLA—13.87 and 2.43, respectively—was significant. When HLA was already positive, the relative risk for AECA was 1.24, a non-significant increase.

Conclusions

Our data identified AECA-positive patients that showed an increased risk to develop an acute rejection episode early after transplantation. Moreover, restricted AECA-positive patients with acute rejection are an important subgroup which otherwise may be wrongly labeled as non-humoral rejection. Among HLA-negative cases, AECA conferred a significantly greater risk for rejection.     

Serum levels of interleukin-9 during acute rejection in liver transplantation

Introduction

Interleukin-9 (IL-9) has been cast as a player in autoimmunity, but its role in liver transplantation remains to be clarified. The aim of our study was to investigate the time course of IL-9 serum levels during hepatic allograft rejection.

Methods

IL-9 serum levels were determined in 34 healthy subjects and 50 hepatic transplant recipients. The patients were divided into two groups: group I was composed of 15 patients with acute rejection episodes, and group II, 35 patients free of this problem. Samples were collected on days 1 and 7 after liver transplantation and on the day of liver biopsy.

Results

The concentrations of IL-9 were similar in the rejection and nonrejection groups over the entire postoperative period. The whole transplant group, including those with stable graft function, showed higher IL-9 serum levels than the controls at all times after liver transplantation.

Conclusions

These preliminary results suggest a lack of participation of IL-9 in human liver allograft rejection.     

Combined Heart and Kidney Transplantation: Long-Term Analysis of Renal Function and Major Adverse Events at 20 Years

Background

Combined heart-kidney transplantation (HKTx) is an accepted therapeutic option for patients with end-stage heart disease associated with severely impaired renal function. We report our long-term follow-up with this combined procedure.

Patients and methods

Between April 1989 to November 2009, nine patients underwent combined simultaneous (HKTx) at our center. Seven patients were males (mean age 45.2 ± 10.12 years); seven patients were on dialysis at the time of transplantation.

Results

Surgical procedures were uneventful in all patients. One patient died in the intensive care unit 41 days after transplantation. During long-term follow-up, three patients died: one due to infection and multiorgan failure 148 months after HKTx, one due to a lung neoplasm after 6 years, and one, a cerebral stroke at 34 months after transplantation. Only one patient experience renal allograft failure secondary to hypertension and cyclosporine nephrotoxicity at 10 years after HKTx with the need for renal replacement therapy. Last estimated glomerular filtration rates of all other patients was 61.3 ± 17.4 mL/min.

Conclusions

In selected patients, with coexisting end-stage cardiac and renal failure, combined HKTx with an allograft from the same donor proved to give satisfactory short- and long-term results, with a low incidence of both cardiac and renal allograft complications.