Stephan Busque, MD

Abstract

BACKGROUND: Humoral and cellular immune responses to SARS-CoV-2 vaccination among immunosuppressed patients remain poorly defined, as well as variables associated with poor response.METHODS: We performed a retrospective observational cohort study at a large Northern California healthcare system of infection-naive individuals fully vaccinated against SARS-CoV-2 (mRNA-1273, BNT162b2, or Ad26.COV2.S) with clinical SARS-CoV-2 interferon gamma release assay (IGRA) ordered between January through November 2021. Humoral and cellular immune responses were measured by anti-SARS-CoV-2 S1 IgG ELISA (anti-S1 IgG) and IGRA, respectively, following primary and/or booster vaccination.RESULTS: 496 immunosuppressed patients (54% female; median age 50 years) were included. 62% (261/419) of patients had positive anti-S1 IgG and 71% (277/389) had positive IGRA after primary vaccination, with 20% of patients having a positive IGRA only. Following booster, 69% (81/118) had positive anti-S1 IgG and 73% (91/124) had positive IGRA. Factors associated with low humoral response rates after primary vaccination included anti-CD20 monoclonal antibodies (P<0.001), sphingosine 1-phsophate (S1P) receptor modulators (P<0.001), mycophenolate (P=0.002), and B cell lymphoma (P=0.004); those associated with low cellular response rates included S1P receptor modulators (P<0.001) and mycophenolate (P<0.001). Of patients who had poor humoral response to primary vaccination, 35% (18/52) developed a significantly higher response after the booster. Only 5% (2/42) of patients developed a significantly higher cellular response to the booster dose compared to primary vaccination.CONCLUSIONS: Humoral and cellular response rates to primary and booster SARS-CoV-2 vaccination differ among immunosuppressed patient groups. Clinical testing of cellular immunity is important in monitoring vaccine response in vulnerable populations.

View details for DOI 10.1016/j.jcv.2022.105217

View details for PubMedID 35714462

View details for Web of Science ID 000842606302321

View details for Web of Science ID 000842606303536

View details for Web of Science ID 000842606302167

Abstract

Importance: While recent policy reforms aim to improve access to kidney transplantation for patients with end-stage kidney disease, the cost implications of kidney waiting list expansion are not well understood. The Organ Acquisition Cost Center (OACC) is the mechanism by which Medicare reimburses kidney transplantation programs, at cost, for costs attributable to kidney transplantation evaluation and waiting list management, but these costs have not been well described to date.Objectives: To describe temporal trends in mean OACC costs per kidney transplantation and to identify factors most associated with cost.Design, Setting, and Participants: This economic evaluation included all kidney transplantation waiting list candidates and recipients in the United States from 2012 to 2017. A population-based study of cost center reports was conducted using data from all Center of Medicare & Medicaid-certified transplantation hospitals. Data analysis was conducted from June to August 2021.Exposures: Year, local price index, transplantation and waiting list volume of transplantation program, and comorbidity burden.Main Outcomes and Measures: Mean OACC costs per kidney transplantation.Results: In 1335 hospital-years from 2012 through 2017, Medicare's share of OACC costs increased from $0.95 billion in 2012 to $1.32 billion in 2017 (3.7% of total Medicare End-Stage Renal Disease program expenditure). Median (IQR) OACC costs per transplantation increased from $81000 ($66000 to $103000) in 2012 to $100000 ($82000 to $125000) in 2017. Kidney organ procurement costs contributed to 36% of mean OACC costs per transplantation throughout the study period. During the study period, transplantation hospitals experienced increases in kidney waiting list volume, kidney waiting list active volume, kidney transplantation volume, and comorbidity burden. For a median-sized transplantation program, mean OACC costs per transplantation decreased with more transplants (-$3500 [95% CI, -$4300 to -$2700] per 10 transplants; P<.001) and increased with year ($4400 [95% CI, $3500 to $5300] per year; P<.001), local price index ($1900 [95% CI, $200 to $3700] per 10-point increase; P=.03), patients listed active on the waiting list ($3100 [95% CI, $1700 to $4600] per 100 patients; P<.001), and patients on the waiting list with high comorbidities ($1500 [9% CI, $600 to $2500] per 1% increase in proportion of waitlisted patients with the highest comorbidity score; P=.002).Conclusions and Relevance: In this study, OACC costs increased at 4% per year from 2012 to 2017 and were not solely attributable to the cost of organ procurement. Expanding the waiting list will likely contribute to further increases in the mean OACC costs per transplantation and substantially increase Medicare liability.

View details for DOI 10.1001/jamanetworkopen.2022.1847

View details for PubMedID 35267033

Abstract

Background: Morbidity and mortality associated with coronavirus disease 2019 (COVID-19) infection in kidney transplant recipients are high and early outpatient interventions to prevent progression to severe disease are needed. SARS-CoV-2 neutralizing mAbs, including bamlanivimab and casirivimab-imdevimab, received emergency use authorization in the United States in November 2020 for treatment of mild to moderate COVID-19 disease.Methods: We performed a retrospective analysis of 27 kidney transplant recipients diagnosed with COVID-19 between July 2020 and February 2021 who were treated with bamlanivimab or casirivimab-imdevimab and immunosuppression reduction. We additionally identified 13 kidney transplant recipients with COVID-19 who had mild to moderate disease at presentation, who did not receive mAbs, and had SARS-CoV-2 serology testing available.Results: There were no deaths or graft failures in either group. Both infusions were well tolerated. Four of the 27 patients treated with mAbs required hospitalization due to COVID-19. Four of 13 patients who did not receive mAbs required hospitalization due to COVID-19. Patients who received mAbs demonstrated measurable anti-SARS-CoV-2 IgG with angiotensin-converting enzyme 2 (ACE2) receptor blocking activity at the highest level detectable at 90 days postinfusion, whereas ACE2 blocking activity acquired from natural immunity in the mAb-untreated group was weak.Conclusions: Bamlanivimab and casirivimab-imdevimab combined with immunosuppression reduction were well tolerated and associated with favorable clinical outcomes in kidney transplant recipients diagnosed with mild to moderate COVID-19.

View details for DOI 10.34067/KID.0005732021

View details for PubMedID 35368573

View details for Web of Science ID 000705310101266

View details for Web of Science ID 000546629503362

Abstract

Solid organ transplant recipients are at risk for infectious complications due to chronic immunosuppression. The outbreak of Coronavirus Disease 2019 (COVID-19) in United States has raised growing concerns for the transplant patient population. We seek to add to the current limited literature on COVID-19 in transplant recipients by describing the clinical course of two kidney transplant recipients with SARS-Cov-2 infection monitored by both RT-PCR and serology. Through careful adjustment of their immunosuppression regimen, both patients had excellent recovery with intact graft function and development of anti-SARS-Cov-2 antibodies.

View details for DOI 10.1111/tid.13423

View details for PubMedID 32701196

View details for Web of Science ID 000474897601083

View details for Web of Science ID 000474897601082

View details for Web of Science ID 000474897602134

View details for Web of Science ID 000457809000089

View details for DOI 10.1016/j.humimm.2018.07.157

View details for Web of Science ID 000444782200152

View details for Web of Science ID 000446020500225

Abstract

Kidney transplant waitlist management is becoming increasingly complex. We introduced a novel waitlist management strategy at our center, the Transplant Readiness Assessment Clinic (TRAC), whereby patients whose Kidney Allocation Scores surpass a threshold are actively managed. From January 1, 2016 through June 30, 2017, we evaluated 195 patients through TRAC. Compared to pre-TRAC systems at our institution, TRAC resulted in a higher proportion of activation at 18-months (38% versus 22-26%, p<0.0001), despite being enriched in patients with long dialysis duration. TRAC also resulted in a higher proportion of waitlist removal (15% versus 8-9%, p<0.05) although combined waitlist removal and death on waitlist did not differ (18% versus 16-17%). Median time-to-activation was 356 days from TRAC evaluation. Of the transplant barriers, need for cardiovascular studies was the most common (31%), followed by other medical issues (23%), poor functional status (13%), and psychosocial issues (10%). By concentrating center resources on patients most likely to be transplanted after activation and performing active patient management close to the time of transplant, TRAC has the potential to significantly enhance kidney transplant success in regions with long wait-times. This article is protected by copyright. All rights reserved.

