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induction of immunosuppression in renal transplantation

Mary Helen Foster, Jeffrey Robinson Ord
Autoimmunity is a leading cause of chronic kidney disease and loss of native and transplanted kidneys. Conventional immunosuppressive therapies can be effective but are non-specific, noncurative, and risk serious side effects such as life-threatening infection and cancer. Novel therapies and targeted interventions are urgently needed. In this brief review we explore diverse strategies currently in development and under consideration to interrupt underlying disease mechanisms in immune-mediated renal injury...
December 14, 2018: Human Vaccines & Immunotherapeutics
Alexandra Kreps, Karen Paltoo, Isabel McFarlane
Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease with a wide range of clinical features and variable clinical course. SLE tends to affect women during childbearing years and is characterized by multi-organ involvement. Cardiac complications in SLE, which have been described to occur in about 50% of the cases, contributes to significant morbidity and mortality in this population. We describe a patient with SLE and established lupus nephritis who subsequently developed cardiac manifestations including valvular abnormalities, arrythmia and end stage heart failure...
2018: American journal of medical case reports
Marilena Gregorini, Vincenzo Sepe, Francesca Eleonora Pattonieri, Anna Allesina, Teresa Rampino
BACKGROUND: Post-transplant diabetes mellitus (PTDM) is an emerging problem in kidney transplantation, representing an important risk factor for kidney function loss. Diabetic nephropathy (DN) occurrence in transplanted kidneys is poorly investigated. Current knowledge describes DN recurrence in graft 5.9 years from kidney transplantation however there is little data about PTDM and DN. Here, we report a clinical case peculiar for an early appearance of advanced glomerular diabetic lesions, after kidney transplantation...
December 7, 2018: BMC Nephrology
Nashila AbdulRahim, Lee Anderson, Suman Kotla, Hao Liu, Venkatesh K Ariyamuthu, Mythili Ghanta, Malcolm MacConmara, Shannan R Tujios, Arjmand Mufti, Sumit Mohan, Jorge A Marrero, Parsia A Vagefi, Bekir Tanriover
The number of simultaneous liver kidney transplant (SLKT) and the concomitant use of induction therapy have increased over the last decade. However, there is little data comparing outcomes amongst induction agents in the context of maintenance immunosuppression regimen consisting of tacrolimus and mycophenolic acid (TAC/MPA). We queried the OPTN registry for SLKT recipients maintained on TAC/MPA at discharge in the U.S. between 2002 and 2016. The cohort was divided into three groups based on induction type: r-ATG (N=831), IL2RA (N=1,558), and no-induction (N=2,333)...
December 2, 2018: Liver Transplantation
Evaldo Favi, Carmelo Puliatti, Samuele Iesari, Andrea Monaco, Mariano Ferraresso, Roberto Cacciola
Background: Standard-criteria donation after circulatory death (DCD) kidney transplants (KTx) have higher primary nonfunction, delayed graft function (DGF), and rejection rates than age-matched donation after brain death (DBD) but similar graft survival. Data on expanded-criteria DCD are conflicting and many centers remain concerned regarding their use. Methods: In this single-center observational study with 5-year follow-up, we analyzed data from 112 primary DCD Maastricht category-III single KTx receiving similar organ preservation and maintenance immunosuppression...
October 2018: Transplantation Direct
C I Tsao, M Ting, N K Chou, N-H Chi, Y-S Chen, S-C Huang, C-Y Tsan, C-H Wang, H-Y Yu, C T Shun, S-S Wang
Renal function after heart transplantation (HTx) typically follows a biphasic pattern and an initial decay within 1 to 2 years. Trajectory of renal function after HTx is less reported, especially in Asia. The aims of this cohort study were to describe the changes in HTx recipients' serum creatinine and estimated glomerular filtration rate (eGFR) levels 5 years following HTx in Taiwan. METHODS: We retrospectively reviewed 5 years of 440 consecutive adult patients (≥ 18 years) who underwent first HTx from June 1987 to December 2014 at the National Taiwan University Hospital...
November 2018: Transplantation Proceedings
O Konno, T Yokoyama, Y Kihara, Y Nakamura, T Ueno, H Takeuchi, H Iwamoto
BACKGROUND: Extended-release tacrolimus (TacER), administered once daily, offers improved adherence with reduced side effects while still maintaining an immunosuppressive potency equivalent to that of conventional tacrolimus preparations. METHODS: The study included 83 patients who received consecutive living-donor kidney transplants at our facility from June 2013 to December 2016. Comparisons were made between 48 cases of induction with TacER and 35 cases of induction with cyclosporine (CyA)...
