Mario Vilatobá

Probability of deceased donor kidney transplantation based on % PRA

UNLABELLED Sensitization to HLA antigens creates an obstacle for the accessibility and success of kidney transplantation (KT). Highly sensitized patients have longer waiting times and some may never receive a KT. AIM To determine the probability of patients on the deceased donor (DD) waiting list to receive a KT based on the panel reactive antibody percentage (% PRA) in our center. METHODS The DD waiting list from our institution was analyzed from 01/05 to 08/12 documenting the clinical variables from donor and potential recipients (ABO blood group), lymphocyte cross-match [CxM (CDC-AHG)] results, highest % PRA determination, and time on the waiting list. The patients were classified into 4 groups based on the % PRA: 0%, 1-19%, 20-79% and 80-100%. The data was analyzed using odds ratio and logistic regression (significant p<0.05). RESULTS 58 DD (F:M 34:24, ABO group O=35, A=13, B=10) and 179 potential recipients were analyzed (F:M 98:81, ABO group O=127, A=33, B=19, participating 4.2 ± 3.8 times with different donors to receive KT). The mean PRA for the whole group was 22 ± 32%, median [md] 0 (0-98). A total of 100 patients received KT (mean waiting time 2.2 ± 1.7 years, 12 days-7 years) and their mean % PRA was 11.6 ± 24, md 0 (0-94) vs. 31.4 ± 37 md 8.5 (0-98) in those who have not received a KT. An association between the % PRA group and KT (p<0.003) was observed. The probability of receiving KT with a 0% PRA vs. >0% was higher (OR 2.12, 1.17-3.84). There was no difference between the 0% vs. 1-19% group (OR 1); differences were observed between 0% vs. 20-79% (OR 2.5, 1.18-5.3) and 0% vs. 80-100% (OR 5, 1.67-14.9). For every percent increase in the PRA above 20%, the risk of not receiving a KT increased by 5% (1-9, p<0.01). CONCLUSIONS The probability of receiving a DD kidney transplant is inversely related to the % PRA although a higher risk for not receiving a KT becomes evident with a PRA >20%.

Renal Grafts With Multiple Arteries: A Relative Contraindication for a Renal Transplant?

INTRODUCTION Advances in surgical techniques had achieved good outcomes in renal transplantation. There has been controversy with respect to the impact of multiple arteries on the outcome of the renal transplantations. OBJECTIVES The objectives of this study were to examine the renal function and incidence of complications among grafts with one versus two or more arteries. MATERIALS AND METHODS We evaluated 86 patients with renal transplantations between January 2006 and January 2008 as a retrospective comparative study. The patients were stratified according to the number of renal graft arteries: group 1 had one artery (n = 66); group 2, two or more arteries (n = 16). RESULTS The warm ischemia time was shorter among group 1 compared with group 2 (P < .03). There were significant differences between the groups with respect to mean blood pressure at 1 year (P < .04). The kidney biopsies after 1-year follow-up did not show any difference. CONCLUSION We considered that the presence of anatomic variations was not a contraindication for renal transplantation, but that it is necessary to continue our follow-up to determine the real impact of these variations on graft and patient survivals.

Iatrogenic bile duct injury with loss of confluence.

