RESUMEN
BACKGROUND: In kidney transplantation, concerns have been raised regarding increased incidence of viral opportunistic infections in hepatitis C virus (HCV) nucleic acid test (NAT)-negative (-) recipients who received HCV NAT-positive (+) donor kidneys, specifically BK polyomavirus (BKPyV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV). The purpose of this study was to determine the incidence of these three viral opportunistic infections in HCV NAT- recipients who have undergone kidney transplantation with HCV NAT+ donor kidneys at our institution. METHODS: This was an Institutional Review Board-approved, single-center, retrospective case-control study of HCV NAT- kidney transplant recipients with HCV NAT+ donors from 2018 to 2021. The primary outcome was the cumulative incidence of viral infections of BKPyV, CMV, and/or EBV within 1 year following kidney transplantation. RESULTS: A total of 231 patients were included, 77 in the exposed (donor HCV NAT+) group and 154 in the control (donor HCV NAT-) group. The adjusted cumulative incidence of viremia within 1 year did not statistically differ between groups (77% exposed group versus 66% for the control group, hazard ratio 1.34, 95% confidence interval 0.95-1.89). In addition, no statistically significant differences were observed for secondary outcomes with the exception of CMV viremia (62% exposed versus 49% control, p = 0.021). However, there were more patients in the exposed group at high risk for CMV viremia based on serostatus (CMV Donor+/Recipient-, D+/R-). CONCLUSION: Among patients who received HCV NAT+ donor kidneys, no clear association was observed between exposure to HCV NAT+ donor kidneys and viral infections of BKPyV, CMV, or EBV.
RESUMEN
Cytomegalovirus (CMV) infection poses a significant threat to solid organ transplant (SOT) recipients and can lead to various complications and adverse outcomes. In an effort to prevent CMV infection, it is common to utilize prophylactic strategies, including antiviral medications such as valganciclovir, especially for high-risk patients. Risk factors for CMV infection in kidney transplant recipients (KTRs) include CMV mismatch between donor and recipient (i.e., donor positive, recipient negative), and intensity of immunosuppression, such as the use of T-cell depleting agents. However, little attention has been given to KTRs with a history of prior SOTs, despite their prolonged exposure to immunosuppressive regimens. The aim of this retrospective single-center study was to investigate the incidence and implications of CMV DNAemia in KTRs with prior SOTs. The study included 97 KTRs with prior SOTs and 154 KTRs with no prior transplants as a control group. In the study group, the most common SOT before the current kidney transplantation (KT), was a previous KT. Patients in the KTR group with prior SOTs were more sensitized than those in the control group [calculated panel-reactive antibody > 30%: 49 (50.5%) vs. 30 (19.45%) patients, p = 0.001]. There was a 39.2% incidence of CMV DNAemia in the previous SOT group compared to 48.7% in the control group [non-significant (NS)]. Patients with prior SOTs demonstrated a shorter post-transplant time to CMV DNAemia [median time 1.6 months (interquartile range, IQR 0.7-5.8) in the KTRs with prior SOTs vs. 2.6 months (IQR 1.5-8.1) in the control group (p = 0.001)]. Although the study highlights the need for tailored prophylaxis strategies and vigilant monitoring in KTRs with prior SOTs, its limitations, such as its retrospective nature and single-center design, call for further multicenter research to establish comprehensive guidelines for managing CMV DNAemia in this unique patient population. Despite these limitations, this study underscores the importance of recognizing the heightened risk of CMV infection or reactivation in KTRs overall and the potential benefits of proactive intervention to mitigate associated morbidity and mortality.
