Early application of Met-RANTES ameliorates chronic allograft nephropathy.

PubMed

Song, Erwei; Zou, Hequn; Yao, Yousheng; Proudfoot, Amanda; Antus, Balazs; Liu, Shanying; Jens, Lutz; Heemann, Uwe

2002-02-01

Initial insults to kidney allografts, characterized by infiltration of mononuclear inflammatory cells, contribute to chronic allograft nephropathy. Chemokines such as RANTES (regulated upon activation, normal T cell expressed) are thought to be responsible for the recruitment and activation of infiltrating cells. The present study investigated whether early application of Met-RANTES, a chemokine receptor antagonist that blocks the effects of RANTES, can protect renal allografts from long-term deterioration. Fisher (F344) rat kidneys were orthotopically transplanted into Lewis recipients and treated with cyclosporine A (1.5 mg/kg/day) for the first 10 days following transplantation, together with either Met-RANTES at 40 microg/day, 200 microg/day or vehicle for the first 7 days. Animals were harvested at 2 and 28 weeks after transplantation for histologic, immunohistologic and molecular analysis. Met-RANTES treatment reduced the infiltration of lymphocytes and macrophages in allografts at 2 weeks after transplantation, accompanied by decreased mRNA expression of interleukin (IL)-2, IL-1beta, tumor necrosis factor-alpha (TNF-alpha) and RANTES. At post-transplantation week 28, Met-RANTES treatment at high and low doses reduced urinary protein excretion and significantly ameliorated glomerulosclerosis, interstitial fibrosis, tubular atrophy, intimal proliferation of graft arteries and mononuclear cell infiltration. However, creatinine clearance was not influenced by Met-RANTES. Furthermore, Met-RANTES suppressed the mRNA expression of transforming growth factor-beta (TGF-beta) and platelet-derived growth factor-B (PDGF-B). Blockade of chemokine receptors by Met-RANTES diminishes early infiltration and activation of mononuclear cells in the grafts, and thus reduces the pace of chronic allograft nephropathy.

Reversible renal allograft dysfunction and proteinuria from nutcracker-like syndrome: a case report.

PubMed

Krishnan, S G S; Pritsiolas, J; Susin, M; Linden, E; Beil-Levi, E; Gitman, M; Mossey, R; Bhaskaran, M

2007-06-01

A 27-year-old Hispanic man with hypertension and renal failure was on hemodialysis for 4 years prior to receiving a living donor renal transplant from his 19-year-old sister. His serum creatinine decreased to 1.7 mg/dL at 3 weeks posttransplant with a urine protein creatinine ratio (UP) of 0.1 (g/g). Over the next 2 months, he experienced repeated episodes of allograft dysfunction with elevation of creatinine and proteinuria levels, associated with a lymphocele. Doppler studies of the allograft revealed renal vein compression. His symptoms responded to aspiration of the fluid collection, resolving completely with surgical drainage. We believe that the episodes of allograft dysfunction and proteinuria were related to recurrent lymphocele, causing a nutcracker-like syndrome.

The evolution of the Banff classification schema for diagnosing renal allograft rejection and its implications for clinicians

PubMed Central

Bhowmik, D. M.; Dinda, A. K.; Mahanta, P.; Agarwal, S. K.

2010-01-01

Till the early 1990s there was no standardized international classification of renal allograft biopsies resulting in considerable heterogeneity in reporting among the various centers. A group of dedicated renal pathologists, nephrologists, and transplant surgeons developed a schema in Banff, Canada in 1991. Subsequently there have been updates at regular intervals. The following review presents the evolution of the Banff classification and its utility for clinicians. PMID:20535263

Histomorphological Assessment of Phlebitis in Renal Allografts

PubMed Central

Jurčić, Vesna; Jeruc, Jera; Marić, Stela; Ferluga, Dušan

2007-01-01

Aim To evaluate the histomorphological features of veins in normal and transplanted kidneys. Methods Between 1992 and 1997 at the Institute of Pathology in Ljubljana, we semiquantitatively evaluated histomorphological changes in veins in nephrectomy specimens of 29 renal allografts with rejection and in 31 control kidneys. The structure of different segments of renal veins was additionally analyzed. Results Small interlobular veins were composed of endothelium and basement membrane, similar to capillaries, while the walls of large interlobular and arcuate veins had smooth muscle cell bundles forming the medial layer, similar to large extrarenal veins. In the control group, only focal mononuclear infiltration around small interlobular veins was found (8/31). In rejected kidney allografts, the veins were frequently infiltrated with inflammatory cells, predominantly T lymphocytes and macrophages (29/29). Other changes included thrombosis (16/29), fibrinoid necrosis (7/29), and sclerosis (9/29), and in one case an intimal lipid deposition. Conclusion This study, performed on whole explanted kidney specimens, revealed that rejection vasculitis often involved extrarenal and intrarenal veins, showing a whole spectrum of histopathological changes similar to those in arteries. Since large intrarenal veins have a muscle wall, we believe that the term »rejection phlebitis« could be used in renal transplant pathology. PMID:17589975

The Basics of Renal Allograft Pathology.

PubMed

Troxell, Megan L; Houghton, Donald C

2014-09-01

Renal allograft biopsy provides critical information in the management of renal transplant patients, and must be analyzed in close collaboration with the clinical team. The histologic correlates of acute T-cell mediated rejection are interstitial inflammation, tubulitis, and endothelialitis; polyomavirus nephropathy is a potential mimic. Evidence of antibody-mediated rejection includes C4d deposition; morphologic acute tissue injury; and donor specific antibodies. Acute tubular injury/necrosis is a reversible cause of impaired graft function, especially in the immediate post-transplant period. Drug toxicity, recurrent disease, chronic injury, and other entities affecting both native and transplant kidneys must also be evaluated. Copyright © 2014 Elsevier Inc. All rights reserved.

Diagnosis of BK viral nephropathy in the renal allograft biopsy: role of fluorescence in situ hybridization.

PubMed

Wang, Zhen; Portier, Bryce P; Hu, Bo; Chiesa-Vottero, Andres; Myles, Jonathan; Procop, Gary W; Tubbs, Raymond R

2012-09-01

Early recognition of BK viral nephropathy is essential for successful management. Our aim in this study was to evaluate a novel fluorescence in situ hybridization (FISH) assay for detection of BK virus in renal transplant biopsies in the context of standard detection methods. Renal allograft biopsies (n = 108) were analyzed via H&E, immunohistochemistry (IHC) for simian virus 40, and FISH for BK virus. BK virus was detected in 16 (14.8%) cases by H&E, 13 (12%) cases by IHC, 18 (16.6%) cases by FISH, and 19 (17.6%) cases by real-time PCR; 24 of 108 showed a discrepancy in ≥1 testing modalities. Comparison of H&E, IHC, and FISH showed no statistical difference in detection of BK virus. However, performing comparisons between the different tissue-based assays in the context of plasma or urine real-time PCR results showed significant improvement in detection of BK by FISH over H&E (P = 0.02) but not IHC (P = 0.07). This novel FISH-based approach for BK virus identification in renal allograft biopsy tissue mirrored real-time PCR results and showed superior performance to detection of inclusions by H&E. Therefore, use of FISH for BK virus detection in the setting of renal allograft biopsy is a useful and sensitive detection method and could be adopted in any laboratory that currently performs FISH analysis. Copyright © 2012 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

Antitumor activity of nivolumab on hemodialysis after renal allograft rejection.

PubMed

Ong, Michael; Ibrahim, Andrea Marie; Bourassa-Blanchette, Samuel; Canil, Christina; Fairhead, Todd; Knoll, Greg

2016-01-01

Nivolumab (Opdivo™) is a novel IgG4 subclass programmed death-1 (PD-1) inhibiting antibody that has demonstrated breakthrough-designation anti-tumor activity. To date, clinical trials of nivolumab and other checkpoint inhibitors have generally excluded patients with solid organ transplantation and patients with concurrent immunosuppression. However, organ transplant recipients are at high-risk of development of malignancy as a result of suppressed immune surveillance of cancer. We illustrate the outcomes of a 63 year-old type I diabetic female patient who developed pulmonary metastatic, BRAF wild-type cutaneous melanoma 10 years after renal transplantation. After downward titration of the patient's immunosuppressive medications and extensive multidisciplinary review, she was treated with nivolumab in the first-line setting. Within 1 week of administration, the patient experienced acute renal allograft rejection, renal failure and concurrent diabetic ketoacidosis due to steroid therapy. Allograft function did not return, but patient made a full clinical recovery after being placed on hemodialysis. Subsequently, the patient had clinical disease progression off therapy and required re-challenge with nivolumab on hemodialysis, resulting in ongoing clinical and radiographic response. This case illustrates multiple practical challenges and dangers of administering anti-PD1 immune checkpoint inhibitors to patients with solid-organ transplantation including need for titration of immunosuppressive medications, risks of allograft rejection, and treatment during hemodialysis.

Inhibition of WISE preserves renal allograft function.

PubMed

Qian, Xueming; Yuan, Xiaodong; Vonderfecht, Steven; Ge, Xupeng; Lee, Jae; Jurisch, Anke; Zhang, Li; You, Andrew; Fitzpatrick, Vincent D; Williams, Alexia; Valente, Eliane G; Pretorius, Jim; Stevens, Jennitte L; Tipton, Barbara; Winters, Aaron G; Graham, Kevin; Harriss, Lindsey; Baker, Daniel M; Damore, Michael; Salimi-Moosavi, Hossein; Gao, Yongming; Elkhal, Abdallah; Paszty, Chris; Simonet, W Scott; Richards, William G; Tullius, Stefan G

2013-01-01

Wnt-modulator in surface ectoderm (WISE) is a secreted modulator of Wnt signaling expressed in the adult kidney. Activation of Wnt signaling has been observed in renal transplants developing interstitial fibrosis and tubular atrophy; however, whether WISE contributes to chronic changes is not well understood. Here, we found moderate to high expression of WISE mRNA in a rat model of renal transplantation and in kidneys from normal rats. Treatment with a neutralizing antibody against WISE improved proteinuria and graft function, which correlated with higher levels of β-catenin protein in kidney allografts. In addition, treatment with the anti-WISE antibody reduced infiltration of CD68(+) macrophages and CD8(+) T cells, attenuated glomerular and interstitial injury, and decreased biomarkers of renal injury. This treatment reduced expression of genes involved in immune responses and in fibrogenic pathways. In summary, WISE contributes to renal dysfunction by promoting tubular atrophy and interstitial fibrosis.

Soluble CD30 correlates with clinical but not subclinical renal allograft rejection.

PubMed

Hirt-Minkowski, Patricia; Roth, Michèle; Hönger, Gideon; Amico, Patrizia; Hopfer, Helmut; Schaub, Stefan

2013-01-01

Soluble CD30 (sCD30) has been proposed as a promising noninvasive biomarker for clinical renal allograft rejection, but its diagnostic characteristics regarding detection of subclinical rejection have not been assessed. We investigated sCD30 in 146 consecutive kidney allograft recipients under tacrolimus-mycophenolate-based immunosuppression having 250 surveillance biopsies at 3 and 6 months as well as 52 indication biopsies within the first year post-transplant. Allograft histology results were classified as (i) acute Banff score zero or interstitial infiltrates only, (ii) tubulitis t1, (iii) tubulitis t2-3 and (iv) isolated vascular compartment inflammation. sCD30 correlated well with the extent of clinical (P < 0.0001), but not subclinical tubulointerstitial rejection (P = 0.06). To determine diagnostic characteristics of sCD30, histological groups were assigned to two categories: no relevant inflammation (i.e. acute Banff score zero and interstitial infiltrates only) versus all other pathologies (tubulitis t1-3 and isolated vascular compartment inflammation). For clinical allograft inflammation, AUC was 0.87 (sensitivity 89%, specificity 79%; P = 0.0006); however, for subclinical inflammation, AUC was only 0.59 (sensitivity 50%, specificity 69%; P = 0.47). In conclusion, sCD30 correlated with clinical, but not subclinical renal allograft rejection limiting its clinical utility as a noninvasive rejection screening biomarker in patients with stable allograft function receiving tacrolimus-mycophenolate-based immunosuppression. © 2012 The Authors Transplant International © 2012 European Society for Organ Transplantation.

Early treatment with xenon protects against the cold ischemia associated with chronic allograft nephropathy in rats.

PubMed

Zhao, Hailin; Luo, Xianghong; Zhou, Zhaowei; Liu, Juying; Tralau-Stewart, Catherine; George, Andrew J T; Ma, Daqing

2014-01-01

Chronic allograft nephropathy (CAN) is a common finding in kidney grafts with functional impairment. Prolonged hypothermic storage-induced ischemia-reperfusion injury is associated with the early onset of CAN. As the noble gas xenon is clinically used as an anesthetic and has renoprotective properties in a rodent model of ischemia-reperfusion injury, we studied whether early treatment with xenon could attenuate CAN associated with prolonged hypothermic storage. Exposure to xenon enhanced the expression of insulin growth factor-1 (IGF-1) and its receptor in human proximal tubular (HK-2) cells, which, in turn, increased cell proliferation. Xenon treatment before or after hypothermia-hypoxia decreased cell apoptosis and cell inflammation after reoxygenation. The xenon-induced HK-2 cell proliferation was abolished by blocking the IGF-1 receptor, mTOR, and HIF-1α individually. In the Fischer-to-Lewis rat allogeneic renal transplantation model, xenon exposure of donors before graft retrieval or recipients after engraftment enhanced tubular cell proliferation and decreased tubular cell death and cell inflammation associated with ischemia-reperfusion injury. Compared with control allografts, xenon treatment significantly suppressed T-cell infiltration and fibrosis, prevented the development of CAN, and improved renal function. Thus, xenon treatment promoted recovery from ischemia-reperfusion injury and reduced susceptibility to the subsequent development of CAN in allografts.

Superagonistic CD28 antibody induces donor-specific tolerance in rat renal allografts.

PubMed

Azuma, H; Isaka, Y; Li, X; Hünig, T; Sakamoto, T; Nohmi, H; Takabatake, Y; Mizui, M; Kitazawa, Y; Ichimaru, N; Ibuki, N; Ubai, T; Inamoto, T; Katsuoka, Y; Takahara, S

2008-10-01

The ultimate goal of organ transplantation is to establish graft tolerance where CD4+CD25+FOXP3+ regulatory T (Treg) cells play an important role. We examined whether a superagonistic monoclonal antibody specific for CD28 (CD28 SA), which expands Treg cells in vivo, would prevent acute rejection and induce tolerance using our established rat acute renal allograft model (Wistar to Lewis). In the untreated or mouse IgG-treated recipients, graft function significantly deteriorated with marked destruction of renal tissue, and all rats died by 13 days with severe azotemia. In contrast, 90% of recipients treated with CD28 SA survived over 100 days, and 70% survived with well-preserved graft function until graft recovery at 180 days. Analysis by flow cytometry and immunohistochemistry demonstrated that CD28 SA induced marked infiltration of FOXP3+ Treg cells into the allografts. Furthermore, these long-surviving recipients showed donor-specific tolerance, accepting secondary (donor-matched) Wistar cardiac allografts, but acutely rejecting third-party BN allografts. We further demonstrated that adoptive transfer of CD4+CD25+ Treg cells, purified from CD28 SA-treated Lewis rats, significantly prolonged allograft survival and succeeded in inducing donor-specific tolerance. In conclusion, CD28 SA treatment successfully induces donor-specific tolerance with the involvement of Treg cells, and thus the therapeutic value of this approach warrants further investigation and preclinical studies.

Renal cell carcinoma in the allograft: what is the role of polyomavirus?

PubMed

Neirynck, Valerie; Claes, Kathleen; Naesens, Maarten; De Wever, Liesbeth; Pirenne, Jacques; Kuypers, Dirk; Vanrenterghem, Yves; Poppel, Hendrik Van; Kabanda, Andre; Lerut, Evelyne

2012-07-01

BK virus (BKV) is known to cause subclinical infection in childhood. The virus remains latent in the human body, mainly in the urinary tract epithelium. After initiation of an immunosuppressive treatment, reactivation can occur in renal transplant recipients. BKV can cause hemorrhagic cystitis, ureteral stenosis and BKV nephropathy in immunocompromised patients. Furthermore, a number of case reports suggest an association between BKV infection and the development of urinary tract cancer. So far, an oncogenic potential of BKV has been observed in vitro and in animal models; however, its oncogenic capacity in humans remains unclear. We report the case of a 59-year-old patient who developed a poorly differentiated renal cell carcinoma in her renal allograft, with pulmonary and abdominal metastasis. Surgical removal of the allograft and cessation of the immunosuppressive therapy resulted in complete resolution of the metastatic disease.

Effects of mechanical ventilation on gene expression profiles in renal allografts from brain dead rats.

PubMed

Hottenrott, Maximilia C; Krebs, Joerg; Pelosi, Paolo; Luecke, Thomas; Rocco, Patricia R M; Sticht, Carsten; Breedijk, Annette; Yard, Benito; Tsagogiorgas, Charalambos

2017-12-01

Pathophysiological changes of brain death (BD) are impairing distal organ function and harming potential renal allografts. Whether ventilation strategies influence the quality of renal allografts from BD donors has not been thoroughly studied. 28 adult male Wistar rats were randomly assigned to four groups: 1) no brain death (NBD) with low tidal volume/low positive endexpiratory pressure (PEEP) titrated to minimal static elastance of the respiratory system (LVT/OLPEEP); 2) NBD with high tidal volume/low PEEP (HVT/LPEEP); 3) brain death (BD) with LVT/OLPEEP; and 4) BD with HVT/LPEEP. We hypothesized that HVT/LPEEP in BD leads to increased interleukin 6 (IL-6) gene expression and impairs potential renal allografts after six hours of mechanical ventilation. We assessed inflammatory cytokines in serum, genome wide gene expression profiles and quantitative PCR (qPCR) in kidney tissue. The influence of BD on renal gene-expression profiles was greater than the influence of the ventilation strategy. In BD, LVT ventilation did not influence the inflammatory parameters or kidney function in our experimental model. Copyright © 2017. Published by Elsevier B.V.

Outcomes of Renal Allograft Recipients With Hepatitis C.

PubMed

Carpio, R; Pamugas, G E; Danguilan, R; Que, E

2016-04-01

Studies on the effect of hepatitis C virus (HCV) infection showed decreased graft survival compared to HCV-negative matched patients. It was also identified as an independent risk factor for graft loss and mortality in kidney transplantation patients. This study was designed to evaluate the 10-year graft and patient outcomes of renal allograft recipients with HCV infection at the National Kidney and Transplant Institute. This is a retrospective study of patients who underwent renal transplantation with HCV infection and a group who were HCV-negative in the same post-transplantation period. Data were gathered from the in-patient and out-patient clinic records. Patient survival was significantly lower in the HCV-positive than in the HCV-negative group. The mean duration of patient survival was 154.95 (+4.95) months (12 years and 10 months) in HCV-negative patients compared to 141 (+6.52) months (11 years and 9 months) in the HCV-positive group (P = .05). Graft survival did not differ significantly between HCV-positive and HCV-negative recipients (P = .734). The mean duration of graft survival was 137 (+7.68) months (11 years and 5 months) in HCV-negative patients compared to 130 (+6.84) months (10 years and 10 months) in HCV-positive patients. Short- and long-term outcomes including biopsy-proven acute rejection, transplant glomerulopathy, chronic allograft nephropathy, renal function, and proteinuria were similar in both groups. Rejection, glomerulopathy, and renal function were similar in both groups. HCV progression was also observed in patients with detectable HCV-RNA 6 months before transplantation. Copyright © 2016 Elsevier Inc. All rights reserved.

MicroRNA-10b downregulation mediates acute rejection of renal allografts by derepressing BCL2L11

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liu, Xiaoyou; Dong, Changgui; Jiang, Zhengyao

Kidney transplantation is the major therapeutic option for end-stage kidney diseases. However, acute rejection could cause allograft loss in some of these patients. Emerging evidence supports that microRNA (miRNA) dysregulation is implicated in acute allograft rejection. In this study, we used next-generation sequencing to profile miRNA expression in normal and acutely rejected kidney allografts. Among 75 identified dysregulated miRNAs, miR-10b was the most significantly downregulated miRNAs in rejected allografts. Transfecting miR-10b inhibitor into human renal glomerular endothelial cells recapitulated key features of acute allograft rejection, including endothelial cell apoptosis, release of pro-inflammatory cytokines (interleukin-6, tumor necrosis factor α, interferon-γ, andmore » chemokine (C–C motif) ligand 2) and chemotaxis of macrophages whereas transfection of miR-10b mimics had opposite effects. Downregulation of miR-10b directly derepressed the expression of BCL2L11 (an apoptosis inducer) as revealed by luciferase reporter assay. Taken together, miR-10b downregulation mediates many aspects of disease pathogenicity of acute kidney allograft rejection. Restoring miR-10b expression in glomerular endothelial cells could be a novel therapeutic approach to reduce acute renal allograft loss. - Highlights: • miR-10b was the most downregulated microRNAs in acutely rejected renal allografts. • miR-10b downregulation triggered glomerular endothelial cell apoptosis. • miR-10b downregulation induced release of pro-inflammatory cytokines. • miR-10b downregulation derepressed its pro-apoptotic target BCL2L11.« less

Robotic trans-abdominal transplant nephrectomy for a failed renal allograft.

PubMed

Mulloy, M R; Tan, M; Wolf, J H; D'Annunzio, S H; Pollinger, H S

2014-12-01

Minimally invasive surgery for removal of a failed renal allograft has not previously been reported. Herein, we report the first robotic trans-abdominal transplant nephrectomy (TN). A 34-year-old male with Alport's syndrome lost function of his deceased donor allograft after 12 years and presented with fever, pain over his allograft and hematuria. The operation was performed intra-abdominally using the Da Vinci Robotic Surgical System with four trocars. The total operative time was 235 min and the estimated blood loss was less than 25 cm(3). There were no peri-operative complications observed and the patient was discharged to home less than 24 h postoperatively. The utilization of robotic technology facilitated the successful performance of a minimally invasive, trans-abdominal TN. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Important risk factors of allograft survival in cadaveric renal transplantation. A study of 426 patients.

PubMed Central

Diethelm, A G; Blackstone, E H; Naftel, D C; Hudson, S L; Barber, W H; Deierhoi, M H; Barger, B O; Curtis, J J; Luke, R G

1988-01-01

Multiple risk factors contribute to the allograft survival of patients who have cadaveric renal transplantation. A retrospective review of 19 such factors in 426 patients identified race, DR match, B + DR match, number of transplants, and preservation time to have a significant influence. The parametric analysis confirmed the effect to be primarily in the early phase, i.e., first 6 months. All patients received cyclosporine with other methods of immunosuppression resulting in an overall 1-year graft survival rate of 66%. The overall 1-year graft survival rate in the white race was 73% and in the black race was 57% (p = 0.002). Allograft survival and DR match showed white recipients with a 1 DR match to have 75% survival at 1 year compared with 57% in the black patient (p = 0.009). If HLA B + DR match was considered, the white recipient allograft survival increased to 76%, 84%, and 88% for 1, 2, and 3 match kidneys by parametric analysis. Patients receiving first grafts had better graft survival (68%) than those undergoing retransplantation (58%) (p = 0.05). Organ preservation less than 12 hours influenced allograft survival with a 78% 1-year survival rate compared with 63% for kidneys with 12-18 hours of preservation. Despite the benefits of B + DR typing, short preservation time, and first transplants to the white recipient, the allograft survival in the black recipient remained uninfluenced by these parameters. PMID:3288138

Evaluation of coronary microvascular function in patients with end-stage renal disease, and renal allograft recipients.

PubMed

Bozbas, Huseyin; Pirat, Bahar; Demirtas, Saadet; Simşek, Vahide; Yildirir, Aylin; Sade, Elif; Sayin, Burak; Sezer, Siren; Karakayali, Hamdi; Muderrisoglu, Haldun

2009-02-01

Approximately half of all deaths in patients with end-stage renal disease (ESRD) are due to cardiovascular diseases. Although renal transplant improves survival and quality of life in these patients, cardiovascular events significantly affect survival. We sought to evaluate coronary flow reserve (CFR), an indicator of coronary microvascular function, in patients with ESRD and in patients with a functioning kidney graft. Eighty-six patients (30 with ESRD, 30 with a functioning renal allograft, and 26 controls) free of coronary artery disease or diabetes mellitus were included. Transthoracic Doppler echocardiography was used to measure coronary peak flow velocities at baseline and after dipyridamole infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak flow velocities and was compared among the groups. The mean age of the study population was 36.1+/-7.3 years. No between-group differences were found regarding age, sex, or prevalences of traditional coronary risk factors other than hypertension. Compared with the renal transplant and control groups, the ESRD group had significantly lower mean CFR values. On multivariate regression analysis, serum levels of creatinine, age, and diastolic dysfunction were independent predictors of CFR. CFR is impaired in patients with ESRD suggesting that coronary microvascular dysfunction, an early finding of atherosclerosis, is evident in these patients. Although associated with a decreased CFR compared with controls, renal transplant on the other hand seems to have a favorable effect on coronary microvascular function.

Human Cytomegalovirus-Encoded Receptor US28 Is Expressed in Renal Allografts and Facilitates Viral Spreading In Vitro.