October 2018: Transplantation Proceedings
Y Liu, H Liu, Y Shen, Y Chen, Y Cheng
BACKGROUND: Tacrolimus is widely used in renal transplantation to help prevent acute and chronic rejection, but the nephrotoxicity of tacrolimus may compromise renal function. This study investigates the safety and efficacy in delayed initiation of tacrolimus after antilymphocyte induction therapy in kidney transplant recipients. METHODS: This retrospective cohort analysis involved data from 68 kidney transplant recipients receiving standard induction therapy (basiliximab [Simulect] or thymoglobulin) combined with tacrolimus...
October 2018: Transplantation Proceedings
Su Hooi Teo, Kian-Guan Lee, Gek Hsiang Lim, Si Xuan Koo, Maria Erika Ramirez, Khuan Yew Chow, Terence Kee
INTRODUCTION: Data on post-kidney transplantation (KTX) malignancy is limited in our region, leading to challenges in the care of renal allograft recipients. We aimed to examine the epidemiology, risk factors and outcomes of post-KTX patients. METHODS: A retrospective cohort study was conducted of 491 patients who underwent KTX from 1 January 2000 to 31 December 2011. Data linkage analysis was done between our centre and the National Registry of Disease Office to determine the standardised incidence ratio (SIR), standardised mortality ratio (SMR) and risk factors for malignancy after KTX...
October 10, 2018: Singapore Medical Journal
Cornelius C Thaiss, Tetsu Oura, Hajime Sasaki, Abbas Dehnadi, Masatoshi Matsunami, Ivy A Rosales, Benedict A Cosimi, Tatsuo Kawai
BACKGROUND: Although induction of durable mixed chimerism is required for murine skin allograft tolerance, renal allograft tolerance has been achieved after induction of only transient mixed chimerism in nonhuman primates (NHPs) and humans. To better define the level/duration of chimerism required for stable renal allograft tolerance, we retrospectively analyzed these parameters and compared them with transplant outcomes in NHP combined kidney and bone marrow transplant (CKBMT) recipients...
October 8, 2018: Transplantation
Jonna R Bank, Renée Ruhaak, Darius Soonawala, Oleg Mayboroda, Fred P Romijn, Cees van Kooten, Christa M Cobbaert, Johan W de Fijter
BACKGROUND: Urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP7) have been validated as biomarkers for acute kidney injury. We investigated the performance of both markers in predicting the occurrence and duration of functionally defined delayed graft function (fDGF) in donation after circulatory death (DCD) kidney transplant recipients. METHODS: Urine samples of 74 DCD recipients were analyzed. TIMP-2 and IGFBP7 were measured with ELISA on postoperative day 1 to 7, day 10, week 6 and month 6 and values were corrected for osmolality (mOsm)...
October 8, 2018: Transplantation
Reza Zonozi, John L Niles, Frank B Cortazar
Antineutrophil cytoplasmic antibody-associated vasculitis (AAV) is the most common cause of rapidly progressive glomerulonephritis. ANCAs play an important role in the pathogenesis and diagnosis of AAV. The classic renal lesion in AAV is a pauci-immune necrotizing and crescentic glomerulonephritis. Treatment is divided into 2 phases: (1) induction of remission to eliminate disease activity and (2) maintenance of remission to prevent disease relapse. AAV patients with end-stage renal disease require modification of immunosuppressive strategies and consideration for kidney transplantation...
November 2018: Rheumatic Diseases Clinics of North America
Cristina Dopazo, Ramón Charco, Mireia Caralt, Elizabeth Pando, José Luis Lázaro, Concepción Gómez-Gavara, Lluis Castells, Itxarone Bilbao
We aimed to evaluate the safety and efficacy of low doses of anti-T-lymphocyte globulin (ATG)-based immunosuppression in preserving renal function and preventing liver rejection in liver transplant (LT) recipients with pretransplant renal dysfunction. We designed a prospective single-center cohort study analyzing patients with pre-LT renal dysfunction defined as eGFR<60 mL/min/1.73m2 , who underwent induction therapy with ATG ( ATG group, n=20) . This group was compared with a similar retrospective cohort treated with basiliximab ( BAS group, n=20 )...
2018: Canadian Journal of Gastroenterology & Hepatology
M Wójciak, J Gozdowska, D Dęborska-Materkowska, A Perkowska-Ptasińska, M Kosieradzki, S Nazarewski, M Durlik
INTRODUCTION: Posttransplant lymphoproliferative disorder (PTLD) is a heterogeneous group of lymphoid malignant neoplasms arising after solid organ transplantation or hematopoietic stem cell transplantation. The current World Health Organization classification identified 4 basic histologic types of PTLD: early, polymorphic variant, monomorphic variant, and classical Hodgkin lymphoma-type lesions. METHODS: Data of 12 PTLD cases of was retrospectively analyzed in terms of the transplanted organs, time to diagnosis of PTLD, type of immunosuppressive treatment in regard to the induction treatment and acute transplant rejection, and long-term survival...
