High-risk Kidney Transplant Recipients Research Articles

1378. Impact of Cytomegalovirus Prophylaxis on Clinical Outcomes in Kidney Transplantation: A United States Renal Data System-Medicare Linked Database Study

BackgroundGuidelines recommends cytomegalovirus (CMV) prophylaxis by CMV serostatus/risk status, as the currently available antiviral agents may lead to myelosuppressive events in kidney transplant recipients (KTRs). Limited data exist for the United States (US) on the such clinical outcomes with CMV prophylaxis KTRs especially stratified by CMV risk strata. We examined the associations between clinical outcomes and CMV prophylaxis among adult KTRs stratified by CMV risk strata. MethodsWe employed a retrospective cohort design using the US Renal Data System registry-linked Medicare data (2011-2017). The cohort included 22,918 adult KTRs with continuous Medicare Part A & B coverage for ≥ 6-month pre and ≥ 12-month post KT and Part D coverage for ≥ 12-month post- KT. CMV prophylaxis was defined as ≥ 1 prescription fill or medical claim for valacyclovir or valganciclovir at prophylaxis doses within 28 days post-KT. ResultsCMV prophylaxis was utilized by 75% of the cohort. In no CMV prophylaxis group, 52.2% and 34.2% of high and intermediate risk KTRs received valganciclovir (as either pre-emptive or deferred therapy), respectively. Among high risk KTRs, CMV prophylaxis group had significantly lower proportions of KTRs with CMV infection, opportunistic infections (OIs) including bacterial, and fungal infections, and new onset of diabetes mellitus (NODAT) compared to no prophylaxis group. There were no differences in the rates of acute rejection or death; however, a trend towards lower rate of graft-failure at 12-month post-KT. Nearly 40% of high-risk KTRs had myelosuppressive events (leukopenia: 18%; neutropenia:15% thrombocytopenia :19%); however, their differences were non-significant except for thrombocytopenia by CMV prophylaxis status (Table 1). CMV infection and myelosuppressive event rates were higher in high-risk than intermediate/low risk KTRs irrespective of CMV prophylaxis status. ConclusionCMV prophylaxis was associated with lower rates of CMV infection, OIs, NODAT and graft failure compared to no prophylaxis, however, the burden of CMV infection, OIs and myelosuppression was greater in high-risk KTRs indicating further research is needed on factors associated with greater disease burden in high-risk KTRs. Table 1Disclosures Amit D. Raval, PhD, Merck and Co., Inc. (Employee) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder)

1387. Impact of Cytomegalovirus Prophylaxis on Healthcare Resource Use and Costs among Kidney Transplant Recipients: A United States Renal Data System-Medicare Linked Database Study

BackgroundCytomegalovirus (CMV) management requires a balance between reducing the risk of CMV infection and avoiding anti-viral toxicities. Limited information is available on the impact of CMV prophylaxis on the healthcare resource use (HCRU) and costs among adult kidney transplant recipients (KTRs) in the United States. Therefore, we examined HCRU and cost associated with CMV prophylaxis stratified by the CMV risk categories among KTRs at 1-year post-KT. MethodsWe identified a cohort of 22,918 adults first-time KTRs during 2011–2017 using the US Renal Data System registry-linked Medicare data. Additional inclusion criteria were to have continuous coverage in Medicare Part A & B for ≥ 6-month pre- and ≥ 12-month post KT and Medicare Part D for ≥12-month post-KT. CMV prophylaxis was confirmed as ≥ 1 prescription fill for valacyclovir/(val)ganciclovir prophylaxis doses within 28 days post-KT. ResultsCMV prophylaxis was utilized in 86%, 82%, and 32% of high, intermediate, and low-risk KTRs with an average cost of prophylaxis per KTRs of &16,241, &9481, and &8,648, respectively. In no prophylaxis groups, valganciclovir was utilized in 52%, 34%, and 36% of KTRs (as either pre-emptive or deferred therapy) with an average cost of &6,719, &2,722, and &431 among high, intermediate, and low-risk KTRs, respectively. Among high-risk KTRs, CMV prophylaxis group had a significantly higher prescription drug cost (&26,060 vs. &13,433) but a lower average direct healthcare medical cost (&84,914 vs. &101,268), mainly due to lower all-cause hospitalization cost (&56,758 vs. &69,852) (Table 1). CMV prophylaxis group had lower rates of all-cause rehospitalization, and CMV-and opportunistic infection (OIs)-related hospitalization compared to no prophylaxis (Table 2). In high-risk KTRs, nearly 32% had myelosuppressive events-related hospitalization, and 15% filled granulocyte colony-stimulating factors with an average cost of &4,695 per treated KTR.ConclusionCMV prophylaxis had a higher cost of medications but had a lower medical cost with including all-cause and CMV-related hospitalizations. Myelosuppressive events were frequent and resource-intensive especially in high and intermediate-risk KTRs. Disclosures Amit D. Raval, PhD, Merck and Co., Inc. (Employee) Yuexin Tang, PhD, JnJ (Other Financial or Material Support, Spouse’s employment)Merck & Co., Inc. (Employee, Shareholder)