PubMed

Lollinga, Wouter T; de Wit, Raymond H; Rahbar, Afsar; Vasse, Gwenda F; Davoudi, Belghis; Diepstra, Arjan; Riezebos-Brilman, Annelies; Harmsen, Martin C; Hillebrands, Jan-Luuk; Söderberg-Naucler, Cecilia; van Son, Willem J; Smit, Martine J; Sanders, Jan-Stephan; van den Born, Jacob

2017-03-01

Renal transplantation is the preferred treatment for patients with end-stage renal disease. Human cytomegalovirus (HCMV) activation is associated with decreased renal graft function and survival. Human cytomegalovirus encodes several immune modulatory proteins, including the G protein-coupled receptor US28, which scavenges human chemokines and modulates intracellular signaling. Our aim was to identify the expression and localization of US28 in renal allograft biopsies by immunohistochemistry and determine its role in viral spreading in vitro. Immunohistochemistry revealed US28 in 31 of 34 renal transplant biopsies from HCMV-seropositive donors. Expression was independent of HCMV viremia or IgG serostatus. US28 was predominantly expressed in the cytoplasm of vascular smooth muscle cells (VSMCs) and tubular epithelial cells, with a median positivity of 20% and 40%, respectively. Also, US28-positive cells were present within arterial neointima. In contrast to US28, HCMV-encoded immediate early antigen was detected in less than 5% of VSMCs, tubular epithelial cells, interstitial endothelium, interstitial inflammatory infiltrates, and glomerular cells.Primary VSMCs were infected with green fluorescent protein-tagged wild type or US28-deficient HCMV. The viral spreading of US28-deficient HCMV, via culture medium or cell-to-cell transmission, was significantly impeded as shown by green fluorescent protein (ie, infected) cell quantification and quantitative real-time polymerase chain reaction. Additionally, the number and size of foci was smaller. In summary, HCMV-encoded US28 was detected in renal allografts from HCMV-positive donors independent of viremia and serostatus. Also, US28 facilitates HCMV spreading in VSMCs in vitro. Because the vasculature is affected in chronic renal transplant dysfunction, US28 may provide a potential target for therapeutic intervention.

Adverse effects of meglumine diatrizoate on renal function in the early post-transplant period.

PubMed

Light, J A; Perloff, L J; Etheredge, E E; Hill, G; Spees, E K

1975-11-01

Thirty-four renal transplant recipients received drip infusion urograms from 2-24 days post-transplantation. Twenty-two patients exhibited changes in renal function within 1-4 days of the urogram that were indistinguishable from allograft rejection: a tender, swollen kidney, elevation of serum creatinine, oliguria, decreased urine sodium concentration, weight gain, and hypertension. Two patients developed acute tubular necrosis and required hemodialysis, but renal function in the remaining 20 patients improved after therapy for "graft rejection" with i.v. methyprednisolone sodium succinnate. Kidneys from older-age donors that were functioning suboptimally and kidneys which exhibited subsequent clinical allograft rejection were more at risk for contrast media toxicity. This suggests that occult vascular lesions may have been present in the allograft which were exacerbated when exposed to the irritant vascular effects of contrast media, producing a mild, reversible toxic nephritis. However, several kidneys with normal function and several kidneys which never exhibited rejection activity were also adversely affected by exposure to contrast media. It appears these agents should be used cautiously, if at all, in the early post-transplant period.

Anti-huCD20 Antibody Therapy for Antibody-Mediated Rejection of Renal Allografts in a Mouse Model

PubMed Central

Abe, Toyofumi; Ishii, Daisuke; Gorbacheva, Victoria; Kohei, Naoki; Tsuda, Hidetoshi; Tanaka, Toshiaki; Dvorina, Nina; Nonomura, Norio; Takahara, Shiro; Valujskikh, Anna; Baldwin, William M.; Fairchild, Robert L.

2016-01-01

We have reported that B6.CCR5−/− mice reject renal allografts with high serum donor-specific antibody (DSA) titers and marked C4d deposition in grafts, features consistent with AMR. B6.huCD20/CCR5−/− mice, where human CD20 expression is restricted to B cells, rejected A/J renal allografts by day 26 post-transplant with DSA first detected in serum on day 5 post-transplant and increased thereafter. Recipient treatment with anti-huCD20 mAb prior to the transplant and weekly up to 7 weeks post-transplant promoted long-term allograft survival (> 100 days) with low DSA titers. To investigate the effect of B cell depletion at the time serum DSA was first detected, recipients were treated with anti-huCD20 mAb on days 5, 8 and 12 post-transplant. This regimen significantly reduced DSA titers and graft inflammation on day 15 post-transplant and prolonged allograft survival > 60 days. However, DSA returned to the titers observed in control treated recipients by day 30 post-transplant and histological analyses on day 60 post-transplant indicated severe interstitial fibrosis. These results indicate that anti-huCD20 mAb had the greatest effect as a prophylactic treatment and that the distinct kinetics of DSA responses accounts for acute renal allograft failure versus the development of fibrosis. PMID:25731734

Borderline Changes on Dysfunctional Renal Allograft Biopsies: Clinical Relevance in a Living Related Renal Transplant Setting.

PubMed

Mubarak, Muhammed; Shakeel, Shaheera; Abbas, Khawar; Aziz, Tahir; Zafar, Mirza Naqi; Naqvi, Syed Anwer; Rizvi, Syed Adibul Hasan

2017-02-01

Our aim was to determine the clinical significance of borderline lymphocytic infiltrates on indicated renal allograft biopsies in a living related renal transplant setting. The study was conducted at the histopathology department of Sindh Institute of Urology and Transplantation. A retrospective review of 421 renal transplant patients was conducted from October 2007 to September 2008 to identify patients in whom a histologic diagnosis of borderline changes was made on dysfunctional renal allograft biopsies. Demographic, clinical, and laboratory data; biopsy findings; treatments given; and responses to treatment were collected and analyzed. Standard biopsy indications determined the need for graft biopsies. Biopsies were reported according to Banff criteria. Mean age was 26.92 ± 9.14 years (range, 10-45) for recipients and 38.46 ± 9.16 years (range, 19-50) for donors. Males were predominant among recipients (84.6% vs 15.4%), and females were predominant among donors (57.7% vs 42.3%). The best serum creatinine levels were 1.79 ± 1.15 mg/dL (range, 0.83-6.12). These were achieved after a median of 3 days (interquartile range, 2-7.25). Dysfunctional biopsies exhibiting borderline infiltrates were performed at a median duration of 5.5 days (interquartile range, 3-14.25). Mean serum creatinine at the time of biopsy was 2.34 ± 1.43 mg/dL (range, 1.25-8.25). The biopsies showed borderline cellular infiltrates (interstitial inflammation 1 [i1] and tubulitis 1 and [t1] lesions). All recipients except one received antirejection treatment (antithymocyte globulin, n = 5; escalation of mycophenolate mofetil dosage, n = 1; pulse steroids, n = 19); all recipients responded with a decline in serum creatinine toward baseline, with a mean serum creatinine of 1.31 ± 0.42 mg/dL (range, 0.40-2.71). This response was achieved at a median duration of 9.73 ± 5.32 days (range, 1-23) after starting treatment. The borderline cellular infiltrates on dysfunctional renal allograft biopsies

Impact of specimen adequacy on the assessment of renal allograft biopsy specimens.

PubMed

Cimen, S; Geldenhuys, L; Guler, S; Imamoglu, A; Molinari, M

2016-01-01

The Banff classification was introduced to achieve uniformity in the assessment of renal allograft biopsies. The primary aim of this study was to evaluate the impact of specimen adequacy on the Banff classification. All renal allograft biopsies obtained between July 2010 and June 2012 for suspicion of acute rejection were included. Pre-biopsy clinical data on suspected diagnosis and time from renal transplantation were provided to a nephropathologist who was blinded to the original pathological report. Second pathological readings were compared with the original to assess agreement stratified by specimen adequacy. Cohen's kappa test and Fisher's exact test were used for statistical analyses. Forty-nine specimens were reviewed. Among these specimens, 81.6% were classified as adequate, 6.12% as minimal, and 12.24% as unsatisfactory. The agreement analysis among the first and second readings revealed a kappa value of 0.97. Full agreement between readings was found in 75% of the adequate specimens, 66.7 and 50% for minimal and unsatisfactory specimens, respectively. There was no agreement between readings in 5% of the adequate specimens and 16.7% of the unsatisfactory specimens. For the entire sample full agreement was found in 71.4%, partial agreement in 20.4% and no agreement in 8.2% of the specimens. Statistical analysis using Fisher's exact test yielded a P value above 0.25 showing that - probably due to small sample size - the results were not statistically significant. Specimen adequacy may be a determinant of a diagnostic agreement in renal allograft specimen assessment. While additional studies including larger case numbers are required to further delineate the impact of specimen adequacy on the reliability of histopathological assessments, specimen quality must be considered during clinical decision making while dealing with biopsy reports based on minimal or unsatisfactory specimens.

Comprehensive morphometric analysis of mononuclear cell infiltration during experimental renal allograft rejection.

PubMed

Hoffmann, Ute; Bergler, Tobias; Jung, Bettina; Steege, Andreas; Pace, Claudia; Rümmele, Petra; Reinhold, Stephan; Krüger, Bernd; Krämer, Bernhard K; Banas, Bernhard

2013-01-01

The role of specific subtypes of infiltrating cells in acute kidney allograft rejection is still not clear and was so far not examined by different analyzing methods under standardized conditions of an experimental kidney transplantation model. Immunohistochemical staining of CD3, CD20 and CD68 was performed in rat allografts, in syngeneically transplanted rats and in control rats with a test duration of 6 and 28 days. The detailed expression and localization of infiltrating cells were analyzed manually in different kidney compartments under light microscope and by the two different morphometric software programs. Data were correlated with the corresponding kidney function as well as with histopathological classification. The information provided by the morphometric software programs on the infiltration of the specific cell types after renal transplantation was in accordance with the manual analysis. Morphometric methods were solid to analyze reliably the induction of cellular infiltrates after renal transplantation. By manual analysis we could clearly demonstrate the detailed localization of the specific cell infiltrates in the different kidney compartments. Besides infiltration of CD3 and CD68 infiltrating cells, a robust infiltration of CD20 B-cells in allogeneically transplanted rats, even at early time points after transplantation was detected. Additionally an MHC class I expression could reliable be seen in allogeneically transplanted rats. The infiltration of B-cells and the reliable antigen presentation might act as a silent subclinical trigger for subsequent chronic rejection and premature graft loss. Copyright © 2012 Elsevier B.V. All rights reserved.

[Combined assay of soluble CD30 and hepatocyte growth factor for diagnosis of acute renal allograft rejection].

PubMed

Li, Chuan-jiang; Yu, Li-xin; Xu, Jian; Fu, Shao-jie; Deng, Wen-feng; Du, Chuan-fu; Wang, Yi-bin

2008-02-01

To study the value of detection of both preoperative soluble CD30 (sCD30) and hepatocyte growth factor (HGF) level 5 days after transplantation in the diagnosis of acute rejection of renal allograft. Preoperative serum sCD30 levels and HGF level 5 days after transplantation were determined in 65 renal-transplant recipients using enzyme-linked immunosorbent assay. The recipients were divided according to the sCD30 levels positivity. Receiver operating characteristic (ROC) curves were used to assess the value of HGF level on day 5 posttransplantation for diagnosis of acute renal allograft rejection, and the value of combined assay of the sCD30 and HGF levels was also estimated. After transplantation, 26 recipients developed graft rejection and 39 had uneventful recovery without rejection. With the cut-off value of sCD30 of 120 U/ml, the positivity rate of sCD30 was significantly higher in recipients with graft rejection than in those without (61.5% vs 17.9%, P<0.05). Recipients with acute rejection showed also significantly higher HGF levels on day 5 posttransplantation than those without rejection (P<0.05). ROC curve analysis indicated that HGF levels on day 5 posttransplantation was a good marker for diagnosis of acute renal allograft rejection, and at the cut-off value of 90 ug/L, the diagnostic sensitivity was 84.6% and specificity 76.9%. Evaluation of both the sCD30 and HGF levels significantly enhanced the diagnostic accuracy of acute graft rejection. Combined assay of serum sCD30 and HGF levels offers a useful means for diagnosis of acute renal allograft rejection.

Low serum mannose-binding lectin levels are associated with inflammation and apoptosis in early surveillance allograft biopsies.

PubMed

Ibernon, M; Moreso, F; O'Valle, F; Grinyo, J M; Moral, R G; Seron, D

2014-09-01

Mannose-binding lectin (MBL) is a protein of the innate immune system that participates in host defense and the tissue injury/repair process, enhancing the clearance of apoptotic cells by macrophages. The aim is to characterize the relationship between pre-transplant MBL levels, histological lesions and number of apoptotic cells in early surveillance renal allograft biopsies. Consecutive renal transplant recipients were recruited and MBL levels were classified into tertiles. The first tertile was considered the low MBL group. Surveillance biopsies were done during the first 6 months and were evaluated according to Banff criteria. Renal inflammatory infiltrates were studied by immunohistochemical techniques. Apoptosis was studied using morphological methods in renal tubular cells and was expressed as the number of apoptotic cells/mm(2). MBL was determined in 126 patients and a surveillance biopsy with sufficient tissue was obtained in 41 of them. Patients with low pre-transplant MBL levels showed a higher acute Banff index (3.14 ± 1.96 vs. 1.88 ± 1.56, p = 0.044) and an increased proportion of biopsies with tubular cell apoptosis The proportion of biopsies with tubular cell apoptosis was higher in patients with low pre-transplant MBL levels in comparison with patients with high MBL levels (4.3 ± 3.6 versus 0.2 ± 0.9 p = 0.012) and increased interstitial number of inflammatory cells and significantly the macrophages/mm(2) (109 ± 118 vs. 32 ± 46; p = 0.04). Low pre-transplant serum MBL levels are associated with more severe inflammation and increased apoptosis in early surveillance renal allograft biopsies suggesting that MBL modulates renal inflammation after transplantation. Copyright © 2014 Elsevier B.V. All rights reserved.

Recipient body surface area as a predictor of posttransplant renal allograft evolution.

PubMed

Moreso, F; Serón, D; Anunciada, A I; Hueso, M; Ramón, J M; Fulladosa, X; Gil-Vernet, S; Alsina, J; Grinyó, J M

1998-03-15

The aim of the present study was to analyze whether minor differences in recipient body surface area have any predictive value on renal allograft evolution. For this study, we considered 236 pairs of recipients who received a kidney from the same donor at our center between March 1985 and December 1995. Pairs in whom at least one patient presented any of the following events were excluded: graft loss during the first year of follow-up, diabetes mellitus, noncompliance with treatment, chronic pyelonephritis, and recurrent or de novo glomerulonephritis. Recipients of each pair were classified as large or small according to their body surface area (BSA). The percentage difference of BSA in each pair was calculated, and two cohorts of pairs were defined: BSA difference < or = 10% (n=76 pairs) and BSA difference >10% (n=70 pairs). The large recipients of the cohort with a BSA difference >10% showed a higher incidence of posttransplant delayed graft function (22/70 vs. 12/70, P=0.075), hypertension at 1 year of follow-up (51/70 vs. 35/70, P=0.006), and a higher serum creatinine level at 1-year follow-up (173 vs. 142 micromol/L, P=0.003), whereas in the cohort with a BSA difference < or = 10%, posttransplant evolution in large and small recipients was not different. Multivariate analysis showed that recipient BSA was an independent predictor of delayed graft function, posttransplant hypertension, and serum creatinine at 1-year follow-up. Relatively small differences in recipient BSA influence renal allograft evolution. Consequently, our data support that recipient size should be taken into consideration for renal allograft allocation.

A Case Report of Parvovirus B19 Infection in a Renal Allograft.

PubMed

Oramas, Diana M; Setty, Suman; Yeldandi, Vijay; Cabrera, Julio; Patel, Tushar

2017-10-01

Parvovirus B19 infection is undiagnosed in recipients undergoing solid organ transplantation. It is usually responsible for unexplained acute and chronic red blood cell aplasia that does not respond to erythropoietin therapy. Cases of parvovirus B19 infection associated with pancytopenia, solid organ dysfunction, and allograft rejection have been described in the literature. The deterioration of the immune system as a result of severe immunotherapy favors the reactivation of a previous infection or the acquisition of a new one. We present a case of a 32-year-old woman with a 1-year history of renal allograft transplant and previous cytomegalovirus (CMV) infection who presented with chest pain, polyarthritis, pancytopenia, and renal dysfunction. A serum sample using polymerase chain reaction showed a parvovirus titer of 13.8 trillion IU/mL and a CMV titer of 800 IU/mL. The renal biopsy revealed nucleomegaly with focal viral inclusions, along with changes associated with immunotherapy toxicity. Electron microscopy demonstrated capillary and tubular epithelial cells with "viral factories," thereby confirming the diagnosis. Thus, screening for parvovirus B19 is advised in high-risk patients who present with refractory anemia to avoid the complications of a chronic infection associated with the fatal rejection of the transplanted organ.

Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes

PubMed Central

Naesens, Maarten; Khatri, Purvesh; Li, Li; Sigdel, Tara K.; Vitalone, Matthew J.; Chen, Rong; Butte, Atul J.; Salvatierra, Oscar; Sarwal, Minnie M.

2015-01-01

The degree of progressive chronic histological damage is associated with long-term renal allograft survival. In order to identify promising molecular targets for timely intervention, we examined renal allograft protocol and indication biopsies from 120 low-risk pediatric and adolescent recipients by whole-genome microarray expression profiling. In data-driven analysis, we found a highly regulated pattern of adaptive and innate immune gene expression that correlated with established or ongoing histological chronic injury, and also with development of future chronic histological damage, even in histologically pristine kidneys. Hence, histologically unrecognized immunological injury at a molecular level sets the stage for the development of chronic tissue injury, while the same molecular response is accentuated during established and worsening chronic allograft damage. Irrespective of the hypothesized immune or nonimmune trigger for chronic allograft injury, a highly orchestrated regulation of innate and adaptive immune responses was found in the graft at the molecular level. This occurred months before histologic lesions appear, and quantitatively below the diagnostic threshold of classic T-cell or antibody-mediated rejection. Thus, measurement of specific immune gene expression in protocol biopsies may be warranted to predict the development of subsequent chronic injury in histologically quiescent grafts and as a means to titrate immunosuppressive therapy. PMID:21881554

Progressive histological damage in renal allografts is associated with expression of innate and adaptive immunity genes.

PubMed

Naesens, Maarten; Khatri, Purvesh; Li, Li; Sigdel, Tara K; Vitalone, Matthew J; Chen, Rong; Butte, Atul J; Salvatierra, Oscar; Sarwal, Minnie M

2011-12-01

The degree of progressive chronic histological damage is associated with long-term renal allograft survival. In order to identify promising molecular targets for timely intervention, we examined renal allograft protocol and indication biopsies from 120 low-risk pediatric and adolescent recipients by whole-genome microarray expression profiling. In data-driven analysis, we found a highly regulated pattern of adaptive and innate immune gene expression that correlated with established or ongoing histological chronic injury, and also with development of future chronic histological damage, even in histologically pristine kidneys. Hence, histologically unrecognized immunological injury at a molecular level sets the stage for the development of chronic tissue injury, while the same molecular response is accentuated during established and worsening chronic allograft damage. Irrespective of the hypothesized immune or nonimmune trigger for chronic allograft injury, a highly orchestrated regulation of innate and adaptive immune responses was found in the graft at the molecular level. This occurred months before histologic lesions appear, and quantitatively below the diagnostic threshold of classic T-cell or antibody-mediated rejection. Thus, measurement of specific immune gene expression in protocol biopsies may be warranted to predict the development of subsequent chronic injury in histologically quiescent grafts and as a means to titrate immunosuppressive therapy.

Renal PKC-ε deficiency attenuates acute kidney injury and ischemic allograft injury via TNF-α-dependent inhibition of apoptosis and inflammation.

PubMed

Rong, Song; Hueper, Katja; Kirsch, Torsten; Greite, Robert; Klemann, Christian; Mengel, Michael; Meier, Matthias; Menne, Jan; Leitges, Michael; Susnik, Nathan; Meier, Martin; Haller, Hermann; Shushakova, Nelli; Gueler, Faikah

2014-09-15

Acute kidney injury (AKI) increases the risk of morbidity and mortality after major surgery and transplantation. We investigated the effect of PKC-ε deficiency on AKI and ischemic allograft damage after kidney transplantation. PKC-ε-deficient and wild type (WT) control mice were subjected to 35 min of renal pedicle clamping to induce AKI. PKC-ε deficiency was associated with a marked improvement in survival and an attenuated loss of kidney function. Furthermore, functional MRI experiments revealed better renal perfusion in PKC-ε-deficient mice than in WT mice one day after IRI. Acute tubular necrosis and neutrophil infiltration were markedly reduced in PKC-ε-deficient mice. To determine whether this resistance to ischemia-reperfusion injury resulted from changes in local renal cells or infiltrating leukocytes, we studied a life-supporting renal transplant model of ischemic graft injury. We transplanted kidneys from H(2b) PKC-ε-deficient mice (129/SV) and their corresponding WT littermates into major histocompatibility complex-incompatible H(2d) recipients (BALB/c) and induced ischemic graft injury by prolonged cold ischemia time. Recipients of WT allografts developed severe renal failure and died within 10 days of transplantation. Recipients of PKC-ε-deficient allografts had better renal function and survival; they had less generation of ROS and upregulation of proinflammatory proteins (i.e., ICAM-1, inducible nitric oxide synthase, and TNF-α) and showed less tubular epithelial cell apoptosis and inflammation in their allografts. These data suggest that local renal PKC-ε expression mediates proapoptotic and proinflammatory signaling and that an inhibitor of PKC-ε signaling could be used to prevent hypoxia-induced AKI. Copyright © 2014 the American Physiological Society.

Post-transplantation nephroptosis causing recurrent episodes of acute renal failure and hypertension secondary to intermittent vascular torsion of intraperitoneal renal allograft

PubMed Central

Dosch, Austin R.; Pahl, Madeleine; Reddy, Uttam; Foster, Clarence E.

2017-01-01

Abstract Nephroptosis is a rare complication in renal transplantation, but one with significant associated risk. Due to non-specific clinical features, there may be a substantial delay in diagnosis and loss of the transplanted kidney due to renal pedicle thrombosis. We present a case of post-transplantation nephroptosis after simultaneous pancreas and kidney transplant, which resulted in accelerated hypertension and reversible acute kidney injury >1 year after transplantation. Prompt detection of this rare entity leading to expeditious surgical intervention is necessary to preserve viability of the renal allograft. PMID:28560019

Malignant hemangiosarcoma in a renal allograft: diagnostic difficulties and clinical course after nephrectomy and immunostimulation.

PubMed

Kuntzen, Daniela; Tufail Hanel, Majida; Kuntzen, Thomas; Yurtsever, Hüseyin; Tuma, Jan; Hopfer, Helmut; Springer, Oliver; Bock, Andreas

2014-08-01

Hemangiosarcomas are rare tumors of endothelial cell origin. To date, only 20 cases of hemangiosarcoma have been described after renal transplantation, occurring mostly in the skin or in a dialysis fistula. We report a primary metastasizing hemangiosarcoma arising from a renal allograft. The patient was treated with transplant nephrectomy, discontinuation of immunosuppression, and immunostimulation with pegylated interferon-α-2a and has now been in complete remission for 3 years. © 2014 Steunstichting ESOT.

Kidney-induced cardiac allograft tolerance in miniature swine is dependent on MHC-matching of donor cardiac and renal parenchyma.

PubMed

Madariaga, M L; Michel, S G; La Muraglia, G M; Sekijima, M; Villani, V; Leonard, D A; Powell, H J; Kurtz, J M; Farkash, E A; Colvin, R B; Allan, J S; Cetrulo, C L; Huang, C A; Sachs, D H; Yamada, K; Madsen, J C

2015-06-01

Kidney allografts possess the ability to enable a short course of immunosuppression to induce tolerance of themselves and of cardiac allografts across a full-MHC barrier in miniature swine. However, the renal element(s) responsible for kidney-induced cardiac allograft tolerance (KICAT) are unknown. Here we investigated whether MHC disparities between parenchyma versus hematopoietic-derived "passenger" cells of the heart and kidney allografts affected KICAT. Heart and kidney allografts were co-transplanted into MHC-mismatched recipients treated with high-dose tacrolimus for 12 days. Group 1 animals (n = 3) received kidney and heart allografts fully MHC-mismatched to each other and to the recipient. Group 2 animals (n = 3) received kidney and heart allografts MHC-matched to each other but MHC-mismatched to the recipient. Group 3 animals (n = 3) received chimeric kidney allografts whose parenchyma was MHC-mismatched to the donor heart. Group 4 animals (n = 3) received chimeric kidney allografts whose passenger leukocytes were MHC-mismatched to the donor heart. Five of six heart allografts in Groups 1 and 3 rejected <40 days. In contrast, heart allografts in Groups 2 and 4 survived >150 days without rejection (p < 0.05). These data demonstrate that KICAT requires MHC-matching between kidney allograft parenchyma and heart allografts, suggesting that cells intrinsic to the kidney enable cardiac allograft tolerance. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

The Identification of Novel Potential Injury Mechanisms and Candidate Biomarkers in Renal Allograft Rejection by Quantitative Proteomics*

PubMed Central

Sigdel, Tara K.; Salomonis, Nathan; Nicora, Carrie D.; Ryu, Soyoung; He, Jintang; Dinh, Van; Orton, Daniel J.; Moore, Ronald J.; Hsieh, Szu-Chuan; Dai, Hong; Thien-Vu, Minh; Xiao, Wenzhong; Smith, Richard D.; Qian, Wei-Jun; Camp, David G.; Sarwal, Minnie M.