View details for PubMedID 30218580

Abstract

We present a case of cytomegalovirus (CMV) native kidney nephritis and prostatitis in a CMV D+/R- kidney transplant recipient who had completed six months of CMV prophylaxis four weeks prior to the diagnosis of genitourinary CMV disease. The patient had a history of benign prostatic hypertrophy and urinary retention that required self-catheterization to relieve high post-voiding residual volumes. At 7 months post-transplant, he was found to have a urinary tract infection, moderate hydronephrosis of the transplanted kidney, and severe hydroureteronephrosis of the native left kidney and ureter, and underwent native left nephrectomy and transurethral resection of the prostate. Histopathologic examination of kidney and prostate tissue revealed CMV inclusions consistent with invasive CMV disease. This case highlights that CMV may extend beyond the kidney allograft to involve other parts of the genitourinary tract, including the native kidneys and prostate. Furthermore, we highlight the tissue-specific risk factors that preceded CMV tissue invasion. In addition to concurrent diagnoses, health care providers should have a low threshold for considering late-onset CMV disease in high-risk solid organ transplant recipients presenting with signs and symptoms of genitourinary tract pathology. This article is protected by copyright. All rights reserved.

View details for PubMedID 30203504

View details for Web of Science ID 000444541200630

View details for Web of Science ID 000431965401585

View details for Web of Science ID 000431965402053

View details for Web of Science ID 000404515702196

View details for PubMedID 26551201

Abstract

The effect of preexisting hypertension on living donor nephron number has not been established. In this study, we determined the association between preexisting donor hypertension and glomerular number and volume and assessed the effect of predonation hypertension on postdonation BP, adaptive hyperfiltration, and compensatory glomerular hypertrophy. We enrolled 51 living donors to undergo physiologic, morphometric, and radiologic evaluations before and after kidney donation. To estimate the number of functioning glomeruli (NFG), we divided the whole-kidney ultrafiltration coefficient (Kf) by the single-nephron ultrafiltration coefficient (SNKf). Ten donors were hypertensive before donation. We found that, in donors ages >50 years old, preexisting hypertension was associated with a reduction in NFG. In a comparison of 10 age- and sex-matched hypertensive and normotensive donors, we observed more marked glomerulopenia in hypertensive donors (NFG per kidney, 359,499128,929 versus 558,239205,152; P=0.02). Glomerulopenia was associated with a nonsignificant reduction in GFR in the hypertensive group (8912 versus 9516 ml/min per 1.73 m(2)). We observed no difference in the corresponding magnitude of postdonation BP, hyperfiltration capacity, or compensatory renocortical hypertrophy between hypertensive and normotensive donors. Nevertheless, we propose that the greater magnitude of glomerulopenia in living kidney donors with preexisting hypertension justifies the need for long-term follow-up studies.

View details for DOI 10.1681/ASN.2014030304

View details for Web of Science ID 000355386100007

View details for PubMedID 25525178

View details for PubMedCentralID PMC4446872

View details for Web of Science ID 000370124202084

View details for Web of Science ID 000370124200237

View details for Web of Science ID 000339104603003

View details for Web of Science ID 000339104603107

View details for Web of Science ID 000339104605514

View details for Web of Science ID 000339104605025

View details for Web of Science ID 000339104603024

View details for Web of Science ID 000338033303356

View details for Web of Science ID 000338033302172

View details for Web of Science ID 000338033304108

View details for Web of Science ID 000338033302277

View details for Web of Science ID 000338033302193

View details for Web of Science ID 000328999400137

View details for Web of Science ID 000328232001025

View details for Web of Science ID 000318240300549

View details for Web of Science ID 000318240300588

View details for Web of Science ID 000318240300182

Abstract

The objectives of this study were to evaluate and compare the performance of the deceased donor registries of the 50 states and the District of Columbia and to identify possible predictive factors of donor designation. Data were collected retrospectively by Donate Life America using a questionnaire sent to Donor Designation Collaborative state teams between 2007 and 2010. By the end of 2010, there were 94,669,081 designated donors nationwide. This accounted for 39.8 per cent of the U.S. population aged 18 years and over. The number of designated organ donors and registry-authorized recovered donors increased each year; however, the total number of recovered donors in 2010 was the lowest since 2004. Donor designation rate was significantly higher when license applicants were verbally questioned at the Department of Motor Vehicles (DMV) regarding their willingness to register as a donor and when DMV applicants were not given an option on DMV application forms to contribute money to support organ donation, compared with not being questioned verbally, and being offered an option to contribute money. State registries continue to increase the total number of designated organ donors; however, the current availability of organs remains insufficient to meet the demand. These data suggest that DMV applicants who are approached verbally regarding their willingness to register as a donor and not given an option on DMV application forms to contribute money to support organ donation might be more likely to designate themselves to be a donor.

View details for Web of Science ID 000315606500003

View details for PubMedID 23461946

Abstract

Sensitization remains a major barrier to kidney transplantation. Sensitized patients comprise 30% of the kidney transplant waiting list but fewer than 15% of highly sensitized patients are transplanted each year. Options for highly sensitized patients with an immunologically incompatible living donor include desensitization or kidney paired donation (KPD). However, these options when used alone may still not be sufficient to allow a compatible transplant for recipients who are broadly sensitized with cumulative calculated panel-reactive antibody (cPRA) > 95%. We describe in this report the combined use of both desensitization and KPD to maximize the likelihood of finding a compatible match with a more immunologically favorable donor through a kidney exchange program. This combined approach was used in five very highly sensitized patients, all with cPRA 100%, who ultimately received compatible living and deceased donor kidney transplants. We conclude that early enrollment in paired kidney donor exchange and tailored desensitization protocols are key strategies to improve care and rates of kidney transplantation in highly sensitized patients.

View details for DOI 10.1016/j.transproceed.2012.08.007

View details for PubMedID 23375278

View details for DOI 10.1097/00007890-201211271-00100

View details for Web of Science ID 000209846400101

Abstract

We report the results of a large series of chain transplantations that were facilitated by a multicenter US database in which 57 centers pooled incompatible donor/recipient pairs. Chains, initiated by nondirected donors, were identified using a computer algorithm incorporating virtual cross-matches and potential to extend chains. The first 54 chains facilitated 272 kidney transplants (mean chain length = 5.0). Seven chains ended because potential donors became unavailable to donate after their recipient received a kidney; however, every recipient whose intended donor donated was transplanted. The remaining 47 chains were eventually closed by having the last donor donate to the waiting list. Of the 272 chain recipients 46% were ethnic minorities and 63% of grafts were shipped from other centers. The number of blood type O-patients receiving a transplant (n = 90) was greater than the number of blood type O-non-directed donors (n = 32) initiating chains. We have 1-year follow up on the first 100 transplants. The mean 1-year creatinine of the first 100 transplants from this series was 1.3 mg/dL. Chain transplantation enables many recipients with immunologically incompatible donors to be transplanted with high quality grafts.