AIM To describe our experience concerning the surgical treatment of Strasberg E-4 (Bismuth IV) bile duct injuries. METHODS In an 18-year period, among 603 patients referred to our hospital for surgical treatment of complex bile duct injuries, 53 presented involvement of the hilar confluence classified as Strasberg E4 injuries. Imagenological studies, mainly magnetic resonance imaging showed a loss of confluence. The files of these patients were analyzed and general data were recorded, including type of operation and postoperative outcome with emphasis on postoperative cholangitis, liver function test and quality of life. The mean time of follow-up was of 55.9 ± 52.9 mo (median = 38.5, minimum = 2, maximum = 181.2). All other patients with Strasberg A, B, C, D, E1, E2, E3, or E5 biliary injuries were excluded from this study. RESULTS Patients were divided in three groups: G1 (n = 21): Construction of neoconfluence + Roux-en-Y hepatojejunostomy. G2 (n = 26): Roux-en-Y portoenterostomy. G3 (n = 6): Double (right and left) Roux-en-Y hepatojejunostomy. Cholangitis was recorded in two patients in group 1, in 14 patients in group 2, and in one patient in group 3. All of them required transhepatic instrumentation of the anastomosis and six patients needed live transplantation. CONCLUSION Loss of confluence represents a surgical challenge. There are several treatment options at different stages. Roux-en-Y bilioenteric anastomosis (neoconfluence, double-barrel anastomosis, portoenterostomy) is the treatment of choice, and when it is technically possible, building of a neoconfluence has better outcomes. When liver cirrhosis is shown, liver transplantation is the best choice.

New immunosuppressive strategies in liver transplantation: balancing efficacy and toxicity

Major advancements have been made in the past decade with regard to immunosuppressive therapy in liver transplant recipients. Experimental and clinical evidence suggests that the liver is an immunologically privileged organ, and an episode of acute rejection does not appear to have a negative impact on patient or graft survival. Today, the most pressing issue related to immunosuppression therapy in liver transplantation is minimizing toxicity, the incidence and severity of recurrent disease, and avoiding cardiovascular and cancer risk. Studies have identified a number of factors that have been associated with acute rejection, and similarly a number of factors have been associated with an increased risk of and severity of recurrent disease. Therefore, tailoring immunosuppression to the individual patient should become more popular, particular as it relates to patients with hepatitis C virus. This review aims to highlight the evolving trends in immunosuppressive therapy in liver transplantation.

Pretransplant angiotensin II type 1-receptor antibodies are a risk factor for earlier detection of de novo HLA donor-specific antibodies

BACKGROUND Angiotensin II type 1 receptor antibodies (AT1Rabs) have been associated with significantly reduced graft survival. Earlier graft loss has been observed in patients who had pretransplant AT1Rabs and posttransplant donor-specific antibodies (DSA). METHODS The main goal of this retrospective cohort study was to examine the association between AT1Rabs and the time period to detection of de novo human leukocyte antigen (HLA-DSA) posttransplantation in living donor kidney transplant recipients (KTR). The analysis included 141 KTRs. Pretransplant frozen serum samples were tested for AT1Rabs by ELISA and HLA-DSA by SAB (Luminex) at both the pre- and post-KT time points. RESULTS The median AT1Rab level was 9.13 U (interquartile range 5.22-14.33). After a mean follow-up period of 3.55 years, 48 patients were found to harbour de novo HLA-DSAs. The presence of AT1Rabs [hazard ratio (HR) 1.009, 95% confidence interval (CI) 1.002-1.01, P = 0.010], male-to-male transplantation (HR 2.57, 95% CI 1.42-4.67, P = 0.002) and antecedent borderline changes or acute cellular rejection (ACR) (HR 2.47, 95% CI 1.29-4.75, P = 0.006) were significantly associated with de novo DSA detection. A dose-dependent association between AT1Rab levels (<10 U, 10.1-16.9 U, 17-29.9 U and >30 U) and de novo DSA detection was observed (log-rank P = 0.0031). After multivariate analysis of AT1Rab levels (continuous variable), AT1Rabs >30 U, male-to-male transplantation, donor age, higher class I percentage of Panel Reactive Antibody and antecedent borderline changes or ACR remained as independent significant risk factors for the detection of de novo DSAs. CONCLUSIONS The findings suggest that higher levels of pretransplant circulating antibodies against AT1R (>30 U) in kidney graft recipients constitute an independent risk factor for earlier de novo HLA-DSA detection during the posttransplant period.

Improved reduction in pain in chronic pancreatitis with combined intraoperative celiac axis plexus block and lateral pancreaticojejunostomy.

