Unveiling APOL1 haplotypes in a predominantly African-American cohort of kidney transplant patients: a novel classification using probe-independent quantitative real-time PCR.

Introduction: Apolipoprotein-L1 (APOL1) is a primate-specific protein component of high-density lipoprotein (HDL). Two variants of APOL1 (G1 and G2), provide resistance to parasitic infections in African Americans but are also implicated in kidney-related diseases and transplant outcomes in recipients. This study aims to identify these risk variants using a novel probe-independent quantitative real-time PCR method in a high African American recipient cohort. Additionally, it aims to develop a new stratification approach based on a haplotype-centric model. Methods: Genomic DNA was extracted from recipient PBMCs using SDS lysis buffer and proteinase K. A quantitative PCR assay with modified forward primers and a common reverse primer enabled us to quantitatively identify single nucleotide polymorphisms (SNPs) and the 6-bp deletion. Additionally, we used Sanger sequencing to verify our QPCR findings. Results: Our novel probe-independent qPCR effectively distinguished homozygous wild-type, heterozygous SNPs/deletions, and homozygous SNPs/deletions, with at least 4-fold differences. A high prevalence of APOL1 variants was observed (18% two-risk alleles, 34% one-risk allele) in our recipient cohort. Intriguingly, no significant impact of recipient APOL1 variants on transplant outcomes was observed up to 12-month of follow-ups. Ongoing research will encompass more time points and a larger patient cohort, allowing for a comprehensive evaluation of G1/G2 variant subgroups categorized by new haplotype scores, enriching our understanding. Conclusion: Our cost-effective and rapid qPCR technique facilitates APOL1 genotyping within hours. Prospective and retrospective studies will enable comparisons with long-term allograft rejection, potentially predicting early/late-stage transplant outcomes based on haplotype evaluation in this diverse group of kidney transplant recipients.

A report of a prospective randomized trial of extended-release tacrolimus versus immediate release tacrolimus after liver transplantation with anti-thymocyte induction in a steroid free protocol.

PURPOSE: Our study hypothesis was that once daily dosing of extended-release tacrolimus (XRT) would be a safe and effective immunosuppression (IS) with the potential to decrease adverse events (AEs) associated with immediate release tacrolimus (IRT) after liver transplantation (LT). METHODS: All patients receiving LT at our center received rabbit anti-thymocyte globulin (RATG) induction therapy. Eligible patients were randomized in a 1:1 fashion to receive either XRT or IRT. Antimicrobial prophylaxis was the same between arms, and both groups received an antimetabolite for the first 6 months following LT. Patients were then followed at pre-determined study intervals for the following year after LT. We administered the RAND-36SF survey to assess patient's health-related quality of life at pre-determined intervals. All analysis was performed with an intention to treat basis. RESULTS: We screened 194 consecutive patients and enrolled 110. Our control and study arms were well matched. Transplant characteristics were similar between groups. At all timepoints, both arms had similar serum creatinine and estimated glomerular filtration rate (eGFR), calculated by MDRD6 equation, with post-transplant GFRs between 60 and 70 mL/min/1.73 m2 . Tacrolimus trough levels were similar between arms. The XRT arm had fewer AEs (166) and fewer serious AEs (70) compared to IRT (201 and 99, respectively). AEs most commonly were renal, infectious, or gastrointestinal in nature. While not statistically significant, XRT was held temporarily (25 vs. 35 cases) or discontinued (3 vs. 11 cases) less frequently than IRT and had fewer instances of rejection (7 vs. 12 cases). CONCLUSION: This analysis showed that XRT is safe and effective as de novo maintenance IS in a steroid-free protocol with RATG.

Unveiling APOL1 Haplotypes: A Novel Classification Through Probe-Independent Quantitative Real-Time PCR.