View details for DOI 10.1111/j.1600-6143.2012.04156.x

View details for PubMedID 22812922

Abstract

The presence of kidney stones has been a relative contraindication for living donation. With the widespread use of more sensitive imaging techniques as part of the routine living donor workup, kidney stones are more frequently detected, and their clinical significance in this setting is largely unknown. Records from 325 potential kidney donors who underwent MRA or CT-angiography were reviewed; 294 proceeded to donation. The prevalence of kidney stones found incidentally during donor evaluation was 7.4% (24 of 325). Sixteen donors with stones proceeded with kidney donation. All incidental calculi were nonobstructing and small (median 2 mm; range 1-9 mm). Eleven recipients were transplanted with allografts containing stones. One recipient developed symptomatic nephrolithasis after transplantation. This recipient was found to have newly formed stones secondary to hyperoxaluria, suggesting a recipient-driven propensity for stone formation. The remaining ten recipients have stable graft function, postoperative ultrasound negative for nephrolithiasis, and no sequelae from stones. No donor developed symptomatic nephrolithiasis following donation. Judicious use of allografts with small stones in donors with normal metabolic studies may be acceptable, and careful follow-up in recipients of such allografts is warranted.

View details for DOI 10.1111/j.1399-0012.2011.01567.x

View details for PubMedID 22168332

View details for Web of Science ID 000303235501141

Abstract

Transplanted nephron mass is an important determinant of long-term allograft survival, but accurate assessment before organ retrieval is challenging. Newer radiologic imaging techniques allow for better determination of total kidney and cortical volumes.Using volume measurements reconstructed from magnetic resonance or computed tomography imaging from living donor candidates, we characterized total kidney (n=312) and cortical volumes (n=236) according to sex, age, weight, height, body mass index (BMI), and body surface area (BSA).The mean cortical volume was 204 mL (range 105-355 mL) with no significant differences between left and right cortical volumes. The degree to which existing anthropomorphic surrogates predict nephron mass was quantified, and a diligent attempt was made to derive a better surrogate model for nephron mass. Cortical volumes were strongly associated with sex and BSA, but not with weight, height, or BMI. Four prediction models for cortical volume constructed using combinations of age, sex, race, weight, and height were compared with models including either BSA or BMI.Among existing surrogate measures, BSA was superior to BMI in predicting renal cortical volume. We were able to construct a statistically superior proxy for cortical volume, but whether relevant improvements in predictive accuracy could be gained needs further evaluation in a larger population.

View details for DOI 10.1097/TP.0b013e31823705ef

View details for PubMedID 22011765

View details for Web of Science ID 000295578700034

View details for PubMedID 21991976

View details for PubMedCentralID PMC3334358

Abstract

The proportion of prospective living donors disqualified for medical reasons is unknown. The objective of this study is to delineate and quantify specific reasons for exclusion of prospective living donors from kidney donation.All adult prospective kidney donors who contacted our transplant program between October 1, 2007 and April 1, 2009 were included in our analysis (n=484). Data were collected by review of an electronic transplant database.Of the 484 prospective donors, 39 (8%) successfully donated, 229 (47%) were excluded, 104 (22%) were actively undergoing evaluation, and 112 (23%) were withdrawn before evaluation was complete. Criteria for exclusion were medical (n=150), psychosocial (n=22), or histocompatibility (n=57) reasons. Of the 150 prospective donors excluded for medical reasons, 79% were excluded because of obesity, hypertension, nephrolithiasis, and/or abnormal glucose tolerance. One hundred and forty-seven (61%) intended recipients had only one prospective living donor, of whom 63 (42%) were excluded.A significant proportion of prospective living kidney donors were excluded for medical reasons such as obesity (body mass index >30), hypertension, nephrolithiasis, and abnormal glucose tolerance. Longer-term studies are needed to characterize the risks to medically complex kidney donors and the potential risks and benefits afforded to recipients.

View details for DOI 10.1111/j.1399-0012.2010.01336.x

View details for PubMedID 21044160

Abstract

Kidney donor exchanges enable recipients with immunologically incompatible donors to receive compatible living donor grafts; however, the financial management of these exchanges, especially when an organ is shipped, is complex and thus has the potential to impede the broader implementation of donor exchange programs. Representatives from transplant centers that utilize the National Kidney Registry database to facilitate donor exchange transplants developed a financial model applicable to paired donor exchanges and donor chain transplants. The first tenet of the model is to eliminate financial liability to the donor. Thereafter, it accounts for the donor evaluation, donor nephrectomy hospital costs, donor nephrectomy physician fees, organ transport, donor complications and recipient inpatient services. Billing between hospitals is based on Medicare cost report defined costs rather than charges. We believe that this model complies with current federal regulations and effectively captures costs of the donor and recipient services. It could be considered as a financial paradigm for the United Network for Organ Sharing managed donor exchange program.

View details for DOI 10.1111/j.1600-6143.2011.03690.x

View details for PubMedID 21831153

Abstract

Human leukocyte antigen (HLA) antibodies, especially those that fix complement, are associated with antibody-mediated rejection and graft failure. The C1q assay on single antigen beads detects a subset of HLA antibodies that can fix complement and precede C4d deposition. The aim of this study was to determine whether C1q-fixing antibodies distinguish de novo donor-specific antibodies (DSA) that are clinically relevant and harmful.We retrospectively studied 31 of 274 kidney transplant recipients who had pretransplant and concurrent biopsy and serum specimens, 13 with C4d-positive and 18 with C4d-negative staining. We measured IgG and C1q DSA pretransplant and at the time of biopsy using single antigen bead assays. We identified 13 recipients who developed de novo DSA by IgG or C1q and examined associations with C4d deposition, transplant glomerulopathy, and graft failure.Testing for DSA by IgG is more sensitive for C4d deposition (IgG: 100%, 95% confidence interval [CI] 0.60-1; C1q: 75%, 95% CI 0.36-0.96). Testing for DSA by C1q is more specific for transplant glomerulopathy (C1q: 81%, 95% CI 0.57-0.94; IgG: 67%, 95% CI 0.43-0.85) and graft loss (C1q: 79%, 95% CI 0.54-0.93; IgG: 63%, 95% CI 0.39-0.83). Absence of de novo DSA by IgG and C1q has a high negative predictive value for the absence of C4d deposition (IgG: 100%, 95% CI 0.73-1; C1q: 88%, 95% CI 0.62-0.98), transplant glomerulopathy (IgG: 100%, 95% CI 0.73-1; C1q: 100%, 95% CI 0.77-1), and graft failure (IgG: 86%, 95% CI 0.56-0.97; C1q: 88%, 95% CI 0.62-0.98).Monitoring patients with the C1q assay, which detects antibodies that fix complement, offers a minimally invasive means of identifying patients at risk for transplant glomerulopathy and graft loss.

View details for DOI 10.1097/TP.0b013e318203fd26

View details for Web of Science ID 000286624400014

View details for PubMedID 21116220

Abstract

To elucidate the pathophysiologic changes in the kidney due to aging, we used physiological, morphometric, and imaging techniques to quantify GFR and its determinants in a group of 24 older ( 55 years) compared to 33 younger ( 45 years) living donors. Mathematical modeling was used to estimate the glomerular filtration coefficients for the whole kidney (K(f)) and for single nephrons (SNK(f)), as well as the number of filtering glomeruli (N(FG)). Compared to younger donors, older donors had a modest (15%) but significant depression of pre-donation GFR. Mean whole-kidney K(f), renocortical volume, and derived N(FG) were also significantly decreased in older donors. In contrast, glomerular structure and SNK(f) were not different in older and younger donors. Derived N(FG) in the bottom quartile of older donors was less than 27% of median-derived N(FG) in the two kidneys of younger donors. Nevertheless, the remaining kidney of older donors exhibited adaptive hyperfiltration and renocortical hypertrophy post-donation, comparable to that of younger donors. Thus, our study found the decline of GFR in older donors is due to a reduction in K(f) attributable to glomerulopenia. We recommend careful monitoring for and control of post-donation comorbidities that could exacerbate glomerular loss.

