Experience with a six-month regimen of Pneumocystis pneumonia prophylaxis in 122 HIV-positive kidney transplant recipients.

Anti-Pneumocystis pneumonia (PCP) prophylaxis is recommended for 3 to 6 months post-transplant in HIV-negative kidney transplant recipients. For HIV-positive kidney transplant recipients, there is no definite duration of primary prophylaxis and is often prescribed life-long. The objective of this study was to determine the incidence of PCP in HIV-positive recipients who received 6 months of prophylaxis with trimethoprim-sulfamethoxazole or an alternative agent. One hundred and twenty-two HIV-positive recipients received a kidney transplant from 2001 to 2017 at Hahnemann University Hospital. Most patients received induction immunosuppression with an IL-2 receptor antagonist, with or without intravenous immunoglobulin. Only one patient received anti-thymocyte globulin. Maintenance immunosuppression included a calcineurin-inhibitor (tacrolimus or cyclosporine), an antiproliferative agent (mycophenolate or sirolimus), and prednisone. Mean CD4 cell count was 461 ± 127 cells/uL prior to transplant and 463 ± 229 cells/µL at 6 to 12 months after transplant. None of the recipients developed PCP after a median follow-up of 2.88 years (IQR 1.16-4.87). Based on our observation, a 6-month regimen of PCP prophylaxis may be sufficient among HIV-positive recipients, similar to those without HIV infection.

Kidney Transplantation in HIV-Positive Patients: A Single-Center, 16-Year Experience.

Hahnemann University Hospital has performed 120 kidney transplantations in human immunodeficiency virus (HIV)-positive individuals during the last 16 years. Our patient population represents ∼10% of the entire US population of HIV-positive kidney recipients. In our earlier years of HIV transplantation, we noted increased rejection rates, often leading to graft failure. We have established a multidisciplinary team and over the years have made substantial protocol modifications based on lessons learned. These modifications affected our approach to candidate evaluation, donor selection, perioperative immunosuppression, and posttransplantation monitoring and resulted in excellent posttransplantation outcomes, including 100% patient and graft survival at 1 year and patient and graft survival at 3 years of 100% and 96%, respectively. We present key clinical data, including a granular patient-level analysis of the associations of antiretroviral therapy regimens with long-term survival, cellular and antibody-mediated rejection rates, and the causes of allograft failures. In summary, we provide details on the evolution of our approach to HIV transplantation during the last 16 years, including strategies that may improve outcomes among HIV-positive kidney transplantation candidates throughout the United States.

Association of the kidney allocation system with dialysis exposure before deceased donor kidney transplantation by preemptive wait-listing status.

BACKGROUND: It is unknown whether the new kidney transplant allocation system (KAS) has attenuated the advantages of preemptive wait-listing as a strategy to minimize pretransplant dialysis exposure. METHODS: We performed a retrospective study of adult US deceased donor kidney transplant (DDKT) recipients between December 4, 2011-December 3, 2014 (pre-KAS) and December 4, 2014-December 3, 2017 (post-KAS). We estimated pretransplant dialysis durations by preemptive listing status in the pre- and post-KAS periods using multivariable gamma regression models. RESULTS: Among 65 385 DDKT recipients, preemptively listed recipients (21%, n = 13 696) were more likely to be white (59% vs 34%, P < 0.001) and have private insurance (64% vs 30%, P < 0.001). In the pre- and post-KAS periods, average adjusted pretransplant dialysis durations for preemptively listed recipients were <2 years in all racial groups. Compared to recipients who were listed after starting dialysis, preemptively listed recipients experienced 3.85 (95% Confidence Interval [CI] 3.71-3.99) and 4.53 (95% CI 4.32-4.74) fewer average years of pretransplant dialysis in the pre- and post-KAS periods, respectively (P < 0.001 for all comparisons). CONCLUSIONS: Preemptively wait-listed DDKT recipients continue to experience substantially fewer years of pretransplant dialysis than recipients listed after dialysis onset. Efforts are needed to improve both socioeconomic and racial disparities in preemptive wait-listing.

Oritavancin (Orbactiv): A New-Generation Lipoglycopeptide for the Treatment Of Acute Bacterial Skin and Skin Structure Infections.

Oritavancin (Orbactiv): a new-generation lipoglycopeptide for the treatment of acute bacterial skin and skin structure infections.

Barriers to listing for HIV-infected patients being evaluated for kidney transplantation.