2014-01-01

Early transplant dysfunction and failure because of immunological and nonimmunological factors still presents a significant clinical problem for transplant recipients. A critical unmet need is the noninvasive detection and prediction of immune injury such that acute injury can be reversed by proactive immunosuppression titration. In this study, we used iTRAQ -based proteomic discovery and targeted ELISA validation to discover and validate candidate urine protein biomarkers from 262 renal allograft recipients with biopsy-confirmed allograft injury. Urine samples were randomly split into a training set of 108 patients and an independent validation set of 154 patients, which comprised the clinical biopsy-confirmed phenotypes of acute rejection (AR) (n = 74), stable graft (STA) (n = 74), chronic allograft injury (CAI) (n = 58), BK virus nephritis (BKVN) (n = 38), nephrotic syndrome (NS) (n = 8), and healthy, normal control (HC) (n = 10). A total of 389 proteins were measured that displayed differential abundances across urine specimens of the injury types (p < 0.05) with a significant finding that SUMO2 (small ubiquitin-related modifier 2) was identified as a “hub” protein for graft injury irrespective of causation. Sixty-nine urine proteins had differences in abundance (p < 0.01) in AR compared with stable graft, of which 12 proteins were up-regulated in AR with a mean fold increase of 2.8. Nine urine proteins were highly specific for AR because of their significant differences (p < 0.01; fold increase >1.5) from all other transplant categories (HLA class II protein HLA-DRB1, KRT14, HIST1H4B, FGG, ACTB, FGB, FGA, KRT7, DPP4). Increased levels of three of these proteins, fibrinogen beta (FGB; p = 0.04), fibrinogen gamma (FGG; p = 0.03), and HLA DRB1 (p = 0.003) were validated by ELISA in AR using an independent sample set. The fibrinogen proteins further segregated AR from BK virus nephritis (FGB p = 0.03, FGG p = 0.02), a finding that supports the utility of

Everolimus immunosuppression for renal protection, reduction of allograft vasculopathy and prevention of allograft rejection in de-novo heart transplant recipients: could we have it all?

PubMed

Gude, Einar; Gullestad, Lars; Andreassen, Arne K

2017-06-01

De-novo introduction of everolimus (Eve) in heart transplant recipients opens for early reduction of calcineurin inhibitors (CNI) and potential of preserving renal function, attenuate progression of coronary allograft vasculopathy (CAV) and maintain rejection efficacy. The first trials demonstrated adequate rejection prophylaxis and favorable outcomes on CAV, but observed enhanced nephrotoxicity because of insufficient CNI reduction. The SCHEDULE trial compared de-novo Eve with significantly reduced CNI exposure and conversion to CNI-free treatment week 7-11 postheart transplant, with standard CNI immunosuppression. Improved renal function and attenuation of CAV was found among Eve patients, with higher numbers of treated acute rejections observed. With sustained superior renal and CAV related data also after 36 months with the Eve protocol, cardiac function was equally well preserved in both groups. According to the International Society of Heart and Lunge Transplantation registry, mammalian target of rapamycin inhibitor treatment is uncommon during the first postoperative year, with a prevalence of 20% in patients after 5 years. Current evidence suggests a greater benefit from these immunosuppressives if introduced at an earlier timepoint. Immunosuppressive protocols based on Eve treatment in de-novo patients should be further investigated and developed, enabling CNI avoidance before accelerating side-effects lead to irreversible damage.

BK-virus nephropathy and simultaneous C4d positive staining in renal allografts.

PubMed

Honsová, E; Lodererová, A; Viklický, O; Boucek, P

2005-10-01

The role of antibodies in rejection of transplanted kidneys was the subject of debate at the last two Banff meetings and in medical journals. Diffuse C4d positive staining of peritubular capillaries (PTCs) was recognized as a marker of antibody-mediated rejection and this morphological feature was included in the updated Banff schema. At the same time polyomavirus infection of the renal allografts has been reported more frequently and is emerging as an important cause of renal allograft dysfunction and graft loss. At the present time, BK-virus nephropathy (BKN) represents the most common viral disease affecting renal allografts. BKN was identified in 6 patients in 12 biopsies and 2 graft nephrectomy specimens of 1115 biopsies between September 2000 and December 2003. Definite virus identification was done by immunohistochemistry. The reason for graft nephrectomies was graft failure due to BKN in a recipient after kidney-pancreas transplantation with good function of his pancreas graft and the necessity of continuing immunosuppression. Detection of C4d deposits was performed by immunofluorescence or by immunohistochemistry. In graftectomy samples C4d detection was performed by immunohistochemistry and retrospectively in all cases of BKN. Focal C4d positive PTCs and BKN were found simultaneously in 9 of 12 needle biopsies and in both graft nephrectomy samples. Detection of C4d by immunohistochemistry disclosed focal C4d positive staining in kidney tissue but diffuse in the sites where BK-virus inclusions in tubular epithelial cells were found. The complement system is part of the host defense response and is crucial to our natural ability to ward off infection. In cases of BKN, virus likely gains access to the bloodstream through injured tubular walls and via PTCs. Vascular endothelium in the PTCs represents a potential target antigen for alloresponse, and simultaneously possibly represents an imprint of complement activation or complement production in the places

Risk factors associated with the deterioration of renal function after kidney transplantation.

PubMed

Serón, Daniel; Fulladosa, Xavier; Moreso, Francesc

2005-12-01

Renal function early after transplantation is associated with a large number of risk factors, including donor age and acute rejection. During the 1990s, donor age increased and the incidence of acute rejection decreased. Renal function between the third and sixth month improved slightly, while renal function deterioration between the third or sixth month and the 12th month improved significantly. This modification coincides with the introduction of mycophenolate mofetil and tacrolimus. The tendency for sustained renal improvement early after transplantation became more evident after the introduction of anti-calcineurin-free regimens. Studies of protocol biopsies have shown that there is an increase of glomerular volume after transplantation and that a larger glomerular volume at 4 months is associated with a better glomerular filtration rate. This adaptation mechanism is impaired in patients with chronic allograft nephropathy or in patients with high cyclosporin levels. Taken together, these data suggest that the steady improvement of renal allograft function may be partly explained by a better glomerular adaptation after transplantation because of the avoidance of the vasoconstrictive effect of anti-calcineurinic agents, and a significant decrease in the prevalence of chronic allograft nephropathy early after transplantation.

Results of minimally invasive surgical treatment of allograft lithiasis in live-donor renal transplant recipients: a single-center experience of 3758 renal transplantations.

PubMed

Sarier, Mehmet; Duman, Ibrahim; Yuksel, Yucel; Tekin, Sabri; Demir, Meltem; Arslan, Fatih; Ergun, Osman; Kosar, Alim; Yavuz, Asuman Havva

2018-02-26

Allograft lithiasis is a rare urologic complication of renal transplantation (RT). Our aim is to present our experience with minimally invasive surgical treatment of allograft lithiasis in our series of live-donor renal transplant recipients. In a retrospective analysis of 3758 consecutive live-donor RTs performed in our center between November 2009 and January 2017, the results of minimally invasive surgery for the treatment of renal graft lithiasis diagnosed at follow-up were evaluated. Twenty-two (0.58%) patients underwent minimally invasive surgery for renal graft lithiasis. The mean age was 41.6 years, and duration between RT and surgical intervention was 27.3 months (range 3-67). The mean stone size was 11.6 mm (range 4-29). Stones were located in the urethra in 1, bladder in 2, ureter in 9, renal pelvis in 7 and calices in 3 patients. Surgical treatment included percutaneous nephrolithotomy in 1, cystoscopic lithotripsy in 3, flexible ureteroscopic lithotripsy in 6 and rigid ureteroscopic lithotripsy in 12 patients. No major complications were observed. One patient (4.5%) who underwent flexible ureteroscopy developed postoperative urinary tract infection. All patients were stone-free except two (9%) patients who required a second-look procedure after flexible ureteroscopic lithotripsy for residual stones. Stone recurrence was not observed in any patient during a mean follow-up duration of 30.2 months (range 8-84). Renal transplant lithiasis is uncommon and minimally invasive surgical treatment is rarely performed for its treatment. Endourological surgery may be performed safely, effectively and with a high success rate in these patients.

Scedosporium apiospermum causing brain abscess in a renal allograft recipient.

PubMed

Sharma, Amit; Singh, Divya

2015-11-01

Scedosporium apiospermum is the asexual form of a rare fungus Pseudallescheria boydii that is usually present in the soil, sewage and dirty water. In immunocompromised patients, it is a rare infection involving multiple organs. We present a case of renal allograft recipient who developed fever two weeks post renal transplant. He was initially found to have dengue fever. After five days, he became drowsy and developed right-sided hemiparesis. Magnetic resonance imaging of the brain revealed multiple irregular masses with associated edema consistent with fungal brain abscesses. Left parietal abscess was drained and he was started on voriconazole. His cyclosporine was stopped. Drained pus revealed fungal hyphae on potassium hydroxide stain and Scedosporium apiospermum on culture. Unfortunately, the patient died after five days. Scedosporium infections should be kept as a possibility in transplant recipients with disseminated infections, especially with a brain abscess. Despite antifungal therapy and surgical drainage, mortality rates are high.

Modality-specific occult intrarenal pseudoaneurysm in a renal allograft and the legacy of catheter angiography.

PubMed

Rastogi, Neeraj; Williams, Gethin; Alencar, Herlen

2013-11-01

A 69-year-old man with history of end-stage-renal disease (ESRD) underwent successful kidney transplantation from a cadaveric donor in November 2011. However, posttransplant recovery was complicated by delayed graft function and recurrent gross hematuria. Serial Doppler ultrasound (US) of the renal allograft demonstrated a pseudoaneurysm with interval increase in size. However, it could not be visualized with other modalities, including an initial angiogram (postoperative day 49) and a second angiogram (postoperative day 68), followed by surgical exploration (postoperative day 71), which demonstrated complete intra-aneurysmal thrombosis on intraoperative Doppler US. Unfortunately, the patient's hematuria continued and a repeat Doppler US 48 hours later demonstrated a persistent pseudoaneurysm. Therefore, on postoperative day 75, we performed targeted percutaneous intra-aneurysmal thrombin injection under dual image guidance, which showed complete intra-aneurysmal thrombosis on intraprocedural Doppler US. Hematuria recurred the next day. A third angiogram (postoperative day 77) finally illuminated the hidden pseudoaneurysm occult on the first and second angiographic studies (sensitivity [index case] 33%) and surgery. This allowed for successful coil embolization of a subsegmental feeding branch with an excellent outcome. We support a more aggressive management with serial angiography and embolization of the intrarenal symptomatic pseudoaneurysm rather than surgery in renal allograft recipients, with the benefits outweighing the risks. Copyright © 2013 Elsevier Inc. All rights reserved.

Development of injury in a rat model of chronic renal allograft rejection: effect of dietary protein restriction.

PubMed

Bombas, A; Stein-Oakley, A N; Baxter, K; Thomson, N M; Jablonski, P

1999-01-01

Non-allogeneic factors such as increased nephron "workload" may contribute to chronic renal allograft rejection. Reducing dietary protein from 20% to 8% was tested in a model of chronic rejection: Dark Agouti kidney to Albino Surgery recipient, "tolerised" by previous donor blood transfusions. Survival, weight gain, serum creatinine concentration and creatinine clearance were similar for both groups at all times. Urinary protein was significantly (P < 0.05) lower in the low-protein (LP) group 1 month after transplantation. After 3 and 6 months, both groups demonstrated mild chronic rejection. After 6 months, tubular atrophy was significantly (P < 0.05) less in the LP group and interstitial fibrosis was marginally reduced. Glomerular hypertrophy, glomerular sclerosis, tubular dilatation, leucocyte infiltration, adhesion molecule expression and TGF-beta1 mRNA expression were similarly increased in both groups. Thus, reducing dietary protein to 8% lowered urinary protein, but did not significantly affect the development of chronic rejection in renal allografts beyond affording a degree of protection from tubulointerstitial damage.

Apolipoprotein L1 gene variants in deceased organ donors are associated with renal allograft failure.

PubMed

Freedman, B I; Julian, B A; Pastan, S O; Israni, A K; Schladt, D; Gautreaux, M D; Hauptfeld, V; Bray, R A; Gebel, H M; Kirk, A D; Gaston, R S; Rogers, J; Farney, A C; Orlando, G; Stratta, R J; Mohan, S; Ma, L; Langefeld, C D; Hicks, P J; Palmer, N D; Adams, P L; Palanisamy, A; Reeves-Daniel, A M; Divers, J

2015-06-01

Apolipoprotein L1 gene (APOL1) nephropathy variants in African American deceased kidney donors were associated with shorter renal allograft survival in a prior single-center report. APOL1 G1 and G2 variants were genotyped in newly accrued DNA samples from African American deceased donors of kidneys recovered and/or transplanted in Alabama and North Carolina. APOL1 genotypes and allograft outcomes in subsequent transplants from 55 U.S. centers were linked, adjusting for age, sex and race/ethnicity of recipients, HLA match, cold ischemia time, panel reactive antibody levels, and donor type. For 221 transplantations from kidneys recovered in Alabama, there was a statistical trend toward shorter allograft survival in recipients of two-APOL1-nephropathy-variant kidneys (hazard ratio [HR] 2.71; p = 0.06). For all 675 kidneys transplanted from donors at both centers, APOL1 genotype (HR 2.26; p = 0.001) and African American recipient race/ethnicity (HR 1.60; p = 0.03) were associated with allograft failure. Kidneys from African American deceased donors with two APOL1 nephropathy variants reproducibly associate with higher risk for allograft failure after transplantation. These findings warrant consideration of rapidly genotyping deceased African American kidney donors for APOL1 risk variants at organ recovery and incorporation of results into allocation and informed-consent processes. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Esophageal tuberculosis with coexisting opportunistic infections in a renal allograft transplant recipient.

PubMed

Kumar, Sunil; Minz, Mukut; Sinha, Saroj K; Vaiphei, Kim; Sharma, Ashish; Singh, Sarbpreet; Kenwar, Deepesh B

2017-02-01

We report a renal allograft transplant recipient with esophageal tuberculosis (TB) coinfected with herpes simplex virus (HSV) and Candida. The patient presented with oropharyngeal candidiasis and was started on fluconazole. Upper gastrointestinal endoscopy showed whitish patches with mucosal ulcers in the esophagus. Histopathological examination confirmed TB and HSV infection. The patient recovered after antiviral, antifungal, and anti-tubercular therapy with reduction in immunosuppression. In a TB-endemic zone, TB can coexist with opportunistic infections in an immunocompromised host. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Nitration and inactivation of manganese superoxide dismutase in chronic rejection of human renal allografts.

PubMed Central

MacMillan-Crow, L A; Crow, J P; Kerby, J D; Beckman, J S; Thompson, J A

1996-01-01

Inflammatory processes in chronic rejection remain a serious clinical problem in organ transplantation. Activated cellular infiltrate produces high levels of both superoxide and nitric oxide. These reactive oxygen species interact to form peroxynitrite, a potent oxidant that can modify proteins to form 3-nitrotyrosine. We identified enhanced immunostaining for nitrotyrosine localized to tubular epithelium of chronically rejected human renal allografts. Western blot analysis of rejected tissue demonstrated that tyrosine nitration was restricted to a few specific polypeptides. Immunoprecipitation and amino acid sequencing techniques identified manganese superoxide dismutase, the major antioxidant enzyme in mitochondria, as one of the targets of tyrosine nitration. Total manganese superoxide dismutase protein was increased in rejected kidney, particularly in the tubular epithelium; however, enzymatic activity was significantly decreased. Exposure of recombinant human manganese superoxide dismutase to peroxynitrite resulted in a dose-dependent (IC50 = 10 microM) decrease in enzymatic activity and concomitant increase in tyrosine nitration. Collectively, these observations suggest a role for peroxynitrite during development and progression of chronic rejection in human renal allografts. In addition, inactivation of manganese superoxide dismutase by peroxynitrite may represent a general mechanism that progressively increases the production of peroxynitrite, leading to irreversible oxidative injury to mitochondria. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8876227

Clinical and Biochemical Characteristics of Brain-Dead Donors as Predictors of Early- and Long-Term Renal Function After Transplant.

PubMed

Kwiatkowska, Ewa; Domański, Leszek; Bober, Joanna; Safranow, Krzysztof; Pawlik, Andrzej; Ciechanowski, Kazimierz; Wiśniewska, Magda; Kędzierska, Karolina

2017-08-01

Organs from brain-dead donors are the main source of allografts for transplant. Comparisons between living-donor and brain-dead donor kidneys show that the latter are more likely to demonstrate delayed graft function and lower long-term survival. This study aimed to assess the effects of various clinical and biochemical factors of donors on early- and long-term renal function after transplant. We analyzed data from kidney recipients treated between 2006 and 2008 who received organs from brain-dead donors. Data from 54 donors and 89 recipients were analyzed. No relation was observed between donor sodium concentration and the presence of delayed graft function. Donor height was positively correlated with creatinine clearance in recipients in the 1 to 3 months after renal transplant. Donor diastolic blood pressure was negatively correlated with estimated glomerular filtration rate throughout the observation period. Donor age was negatively correlated with the allograft recipient's estimated glomerular filtration rate throughout 4 years of observation. Donor estimated glomerular filtration rate was positively correlated with that of the recipient throughout 3 years of observation. The results of this study indicate that various factors associated with allograft donors may influence graft function.

Use of capecitabine to prevent acute renal allograft rejection in dog erythrocyte antigen-mismatched mongrel dogs.

PubMed

Milovancev, Milan; Schmiedt, Chad W; Bentley, Ellison; Schwab, Michelle; Dubielzig, Richard R; Gendron-Fitzpatrick, Annette P; McAnulty, Jonathan F

2007-01-01

To assess efficacy and toxicity of a capecitabine (CAP)-based regimen for preventing rejection of renal allografts in dog erythrocyte antigen (DEA)-mismatched mongrel dogs. Prospective, pilot study. Eight healthy, unrelated, DEA mismatched, adult mongrel dogs. All dogs received CAP, starting at 50 mg/m2 PO b.i.d. 4 days preoperatively, increasing to 200 mg/m2 PO b.i.d. by the day of surgery. All dogs received cyclosporine-A (CsA) and prednisolone starting 2 days preoperatively. Standard heterotopic renal transplantation with native nephrectomy was performed. After 90 days, surviving dogs were euthanatized and histopathologic examination was performed. Two of 8 dogs developed acute neurotoxicity leading to death or euthanasia within 5 days of surgery. For the 6 remaining dogs, there were no statistically significant changes in complete blood count or serum biochemical values. No opportunistic infections developed during the study period. Five of 6 dogs had no to minimal evidence of graft rejection. Two of 6 dogs developed superficial and pigmentary keratitis. Significant histopathologic findings in all dogs included mild lymphoplasmacytic gastroenteritis, steroid hepatopathy, and corneal epithelial thinning. One dog had moderate interstitial nephritis and pyelitis. In this experimental model, a CAP-CsA-prednisolone immunosuppressive regimen was effective in preventing rejection of allografts in DEA-mismatched dogs. Severe, unpredictable neurotoxicity and variable ocular toxicity significantly limit clinical applications at this time. A CAP-CsA-prednisolone protocol is an effective, oral immunosuppressive regimen for prevention of allograft rejection in DEA-mismatched mongrel dogs. For clinical application, identification of patients susceptible to toxic side effects would be necessary.

Longitudinal Analysis of Whole Blood Transcriptomes to Explore Molecular Signatures Associated With Acute Renal Allograft Rejection

PubMed Central

Shin, Heesun; Günther, Oliver; Hollander, Zsuzsanna; Wilson-McManus, Janet E.; Ng, Raymond T.; Balshaw, Robert; Keown, Paul A.; McMaster, Robert; McManus, Bruce M.; Isbel, Nicole M.; Knoll, Greg; Tebbutt, Scott J.

2014-01-01

In this study, we explored a time course of peripheral whole blood transcriptomes from kidney transplantation patients who either experienced an acute rejection episode or did not in order to better delineate the immunological and biological processes measureable in blood leukocytes that are associated with acute renal allograft rejection. Using microarrays, we generated gene expression data from 24 acute rejectors and 24 nonrejectors. We filtered the data to obtain the most unambiguous and robustly expressing probe sets and selected a subset of patients with the clearest phenotype. We then performed a data-driven exploratory analysis using data reduction and differential gene expression analysis tools in order to reveal gene expression signatures associated with acute allograft rejection. Using a template-matching algorithm, we then expanded our analysis to include time course data, identifying genes whose expression is modulated leading up to acute rejection. We have identified molecular phenotypes associated with acute renal allograft rejection, including a significantly upregulated signature of neutrophil activation and accumulation following transplant surgery that is common to both acute rejectors and nonrejectors. Our analysis shows that this expression signature appears to stabilize over time in nonrejectors but persists in patients who go on to reject the transplanted organ. In addition, we describe an expression signature characteristic of lymphocyte activity and proliferation. This lymphocyte signature is significantly downregulated in both acute rejectors and nonrejectors following surgery; however, patients who go on to reject the organ show a persistent downregulation of this signature relative to the neutrophil signature. PMID:24526836

Accumulation of p53 is associated with tumour progression in cutaneous lesions of renal allograft recipients.

PubMed Central

Stark, L. A.; Arends, M. J.; McLaren, K. M.; Benton, E. C.; Shahidullah, H.; Hunter, J. A.; Bird, C. C.

1994-01-01

Renal allograft recipients suffer from a markedly increased susceptibility to premalignant and malignant cutaneous lesions. Although various aetiological factors have been implicated, little is known of the associated genetic events. In this study we initially employed immunocytochemical techniques to investigate the prevalence and localisation of accumulated p53 in over 200 cutaneous biopsies (including 56 squamous cell carcinomas) from renal allograft recipients and immunocompetent controls. In renal allograft recipients accumulated p53 was present in 24% of uninvolved skin samples, 14% of viral warts, 41% of premalignant keratoses, 65% of intraepidermal carcinomas and 56% of squamous cell carcinomas [squamous cell carcinoma and intraepidermal carcinoma differed significantly from uninvolved skin (P < 0.005) and viral warts (P < 0.01)]. A similar trend was revealed in immunocompetent patients (an older, chronically sun-exposed population) but with lower prevalence of p53 immunoreactivity: 25% of uninvolved skin samples, 0% of viral warts, 25% of keratoses, 53% of intraepidermal carcinomas and 53% of squamous cell carcinomas. These differences were not statistically significant. Morphologically, p53 immunoreactivity strongly associated with areas of epidermal dysplasia and the abundance of staining correlated positively with the severity of dysplasia. These data suggest that p53 plays a role in skin carcinogenesis and is associated with progression towards the invasive state. No correlation was observed between accumulated p53 and the presence of human papillomavirus (HPV) DNA in any of the lesions. Single-strand conformational polymorphism analysis (exons 5-8) was used to determine the frequency of mutated p53 in 28 malignancies with varying degrees of immunopositivity. p53 mutations were found in 5/9 (56%) malignancies with p53 staining in > 50% of cells, reducing to 1/6 (17%) where 10-50% of cells were positively stained and none where < 10% of cells were

Racial Disparity in Renal Transplantation: Alemtuzumab the Great Equalizer?

PubMed

Smith, Alison A; John, Mira M; Dortonne, Isabelle S; Paramesh, Anil S; Killackey, Mary; Jaffe, Bernard M; Buell, Joseph F

2015-10-01

Racial disparity as a barrier to successful outcomes in renal transplants for African Americans has been well described. Numerous unsuccessful attempts have been made to identify specific immunologic and socioeconomic factors. The objective of our study was to determine whether alemtuzumab (AL) induction abolishes this discrepancy and improves allograft survival in African American recipients. A retrospective chart review of consecutive adult renal transplants was conducted between 2006 and 2014. Kaplan-Meier analysis and hazard ratios were calculated for the African Americans (AA) and white groups. Multiple linear regressions were performed to assess independent variables (race, retransplant, sex, donor type, induction agent) on allograft survival. A significant difference in allograft survival was identified between whites (n = 272) and AA (n = 445), with AA experiencing more graft losses (18.2% vs 12.1%, P = 0.0351). Induction with AL improved outcomes in all transplant recipients. Multiple linear regression identified that the strongest predictor of allograft failure was induction without AL (P < 0.0001). The data for a subset analysis matched for follow-up length demonstrated that whites compared with AA (n = 157, 67 whites and 90 AA) had lower rates of allograft failure in the absence of AL induction (14.9% vs 44.4%, P = 0.0156, hazard ratio = 2.077). In contrast, AL induction (n = 275, 105 whites and 170 AA) eliminated the racial disparity in allograft failure (5.7% vs 9.4%, P = 0.8248, hazard ratio = 1.504). This is the first study to describe the effects of AL induction therapy on AA renal transplant recipients beyond the first posttransplant year. Our early results suggest that AL induction therapy abolishes the disparity in renal allograft failure.