View details for DOI 10.1038/ki.2010.128

View details for Web of Science ID 000281824200011

View details for PubMedID 20463656

View details for PubMedCentralID PMC3353650

Abstract

To ensure long-term safety of living kidney donors, it is now recommended that they be followed for at least 2 years after donation and that serum creatinine levels be monitored. Such levels are often subjected by clinical laboratories to estimating equations and are reported as estimated GFR (eGFR). The accuracy of such equations in uninephric living donors has yet to be validated. This is especially important in older living donors, who often have senescence-related depression of GFR.We compared urinary creatinine clearance, four-variable Modification of Diet in Renal Disease estimating equation (eGFR), and the recently reported CKD-EPI GFR estimating equation with true GFR measured by the urinary iothalamate clearance (iGFR) in 64 subjects after kidney donation.Creatinine clearance overestimated iGFR. Both creatinine-based estimating equations were poorly correlated with and underestimated iGFR. More than half of kidney donors had eGFR <60 ml/min per 1.73 m(2) after donation, a level that categorized them as having stage 3 chronic kidney disease by our current laboratory reporting, whereas only 25% had iGFR <60 ml/min per 1.73 m(2). This misclassification disproportionately affected older donors age > or =55 years, of whom 80% had eGFR <60 ml/min per 1.73 m(2). Neither significant albuminuria nor hypertension was observed.The current practice of reporting eGFR after donation commonly leads to a misclassification of chronic kidney disease, particularly in older donors. To ensure long-term well-being of living kidney donors, more precise estimates of GFR are required, particularly among older potential donors.

View details for DOI 10.2215/CJN.05280709

View details for Web of Science ID 000275325000017

View details for PubMedID 20110343

View details for PubMedCentralID PMC2827575

Abstract

We recently reported a randomized study in renal transplant patients (RTP) receiving tacrolimus, mycophenolate mofetil, and prednisone in which patients who had early protocol biopsies (PBx) derived no benefit compared with controls (no PBx) at 6 months, likely due to the low prevalence of subclinical rejection. We report on the follow-up of these patients to 24 months at which time a repeat PBx and tests of renal function were performed.Of the 240 RTP randomized, 22 were excluded for a protocol violation. Approximately 75% of the remaining 218 (111 PBx and 107 controls) completed the study.At 24 months, graft function was excellent with a mean creatinine clearance of approximately 74 mL/min and negligible proteinuria; however, the prevalence of interstitial fibrosis and tubular atrophy (IF/TA)-ci + ct more than or equal to 2-increased from approximately 3% at baseline to up to 40% to 50%. By logistic regression analysis, the only independent positive correlate of IF/TA was transplantation with a deceased donor. However, by post hoc analysis, use of angiotensin-II-converting enzyme inhibitors or angiotensin II receptor blockers was negatively correlated with both the prevalence of IF/TA at 24 months and its progression between 6 and 24 months in RTP that had paired biopsies.A regimen of tacrolimus, mycophenolate mofetil, and prednisone results in excellent renal function at 24 months posttransplant but with a progressive increase in IF/TA. A potential inhibitory effect of angiotensin-II-converting enzyme inhibitor/angiotensin II receptor blockers on IF/TA is suggested that requires confirmation in a randomized study.

View details for DOI 10.1097/TP.0b013e3181b723f4

View details for Web of Science ID 000270842500009

View details for PubMedID 19935461

Abstract

The organ donor shortage has been the most important hindrance in getting listed patients transplanted. Living kidney donors who are incompatible with their intended recipients are an untapped resource for expanding the donor pool through participation in transplant exchanges. Chain transplantation takes this concept further, with the potential to benefit even more recipients. We describe the first asynchronous, out of sequence transplant chain that was initiated by transcontinental shipment of an altruistic donor kidney 1 week after that recipient's incompatible donor had already donated his kidney to the next recipient in the chain. The altruistic donor kidney was transported from New York to Los Angeles and functioned immediately after transplantation. Our modified-sequence asynchronous transplant chain (MATCH) enabled eight recipients, at four different institutions, to benefit from the generosity of one altruistic donor and warrants further exploration as a promising step toward addressing the organ donor shortage.

View details for DOI 10.1111/j.1600-6143.2009.02730.x

View details for Web of Science ID 000269180500027

View details for PubMedID 19563335

Abstract

The 5-yr survival rate of renal allografts is significantly lower for grafts from older deceased donors than from younger deceased donors. For evaluation of the potential contribution of renal senescence in this shortened graft survival, glomerular function and structure were analyzed in allografts from deceased donors older than 55 yr ("aging") or younger than 40 yr ("youthful"). Aging donors had a significantly higher prevalence of sclerotic glomeruli (P < 0.002), and their nonsclerotic glomeruli tended to be larger, had a larger filtration surface area (P = 0.02), and had a higher single-nephron ultrafiltration coefficient (K(f); P = 0.07), suggesting a compensatory response to functional loss of glomeruli. After serum creatinine reached a stable nadir in the transplant recipients, GFR and its hemodynamic determinants were evaluated and the whole allograft K(f) was computed. Compared with the allografts from youthful donors, allografts from aging donors exhibited a 32% lower GFR, which was exclusively attributable to a 45% reduction in allograft K(f) (both P < 0.001). In addition, the number of functioning glomeruli per allograft was profoundly lower in grafts from aging donors than from youthful donors (3.6 +/- 2.1 x 10(5) versus 8.5 +/- 3.4 x 10(5); P < 0.01), and this could not be explained by the relatively modest 17% prevalence of global glomerulosclerosis in the aging group. The marked reduction in overall glomerular number in many aging donors may lead to a "remnant kidney" phenomenon, potentially explaining the shorter mean survival of these allografts.

View details for DOI 10.1681/ASN.2008030306

View details for Web of Science ID 000262677200025

View details for PubMedID 18815243

View details for PubMedCentralID PMC2615719

Abstract

Strategies inhibiting cell death signaling pathways may enhance the availability of islet transplantation for patients with type 1 diabetes mellitus. The epsilon isoform of protein kinase C (PKC epsilon) has been shown to have an anti-apoptotic effect in many cell types. The present study investigated whether activation of PKC epsilon may improve the yield of functional islet cells for transplantation. Islet cells were isolated from wild-type BALB/c mice preconditioned with either a PKC epsilon activator (psi epsilon RACK) or a TAT carrier control peptide and further treated with the same agents during isolation and in vitro for either 0, 1, 16, or 40 hours. Islet cells were assessed at each time point for viability, apoptosis, and function. psi epsilon RACK-treated islets showed significantly decreased islet cell death up to 40 hours after isolation compared with TAT-treated control islets. Beta-cell function in response to high glucose challenge remained unchanged.

View details for DOI 10.1016/j.transproceed.2008.01.014

View details for Web of Science ID 000254695600014

View details for PubMedID 18374073

Abstract

We describe a recipient of combined kidney and hematopoietic-cell transplants from an HLA-matched donor. A post-transplantation conditioning regimen of total lymphoid irradiation and antithymocyte globulin allowed engraftment of the donor's hematopoietic cells. The patient had persistent mixed chimerism, and the function of the kidney allograft has been normal for more than 28 months since discontinuation of all immunosuppressive drugs. Adverse events requiring hospitalization were limited to a 2-day episode of fever with neutropenia. The patient has had neither rejection episodes nor clinical manifestations of graft-versus-host disease.