RESUMEN
Objectives: Tacrolimus remains the mainstay of immunosuppression in kidney transplantation. Understanding the relationship between therapeutic tacrolimus levels and outcomes of acute rejection, patient/graft survival, and tolerability are important. The relationship between time to therapeutic tacrolimus levels and outcomes has not been well established, specifically with the use of extended release tacrolimus formulation (LCP-Tac). This study investigated time to therapeutic tacrolimus levels of 2 tacrolimus formulations, LCP-Tac and immediate release tacrolimus (IR-Tac), as a predictor of clinical outcomes. Methods: This was a single-center, retrospective, cohort study of kidney transplant recipients at Duke Hospital between 2013-2021. The primary objective evaluated the difference in time to therapeutic tacrolimus levels with LCP-Tac vs IR-Tac regimens. Secondary endpoints included time within therapeutic range during the first 3 months post-transplant, incidence of biopsy-proven rejection, development of de novo donor specific antibodies, and patient and allograft survival at 12 months post-transplant. Results: 128 patients were included (63 in LCP-Tac group and 65 in IR-Tac group). The time to therapeutic tacrolimus level was similar between formulations (7.2 days with LCP-Tac compared to 6.7 days with IR-Tac, P = .63). The time within therapeutic range during the first 3 months post-transplant, via modified Rosendaal, was similar with LCP-Tac and IR-Tac (56.1% vs 64.8%, respectively). Rates of biopsy-proven acute rejection at 12 months were similar (7/63 (11.1%) compared to 4/65 (6.2%)). There was no difference in patient/graft survival between groups. Conclusions: The time to therapeutic tacrolimus levels did not differ based on tacrolimus formulation and was not correlated with clinical outcomes.
RESUMEN
Rationale & Objective: Pregnancy in females with kidney disease is not uncommon and is associated with adverse maternal and fetal outcomes. The use of contraception in females with chronic kidney disease remains low. We sought to describe the perspectives of female patients with advanced chronic kidney disease on the use of contraception. Study Design: Qualitative study. Setting & Participants: We conducted 5 focus group interviews involving 16 adult female patients with advanced chronic kidney disease (n = 3 nondialysis nontransplant chronic kidney disease, n = 9 kidney transplant, and n = 4 kidney failure receiving dialysis) in the United States, following which thematic saturation was reached. Analytical Approach: Interview transcripts were analyzed thematically. Results: We identified the following 5 themes: 1) variable knowledge regarding reproductive health with kidney disease, 2) inadequate counseling about contraceptive use, 3) lack of interdisciplinary coordination regarding contraceptive use, 4) insufficient educational resources available to guide the contraceptive discussion, and 5) need for research to better understand reproductive needs in females with kidney disease. Limitations: Patients were from a single center in the United States, and the study is limited by the transferability of findings to other settings. Conclusions: Patients with chronic kidney disease report emotional challenges with reproductive health, lack of counseling and care coordination, and insufficient resources for contraceptive use. Strategies to strengthen these factors may improve the quality of reproductive care and increase contraceptive use for females with chronic kidney disease. Plain-Language Summary: Pregnancy in females with kidney disease is common and associated with a higher risk of adverse maternal and fetal outcomes, but the use of contraception remains low. Little is known about female patients' experiences in contraceptive use that may contribute to low contraceptive use in this high-risk population. In the present study using focus group interviews, patients with chronic kidney disease reported emotional challenges with reproductive health, lack of counseling and care coordination, and insufficient resources for contraceptive use. Interventions are needed to strengthen these factors to improve the quality of reproductive care and increase contraceptive use for females with chronic kidney disease.
RESUMEN
BACKGROUND: To evaluate the effect of the Affordable Care Act (ACA) Medicaid expansion on payor mix among patients on the kidney and liver transplant waiting list as well as waiting list and post-transplant outcomes. DESIGN: Using the Scientific Registry of Transplant Recipients, we performed a secondary data analysis of all patients on the kidney and liver transplant waiting list from 2007 to 2018. We described changes in payor mix by timing of state Medicaid expansion. We used competing risks models to estimate cause-specific hazard ratios for the effects of insurance and era on death/delisting and transplant. We used a Poisson regression model to estimate the effect of insurance and era on incidence rate ratio of inactivations on the waiting list. We used Cox proportional hazards models to estimate the effect of insurance and era on graft and patient survival. RESULTS: A decade after implementation of the ACA, the prevalence of Medicaid beneficiaries listed for transplant increased by 2.5% (from 7.4% to 9.9%) for kidney and by 2.6% (15.3% to 17.9%) for liver. Expansion states had greater increases than nonexpansion states (kidney 3.8% vs 0.6%, liver 5.3% vs -1.8%). Among wait-listed patients, the magnitude of association of Medicaid insurance vs private insurance with transplant decreased over time for kidney candidates (era 1 subdistribution hazard ratio (SHR), 0.62 [95% CI, 0.60-0.64] vs era 3 SHR, 0.77 [95% CI, 0.74-0.70]) but increased for liver candidates (era 1 SHR, 0.85 [95% CI, 0.83-0.90] vs era 3 SHR 0.79 [95% CI, 0.77-0.82]). Medicaid-insured kidney and liver recipients had greater hazards of graft failure; this did not change over time (kidney: HR, 1.23 [95% CI, 1.06-1.44] liver: HR, 1.05 [95% CI, 0.94-1.17]). CONCLUSIONS: For the millions of patients with chronic kidney and liver diseases, implementation of the ACA has resulted in only modest increases in access to transplant for the publicly insured vs the privately insured.
