Weight-based vs fixed dosing of darbepoetin alfa for anemia following kidney transplantation.

PURPOSE: Post-transplantation anemia (PTA) is common in kidney transplant recipients, with patients frequently treated with erythropoietin-stimulating agents such as darbepoetin alfa. The optimal dosing for darbepoetin alfa remains controversial. METHODS: This retrospective cohort study involved kidney transplant recipients who received darbepoetin alfa at 2 clinics. Patients were stratified into 2 groups: those who received a fixed dose of 200 µg and those who received a weight-based dose of 0.45 µg/kg. The dosing interval varied depending on clinical response, clinic visit timing, and frequency allowed by insurance. The primary outcome was achieving a hemoglobin concentration of at least 10 g/dL without blood transfusion by 12 weeks after darbepoetin alfa initiation. RESULTS: Of the 110 patients in the study, 45% received weight-based dosing and 55% received fixed dosing. Darbepoetin alfa was initiated significantly earlier after transplantation in the fixed-dose group (median of 14 vs 20 days; P = 0.003). The weight-based group received more doses of darbepoetin alfa (median of 4 vs 2 doses; P = 0.002) and had a significantly lower cumulative exposure to darbepoetin alfa (125 vs 590 µg; P < 0.001). The median time between doses was 9 days (interquartile range, 7-14 days) in the weight-based group and 12 days (7-32 days) in the fixed-dose group (P = 0.04). Patients in the weight-based group more frequently achieved the primary outcome (67.3% vs 47.5%; P = 0.059). There was no significant difference in secondary or safety outcomes between the groups. CONCLUSION: Weight-based and fixed dosing approaches for darbepoetin alfa were not different in the achievement of a hemoglobin concentration of at least 10 g/dL without blood transfusion at 12 weeks after darbepoetin alfa initiation, with significantly lower cumulative darbepoetin alfa utilization in the weight-based group. Weight-based dosing of darbepoetin alfa in PTA appears to be safe and effective, with the potential for significant patient and health-system cost savings.

Vaccination with HepB-CpG vaccine in individuals undergoing immune suppressive drug therapy.

BACKGROUND: Immunosuppressed patients are a targeted group for HBV vaccination but suboptimal antibody responses occur when traditional recombinant vaccines are used. METHODS: We tested an FDA approved immune adjuvanted HBV vaccine (HEPLISAV--B® or HepB-CpG) in medically immune suppressed individuals. HepB-CpG was given to 10 patients taking biologic agents or anti-rejection therapy. Each received vaccine at time 0 and week 4 with a third dose at week 12 if anti-HBs remained less than 10 mIU/mL. RESULTS: Seroprotective anti-HBs developed in 70 % of participants by week 24. Those taking biologic agents responded more rapidly and a third dose was generally needed in those transplanted. By week 24, most taking biologics but only 2 of 6 on anti-rejection treatment had antibody levels exceeding 100 mIU/mL. CONCLUSIONS: Seroprotective anti-HBs developed in 70 % with HepB-CpG. Antibody responses were more rapid in those taking biologic agents but a third dose improved antibody responses in transplanted participants.

Six-month abdominal transplant recipient outcomes from donation after circulatory death heart donors: A retrospective analysis by procurement technique.

Standard US practice for donation after circulatory death (DCD) abdominal organ procurement is superrapid recovery (SRR). A newer approach using thoracoabdominal normothermic regional perfusion (TA-NRP) shows promise for better recipient outcomes for all organs, but there are few reports of abdominal recipient outcomes from TA-NRP donors. We used the United Network for Organ Sharing data to identify all cardiac DCD donors from October 1, 2020, to May 20, 2022, and categorized them by recovery procedure (SRR vs TA-NRP). We then identified all liver, kidney, and pancreas recipients of these donors for whom 6-month outcome data were available and compared patient and graft survival, kidney delayed graft function (DGF), and biliary complications between TA-NRP DCD and SRR DCD organ recipients. Patient and graft survival did not differ significantly between groups for either kidney or liver recipients. Significantly fewer TA-NRP kidney recipients developed DGF (12.7% [15/118] vs 42.0% [84/200], P <.001), and TA-NRP and pumped kidneys had lower odds for DGF on multivariate analysis. No liver recipients in either group had biliary complications or were relisted for transplantation for ischemic cholangiopathy. Although long-term outcomes need to be investigated, our early results show similar outcomes for recipients of TA-NRP DCD abdominal organs versus recipients of SRR DCD abdominal organs. We believe that TA-NRP is an effective approach to expand the use of DCD organs.