Bimonthly viral monitoring for late-onset cytomegalovirus infection in kidney transplant recipients.

Kidney transplant recipients with high-risk cytomegalovirus (CMV) serostatus (seropositive donor to seronegative recipient) are at risk for late-onset CMV after cessation of antiviral prophylaxis. We report findings from a strategy of bimonthly (every 2weeks) CMV screening for late-onset CMV. This is a single-center retrospective cohort study of 70 high-risk CMV kidney transplant recipients transplanted between June 2016 and September 2018. Patients were monitored at 6-12months post-transplantation for late-onset CMV using bimonthly CMV nucleic acid testing (NAT). Adherence to screening and its correlation with CMV-related hospitalizations were assessed. Failure to prevent CMV-related hospitalization was classified into three categories (non-adherence to CMV testing, rapid CMV progression, and health system failure). Twenty-one (30%) patients developed CMV DNAemia, of whom 10 (14%) required hospitalization. Reasons for CMV-related hospitalization despite screening were (i) screening non-adherence (50%), (ii) rapid progression (40%), and (iii) health system failure (10%). Adherence to screening was associated with lower viral counts at diagnosis (r=-.44, p=.049) and a trend towards lower risk of CMV-related hospitalization (OR: 0.97 per 1% increase in adherence; 95% CI: 0.94-1.00; p=.06). Bimonthly monitoring for late-onset CMV allows for early CMV detection and may lower CMV-related hospitalization.

The burden of cytomegalovirus infection remains high in high-risk kidney transplant recipients despite six-month valganciclovir prophylaxis.

Cytomegalovirus continues to be a concern after transplantation despite prophylaxis regimens. Our aim was to analyse post-prophylaxis primary cytomegalovirus infections among kidney transplant recipients after 6-month valganciclovir prophylaxis and to determine the usefulness of surveillance after prophylaxis. Data from all cytomegalovirus D+/R- kidney transplant recipients from January 2004 to October 2018 at our center who received 6-month prophylaxis with valganciclovir were retrospectively analysed (N=481). Detailed analyses were performed for 136 patients who were monitored every 2-4weeks for DNAemia after the discontinuation of prophylaxis. Post-prophylaxis primary cytomegalovirus infection occurred in 182/481 (38%) patients median 264days after transplantation (IQR: 226-367) and median 84days after the end of prophylaxis (IQR: 46-187). In 49% patients, cytomegalovirus infection occurred over 3 months after the end of prophylaxis. Cytomegalovirus infection was not associated with lower patient or graft survival and no independent risk factors for infection were found. From patients monitored closely, 71/136 (52%) patients developed post-prophylaxis primary cytomegalovirus infection. Altogether, 52/136 (38%) patients were diagnosed with probable post-prophylaxis cytomegalovirus disease and 19/136 (14%) patients had asymptomatic CMV infection. Recurrent infection occurred in 38/71 (39%) patients. The incidence of post-prophylaxis primary cytomegalovirus infection among D+/R- kidney transplant recipients remains high despite 6-month prophylaxis. Surveillance after prophylaxis was challenging as a considerable portion of the infections occurred late and already symptomatic.

