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De novo cancer incidence after kidney and liver transplantation: Results from a nationwide population based data.

ABSTRACT: The cancer risk among solid organ transplantation recipients in East-Asia has been insufficiently studied. This study estimated de novo cancer incidence in kidney and liver recipients 2008-2015, compared with the general population in Korea using nationwide data. This is a retrospective cohort study using nationwide health insurance claims data. The study population was comprised of cancer-free 10,085 kidney recipients and 3,822 liver recipients. Standardized incidence ratio (SIR) of cancer using indirect standardization was calculated. Compared with the general population, the cancer risk increased by 3.19-fold in male and 2.56-fold in female kidney recipients. By cancer type, a notably increased SIR was observed for Kaposi sarcoma, renal cancer, skin cancer, and non-Hodgkin's lymphoma in male and for bladder cancer, renal cancer, and non-Hodgkin's lymphoma in female kidney recipients. In liver recipients, the SIR of all cancers was 3.43 in males and 2.30 in females. In male liver recipients, the SIRs for Kaposi sarcoma, non-Hodgkin's lymphoma, myeloid leukemia, and skin cancer and in female recipients those for non-Hodgkin's lymphoma and liver cancer were prominent. A greatly higher SIRs for overall cancer and non-Hodgkin's lymphoma in kidney and liver recipients aged 0-19 were observed, compared with recipients in other age group. The incidence of de novo cancer in kidney and liver recipients was higher than the general population and common types were different. Strategies of cancer prevention and screening after kidney and liver transplantation should be developed in response to the incidence of common types of de novo cancers.

SUBMITTER: Park B

PROVIDER: S-EPMC6868238 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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De novo cancer incidence after kidney and liver transplantation: Results from a nationwide population based data.

Park Boyoung B Yoon Junghyun J Choi Dongho D Kim Han Joon HJ Jung Yun Kyung YK Kwon Oh Jung OJ Lee Kyeong Geun KG

Scientific reports 20191120 1

The cancer risk among solid organ transplantation recipients in East-Asia has been insufficiently studied. This study estimated de novo cancer incidence in kidney and liver recipients 2008-2015, compared with the general population in Korea using nationwide data. This is a retrospective cohort study using nationwide health insurance claims data. The study population was comprised of cancer-free 10,085 kidney recipients and 3,822 liver recipients. Standardized incidence ratio (SIR) of cancer usin ...[more]

PMID: 31748582

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Project description:IntroductionAntibody mediated rejection (ABMR) is a major factor limiting outcome after organ transplantation. Anti-HLA donor-specific antibodies (DSA) of the IgG isotype are mainly responsible for ABMR. Recently DSA of the IgE isotype were demonstrated in murine models as well as in a small cohort of sensitized transplant recipients. In the present study, we aimed to determine the frequency of pre-existing and de novo anti-HLA IgE antibodies in a cohort of 105 solid organ transplant recipients.MethodsWe prospectively measured anti-HLA IgE antibodies in a cohort of kidney (n=60), liver, heart and lung (n=15 each) transplant recipients before and within one-year after transplantation, employing a single-antigen bead assay for HLA class I and class II antigens. Functional activity of anti-HLA IgE antibodies was assessed by an in vitro mediator release assay. Antibodies of the IgG1-4 subclasses and Th1 and Th2 cytokines were measured in anti-HLA IgE positive patients.ResultsPre-existing anti-HLA IgE antibodies were detected in 10% of renal recipients (including 3.3% IgE-DSA) and in 4.4% of non-renal solid organ transplant recipients (heart, liver and lung cohort). Anti-HLA IgE occurred only in patients that were positive for anti-HLA IgG, and most IgE positive patients had had a previous transplant. Only a small fraction of patients developed de novo anti-HLA IgE antibodies (1.7% of kidney recipients and 4.4% of non-renal recipients), whereas no de novo IgE-DSA was detected. IgG subclass antibodies showed a distinct pattern in patients who were positive for anti-HLA IgE. Moreover, patients with anti-HLA IgE showed elevated Th2 and also Th1 cytokine levels. Serum from IgE positive recipients led to degranulation of basophils in vitro, demonstrating functionality of anti-HLA IgE.DiscussionThese data demonstrate that anti-HLA IgE antibodies occur at low frequency in kidney, liver, heart and lung transplant recipients. Anti-HLA IgE development is associated with sensitization at the IgG level, in particular through previous transplants and distinct IgG subclasses. Taken together, HLA specific IgE sensitization is a new phenomenon in solid organ transplant recipients whose potential relevance for allograft injury requires further investigation.