Doppler Flow Indices and Prediction of Embryo Transfer Success and Pregnancy Outcome in Uterus Transplant Recipients.

OBJECTIVE: Doppler velocimetry of the uterine and umbilical arteries is used to predict preeclampsia and monitor fetal outcomes. There have been no reports of Doppler velocimetry indices in pregnancies conceived after uterus transplantation, which differ from traditional pregnancies because of different uterine vascular inflow and outflow and exposure to immunosuppressive agents. We sought to examine whether Doppler indices can be used to predict embryo transfer success after uterus transplantation and whether Doppler indices across pregnancy predict fetal growth restriction. STUDY DESIGN: This was a single-center cohort observational study of 14 uterus transplant recipients who underwent embryo transfer. Of these, 12 women successfully delivered 14 babies. Five Doppler investigations were performed within the cohort: (1) prepregnancy; (2) uterine artery assessment across pregnancy; (3) umbilical artery assessment across pregnancy; (4) successive pregnancies; and (5) fetal growth. RESULTS: Prepregnancy uterine artery Doppler indices did not correlate with successful implantation after embryo transfer. Uterine artery Doppler indices in uterus transplant recipients decreased across pregnancy as described in pregnancies without uterus transplantation. The umbilical artery systolic/diastolic velocity ratio was lower at all weeks of gestation after uterus transplantation compared with values described in pregnancies without uterus transplantation. In those women who delivered two successive babies after uterus transplant, umbilical artery Doppler indices were significantly lower during the second pregnancy. There was always forward flow throughout diastole in the umbilical arteries, and no babies experienced fetal growth restriction. CONCLUSION: In our study, uterus transplantation was not associated with abnormal blood flow indices in either the uterine or umbilical arteries. Although Doppler indices were not predictive of embryo transfer success, they supported the expectation that pregnancies after uterus transplantation at our center result in normally grown babies. KEY POINTS: · Uterus transplantation is not associated with abnormal blood flow indices.. · Prepregnancy uterine artery Doppler indices did not correlate with successful embryo implantation.. · Doppler assessment supports the expectation of normal placentation, fetal growth, and healthy live births after uterus transplantation..

Living donor liver transplantation versus donation after brain death and donation after circulatory death liver transplantation in the US.

While previous research has compared outcomes between living donor liver transplantation (LDLT) and deceased donor liver transplantation, evidence is lacking regarding how donation after circulatory death (DCD) vs donation after brain death (DBD) affects this comparison. Using data from the Scientific Registry of Transplant Recipients for adults listed for liver transplant from 2012 to 2018, we compared 5-year patient and graft survival, readmissions, posttransplant chronic kidney disease (CKD), and return to work for 25,151 patients who underwent LDLT (1223 [4.9%]), DCD-LT (1431 [6.4%]), and DBD-LT (22,497 [89.4%]). LDLT recipients were significantly more likely to have a Model for End-Stage Liver Disease (MELD) score < 15 and to be working prior to transplant (P < 0.001 for both). At 5 years posttransplant, LDLT recipients had significantly more readmissions, but significantly less CKD and better survival than DBD-LT and DCD-LT recipients, as well as significantly better graft survival than DCD-LT recipients (P ≤ 0.01 for all). Significantly more LDLT recipients also returned to work for income (P < 0.01). This study shows a clear advantage of LDLT vs DCD-LT. This information should be weighed in transplantation decisions for patients such as those with low MELD scores who will realistically only be considered for DCD-LT.

Clinicopathological Analysis of Uterine Allografts Including Proposed Scoring of Ischemia Reperfusion Injury and T-cell-mediated Rejection-Dallas UtErus Transplant Study: A Pilot Study.