Acute renal failure in a pediatric kidney allograft recipient treated with intravenous immunoglobulin for parvovirus B19 induced pure red cell aplasia.

PubMed

Subtirelu, Mihail M; Flynn, Joseph T; Schechner, Richard S; Pullman, James M; Feuerstein, Dianne; Del Rio, Marcela

2005-12-01

Infection with parvovirus B19 (PV-B19) after solid organ transplantation may cause pure red cell aplasia (PRCA). Intravenous immunoglobulin (IVIg) may be of benefit in clearing the infection. Acute renal failure is a known adverse effect of IVIg administration. A 14-yr-old male received a cadaveric renal transplant. Three weeks after surgery he developed symptomatic anemia (hemoglobin 4.5 g/dL, reticulocyte count 0.2%). Anti-PV-B19 IgM and IgG titers, which had been negative pretransplant, were positive. He received two IVIg infusions as treatment for the PV-B19 infection. Four days after the IVIg infusions he developed non-oliguric acute renal failure (ARF) with a rise in serum creatinine from 1 to 1.8 mg/dL. Allograft biopsy showed changes consistent with an osmotic load. Anemia and the renal failure resolved after transfusions and IVIg. PV-B19 infection in immunosuppressed transplant recipients is associated with significant morbidity and may respond to IVIg therapy. High sucrose IVIg preparations may be associated with renal failure in renal allograft recipients. Adding PV-B19 testing of the donor and recipient to the standard pretransplant evaluation may be beneficial in diagnosing and managing a potential infection. If IVIg is to be used it may be safer to use a sucrose-free IVIg preparation.

Open-Label, Randomized Study of Transition From Tacrolimus to Sirolimus Immunosuppression in Renal Allograft Recipients

PubMed Central

Tedesco-Silva, Helio; Peddi, V. Ram; Sánchez-Fructuoso, Ana; Marder, Brad A.; Russ, Graeme R.; Diekmann, Fritz; Flynn, Alison; Hahn, Carolyn M.; Li, Huihua; Tortorici, Michael A.; Schulman, Seth L.

2016-01-01

Background Calcineurin inhibitor–associated nephrotoxicity and other adverse events have prompted efforts to minimize/eliminate calcineurin inhibitor use in kidney transplant recipients. Methods This open-label, randomized, multinational study evaluated the effect of planned transition from tacrolimus to sirolimus on kidney function in renal allograft recipients. Patients received tacrolimus-based immunosuppression and then were randomized 3 to 5 months posttransplantation to transition to sirolimus or continue tacrolimus. The primary end point was percentage of patients with 5 mL/min per 1.73 m2 or greater improvement in estimated glomerular filtration rate from randomization to month 24. Results The on-therapy population included 195 patients (sirolimus, 86; tacrolimus, 109). No between-group difference was noted in percentage of patients with 5 mL/min per 1.73 m2 or greater estimated glomerular filtration rate improvement (sirolimus, 34%; tacrolimus, 42%; P = 0.239) at month 24. Sirolimus patients had higher rates of biopsy-confirmed acute rejection (8% vs 2%; P = 0.02), treatment discontinuation attributed to adverse events (21% vs 3%; P < 0.001), and lower rates of squamous cell carcinoma of the skin (0% vs 5%; P = 0.012). Conclusions Our findings suggest that renal function improvement at 24 months is similar for patients with early conversion to sirolimus after kidney transplantation versus those remaining on tacrolimus. PMID:27500260

Randomized trial of single-dose versus divided-dose rabbit anti-thymocyte globulin induction in renal transplantation: an interim report.

PubMed

Stevens, R Brian; Mercer, David F; Grant, Wendy J; Freifeld, Alison G; Lane, James T; Groggel, Gerald C; Rigley, Theodore H; Nielsen, Kathleen J; Henning, Megan E; Skorupa, Jill Y; Skorupa, Anna J; Christensen, Kecia A; Sandoz, John P; Kellogg, Anna M; Langnas, Alan N; Wrenshall, Lucile E

2008-05-27

The optimal dosing protocol for rabbit anti-thymocyte globulin (rATG) induction in renal transplantation has not been determined, but evidence exists that rATG infusion before renal allograft reperfusion improves early graft function. Infusing a large rATG dose over a short interval has not previously been evaluated for its effect on renal function and allograft nephropathy in a prospective, randomized comparison against conventional rATG induction. Between April 20, 2004 and December 26, 2007 we enrolled renal transplant patients into a prospective, randomized, nonblinded trial of two rATG dosing protocols (single dose, 6 mg/kg vs. divided doses, 1.5 mg/kg every other day x 4; target enrollment=160) followed after 6 months by calcineurin-inhibitor withdrawal. Primary endpoints are renal function by calculated glomerular filtration rate (GFR) and chronic allograft nephropathy at protocol biopsy. We now present the early GFR data of all 160 patients and safety and efficacy data of the first 142 patients with 6 months follow up and before calcineurin inhibitor withdrawal (average follow up=23.3+/-11.6 months). There were no differences between groups in rATG-related adverse events, patient and graft survival, acute rejection, or chronic allograft nephropathy rate at 6 months. Calculated DeltaGFR (POD 1-4) was significantly better in the single-dose group (P=0.02), with a trend toward improved renal function from months 2 to 6 in recipients of deceased donor kidneys (P=0.08). This study demonstrates that administering 6 mg/kg of rATG over 24 hr is safe and is associated with improved early renal function compared with administering rATG in alternate-day doses.

Long-term tolerance to kidney allografts in a preclinical canine model.

PubMed

Kuhr, Christian S; Yunusov, Murad; Sale, George; Loretz, Carol; Storb, Rainer

2007-08-27

Durable immune tolerance supporting vascularized allotransplantation offers the possibility of extending graft survival and avoiding harmful complications of chronic immunosuppression. Immune tolerance to renal allografts was induced in a preclinical canine model through engraftment of donor hematopoietic cells using a combination of low-dose total body irradiation and a short course of immunosuppression. Subsequently, donor renal allografts were transplanted accompanied by bilateral native nephrectomies. With 5-year follow up, we found normal renal function in all recipients and no histological evidence of acute or chronic rejection. This tolerance does not extend universally to donor skin grafts, however, with two of four animals rejecting delayed donor skin grafts. Hematopoietic chimerism produces durable and robust immune tolerance to kidney allografts, although incomplete tolerance to donor skin grafting.

Evaluating Renal Transplant Status Using Viscoelastic Response (VisR) Ultrasound.

PubMed

Hossain, Md Murad; Selzo, Mallory R; Hinson, Robert M; Baggesen, Leslie M; Detwiler, Randal K; Chong, Wui K; Burke, Lauren M; Caughey, Melissa C; Fisher, Melrose W; Whitehead, Sonya B; Gallippi, Caterina M

2018-05-10

Chronic kidney disease is most desirably and cost-effectively treated by renal transplantation, but graft survival is a major challenge. Although irreversible graft damage can be averted by timely treatment, intervention is delayed when early graft dysfunction goes undetected by standard clinical metrics. A more sensitive and specific parameter for delineating graft health could be the viscoelastic properties of the renal parenchyma, which are interrogated non-invasively by Viscoelastic Response (VisR) ultrasound, a new acoustic radiation force (ARF)-based imaging method. Assessing the performance of VisR imaging in delineating histologically confirmed renal transplant pathologies in vivo is the purpose of the study described here. VisR imaging was performed in patients with (n = 19) and without (n = 25) clinical indication for renal allograft biopsy. The median values of VisR outcome metrics (τ, relative elasticity [RE] and relative viscosity [RV]) were calculated in five regions of interest that were manually delineated in the parenchyma (outer, center and inner) and in the pelvis (outer and inner). The ratios of a given VisR metric for all possible region-of-interest combinations were calculated, and the corresponding ratios were statistically compared between biopsied patients subdivided by diagnostic categories versus non-biopsied, control allografts using the two-sample Wilcoxon test (p <0.05). Although τ ratios non-specifically differentiated allografts with vascular disease, tubular/interstitial scarring, chronic allograft nephropathy and glomerulonephritis from non-biopsied control allografts, RE distinguished only allografts with vascular disease and tubular/interstitial scarring, and RV distinguished only vascular disease. These results suggest that allografts with scarring and vascular disease can be identified using non-invasive VisR RE and RV metrics. Copyright © 2018 World Federation for Ultrasound in Medicine and Biology. Published by

In vivo effects of high-dose steroids on nucleic acid content of immunocompetent cells of renal allograft recipients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Walle, A.J.; Wong, G.Y.; Suthanthiran, M.

1988-03-01

High-dose steroids administered to renal allograft recipients for treatment of acute graft rejection episodes may affect cell cycle progression of peripheral blood mononuclear (PBM) cells. DNA synthesis and cellular DNA and RNA contents of PBM cells were measured in 8 patients during clinically stable periods, and in another 10 patients both during acute rejection episodes and during 7 days of administration of high-dose steroids. Improved renal function documented successful reversal of the rejection episodes in the 10 patients. Compared with the stable patients, the rejecting patients had higher numbers of cells undergoing clonal expansion--namely, higher proportions of G1-cells and ofmore » proliferating, or S, G2, and M (SG2M) cells. Steroid treatment had no acute effects on proportions of G1 or SG2M cells in vivo or on incorporation of /sup 3/H thymidine by PBM cells in vitro. However, cells in the prereplicative compartment of the cell cycle (G0/1 cells) had significantly lower RNA content within 7 days of treatment with high doses of steroids. The results suggest that steroids do not acutely influence the posttranscriptional synthesis and the contents of nucleic acids of cells undergoing clonal expansion in vivo. The prereplicative phase of allogeneically stimulated PBM cells of renal allograft recipients may therefore be the cell cycle phase most sensitive to steroids in vivo.« less

Achieving donor-specific hyporesponsiveness is associated with FOXP3+ regulatory T cell recruitment in human renal allograft infiltrates.

PubMed

Bestard, Oriol; Cruzado, Josep M; Mestre, Mariona; Caldés, Anna; Bas, Jordi; Carrera, Marta; Torras, Joan; Rama, Inés; Moreso, Francesc; Serón, Daniel; Grinyó, Josep M

2007-10-01

Exploring new immunosuppressive strategies inducing donor-specific hyporesponsiveness is an important challenge in transplantation. For this purpose, a careful immune monitoring and graft histology assessment is mandatory. Here, we report the results of a pilot study conducted in twenty renal transplant recipients, analyzing the immunomodulatory effects of a protocol based on induction therapy with rabbit anti-thymocyte globulin low doses, sirolimus, and mofetil mycophenolate. Evolution of donor-specific cellular and humoral alloimmune response, peripheral blood lymphocyte subsets and apoptosis was evaluated. Six-month protocol biopsies were performed to assess histological lesions and presence of FOXP3+ regulatory T cells (Tregs) in interstitial infiltrates. After transplantation, there was an early and transient apoptotic effect, mainly within the CD8+ HLADR+ T cells, combined with a sustained enhancement of CD4+ CD25(+high) lymphocytes in peripheral blood. The incidence of acute rejection was 35%, all steroid sensitive. Importantly, only pretransplant donor-specific cellular alloreactivity could discriminate patients at risk to develop acute rejection. Two thirds of the patients became donor-specific hyporesponders at 6 and 24 mo, and the achievement of this immunologic state was not abrogated by prior acute rejection episodes. Remarkably, donor-specific hyporesponders had the better renal function and less chronic renal damage. Donor-specific hyporesponsiveness was inhibited by depleting CD4+ CD25(+high) T cells, which showed donor-Ag specificity. FOXP3+ CD4+ CD25(+high) Tregs both in peripheral blood and in renal infiltrates were higher in donor-specific hyporesponders than in nonhyporesponders, suggesting that the recruitment of Tregs in the allograft plays an important role for renal acceptance. In conclusion, reaching donor-specific hyporesponsiveness is feasible after renal transplantation and associated with Treg recruitment in the graft.

Poly[ADP-ribose] polymerase-1 expression is related to cold ischemia, acute tubular necrosis, and delayed renal function in kidney transplantation.

PubMed

O'Valle, Francisco; Del Moral, Raimundo G M; Benítez, María del Carmén; Martín-Oliva, David; Gómez-Morales, Mercedes; Aguilar, David; Aneiros-Fernández, José; Hernández-Cortés, Pedro; Osuna, Antonio; Moreso, Francesc; Serón, Daniel; Oliver, Francisco J; Del Moral, Raimundo G

2009-09-28

Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN). Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls) and in murine Parp-1 knockout model of IR injury. PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603), time to effective diuresis (r = 0.770), serum creatinine levels at biopsy (r = 0.649), and degree of ATN (r = 0.810) (p = 0.001, Pearson test). In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function.

Defining kidney allograft benefit from successful pancreas transplant: separating fact from fiction.

PubMed

Wiseman, Alexander C; Stites, Erik; Kennealey, Peter

2018-06-06

To define the natural history of kidney allograft loss related to recurrent diabetes following transplant, and to understand the potential benefit of pancreas transplantation upon kidney allograft survival. A postulated benefit of simultaneous pancreas kidney transplant is that, unlike kidney transplant alone, euglycemia from the added pancreas allograft may confer a nephroprotective benefit and prevent recurrent diabetic nephropathy in the renal allograft. Recent large database analyses and long-term histological assessments have been published that assist in quantifying the problem of recurrent diabetic nephropathy and answering the question of the potential benefits of euglycemia. Further data may be extrapolated from larger single-center series that follow the prognosis of early posttransplant diabetes mellitus as another barometer of risk from diabetic nephropathy and graft loss. Recurrent diabetic nephropathy following kidney transplant is a relatively rare, late occurrence and its clinical significance is significantly diminished by the competing risks of death and chronic alloimmune injury. Although there are hints of a protective effect upon kidney graft survival with pancreas transplant, these improvements are small and may take decades to appreciate. Clinical decision-making regarding pancreas transplant solely based upon nephroprotective effects of the kidney allograft should be avoided.

Early allograft dysfunction in liver transplantation with donation after cardiac death donors results in inferior survival.

PubMed

Lee, David D; Singh, Amandeep; Burns, Justin M; Perry, Dana K; Nguyen, Justin H; Taner, C Burcin

2014-12-01

Donation after cardiac death (DCD) liver allografts have been associated with increased morbidity from primary nonfunction, biliary complications, early allograft failure, cost, and mortality. Early allograft dysfunction (EAD) after liver transplantation has been found to be associated with inferior patient and graft survival. In a cohort of 205 consecutive liver-only transplant patients with allografts from DCD donors at a single center, the incidence of EAD was found to be 39.5%. The patient survival rates for those with no EAD and those with EAD at 1, 3, and 5 years were 97% and 89%, 79% and 79%, and 61% and 54%, respectively (P = 0.009). Allograft survival rates for recipients with no EAD and those with EAD at 1, 3, and 5 years were 90% and 75%, 72% and 64%, and 53% and 43%, respectively (P = 0.003). A multivariate analysis demonstrated a significant association between the development of EAD and the cold ischemia time [odds ratio (OR) = 1.26, 95% confidence interval (CI) = 1.01-1.56, P = 0.037] and hepatocellular cancer as a secondary diagnosis in recipients (OR = 2.26, 95% CI = 1.11-4.58, P = 0.025). There was no correlation between EAD and the development of ischemic cholangiopathy. In conclusion, EAD results in inferior patient and graft survival in recipients of DCD liver allografts. Understanding the events that cause EAD and developing preventive or early therapeutic approaches should be the focus of future investigations. © 2014 American Association for the Study of Liver Diseases.

Treatment of erectile dysfunction with sildenafil citrate in renal allograft recipients: a randomized, double-blind, placebo-controlled, crossover trial.

PubMed

Sharma, Raj K; Prasad, Narayan; Gupta, Amit; Kapoor, Rakesh

2006-07-01

Erectile dysfunction (ED) is observed frequently in patients with end-stage renal disease, hemodialysis patients, and renal allograft recipients. There are few studies of sildenafil use in renal allograft recipients. The study is designed as a randomized, double-blind, placebo-controlled, crossover trial. Efficacy was assessed by using the self-administered International Index of Erectile Function (IIEF), a 15-question validated measure of ED, and a global efficacy question (Did the treatment improve your erection?). Thirty-two eligible renal transplant recipients were included in this study. After treatment with sildenafil citrate, patients had significantly better scores in 13 of 15 questions, except for questions 11 (desire frequency; P = 0.39) and 12 (desire level; P = 0.61). Treatment efficacy assessed through questions 3 (penetration ability; P < 0.001) and 4 (maintenance frequency; P < 0.001) was significantly better after sildenafil therapy. There were no significant differences between baseline and post-placebo treatment scores, except for question 13 (relationship satisfaction). Patients treated with sildenafil had significantly better scores in 4 domains compared with baseline, but a difference was not observed in the sexual desire domain (P = 0.32). There were no significant differences in scores between placebo and baseline in any domain. On the global efficacy question, 81.3% of patients showed improvement compared with 18.7% with placebo. There were no differences in areas under the curve and maximum cyclosporine concentrations before and after sildenafil therapy. No patient discontinued the drug because of side effects except for 1 patient with visual hallucination. Treatment with sildenafil in renal transplant recipients is a valid option with an effective response.

RNA-seq Analysis of Clinical-Grade Osteochondral Allografts Reveals Activation of Early Response Genes

PubMed Central

Lin, Yang; Lewallen, Eric A.; Camilleri, Emily T.; Bonin, Carolina A.; Jones, Dakota L.; Dudakovic, Amel; Galeano-Garces, Catalina; Wang, Wei; Karperien, Marcel J.; Larson, Annalise N.; Dahm, Diane L.; Stuart, Michael J.; Levy, Bruce A.; Smith, Jay; Ryssman, Daniel B.; Westendorf, Jennifer J.; Im, Hee-Jeong; van Wijnen, Andre J.; Riester, Scott M.; Krych, Aaron J.

2016-01-01

Preservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA-seq) and real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) to assess genome-wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of “early response genes” that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND). The elevated expression of “early response genes” and reduced levels of ECM-related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation. PMID:26909883

Clinical assessment and determinants of chronic allograft nephropathy in maintenance renal transplant patients.

PubMed

Grinyo, Josep M; Saval, Nuria; Campistol, Josep M

2011-11-01

Current knowledge about the natural history, treatment and physicians' perception of chronic allograft nephropathy (CAN) is limited. The present study evaluated the prevalence and determinants of CAN in renal transplant patients. Epidemiological, cross-sectional multi-centre study conducted in Spain. A total of 872 renal transplant recipients with a functioning graft and at least 2 years of post-transplant data on renal function were consecutively included. CAN diagnosis was recorded based on physician's clinical criteria and on laboratory criteria (serum creatinine ≥ 2 mg/dL and/or glomerular filtration rate ≤ 50 mL/min). The mean time from transplantation until the time of this study was 8.2 years. CAN was diagnosed in 35% of patients (n = 305) according to the physician's criteria (31% of whom with histological assessment) and in 55.5% (n = 482) according to laboratory objective criteria. An older donor age, lack of induction therapy, cyclosporine use, lower tacrolimus levels at 1 year, acute rejection, hypertension and worse initial renal function were associated with CAN development. Time from transplant to biopsy was greater in patients with anti-proteinuric treatment. Immunosuppression was modified in 46.9% of patients with CAN diagnosis [calcineurin inhibitor (CNI) reduction alone in 18.9% of cases; CNI reduction and mycophenolate modification in 17.8% and CNI reduction or withdrawal with introduction of proliferation signal inhibitors in 12.9%). After ~8 years from renal transplantation, 55.5% of patients presented CAN, which was considerably underestimated by physicians. An older donor age and less initial immunosuppression seemed to be related to CAN development.

Poly[ADP-Ribose] Polymerase-1 Expression Is Related To Cold Ischemia, Acute Tubular Necrosis, and Delayed Renal Function In Kidney Transplantation

PubMed Central

O'Valle, Francisco; Del Moral, Raimundo G. M.; Benítez, María del Carmén; Martín-Oliva, David; Gómez-Morales, Mercedes; Aguilar, David; Aneiros-Fernández, José; Hernández-Cortés, Pedro; Osuna, Antonio; Moreso, Francesc; Serón, Daniel; Oliver, Francisco J.; Del Moral, Raimundo G.

2009-01-01

Cold ischemia time especially impacts on outcomes of expanded-criteria donor (ECD) transplantation. Ischemia-reperfusion (IR) injury produces excessive poly[ADP-Ribose] Polymerase-1 (PARP-1) activation. The present study explored the hypothesis that increased tubular expression of PARP-1 contributes to delayed renal function in suboptimal ECD kidney allografts and in non-ECD allografts that develop posttransplant acute tubular necrosis (ATN). Materials and Methods Nuclear PARP-1 immunohistochemical expression was studied in 326 paraffin-embedded renal allograft biopsies (193 with different degrees of ATN and 133 controls) and in murine Parp-1 knockout model of IR injury. Results PARP-1 expression showed a significant relationship with cold ischemia time (r coefficient = 0.603), time to effective diuresis (r = 0.770), serum creatinine levels at biopsy (r = 0.649), and degree of ATN (r = 0.810) (p = 0.001, Pearson test). In the murine IR model, western blot showed an increase in PARP-1 that was blocked by Parp-1 inhibitor. Immunohistochemical study of PARP-1 in kidney allograft biopsies would allow early detection of possible delayed renal function, and the administration of PARP-1 inhibitors may offer a therapeutic option to reduce damage from IR in donor kidneys by preventing or minimizing ATN. In summary, these results suggest a pivotal role for PARP-1 in the ATN of renal transplantation. We propose the immunohistochemical assessment of PARP-1 in kidney allograft biopsies for early detection of a possible delayed renal function. PMID:19784367

Urinary C‑X‑C motif chemokine 13 is a noninvasive biomarker of antibody‑mediated renal allograft rejection.

PubMed

Chen, Dajin; Zhang, Jian; Peng, Wenhan; Weng, Chunhua; Chen, Jianghua

2018-06-22

Noninvasive monitoring methods of immune status are preferred by transplant recipients. The present study investigated whether urinary C‑X‑C motif chemokine 13 (CXCL13) had the potential to reflect ongoing immune processes within renal allografts. Using an ELISA assay, the level of urinary CXCL13 was quantified in a total of 146 renal allograft recipients and 40 healthy controls at scheduled intervals and at the time of the indicated or protocol biopsy. The results of the present study revealed that urinary CXCL13/creatinine (Cr) was lower in normal transplants compared with in those with acute tubular necrosis (ATN; P=0.001), chronic allograft nephropathy (CAN; P=0.01), and acute rejection (AR; P<0.0001), which was associated with a good diagnostic performance for AR [area under the curve (AUC)=0.818, P<0.0001). In addition, urinary CXCL13/Cr levels in patients with AR were also higher than that of patients with graft dysfunction but no rejection, including ATN and CAN (P=0.034). Notably, urinary CXCL13 distinguished between acute antibody‑mediated rejection (ABMR) and acute cellular rejection, with an AUC of 0.856. Furthermore, patients with steroid‑resistant AR exhibited significantly increased urinary CXCL13/Cr levels than patients with reversible AR (P=0.001). Additionally, elevated levels of urinary CXCL13/Cr within the first month of transplant were predictive of graft function at 3 and 6 months (P=0.044 and P=0.04, respectively). Collectively, the findings of the present study indicated that the noninvasive investigation of urinary CXCL13/Cr may be valuable for the detection of AR, particularly ABMR. In addition, high urinary CXCL13/Cr levels predicted a poor response to steroid treatment and compromised graft function.

Growth in pediatric renal transplant recipients.

PubMed

Vasudevan, A; Phadke, K

2007-04-01

One of the fundamental challenges in managing pediatric renal transplant recipient is to ensure normal growth and development. The goal of renal transplant is not just to prolong life but to optimize quality of life. Short stature during childhood may be associated with academic underachievement and development of comorbidities such as attention deficit hyperactivity disorder, learning disability, and mood disorders. The most important factors affecting growth are use of corticosteroids, allograft function, and age and height deficit at the time of transplant. Aggressive conservative management of chronic renal failure and early use of growth hormone therapy will help in optimizing height at time of transplant. Early transplant, steroid minimization or withdrawal, and growth hormone therapy will help in achieving normal adult height in a majority of renal post transplant population. Steroid avoidance to achieve good growth still needs to be validated.

Metabolomic Profiling in Individuals with a Failing Kidney Allograft

PubMed Central

Biancone, Luigi; Bussolino, Stefania; Merugumala, Sai; Tezza, Sara; D’Addio, Francesca; Ben Nasr, Moufida; Valderrama-Vasquez, Alessandro; Usuelli, Vera; De Zan, Valentina; El Essawy, Basset; Venturini, Massimo; Secchi, Antonio; De Cobelli, Francesco; Lin, Alexander; Chandraker, Anil; Fiorina, Paolo

2017-01-01

Background Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease. Methods To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls. Results LC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA) and short-chain acylcarnitines (C4 and C12), (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively). The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively). In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05) in individuals with lower GFR levels. Conclusions We report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function. PMID:28052095

Metabolomic Profiling in Individuals with a Failing Kidney Allograft.