Asunto(s)
Trasplante de Hígado , Patient Protection and Affordable Care Act , Estados Unidos , Humanos , Medicaid , Sistema de Registros , RiñónRESUMEN
Background: Acute kidney injury (AKI) is most commonly caused by tubular injury and is associated with a wide variety of critical illnesses. It is well known that urinary biomarkers can lead to the early identification of AKI. However, the ability of urinary biomarkers to distinguish between different types of critical illness has been less studied. Methods: In this prospective cohort study, urinary neutrophil gelatinase-associated lipocalin (uNGAL) was measured in 107 patients consecutively admitted to the ICUs in our tertiary medical center. uNGAL samples were collected within 3-6 hours of admission to an ICU and measured by ELISA. All data were analyzed using R statistical software, and univariate analysis was used to determine the correlations of uNGAL levels with AKI stage, admission diagnoses, and ICU course. Results: uNGAL level increased by a mean of 24-fold (SD 10-59) in ICU patients with AKI and demonstrated a significant correlation with the different AKI stages. uNGAL predicted the need for RRT, with values increased by more than 15-fold (P<0.05) in patients needing RRT, and remained a useful tool to predict AKI in ICU patients with a urinary tract infection. uNGAL level was correlated with certain ICU admitting diagnoses whereby uNGAL levels were lower in ICU patients with cardiogenic shock compared with other admission diagnoses (ß=-1.92, P<0.05). Conclusions: uNGAL can be used as an early predictor of AKI and its severity in patients admitted to the ICU, including the need for RRT. uNGAL may also help in distinguishing patients with cardiogenic shock from those with other critical illnesses and identifying those at risk for poor outcomes irrespective of the presence of AKI.
Asunto(s)
Lesión Renal Aguda , Lipocalinas , Lesión Renal Aguda/diagnóstico , Proteínas de Fase Aguda/metabolismo , Biomarcadores/orina , Enfermedad Crítica , Humanos , Unidades de Cuidados Intensivos , Lipocalina 2 , Lipocalinas/orina , Estudios Prospectivos , Proteínas Proto-Oncogénicas/metabolismo , Choque Cardiogénico/complicacionesRESUMEN
Sex and gender disparity exist in various stages of kidney transplantation. Females were found to be less likely to be referred for kidney transplant, complete pre-transplant evaluation, be placed on the waitlist, and receive a kidney transplant compared to their male counterparts. Interestingly, females comprise the majority of living kidney donors. This review explores the biological and psychosocial factors that contribute to sex and gender disparity in kidney transplantation and proposes ways to address the disparity.
Asunto(s)
Trasplante de Riñón , Femenino , Humanos , Masculino , Trasplante de Riñón/psicología , Donadores Vivos/psicología , Listas de EsperaRESUMEN
Sex and gender often are used interchangeably, but are two distinct entities, with sex being the biological attribute and gender including the social, psychological, and cultural aspects of one's identity. Kidney transplantation has been proven to be the best treatment for end-stage kidney disease, improving both quality of life and life-expectancy for most patients. However, gender disparities in access to and outcomes of kidney transplantation remain despite the plethora of evidence showing the advantages of kidney transplantation to our patients. Data have shown that women are less likely to be waitlisted for a kidney transplant and to receive a deceased donor or a living donor kidney. On the other hand, women are more likely than men to become living kidney donors. Although some state the latter is the result of the female gender to nurture and care for loved ones, others believe this observation is because women often are incompatible with their spouse or child because pregnancy is a strong sensitizing event, which stems from the biological rather than the social differences between the sexes. Influence of sex and gender is not limited to access to kidney transplantation, but rather exist in other areas of transplant medicine, such as the difference observed in transplant outcomes between the sexes, variability in immunosuppression metabolism, and even in more contemporary areas such as recent data showing sex-based differences in outcomes of kidney transplant recipients with coronavirus disease-2019, with males having an increased incidence of acute kidney injury and death.