View details for Web of Science ID 000252507900006

Abstract

We conducted a randomized, multicenter study to determine whether treatment of subclinical rejection with increased corticosteroids resulted in beneficial outcomes in renal transplant patients receiving tacrolimus (TAC), mycophenolate mofetil (MMF) and prednisone. One hundred and twenty-one patients were randomized to biopsies at 0,1,2,3 and 6 months (Biopsy arm), and 119 to biopsies at 0 and 6 months only (Control arm). The primary endpoint of the study was the prevalence of the sum of the interstitial and tubular scores (ci + ct)> 2 (Banff) at 6 months. Secondary endpoints included clinical and subclinical rejection and renal function. At 6 months, 34.8% of the Biopsy and 20.5% of the Control arm patients had a ci + ct score >or= 2 (p = 0.07). Between months 0 and 6, clinical rejection episodes were 12 in 10 Biopsy arm patients and 8 in 8 Control arm patients (p = 0.44). Overall prevalence of subclinical rejection in the Biopsy arm was 4.6%. Creatinine clearance at 6 months was 72.9 +/- 21.7 in the Biopsy and 68.90 mL/min +/- 18.35 mL/min in the Control arm patients (p = 0.18). In conclusion, we found no benefit to the procurement of early protocol biopsies in renal transplant patients receiving TAC, MMF and prednisone, at least in the short term. This is likely due to their low prevalence of subclinical rejection.

View details for DOI 10.1111/j.1600-6143.2007.01979.x

View details for Web of Science ID 000250077600014

View details for PubMedID 17908280

View details for Web of Science ID 000249201700445

Abstract

Compliance with complex immunosuppressant drug therapies in transplant recipients might be improved with regimens that require less frequent dosing. A once-daily extended release (XL) formulation of tacrolimus has been developed that allows a 1:1 conversion from the twice-a-day tacrolimus (TAC) formulation and has a good exposure to trough concentration correlation. In an open-label, multicenter study, stable liver transplant recipients (n=69) were converted from twice-a-day TAC to XL once-daily in the morning, and were maintained for at least 2 years postconversion using the same therapeutic monitoring and patient care techniques employed with TAC. Two years after conversion, the incidence of biopsy-confirmed acute rejection was 5.8% (4 of 69); patient and graft survival was 98.6% (68 of 69). The safety profile of XL was consistent with that previously reported for TAC. Liver transplant recipients can be converted from twice-a-day TAC to once-daily XL and maintained for at least 2 years postconversion with neither unique efficacy nor safety concerns.

View details for DOI 10.1097/01.tp.0000265445.09987.f1

View details for Web of Science ID 000247578200019

View details for PubMedID 17589349

Abstract

Polycystic liver disease (PCLD) has long been considered to represent a contraindication to transjugular intrahepatic portosystemic shunt (TIPS) creation, primarily because of the risk of hemorrhage. Three-dimensional (3D) navigation within the enlarged and potentially disorienting parenchyma can now be performed during the procedure with the development of C-arm cone-beam computed tomography, which relies on the same equipment already used for angiography. Such a hybrid 3D reconstruction-enabled angiography system was used for safe image guidance of a TIPS procedure in a patient with PCLD. This technology has the potential to expedite any image-guided procedure that requires 3D navigation.

View details for DOI 10.1097/01.RVI.0000208984.17697.58

View details for Web of Science ID 000236836700015

View details for PubMedID 16614155

Abstract

Resistance to growth hormone (GH) in end-stage renal disease (ESRD) causes growth retardation and muscle wasting. In humans, circulating GH binding protein (GHBP), the extracellular domain of the GH receptor that is shed into the circulation and is believed to reflect tissue GH receptor levels, is reduced in uremia and suggests that cellular GH receptor levels are correspondingly reduced. If true, this could be a cause of GH resistance. We set out to establish whether serum GHBP levels reflect cellular GH receptor levels and whether changes in serum GHBP levels are related to nutritional or inflammatory status.GH receptor protein expression in peripheral blood mononuclear cells (PBMC) from 21 ESRD and 14 normal subjects were analyzed by fluorochrome flow cytometry.The GH receptor density and percent total PBMCs expressing the GH receptor were similar in the 2 groups, and there was no difference in percent GH receptor positive T or B cells or monocytes. In contrast, serum GHBP levels were 80% lower in ESRD. GHBP levels did not correlate with serum albumin, body mass index, or muscle mass but seemed to be partly related to the log serum C-reactive protein levels.Serum GHBP levels are markedly reduced in ESRD; this seems to occur independent of nutritional status and may in part be caused by inflammation. Because GH receptor expression on PBMC of ESRD and control subjects was similar, our findings argue against a reduction in GH receptor as a cause of GH resistance and the use of serum GHBP levels as a reliable marker of specific tissue GH receptor levels.

View details for DOI 10.1053/j.jrn.2006.01.007

View details for Web of Science ID 000236735600007

View details for PubMedID 16567271

Abstract

Certain clinical risk factors are associated with significant coronary artery disease in kidney transplant candidates with diabetes mellitus. We sought to validate the use of a clinical algorithm in predicting post-transplantation mortality in patients with type 1 diabetes. We also examined the prevalence of significant coronary lesions in high-risk transplant candidates.All patients with type 1 diabetes evaluated between 1991 and 2001 for kidney with/without pancreas transplantation were classified as high-risk based on the presence of any of the following risk factors: age >or=45 yr, smoking history >or=5 pack years, diabetes duration >or=25 yr or any ST-T segment abnormalities on electrocardiogram. Remaining patients were considered low risk. All high-risk candidates were advised to undergo coronary angiography. The primary outcome of interest was all-cause mortality post-transplantation.Eighty-four high-risk and 42 low-risk patients were identified. Significant coronary artery stenosis was detected in 31 high-risk candidates. Mean arterial pressure was a significant predictor of coronary stenosis (odds ratio 1.68; 95% confidence interval 1.14-2.46), adjusted for age, sex and duration of diabetes. In 75 candidates who underwent transplantation with median follow-up of 47 months, the use of clinical risk factors predicted all eight deaths. No deaths occurred in low-risk patients. A significant mortality difference was noted between the two risk groups (p = 0.03).This clinical algorithm can identify patients with type 1 diabetes at risk for mortality after kidney with/without pancreas transplant. Patients without clinical risk factors can safely undergo transplantation without further cardiac evaluation.

View details for DOI 10.1111/j.1399-0012.2005.00461.x

View details for Web of Science ID 000237095200001

View details for PubMedID 16640517

Abstract

To evaluate retrospectively the endovascular management of hepatic venous outflow obstruction after piggyback orthotopic liver transplantation.The study was performed with the approval and under the guidelines of the institutional review board and complied with the Health Insurance Portability and Accountability Act. Informed consent from patients was not required by the institutional review board for this retrospective study. From 1995 to 2003, 13 patients (eight male, five female), including 12 adults and one adolescent (age range, 14-67 years; median age, 52 years), underwent endovascular treatment of hepatic venous outflow obstruction after piggyback orthotopic liver transplantation. Patients gave informed consent for all procedures. Eleven patients received whole livers, and two received living-related donor right liver lobes. Four underwent repeat piggyback orthotopic liver transplantation prior to intervention. Primary stent placement was performed in 12 patients. One patient refused primary stent placement and chose venoplasty alone, but required a stent 5 months later. Short balloon-expandable stents (mean diameter, 14.6 mm +/- 1.1 [standard deviation]) were used to minimize jailing of branch vessels and to resist recoil. Pre- and post-procedural pressure gradients were measured. Follow-up included venography, cross-sectional imaging, and laboratory tests. The Wilcoxon signed rank test or the sign test was performed to compare pre- and post-procedural pressure gradients, body weights, and laboratory values.Technical success (pressure gradient < or = 3 mm Hg) was achieved in 13 of 13 patients, and clinical success, in 12 of 13. Mean pre- and post-procedural pressure gradients were 13.0 mm Hg +/- 1.4 and 0.8 mm Hg +/- 0.3. Mean interval from transplantation to intervention was 348 days +/- 159. Mean follow-up was 678 days (range, 16-2880 days). Technical success did not result in clinical improvement in one patient. Biopsy demonstrated severe hepatic necrosis, likely from prolonged venous congestion, and the patient required repeat transplantation. Only one patient required reintervention for stent migration, and no other complications occurred. No significant restenosis was encountered after stent placement.Hepatic venous outflow obstruction is an uncommon but potentially fatal complication of piggyback orthotopic liver transplantation. Endovascular treatment with balloon-expandable stents is effective, safe, and apparently durable.