Project description:Background: Despite significant improvements in short-term kidney transplant survival, comparable increases in 5 and 10-year outcomes have not been achieved. Chronic allograft nephropathy (CAN) is a major cause of late graft loss. Toxic nephropathy and inadequate long-term immunosuppression are possible factors. We performed a randomized prospective trial comparing calcineurin inhibitor (CNI)-free to CNI-based immunosuppression to determine the impact on renal function, structure, and gene expression. Methods: Sixty-one kidney recipients received mycophenolate mofetil (MMF), and prednisone (P). Randomized patients received concentration-controlled sirolimus or cyclosporine. Two years post-transplant 55 patients underwent renal function studies, 48 (87%) underwent transplant biopsies; all classified by Banff scoring and 41 by DNA microarrays. Findings: Comparing sirolimus/MMF/P to cyclosporine/MMF/P at two years, there was a significantly lower serum creatinine (1.35 vs. 1.81 mg/dl; p=0.008), significantly higher Cockroft-Gault glomerular filtration rate (GFR) (80.4 vs. 63.4 cc/min; p=0.008), iothalamate GFR (60.6 vs. 49.2 cc/min; p= 0.018), and Banff 0 (normal) biopsies (66.6 vs. 20.8%; p=0.013). Regression analysis of calculated GFR’s from 1 to 36 months yielded a positive slope for sirolimus of 3.36 ml/min/year, and a negative slope for cyclosporine of –1.58 ml/min/year (p=0.008). Gene expression profiles of kidney biopsies with higher Banff CAN scores confirmed significant up regulation of genes responsible for immune/inflammation and fibrosis/tissue remodeling. Interpretation: At two years the sirolimus-treated patients have better renal transplant function, a diminished prevalence of CAN, and down regulated expression of genes responsible for the progression of CAN. All may provide for an alternative natural history with improved graft survival. Keywords = Cyclosporine Keywords = Sirolimus Keywords = Transplantation Keywords = DNA microarrays Keywords = calcineurin inhibitors Keywords: parallel sample. This dataset is part of the TransQST collection.

Project description:The study's aim was to summarize the incidence and impacts of post-liver transplant (LTx) acute kidney injury (AKI) on outcomes after LTx. A literature search was performed using the MEDLINE, EMBASE and Cochrane Databases from inception until December 2018 to identify studies assessing the incidence of AKI (using a standard AKI definition) in adult patients undergoing LTx. Effect estimates from the individual studies were derived and consolidated utilizing random-effect, the generic inverse variance approach of DerSimonian and Laird. The protocol for this systematic review is registered with PROSPERO (no. CRD42018100664). Thirty-eight cohort studies, with a total of 13,422 LTx patients, were enrolled. Overall, the pooled estimated incidence rates of post-LTx AKI and severe AKI requiring renal replacement therapy (RRT) were 40.7% (95% CI: 35.4%⁻46.2%) and 7.7% (95% CI: 5.1%⁻11.4%), respectively. Meta-regression showed that the year of study did not significantly affect the incidence of post-LTx AKI (p = 0.81). The pooled estimated in-hospital or 30-day mortality, and 1-year mortality rates of patients with post-LTx AKI were 16.5% (95% CI: 10.8%⁻24.3%) and 31.1% (95% CI: 22.4%⁻41.5%), respectively. Post-LTx AKI and severe AKI requiring RRT were associated with significantly higher mortality with pooled ORs of 2.96 (95% CI: 2.32⁻3.77) and 8.15 (95%CI: 4.52⁻14.69), respectively. Compared to those without post-LTx AKI, recipients with post-LTx AKI had significantly increased risk of liver graft failure and chronic kidney disease with pooled ORs of 3.76 (95% CI: 1.56⁻9.03) and 2.35 (95% CI: 1.53⁻3.61), respectively. The overall estimated incidence rates of post-LTx AKI and severe AKI requiring RRT are 40.8% and 7.0%, respectively. There are significant associations of post-LTx AKI with increased mortality and graft failure after transplantation. Furthermore, the incidence of post-LTx AKI has remained stable over the ten years of the study.

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De novo cancer incidence after kidney and liver transplantation: Results from a nationwide population based data.

Publications

De novo cancer incidence after kidney and liver transplantation: Results from a nationwide population based data.

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