BACKGROUND: Uterus transplantation (UTx) enables pregnancy in infertile women. This study describes the histopathological changes of ischemia reperfusion injury and mostly acute T-cell-mediated rejection (TCMR) in UTx and proposes modification toward a working formulation grading system with associated treatments. METHODS: Protocol and indication biopsies from 11 living and 2 deceased donor UTx recipients were analyzed. Serving as a control were 49 age-matched nontransplanted uteri. All posttransplant histopathological specimens were evaluated in a blinded fashion by 3 pathologists. Response to treatment was assessed by follow-up biopsies. Serial serum donor-specific antibody (DSA) responses were also recorded. RESULTS: Changes attributed to ischemia reperfusion resolved within 2 wk of UTx in most of the patients. For TCMR grading, perivascular inflammation, focal capillary disruption, and interstitial hemorrhage were added to interface inflammation, intercellular edema, stromal inflammation, and epithelial apoptotic bodies. Of the 173 protocol biopsies, 98 were classified as negative for TCMR; 34 as indeterminate-borderline; 35 as mild; 3 as moderate; and 3 as severe, 1 of which occurred in a DSA-positive recipient and also showed microvascular injury. Corticosteroids successfully treated all moderate-to-severe TCMR episodes. Mild TCMR was treated by increasing existing baseline immunosuppression. Indeterminate-borderline episodes were not treated. Neither ischemia-reperfusion injury nor TCMR with DSA adversely affected embryo transfer. CONCLUSIONS: Relying on a modified histopathological grading system, we developed a treatment strategy resulting in resolution of TCMR and successful pregnancies.

Estimating Glomerular Filtration Rate in Cirrhosis Using Creatinine-Based and Cystatin C-Based Equations: Systematic Review and Meta-Analysis.

Accurate estimation of kidney function in cirrhosis is crucial for prognosis and decisions regarding dual-organ transplantation. We performed a systematic review/meta-analysis to assess the performance of creatinine-based and cystatin C (CysC)-based eGFR equations compared with measured GFR (mGFR) in patients with cirrhosis. A total of 25 studies (n = 4565, 52.0 years, 37.0% women) comprising 18 equations met the inclusion criteria. In all GFR equations, the creatinine-based equations overestimated GFR (standardized mean difference, SMD, 0.51; 95% confidence interval [CI], 0.31-0.71) and CysC-based equations underestimated GFR (SMD, -0.3; 95% CI, -0.60 to -0.02). Equations based on both creatinine and CysC were the least biased (SMD, -0.14; 95% CI, -0.46 to 0.18). Chronic kidney disease-Epi-serum creatinine-CysC (CESC) was the least biased but had low precision and underestimated GFR by -3.6 mL/minute/1.73 m2 (95% CI, -17.4 to 10.3). All equations significantly overestimated GFR (+21.7 mL/minute/1.73 m2 ; 95% CI, 17.7-25.7) at GFR <60 mL/minute/1.73 m2 ; of these, chronic kidney disease-Epi-CysC (10.3 mL/minute/1.73 m2 ; 95% CI, 2.1-18.4) and GFR Assessment in Liver Disease (12.6 mL/minute/1.73 m2 ; 95% CI, 7.2-18.0) were the least biased followed by Royal Free Hospital (15 mL/minute/1.73 m2 ; 95% CI, 5.5-24.6) and Modification of Diet in Renal Disease 6 (15.7 mL/minute/1.73 m2 ; 95% CI, 10.6-20.8); however, there was an overlap in the precision of estimates, and the studies were limited. In ascites, overestimation of GFR was common (+8.3 mL/minute/1.73 m2 ; 95% CI, -3.1 to 19.7). However, overestimation of GFR by 10 to 20 mL/minute/1.73m2 is common in patients with cirrhosis with most equations in ascites and/or kidney dysfunction. A tailored approach is required especially for decisions regarding dual-organ transplantation.

Selective screening imaging of the aortoiliac arterial system in kidney transplant candidates with non-contrast pelvic computed tomography.