View details for DOI 10.1148/radiol.2361040327

View details for Web of Science ID 000229905300046

View details for PubMedID 15955856

Abstract

Tacrolimus improves lipid profile in renal and liver transplant recipients. The impact of conversion from cyclosporine microemulsion (Neoral) to tacrolimus (Prograf) in a large randomized study of stable heart transplant recipients with treated but persistent mild dyslipidemia is reported.One hundred twenty-nine long-term (>or=12 months) cyclosporine microemulsion-treated heart transplant recipients with low-density lipoprotein cholesterol >2.5 mmol/liter and/or a total cholesterol/high-density lipoprotein cholesterol ratio >4 were recruited for the study. Complete lipid profile was assessed before (baseline) and after 6 months of treatment with either cyclosporine microemulsion maintenance (n=64) or tacrolimus conversion (n=65).At 6 months, tacrolimus-converted patients exhibited a greater decrease in total cholesterol (from 5.51 +/- 0.16 to 4.88 +/- 1.22 mmol/liter [tacrolimus], vs 5.61 +/- 1.36 to 5.38 +/- 0.87 mmol/liter [cyclosporine]; p = 0.0078). This decrease in cholesterol was caused largely by a decrease in low-density lipoprotein cholesterol (-0.41 +/- 0.54 [tacrolimus] vs -0.13 +/- 0.55 [cyclosporine]; p=0.0018). There were no changes in high-density lipoprotein cholesterol and triglyceride levels, but apolipoprotein B therapy was reduced in tacrolimus-converted vs cyclosporine-maintained patients (p=0.0003). By 6 months, 23.7% of tacrolimus- vs 6.7% of cyclosporine-treated patients met the target lipid levels for high-risk patients (p=0.0094). Conversion from cyclosporine to tacrolimus resulted in decreases in blood urea nitrogen, creatinine, and uric acid without any changes in glucose, HbA(1C), and insulin levels.Conversion from cyclosporine microemulsion- to tacrolimus-based immunoprophylaxis resulted in decreased cholesterol, apolipoprotein B, urea, creatinine, and uric acid without any clinically evident perturbation of glucose metabolism in stable heart transplant recipients with treated but persistent mild dyslipidemia.

View details for DOI 10.1016/j.healun.2004.05.023

View details for Web of Science ID 000230423400002

View details for PubMedID 15982605

View details for Web of Science ID 000229231600418

View details for Web of Science ID 000229231602300

Abstract

Modified release (MR) tacrolimus is an extended release formulation administered once daily. The purpose of this pharmacokinetic (PK) study was to evaluate tacrolimus exposure in stable liver transplant recipients converted from Prograf twice a day to MR tacrolimus once daily.This was an open-label, multicenter study with a single sequence, four-period crossover design. Eligible patients were 18 to 65 years of age, >6 months posttransplant with stable renal and hepatic function and receiving stable doses of Prograf twice a day for >2 weeks prior to enrollment. Patients received Prograf twice a day on days 1 to 14 and 29 to 42. Patients were converted to the same milligram-for-milligram daily dose of MR once daily on days 15 to 28 and 43 to 56. Twenty-four-hour PK profiles were obtained on days 14, 28, 42, and 56. Laboratory and safety parameters were also evaluated.Of 70 patients, 62 completed all four PK profiles. The AUC0-24 of tacrolimus was comparable for Prograf twice a day (days 14 and 42) and MR tacrolimus once daily (days 28 and 56). The 90% confidence intervals for MR tacrolimus versus Prograf at steady state (days 28 and 56 vs days 14 and 42) was 0.85 to 0.92 for AUC0-24. MR tacrolimus was well tolerated with a safety profile comparable to that of Prograf. AUC0-24 was highly correlated to Cmin for Prograf (day 14, r = .93; Day 42, r = .89) and for MR tacrolimus (day 28, r = .93; day 56, r = .92). Renal and liver function remained stable. One patient experienced acute rejection.The steady-state tacrolimus exposure of MR tacrolimus once daily is equivalent to Prograf twice a day after a milligram-for-milligram conversion in stable liver transplant recipients.

View details for DOI 10.1016/j.transproceed.2004.11.086

View details for Web of Science ID 000228568900224

View details for PubMedID 15848672

Abstract

There have been no published data on use of the the newer immunosuppressants tacrolimus and mycophenolate mofetil (MMF) in high immunological risk renal transplantation. We therefore undertook a prospective study to systematically assess outcomes using these agents as part of an aggressive immunosuppressive regimen.Fifty-nine high-risk renal allograft recipients were enrolled at 10 Canadian sites and given a regimen of: a biological induction agent, tacrolimus, MMF, and corticosteroids. Patients included 10 (17%) who had lost a previous graft to rejection <1 yr, 31 (53%) with a current panel reactive antibody (PRA) >30%, 47 (80%) with a historic PRA >50%, four (7%) who had a positive historical T-cell crossmatch with the current donor, and six (10%) with a current positive B-cell crossmatch. The mean peak PRA was 76 +/- 33%.The estimated 3-yr Kaplan-Meier patient and graft survival estimates were 89% and 75%, respectively. There were nine graft losses other than deaths with a functioning graft, of which six were preceded by delayed graft function (p = 0.01, chi2). Sixteen (27%) recipients experienced at least one episode of biopsy-confirmed acute rejection. Infections included cytomegalovirus in 16 patients, eight of whom had tissue-invasive disease. Only one malignancy occurred.The immunosuppressive strategy investigated is effective and displays a satisfactory safety profile in high immunological risk renal allograft recipients.

View details for DOI 10.1111/j.1399-0012.2005.00275.x

View details for Web of Science ID 000226347700005

View details for PubMedID 15659130

Abstract

Nephron underdosing and donor kidney-recipient body size mismatch can lead to poor allograft function. The purpose of this study is to examine the relationship between donor kidney volume and posttransplantation graft function by using magnetic resonance imaging (MRI) to obtain renal volumes. Previous investigators used donor body surface area as a surrogate for kidney size or measured renal volume by using ultrasonography; both these techniques are inaccurate measures of renal volume. Intraoperative weights are more accurate, but provide information only after the transplantation is underway. More recently, MRI has been used preoperatively to screen living donors; these novel MRI techniques also provide information regarding renal size.We performed a retrospective analysis of 54 patients who underwent living donor transplantation at our institution from 2000 to 2002. All living donors underwent preoperative renovascular imaging using MRI, and renal volumes were obtained for each donor. A transplant kidney volume-recipient body weight (Vol/Wt) ratio was determined for each donor-recipient pair, and patients were divided into tertiles corresponding to 3 groups: high (>2.7), medium (2 to 2.7), and low (<2) "nephron dose" ratios.Glomerular filtration rate (GFR) correlated with Vol/Wt ratio at 6 and 12 months (r = 0.46; P = 0.0005 and r = 0.41; P = 0.003). At 6 months, mean GFRs in the low, medium, and high groups were 52.4 +/- 2.8 (SEM), 64.5 +/- 6.2, and 82.0 +/- 4.4 mL/min, respectively (P < 0.0005). At 12 months, GFRs in the low, medium, and high groups were 51.6 +/- 3.6, 63.3 +/- 3.8, and 83.9 +/- 5.4 mL/min, respectively (P < 0.0001).Transplantation of donor-recipient pairs with a Vol/Wt ratio less than 2 cm 3 /kg was associated with significantly worse graft function. Donor kidney volumes measured by means of preoperative MRI can be used to calculate Vol/Wt ratios before transplantation and identify patients at risk for a low GFR posttransplantation.