PURPOSE:Severe abdominal pain secondary to chronic pancreatitis is often multifactorial in origin. Lateral pancreaticojejunostomy (LPJ) is currently the accepted surgical treatment of choice when the main pancreatic duct is dilated. Chemical ablation of the celiac plexus for the treatment of intractable pain in chronic pancreatitis has been used without clear benefit. The aim of this study is to compare treatment outcomes of 2 groups of patients with the diagnosis of chronic pancreatitis and intractable abdominal pain (LPJ alone versus LPJ with intraoperative alcohol celiac ablation).Between 1994 and 1997, 34 patients underwent LPJ to control intractable pain secondary to chronic pancreatitis. These patients were divided into 2 groups, group 1 was LPJ only (16 patients) and group 2 was LPJ and intraoperative celiac ablation with 50% absolute alcohol (18 patients). Preoperative diagnosis and treatment criteria were similar for both groups. The clinical characteristics and outcome of both groups were retrospectively analyzed. Fisher exact test was used for statistical analysis.Demographic characteristics were similar in both groups. Pain control at short- and long-term follow-up was significantly improved in group 2 compared with group 1 (p < 0.035).Intraoperative celiac ablation in addition to LPJ appears to have a better response than does LPJ alone. Even though the number of patients is small, these results provide a basis for pursuing a prospective, randomized study to definitively answer this question.

Tacrolimus Trough Levels as a Risk Factor for Acute Rejection in Renal Transplant Patients.

BACKGROUND Use of tacrolimus (TAC) is pivotal to renal transplant (RT) immunosuppressive maintenance regimens. The aim of this study was to evaluate the relationship between TAC trough levels and the development of acute rejection (AR). MATERIAL AND METHODS This was a retrospective cohort study. We included recipients transplanted between 01/2008 and 05/2012. Regression analyses (Coxs proportional hazards model) and sub-analysis of AR and TAC levels over different time periods were performed. RESULTS We included 198 patients with an average age of 32 years (±12.1) and predominantly male (54.5%). Mean follow-up was 2 years (min-max 15d - 5.2yrs). Sixty-two AR events were documented (BL: 31, Cellular AR: 19, Humoral AR: 12). We found that TAC levels (HR 0.76, 0.65-0.88, p<0.001), a high risk for CMV infection (D+/R-) (HR 2.92, 1.47-1.014, p=0.002), pre-transplant donor-specific HLA antibodies (DSA) (HR 3.04 1.29-7.16, p=0.011), and post-RT DSA (HR 2.4, 1.16-4.9, p=0.018) were significantly associated with AR. The relationship between TAC levels and rejection was independent of follow-up duration. CONCLUSIONS In this analysis, TAC though levels were directly related to AR events; trough levels >8 ng/ml were the most effective in decreasing immunological adverse events. A decrease in TAC levels throughout the post-transplant follow-up period should be considered due to its possible association with AR events.

C1Q Assay Results in Complement-Dependent Cytotoxicity Crossmatch Negative Renal Transplant Candidates with Donor-Specific Antibodies: High Specificity but Low Sensitivity When Predicting Flow Crossmatch.

The aim of the present study was to describe the association of positive flow cross match (FXM) and C1q-SAB. Methods. In this observational, cross-sectional, and comparative study, patients included had negative AHG-CDC-XM and donor specific antibodies (DSA) and were tested with FXM. All pretransplant sera were tested with C1q-SAB assay. Results. A total of 50 donor/recipient evaluations were conducted; half of them had at least one C1q+ Ab (n = 26, 52%). Ten patients (20.0%) had DSA C1q+ Ab. Twenty-five (50%) FXMs were positive. Factors associated with a positive FXM were the presence of C1q+ Ab (DSA C1q+ Ab: OR 27, 2.80–259.56, P = 0.004, and no DSA C1q+ Ab: OR 5, 1.27–19.68, P = 0.021) and the DSA LABScreen-SAB MFI (OR 1.26, 95% CI 1.06–1.49, P = 0.007). The cutoff point of immunodominant LABScreen SAB DSA-MFI with the greatest sensitivity and specificity to predict FXM was 2,300 (sensitivity: 72% and specificity: 75%). For FXM prediction, DSA C1q+ Ab was the most specific (95.8%, 85–100) and the combination of DSA-MFI > 2,300 and C1q+ Ab was the most sensitive (92.0%, 79.3–100). Conclusions. C1q+ Ab and LABScreen SAB DSA-MFI were significantly associated with FXM. DSA C1q+ Ab was highly specific but with low sensitivity.