Early cytomegalovirus DNAemia and antiviral dose adjustment in high vs intermediate risk kidney transplant recipients.

Cytomegalovirus (CMV) infection continues to negatively affect outcomes for solid organ transplant recipients, despite the advent of strategies for preemptive surveillance and prophylaxis. The impact is especially great for CMV seronegative recipients of donor seropositive organs, who typically lack the ability to control CMV infection at the time of transplantation. We reviewed episodes of CMV DNAemia in a modern cohort of kidney transplant recipients over a 3-year period at a high-volume transplant center to investigate the frequency of DNAemia during antiviral prophylaxis. Despite receipt of antiviral prophylaxis per current guidelines, 75 cases of CMV DNAemia were observed in the first 100days after transplantation. For high risk patients, median time to DNAemia was 75days after transplantation, and the majority of patients had experienced dose-reduction of valganciclovir due to renal insufficiency. Review of CMV seropositive intermediate risk patients demonstrated DNAemia occurring earlier after transplantation compared with high risk patients with a median time of 64days (P=.029). The impact of valganciclovir dose adjustment was less notable in the intermediate risk group. Guidelines recommend beginning routine surveillance for CMV after the completion of antiviral prophylaxis. Our findings suggest that closer monitoring may be beneficial, especially for high risk patients at risk for DNAemia. Patients requiring dose adjustment of valganciclovir due to renal insufficiency may be at increased risk for CMV DNAemia. Improved methods for CMV prophylaxis and evaluation of immunologic risk for CMV DNAemia and disease are needed to improve patient outcomes after kidney transplantation.

Effect of mTOR inhibitors during CMV disease in kidney transplant recipients: Results of a pilot retrospective study.

mTOR inhibitors exert a preventive effect on cytomegalovirus (CMV) disease in CMV seropositive (R+) kidney transplant recipients, but their impact during the curative treatment of CMV disease in high-risk kidney transplant recipients has not been investigated. We aimed to evaluate the efficacy and tolerance of mTOR inhibitors compared with mycophenolic acid in 63 consecutive kidney transplant recipients (80% of D+R-) suffering from CMV disease with a persistent or a recurrent CMV DNAemia. In this monocentric retrospective study, 16 had their treatment converted to mTOR inhibitors and 47 did not. The Kaplan-Meier curves did not show any significant differences in CMV DNAemia eradication (77% vs. 88% respectively; hazard ratio (HR), 1.648 [95% confidence interval (CI), 0.913-2.973]; log-rank test, P = .132), DNAemia recurrence (36% vs. 47%; HR, 1.517 [95% CI, 0.574-4.007]; log-rank test, P = .448) and CMV clinical recurrence (17% vs. 27%; HR, 1.375 [95% CI, 0.340-5.552]; log-rank test, P = .677) between patients who received mTOR inhibitors and those who did not. These results were confirmed in uni- and multivariate time-dependent Cox regressions. In summary, conversion from mycophenolic acid to mTOR inhibitors seems inadequate for improving CMV clearance or in better preventing CMV recurrences during severe or persistent CMV disease.