Introduction: Apolipoprotein-L1 (APOL1) is a primate-specific protein component of high- density lipoprotein (HDL). Two variants of APOL1 (G1 and G2), provide resistance to parasitic infections in African Americans but are also implicated in kidney-related diseases and transplant outcomes in recipients. This study aims to identify these risk variants using a novel probe- independent quantitative real-time PCR method in a high African American recipient cohort. Additionally, it aims to develop a new stratification approach based on haplotype-centric model. Methods: Genomic DNA was extracted from recipient PBMCs using SDS lysis buffer and proteinase K. Quantitative PCR assay with modified forward primers and a common reverse primer enabled us to identify single nucleotide polymorphisms (SNPs) and the 6-bp deletion quantitatively. Additionally, we used sanger sequencing to verify our QPCR findings. Results: Our novel probe-independent qPCR effectively distinguished homozygous wild-type, heterozygous SNPs/deletion, and homozygous SNPs/deletion, with at least 4-fold differences. High prevalence of APOL1 variants was observed (18% two-risk alleles, 34% one-risk allele) in our recipient cohort. Intriguingly, up to 12-month follow-up revealed no significant impact of recipient APOL1 variants on transplant outcomes. Ongoing research will encompass more time points and a larger patient cohort, allowing a comprehensive evaluation of G1/G2 variant subgroups categorized by new haplotype scores, enriching our understanding. Conclusions: Our cost-effective and rapid qPCR technique facilitates APOL1 genotyping within hours. Prospective and retrospective studies will enable comparisons with long-term allograft rejection, potentially predicting early/late-stage transplant outcomes based on haplotype evaluation in this diverse group of kidney transplant recipients.

The utility of intraoperative nerve monitoring in secondary and tertiary Hyperparathyroid surgery.

OBJECTIVES: Recurrent laryngeal nerve (RLN) injury is a well-known complication of parathyroid surgery. Despite ample data, there is still uncertainty about the role of intraoperative monitoring (IONM) in mitigating RLN damage. STUDY DESIGN: A retrospective review. METHODS: We included all patients presenting for total, subtotal, or completion parathyroidectomy at a tertiary referral hospital from 2013 to 2018. Information about demographics, previous neck surgery, perioperative data, pathology, and possible RLN injury was collected. Two groups were formed for analysis: IONM vs. nonmonitored (NM). RESULTS: 105 patients underwent 107 surgeries with IONM utilized in 71 cases. The groups were similar in demographics, but significantly differed (all P < 0.05) in preincision parathyroid hormone level (IONM = 2091.44 vs NM = 1334.87), surgery type (IONM = 62.9% vs NM = 27.8% subtotal), and surgery length in minutes (IONM = 155.21 vs NM = 182.22). We observed six cases (6/71 = 8.45%) of persistent RLN complaints (three or more weeks postoperatively) and four cases (4/71 = 5.63%) of temporary complaints with the use of IONM compared with only one temporary complaint (1/36 = 2.78%) in unmonitored procedures (P = 0.129). CONCLUSIONS: These results suggest that the use of IONM does not provide a protective effect on the RLN in patients with secondary or tertiary hyperparathyroidism undergoing total, subtotal, or completion parathyroidectomy. Prospective, randomized studies with pre- and postoperative flexible laryngoscopy are needed to explore the use of IONM in this patient population further.

Transplantation of kidneys from hepatitis C-infected donors to hepatitis C-negative recipients: Single center experience.

Our aim was to evaluate the safety of transplanting kidneys from HCV-infected donors in HCV-uninfected recipients. Data collected from 53 recipients in a single center, observational study included donor and recipient characteristics, liver and kidney graft function, new infections and de novo donor-specific antibodies and renal histology. Treatment with a direct-acting antiviral regimen was initiated when HCV RNA was detected. The mean ± SD age of recipients was 53 ± 11 years, 34% were female, 19% and 79% of recipients were white and African American, respectively. The median and interquartile range (IQR) time between transplant and treatment initiation was 76 (IQR: 68-88) days. All 53 recipients became viremic (genotype: 1a [N = 34], 1b [N = 1], 2 [N = 3], and 3 [N = 15]). The majority (81%) of recipients did not experience clinically significant increases (>3 times higher than upper limit of the normal value) in aminotransferase levels and their HCV RNA levels were in the 5 to 6 log range. One patient developed fibrosing cholestatic hepatitis with complete resolution. All recipients completed antiviral treatment and 100% were HCV RNA-negative and achieved 12-week sustained virologic response. The estimated GFRs at end of treatment and 12-week posttreatment were 67 ± 21 mL/min/1.73 m2 and 67 ± 17 mL/min/1.73 m2 , respectively. Four recipients developed acute rejection. Kidney transplantation from HCV-infected donors to HCV-negative recipients should be considered in all eligible patients.

