Alden Doyle

Low rates of vaccination in listed kidney transplant candidates.

Despite clear consensus and strong recommendations, vaccination rates of kidney transplant (KT) recipients have remained below targets. As vaccination is most effective if it is given prior to transplantation and the initiation of immunosuppression, patients should ideally have their vaccination status assessed and optimized in the pre‐transplant period. We performed a retrospective chart review to characterize vaccination rates and factors associated with gaps in vaccination in a single‐center population of waitlisted patients being evaluated for kidney transplantation. We evaluated 362 KT patients. Three‐quarters were receiving dialysis at the time of evaluation. Immunization rates were low with 35.9% of patients having completed vaccination for Pneumococcus, 55% for influenza, 6.9% for zoster, and 2.5% for tetanus. On multivariable analysis, patients who received other vaccines, including influenza, tetanus, or zoster vaccine (odds ratio [OR] 10.55, 95% confidence interval [CI] 5.65–19.71) were more likely to receive pneumococcal vaccine. Blacks (OR 0.24, 95% CI 0.12–0.47) were less likely to receive pneumococcal vaccine compared to whites. Patients on dialysis, and those active on the waiting list were more likely to receive pneumococcal vaccine than other groups (OR 2.81, 95% CI 1.44–5.51, and OR 1.84, 95% CI 1.08–3.14, respectively). We found that the overall immunization rate against common vaccine‐preventable infections was low among patients evaluated for kidney transplantation. A significant gap remains between recommendations and vaccine uptake in clinical practice among this high‐risk population.

Liver and Kidney Transplantation: A Half-Century Historical Perspective

This article describes the evolution of solid organ kidney and liver transplantation and expounds on the challenges and successes that the early transplant researchers and clinicians encountered. The article highlights the surgical pioneers, delves into the milestones of enhanced immunosuppression protocols, discusses key federal legislative and policy changes, and expounds on the ongoing disparities of organ supply and demand and the need for extended criteria and live donor organs to combat these shortages. Finally, recent changes in organ allocation and distribution policies are discussed. The authors also spotlight novel interventions that will further revolutionize abdominal transplantation in the next 50 years.

Nonmelanoma Skin Cancer in Nonwhite Organ Transplant Recipients

ImportancenOrgan 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.nnnObjectivenTo describe demographic and clinical factors and the incidence of skin cancer in nonwhite organ transplant recipients.nnnDesign, Setting, and ParticipantsnWe 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.nnnMain Outcomes and MeasuresnVariables 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.nnnResultsnMost 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.nnnConclusions and RelevancenNonwhite 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.

Vismodegib for Locally Advanced Basal Cell Carcinoma in a Heart Transplant Patient

IMPORTANCEnImmunosuppressed patients with solid organ transplants have an increased risk for nonmelanoma skin cancer. Vismodegib has been reported to be effective for select locally advanced or metastatic basal cell carcinomas. However, there is no data documenting the use and safety of vismodegib in immunosuppressed organ transplant patients.nnnOBSERVATIONSnWe describe a 78-year-old white man with a history of orthotopic heart transplant, immunosuppressed with low-dose cyclosporine, who presented to a specialty dermatology transplant clinic with multiple, recurrent, locally aggressive facial basal cell carcinomas. Through a multidisciplinary approach, the patient was started on vismodegib therapy. The pharmacokinetics of cyclosporine in the setting of vismodegib administration and weekly monitoring of cyclosporine levels ensured that therapeutic immunosuppression levels were achieved without toxic effects.nnnCONCLUSIONS AND RELEVANCEnTo our knowledge, this is the first report that details vismodegib use in an immunosuppressed heart transplant patient receiving cyclosporine therapy. With a growing immunosuppressed organ transplant population at high risk for basal cell carcinoma, therapeutic options for locally advanced or metastatic disease are limited. Vismodegib appears to be a safe option for patients receiving cyclosporine therapy with routine monitoring. Future research is needed to evaluate the safety profile of vismodegib with other immunosuppressive agents.

Successful Treatment of Acute Severe Graft-Versus-Host-Disease in a Pancreas-After-Kidney Transplant Recipient: Case Report

The development of acute graft-versus-host-disease (GVHD) in recipients of pancreas transplants is a rare and quite often a fatal post-transplantation complication. We present a 38-year-old male with a longstanding history of type 1 diabetes mellitus and end-stage kidney disease, with a living unrelated kidney transplant from his wife for 3 years, who received an enteric-drained 5-antigen HLA-mismatched deceased-donor pancreas. Five weeks after transplantation, he presented with spiking fevers, severe skin rash, diarrhea, pancytopenia, and increasingly abnormal liver function tests. Skin biopsies were consistent with grade 3 acute GVHD. The patient was treated for GVHD with escalated doses of tacrolimus, pulse doses of steroids, and basiliximab. He was discharged after a 4-week hospital stay with complete resolution of his rash, fever, abnormal liver enzymes, and leukopenia. He remained in good health with excellent kidney and pancreas allograft function 3 years later.

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.

Identification of Risk Factors Associated With Clostridium difficile Infection in Liver Transplantation Recipients: A Single-Center Analysis

Clostridium difficile remains the leading cause of health care-associated infectious diarrhea, and its incidence and severity are increasing in liver transplant recipients. Several known risk factors for C difficile infection (CDI) are inherently associated with liver transplantation, such as severe underlying illness, immunosuppression, abdominal surgery, and broad-spectrum antibiotic use. We conducted a single-center retrospective case control study to characterize risk factors for CDI among patients who received a liver transplant from January 2008 to December 2012. We also examined the associations of post-transplantation CDI with transplant outcomes. Cases were defined as having diarrhea with a positive test for C difficile by either toxin A/B enzyme immunoassay (EIA) or glutamate dehydrogenase EIA and polymerase chain reaction within 1 year after transplantation. Sixty-five consecutive patients were evaluated, of which 15 (23%) developed CDI. The median time from transplantation to CDI diagnosis was 65 days (interquartile range [IQR] 13-208) and more than one-half (53%) had severe infection. Risk factors that were associated with CDI among liver transplant recipients included: (1) previous history of CDI (20% vs 0%; Pxa0= .001); (2) exposure to proton-pump inhibitor therapy (93% vs 60%; Pxa0= .015); (3) antimicrobial therapy before transplantation (47% vs 18%; Pxa0= .039); (4) a prolonged length of stay before transplantation (1 day [IQR, 1-19] vs 1 day [IQR, 0-1]; Pxa0= .028); and (5) chronic kidney disease (53% vs 20%; Pxa0= .011). There was no significant differences in patient survivals at 6 months (93% vs 96%; Pxa0= .67) and 12 months (87% vs 94%; Pxa0= .35) among CDI case and control subjects, respectively.

Serum creatinine elevation after switch to dolutegravir in a human immunodeficiency virus–positive kidney transplant recipient

Dolutegravir is a preferred antiretroviral drug for human immunodeficiency virus (HIV)‐infected patients following solid organ transplantation. It has potent antiretroviral activity and does not interact with calcineurin inhibitors. We describe a case of an HIV‐infected kidney transplant patient, who was noted to have a rising serum creatinine following initiation of dolutegravir. At first, an acute rejection episode was suspected, but this finding was later attributed to inhibition of creatinine secretion by dolutegravir. We suggest that an awareness of this potential effect of dolutegravir is important for providers who take care of HIV‐positive kidney transplant recipients, in order to prevent potentially unnecessary testing.

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.

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.