Non-contrast pelvic computed tomography (CT) can detect severe iliac artery calcifications that present technical contraindications to kidney transplantation (TCT). We screened 454 asymptomatic patients with a history of any of the following: hemodialysis >10 years, diabetes mellitus >20 years, coronary artery disease (CAD) with percutaneous or surgical interventions, carotid disease, diabetes with below-/above-knee amputations, and heart-kidney transplantation candidacy. Patients with normal dorsalis pedis and/or tibialis posterior pulses were not screened. A total of 8.4% had severe calcifications with TCT; CT determined laterality for implantation in 13.9%. No patients with the following characteristics were classified as TCT: age <40 years, hemodialysis >10 years, carotid arterial disease, prior lower extremity amputation, or heart-kidney transplantation candidacy. CAD was associated with TCT in univariate though not multivariate analysis. Limiting screening to patients >40 years, with DM >20 years, or with CAD, 9.8% had a TCT and CT determined transplant laterality in 14.2%. Screening for severe iliac artery calcifications is useful for selected kidney transplantation candidates over age 40. It can assist with laterality choice or surgeon determination of TCT. Cost and radiation exposure risks should be weighed against the morbidity risks from unnecessary surgery.

A Phase I/II Study of Nab-Paclitaxel, Cisplatin, and Cetuximab With Concurrent Radiation Therapy for Locally Advanced Squamous Cell Cancer of the Head and Neck.

Nab-paclitaxel might impact efficacy of radiation for head and neck (H&N) cancer. Nab-paclitaxel, cisplatin, cetuximab, and radiation were evaluated in patients with locally advanced head and neck cancer in this phase I/II trial. Median follow-up was 24 months for 34 patients. The maximum tolerated dose of nab-paclitaxel was 20 mg/m2 with 20 mg/m2 cisplatin and 250 mg/m2 cetuximab. The 2-year progression-free survival (PFS) was 60% (95% confidence interval (CI) 0.42, 0.78), local control 71% (95% CI 0.55, 0.87), and overall survival 68% (95% CI 0.50, 0.86). This is the first study evaluating these agents with radiation in humans, with similar 2-year PFS as historic control.

Comparison of Ambulatory Blood Pressure Patterns in Patients With Intradialytic Hypertension and Hemodialysis Controls.

BACKGROUND/AIMS: Intradialytic hypertension (IH) patients have higher mortality risk than other hemodialysis patients and have been shown to have higher ambulatory blood pressure (BP). We hypothesized that interdialytic BP patterns would differ in IH patients and hypertensive hemodialysis controls. METHODS: We consecutively screened hemodialysis patients at our university-affiliated units. Based on pre and post-HD BP measurements during the prior 2 week period, we identified IH patients and demographically matched hemodialysis controls. We measured ambulatory interdialytic BP, flow-mediated vasodilation, and intradialytic endothelin-1 (ET-1). Using linear mixed-models, we compared BP slopes during the following intervals: 1-24 hours post-dialysis, 25-44 hours post-dialysis, and 1-44 hours post-dialysis. RESULTS: There were 25 case subjects with IH and 24 controls. Systolic BP during hours 1-44, 1-24, and 25-44 were 143.1 (16.5), 138.0 (21.2), and 150.8 (22.3) mmHg in controls. For IH subjects, they were 155.4 (14.2), 152.7 (22.8), and 156.5 (20.8) mmHg (p=0.008, 0.02, 0.4). In controls, the slopes were +0.6, +0.6, and +0.4 mmHg/hr. In IH subjects, they were +0.1, -0.3, and +0.3 mmHg/hr. The IH 1-24 hour slope differed from the IH 25-44 hour slope (p=0.001) and the control 1-24 hour slope (p=0.002). The change in ET-1 from pre to post dialysis was 0.5 (1.5) pg/mL in controls and 1.0 (2.3) pg/mL in IH patients (p=0.4). In a univariate model, there was an association with screening BP and BP slope (p=0.002 for controls and p=0.1 for IH patients). CONCLUSIONS: Interdialytic BP patterns differ in IH patients and hemodialysis controls. The elevated post dialysis blood pressure persists for many hours in IH patients contributing to the overall increased BP burden.