Chimney-Patch Arterial Graft in Kidney or Pancreas Transplantation for Recipients with Heavily Calcified Iliac Arteries.

Iliac artery calcification is a common phenomenon complicating renal transplantation, particularly in those with diabetes. The potential for vascular clamp injury can threaten the renal allograft, ipsilateral lower extremity, or both. Utilization of internal balloon occlusion can allow for placement of a "Chimney Patch" graft, fashioned from a deceased donor artery, to the calcified vessel, eliminating the risk of clamp injury and minimizing warm ischemic time. We present a series of 6 patients transplanted with internal balloon occlusion with successful renal and pancreatic allograft function and no ipsilateral vascular complications. Internal balloon occlusion is a safe and effective adjunct for renal or pancreas transplant to prevent clamp injury with no adverse effect on allograft function.

A technique for the salvage of megafistulas allowing immediate dialysis access.

OBJECTIVE: Almost two million individuals are undergoing renal replacement therapy worldwide, with hemodialysis being the common form. Many factors influence the primary patency of an arteriovenous fistula (AVF), including vessel size, fistula flow rates, cannulation practice, and thrombotic tendencies. Excess dilation of the AVF, resulting in the development of a megafistula, is a complication that can result in a need for AVF revision and subsequent failure. METHODS: The charts of patients who underwent autogenous AVF revision because of the development of a megafistula with aneurysmectomy and vein transposition by a single surgeon during a 7-year period from 2009 through 2016 were reviewed. A technique is described in which after aneurysmorrhaphy, the repaired venous component of the AVF is transposed through a new tunnel while the vein is rotated 90 degrees. This allows the AVF to be accessed immediately, making placement of a tunneled dialysis catheter unnecessary. RESULTS: There were 102 patients included in the study, with follow-up ranging from 7 to 95 months. In our cohort, 92 of the 102 revised AVFs (90.2%) maintained primary functional patency. Of the 102 patients who underwent this revision technique, there were 10 fistulas that subsequently failed after a mean of 29 months. There were only seven patients who experienced recurrent fistula dilation requiring repeated aneurysmectomy. CONCLUSIONS: We describe a technique for management of the development of a megafistula that uses only autogenous tissue and, perhaps most important, eliminates the need for temporary dialysis catheter placement.

Outcomes of Simultaneous Peritoneal Dialysis and Arteriovenous Fistula Placement in End-Stage Renal Disease Patients.

Peritoneal dialysis (PD) interruption requiring hemodialysis (HD) is not uncommon and its frequently abrupt nature prevents timely creation of permanent HD access and avoidance of central venous catheters (CVC). We retrospectively studied a cohort of 24 end-stage renal disease (ESRD) patients (mean age 50.7 years, 83.3% African-Americans, 58.3% females, time on dialysis interquartile range [IQR] 0 - 65 days) who had simultaneous PD catheter insertion and backup arteriovenous fistula (AVF) creation between January 1, 2012, and December 31, 2013. The primary outcome of interest was the percent of patients receiving HD through the backup AVF at the time of PD interruption. A median (IQR) for PD catheter use after its insertion was 10.5 (2 - 20) days. After the mean follow-up of 19.6 months, 12 patients remained on PD, 2 patients received a kidney transplant, and 1 patient died. The overall AVF patency was 66.7%. A total of 9 (37.5%) patients had PD interruption requiring permanent (8 patients) or temporary (1 patient) HD after the mean (standard deviation [SD]) follow-up of 12.3 (8.2) months. Arteriovenous fistula was used as the initial access in 4 patients, and in 3 patients the original AVF was used after additional surgical revision. Forty-four percent of patients with a backup AVF fistula avoided CVC at the time of PD interruption requiring HD. The simultaneous AVF creation at the time of PD catheter insertion reduced but did not fully eliminate CVC at the time of PD interruption. Larger studies are needed to evaluate the utility of a backup AVF in PD patients.