Anti-HLA-DQ antibodies are highly and independently related to the C1q-binding capacity of HLA antibodies

The complement-binding capacity of anti-HLA antibodies (HLAabs) is recognized as a key pathogenic factor. The aim of this study is to describe the patient characteristics associated to the presence of C1q+ as well as those of the Abs per se when associated to C1q binding. METHODOLOGY This is a cross-sectional, observational, descriptive study of patients with previous sensitizing factors and awaiting a kidney transplant (KT). We determined anti-HLA antibodies and their C1q binding capacity with the C1q assay. RESULTS Among the 55 included patients, 26 (47.2%) had at least one C1q+ anti-HLAab. A previous transplant history, a greater number of HLAabs, a greater % of class I or class II PRA, the average MFI of all HLAabs, the MFI of the dominant HLAab and the HLAab antigenic specificities against HLA-B, -C and -DQ, all proved to be risk factors associated to the presence of C1q binding HLAabs (C1q+). In the total population, were detected 1268 HLAabs, 230 (18.1%) of which were C1q+. On multivariate analysis, both HLAabs against the HLA-DQ antigenic specificity (OR 9.82 95% CI 5.4-17.6, p<0.001) and the MFI documented by LABScreen®SAB (OR 1.2% CI 1.22-1.3, p<0.001), proved to be risk factors. CONCLUSION Anti-HLA-DQ antibodies and the MFI (LABScreen®SAB) are highly and independently related to the C1q-binding capacity of HLA antibodies.

Graft immunologic events in deceased donor kidney transplant recipients with preformed HLA-donor specific antibodies

INTRODUCTION Pretransplant donor-specific HLA alloantibodies detected with the Single Antigen Bead (SAB) assay reflect an increased risk for acute antibody-mediated rejection (AMR). We herein report the incidence of both acute AMR and acute cellular rejection (ACR) during the first year posttransplantation, in a cohort of kidney transplant recipients (KTR) of deceased donor (DD) grafts, according to their DSA status. Pretransplant DSA do not preclude DD-KT in negative CDC-XM recipients at our center. PATIENTS AND METHODS 246 KT were performed at our center between 01/2012 and 12/2015 and 100 KTR obtained from a DD were analyzed; 24% harbored DSA by SAB assay, MFI values >500 were considered positive. All recipients received thymoglobulin induction and generic tacrolimus-based maintenance therapy. Graft biopsies were performed by protocol on months 3 and 12 as well as per indication. The incidence of AMR and ACR was correlated with the existence of pretransplant DSA. RESULTS Overall, 34% of patients developed an acute rejection episode, 54.2% in the DSA group versus 27.6% in the non-DSA group (p=0.032), and most of these events were detected as subclinical conditions in protocol biopsies. AMR events developed in 33.3% and 19.7% (p=0.176) in the DSA and the non-DSA groups, respectively. ACR events were found in 16.6% and 6.6% (p=0.127) in the DSA and non-DSA groups, respectively. Graft function was similar between groups at the end of the 1st year posttransplant and no immunological graft loss occurred. CONCLUSION Despite the use of depleting induction therapy and adequate tacrolimus trough levels along with MMF and steroids, a high rate of rejection events was observed during the first year post-transplantation.