PubMed

Bassi, Roberto; Niewczas, Monika A; Biancone, Luigi; Bussolino, Stefania; Merugumala, Sai; Tezza, Sara; D'Addio, Francesca; Ben Nasr, Moufida; Valderrama-Vasquez, Alessandro; Usuelli, Vera; De Zan, Valentina; El Essawy, Basset; Venturini, Massimo; Secchi, Antonio; De Cobelli, Francesco; Lin, Alexander; Chandraker, Anil; Fiorina, Paolo

2017-01-01

Alteration of certain metabolites may play a role in the pathophysiology of renal allograft disease. To explore metabolomic abnormalities in individuals with a failing kidney allograft, we analyzed by liquid chromatography-mass spectrometry (LC-MS/MS; for ex vivo profiling of serum and urine) and two dimensional correlated spectroscopy (2D COSY; for in vivo study of the kidney graft) 40 subjects with varying degrees of chronic allograft dysfunction stratified by tertiles of glomerular filtration rate (GFR; T1, T2, T3). Ten healthy non-allograft individuals were chosen as controls. LC-MS/MS analysis revealed a dose-response association between GFR and serum concentration of tryptophan, glutamine, dimethylarginine isomers (asymmetric [A]DMA and symmetric [S]DMA) and short-chain acylcarnitines (C4 and C12), (test for trend: T1-T3 = p<0.05; p = 0.01; p<0.001; p = 0.01; p = 0.01; p<0.05, respectively). The same association was found between GFR and urinary levels of histidine, DOPA, dopamine, carnosine, SDMA and ADMA (test for trend: T1-T3 = p<0.05; p<0.01; p = 0.001; p<0.05; p = 0.001; p<0.001; p<0.01, respectively). In vivo 2D COSY of the kidney allograft revealed significant reduction in the parenchymal content of choline, creatine, taurine and threonine (all: p<0.05) in individuals with lower GFR levels. We report an association between renal function and altered metabolomic profile in renal transplant individuals with different degrees of kidney graft function.

Impact of Banff borderline acute rejection among renal allograft recipients.

PubMed

Matoza, J R A; Danguilan, R A; Chicano, S

2008-09-01

This study was performed to determine the incidence, treatment, and outcomes of Banff borderline acute rejection (AR) among renal transplant recipients. We reviewed the courses of adult kidney transplant recipients with borderline AR on clinically indicated biopsies performed at our center from January 2003 to July 2006. Patients with complete transplant records and serum creatinine values at 6 and 12 months were included in this study. The primary outcome measures were serum creatinine values at 1 to 2 weeks after treatment, and at 6 and 12 months after graft biopsy. Among 428 renal graft biopsies, borderline AR was observed in 100 cases (23%). Patients were maintained on the same immunosuppression. The 86 who had complete data were included in the study. Seventy-eight percent of the patients received treatment with 3 days of methylprednisolone, while 22% were untreated. Mean serum creatinine values in the treated group were 2.9 +/- 1.0, 2.6 +/- 2.5, and 3.0 +/- 2.9 mg/dL at the time of biopsy, and at 6 and 12 months thereafter, respectively. In the untreated group, mean serum creatinine values were 2.2 +/- 1.0, 1.9 +/- 0.8, and 2.3 +/- 1.2 mg/dL during biopsy, and at 6 and 12 months thereafter, respectively. There was no significant difference in the serum creatinine at any of the measured time points between the 2 groups. Twelve patients had repeat renal graft biopsies which showed AR (6%), chronic allograft nephropathy (2.4%), and borderline changes (3.8%). Nine of the patients in the treated group eventually developed graft loss. Patients with borderline AR showed a progressive increase in serum creatinine over time. They should be followed closely; immunosuppression may need to be intensified.

Effect of a single intraoperative high-dose ATG-Fresenius on delayed graft function in donation after cardiac-death donor renal allograft recipients: a randomized study.

PubMed

van den Hoogen, Martijn W F; Kho, Marcia M L; Abrahams, Alferso C; van Zuilen, Arjan D; Sanders, Jan-Stephan; van Dijk, Marja; Hilbrands, Luuk B; Weimar, Willem; Hoitsma, Andries J

2013-04-01

Reducing the incidence of delayed graft function after transplant with donation after cardiac death donor renal allografts would facilitate managing recipients during their first weeks after a transplant. To reduce this incidence, in most studies, induction therapy with depleting anti-T-lymphocyte antibodies is coupled with a reduction of the dosage of the calcineurin inhibitor. The separate effect of anti-T-cell therapy on the incidence and duration of delayed graft function is therefore difficult to assess. We performed a randomized study to evaluate the effect of a single intraoperative high-dose of anti-T-lymphocyte immunoglobulin (ATG)-Fresenius (9 mg/kg body weight) on the incidence of delayed graft function. Eligible adult recipients of a first donation after cardiac death donor renal allograft were randomly assigned to ATG-Fresenius or no induction therapy. Maintenance immunosuppression consisted of tacrolimus, in an unadjusted dose, mycophenolate mofetil, and steroids. The study was prematurely terminated because of a lower-than-anticipated inclusion rate. Baseline characteristics were comparable in the ATG-Fresenius group (n=28) and the control group (n=24). Twenty-two patients in the ATG-Fresenius group (79%) had delayed graft function, compared with 13 in the control group (54%; P = .06). Allograft and patient survival were comparable in both groups. Serious adverse events occurred more frequently in the ATG-Fresenius group than they did in the control group (57% vs 29%; P < .05). Intraoperative administration of a single high-dose of ATG-Fresenius in donation after cardiac death donor renal allograft recipients, followed by triple immunosuppression with an unadjusted tacrolimus dose, seems ineffective to reduce the incidence of delayed graft function. Moreover, this was associated with a higher rate of serious adverse events (EudraCT-number, 2007-000210-36.).

RNA-seq analysis of clinical-grade osteochondral allografts reveals activation of early response genes.

PubMed

Lin, Yang; Lewallen, Eric A; Camilleri, Emily T; Bonin, Carolina A; Jones, Dakota L; Dudakovic, Amel; Galeano-Garces, Catalina; Wang, Wei; Karperien, Marcel J; Larson, Annalise N; Dahm, Diane L; Stuart, Michael J; Levy, Bruce A; Smith, Jay; Ryssman, Daniel B; Westendorf, Jennifer J; Im, Hee-Jeong; van Wijnen, Andre J; Riester, Scott M; Krych, Aaron J

2016-11-01

Preservation of osteochondral allografts used for transplantation is critical to ensure favorable outcomes for patients after surgical treatment of cartilage defects. To study the biological effects of protocols currently used for cartilage storage, we investigated differences in gene expression between stored allograft cartilage and fresh cartilage from living donors using high throughput molecular screening strategies. We applied next generation RNA sequencing (RNA-seq) and real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) to assess genome-wide differences in mRNA expression between stored allograft cartilage and fresh cartilage tissue from living donors. Gene ontology analysis was used to characterize biological pathways associated with differentially expressed genes. Our studies establish reduced levels of mRNAs encoding cartilage related extracellular matrix (ECM) proteins (i.e., COL1A1, COL2A1, COL10A1, ACAN, DCN, HAPLN1, TNC, and COMP) in stored cartilage. These changes occur concomitantly with increased expression of "early response genes" that encode transcription factors mediating stress/cytoprotective responses (i.e., EGR1, EGR2, EGR3, MYC, FOS, FOSB, FOSL1, FOSL2, JUN, JUNB, and JUND). The elevated expression of "early response genes" and reduced levels of ECM-related mRNAs in stored cartilage allografts suggests that tissue viability may be maintained by a cytoprotective program that reduces cell metabolic activity. These findings have potential implications for future studies focused on quality assessment and clinical optimization of osteochondral allografts used for cartilage transplantation. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1950-1959, 2016. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Early Allograft Dysfunction After Liver Transplantation Is Associated With Short- and Long-Term Kidney Function Impairment.

PubMed

Wadei, H M; Lee, D D; Croome, K P; Mai, M L; Golan, E; Brotman, R; Keaveny, A P; Taner, C B

2016-03-01

Early allograft dysfunction (EAD) after liver transplantation (LT) is related to ischemia-reperfusion injury and may lead to a systemic inflammatory response and extrahepatic organ dysfunction. We evaluated the effect of EAD on new-onset acute kidney injury (AKI) requiring renal replacement therapy within the first month and end-stage renal disease (ESRD) within the first year post-LT in 1325 primary LT recipients. EAD developed in 358 (27%) of recipients. Seventy-one (5.6%) recipients developed AKI and 38 (2.9%) developed ESRD. Compared with those without EAD, recipients with EAD had a higher risk of AKI and ESRD (4% vs. 9% and 2% vs. 6%, respectively, p < 0.001 for both). Multivariate logistic regression analysis showed an independent relationship between EAD and AKI as well as ESRD (odds ratio 3.5, 95% confidence interval 1.9-6.4, and odds ratio 3.1, 95% confidence interval 11.9-91.2, respectively). Patients who experienced both EAD and AKI had inferior 1-, 3-, 5-, and 10-year patient and graft survival compared with those with either EAD or AKI alone, while those who had neither AKI nor EAD had the best outcomes (p < 0.001). Post-LT EAD is a risk factor for both AKI and ESRD and should be considered a target for future intervention to reduce post-LT short- and long-term renal dysfunction. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Presence of FoxP3+ regulatory T Cells predicts outcome of subclinical rejection of renal allografts.

PubMed

Bestard, Oriol; Cruzado, Josep M; Rama, Inés; Torras, Joan; Gomà, Montse; Serón, Daniel; Moreso, Francesc; Gil-Vernet, Salvador; Grinyó, Josep M

2008-10-01

Subclinical rejection (SCR) of renal allografts refers to histologic patterns of acute rejection despite stable renal function. The clinical approach to SCR is controversial; it would be helpful to identify biomarkers that could determine whether the identified cellular infiltrates were detrimental. For investigation of whether the presence of FoxP3+ regulatory T cells (Treg) could help determine the functional importance of tubulointerstitial infiltrates observed in 6-mo protocol biopsies, 37 cases of SCR were evaluated. The presence of FoxP3+ Treg discriminated harmless from injurious infiltrates, evidenced by independently predicting better graft function 2 and 3 yr after transplantation. Furthermore, the FoxP3+ Treg/CD3+ T cell ratio positively correlated with graft function at 2 yr after transplantation, suggesting that an increasing proportion of Treg within the global T cell infiltrate may facilitate renal engraftment; therefore, immunostaining for FoxP3+ Treg in patients with SCR on protocol biopsies may ultimately be useful to identify patients who may require alterations in their immunosuppressive regimens.

Presence of FoxP3+ Regulatory T Cells Predicts Outcome of Subclinical Rejection of Renal Allografts

PubMed Central

Bestard, Oriol; Cruzado, Josep M.; Rama, Inés; Torras, Joan; Gomà, Montse; Serón, Daniel; Moreso, Francesc; Gil-Vernet, Salvador; Grinyó, Josep M.

2008-01-01

Subclinical rejection (SCR) of renal allografts refers to histologic patterns of acute rejection despite stable renal function. The clinical approach to SCR is controversial; it would be helpful to identify biomarkers that could determine whether the identified cellular infiltrates were detrimental. For investigation of whether the presence of FoxP3+ regulatory T cells (Treg) could help determine the functional importance of tubulointerstitial infiltrates observed in 6-mo protocol biopsies, 37 cases of SCR were evaluated. The presence of FoxP3+ Treg discriminated harmless from injurious infiltrates, evidenced by independently predicting better graft function 2 and 3 yr after transplantation. Furthermore, the FoxP3+ Treg/CD3+ T cell ratio positively correlated with graft function at 2 yr after transplantation, suggesting that an increasing proportion of Treg within the global T cell infiltrate may facilitate renal engraftment; therefore, immunostaining for FoxP3+ Treg in patients with SCR on protocol biopsies may ultimately be useful to identify patients who may require alterations in their immunosuppressive regimens. PMID:18495961

A score model for the continuous grading of early allograft dysfunction severity.

PubMed

Pareja, Eugenia; Cortes, Miriam; Hervás, David; Mir, José; Valdivieso, Andrés; Castell, José V; Lahoz, Agustín

2015-01-01

Early allograft dysfunction (EAD) dramatically influences graft and patient outcomes. A lack of consensus on an EAD definition hinders comparisons of liver transplant outcomes and management of recipients among and within centers. We sought to develop a model for the quantitative assessment of early allograft function [Model for Early Allograft Function Scoring (MEAF)] after transplantation. A retrospective study including 1026 consecutive liver transplants was performed for MEAF score development. Multivariate data analysis was used to select a small number of postoperative variables that adequately describe EAD. Then, the distribution of these variables was mathematically modeled to assign a score for each actual variable value. A model, based on easily obtainable clinical parameters (ie, alanine aminotransferase, international normalized ratio, and bilirubin) and scoring liver function from 0 to 10, was built. The MEAF score showed a significant association with patient and graft survival at 3-, 6- and 12-month follow-ups. Hepatic steatosis and age for donors; cold/warm ischemia times and postreperfusion syndrome for surgery; and intensive care unit and hospital stays, Model for End-Stage Liver Disease and Child-Pugh scores, body mass index, and fresh frozen plasma transfusions for recipients were factors associated significantly with EAD. The model was satisfactorily validated by its application to an independent set of 200 patients who underwent liver transplantation at a different center. In conclusion, a model for the quantitative assessment of EAD severity has been developed and validated for the first time. The MEAF provides a more accurate graft function assessment than current categorical classifications and may help clinicians to make early enough decisions on retransplantation benefits. Furthermore, the MEAF score is a predictor of recipient and graft survival. The standardization of the criteria used to define EAD may allow reliable comparisons of

Elevated pretransplantation soluble CD30 is associated with decreased early allograft function after human lung transplantation.

PubMed

Shah, Ashish S; Leffell, M Sue; Lucas, Donna; Zachary, Andrea A

2009-02-01

Early allograft function after lung transplantation is variable. Clinical criteria have limited predictive value for early graft function. Recipient immunologic state before LTx may affect early lung function. We investigated the association between pretransplantation soluble CD30 (sCD30), a marker of Th2-type T-cell activation, and early clinical parameters of allograft function. Between September 2002 and January 2007, a total of 80 transplantations were performed at Johns Hopkins Hospital. Of the patients, 43 had a pretransplantation sCD30 level determined. Pre- and postoperative patient variables were collected, and patients were stratified into two groups: sCD30 <20 (low sCD30) and >20 (high sCD30). High sCD30 (n = 26) and low sCD30 (n = 17) groups were similar in age, gender, and ischemia time. In the high sCD30 group, a higher percentage of patients had pulmonary fibrosis and a lower percentage had emphysema. Oxygenation at 48 hours was significantly worse in the high sCD30 group as compared with the low sCD30 (p = 0.003). Moreover, prolonged intubation and 90-day mortality were greater in the high sCD30 group. This represents the first report of the use of sCD30 as a marker for early allograft function in human lung transplanation. Increased pretransplantation recipient sCD30 appears to be associated with decreased early post-transplantation gas exchange, prolonged intubation, and early mortality.

Do Alloreactivity and Prolonged Cold Ischemia Cause Different Elementary Lesions in Chronic Allograft Nephropathy?

PubMed Central

Herrero-Fresneda, Immaculada; Torras, Joan; Cruzado, Josep M.; Condom, Enric; Vidal, August; Riera, Marta; Lloberas, Nuria; Alsina, Jeroni; Grinyo, Josep M.

2003-01-01

This study assesses the individual contributions of the nonalloreactive factor, cold ischemia (CI), and alloreactivity to late functional and structural renal graft changes, and examines the effect of the association of both factors on the progression of chronic allograft nephropathy. Lewis rats acted as receptors of kidneys from either Lewis or Fischer rats. For CI, kidneys were preserved for 5 hours. The rats were divided into four groups: Syn, syngeneic graft; SynI, syngeneic graft and CI; Allo, allogeneic graft; AlloI, allogeneic graft and CI. Renal function was assessed every 4 weeks for 24 weeks. Grafts were evaluated for acute inflammatory response at 1 week and for chronic histological damage at 24 weeks. Only when CI and allogenicity were combined did immediate posttransplant mortality occur, while survivors showed accelerated renal insufficiency that induced further mortality at 12 weeks after transplant. Solely ischemic rats developed renal insufficiency. Renal structural damage in ischemic rats was clearly tubulointerstitial, while significant vasculopathy and glomerulosclerosis appeared only in the allogeneic groups. There was increased infiltration of macrophages and expression of mRNA-transforming growth factor-β1 in the ischemic groups, irrespective of the allogeneic background. The joint association of CI plus allogenicity significantly increased cellular infiltration at both early and late stages, aggravating tubulointerstitial and vascular damage considerably. In summary, CI is mainly responsible for tubulointerstitial damage, whereas allogenicity leads to vascular lesion. The association of both factors accelerates and aggravates the progression of experimental chronic allograft nephropathy. PMID:12507896

Donor information based prediction of early allograft dysfunction and outcome in liver transplantation.

PubMed

Hoyer, Dieter P; Paul, Andreas; Gallinat, Anja; Molmenti, Ernesto P; Reinhardt, Renate; Minor, Thomas; Saner, Fuat H; Canbay, Ali; Treckmann, Jürgen W; Sotiropoulos, Georgios C; Mathé, Zoltan

2015-01-01

Poor initial graft function was recently newly defined as early allograft dysfunction (EAD) [Olthoff KM, Kulik L, Samstein B, et al. Validation of a current definition of early allograft dysfunction in liver transplant recipients and analysis of risk factors. Liver Transpl 2010; 16: 943]. Aim of this analysis was to evaluate predictive donor information for development of EAD. Six hundred and seventy-eight consecutive adult patients (mean age 51.6 years; 60.3% men) who received a primary liver transplantation (LT) (09/2003-12/2011) were included. Standard donor data were correlated with EAD and outcome by univariable/multivariable logistic regression and Cox proportional hazards to identify prognostic donor factors after adjustment for recipient confounders. Estimates of relevant factors were utilized for construction of a new continuous risk index to develop EAD. 38.7% patients developed EAD. 30-day survival of grafts with and without EAD was 59.8% and 89.7% (P < 0.0001). 30-day survival of patients with and without EAD was 68.5% and 93.1% (P < 0.0001) respectively. Donor body mass index (P = 0.0112), gGT (P = 0.0471), macrosteatosis (P = 0.0006) and cold ischaemia time (CIT) (P = 0.0031) were predictors of EAD. Internal cross validation showed a high predictive value (c-index = 0.622). Early allograft dysfunction correlates with early results of LT and can be predicted by donor data only. The newly introduced risk index potentially optimizes individual decisions to accept/decline high risk organs. Outcome of these organs might be improved by shortening CIT. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Do the outcomes of living donor renal allograft recipients differ with peritoneal dialysis and hemodialysis as a bridge renal replacement therapy?

PubMed

Prasad, Narayan; Vardhan, Harsh; Baburaj, Vinod P; Bhadauria, Dharmendra; Gupta, Amit; Sharma, Raj K; Kaul, Anupama

2014-11-01

This study was undertaken to compare the outcomes of living donor renal transplant recipients using peritoneal dialysis (PD) and hemodialysis (HD) as a bridge modality for renal replacement therapy till renal transplantation. The demographic profiles of the recipients and donors, the patients' native kidney disease (diabetic versus non-diabetic), duration on dialysis, requirement of anti-hypertensive drugs, number of blood transfusions, human leukocyte antigen (HLA) mismatch status, pre- and post-transplant infectious complications, and post-transplant outcomes of patients were compared between the two groups. The demographic features of the study patients were similar in the two groups. The duration of dialysis prior to transplant was significantly longer in the PD group than in the HD group of patients. The anti-hypertensive drug requirement was lower and the hemoglobin level and residual urine volume at the time of transplant were relatively better in the PD patients compared to the HD patients. The number of acute rejection episodes, delayed graft function, surgical complications, glomerular filtration rate at one month and at the last follow-up, were also similar in both groups. The short-term and long-term graft survival was similar in both groups of patients. The one-, two-, five-, and eight-year death-censored graft survival rates of the PD patients were 98, 95, 85, and 73%, respectively, and in the HD group of patients, they were 100, 93, 84, and 79%, respectively. The one-, two-, five-, and eight-year patient survival rates in the PD group were 97, 92, 77, and 66%, respectively, and in the HD group, they were 97, 92, 79, and 69%, respectively. Our study suggests that the outcomes of the living donor renal allograft recipients did not differ between the groups of patients who used PD or HD as renal replacement therapy prior to renal transplantation.

Evaluation of posttransplantation soluble CD30 for diagnosis of acute renal allograft rejection.

PubMed

Pelzl, Steffen; Opelz, Gerhard; Daniel, Volker; Wiesel, Manfred; Süsal, Caner

2003-02-15

Posttransplantation measurement of soluble CD30 (sCD30) may be useful for identifying kidney graft recipients at risk of impending graft rejection in the early posttransplantation period. We measured plasma sCD30 levels and evaluated the levels in relation to the diagnosis of rejection. Receiver operating characteristic curves demonstrated that on posttransplantation days 3 to 5, sCD30 allowed a differentiation of recipients who subsequently developed acute allograft rejection (n=25) from recipients with an uncomplicated course (n=20, P<0.0001) (area under the receiver operating characteristic curve 0.96, specificity 100%, sensitivity 88%) and recipients with acute tubular necrosis in the absence of rejection (n=11, P=0.001) (area under the receiver operating characteristic curve 0.85, specificity 91%, sensitivity 72%). sCD30 measured on posttransplantation days 3 to 5 offers a noninvasive means for differentiating patients with impending acute allograft rejection from patients with an uncomplicated course or with acute tubular necrosis.

Development of CD3 cell quantitation algorithms for renal allograft biopsy rejection assessment utilizing open source image analysis software.

PubMed

Moon, Andres; Smith, Geoffrey H; Kong, Jun; Rogers, Thomas E; Ellis, Carla L; Farris, Alton B Brad

2018-02-01

Renal allograft rejection diagnosis depends on assessment of parameters such as interstitial inflammation; however, studies have shown interobserver variability regarding interstitial inflammation assessment. Since automated image analysis quantitation can be reproducible, we devised customized analysis methods for CD3+ T-cell staining density as a measure of rejection severity and compared them with established commercial methods along with visual assessment. Renal biopsy CD3 immunohistochemistry slides (n = 45), including renal allografts with various degrees of acute cellular rejection (ACR) were scanned for whole slide images (WSIs). Inflammation was quantitated in the WSIs using pathologist visual assessment, commercial algorithms (Aperio nuclear algorithm for CD3+ cells/mm 2 and Aperio positive pixel count algorithm), and customized open source algorithms developed in ImageJ with thresholding/positive pixel counting (custom CD3+%) and identification of pixels fulfilling "maxima" criteria for CD3 expression (custom CD3+ cells/mm 2 ). Based on visual inspections of "markup" images, CD3 quantitation algorithms produced adequate accuracy. Additionally, CD3 quantitation algorithms correlated between each other and also with visual assessment in a statistically significant manner (r = 0.44 to 0.94, p = 0.003 to < 0.0001). Methods for assessing inflammation suggested a progression through the tubulointerstitial ACR grades, with statistically different results in borderline versus other ACR types, in all but the custom methods. Assessment of CD3-stained slides using various open source image analysis algorithms presents salient correlations with established methods of CD3 quantitation. These analysis techniques are promising and highly customizable, providing a form of on-slide "flow cytometry" that can facilitate additional diagnostic accuracy in tissue-based assessments.

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival.

PubMed

Trailin, Andriy V; Ostapenko, Tetyana I; Nykonenko, Tamara N; Nesterenko, Svitlana N; Nykonenko, Olexandr S

2017-01-01

We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day-6 months), late AR (>6 months), and early pyelonephritis (the 8th day-2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes.

Peritransplant Soluble CD30 as a Risk Factor for Slow Kidney Allograft Function, Early Acute Rejection, Worse Long-Term Allograft Function, and Patients' Survival

PubMed Central

Ostapenko, Tetyana I.; Nykonenko, Tamara N.; Nesterenko, Svitlana N.; Nykonenko, Olexandr S.

2017-01-01

Background We aimed to determine whether serum soluble CD30 (sCD30) could identify recipients at high risk for unfavorable early and late kidney transplant outcomes. Methods Serum sCD30 was measured on the day of kidney transplantation and on the 4th day posttransplant. We assessed the value of these measurements in predicting delayed graft function, slow graft function (SGF), acute rejection (AR), pyelonephritis, decline of allograft function after 6 months, and graft and patient survival during 5 years of follow-up in 45 recipients. Results We found the association between low pretransplant serum levels of sCD30 and SGF. The absence of significant decrease of sCD30 on the 4th day posttransplant was characteristic for SGF, early AR (the 8th day–6 months), late AR (>6 months), and early pyelonephritis (the 8th day–2 months). Lower pretransplant and posttransplant sCD30 predicted worse allograft function at 6 months and 2 years, respectively. Higher pretransplant sCD30 was associated with higher frequency of early AR, and worse patients' survival, but only in the recipients of deceased-donor graft. Pretransplant sCD30 also allowed to differentiate patients with early pyelonephritis and early AR. Conclusions Peritransplant sCD30 is useful in identifying patients at risk for unfavorable early and late transplant outcomes. PMID:28694560

Effect of Cordyceps sinensis on renal function of patients with chronic allograft nephropathy.