View details for DOI 10.1053/j.ajkd.2004.07.012

View details for Web of Science ID 000225044100015

View details for PubMedID 15492954

View details for Web of Science ID 000221322500721

View details for Web of Science ID 000186219100048

Abstract

The combined effects of RAD and Neoral were tested in a rat orthotopic small-bowel transplantation model. Seven groups (n = 6) were involved in this study, and each one was included in three rejection models for the evaluation of host-vs.-graft disease (HVG) (LBN-F1 to LEW), graft-vs.-host disease (GVH) (LEW to LBN-F1), and combined HVG and GVH immune responses (BN to LEW). Both drugs were administered orally throughout the study. Low doses of RAD (1.0-2.5 mg/kg/day) combined with Neoral (2.0-5.0 mg/kg/day) produced strong synergistic effects in the prolongation of small-bowel graft survival in HVG (combination index, CI = 0.095, 0.1212), GVH (CI = 0.027, 0.020), and combined HVG and GVH immune responses (CI = 0.070, 0.301). The combination therapy of RAD and Neoral produces a strong synergistic effect toward the inhibition of HVG, GVH, and combined HVG and GVH immune responses in a rat small-bowel transplantation model.

View details for DOI 10.1002/micr.10167

View details for Web of Science ID 000186223500016

View details for PubMedID 14558006

View details for Web of Science ID 000177757500945

View details for Web of Science ID 000177369700141

View details for PubMedID 12176540

View details for Web of Science ID 000177320600079

View details for PubMedID 12173862

Abstract

Mycophenolate mofetil (MMF), an immunosuppressant drug used in organ transplantation to prevent rejection, is being used increasingly in association with cyclosporine and tacrolimus. Mycophenolic acid (MPA) is primarily metabolized in the liver to its 7-O-glucuronide (MPAG) derivative. The concentrations of MPAG in serum are many times the concentrations of MPA. Although MPAG has not shown immunosuppressant activity, it was postulated that it could displace MPA from its binding sites on albumin and hence increase the biologic effects of MPA. This effect could be important for patients with acute renal failure; under this condition, MPAG was shown to accumulate. The goal of this study was to document the MPAG/MPA concentration ratio in 100 renal transplant patients under a mixed immunosuppressive therapy. Further, the study addressed the question of whether MPAG can displace MPA in vivo from bound albumin in a representative renal transplant patient population under immunosuppressive therapy. Levels of MPAG and MPA were measured by high-performance liquid chromatography. The distribution of the ratios was not parametric as it tailed toward elevated values. After a square root transformation of the data, parametric analysis was possible. The average MPAG/MPA ratio was 15.0 +/- 2.2 for men versus 7.7 +/- 0.9 for women. Men treated with MMF and tacrolimus showed a lower ratio than patients treated with MMF and cyclosporine, confirming that tacrolimus inhibits glucuronidation of MPA. Further, it was determined that at physiologic concentrations, MPAG does not increase the amount of free MPA. Because MPAG can favor the elimination of MPA, it can be concluded that gender differences and cotreatment with tacrolimus must be taken into consideration when MMF is being administered.

View details for Web of Science ID 000171210300004

View details for PubMedID 11591897

View details for Web of Science ID 000167629900490

View details for PubMedID 11267183

View details for Web of Science ID 000167629900592

View details for PubMedID 11267285

Abstract

To evaluate the effect of intraoperative transfusion of red blood cells (RBCs) on patient and graft survival.A retrospective study.A tertiary care referral center.Between January 1, 1992, and December 31, 1994, medical records from 225 adult patients who underwent primary liver transplantations were analyzed.Overall patient survival was 90% at 1 year and 86% at 3 years, while graft survival was 89% at 1 year and 85% at 3 years. The following factors were associated with patient and graft survival: age, sex, medical condition at the time of transplantation, and intraoperative transfusion of RBCs. When these factors were subjected to a multivariate analysis, all were independently associated with survival. Fifty-four recipients (24%) underwent transplantation without intraoperative transfusion of RBCs, while 171 recipients (76%) received at least 1 U of RBCs intraoperatively. Recipients who did not receive transfusion of RBCs had higher patient and graft survival rates than patients who did receive RBCs. By multivariate analysis, transplantation without intraoperative transfusion of RBCs no longer remained statistically significant, and only sex and the patient's medical condition were independently associated with patient and graft survival. Patient and graft survival decreased if 5 or more U were transfused, but transfusion of 5 or more U was not independently associated with survival by multivariate analysis.Increased transfusion requirement for RBCs was independently associated with patient and graft survival. While transplantation without transfusion of intraoperative RBCs was associated with superior patient and graft survival, these effects were overridden by patient sex and medical condition at the time of transplantation.

View details for Web of Science ID 000078053500006

View details for PubMedID 9927126

View details for Web of Science ID 000083530400001

Abstract

Gingival Hyperplasia (GH) and hypertrichosis (HT) are two sides effects associated with the usage of cyclosporine (CyA) but not with tacrolimus (FK 506). The aim of this study is to evaluate the efficacy and security of the conversion from CsA to FK 506 to treat those two complications. From August 1996 to May 1997, 15 patients (9 males, 6 females) aged from 23 to 63 years old (38 +/- 14, mean +/- SD) were switched from CsA to FK 506, 12 for GH, 2 for HT and one for combined presentation. FK 506 was first initiated at a dose of 0.15 mg/kg/day and then adjusted to a level target of 8 ng/ml. The conversion was done on an out patient basis at average 35 (5-83) months after transplantation. Patients were followed prospectively for 12 months. There was a significant reduction in GH in all patients within 3 months. Five out 13 patients had a complete resolution of GH within three months of conversion, 9/12 within 6 months and all by 12 months. HT resolved completely within 6 months. No rejection episode occurred and the serum creatinin remain stable over one year post conversion. Conversion from CsA to FK 506 is thus a safe and valid option to treat CsA induced GH and HT.

View details for PubMedID 10584376

View details for Web of Science ID 000074150800049

View details for PubMedID 9636424

View details for Web of Science ID 000074150800132

View details for PubMedID 9636507

Abstract

To assess the feasibility and outcome of a piggyback technique without caval occlusion or veno-venous bypass (VB), we retrospectively reviewed 131 consecutive adult orthotopic liver transplantation (OLT) performed in 129 patients between May 1993 and February 1995. Six were second transplants, and six were combined liver-kidney transplants. The piggyback technique was attempted in all cases.We were able to perform the piggyback technique in 98 OLTs (75%). The remaining 33 OLTs (25%) were converted to the standard technique; of these, 20 (15%) required VB. The reasons for conversion to the standard technique were: anatomical (22 transplants), severe portal hypertension requiring VB (8 transplants), tumor (1 transplant), and other reasons (2 transplants). Six retransplantations were performed (four piggyback, two standard).There was no significant difference in age, United Network for Organ Sharing status, Child's classification, and diagnosis between the patients in whom piggyback was possible or not. The actuarial patient and graft survival at 1 year were similar between the piggyback group and the group of patients converted to standard technique (87/85% vs. 86/86%, respectively). No death was related to either technique. With piggyback, the average operative time was 8.6+/-1.9 hr, median amount of blood transfused intraoperatively was 2 U (33% did not require transfusion), and median intensive care unit and hospital stays were 3 and 11 days, respectively. With the piggyback technique, the mean preoperative and maximum postoperative serum creatinine levels were 1.4+/-1.0 and 1.8+/-1.5 mg/dl.The piggyback technique without caval occlusion is possible in the majority of patients. It is safe and has reduced the use of VB to 15% of our adult OLTs. The piggyback technique avoids retrocaval dissection, facilitates retransplantation, and is associated with a short anhepatic phase, low blood product usage, and short intensive care unit stay.