TruGraf® Testing in High-Risk Kidney Transplant Recipients

TruGraf® Testing in High-Risk Kidney Transplant Recipients

Prevalence of Perineural Invasion in keratinocyte cancer in the general population and among organ transplant recipients

Basal cell carcinomas (BCCs) and cutaneous squamous cell carcinomas (SCCs) are the most commonly encountered cancers in fair-skinned populations worldwide. Perineural invasion is associated with worse outcomes for patients with BCC or SCC. Estimates of perineural invasion prevalence range widely, likely reflecting non-representative patient samples. We sought to determine the prevalence of perineural invasion in BCC and SCC in the general population, as well as among cancers arising in solid organ transplant recipients. We retrospectively analysed histopathology reports of BCC and SCC from patients enrolled in the QSkin Study (a population-based cohort of 43794 Queensland residents recruited 2010-2011) and the Skin Tumours in Allograft Recipients (STAR) study (a cohort of 509 high-risk kidney or liver transplant recipients at the Princess Alexandra Hospital, Brisbane, recruited 2012-2014.) We estimated the prevalence of perineural invasion (and 95% confidence interval) in BCC and SCC, respectively, and identified clinical factors associated with perineural invasion. In QSkin, we observed 35 instances of perineural invasion in 9850 histopathologically confirmed BCCs (0.36%) and 9 instances of perineural invasion in 3982 confirmed SCC (0.23%) lesions. In the STAR cohort, we identified 4 lesions with perineural invasion in 692 BCCs (0.58%) and 16 reports of perineural invasion in 875 SCC lesions (1.9%). These data suggest that the overall prevalence of perineural invasion in keratinocyte cancer is low, although perineural invasion prevalence may be slightly higher among organ transplant recipients when compared to the general population.

Development and outcomes of de novo donor-specific antibodies in low, moderate, and high immunological risk kidney transplant recipients.

De novo donor-specific antibodies (dnDSA) play an important role in antibody-mediated rejection (ABMR) and graft failure, yet their development in kidney transplant recipients (KTx) of higher immunological risk has not been characterized. We prospectively determined the incidence of dnDSA at 3 and 12months posttransplant and assessed their associations with outcomes in recipients stratified by low, moderate, and high immunological risk. Adult KTx were screened for DSA pretransplant, months 3 and 12 posttransplant, and when clinically indicated. Outcomes included incidence of dnDSA, death-censored graft survival (DCGS), and ABMR. Of 371 recipients, 154 (42%) were transplanted across a pretransplant DSA that became undetectable by 12months posttransplant in 78% of cases. dnDSA were detected in 16% (95% confidence interval [CI]: 12-20%) by 3months and 23% (95% CI: 18-29%) by 12months posttransplant. Incidence at 12months was higher in the moderate (30%) and high-risk groups (29%) compared to the low-risk group (16%). dnDSA were associated with an increased risk of ABMR (hazard ratio [HR] 2.2; 95% CI: 1.1-4.4; P=.04) but were not an independent risk factor for DCGS. In conclusion, dnDSA were more frequent in transplant recipients of higher immune risk and associated with an increased risk of ABMR.

The Influence of Antithymocyte Globulin Dose on the Incidence of CMV Infection in High-risk Kidney Transplant Recipients Without Pharmacological Prophylaxis.

Optimizing antithymocyte globulin (ATG) dosage is critical, particularly for high-risk kidney transplant (KT) recipients without cytomegalovirus (CMV) prophylaxis. We studied 630 KT recipients with expanded criteria donors or panel reactive antibody ≥50% at Hospital do Rim, Brazil (January 1, 2013 to May 21, 2015) to determine whether a single ATG dose was safe and effective in patients without CMV prophylaxis. Patients received ≥4 doses (1-1.5 mg/kg/per dose) until June 17, 2014, when the induction protocol changed to a single ATG dose (3 mg/kg). We used Cox regression to compare the risk of CMV infection and acute rejection (AR) among KT recipients by ATG dose. Adjusting for clinical and transplant factors, a single ATG dose was associated with a lower risk of CMV infection (adjusted hazard ratio [aHR]: 0.63; 95% confidence interval [CI], 0.42-0.93; P = 0.02) and a similar risk of AR (aHR: 1.16; 95% CI, 0.47-2.83; P = 0.8), compared to multiple doses. We found no differences in death-censored graft loss (5.0% versus 4.8%, aHR: 1.06; 95% CI, 0.51-2.23; P = 0.9) or mortality (4.7% versus 3.4%; aHR: 1.42; 95% CI, 0.62-3.24; P = 0.4) at 1-year post-KT by ATG dose. In our study of high-risk KT recipients without CMV prophylaxis, a single ATG dose decreased the risk of CMV infection without increasing the risk of AR or compromising graft or patient survival.