Steroid-free Liver Transplantation Using Rabbit Antithymocyte Globulin Induction in 500 Consecutive Patients.

BACKGROUND: We have previously documented the efficacy of a steroid-free immunosuppression protocol using rabbit antithymocyte globulin (RATG) induction in orthotopic liver transplantation (OLT) with tacrolimus minimization. The purpose of this report is to demonstrate the benefits of this protocol in a large cohort of patients. METHODS: We evaluated outcomes of 500 consecutive OLT recipients who received RATG induction and a single dose of solumedrol given before the first dose of RATG. Mycophenolate mofetil was initiated postoperatively with delayed initiation of tacrolimus. Sirolimus replaced tacrolimus if serum creatinine remained above 2.0 mg/dL by day 7. Patients were weaned to tacrolimus or sirolimus monotherapy at 3 months. Mean model for end-stage liver disease (MELD) at transplantation was 22 ± 6. RESULTS: Forty-four percent of patients had hepatitis C. Posttransplant creatinine was highest at 1 month (1.43 ± 0.95 mg/dL) and improved to 1.26 ± 0.60 mg/dL (P < 0.05) at 2.5 years. Glomerular filtration rate was lowest at 1 month (65.6 ± 30.0) and improved by 1 year (72.7 ± 28.2, P < 0.01). Tacrolimus was initiated at 4.79 ± 13.3 days with a level of 4.95 ± 2.45 ng/mL at 1 year. One-year patient and graft survival were 92.8% and 89.6%, respectively, with a 3-year patient survival of 82.9%. Rejection occurred in 114 (22.8%) patients, 33 (6.6%) patients requiring steroids. Univariate and multivariate Cox proportional hazard analyses were performed to evaluate the effects of donor and recipient characteristics on patient and graft survivals. Pretransplant creatinine was consistently a statistically significant predictor for patient and graft survival. CONCLUSION: This is the largest reported series of OLT recipients using a steroid-free protocol with RATG induction demonstrating excellent outcomes, low complication rates, and preservation of renal function.

Liver transplant using donors after cardiac death: a single-center approach providing outcomes comparable to donation after brain death.

OBJECTIVES: Organ donation after cardiac death remains an available resource to meet the demand for transplant. However, concern persists that outcomes associated with donation after cardiac death liver allografts are not equivalent to those obtained with organ donation after brain death. The aim of this matched case control study was to determine if outcomes of liver transplants with donation after cardiac death donors is equivalent to outcomes with donation after brain death donors by controlling for careful donor and recipient selection, surgical technique, and preservation solution. MATERIALS AND METHODS: A retrospective, matched case control study of adult liver transplant recipients at the University of Tennessee/Methodist University Hospital Transplant Institute, Memphis, Tennessee was performed. Thirty-eight donation after cardiac death recipients were matched 1:2, with 76 donation after brain death recipients by recipient age, recipient laboratory Model for End Stage Liver Disease score, and donor age to form the 2 groups. A comprehensive approach that controlled for careful donor and recipient matching, surgical technique, and preservation solution was used to minimize warm ischemia time, cold ischemia time, and ischemia-reperfusion injury. RESULTS: Patient and graft survival rates were similar in both groups at 1 and 3 years (P = .444 and P = .295). There was no statistically significant difference in primary nonfunction, vascular complications, or biliary complications. In particular, there was no statistically significant difference in ischemic-type diffuse intrahepatic strictures (P = .107). CONCLUSIONS: These findings provide further evidence that excellent patient and graft survival rates expected with liver transplants using organ donation after brain death donors can be achieved with organ donation after cardiac death donors without statistically higher rates of morbidity or mortality when a comprehensive approach that controls for careful donor and recipient matching, surgical technique, and preservation solution is used.