PubMed

Zhang, Zhihong; Wang, Xiangwei; Zhang, Yuanning; Ye, Gang

2011-01-01

To investigate the effect of Cordyceps sinensis (Bailing capsule, fermented agent of C. sinensis) on renal function of patients with chronic allograft nephropathy (CAN). A total of 231 CAN patients who underwent transplantation between 2005 and 2008 and experienced chronic graft dysfunction were randomly divided into 2 groups. Patients in group A (n = 122) were treated with immunosuppressive agents and C. sinensis (2.0 g/day, 3 times a day), while patients in group B (n = 109) were treated with traditional immunosuppressive drugs. Serum creatinine (SCr), blood urea nitrogen (BUN), creatinine clearance rate (C(Cr)) and urinary protein in 24 h (24-hour Upro) of all patients were measured before and after treatment. Urinary concentrations of transforming growth factor (TGF)-β(1), retinol-binding protein (RBP) and β(2)-microglobulin (β(2)-MG) were detected at the same time. After 6-month treatment with C. sinensis, SCr and C(Cr) in group A were significantly improved (p < 0.05), while there was no significant improvement observed for group B. There was no significant change in BUN in groups A and B (p > 0.05). 24-hour Upro, RBP and β(2)-MG were lower in group A after treatment with C. sinensis (p < 0.05 or p < 0.01), and urinary TGF-β(1) in group A was significantly lower than the values before C. sinensis treatment (p < 0.05), but showed no change in patients of group B. In group A, renal function had improved in 72 cases, stabilized in 38 cases, and worsened in 12 cases. In group B, renal function had improved in 14 cases, stabilized in 50 cases, and worsened in 45 cases (p < 0.05). C. sinensis therapy is advantageous in improving renal function of CAN patients by retarding CAN progression. Copyright © 2011 S. Karger AG, Basel.

Serum Iron Protects from Renal Postischemic Injury.

PubMed

Vaugier, Céline; Amano, Mariane T; Chemouny, Jonathan M; Dussiot, Michael; Berrou, Claire; Matignon, Marie; Ben Mkaddem, Sanae; Wang, Pamella H M; Fricot, Aurélie; Maciel, Thiago T; Grapton, Damien; Mathieu, Jacques R R; Beaumont, Carole; Peraldi, Marie-Noëlle; Peyssonnaux, Carole; Mesnard, Laurent; Daugas, Eric; Vrtovsnik, François; Monteiro, Renato C; Hermine, Olivier; Ginzburg, Yelena Z; Benhamou, Marc; Camara, Niels O S; Flamant, Martin; Moura, Ivan C

2017-12-01

Renal transplants remain a medical challenge, because the parameters governing allograft outcome are incompletely identified. Here, we investigated the role of serum iron in the sterile inflammation that follows kidney ischemia-reperfusion injury. In a retrospective cohort study of renal allograft recipients ( n =169), increased baseline levels of serum ferritin reliably predicted a positive outcome for allografts, particularly in elderly patients. In mice, systemic iron overload protected against renal ischemia-reperfusion injury-associated sterile inflammation. Furthermore, chronic iron injection in mice prevented macrophage recruitment after inflammatory stimuli. Macrophages cultured in high-iron conditions had reduced responses to Toll-like receptor-2, -3, and -4 agonists, which associated with decreased reactive oxygen species production, increased nuclear localization of the NRF2 transcription factor, increased expression of the NRF2-related antioxidant response genes, and limited NF- κ B and proinflammatory signaling. In macrophage-depleted animals, the infusion of macrophages cultured in high-iron conditions did not reconstitute AKI after ischemia-reperfusion, whereas macrophages cultured in physiologic iron conditions did. These findings identify serum iron as a critical protective factor in renal allograft outcome. Increasing serum iron levels in patients may thus improve prognosis of renal transplants. Copyright © 2017 by the American Society of Nephrology.

SWOT analysis of Banff: strengths, weaknesses, opportunities and threats of the international Banff consensus process and classification system for renal allograft pathology.

PubMed

Mengel, M; Sis, B; Halloran, P F

2007-10-01

The Banff process defined the diagnostic histologic lesions for renal allograft rejection and created a standardized classification system where none had existed. By correcting this deficit the process had universal impact on clinical practice and clinical and basic research. All trials of new drugs since the early 1990s benefited, because the Banff classification of lesions permitted the end point of biopsy-proven rejection. The Banff process has strengths, weaknesses, opportunities and threats (SWOT). The strength is its self-organizing group structure to create consensus. Consensus does not mean correctness: defining consensus is essential if a widely held view is to be proved wrong. The weaknesses of the Banff process are the absence of an independent external standard to test the classification; and its almost exclusive reliance on histopathology, which has inherent limitations in intra- and interobserver reproducibility, particularly at the interface between borderline and rejection, is exactly where clinicians demand precision. The opportunity lies in the new technology such as transcriptomics, which can form an external standard and can be incorporated into a new classification combining the elegance of histopathology and the objectivity of transcriptomics. The threat is the degree to which the renal transplant community will participate in and support this process.

Percutaneous Balloon Dilatation for the Treatment of Early and Late Ureteral Strictures After Renal Transplantation: Long-Term Follow-Up

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bachar, Gil N.; Mor, E.; Bartal, G.

2004-08-15

We report our experience with percutaneous balloon dilatation (PBD) for the treatment of ureteral strictures in patients with renal allografts. Of the 422 consecutive patients after renal transplantation in our center 10 patients had ureteral strictures. An additional 11 patients were referred from other centers. The 21 patients included 15 men and 6 women aged 16 to 67 years. Strictures were confirmed by sonography and scintigraphy in all cases. Patients underwent 2 to 4 PBDs at 7-10-day intervals. Clinical success was defined as resolution of the stenosis and hydronephrosis on sequential ultrasound and normalization of creatinine levels. Patients were dividedmore » into two groups: those who underwent transplantation more than 3 months previously and those who underwent transplantation less than 3 months previously. PBD was successful in 13 of the 21 patients (62%). There was no statistically significant difference in success rate between the patients with early (n 12) and those with late (n = 9) obstruction: 58.4% and 66%, respectively. No major complications were documented. PBD is a safe and simple tool for treating ureteral strictures and procedure-related morbidity is low. It can serve as an initial treatment in patients with early or late ureteral strictures after renal transplantation.« less

Urinary mRNA for the Diagnosis of Renal Allograft Rejection: The Issue of Normalization.

PubMed

Galichon, P; Amrouche, L; Hertig, A; Brocheriou, I; Rabant, M; Xu-Dubois, Y-C; Ouali, N; Dahan, K; Morin, L; Terzi, F; Rondeau, E; Anglicheau, D

2016-10-01

Urinary messenger RNA (mRNA) quantification is a promising method for noninvasive diagnosis of renal allograft rejection (AR), but the quantification of mRNAs in urine remains challenging due to degradation. RNA normalization may be warranted to overcome these issues, but the strategies of gene normalization have been poorly evaluated. Herein, we address this issue in a case-control study of 108 urine samples collected at time of allograft biopsy in kidney recipients with (n = 52) or without (n = 56) AR by comparing the diagnostic value of IP-10 and CD3ε mRNAs-two biomarkers of AR-after normalization by the total amount of RNA, normalization by one of the three widely used reference RNAs-18S, glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and Hypoxanthine-guanine phosphoribosyltransferase (HPRT)-or normalization using uroplakin 1A (UPK) mRNA as a possible urine-specific reference mRNA. Our results show that normalization based on the total quantity of RNA is not substantially improved by additional normalization and may even be worsened with some classical reference genes that are overexpressed during rejection. However, considering that normalization by a reference gene is necessary to ensure polymerase chain reaction (PCR) quality and reproducibility and to suppress the effect of RNA degradation, we suggest that GAPDH and UPK1A are preferable to 18S or HPRT RNA. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Renal Blood Flow, Glomerular Filtration Rate, and Renal Oxygenation in Early Clinical Septic Shock.

PubMed

Skytte Larsson, Jenny; Krumbholz, Vitus; Enskog, Anders; Bragadottir, Gudrun; Redfors, Bengt; Ricksten, Sven-Erik

2018-06-01

Data on renal hemodynamics, function, and oxygenation in early clinical septic shock are lacking. We therefore measured renal blood flow, glomerular filtration rate, renal oxygen consumption, and oxygenation in patients with early septic shock. Prospective comparative study. General and cardiothoracic ICUs. Patients with norepinephrine-dependent early septic shock (n = 8) were studied within 24 hours after arrival in the ICU and compared with postcardiac surgery patients without acute kidney injury (comparator group, n = 58). None. Data on systemic hemodynamics and renal variables were obtained during two 30-minute periods. Renal blood flow was measured by the infusion clearance of para-aminohippuric acid, corrected for renal extraction of para-aminohippuric acid. Renal filtration fraction was measured by renal extraction of chromium-51 labeled EDTA. Renal oxygenation was estimated from renal oxygen extraction. Renal oxygen delivery (-24%; p = 0.037) and the renal blood flow-to-cardiac index ratio (-21%; p = 0.018) were lower, renal vascular resistance was higher (26%; p = 0.027), whereas renal blood flow tended to be lower (-19%; p = 0.068) in the septic group. Glomerular filtration rate (-32%; p = 0.006) and renal sodium reabsorption (-29%; p = 0.014) were both lower in the septic group. Neither renal filtration fraction nor renal oxygen consumption differed significantly between groups. Renal oxygen extraction was significantly higher in the septic group (28%; p = 0.022). In the septic group, markers of tubular injury were elevated. In early clinical septic shock, renal function was lower, which was accompanied by renal vasoconstriction, a lower renal oxygen delivery, impaired renal oxygenation, and tubular sodium reabsorption at a high oxygen cost compared with controls.

Comparison of sirolimus plus tacrolimus versus sirolimus plus cyclosporine in high-risk renal allograft recipients: results from an open-label, randomized trial.

PubMed

Gaber, A Osama; Kahan, Barry D; Van Buren, Charles; Schulman, Seth L; Scarola, Joseph; Neylan, John F

2008-11-15

The efficacy and safety of sirolimus (SRL) plus tacrolimus (TAC) versus SRL plus cyclosporine (CsA) were compared in high-risk renal allograft recipients. Evaluable patients (448) were randomly assigned (1:1) before transplant to receive SRL+TAC or SRL+CsA with corticosteroids. Eligible patients were black and/or repeat transplant recipients, and/or those with high titer of panel-reactive antibodies. Demographics were similar between groups. Both treatments demonstrated equivalent efficacy of the composite endpoint at 12 months with efficacy failure rates of 21.9% vs. 23.2% (SRL+TAC vs. SRL+CsA, respectively, 95% CI -10.0 to 7.1, P=0.737). Biopsy-confirmed acute rejection rate (13.8% vs. 17.4%) and graft survival rate (89.7% vs. 90.2%) were similar (SRL+TAC vs. SRL+CsA, respectively). In evaluable patients (received at least 1 dose of study drug), renal function (calculated Nankivell glomerular filtration rate) was not superior in SRL+TAC versus SRL+CsA (54.5 vs. 52.6 mL/min, P=0.466); however, in on-therapy patients, glomerular filtration rate was significantly higher in SRL+TAC at most time points. At 12 months, there were no significant differences in rates of death, discontinuation because of adverse events, hypercholesterolemia, hyperlipemia, or proteinuria. Diarrhea and herpes simplex infections occurred significantly more often in SRL+TAC patients. Hypertension, cardiomegaly, increased creatinine, overdose (primarily calcineurin inhibitor toxicity), acne, urinary tract disorders, lymphocele, and ovarian cysts occurred significantly more often in SRL+CsA patients. This study demonstrated that SRL-based therapy was efficacious in high-risk renal allograft recipients in the first year after transplant, providing equivalent efficacy with CsA or TAC, similar graft survival, low biopsy-confirmed acute rejection rates, excellent renal function, and an acceptable safety profile.

Pre-lung transplant measures of reflux on impedance are superior to pH testing alone in predicting early allograft injury

PubMed Central

Lo, Wai-Kit; Burakoff, Robert; Goldberg, Hilary J; Feldman, Natan; Chan, Walter W

2015-01-01

AIM: To evaluate pre-lung transplant acid reflux on pH-testing vs corresponding bolus reflux on multichannel intraluminal impedance (MII) to predict early allograft injury. METHODS: This was a retrospective cohort study of lung transplant recipients who underwent pre-transplant combined MII-pH-testing at a tertiary care center from January 2007 to November 2012. Patients with pre-transplant fundoplication were excluded. Time-to-event analysis was performed using a Cox proportional hazards model to assess associations between measures of reflux on MII-pH testing and early allograft injury. Area under the receiver operating characteristic (ROC) curve (c-statistic) of the Cox model was calculated to assess the predictive value of each reflux parameter for early allograft injury. Six pH-testing parameters and their corresponding MII measures were specified a priori. The pH parameters were upright, recumbent, and overall acid reflux exposure; elevated acid reflux exposure; total acid reflux episodes; and acid clearance time. The corresponding MII measures were upright, recumbent, and overall bolus reflux exposure; elevated bolus reflux exposure; total bolus reflux episodes; and bolus clearance time. RESULTS: Thirty-two subjects (47% men, mean age: 55 years old) met the inclusion criteria of the study. Idiopathic pulmonary fibrosis (46.9%) represented the most common pulmonary diagnosis leading to transplantation. Baseline demographics, pre-transplant cardiopulmonary function, number of lungs transplanted (unilateral vs bilateral), and post-transplant proton pump inhibitor use were similar between reflux severity groups. The area under the ROC curve, or c-statistic, of each acid reflux parameter on pre-transplant pH-testing was lower than its bolus reflux counterpart on MII in the prediction of early allograft injury. In addition, the development of early allograft injury was significantly associated with three pre-transplant MII measures of bolus reflux: overall reflux

Treatment of Autonomous Hyperparathyroidism in Post Renal Transplant Recipients

ClinicalTrials.gov

2017-02-07

Chronic Allograft Nephropathy; Chronic Kidney Disease; Chronic Renal Failure; Disordered Mineral Metabolism; End Stage Renal Disease; Hyperparathyroidism; Hypophosphatemia; Kidney Disease; Kidney Transplantation; Post Renal Transplantation

Multiplexed color-coded probe-based gene expression assessment for clinical molecular diagnostics in formalin-fixed paraffin-embedded human renal allograft tissue.

PubMed

Adam, Benjamin; Afzali, Bahman; Dominy, Katherine M; Chapman, Erin; Gill, Reeda; Hidalgo, Luis G; Roufosse, Candice; Sis, Banu; Mengel, Michael

2016-03-01

Histopathologic diagnoses in transplantation can be improved with molecular testing. Preferably, molecular diagnostics should fit into standard-of-care workflows for transplant biopsies, that is, formalin-fixed paraffin-embedded (FFPE) processing. The NanoString(®) gene expression platform has recently been shown to work with FFPE samples. We aimed to evaluate its methodological robustness and feasibility for gene expression studies in human FFPE renal allograft samples. A literature-derived antibody-mediated rejection (ABMR) 34-gene set, comprised of endothelial, NK cell, and inflammation transcripts, was analyzed in different retrospective biopsy cohorts and showed potential to molecularly discriminate ABMR cases, including FFPE samples. NanoString(®) results were reproducible across a range of RNA input quantities (r = 0.998), with different operators (r = 0.998), and between different reagent lots (r = 0.983). There was moderate correlation between NanoString(®) with FFPE tissue and quantitative reverse transcription polymerase chain reaction (qRT-PCR) with corresponding dedicated fresh-stabilized tissue (r = 0.487). Better overall correlation with histology was observed with NanoString(®) (r = 0.354) than with qRT-PCR (r = 0.146). Our results demonstrate the feasibility of multiplexed gene expression quantification from FFPE renal allograft tissue. This represents a method for prospective and retrospective validation of molecular diagnostics and its adoption in clinical transplantation pathology. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Renal Allograft Function Is a Risk Factor of Left Ventricular Remodeling After Kidney Transplantation.

PubMed

Koo, T Y; Ahn, C; Yang, J

2017-06-01

Cardiovascular disease is the leading cause of morbidity and mortality in kidney transplantation (KT) patients. The prevalence of left ventricular hypertrophy increases with the progression of renal insufficiency. We investigated the association between the progression of renal insufficiency and left ventricular hypertrophy after KT. We reviewed KT patients at Seoul National University Hospital from January 1973 to December 2009. The creatinine elevation ratio (CER, the percentage change in the creatinine level from 1 month to 5 years after transplant) was calculated as follows: (creatinine level at 5 years minus creatinine level at 1 month)/creatinine level at 1 month × 100. The study population was classified into a high-CER group (CER ≥25%) and low-CER group (CER <25%). Mean left ventricular mass index (LVMI) values were 135.7 and 134.7 g/m 2 before KT and 101.7 and 123.7 g/m 2 at 5 years after KT in the low-CER and high-CER groups, respectively. The LVMI before or 1 year after KT was not different between the 2 groups, but the LVMI at 5 years post-transplant was higher in the high-CER group than in the low-CER group. The LVMI increased after its initial decrease in the high-CER group, whereas its reduction was maintained in the low-CER group during the 5 years after KT (P = .009, repeated-measures analysis of variance). These data suggest that deterioration of renal allograft function is associated with left ventricular remodeling after KT. Copyright © 2017 Elsevier Inc. All rights reserved.

The early and midterm function of decellularized aortic valve allografts.

PubMed

da Costa, Francisco D A; Costa, Ana Claudia B A; Prestes, Roberta; Domanski, Ana Carolina; Balbi, Eduardo Mendel; Ferreira, Andreia D A; Lopes, Sergio Veiga

2010-12-01

This study evaluates the early and midterm results of decellularized aortic valve allografts (DAVA) as an aortic valve replacement. Between October 2005 and February 2010, 41 patients, 28 of whom were male, with a median age of 34 years (range, 0.1 to 71), had aortic valve replacement with DAVA. Decellularization was obtained with a 0.1% sodium dodecyl sulfate solution. Postoperative evaluation was performed with serial echocardiograms, magnetic resonance imaging, and multislice computed tomography studies to evaluate valve hemodynamics, allograft conduit dimensions, and calcification scores. There were 3 early deaths and 1 late death, with a mean follow-up of 19 months (range, 1 to 53). There was 1 reoperation due to a failed mitral valve repair. By echocardiography in all patients, the median immediate postoperative peak gradient was 7 mm Hg (range, 1 to 26 mm Hg), and at last follow-up it was 4 mm Hg (range, 1 to 16 mm Hg); valvular regurgitation was graded as none or trivial in all but 1 patient, who had a regurgitation graded as mild to moderate. By magnetic resonance imaging (n = 4), mean root dimensions were stable at the annulus (24 mm), sinus of Valsalva (33 mm), and sinotubular junction (28 mm). By computed tomography (n = 22), there was only discrete conduit calcification (median calcium score 63 Hounsfield units [HU]; range, 0 to 894 HU) to 3 years of follow-up. Conduit biopsy in the patient who underwent reoperation demonstrated well-preserved wall structure, absence of calcification, and limited in vivo host repopulation. The early and midterm results with DAVA demonstrated stable structural integrity, low rate of calcification, and adequate hemodynamics. Although longer periods of observation are necessary, DAVA appears to be a promising alternative for aortic valve replacement in selected patients. Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

[Identifying the specific causes of kidney allograft loss: A population-based study].

PubMed

Lohéac, Charlotte; Aubert, Olivier; Loupy, Alexandre; Legendre, Christophe

2018-04-01

Results of kidney transplantation have been improving but long-term allograft survival remains disappointing. The objective of the present study was to identify the specific causes of renal allograft loss, to assess their incidence and long-term outcomes. A total of 4783 patients from four French centres, transplanted between January 2004 and January 2014 were prospectively included. A total of 9959 kidney biopsies (protocol and for cause) performed between January 2004 and March 2015 were included. Donor and recipient clinical and biological parameters as well as anti-HLA antibody directed against the donor were included. The main outcome was the long-term kidney allograft survival, including the study of the associated causes of graft loss, the delay of graft loss according to their causes and the determinants of graft loss. There were 732 graft losses during the follow-up period (median time: 4.51 years) with an identified cause in 95.08 %. Kidney allograft survival at 9 years post-transplant was 78 %. The causes of allograft loss were: antibody-mediated rejection (31.69 %), thrombosis (25.55 %), medical intercurrent disease (14.62 %), recurrence of primary renal disease (7.1 %), BK- or CMV-associated nephropathy (n=35, 4.78 %), T cell-mediated rejection (4.78 %), urological disease (2.46 %) and calcineurin inhibitor nephrotoxicity (1.09 %). The main causes of allograft loss were antibody-mediated rejection and thrombosis. These results encourage efforts to prevent and detect these complications earlier in order to improve allograft survival. Copyright © 2018 Association Société de néphrologie. Published by Elsevier Masson SAS. All rights reserved.

Use of capecitabine after renal allograft transplantation in dog erythrocyte antigen-matched dogs.

PubMed

Schmiedt, Chad; Penzo, Chiara; Schwab, Michelle; Dubielzig, Richard; McAnulty, Jonathan

2006-02-01

To investigate the use of a capecitabine (CAP)-based regimen after renal transplantation in dogs. Prospective, pilot study. Healthy, unrelated, dog erythrocyte antigen (DEA)-matched, adult beagles. Standard heterotopic renal transplantation with native nephrectomy was performed in 7 dogs. Dogs received oral, twice daily, CAP (250 mg/m2), cyclosporine-A (CsA) (4 mg/kg), ketoconazole (5 mg/kg), and prednisolone (0.25 mg/kg). After 90 days the surviving dogs were euthanatized and complete necropsy was performed. Seven transplants were performed. All dogs survived surgery. Six dogs had acute neurotoxicity, which resulted in death or euthanasia of 2 dogs within 2 days of surgery. In the remaining dogs, toxicity resolved rapidly with cessation of drug administration. Thereafter, modification of the regimen minimized toxicity. The 5 remaining dogs survived to study end; 4 dogs had no evidence of graft rejection. Necropsy examination was mostly unremarkable in all dogs. There were no major changes in CBC or biochemical values, except for a significant increase in serum calcium. CAP appeared well tolerated in most dogs. Toxicity occurred but abated with modification of the drug regimen. Efficacy for postoperative immunosuppression cannot be determined by this study, although results are promising. CAP-CsA-prednisolone is an effective, oral immunosuppressive regimen for prevention of acute allograft rejection in DEA-matched beagles. Further studies on dose, toxicity, and efficacy compared with current immunosuppressive regimens are needed before use in clinical practice.

Prediction of acute renal allograft rejection in early post-transplantation period by soluble CD30.

PubMed

Dong, Wang; Shunliang, Yang; Weizhen, Wu; Qinghua, Wang; Zhangxin, Zeng; Jianming, Tan; He, Wang

2006-06-01

To evaluate the feasibility of serum sCD30 for prediction of acute graft rejection, we analyzed clinical data of 231 patients, whose serum levels of sCD30 were detected by ELISA before and after transplantation. They were divided into three groups: acute rejection group (AR, n = 49), uncomplicated course group (UC, n = 171) and delayed graft function group (DGF, n = 11). Preoperative sCD30 levels of three groups were 183 +/- 74, 177 +/- 82 and 168 +/- 53 U/ml, respectively (P = 0.82). Significant decrease of sCD30 was detected in three groups on day 5 and 10 post-transplantation respectively (52 +/- 30 and 9 +/- 5 U/ml respectively, P < 0.001). Compared with Group UC and DGF, patients of Group AR had higher sCD30 values on day 5 post-transplantation (92 +/- 27 U/ml vs. 41 +/- 20 U/ml and 48 +/- 18 U/ml, P < 0.001). However, sCD30 levels on day 10 post-transplantation were virtually similar in patients of three groups (P = 0.43). Receiver operating characteristic (ROC) curve demonstrated that sCD30 level on day 5 post-transplantation could differentiate patients who subsequently suffered acute allograft rejection from others (area under ROC curve 0.95). According to ROC curve, 65 U/ml may be the optimal operational cut-off level to predict impending graft rejection (specificity 91.8%, sensitivity 87.1%). Measurement of soluble CD30 on day 5 post-transplantation might offer a noninvasive means to recognize patients at risk of impending acute graft rejection during early post-transplantation period.

Structural and functional correlations in stable renal allografts.