P161 Clinical features and outcomes using rituximab for high immunologic risk kidney transplant recipients with historic DSA

P161 Clinical features and outcomes using rituximab for high immunologic risk kidney transplant recipients with historic DSA

Universal prophylaxis with valganciclovir versus preemptive therapy in minimizing the risk of cytomegalovirus infection and disease in high-risk and intermediate-risk kidney transplant recipients: a single-center experience

Objective Cytomegalovirus (CMV) is one of the most frequent viral pathogens that results in post-transplantation infection. Universal prophylaxis and preemptive therapy have long been used to prevent and treat CMV infection, respectively, in post-transplantation cases. The aim of this study was to compare the universal prophylaxis with valganciclovir versus preemptive therapy in minimizing the risk of CMV infection and disease in high-risk and intermediate-risk kidney transplant recipients. Patients and methods This single-center, retrospective cohort study enrolled 63 kidney transplant recipients between March 2017 and January 2018. The outcome variables were occurrence of CMV infection and CMV disease, 1-year estimated glomerular filtration rate (eGFR), allograft rejection, allograft loss, and mortality within the first year after transplantation in high-risk (D+/R−) patients managed with universal prophylaxis of oral valganciclovir and intermediate-risk (D+/R+ or D−/R+) patients receiving preemptive treatment. Results Of the 63 kidney transplant recipients, 19 (30.2%) were grouped as high risk for CMV infection/disease and 44 (69.8%) were intermediate risk for CMV infection/disease. The average duration of post-transplantation follow-up was 349 (SD 136) days in the high-risk cohort and 335 (SD 112) days in the intermediate-risk cohort (P=0.56). CMV infection was found in 15 (34.1%) of the 44 intermediate-risk patients receiving preemptive therapy and in four (21.1%) of the 19 high-risk patients receiving universal prophylaxis (P Conclusion Intermediate-risk (D+/R+ or D−/R+) kidney transplant recipients receiving preemptive therapy had significantly higher frequency of CMV infection/disease than high-risk (D+/R−) kidney transplant recipients receiving oral valganciclovir universal prophylaxis during early post-transplantation period. No statistically significant differences were found in relation to allograft rejection, allograft loss, eGFR, and mortality at 1 year in both the cohorts.

Preemptive anti-cytomegalovirus therapy in high-risk (donor-positive, recipient-negative cytomegalovirus serostatus) kidney transplant recipients

ObjectivesUniversal prophylaxis and preemptive therapy are used to prevent cytomegalovirus (CMV) disease post-transplantation. Data regarding which strategy is superior are sparse, especially in high-risk recipients (donor CMV seropositive (D+) and recipient CMV seronegative (R−)). MethodsThis retrospective, single-center cohort study included recipients who underwent kidney transplantation between 2009 and 2015. The incidence of CMV infection/disease and patient and graft outcomes were analyzed and compared between high-risk recipients (D+/R−) and intermediate-risk recipients (D+/R+ or D−/R+), all managed with preemptive therapy. ResultsOf 118 kidney transplant recipients, 21 were high-risk and 97 were intermediate-risk. Over a median follow-up period of 3 years, asymptomatic CMV infection developed significantly more frequently in high-risk patients than in intermediate-risk patients (38.1% vs. 16.5%, p=0.04), and CMV disease developed in a similar manner (28.6% vs. 3.1%, p<0.01). Among high-risk patients, CMV infection developed within the first 3 months post-transplantation and CMV disease within the first 9 months post-transplantation. Kaplan–Meier analysis showed no difference in the probability of mortality (log-rank p=0.63) or graft loss (log-rank p=0.50) between the patient groups. Graft rejection occurred more frequently in high-risk than in intermediate-risk patients, but the difference was not significant (log-rank p=0.24). ConclusionsThese results suggest that further studies on universal prophylaxis in high-risk patients are needed to elucidate whether preventing CMV infection/disease during the early post-transplant period leads to better outcomes, especially in terms of reducing graft rejection.