Outcomes of orthotopic liver transplantation for hepatic sarcoidosis: an analysis of the United Network for Organ Sharing/Organ Procurement and Transplantation Network data files for a comparative study with cholestatic liver diseases.

Hepatic sarcoidosis is a rare indication for liver transplantation. Using the United Network for Organ Sharing (UNOS)/Organ Procurement and Transplantation Network (OPTN) database, we evaluated patient and graft survival after orthotopic liver transplantation for sarcoidosis between October 1987 and December 2007. We assessed the potential prognostic value of multiple demographic and clinical variables, and we also compared these patients to a case-matched group of patients with primary sclerosing cholangitis (PSC) or primary biliary cirrhosis (PBC). The 1- and 5-year survival rates for the sarcoidosis group were 78% and 61%, respectively, and these rates were significantly worse than the rates for the PSC/PBC group (P = 0.001). Disease recurrence in the liver is a rare cause of graft loss or patient death. Three deaths occurred in the sarcoidosis group because of recurrent hepatic sarcoidosis, and 1 death was a result of cardiac sarcoidosis. A univariate analysis identified an increasing donor risk index as a significant negative factor for outcomes for the sarcoidosis group [hazard ratio (HR) = 2.06, confidence interval (CI) = 1.04-4.06, P = 0.037], but this finding was not found in a multivariate analysis, in which no independent predictors were found to have a significant impact. A case-matched univariate analysis demonstrated that sarcoidosis and morbid obesity were significant negative factors for outcomes, and in a multivariate analysis, sarcoidosis continued to predict worse outcomes (HR = 2.39, CI = 1.21-4.73, P = 0.012). In conclusion, an analysis of the UNOS/OPTN database indicates that the patient and allograft survival rates for hepatic sarcoidosis are satisfactory, but they are worse in comparison with the rates for other cholestatic liver diseases.

Rabbit antithymocyte induction and dosing in deceased donor renal transplant recipients over 60 yr of age.

BACKGROUND: Antithymocyte globulin (rATG) is a commonly used induction agent in renal transplantation; however, data in older kidney recipients are limited. METHODS: We reviewed charts of 301 deceased donor renal transplants who received a protocol consisting of 3-7 doses of rATG and triple maintenance therapy. Outcomes of patients >60 yr of age (n = 45) were compared to those aged 18-59 yr (n = 256). RESULTS: Older recipients had more diabetics, were more likely to receive expanded criteria donor kidneys (p < 0.01), and over 30% were sensitized. Recipients >60 received less cumulative rATG (4.6 vs. 5.1 mg/kg; p < 0.01). Three-yr acute rejection was lower in the >60 group (2% vs. 16%, p < 0.01) although glomerular filtration rates were similar between groups. Actuarial graft survival was similar; however, patient survival in the >60 group at three yr was lower (80% vs. 95%; p = 0.02). Specifically, patients >60 with delayed graft function and rATG cumulative dosing >6 mg/kg had a survival of <50% by two yr. CONCLUSION: Recipients over 60 yr receiving rATG induction have acceptable renal function and a low risk of rejection; however, reduced survival was noted among those receiving >6 mg/kg. These data suggest that when used, lower cumulative dosages of rATG are preferable in the older recipient.

Prospective observational study of sirolimus as primary immunosuppression after renal transplantation.

