Outcomes of Delayed Graft Function in Kidney Transplant Recipients Stratified by Histologic Biopsy Findings

Delayed graft function (DGF) after kidney transplantation is associated with an increased risk of graft failure. We studied the histologic findings among adult kidney transplant recipients transplanted between January 2000 and June 2015 who had DGF and had a kidney biopsy within 14 days of transplant. Death censored graft failure (DCGF) and death at 1 and 3 years after transplant were examined. A total of 269 transplant recipients fulfilled our selection criteria, of which 152 (56.51%) had acute tubular necrosis (ATN), 44 (16.4%) had acute rejection (AR), mainly T-cell mediated rejection (n = 31), 35 (13%) had ATN with AR (mainly T-cell mediated rejection, n = 26), and 38 (14.1%) had other pathology. Compared with those with ATN alone, kidney transplant recipients with AR alone had a significantly higher risk of DCGF at 1 year post transplant (adjusted hazard ratio = 3.70; 95% confidence interval 1.5-9.5; P = .006). Those with AR alone had an increased risk of DCGF at 3 years post transplant (hazard ratio = 3.10; 95% confidence interval 1.3-8.5; P = .01) in crude analyses. There was no association between DGF etiology and mortality. Early renal biopsy can be used to distinguish AR, which has protocolized treatments, from other etiologies. This could potentially alter allograft survival within 1 year of transplant complicated by DGF.     

Pretransplant solid organ malignancy and organ transplant candidacy: A consensus expert opinion statement

Patients undergoing evaluation for solid organ transplantation (SOT) often have a history of malignancy. Although the cancer has been treated in these patients, the benefits of transplantation need to be balanced against the risk of tumor recurrence, especially in the setting of immunosuppression. Prior guidelines of when to transplant patients with a prior treated malignancy do not take in to account current staging, disease biology, or advances in cancer treatments. To develop contemporary recommendations, the American Society of Transplantation held a consensus workshop to perform a comprehensive review of current literature regarding cancer therapies, cancer stage-specific prognosis, the kinetics of cancer recurrence, and the limited data on the effects of immunosuppression on cancer-specific outcomes. This document contains prognosis based on contemporary treatment and transplant recommendations for breast, colorectal, anal, urological, gynecological, and nonsmall cell lung cancers. This conference and consensus documents aim to provide recommendations to assist in the evaluation of patients for SOT given a history of a pretransplant malignancy.     

Ten‐year attrition and antiretroviral therapy response among HIV‐positive adults: a sex‐based cohort analysis from eight West African countries

IntroductionSex differences have already been reported in sub‐Saharan Africa for attrition and immunological response after antiretroviral therapy (ART) initiation, but follow‐up was usually limited to the first two to three years after ART initiation. We evaluated sex differences on the same outcomes in the 10 years following ART initiation in West African adults.MethodsWe used cohort data of patients included in the IeDEA West Africa collaboration, who initiated ART between 2002 and 2014. We modelled no‐follow‐up and 10‐year attrition risks, and immunological response by sex using logistic regression analysis, survival analysis with random effect and linear mixed models respectively.ResultsA total of 71,283 patients (65.8% women) contributed to 310,007 person‐years of follow‐up in 16 clinics in eight West African countries. The cumulative attrition incidence at 10‐year after ART initiation reached 75% and 68% for men and women respectively. Being male was associated with an increased risk of no follow‐up after starting ART (5.1% vs. 4.0%, adjusted Odds Ratio: 1.25 [95% CI: 1.15 to 1.35]) and of 10‐year attrition throughout the 10‐year period following ART initiation: adjusted Hazard Ratios were 1.22 [95% CI: 1.17 to 1.27], 1.08 [95% CI: 1.04 to 1.12] and 1.04 [95% CI: 1.01 to 1.08] during year 1, years 2 to 4 and 5 to 10 respectively. A better immunological response was achieved by women than men: monthly CD4 gain was 30.2 and 28.3 cells/mL in the first four months and 2.6 and 1.9 cells/μL thereafter. Ultimately, women reached the average threshold of 500 CD4 cells/μL in their sixth year of follow‐up, whereas men failed to reach it even at the end of the 10‐year follow‐up period. The proportion of patients reaching the threshold was much higher in women than in men after 10 years since ART initiation (65% vs. 44%).ConclusionsIn West Africa, attrition is unacceptably high in both sexes. Men are more vulnerable than women on both attrition and immunological response to ART in the 10 years following ART initiation. Innovative tracing strategies that are sex‐adapted are needed for patients in care to monitor attrition, detect early high‐risk groups so that they can stay in care with a durably controlled infection.     