Cytomegalovirus infection in high-risk kidney transplant recipients receiving thymoglobulin induction-a single-center experience.

The burden of cytomegalovirus infection in CMV high-risk (donor positive to recipient negative) kidney transplant recipients getting thymoglobulin induction and six months of valganciclovir is not well characterized. Additionally, the role of post-prophylaxis surveillance remains unclear. One-year observational study of forty-eight high-risk CMV kidney transplant recipients transplanted under thymoglobulin between January 2013 and July 2014. All received valganciclovir for six months, followed by monthly CMV PCR for three months. CMV infection defined as viremia with or without symptoms occurred in 40% (19/48). Of these, 47% (9/19) occurred during prophylaxis, 32% (6/19) during surveillance and 21% (4/19) during post-surveillance period (9-12months). Among breakthrough infections, suboptimal valganciclovir dosing was present in 55% (5/9). With routine surveillance, there was a trend toward lower CMV-related hospitalization (17% vs 56% and 75% during prophylaxis and post-surveillance, respectively [P=.23]) and lower mean peak viral loads (19432 copies/mL vs 97925 copies/mL and 536021 copies/mL during prophylaxis and post-surveillance, respectively [P=.07]). CMV infection remains a significant problem with thymoglobulin induction despite six months of valganciclovir. Suboptimal valganciclovir dosing was common among breakthrough infections. Monthly surveillance post-prophylaxis appears to detect early CMV infection with lower degree of viremias requiring fewer hospitalizations.

Failure of Calcineurin Inhibitor (Tacrolimus) Weaning Randomized Trial in Long-Term Stable Kidney Transplant Recipients.

Long-term renal transplant outcome is limited by side effects of immunosuppressive drugs, particularly calcineurin inhibitor (CNI). We assumed that some patients selected for a "low immunological risk of rejection" could be eligible and benefit from a CNI weaning strategy. We designed a prospective, randomized, multicenter, double-blind placebo-controlled clinical study (Eudract: 2010-019574-33) to analyze the benefit-risk ratio of tacrolimus weaning on highly selected patients (≥4 years of transplantation, normal histology, stable graft function, no anti-HLA immunization). The primary endpoint was improvement of renal function. Fifty-two patients were scheduled in each treatment arm, placebo compared to the CNI maintenance arm. Only 10 patients were eligible and randomized. Five patients were assigned to the placebo arm and five were assigned to the tacrolimus maintenance arm. In the tacrolimus maintenance arm, all patients maintained stable graft function and no immunological events occurred. Contrastingly, in the placebo arm, all five patients had to reintroduce a full dose of tacrolimus since three of them presented an acute rejection episode (one humoral, one mixed, and one borderline) and two displayed anti-HLA antibodies without histological lesion (one donor-specific antibodies [DSA] and one non-DSA). Clearly, tacrolimus withdrawal must be avoided even in long-term highly selective stable kidney recipients.

Extended Low-Dose Valganciclovir Is Effective Prophylaxis Against Cytomegalovirus in High-Risk Kidney Transplant Recipients With Near-Complete Eradication of Late-Onset Disease.