Human immunodeficiency virus (HIV)-infected patients have excellent outcomes following kidney transplantation (KT) but still might face barriers in the evaluation and listing process. The aim of this study was to characterize the patient population, referral patterns, and outcomes of HIV-infected patients who present for KT evaluation. We performed a single-center retrospective cohort study of HIV-infected patients who were evaluated for KT. The primary outcome was time to determination of eligibility for KT. Between 2011 and 2015, 105 HIV-infected patients were evaluated for KT. Of the 105 patients, 73 were listed for transplantation by the end of the study period. For those who were deemed ineligible, the most common reasons cited were active substance abuse (n = 7, 22%) and failure to complete the full transplant evaluation (n = 7, 22%). Our cohort demonstrated a higher proportion of HIV-infected patients eligible for KT than in previous studies, likely secondary to advances in HIV management. Among those who were denied access to transplantation, we identified that many were unable to complete the evaluation process, and that active substance abuse was common. Future prospective studies should examine reasons and potential interventions for the lack of follow-through and drug use we observed in this population.

Validation of the Maryland Aggregate Pathology Index (MAPI), a pre-implantation scoring system that predicts graft outcome.

Predicting graft outcome after renal transplantation based on donor histological features has remained elusive and is subject to institutional variability. We have shown in a retrospective study that the Maryland Aggregate Pathology Index score reliably predicts graft outcome. We sought to validate the scoring system in our center and a second transplant center. We analyzed 140 deceased donor kidneys pre-implantation biopsies from center 1 and 65 from center 2. The patients had a mean follow-up of 695 ± 424 and 656 ± 305 d respectively. Although MAPI scores were similar, there were significant differences in donor and recipient parameters between both centers. Despite this, MAPI was predictive of graft outcome for both centers by Cox univariate, multivariate and time dependent ROC analysis. For center 1 and 2, three yr graft survival within each MAPI group was statistically equivalent. The three-yr graft survival at center 1 for low, intermediate, and high MAPI groups were 84.3%, 56.5%, and 50.0%, respectively, p ≤ 0.0001, and at center 2 were 83.3%, 33.3%, and 33.3%, p = 0.006. MAPI, which is based on a pre-implantation biopsy, demonstrated similar predictive and outcome results from both centers. As expanded criteria donors (ECD) criteria have redefined marginal kidneys, MAPI has the potential to further define ECD kidneys, increase utilization, and ultimately improve outcomes.

Association between Medicaid Expansion under the Affordable Care Act and Preemptive Listings for Kidney Transplantation.

BACKGROUND AND OBJECTIVES: Before 2014, low-income individuals in the United States with non-dialysis-dependent CKD had fewer options to attain health insurance, limiting their opportunities to be preemptively wait-listed for kidney transplantation. We examined whether expanding Medicaid under the Affordable Care Act was associated with differences in the number of individuals who were pre-emptively wait-listed with Medicaid coverage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using the United Network of Organ Sharing database, we performed a retrospective observational study of adults (age≥18 years) listed for kidney transplantation before dialysis dependence between January 1, 2011-December 31, 2013 (pre-Medicaid expansion) and January 1, 2014-December 31, 2016 (post-Medicaid expansion). In multinomial logistic regression models, we compared trends in insurance types used for pre-emptive wait-listing in states that did and did not expand Medicaid with a difference-in-differences approach. RESULTS: States that fully implemented Medicaid expansion on January 1, 2014 ("expansion states," n=24 and the District of Columbia) had a 59% relative increase in Medicaid-covered pre-emptive listings from the pre-expansion to postexpansion period (from 1094 to 1737 listings), compared with an 8.8% relative increase (from 330 to 359 listings) among 19 Medicaid nonexpansion states (P<0.001). From the pre- to postexpansion period, the adjusted proportion of listings with Medicaid coverage decreased by 0.3 percentage points among nonexpansion states (from 4.0% to 3.7%, P=0.09), and increased by 3.0 percentage points among expansion states (from 7.0% to 10.0%, P<0.001). Medicaid expansion was associated with absolute increases in Medicaid coverage by 1.4 percentage points among white listings, 4.0 percentage points among black listings, 5.9 percentage points among Hispanic listings, and 5.3 percentage points among other listings (P<0.001 for all comparisons). CONCLUSIONS: Medicaid expansion was associated with an increase in the proportion of new pre-emptive listings for kidney transplantation with Medicaid coverage, with larger increases in Medicaid coverage among racial and ethnic minority listings than among white listings.