September 2018: Transplantation Proceedings
M S Gniewkiewicz, M Czerwińska, J Gozdowska, J Wyzgał, T Grochowiecki, S Nazarewski, M Kosieradzki, M Durlik
BACKGROUND: Simultaneous pancreas-kidney transplantation (SPKT) is the treatment of choice for patients with end-stage renal disease (ESRD) due to type 1 diabetes mellitus (DM1). Since the 1980s, pancreas transplantation has become the most effective strategy to restore normoglycemia in patients with DM1. The aim of this study was to present long-term outcomes data for SPKT. METHODS: We performed a retrospective analysis of 73 SPKT recipients followed in our outpatient center who underwent transplantation between 1988 and 2015...
September 2018: Transplantation Proceedings
Kadiyala V Ravindra, Scott Sanoff, Deepak Vikraman, Ahmad Zaaroura, Aditya Nanavati, Debra Sudan, William Irish
Delayed graft function (DGF) is a risk factor for acute rejection (AR) in renal transplant recipients, and KDIGO guidelines suggest use of lymphocyte-depletion induction when DGF is anticipated. We analyzed the United Network for Organ Sharing/Organ Procurement and Transplantation Network (UNOS/OPTN) database to assess the impact of induction immunosuppression on the risk of AR in deceased kidney recipients based on pretransplant risk of DGF using a validated model. Recipients were categorized into 4 groups based upon the induction immunosuppression: (1) Rabbit anti-thymocyte globulin (rATG); (2) Alemtuzumab (C1H); (3) IL2-receptor antagonists (IL2-RA; basiliximab or daclizumab), and (4) No antibody induction...
September 1, 2018: American Journal of Transplantation
Jacek Wojarski, Sławomir Żegleń, Marek Ochman, Wojtek Karolak
BACKGROUND Sirolimus, a mechanistic target of sirolimus inhibitor, is an immunosuppression medication for patients undergoing heart and abdominal transplantation. Sirolimus-based immunosuppression administered de novo post-lung transplantation is associated with bronchial anastomosis healing-related complications. We hypothesized that sirolimus administration within the first postoperative month in selected lung transplant recipients is safe and may be associated with favorable short-term and long-term outcomes due to its anti-proliferative properties and minimal adverse side effects...
August 23, 2018: Annals of Transplantation: Quarterly of the Polish Transplantation Society
Tetsu Oura, Kiyohiko Hotta, Ivy Rosales, Abbas Dehnadi, Kent Kawai, Hang Lee, A Benedict Cosimi, Tatsuo Kawai
BACKGROUND: We recently reported anti-CD40 monoclonal antibody and rapamycin (aCD40/rapa) to be a reliable, nontoxic, immunosuppressive regimen for combined islet and kidney transplantation (CIKTx) in nonhuman primates (NHPs). In the current study, we attempted to induce allograft tolerance through the mixed chimerism approach using a conditioning regimen with aCD40 and belatacept (Bela). METHODS: Five CIKTx or kidney transplant (KTx) recipients were treated with aCD40/rapa for 4 months...
August 15, 2018: Transplantation
A Furmańczyk-Zawiska, T Bączkowska, D Dęborska-Materkowska, S Nazarewski, M Kosieradzki, M Durlik
BACKGROUND: Optimization of immunosuppressive therapy reduced the incidence of acute rejection, and therefore vascular complications, including graft thrombosis, which have emerged as the main cause of graft loss in the early post-transplant period. A thrombophilic condition may lead to renal graft loss. The aim of the study was to assess renal graft function in thrombophilic renal recipients receiving anticoagulation treatment. METHODS: This is a retrospective study including 29 renal recipients (ktx group) with a history of thrombosis and confirmed thrombophilic factor...
July 2018: Transplantation Proceedings
Michael Stöckle, Kerstin Junker, Paolo Fornara
CONTEXT: Organ transplantation requires immunosuppression, which was regarded as a risk factor for tumor induction and tumor progression in all types of malignancy. Until recently, any form of active neoplasia was, therefore, regarded as contraindicative to organ transplantation. However, there is growing evidence that the increased tumor risk by immunosuppression is restricted to particular subgroups of malignancy, whereas others such as prostate cancer (PCa) are not negatively influenced...
March 2018: European Urology Focus
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