Differential effects of zidovudine and zidovudine triphosphate on mitochondrial permeability transition and oxidative phosphorylation

1. The effects of zidovudine (ZDV) and zidovudine triphosphate (ZDV-3P) on Ca²⁺-induced mitochondrial permeability transition (MPT), respiratory control ratio (RCR) and ATP synthesis have been investigated on isolated rat liver mitochondria.
2. ZDV slightly but significantly decreased RCR and ATP synthesis but was ineffective in inhibiting MPT. In contrast, ZDV-3P did not alter RCR and ATP synthesis but strongly inhibited MPT (IC₅₀=3.0±0.9 μM).
3. The effect of ZDV-3P on mitochondrial swelling required a preincubation time. When incubated 10 min with mitochondria, ZDV-3P (8 μM) totally inhibited the rate of swelling.
4. ADP, ATP and atractyloside, which are agents known to interact with the mitochondrial adenine nucleotide carrier (ANC), antagonized the effect of ZDV-3P on mitochondrial swelling. Indeed, the IC₅₀ value of ZDV-3P increased from 3.0 to 17.4, 93.6 and 66.5 μM, in the presence of 20 μM, ADP, ATP or atractyloside, respectively.
5. ZDV-3P did not displace [³H]-ATP from its mitochondrial binding site(s) whereas ADP and atractyloside did, suggesting that ZDV-3P and [³H]-ATP do not share the same binding sites.
6. ZDV-3P did not affect either mitochondrial respiration or ATP synthesis but inhibited Ca²⁺-dependent mitochondrial swelling. It was concluded that mitochondrial toxic effects observed during the chronic administration of ZDV cannot be related to its active metabolite (ZDV-3P).

     

Significance of incidental 18F-FDG accumulations in the gastrointestinal tract in PET/CT: correlation with endoscopic and histopathologic results.

This study was undertaken to identify the clinical value of incidentally detected lesions (IDLs) in the gastrointestinal tract (GIT) with (18)F-FDG PET/CT. METHODS: The reported database of 3,281 patients who underwent partial-body (18)F-FDG PET/CT scans from April 2001 to September 2003 was reviewed. Patients with incidental (18)F-FDG accumulations in the GIT that were associated with concomitant abnormal soft-tissue density or wall thickening on the native CT were evaluated. Incidental PET/CT findings were correlated with endoscopic and histopathologic results. RESULTS: According to our selection criteria, 98 (3%) of the 3,281 patients had an IDL of the GIT on (18)F-FDG PET/CT. Correlative endoscopic findings were available in 69 (70%) of 98 patients. Of these, 13 patients (19%) were harboring newly occurring cancers of the GIT in addition to preexisting aerodigestive tract tumors (n = 12) and malignant melanoma (n = 1). Twenty-nine (42%) patients were identified with precancerous lesions, such as advanced colonic adenomas (n = 27), Barrett's esophagus (n = 1), and intestinal metaplasia of the gastric mucosa (n = 1). Inflammatory and other benign GIT lesions were detected in 12 (17%) and 6 (8%) patients, respectively. In 9 (13%) patients, PET/CT was false-positive, showing normal findings in subsequent endoscopic examinations. In 20 (28%) of 69 patients, PET/CT findings had a relevant impact on the clinical management. Twenty-nine (30%) of the 98 patients were not subject to a further endoscopic examination because of the extent and nature of the primary tumor (n = 17), loss to follow-up (n = 7), death shortly after PET (n = 3), and patient unwillingness (n = 2). CONCLUSION: Although IDLs of the GIT on (18)F-FDG PET/CT scans are found only in about 3% of cases, they are associated with a substantial risk of an underlying cancerous or precancerous lesion. Early identification of these occult lesions may have a major impact on the patients' management and outcome.