Asunto(s)
COVID-19 , Trasplante de Riñón , Niño , Femenino , Humanos , Trasplante de Riñón/efectos adversos , Donadores Vivos , Masculino , Embarazo , Calidad de Vida , Factores SexualesRESUMEN
Post-transplant lymphoproliferative disorders (PTLD) are among the most serious complications after solid organ transplantation (SOT). Monomorphic diffuse large B-cell lymphoma (DLBCL) is the most common subtype of PTLD. Historically, outcomes of PTLD have been poor with high mortality rates and allograft loss, although this has improved in the last 10 years. Most of our understanding about PTLD DLBCL is extrapolated from studies in non-PTLD DLBCL, and while several clinical factors have been identified and validated for predicting non-PTLD DLBCL outcomes, the molecular profile of PTLD DLBCL has not yet been characterized. Compartment-specific metabolic reprograming has been described in non-PTLD DLBCL with a lactate uptake metabolic phenotype with high monocarboxylate transporter 1 (MCT1) expression associated with worse outcomes. The aim of our study was to compare the outcomes of PTLD in our transplant center to historic cohorts, as well as study a subgroup of our PTLD DLBCL tumors and compare metabolic profiles with non-PTLD DLBCL. We performed a retrospective single institution study of all adult patients who underwent a SOT between the years 1992-2018, who were later diagnosed with PTLD. All available clinical information was extracted from the patients' medical records. Tumor metabolic markers were studied in a subgroup of PTLD DLBCL and compared to a group of non-PTLD DLBCL. Thirty patients were diagnosed with PTLD following SOT in our center. Median time from SOT to PTLD diagnosis was 62.8 months (IQR 7.6; 134.4), with 37% of patients diagnosed with early PTLD, and 63% with late PTLD. The most common PTLD subtype was DLBCL. Most patients were treated with reduction of their immunosuppression (RIS) including a group who were switched from calcineurin inhibitor (CNI) to mTOR inhibitor based IS, in conjunction with standard anti-lymphoma chemoimmunotherapy. Progression free survival of the PTLD DLBCL cohort was calculated at 86% at 1 year, and 77% at 3 and 5-years, with overall survival of 86% at 1 and 3-years, and 75% at 5 years. Death censored allograft survival in the kidney cohort was 100% at 1 year, and 93% at 3, 5 and 10 years. MCT1 H scores were significantly higher in a subset of the non-PTLD DLBCL patients than in a PTLD DLBCL cohort. Our data is concordant with improved PTLD outcomes in the last 10 years. mTOR inhibitors could be an alternative to CNI as a RIS strategy. Finally, PTLD DLBCL may have a distinct metabolic profile with reduced MCT1 expression compared to non-PTLD DLBCL, but further studies are needed to corroborate our limited cohort findings and to determine if a specific metabolic profile is associated with outcomes.
RESUMEN
In obesity, adipose tissue derived inflammation is associated with unfavorable metabolic consequences. Uremic inflammation is prevalent and contributes to detrimental outcomes. However, the contribution of adipose tissue inflammation in uremia has not been characterized. We studied the contribution of adipose tissue to uremic inflammation in-vitro, in-vivo and in human samples. Exposure to uremic serum resulted in activation of inflammatory pathways including NFκB and HIF1, upregulation of inflammatory cytokines/chemokines and catabolism with lipolysis, and lactate production. Also, co-culture of adipocytes with macrophages primed by uremic serum resulted in higher inflammatory cytokine expression than adipocytes exposed only to uremic serum. Adipose tissue of end stage renal disease subjects revealed increased macrophage infiltration compared to controls after BMI stratification. Similarly, mice with kidney disease recapitulated the inflammatory state observed in uremic patients and additionally demonstrated increased peripheral monocytes and inflammatory polarization of adipose tissue macrophages (ATMS). In contrast, adipose tissue in uremic IL-6 knock out mice showed reduced ATMS density compared to uremic wild-type controls. Differences in ATMS density highlight the necessary role of IL-6 in macrophage infiltration in uremia. Uremia promotes changes in adipocytes and macrophages enhancing production of inflammatory cytokines. We demonstrate an interaction between uremic activated macrophages and adipose tissue that augments inflammation in uremia.