Comparison of Posttransplant Dermatologic Diseases by Race.

Importance: The risk for skin cancer has been well characterized in white organ transplant recipients (OTRs); however, most patients on the waiting list for organ transplant in the United States are nonwhite. Little is known about cutaneous disease and skin cancer risk in this OTR population. Objective: To compare the incidence of cutaneous disease between white and nonwhite OTRs. Design, Setting, and Participants: This retrospective review of medical records included 412 OTRs treated from November 1, 2011, through April 22, 2016, at an academic referral center. Prevalence and characteristics of cutaneous disease were compared in 154 white and 258 nonwhite (ie, Asian, Hispanic, and black) OTRs. Clinical factors of cutaneous disease and other common diagnoses assessed in OTRs included demographic characteristics, frequency and type of cancer, anatomical location, time course, sun exposure, risk awareness, and preventive behavior. Main Outcomes and Measures: Primary diagnosis of malignant or premalignant, infectious, and inflammatory disease. Results: The 412 patients undergoing analysis included 264 men (64.1%) and 148 women (35.9%), with a mean age of 60.1 years (range, 32.1-94.3 years). White OTRs more commonly had malignant disease at their first visit (82 [67.8%]), whereas nonwhite OTRs presented more commonly with infectious (63 [37.5%]) and inflammatory (82 [48.8%]) conditions. Skin cancer was diagnosed in 64 (41.6%) white OTRs and 15 (5.8%) nonwhite OTRs. Most lesions in white (294 of 370 [79.5%]) and Asian (5 of 6 [83.3%]) OTRs occurred in sun-exposed areas. Among black OTRs, 6 of 9 lesions (66.7%) occurred in sun-protected areas, specifically the genitals. Fewer nonwhite than white OTRs reported having regular dermatologic examinations (5 [11.4%] vs 8 [36.4%]) and knowing the signs of skin cancer (11 [25.0%] vs 10 [45.4%]). Conclusions and Relevance: Early treatment of nonwhite OTRs should focus on inflammatory and infectious diseases. Sun protection should continue to be emphasized in white, Asian, and Hispanic OTRs. Black OTRs should be counseled to recognize the signs of genital human papillomavirus infection. Optimal posttransplant dermatologic care may be determined based on the race or ethnicity of the patients, but a baseline full-skin assessment should be performed in all patients. All nonwhite OTRs should be counseled more effectively on the signs of skin cancer, with focused discussion points contingent on skin type and race or ethnicity.

Nonmelanoma Skin Cancer in Nonwhite Organ Transplant Recipients.

Importance: Organ transplant recipients have a higher incidence of skin cancer. This risk is magnified over time and with continued exposure to immunosuppression. Skin cancer in nonwhite patients is associated with greater morbidity and mortality owing to diagnosis at a more advanced stage, which suggests that nonwhite organ transplant recipients are at even higher risk. Objective: To describe demographic and clinical factors and the incidence of skin cancer in nonwhite organ transplant recipients. Design, Setting, and Participants: We performed a retrospective medical record review of patients who were organ transplant recipients (154 were white and 259 nonwhite [black, Asian, Hispanic, Pacific Islander]) seen from November 1, 2011, to April 18, 2016 at an academic referral center. Main Outcomes and Measures: Variables were analyzed and compared between racial groups, including sex, age, race/ethnicity, Fitzpatrick type, type and location of skin cancer, type of organ transplanted, time to diagnosis of skin cancer after transplantation, and history of condyloma acuminata and/or verruca vulgaris. Results: Most of the 413 patients (62.7%) evaluated were nonwhite organ transplant recipients; 264 were men, and 149 were women. Their mean (SD) age was 60.09 (13.59) years. Nineteen skin cancers were identified in 15 patients (5.8%) representing 3 racial/ethnic groups: black (6 patients), Asian (5), and Hispanic (4). All squamous cell carcinomas in blacks were diagnosed in the in situ stage, located on sun-protected sites, and occurred in patients whose lesions tested positive for human papilloma virus (HPV) and/or who endorsed a history of condyloma acuminata or verruca vulgaris. Most skin cancers in Asians were located on sun-exposed areas and occurred in individuals who emigrated from equatorial locations. Conclusions and Relevance: Nonwhite organ transplant recipients are at risk for developing skin cancer posttransplantation. Follow-up in a specialized transplant dermatology center and baseline total-body skin examination should be part of posttransplantation care in all organ transplant recipients, including nonwhite patients. A thorough inspection of the groin and genitalia is imperative in black organ transplant recipients. History of HPV infection, particularly in black organ transplant recipients, and sun exposure/emigration history in Asian organ transplant recipients should be documented. Vigilant photoprotection may be of lesser importance in the prevention of skin cancer in black organ transplant recipients. Risk factors for nonwhite organ transplant recipients differ between races/ethnicities and warrant further study in efforts to better counsel and prevent skin cancer in these patients.