Cytomegalovirus (CMV)-seronegative kidney transplant (KTx) recipients of organs from CMV-seropositive donors (D+/R-) are at increased risk for CMV infection. Despite valganciclovir (VGCV) prophylaxis (900mg daily for 200 days), late-onset CMV (LO-CMV) occurs at excessive rates. VGCV-associated cost and toxicities remain problematic. We retrospectively evaluated 50 D+/R- adult KTx recipients from August 2008 to August 2014 who received low-dose VGCV (450mg daily) prophylaxis for an extended duration. The primary outcome was occurrence of CMV disease. All patients received depletion induction and underwent ABO-compatible KTx. Mean prophylaxis and follow-up durations were 22.8 and 40.7 months, respectively. Eight patients developed CMV: 5 breakthrough cases (1 case of colitis [2%] and 4 cases of infection [8%]) and 3 cases of LO-CMV (1 syndrome [2.9%] and 2 cases of infection [5.7%]). On logistic regression, longer duration of VGCV prophylaxis was protective against CMV infection or disease (P= .044; odds ratio, 1.12 [95% confidence interval, 1.03-1.29]). None of 19 recipients with prophylaxis for≥12 months developed LO-CMV compared with 3 of 16 recipients with prophylaxis for<12 months (18.8%) (P= .086). Four patients had recurrence of CMV, and 1 patient developed resistance. CMV was not responsible for graft or patient loss and did not affect survival. Low-dose VGCV is an effective prophylaxis for D+/R- KTx recipients despite depleting induction. Longer prophylaxis is more protective, and receiving VGCV for≥12 months nearly eradicated LO-CMV without increasing antiviral resistance.

Optimal Dose of Thymoglobulin for Induction Therapy in High Risk Kidney Transplant Recipients

Background: Thymoglobulin has been used for induction therapy to prevent acute rejection and delayed graft function (DGF) in kidney transplant patients. However, the usual dose of thymoglobulin is considered to be related with frequent infection. We compared the efficacy and safety of low-dose thymoglobulin to high-dose treatment in high risk recipients with kidney transplantation. Methods: Twenty-one kidney transplant recipients underwent induction treatment with thymoglobulin and were divided into two groups: patients treated with low-dose (＜6.0 mg/kg) and high-dose thymoglobulin (≥6.0 mg/kg). All patients showed one or more risk factors for acute rejection or DGF. The risk factors were re-transplantation, recipient or donor age over 60 years, human leukocyte antigen full mismatch, and panel-reactive antibody more than 50%. We compared incidence of acute rejection, infection, hematologic complications, and graft survival between two groups. Results: The demographic characteristics of the two groups were comparable. Mean follow-up duration was 11.9±4.3 months, and cumulative thymoglobulin dosage was 6.3±1.6 mg/kg. The incidence rates of acute antibody-mediated rejection (AMR), DGF and infectious events as cytomegalovirus disease, or urinary tract infection were not significantly different between the two groups. Neutropenia occurred more frequently in the high-dose thymoglobulin group, but there was no statistically significant difference. The rate of graft loss were similar between the two groups. Conclusions: There were no differences in graft survival, infectious disease, and hematologic problems between the two groups. We suggest to lower the dose of thymoglobulin to less than 6 mg/kg for prevent acute AMR and DGF in high risk patients.

Prevalence of Skin Cancer and Related Skin Tumors in High-Risk Kidney and Liver Transplant Recipients in Queensland, Australia

The increased skin cancer incidence in organ transplant recipients is well-known, but the skin cancer burden at any one time is unknown. Our objective was to estimate the period prevalence of untreated skin malignancy and actinic keratoses in high-risk kidney and liver transplant recipients and to assess associated factors. Organ transplant recipients underwent full skin examinations by dermatologically trained physicians. The proportion of examined organ transplant recipients with histopathologically confirmed skin cancer in the 3-month baseline period was estimated. Prevalence ratios with 95% confidence intervals indicated significant associations. Of 495 high-risk organ transplant recipients (average age= 54 years, time immunosuppressed= 8.9 years), 135 (27%) had basal cell carcinoma, squamous cell carcinoma or Bowen's disease (intraepidermal carcinoma) present and confirmed in the baseline period, with respective prevalence proportions of 10%, 11%, and 18% in kidney transplant recipients and 10%, 9%, and 13% in liver transplant recipients. Over 80% had actinic keratosis present, with approximately 30% having 5 or more actinic keratoses. Organ transplant recipients with the highest skin cancer burden were Australian born, were fair skinned (prevalence ratio= 1.61, 95% confidence interval= [1.07, 2.43]), reported past skin cancer (prevalence ratio=3.39, 95% confidence interval= [1.93, 5.95]), and were receiving the most frequent skin checks (prevalence ratio= 1.76, 95% confidence interval= [1.15, 2.70]). In conclusion, high-risk organ transplant recipients carry a substantial measurable skin cancer burden at any given time and require frequent review through easily accessible, specialized services.