PubMed

Fulladosa, Xavier; Moreso, Francesc; Torras, Joan; Hueso, Miquel; Grinyó, Josep M; Serón, Daniel

2003-05-01

Renal functional reserve (RFR) has been proposed as a surrogate marker of renal mass, but its significance in well-functioning renal transplants is controversial. Thus, we used early protocol biopsies to analyze structural and functional correlations in stable grafts. We studied 32 cyclosporine (CsA)-treated stable cadaveric transplants at 5 months. Biopsies were evaluated according to Banff criteria and histomorphometry. Inulin and p-aminohippurate clearances were used to calculate glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). RFR after an amino acid infusion (RFR-AA) and after a combined amino acid and dopamine infusion (RFR-AA-DOPA) was evaluated. Baseline GFR was 54 +/- 16 mL/min/1.73 m2, and ERPF was 219 +/- 55 mL/min/1.73 m2. RFR-AA was 9% +/- 13%, and RFR-AA-DOPA was 22% +/- 20%. RFR-AA correlated with CsA dose (R = 0.39; P = 0.02), whereas RFR-AA-DOPA correlated with CsA dose (R = 0.36; P = 0.04) and CsA levels (R = 0.40; P = 0.02). The only histological parameter associated with RFR was the presence of arteriolar hyalinosis (AH). Patients showing an AH score of 1 or greater (n = 7) had lower RFR-AA (0% +/- 9% versus 11% +/- 13%; P = 0.02) and lower RFR-AA-DOPA (9% +/- 17% versus 26% +/- 19%; P = 0.03). Multivariate analysis showed that an AH score of 1 or greater, but not CsA dose or levels, was associated with RFR-AA (R = 0.42; P = 0.01). RFR-AA-DOPA was associated with hyaline arteriolar damage (R = 0.43; P = 0.01), as well as CsA levels (R = 0.54; P = 0.006). The presence of AH is the only histological parameter associated with impaired RFR in well-functioning grafts.

High soluble CD30 levels and associated anti-HLA antibodies in patients with failed renal allografts.

PubMed

Karahan, Gonca E; Caliskan, Yasar; Ozdilli, Kursat; Kekik, Cigdem; Bakkaloglu, Huseyin; Caliskan, Bahar; Turkmen, Aydin; Sever, Mehmet S; Oguz, Fatma S

2017-01-13

Serum soluble CD30 (sCD30), a 120-kD glycoprotein that belongs to the tumor necrosis factor receptor family, has been suggested as a marker of rejection in kidney transplant patients. The aim of this study was to evaluate the relationship between sCD30 levels and anti-HLA antibodies, and to compare sCD30 levels in patients undergoing hemodialysis (HD) with and without failed renal allografts and transplant recipients with functioning grafts. 100 patients undergoing HD with failed grafts (group 1), 100 patients undergoing HD who had never undergone transplantation (group 2), and 100 kidney transplant recipients (group 3) were included in this study. Associations of serum sCD30 levels and anti-HLA antibody status were analyzed in these groups. The sCD30 levels of group 1 and group 2 (154 ± 71 U/mL and 103 ± 55 U/mL, respectively) were significantly higher than those of the transplant recipients (group 3) (39 ± 21 U/mL) (p<0.001 and p<0.001). The serum sCD30 levels in group 1 (154 ± 71 U/mL) were also significantly higher than group 2 (103 ± 55 U/mL) (p<0.001). Anti-HLA antibodies were detected in 81 (81%) and 5 (5%) of patients in groups 1 and 2, respectively (p<0.001). When multiple regression analysis was performed to predict sCD30 levels, the independent variables in group 1 were the presence of class I anti-HLA antibodies (β = 0.295; p = 0.003) and age (β = -0.272; p = 0.005), and serum creatinine (β = 0.218; p = 0.027) and presence of class II anti-HLA antibodies (standardized β = 0.194; p = 0.046) in group 3. Higher sCD30 levels and anti-HLA antibodies in patients undergoing HD with failed renal allografts may be related to higher inflammatory status in these patients.

Monocyte-secreted inflammatory cytokines are associated with transplant glomerulopathy in renal allograft recipients.

PubMed

De Serres, Sacha A; Vadivel, Nidyanandh; Mfarrej, Bechara G; Grafals, Monica; DeJoseph, Maura; Dyer, Christine; Magee, Ciara N; Chandraker, Anil; Gallon, Lorenzo G; Najafian, Nader

2011-03-15

Although there is ample evidence about the role of adaptive immunity in the development of chronic allograft dysfunction, little is known about the contribution of innate immunity to this process. Herein, we studied the relationship between inflammation, chronic biopsy scores, and anti-human leukocyte antigen (HLA) circulating alloantibodies in a cohort of 57 patients recruited at our center. Available biopsies (n=27) were graded for chronic lesion scores according to Banff criteria. The production of cytokines by peripheral blood mononuclear cells after 48 hr of culture under resting conditions was quantified by Luminex. Tumor necrosis factor (TNF)-α secretion assay and depletion studies were used to identify the source of these cytokines. There was a high correlation between the levels of interleukin (IL)-1β, IL-6, and TNF-α (r>0.8, P<0.001 for all correlations). The levels of these cytokines were associated with transplant glomerulopathy (IL-1β, P=0.019; IL-6, P=0.015; and TNF-α, P=0.006) but not with other chronic lesions or anti-HLA circulating alloantibodies. TNF-α was predominantly secreted by monocytes (percent of TNF-α secreting cells: 20.4±4.8 vs. 1.2±0.5 vs. 1.4±0.6 vs. 1.7±0.5 for CD14, CD4, CD8, and CD19 cells, respectively; all P<0.01 vs. CD14). The levels of all three proinflammatory cytokines were significantly reduced after monocyte depletion. Intriguingly, cytokine levels increased after ex vivo depletion of regulatory T cells (all P<0.001). Taken together, these data suggest that in vivo-activated monocytes in peripheral blood spontaneously secrete proinflammatory cytokines in renal allograft recipients with transplant glomerulopathy and seem to be under the regulation of functional regulatory T cells in this setting.

Validation of systems biology derived molecular markers of renal donor organ status associated with long term allograft function.

PubMed

Perco, Paul; Heinzel, Andreas; Leierer, Johannes; Schneeberger, Stefan; Bösmüller, Claudia; Oberhuber, Rupert; Wagner, Silvia; Engler, Franziska; Mayer, Gert

2018-05-03

Donor organ quality affects long term outcome after renal transplantation. A variety of prognostic molecular markers is available, yet their validity often remains undetermined. A network-based molecular model reflecting donor kidney status based on transcriptomics data and molecular features reported in scientific literature to be associated with chronic allograft nephropathy was created. Significantly enriched biological processes were identified and representative markers were selected. An independent kidney pre-implantation transcriptomics dataset of 76 organs was used to predict estimated glomerular filtration rate (eGFR) values twelve months after transplantation using available clinical data and marker expression values. The best-performing regression model solely based on the clinical parameters donor age, donor gender, and recipient gender explained 17% of variance in post-transplant eGFR values. The five molecular markers EGF, CD2BP2, RALBP1, SF3B1, and DDX19B representing key molecular processes of the constructed renal donor organ status molecular model in addition to the clinical parameters significantly improved model performance (p-value = 0.0007) explaining around 33% of the variability of eGFR values twelve months after transplantation. Collectively, molecular markers reflecting donor organ status significantly add to prediction of post-transplant renal function when added to the clinical parameters donor age and gender.

Renal Allograft Outcome After Simultaneous Heart and Kidney Transplantation.

PubMed

Grupper, Avishay; Grupper, Ayelet; Daly, Richard C; Pereira, Naveen L; Hathcock, Matthew A; Kremers, Walter K; Cosio, Fernando G; Edwards, Brooks S; Kushwaha, Sudhir S

2017-08-01

Chronic kidney disease frequently accompanies end-stage heart failure and may result in consideration of simultaneous heart and kidney transplantation (SHKT). In recent years, there has been a significant increase in SHKT. This single-center cohort consisted of 35 patients who underwent SHKT during 1996 to 2015. The aim of this study was to review factors that may predict better long-term outcome after SKHT. Thirteen patients (37%) had delayed graft function (DGF) after transplant (defined as the need for dialysis during the first 7 days after transplant), which was significantly associated with mechanical circulatory support device therapy and high right ventricular systolic pressure before transplant. Most of the recipients had glomerular filtration rate (GFR) ≥50 ml/min/1.73 m 2 at 1 and 3 years after transplant (21 of 26 [81%] and 20 of 21 [95%], respectively). Higher donor age was associated with reduced 1-year GFR (p = 0.017), and higher recipient pretransplant body mass index was associated with reduced 3-year GFR (p = 0.008). There was a significant association between DGF and reduced median GFR at 1 and 3 years after transplant (p <0.005). Patient survival rates at 6 months, 1, and 3 years after transplant were 97%, 91%, and 86% respectively. In conclusions, our data support good outcomes after SHKT. Mechanical circulatory support device therapy and pulmonary hypertension before transplant are associated with DGF, which is a risk factor for poor long-term renal allograft function. Copyright © 2017 Elsevier Inc. All rights reserved.

Late-onset renal vein thrombosis: A case report and review of the literature

PubMed Central

Hogan, Jessica L.; Rosenthal, Stanton J.; Yarlagadda, Sri G.; Jones, Jill A.; Schmitt, Timothy M.; Kumer, Sean C.; Kaplan, Bruce; Deas, Shenequa L.; Nawabi, Atta M.

2014-01-01

INTRODUCTION Renal vein thrombosis, a rare complication of renal transplantation, often causes graft loss. Diagnosis includes ultrasound with Doppler, and it is often treated with anticoagulation or mechanical thrombectomy. Success is improved with early diagnosis and institution of treatment. PRESENTATION OF CASE We report here the case of a 29 year-old female with sudden development of very late-onset renal vein thrombosis after simultaneous kidney pancreas transplant. This resolved initially with thrombectomy, stenting and anticoagulation, but thrombosis recurred, necessitating operative intervention. Intraoperatively the renal vein was discovered to be compressed by a large ovarian cyst. DISCUSSION Compression of the renal vein by a lymphocele or hematoma is a known cause of thrombosis, but this is the first documented case of compression and thrombosis due to an ovarian cyst. CONCLUSION Early detection and treatment of renal vein thrombosis is paramount to restoring renal allograft function. Any woman of childbearing age may have thrombosis due to compression by an ovarian cyst, and screening for this possibility may improve long-term graft function in this population. PMID:25528029

Late-onset renal vein thrombosis: A case report and review of the literature.

PubMed

Hogan, Jessica L; Rosenthal, Stanton J; Yarlagadda, Sri G; Jones, Jill A; Schmitt, Timothy M; Kumer, Sean C; Kaplan, Bruce; Deas, Shenequa L; Nawabi, Atta M

2015-01-01

Renal vein thrombosis, a rare complication of renal transplantation, often causes graft loss. Diagnosis includes ultrasound with Doppler, and it is often treated with anticoagulation or mechanical thrombectomy. Success is improved with early diagnosis and institution of treatment. We report here the case of a 29 year-old female with sudden development of very late-onset renal vein thrombosis after simultaneous kidney pancreas transplant. This resolved initially with thrombectomy, stenting and anticoagulation, but thrombosis recurred, necessitating operative intervention. Intraoperatively the renal vein was discovered to be compressed by a large ovarian cyst. Compression of the renal vein by a lymphocele or hematoma is a known cause of thrombosis, but this is the first documented case of compression and thrombosis due to an ovarian cyst. Early detection and treatment of renal vein thrombosis is paramount to restoring renal allograft function. Any woman of childbearing age may have thrombosis due to compression by an ovarian cyst, and screening for this possibility may improve long-term graft function in this population. Published by Elsevier Ltd.

The Spectrum of Renal Allograft Failure

PubMed Central

Chand, Sourabh; Atkinson, David; Collins, Clare; Briggs, David; Ball, Simon; Sharif, Adnan; Skordilis, Kassiani; Vydianath, Bindu; Neil, Desley; Borrows, Richard

2016-01-01

Background Causes of “true” late kidney allograft failure remain unclear as study selection bias and limited follow-up risk incomplete representation of the spectrum. Methods We evaluated all unselected graft failures from 2008–2014 (n = 171; 0–36 years post-transplantation) by contemporary classification of indication biopsies “proximate” to failure, DSA assessment, clinical and biochemical data. Results The spectrum of graft failure changed markedly depending on the timing of allograft failure. Failures within the first year were most commonly attributed to technical failure, acute rejection (with T-cell mediated rejection [TCMR] dominating antibody-mediated rejection [ABMR]). Failures beyond a year were increasingly dominated by ABMR and ‘interstitial fibrosis with tubular atrophy’ without rejection, infection or recurrent disease (“IFTA”). Cases of IFTA associated with inflammation in non-scarred areas (compared with no inflammation or inflammation solely within scarred regions) were more commonly associated with episodes of prior rejection, late rejection and nonadherence, pointing to an alloimmune aetiology. Nonadherence and late rejection were common in ABMR and TCMR, particularly Acute Active ABMR. Acute Active ABMR and nonadherence were associated with younger age, faster functional decline, and less hyalinosis on biopsy. Chronic and Chronic Active ABMR were more commonly associated with Class II DSA. C1q-binding DSA, detected in 33% of ABMR episodes, were associated with shorter time to graft failure. Most non-biopsied patients were DSA-negative (16/21; 76.1%). Finally, twelve losses to recurrent disease were seen (16%). Conclusion This data from an unselected population identifies IFTA alongside ABMR as a very important cause of true late graft failure, with nonadherence-associated TCMR as a phenomenon in some patients. It highlights clinical and immunological characteristics of ABMR subgroups, and should inform clinical practice and

Metabolic syndrome, insulin resistance, and chronic allograft dysfunction.

PubMed

Porrini, Esteban; Delgado, Patricia; Torres, Armando

2010-12-01

Metabolic syndrome (MS) is a cluster of cardiovascular (CV) risk factors (hypertension, dyslipidemia, obesity, and glucose homeostasis alterations), and insulin resistance (IR) is suggested to be a common pathogenic background. In the general population, MS and IR have been proven to be risk factors for diabetes, CV disease, and chronic kidney disease. In the renal transplant setting, few studies have analyzed the relevance of MS and IR. According to the few data available, the prevalence of MS in renal transplant patients has been described as 22.6% at 12 months, 37.7% at 36 months, and 64% at 6 years after transplantation. Importantly, MS has been shown to be an independent risk factor for chronic allograft dysfunction (CAD), graft failure, new-onset diabetes, and CV disease. Also, persistent hyperinsulinemia during the first posttransplant year has been related to an increase in glomerular filtration rate, probably reflecting glomerular hyperfiltration as observed in prediabetes and early type 2 diabetes. Importantly, prediabetes (impaired fasting glucose and impaired glucose tolerance), a state hallmarked by IR, proved to be highly frequent among stable renal transplant recipients (30%), which is nearly three times its incidence in the general population. Posttransplant IR has been associated with subclinical atheromatosis as assessed by carotid intima-media thickness, and with chronic subclinical inflammation. In conclusion, MS and IR are important modifiable risk factors in renal transplant recipients, and prompt interventions to avoid its deleterious effects at the metabolic, CV, and graft function levels are needed.

Evaluation of arteriovenous fistulas and pseudoaneurysms in renal allografts following percutaneous needle biopsy. Color-coded Doppler sonography versus duplex Doppler sonography.

PubMed

Hübsch, P J; Mostbeck, G; Barton, P P; Gritzmann, N; Fruehwald, F X; Schurawitzki, H; Kovarik, J

1990-02-01

One hundred one patients with renal allografts were studied by two independent observers using duplex Doppler sonography (DDS) and color-coded Doppler sonography (CCDS). In all patients, single or multiple percutaneous needle biopsies of the transplant had been performed 1 to 30 days before. In 6 patients CCDS following the biopsy demonstrated an area of combined red and blue color-coded blood flow within the renal parenchyma (n = 5) or within the sinus (n = 1); the Doppler waveform was abnormal in these areas with signals above and below the zero line indicating turbulent blood flow. Consecutive intraarterial digital subtraction angiography (DSA) revealed the presence of an arteriovenous fistula (n = 4) or of a pseudoaneurysm (n = 2). In one patient, gross hematuria with obstruction of the bladder occurred as a complication of a pseudoaneurysm within the renal sinus; the bleeding could not be stopped by embolization of the lesion and the kidney had to be removed. DDS demonstrated the lesion in only one of the six patients. Thus, CCDS is the method of choice for noninvasive detection of vascular lesions due to percutaneous biopsy.

Incidence of C4d stain in protocol biopsies from renal allografts: results from a multicenter trial.

PubMed

Mengel, Michael; Bogers, Johannes; Bosmans, Jean-Louis; Serón, Daniel; Moreso, Francesc; Carrera, Marta; Gwinner, Wilfried; Schwarz, Anke; De Broe, Marc; Kreipe, Hans; Haller, Hermann

2005-05-01

C4d staining of renal allografts is regarded as an in situ marker of active humoral rejection. Few data are available about the incidence of C4d deposition in protocol biopsies compared to indication biopsies. To evaluate whether center-specific factors influence the incidence of C4d detection, we performed a multicenter study. From three European centers, 551 protocol and 377 indication biopsies were reclassified according to the updated Banff criteria and stained for C4d. C4d results were recorded as diffuse or focal positive and statistically correlated to clinical parameters, morphology and graft survival. In the protocol biopsies, a diffuse C4d stain was found in 2.0%, and a focal stain in 2.4%. In indication biopsies, 12.2% were diffusely and 8.5% focally C4d positive (protocol:indication p < 0.0001). The incidence of C4d deposition varied significantly between centers, attributable to variable numbers of presensitized patients with more C4d positive indication and protocol biopsies. Diffuse and focal C4d stain correlated with morphology of humoral rejection in protocol as well as in indication biopsies. Protocol biopsies show a significantly lower incidence of C4d deposition than indication biopsies. Subclinical C4d detection in protocol biopsies had no significant impact on allograft survival in our series.

A Novel Therapy to Attenuate Acute Kidney Injury and Ischemic Allograft Damage after Allogenic Kidney Transplantation in Mice

PubMed Central

Gueler, Faikah; Shushakova, Nelli; Mengel, Michael; Hueper, Katja; Chen, Rongjun; Liu, Xiaokun; Park, Joon-Keun; Haller, Hermann

2015-01-01

Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20–50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells. PMID:25617900

A novel therapy to attenuate acute kidney injury and ischemic allograft damage after allogenic kidney transplantation in mice.

PubMed

Gueler, Faikah; Shushakova, Nelli; Mengel, Michael; Hueper, Katja; Chen, Rongjun; Liu, Xiaokun; Park, Joon-Keun; Haller, Hermann; Wensvoort, Gert; Rong, Song

2015-01-01

Ischemia followed by reperfusion contributes to the initial damage to allografts after kidney transplantation (ktx). In this study we tested the hypothesis that a tetrapeptide EA-230 (AQGV), might improve survival and attenuate loss of kidney function in a mouse model of renal ischemia/reperfusion injury (IRI) and ischemia-induced delayed graft function after allogenic kidney transplantation. IRI was induced in male C57Bl/6N mice by transient bilateral renal pedicle clamping for 35 min. Treatment with EA-230 (20-50mg/kg twice daily i.p. for four consecutive days) was initiated 24 hours after IRI when acute kidney injury (AKI) was already established. The treatment resulted in markedly improved survival in a dose dependent manner. Acute tubular injury two days after IRI was diminished and tubular epithelial cell proliferation was significantly enhanced by EA-230 treatment. Furthermore, CTGF up-regulation, a marker of post-ischemic fibrosis, at four weeks after IRI was significantly less in EA-230 treated renal tissue. To learn more about these effects, we measured renal blood flow (RBF) and glomerular filtration rate (GFR) at 28 hours after IRI. EA-230 improved both GFR and RBF significantly. Next, EA-230 treatment was tested in a model of ischemia-induced delayed graft function after allogenic kidney transplantation. The recipients were treated with EA-230 (50 mg/kg) twice daily i.p. which improved renal function and allograft survival by attenuating ischemic allograft damage. In conclusion, EA-230 is a novel and promising therapeutic agent for treating acute kidney injury and preventing IRI-induced post-transplant ischemic allograft injury. Its beneficial effect is associated with improved renal perfusion after IRI and enhanced regeneration of tubular epithelial cells.

Elevated alanine aminotransferase (ALT) in the deceased donor: impact on early post-transplant liver allograft function.

PubMed

Mangus, Richard S; Fridell, Jonathan A; Kubal, Chandrashekhar A; Davis, Jason P; Tector, A Joseph

2015-02-01

Serum alanine aminotransferase (ALT) levels are frequently elevated with liver injury and such elevations are common in deceased organ donors. The impact of this injury on early liver allograft function has not been well described. This study analyses the immediate function and 1-year graft and patient survival for liver allografts stratified by peak serum ALT levels in the deceased donor. The on-site organ procurement records for 1348 consecutive deceased liver donors were reviewed (2001–2011). Serum ALT was categorized into three study groups: normal/mild elevation, 0–499 μ/L; moderate elevation, 500–999 μ/L (>10× upper limit of normal) and severe elevation, ≥1000 μ/L (>20× upper limit of normal). Outcomes included early graft function and graft loss, and 1-year graft and patient survival. Distribution of subjects included: normal/mild, 1259 (93%); moderate, 34 (3%) and severe, 55 (4%). Risk of 30-day graft loss for the three study groups was: 72 (6%), 3 (9%) and 3 (6%) (P = 0.74). Graft and patient survival at 1 year for the three groups was: normal/mild, 1031 (87%), 1048 (88%); moderate, 31 (91%), 31 (91%) and severe, 43 (88%), 44 (90%) (P = 0.71, 0.79). Cox proportional hazards modelling of survival while controlling for donor age and recipient model for end-stage liver disease score (MELD) demonstrates no statistically significant difference among the three study groups. This study demonstrates clinical equivalence in early graft function and 1-year graft and patient survival for donor livers with varying peak levels of serum ALT. These donor allografts may, therefore, be utilized successfully.

Serum Uromodulin: A Biomarker of Long-Term Kidney Allograft Failure.

PubMed

Bostom, Andrew; Steubl, Dominik; Garimella, Pranav S; Franceschini, Nora; Roberts, Mary B; Pasch, Andreas; Ix, Joachim H; Tuttle, Katherine R; Ivanova, Anastasia; Shireman, Theresa; Kim, S Joseph; Gohh, Reginald; Weiner, Daniel E; Levey, Andrew S; Hsu, Chi-Yuan; Kusek, John W; Eaton, Charles B

2018-01-01

Uromodulin is a kidney-derived glycoprotein and putative tubular function index. Lower serum uromodulin was recently associated with increased risk for kidney allograft failure in a preliminary, longitudinal single-center -European study involving 91 kidney transplant recipients (KTRs). The Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial is a completed, large, multiethnic controlled clinical trial cohort, which studied chronic, stable KTRs. We conducted a case cohort analysis using a randomly selected subset of patients (random subcohort, n = 433), and all individuals who developed kidney allograft failure (cases, n = 226) during follow-up. Serum uromodulin was determined in this total of n = 613 FAVORIT trial participants at randomization. Death-censored kidney allograft failure was the study outcome. The 226 kidney allograft failures occurred during a median surveillance of 3.2 years. Unadjusted, weighted Cox proportional hazards modeling revealed that lower serum uromodulin, tertile 1 vs. tertile 3, was associated with a threefold greater risk for kidney allograft failure (hazards ratio [HR], 95% CI 3.20 [2.05-5.01]). This association was attenuated but persisted at twofold greater risk for allograft failure, after adjustment for age, sex, smoking, allograft type and vintage, prevalent diabetes mellitus and cardiovascular disease (CVD), total/high-density lipoprotein cholesterol ratio, systolic blood pressure, estimated glomerular filtration rate, and natural log urinary albumin/creatinine: HR 2.00, 95% CI (1.06-3.77). Lower serum uromodulin, a possible indicator of less well-preserved renal tubular function, remained associated with greater risk for kidney allograft failure, after adjustment for major, established clinical kidney allograft failure and CVD risk factors, in a large, multiethnic cohort of long-term, stable KTRs. © 2018 S. Karger AG, Basel.

Renal transplantation: a twenty-five year experience.

PubMed Central

Murray, J E; Tilney, N L; Wilson, R E

1976-01-01

Boston has played a significant role in the development of renal transplantation. In Boston was performed the first successful isograft between identical twins (1954) the first successful allograft between fraternal twins (1959) and the first successful allograft from a cadaveric donor (1962). An immunosuppressive drug was also described in Boston by hematologists Schwartz and Dameschek (1959) and modified for renal transplantation in dogs (1961) and used for the first time in a human recipient in March 1962. By 1965 renal transplantation had become a clinical reality. Three hundred and ninety-eight of 589 recipients (68%) since 1950 are still alive, a remarkable figure considering that it includes all the earliest experimental transplants. One hundred and ninety-five of 295 (68%) with living-related donor transplants still have functioning allografts; 104/265 (39%) with cadaveric donor transplants have functioning grafts currently. Since 1968 transplants from living-related donors have an 80% one year survival whereas cadaveric donor transplants have approximately a 50% one year survival. Seventy-nine per cent of all one year survivors have had excellent psycho-social rehabilitation. PMID:791162

[Estimation of soluble serum CD30 in the diagnosis of early renal allograft dysfunction].

PubMed

Trailin, A V

2009-10-01

We aimed to reveal factors influencing serum soluble CD30 level in the recipients of kidney allograft and to estimate its pathogenetic significance. We tested the sCD30 level in the serum before and the 4th day after operation by ELISA. It was established, thats CD30 levels before transplantation were virtually the same in patients who experienced rejection and in non-rejecting patients. However, there was a significant decrease in the level of sCD30 after transplantation in non-rejecting patients, contrary to rejecting patients. A significant decrease of sCD30 level was detected on the day 4th after the transplantation independently of dialysis requirement. The decrease of sCD30 on the day 4th after operation in the patients with delayed graft function and its stability in the patients with acute rejection may be used distinguish these complications.