BACKGROUND.: Sirolimus (SRL) is an important component of clinical immunosuppression in renal transplantation, but few international studies have examined how this agent is used in routine practice. METHODS.: Within a large prospective pharmacoepidemiological study, 718 de novo renal graft recipients treated with SRL in 65 centers in 10 countries were monitored for up to 5 years posttransplant to compare the principal outcomes and adverse effects by treatment regimen. RESULTS.: Principal treatment regimens were SRL without a calcineurin inhibitor (33%), SRL+cyclosporine A (CsA) (33%), and SRL+tacrolimus (TAC) (34%); 18% of subjects discontinued SRL, 124/718 (17%) developed biopsy-confirmed acute rejection (BCAR), 64/718 (9%) lost their graft, and 50/718 (7%) died during follow-up. Calculated creatinine clearance was 66+/-26 mL/min at 2 years. The most common adverse events were hypertension, hyperlipidemia, anemia, urinary tract infections, and diabetes. BCAR was significantly lower in subjects receiving SRL+TAC (hazard ratio [HR] 0.46, P=0.009) but not significantly lower in those receiving SRL+CsA (HR 0.62, P=0.102) compared with SRL without a calcineurin inhibitor. Graft loss or death did not significantly differ between treatment groups but were associated, respectively, with deceased donor grafts (HR 3.33, P<0.001) and increased age (HR 1.04, P<0.001). No improvement was observed in patients receiving mycophenolate mofetil in any treatment combination (HR 0.80, P=0.438 for BCAR; HR 0.93, P=0.849 for graft loss; and HR 0.75, P=0.531 for death). CONCLUSIONS.: SRL is most commonly used in combination with mycophenolate mofetil, CsA, or TAC. BCAR was least common in subjects receiving SRL+TAC, but other outcomes seemed comparable between the treatment regimens in routine practice.

Foregut cystic developmental malformation: new taxonomy and classification--unifying embryopathological concepts.

Foregut cystic developmental malformations are rare developmental anomalies. The problems inherent to these malformations are their presentation across specialties that include embryology, anatomy, pathology, thoracic foregut surgery, pediatric surgery and general abdominal surgery. The direct consequence of this variation has resulted in diverse terminology, classification and a failure to identify the correlation. The article aims to summarize and unify the embryological concepts of foregut cystic malformation, to suggest a generic title to the various groups of these interrelated disorders and a uniform use of nomenclature on the basis of unifying concepts of embryopathogeneis.

Salvage of inaccessible arteriovenous fistulas in obese patients: a review of 132 brachiocephalic fistulas.

The two main factors leading to a functional fistula are maturity and accessibility. The aim of this review was to describe a technique of superficialization for inaccessible brachiocephalic fistulas, and to identify the patients that benefit from superficialization. One hundred and thirty-two brachiocephalic arteriovenous fistulas developed from November 2003 to December 2006 were reviewed for primary maturation. In the mature group, patients were evaluated for fistula accessibility. Inaccessible fistulas were selected for superficialization via our technique of vein mobilization using small skip incisions. Analysis of superficialized and nonsuperficialized groups included age, demographics, and comorbidities. Ninety-nine patients were in the mature group, and 33 in the immature group; primary nonmaturation was 25 per cent. Analysis within the mature group was between nonsuperficialized (n = 81) and superficialized (n = 18) patients. The superficialized group had less hypertension (83% vs 98%, P < 0.05), significantly higher BMI (31 vs 27, P < 0.05), and was mostly female (78% vs 49%, P < 0.05). All superficialized fistulas accommodated successful hemodialysis postoperatively. To conclude, patients with mature but inaccessible fistulas were salvaged by superficialization. This population had significantly higher BMI, less hypertension, and female prevalence. Identifying these patients is important because salvage of their fistula can prevent premature progression to alternate autogenous arteriovenous access procedures.

Ipsilateral placement in double-kidney transplantation.

Ipsilateral placement of double kidneys from marginal donors into older recipients may reduce the stress of the operation on the patient and allow for extension of the utility of older donor kidneys. A separate bench preparation of the kidneys is performed to aid in assessing the quality of the kidneys before placement in the recipient. Multiple renal arteries and proximal calcifications may require extracorporeal anastomosis or multiple anastomoses in the recipient depending on length and size of the renal vessels. In the recipient, the incision should allow complete dissection of the common external and internal iliac arteries. This report provides a detail of the technique used for ipsilateral placement of double kidneys.