View details for Web of Science ID 000071516900014

View details for PubMedID 9448148

Abstract

Combined use of tacrolimus (FK506) with sirolimus (rapamycin [RAPA]) was examined in a model of vascularized heart allograft in the rat. For prevention of acute rejection, three different combinations of low doses of FK506 and RAPA from day 1 up to day 14 after transplantation produced significantly longer cardiac allograft survival than each agent alone (P<0.05). Identical results were observed in a model of reversal of ongoing acute rejection, where two combinations of low doses of FK506 and RAPA from day 4 up to day 18 after surgery also demonstrated significantly longer graft survival than each immunosuppressant alone (P<0.05). All the low-dose-treated groups in these two models presented significantly longer heart graft survival than naive controls (P<0.05), confirming that both agents are potent immunosuppressants in the models chosen. These results also indicate that, in contrast with in vitro studies, the combined use of FK506 and RAPA in vivo did not produce antagonism, but rather had synergistic effect in prolonging the allograft survival as compared with each agent alone. It appears likely that the abundance of FKBP-12 available for binding in vivo prevents inhibitive competition of the two agents for their receptor.

View details for Web of Science ID 000071404400039

View details for PubMedID 9422432

Abstract

To evaluate the long-term results of peripheral biliary diversion by means of anastomoses of the left lobe of the liver to the stomach.Transhepatic perforation of the left lobe of the liver into the lesser curvature of the stomach was performed in 35 patients with a presumed diagnosis of malignant obstructive jaundice. Jaundice was found to be caused by a malignant stricture in 32 patients and a benign stricture in three. Perforation was performed under fluoroscopic, endoscopic, and laparoscopic guidance in 33 patients and without laparoscopy in the other two. The hepaticogastric anastomosis was secured with a gastrostomy tube; patency of the tract was maintained with placement of a metallic stent. Kaplan-Meier analysis was used to evaluate survival, anastomosis patency rate, and jaundice recurrence.Technical success was achieved in all patients. Two (6%) patients had anastomotic obstruction. The actuarial survival rate was 91%, 80%, 59%, and 26% at 1, 3, 6, and 12 months. The mean patency was 234 days +/- 252. The jaundice-free rate among surviving patients was 100%, 96%, 93%, and 80% at 1, 3, 6, and 12 months. The reintervention rate was 14%. Late cholangitis occurred in seven (20%) patients.This peripheral diversion procedure appears to be safe and shows good long-term patency.

View details for Web of Science ID A1997XR60200031

View details for PubMedID 9280259

View details for Web of Science ID A1997WM12700297

View details for PubMedID 9123486

Abstract

To determine the loss of endogenous GSH from livers cold-stored and reperfused, using a model of liver transplantation in the pig.Four female Yorkshire pigs weighing 19 to 40 kg received a liver allograft. Donor livers were cold-stored in the UW solution. Mean cold ischemic time was 6.5 hours. Malondialdehyde (MDA) levels were used as an index of oxidative stress. MDA plasma levels were measured following recipient laparotomy (H0), immediately (H1), and 90 minutes after liver reperfusion (H2). MDA and GSH levels in liver were measured following donor laparotomy (T0), at the end of cold ischemic period (T1), and at 90 minutes following liver reperfusion (T2).Three animals survived. MDA liver levels decreased of 44% between T0 and T1, then increased to 92% at T2. In contrast, in plasma, graft reperfusion was associated with an increase of MDA to 140% of the baseline values which reached 188% at H2. Intrahepatic GSH levels decreased of 49% at T1, then to 72% at T2.our study suggests that in liver transplantation: (1) Hepatic GSH is depleted to 49% during cold-storage, and an additional 23% is lost after reperfusion; (2) GSH contained in the UW solution does not prevent the loss of hepatocellular glutathione during preservation and reperfusion; (3) after short periods of cold ichemia, endogenous hepatic GSH may protect against oxydative stress in the transplanted liver.

View details for Web of Science ID A1997YF47800002

View details for PubMedID 9734091

Abstract

This study examines factors associated with the performance of orthotopic liver transplantation (OLT) without red blood cell (RBC) transfusion.Between January 1992 and December 1994, 306 primary OLTs were performed with recipients divided into two groups: group 1 patients (61 recipients, 20% of total) underwent transplantation without packed RBCs, and group 2 patients (245 recipients, 80% of cases) received a transfusion of at least 1 unit of RBCs during operation.Recipients in group 1 compared with group 2 had less advanced liver disease (20% hospitalized and 48% Child's class C versus 58% hospitalized and 73% Child's class C, p < 0.01) and lower frequency of right upper quadrant surgery (13% versus 25%, p < 0.05). Group 1 recipients also had significantly higher preoperative hematocrits (38% versus 33%, p < 0.01), lower prothrombin times (15.4 versus 16.7 seconds, p < 0.001) and partial thromboplastin times (36.9 versus 42.2 seconds, p < 0.01), a greater proportion of patients transplanted by piggyback technique (87% versus 59%, p < 0.001), and shorter operative times (7.9 hours versus 9.2 hours, p < 0.001). Moreover, a greater percentage of patients underwent OLT without RBC transfusion in each successive year: 9% in 1992, 21% in 1993, and 31% in 1994 (p < 0.001). Logistic regression analysis showed the following factors to be independent predictors of OLT without RBC transfusion. Preoperative Hct, United Network of Organ Sharing status, piggyback technique, operative time, and year of transplantation.OLT can be performed without transfusion of RBCs in recipients with less advanced liver disease, and surgical technique, along with increased experience by the transplant team, are important factors.

View details for Web of Science ID A1996VP42300036

View details for PubMedID 8862380

Abstract

A model of chronic vascular rejection of cardiac allografts has been developed in inbred rats using the WF.1L/Gut congenic strain as donor into LEW recipients. The hearts beat for more than 200 days without the need for exogenous immunosuppression. The histopathology is characterized by cellular rejection, vasculitis, and myointimal arterial wall thickening, and by day 60 posttransplant, there are widespread occlusive vascular changes similar to those seen in human cardiac allografts. CsA, at a dose of 15 mg/kg/d, is effective in preventing as well as reversing the vasculopathy. These data (1) confirm other studies of ours on the reliability of the experimental model using this strain combination, (2) establish the time window of days 40 to 60 whereby mechanisms of lesion regression can be studied, (3) prove the MHC class I and class II antigen incompatibility are not a necessary condition for the generation of the vascular lesions, (4) show that CsA is a useful probe for study of the vasculopathy, and (5) suggest that the model is a useful probe of the mechanism of action of CsA.

View details for Web of Science ID A1994PM60300032

View details for PubMedID 7940792

View details for Web of Science ID A1993KN62100029

View details for PubMedID 8438504

Abstract

Simultaneous harvesting of the liver and whole pancreas is usually not performed because it is believed that the shared vascular supply of both organs is incompatible with safe grafting. A careful review of the vascular anatomy, however, shows that simultaneous removal of the two organs is feasible, and a technique is described by which the liver is revascularized in the recipient through the celiac axis or the common hepatic artery and the pancreas is revascularized through the superior mesenteric and splenic arteries. When the vascular supply is abnormal, reconstruction of the vascular tree of one or both organs may be needed. The results of this technique used on 10 recipients are analysed.

View details for Web of Science ID A1990DV37100008

View details for PubMedID 2383835