High frequency of rejections in HIV-positive recipients of kidney transplantation: a single center prospective trial.

BACKGROUND: This is a single institution report of the incidence of combined acute antibody-mediated rejection (ABMR) + acute cellular rejection (ACR) [mixed rejection] in HIV (+) kidney transplant recipients. METHODS: We prospectively enrolled 92 HIV (+) patients who received a kidney transplant between 2001 and 2009. There were three cohorts: no rejection [n=26], ACR [n=53], and mixed rejections (ABMR and ACR) [n=13]. Immunosuppression comprised of basiliximab, cyclosporine, sirolimus, and steroid minimization. Fisher exact tests for categorical variables, t test for continuous variables, and Kaplan-Meier estimates were used to describe events. RESULTS: Mixed rejections were seen in all 13 HIV (+) kidney transplant recipients (14%) with a median time to ABMR of 48 days. Acute cellular rejection occurred in 28% at 1 month and 55% at 12 months. eGFR was lower for recipients who experienced ABMR versus those experiencing ACR and those never experiencing rejection up to 3 years (14 ± 9.4 vs 19 ± 3.3 vs 29 ± 7.3 mL/min, respectively). Kaplan-Meier showed that graft survival up to 9 years was worse in recipients experiencing mixed rejection. Suboptimal donors with terminal creatinine greater than 2.5 mg/dL was associated with increased incidence of mixed rejections versus cellular rejections and no rejection (42% vs 17% vs. 8%, respectively). CONCLUSIONS: Our single center study showed a relatively higher incidence of mixed rejection compared with that reported for non-HIV transplant recipients. A donor terminal serum creatinine greater than 2.5 mg/dL predicted mixed rejection, which was associated with poor outcomes. Donor selection and optimization of immunosuppression may be critical in these patients.

African American kidney transplantation survival: the ability of immunosuppression to balance the inherent pre- and post-transplant risk factors.

Among organ transplant recipients, the African American population historically has received special attention. This is because secondary to their disposition to certain disease states, for example hypertension, an African American patient has a propensity to reach end-stage renal disease and require renal replacement earlier than a Caucasian patient. Regardless of the initiative to replace dialysis therapy with organ transplantation, the African American patient has many barriers to kidney transplantation, thus extending their time on dialysis and waiting time on the organ transplant list. These factors are among the many negative causes of decreased kidney graft survival, realized before kidney transplantation. Unfortunately, once the African American recipient receives a kidney graft, the literature documents that many post-transplant barriers exist which limit successful outcomes. The primary post-transplant barrier relates to designing proper immunosuppression protocols. The difficulty in designing protocols revolves around (i) altered genetic metabolism/lower absorption, (ii) increased immuno-active cytokines and (iii) detrimental effects of noncompliance. Based on the literature, dosing of immunosuppression must be aggressive and requires a diligent practitioner. Research has indicated that, despite some success with proven levels of immunosuppression, the African American recipient usually requires a higher 'dose per weight' regimen. However, even with aggressive immunosuppressant dosing, African Americans still have worse outcomes than Caucasian recipients. Additionally, many of the targeted sites of action that immunosuppression exerts its effects on have been found to be amplified in the African American population. Finally, noncompliance is the most discouraging inhibitor of long-term success in organ transplantation. The consequences of noncompliance are biased by ethnicity and affect the African American population more severely. All of these factors are discussed further in this review in the hope of identifying an ideal healthcare model for caring for the African American transplant recipient, from diagnosing chronic kidney disease through to successful kidney graft outcomes. An indepth review of the literature is described and organized in a fashion that highlights all of the issues affecting success in African Americans. The compilation of the literature in this review will enable the reader to get closer to understanding the caveats of kidney transplantation in the African American patient, but falls short of delivering an actual 'equation' for post-transplant care in an African American kidney recipient.