Use of a "composite" vascular access graft in a young child on hemodialysis.

Although arterio-venous fistulae (AVF) are currently considered to be the first choice of permanent vascular access for hemodialysis, there are some patients who are not candidates for fistulae and synthetic grafts provide other options. The Thoratec (Vectra) polyurethane vascular access graft is a new prosthetic graft that may be cannulated within days of insertion due to "self-sealing" properties. However, a tendency for kinking at the suture site due to the strong elasticity of this graft, leading to undesirable complications such as thrombosis, have been reported. We describe a surgical modification of the anastomosis by interposing a segment of expanded polytetrafluoroethylene graft (ePTFE, Venaflo) between the native vessels and the polyurethane graft sections in a pediatric patient. This modification may overcome the kinking complication associated with use of the polyurethane graft and the resulting thrombosis.

Comparison of sirolimus-based calcineurin inhibitor-sparing and calcineurin inhibitor-free regimens in cadaveric renal transplantation.

INTRODUCTION: This study examines the efficacy and toxicity of sirolimus used as primary immunosuppression in combination with reduced dose tacrolimus (calcineurin inhibitor [CI]-sparing regimen) or mycophenolate mofetil (CI-free regimen) in high-risk cadaveric renal transplantation. METHODS: Seventy subjects were treated in a quadruple sequential protocol in which 41 were treated with a CI-sparing regimen and 29 were treated with a CI-free regimen. The efficacy and toxicity profiles of these regimens were prospectively monitored and compared. RESULTS: The study consisted of African Americans (71%), cadaveric donors (100%), donors aged more than 50 years (30%), and patients with delayed graft function (47%). At 1 year, patient survival, graft survival, and incidence of biopsy-proven acute rejection were 98%, 80%, and 10%, respectively, in the CI-sparing group and 100%, 89%, and 7%, respectively, in the CI-free group. Three-month protocol biopsies were performed in 41% (17/41) and 67% (20/29) of the subjects in the CI-sparing and CI-free groups, respectively. Subclinical rejection was detected in 6% (1/17) and 15% (3/20) of the subjects in the CI-sparing and CI-free groups, respectively. Histologic evidence of chronic allograft nephropathy was more prevalent in the CI-sparing group. At 1 year, the mean estimated creatinine clearance was higher in the CI-free group than in the CI-sparing group (72.4 +/-20.0 mL/min vs. 50.5 +/-20.8 mL/min, P <0.01). The two regimens had similar toxicity profiles (hospital readmission, infection, wound complications, and metabolic complications). CONCLUSIONS: Both sirolimus-based CI-sparing and CI-free regimens are safe and effective in a population with high immunologic risk. The CI-free regimen is associated with better renal function at 1 year post-transplant. Long-term follow-up will aid in determining the risk and benefit ratio of these regimens.

Liver transplantation for acute Budd-Chiari syndrome in identical twin sisters with Factor V leiden mutation.

BACKGROUND: Budd-Chiari syndrome (BCS) is uncommon in the children. The cause of BCS comprises several diseases leading to thrombophilia. Activated protein C resistance as a result of a single gene mutation in factor V, the so called factor V Leiden (FVL), is the most common cause of thrombophilia. METHODS: We report a simultaneous occurrence of BCS in identical twin sisters of 13 years of age with heterozygous FVL mutation. RESULTS: One sister presented with acute BCS leading to fulminant hepatic failure. She underwent liver transplantation with subsequent normalization of activated protein C resistance. The other twin sister, who was diagnosed with extensive thromboses of the inferior vena cava, portal vein, and hepatic veins, was successfully managed by aggressive chemical and mechanical thrombolysis followed by therapeutic anticoagulation. Genomic DNA studies confirmed heterozygosity of FVL mutation in the sisters' father and older brother. CONCLUSIONS: The exact cause of the BCS in children should be thoroughly and rapidly investigated, and, if necessary, immediate family members should also be tested for genetic defects in factor V or concomitant thrombophilia.