Pre-transplant soluble CD30 in combination with total DSA but not pre-transplant C1q-DSA predicts antibody-mediated graft loss in presensitized high-risk kidney transplant recipients.

Presensitized kidney transplant recipients are at high-risk for early antibody-mediated rejection. We studied the impact of pre- and post-transplant donor-specific human leukocyte antigen (HLA) antibodies (DSA) and T-cell-activation on the occurrence of antibody-mediated rejection episodes (AMR) and graft loss (AMR-GL) in a unique cohort of 80 desensitized high-risk kidney transplant recipients. Patients with pre-transplant DSA demonstrated more AMR episodes than patients without DSA, but did not show a significantly increased rate of AMR-GL. The rates of AMR and AMR-GL were not significantly increased in patients with complement split product (C1q)-binding pre-transplant DSA. Pre-transplant C1q-DSA became undetectable post-transplant in 11 of 13 (85%) patients; 2 (18%) of these 11 patients showed AMR but no AMR-GL. In contrast, the post-transplant presence of C1q-DSA was associated with significantly higher rates of AMR (86 vs 33 vs 0%; P < 0.001) and AMR-GL (86 vs 0 vs 0%; log-rank P < 0.001) compared with post-transplant DSA without C1q-binding or the absence of DSA. Patients with both pre-transplant DSA and evidence of pre-transplant T-cell-activation as indicated by soluble CD30-positivity showed a significantly increased risk for AMR-GL [HR = 11.1, 95% confidence interval (CI) = 1.68-73.4; log-rank P = 0.013]. In these high-risk patients, AMR-GL was associated with total DSA in combination with T-cell-activation pre-transplant, and de novo or persistent C1q-binding DSA post-transplant.

Effects of Ideal Versus Total Body Weight Dosage of Rabbit Antithymocyte Globulin on Outcomes of Kidney Transplant Patients With High Immunologic Risk.

The optimal dose of rabbit antithymocyte globulin induction therapy in kidney transplant recipients with high immunologic risk lacks consensus. The purpose of this study was to evaluate the effect of using ideal body weight rather than total body weight for the weight-based dose calculations in this patient population. Data were retrospectively collected on 89 adult patients who received rabbit antithymocyte globulin induction therapy for high immunologic risk kidney transplant. Hospital protocol changed from the use of cumulative rabbit antithymocyte globulin doses of 7.5 mg/kg total body weight to 7.5 mg/kg ideal body weight in 2009. Patients were separated into 2 cohorts based on the amount of rabbit antithymocyte globulin (in mg/kg total body weight) received. Rate of biopsy-proven acute rejection, patient survival, and allograft function were evaluated at 90 days and 1 year after transplant. Cost of induction therapy was also evaluated. Baseline demographics were predominantly similar between the 2 cohorts. No significant difference in maintenance immunosuppression was identified. Rates of biopsy-proven acute rejection at 90 days and 1 year were similar between ideal and total body weight cohorts (4.2% vs 0% at 90 days, P = .5; 8.7% vs 0% at 1 year, P = .13). Patient survival and allograft function were also similar. Median cost of rabbit antithymocyte globulin induction therapy per patient was lower in the ideal body weight cohort, but this difference was not statistically significant ($17 542 vs $19 934; P = .3). Our results suggest that use of ideal body weight for dose calculations of rabbit antithymocyte globulin induction therapy in high immunologic risk kidney transplant recipients at 7.5 mg/kg results in low rates of acute rejection with a safety profile similar to that shown with a total body weight dosage. Use of ideal body weight for lower cumulative doses may still need further evaluation in this patient population.