Detection and measurement of tubulitis in renal allograft rejection

NASA Astrophysics Data System (ADS)

Hiller, John B.; Chen, Qi; Jin, Jesse S.; Wang, Yung; Yong, James L. C.

1997-04-01

Tubulitis is one of the most reliable signs of acute renal allograft rejection. It occurs when mononuclear cells are localized between the lining tubular epithelial cells with or without disruption of the tubular basement membrane. It has been found that tubulitis takes place predominantly in the regions of the distal convoluted tubules and the cortical collecting system. The image processing tasks are to find the tubule boundaries and to find the relative location of the lymphocytes and epithelial cells and tubule boundaries. The requirement for accuracy applies to determining the relative locations of the lymphocytes and the tubule boundaries. This paper will show how the different sizes and grey values of the lymphocytes and epithelial cells simplify their identification and location. Difficulties in finding the tubule boundaries image processing will be illustrated. It will be shown how proximate location of epithelial cells and the tubule boundary leads to distortion in determination of the calculated boundary. However, in tubulitis the lymphocytes and the tubule boundaries are proximate.In these cases the tubule boundary is adequately resolved and the image processing is satisfactory to determining relativity in location. An adaptive non-linear anisotropic diffusion process is presented for image filtering and segmentation. Multi-layer analysis is used to extract lymphocytes and tubulitis from images. This paper will discuss grading of tissue using the Banff system. The ability to use computer to use computer processing will be argued as obviating problems of reproducability of values for this classification. This paper will also feature discussion of alternative approaches to image processing and provide an assessment of their capability for improving the identification of the tubule boundaries.

[The role of percutaneous renal biopsy in kidney transplant].

PubMed

Manfro, R C; Lee, J Y; Lewgoy, J; Edelweiss, M I; Gonçalves, L F; Prompt, C A

1994-01-01

Percutaneous renal biopsy (PRB) is an useful tool for diagnostic and therapeutic orientation in renal transplantation. PURPOSE--To evaluate the current role of PRB in post-transplant acute renal dysfunction (ARD) of renal allografts. METHODS--Sixty-five renal transplant patients were submitted to 95 valid renal biopsies with no major complications. RESULTS--There was disagreement between the clinical and the pathological diagnosis in 28 occasions (29.5%). In 36 cases (37.9%) the results of the pathological examination led to a modification in patient's management. These modifications were most commonly the avoidance or witholding of a steroid pulse (8 cases); nephrectomy of the renal allograft (8 cases); witholding or decrease of cyclosporine dosage (6 cases); giving a steroid pulse (5 cases) and giving antibiotics to treat acute pyelonephritis in 4 cases. The use of kidneys from cadaveric donors was significantly associated with an increased number of biopsies (p < 0.05). CONCLUSION--These results demonstrate that even though several less invasive procedures are currently employed, renal biopsy is still an indispensable method to the management of ARD in renal transplant patients.

Kidney versus Islet Allograft Survival after Induction of Mixed Chimerism with Combined Donor Bone Marrow Transplantation

PubMed Central

Oura, Tetsu; Ko, Dicken S.C.; Boskovic, Svjetlan; O'Neil, John J.; Chipashvili, Vaja; Koulmanda, Maria; Hotta, Kiyohiko; Kawai, Kento; Nadazdin, Ognjenka; Smith, R. Neal; Cosimi, A. B.; Kawai, Tatsuo

2016-01-01

Background We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC-mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. Methods A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that includes low dose total body and thymic irradiation, horse ATG (Atgam), six doses of anti-CD154 monoclonal antibody (mAb) and a one month course of cyclosporine (CyA) (Islet-A). In Islet-B, anti-CD8 mAb was administered in place of CyA. In Islet-C, two recipients were treated with Islet-B but without Atgam. The results were compared with previously reported results of eight cynomolgus monkeys that received combined kidney and bone marrow transplantation (Kidney-A) following the same conditioning regimen used in Islet-A. Results The majority of Kidney/BM recipients achieved long-term renal allograft survival after induction of transient chimerism. However, prolonged islet survival was not achieved in similarly conditioned Islet/BM recipients (Islet-A), despite induction of comparable levels of chimerism. In order to rule out islet allograft loss due to calcineurin inhibitor (CNI) toxicity, three recipients were treated with anti-CD8 mAb in place of CNI. Although these recipients developed significantly superior mixed chimerism and more prolonged islet allograft survival (61, 103, and 113 days), islet function was lost soon after the disappearance of chimerism. In Islet-C recipients, neither prolonged chimerism nor islet survival was observed (30 and 40 days). Conclusion Significant improvement of mixed chimerism induction and islet allograft survival were achieved with a CNI-free regimen that includes anti-CD8 mAb. However, unlike the kidney allograft, islet allograft

Kidney Versus Islet Allograft Survival After Induction of Mixed Chimerism With Combined Donor Bone Marrow Transplantation.

PubMed

Oura, Tetsu; Ko, Dicken S C; Boskovic, Svjetlan; O'Neil, John J; Chipashvili, Vaja; Koulmanda, Maria; Hotta, Kiyohiko; Kawai, Kento; Nadazdin, Ognjenka; Smith, R Neal; Cosimi, A B; Kawai, Tatsuo

2016-01-01

We have previously reported successful induction of transient mixed chimerism and long-term acceptance of renal allografts in MHC mismatched nonhuman primates. In this study, we attempted to extend this tolerance induction approach to islet allografts. A total of eight recipients underwent MHC mismatched combined islet and bone marrow (BM) transplantation after induction of diabetes by streptozotocin. Three recipients were treated after a nonmyeloablative conditioning regimen that included low-dose total body and thymic irradiation, horse Atgam (ATG), six doses of anti-CD154 monoclonal antibody (mAb), and a 1-month course of cyclosporine (CyA) (Islet A). In Islet B, anti-CD8 mAb was administered in place of CyA. In Islet C, two recipients were treated with Islet B, but without ATG. The results were compared with previously reported results of eight cynomolgus monkeys that received combined kidney and BM transplantation (Kidney A) following the same conditioning regimen used in Islet A. The majority of kidney/BM recipients achieved long-term renal allograft survival after induction of transient chimerism. However, prolonged islet survival was not achieved in similarly conditioned islet/BM recipients (Islet A), despite induction of comparable levels of chimerism. In order to rule out islet allograft loss due to CyA toxicity, three recipients were treated with anti-CD8 mAb in place of CyA. Although these recipients developed significantly superior mixed chimerism and more prolonged islet allograft survival (61, 103, and 113 days), islet function was lost soon after the disappearance of chimerism. In Islet C recipients, neither prolonged chimerism nor islet survival was observed (30 and 40 days). Significant improvement of mixed chimerism induction and islet allograft survival were achieved with a CyA-free regimen that included anti-CD8 mAb. However, unlike the kidney allograft, islet allograft tolerance was not induced with transient chimerism. Induction of more

Histologic findings in protocol biopsies performed in stable renal allografts under different immunosuppressive schedules.

PubMed

Moreso, F; Alperovich, G; Fulladosa, X; Gil-Vernet, S; Ibernon, M; Carrera, M; Castelao, A M; Hueso, M; Grinyo, J M; Serón, D

2003-08-01

Protocol biopsies performed in stable renal allografts show different degrees of acute and chronic lesions. Histologic findings in protocol biopsies have been related to graft outcome. We evaluated histologic lesions observed in protocol biopsies performed in patients under different immunosuppression therapies. From June 1988 a protocol biopsy was performed at approximately 4 months in patients who fulfilled the following criteria: serum creatinine <300 micromol/L; stable renal function; and proteinuria <1 g/d. Histologic lesions were graded according to 1997 Banff criteria. For the present study we considered the following groups according to immunosuppressive schedule: (i) induction therapy with polyclonal or monoclonal antilymphocytic antibodies associated with cyclosporine and prednisone (n=201); (ii) cyclosporine, mycophenolate mofetil, and prednisone (n=127); and (iii) tacrolimus, mycophenolate mofetil, and prednisone (n=51). On protocol biopsy patients treated with tacrolimus displayed a lower acute score (0.61+/-1.01 vs 1.24+/-1.23 in group I, 1.28+/-1.41 in group II; P<.0001) and a higher proportion of normal biopsies (57.1% vs 41.9% in group I, 45.1% in group II; P=.016). A similar proportion of chronic lesions (chronic score of group I: 1.30+/-1.56; group II: 1.34+/-1.80; group III: 1.51+/-0.95; P=NS) was observed in the three groups. Protocol biopsies displayed fewer acute lesions in patients treated with tacrolimus. This result suggests that the efficacy of new immunosuppression schedules can be evaluated using the protocol biopsy as a surrogate marker of graft outcome.

Acute allograft failure in thoracic organ transplantation.

PubMed

Jahania, M S; Mullett, T W; Sanchez, J A; Narayan, P; Lasley, R D; Mentzer, R M

2000-01-01

Thoracic organ transplantation is an effective form of treatment for end-stage heart and lung disease. Despite major advances in the field, transplant patients remain at risk for acute allograft dysfunction, a major cause of early and late mortality. The most common causes of allograft failure include primary graft failure secondary to inadequate heart and lung preservation during cold storage, cellular rejection, and various donor-recipient-related factors. During cold storage and early reperfusion, heart and lung allografts are vulnerable to intracellular calcium overload, acidosis, cell swelling, injury mediated by reactive oxygen species, and the inflammatory response. Brain death itself is associated with a reduction in myocardial contractility, and recipient-related factors such as preexisting pulmonary hypertension can lead to acute right heart failure and the pulmonary reimplantation response. The development of new methods to prevent or treat these various causes of acute graft failure could lead to a marked improvement in short- and long-term survival of patients undergoing thoracic organ transplantation.

Mortality after Renal Allograft Failure and Return to Dialysis.

PubMed

Brar, Amarpali; Markell, Mariana; Stefanov, Dimitre G; Timpo, Edem; Jindal, Rahul M; Nee, Robert; Sumrani, Nabil; John, Devon; Tedla, Fasika; Salifu, Moro O

2017-01-01

The outcomes of patients who fail their kidney transplant and return to dialysis (RTD) has not been investigated in a nationally representative sample. We hypothesized that variations in management of transplant chronic kidney disease stage 5 leading to kidney allograft failure (KAF) and RTD, such as access, nutrition, timing of dialysis, and anemia management predict long-term survival. We used an incident cohort of patients from the United States Renal Data System who initiated hemodialysis between January 1, 2003 and December 31, 2008, after KAF. We used Cox regression analysis for statistical associations, with mortality as the primary outcome. We identified 5,077 RTD patients and followed them for a mean of 30.9 ± 22.6 months. Adjusting for all possible confounders at the time of RTD, the adjusted hazards ratio (AHR) for death was increased with lack of arteriovenous fistula at initiation of dialysis (AHR 1.22, 95% CI 1.02-1.46, p = 0.03), albumin <3.5 g/dL (AHR 1.33, 95% CI 1.18-1.49, p = 0.0001), and being underweight (AHR 1.30, 95% CI 1.07-1.58, p = 0.006). Hemoglobin <10 g/dL (AHR 0.96, 95% CI 0.86-1.06, p = 0.46), type of insurance, and zip code-based median household income were not associated with higher mortality. Glomerular filtration rate <10 mL/min/1.73 m2 at time of dialysis initiation (AHR 0.83, 95% CI 0.75-0.93, p = 0.001) was associated with reduction in mortality. Excess mortality risk observed in patients starting dialysis after KAF is multifactorial, including nutritional issues and vascular access. Adequate preparation of patients with failing kidney transplants prior to resuming dialysis may improve outcomes. © 2017 S. Karger AG, Basel.

Estimation of renal allograft half-life: fact or fiction?

PubMed

Azancot, M Antonieta; Cantarell, Carme; Perelló, Manel; Torres, Irina B; Serón, Daniel; Seron, Daniel; Moreso, Francesc; Arias, Manuel; Campistol, Josep M; Curto, Jordi; Hernandez, Domingo; Morales, José M; Sanchez-Fructuoso, Ana; Abraira, Victor

2011-09-01

Renal allograft half-life time (t½) is the most straightforward representation of long-term graft survival. Since some statistical models overestimate this parameter, we compare different approaches to evaluate t½. Patients with a 1-year functioning graft transplanted in Spain during 1990, 1994, 1998 and 2002 were included. Exponential, Weibull, gamma, lognormal and log-logistic models censoring the last year of follow-up were evaluated. The goodness of fit of these models was evaluated according to the Cox-Snell residuals and the Akaike's information criterion (AIC) was employed to compare these models. We included 4842 patients. Real t½ in 1990 was 14.2 years. Median t½ (95% confidence interval) in 1990 and 2002 was 15.8 (14.2-17.5) versus 52.6 (35.6-69.5) according to the exponential model (P < 0.001). No differences between 1990 and 2002 were observed when t½ was estimated with the other models. In 1990 and 2002, t½ was 14.0 (13.1-15.0) versus 18.0 (13.7-22.4) according to Weibull, 15.5 (13.9-17.1) versus 19.1 (15.6-22.6) according to gamma, 14.4 (13.3-15.6) versus 18.3 (14.2-22.3) according to the log-logistic and 15.2 (13.8-16.6) versus 18.8 (15.3-22.3) according to the lognormal models. The AIC confirmed that the exponential model had the lowest goodness of fit, while the other models yielded a similar result. The exponential model overestimates t½, especially in cohorts of patients with a short follow-up, while any of the other studied models allow a better estimation even in cohorts with short follow-up.

Antibody-Mediated Rejection of Single Class I MHC-Disparate Cardiac Allografts

PubMed Central

Hattori, Yusuke; Bucy, R. Pat; Kubota, Yoshinobu; Baldwin, William M.; Fairchild, Robert L.

2012-01-01

Murine CCR5−/− recipients produce high titers of antibody to complete MHC-mismatched heart and renal allografts. To study mechanisms of class I MHC antibody-mediated allograft injury, we tested the rejection of heart allografts transgenically expressing a single class I MHC disparity in wild-type C57BL/6 (H-2b) and B6.CCR5−/− recipients. Donor-specific antibody titers in CCR5−/− recipients were 30-fold higher than in wild-type recipients. B6.Kd allografts survived longer than 60 days in wild-type recipients whereas CCR5−/− recipients rejected all allografts within 14 days. Rejection was accompanied by infiltration of CD8 T cells, neutrophils, and macrophages and C4d deposition in the graft capillaries. B6.Kd allografts were rejected by CD8−/−/CCR5−/−, but not μMT−/−/CCR5−/−, recipients indicating the need for antibody but not CD8 T cells. Grafts retrieved at day 10 from CCR5−/− and CD8−/−/CCR5−/− recipients and from RAG-1−/− allograft recipients injected with anti-Kd antibodies expressed high levels of perforin, myeloperoxidase and CCL5 mRNA. These studies indicate that the continual production of anti-donor class I MHC antibody can mediate allograft rejection, that donor-reactive CD8 T cells synergize with the antibody to contribute to rejection, and that expression of three biomarkers during rejection can occur in the absence of this CD8 T cell activity. PMID:22578247

Use of cultured human epidermal keratinocytes for allografting burns and conditions for temporary banking of the cultured allografts.

PubMed

Bolívar-Flores, J; Poumian, E; Marsch-Moreno, M; Montes de Oca, G; Kuri-Harcuch, W

1990-02-01

Five children who suffered burns clinically regarded as full skin thickness loss were grafted with cultured allogeneic skin from newborn prepuce. The wounds had remained open and infected without healing for about 20 days before the patients were received in the burn unit. To avoid losing surviving deep epidermal cells the wounds were débrided but not deeply excised and, a few days before allografting, they were washed with isodine solution and sterile water, and treated with silvadene cream application. All children received 76 cultured allografts of about 60 cm2 each. After allografting, the wounds were epithelized in 7-10 days and the allogeneic grafted skin began desquamation suggesting that the allograft did not 'take' permanently but was replaced by the newly formed skin. On the other hand, since allografting is an adequate therapy to provide early temporary coverage in extensively burned patients, we developed conditions for banking cultured skin to make it available for immediate use. The conditions described allow banking of the cultured grafts for 15-20 days with retention of clonal growth ability similar to that of unstored epithelia. The results show that cultured epidermal cells obtained from human newborn foreskin, when used as allografts for coverage of full skin or deep partial skin thickness burns, allow rapid epithelization of the burn wounds.

Intra-arterial nitroglycerin for intra-operative arterial vasospasm during pediatric renal transplantation.

PubMed

Penna, Frank J; Harvey, Elizabeth; John, Philip; Armstrong, Derek; Luginbuehl, Igor; Odeh, Rakan I; Alyami, Fahad; Koyle, Martin A; Lorenzo, Armando J

2016-05-01

Intra-operative arterial vasospasm during pediatric renal transplantation is an urgent clinical situation resulting in end-organ ischemia, associated changes in parenchymal turgor and color, diminished flow on ultrasound, and if left untreated, allograft loss. We hypothesized that intra-operative intra-arterial injection of nitroglycerin would reverse vasospasm and improve renal perfusion. A three-yr-old girl with end-stage renal disease due to autosomal recessive polycystic kidney disease on peritoneal dialysis underwent deceased donor renal transplantation. After optimal immediate reperfusion and hemodynamic parameters, the kidney lost turgor and became mottled in appearance despite adequate hilar arterial and venous Doppler waveforms. Two aliquots of 40 μg (0.4 mL of a 100 μg/mL) nitroglycerin solution were injected directly into the renal artery 10 min apart. Nitroglycerin resulted in dramatic change in the consistency and appearance of the allograft. An improvement in renal blood flow was demonstrated by ultrasound after the second intra-arterial nitroglycerin injection with only a transient decrease in systemic arterial blood pressure. The child experienced normal allograft perfusion on serial postoperative ultrasounds, with a prompt decrease in serum creatinine and excellent diuresis. Intra-arterial nitroglycerin is a promising option for intra-operative arterial vasospasm during pediatric renal transplantation with objective improvement in blood flow and perfusion. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Serum and Urinary Levels of Tumor Necrosis Factor-Alpha in Renal Transplant Patients.

PubMed

Senturk Ciftci, Hayriye; Demir, Erol; Savran Karadeniz, Meltem; Tefik, Tzevat; Yazici, Halil; Nane, Ismet; Savran Oguz, Fatma; Aydin, Filiz; Turkmen, Aydin

2017-12-18

Allograft rejection is an important cause of early and long-term graft loss in kidney transplant recipients. Tumor necrosis factor-alpha promotes T-cell activation, the key reaction leading to allograft rejection. Here, we investigated whether serum and urinary tumor necrosis factor-alpha levels can predict allograft rejection. This study included 65 living related-donor renal transplant recipients with mean follow-up of 26 ± 9 months. Serum and urinary tumor necrosis factor-alpha levels were measured at pretransplant and at posttransplant time points (days 1 and 7 and months 3 and 6); serum creatinine levels were also monitored during posttransplant follow-up. Standard enzyme-linked immunoabsorbent assay was used to detect tumor necrosis factor-alpha levels. Clinical variables were monitored. Nine of 65 patients (13.8%) had biopsy-proven rejection during follow-up. Preoperative serum and urinary tumor necrosis factor-alpha levels were not significantly different when we compared patients with and without rejection. Serum tumor necrosis factor-alpha levels (in pg/mL) were significantly higher in the allograft rejection versus nonrejection group at day 7 (11.5 ± 4.7 vs 15.4 ± 5.8; P = .029) and month 1 (11.1 ± 4.8 vs 17.8 ± 10.9; P =.003). Urinary tumor necrosis factor-alpha levels (in pg/mL) were also elevated in the allograft rejection versus the nonrejection group at days 1 (10.2 ± 2.5 vs 14.1 ± 6.8; P = .002) and 7 (9.8 ± 2.2 vs 14.5 ± 2.7; P < .001) and at months 1 (8.0 ± 1.7 vs 11.8 ± 2.4; P < .001), 3 (7.7 ± 1.6 vs 9.6 ± 1.7; P = .002), and 6 (7.4 ± 1.6 vs 8.9 ± 0.9; P = .005). Our preliminary findings suggest that tumor necrosis factor-alpha has a role in diagnosing renal transplant rejection. Serum and urinary tumor necrosis factor-alpha levels may be a possible predictor for allograft rejection.

Association of vitamin D binding protein polymorphism with long-term kidney allograft survival in Hispanic kidney transplant recipients.

PubMed

Vu, Don; Sakharkar, Prashant; Tellez-Corrales, Eglis; Shah, Tariq; Hutchinson, Ian; Min, David I

2013-02-01

Polymorphism of genes encoding components of the vitamin D pathway including vitamin D receptor (VDR) and vitamin D binding protein (VDBP), have been widely explored due to the complex role played by vitamin D in renal transplant outcomes. In this study, we investigated whether polymorphisms of genes encoding VDR and VDBP were associated with allograft survival or acute rejection (AR) among a Hispanic kidney transplant population. A total of 502 Hispanic renal allograft recipients at the St. Vincent Medical Center between 2001 and 2010 were genotyped for four different single nucleotide polymorphisms of VDR: FokI C>T (rs2228570), BsmI G>A (rs1544410), ApaI T>G (rs7975232), and TaqI T>C (rs731236). We also performed genotyping for one common polymorphism in the VDBP gene (rs4588). Survival was significantly improved for patients who were homozygous GG for the rs4588 G>T allele in the VDBP gene (GG vs. GT + TT, OR = 0.63, p = 0.02) while GT genotype was associated with a higher risk of graft loss (GT vs. GG + TT, OR = 1.67, p = 0.01). We found no association for polymorphic markers in VDR with allograft survival and AR. The frequency of the haplotype GTCG (in the order of VDR FokI C>T, BsmI G>A, ApaI T>G, and TaqI T>C), was significantly different in the patients with graft rejection compared to the control (p = 0.007) while ACCA haplotype was found to be associated with graft loss (p = 0.02). Hence, the VDBP G>T polymorphism (rs4588) and two haplotypes (GTCG and ACCA) of VDR appear to be associated with renal allograft outcomes among Hispanic allograft recipients.

Male kidney allograft recipients at risk for urinary tract infection?

PubMed Central

Schuette-Nuetgen, Katharina; Vogl, Thomas; Dobrindt, Ulrich; Kahl, Barbara C.; Brand, Marcus; Pavenstädt, Hermann; Suwelack, Barbara

2017-01-01

Background Urinary tract infection (UTI) is the most common infection after renal transplantation (RTx). Although female sex is a well-known risk factor for the development of UTI after RTx, the role of the donor sex in this context remains unclear. Methods In this case control study 6,763 RTx cases were screened for UTI when presenting at our transplant outpatient clinics. 102 different RTx patients fulfilled the inclusion criteria and were compared to 102 controls. Data on renal function was prospectively followed for 12 months. Results were compared to a previous RTx cohort from our transplant center. Additionally, we assessed the immunological response of leukocytes from 58 kidney recipients and 16 controls to lipopolysaccharide stimulation. Result After identification by univariate analysis, multivariate logistic regression analysis indicated female sex, minor height, advanced age and male kidney allograft sex to be associated with the occurrence of UTI after RTx. Female recipients who received male grafts had the best renal function 12 months after presentation. However, leukocyte response of recipients to lipopolysaccharide was impaired irrespective of donor and recipient sex to the same extend. Conclusions We conclude from our data that male kidney allografts are associated with the occurrence of UTI after RTx but did not influence the response of leukocytes to lipopolysaccharide. Further prospective studies are needed to identify the underlying mechanisms of higher male kidney donor dependent UTI. PMID:29145515

Should fractures in massive intercalary bone allografts of the lower limb be treated with ORIF or with a new allograft?

PubMed

Aponte-Tinao, Luis A; Ayerza, Miguel A; Muscolo, D Luis; Farfalli, Germán L

2015-03-01

Massive bone allografts have been used for limb salvage of bone tumor resections as an alternative to endoprostheses, although they have different outcomes and risks. There is no general consensus about when to use these alternatives, but when it is possible to save the native joints after the resection of a long bone tumor, intercalary allografts offer some advantages despite complications, such as fracture. The management and outcomes of this complication deserve more study. The purposes of this study were to (1) analyze the fracture frequency in a group of patients treated with massive intercalary bone allografts of the femur and tibia; (2) compare the results of allografts treated with open reduction and internal fixation (ORIF) with those treated with resection and repeat allograft reconstruction; and (3) determine the likelihood that treatment of a fracture resulted in a healed intercalary reconstruction. We reviewed patients treated with intercalary bone allografts between 1991 and 2011. During this period, patients were generally treated with intercalary allografts when after tumor resection at least 1 cm of residual epiphysis remained to allow fixation of the osteotomy junction. To obtain a homogeneous group of patients, we excluded allograft-prosthesis composites and osteoarticular and hemicylindrical intercalary allografts from this study. We analyzed the fracture rate of 135 patients reconstructed with segmental intercalary bone allografts of the lower extremities (98 femurs and 37 tibias). In patients whose grafts fractured were treated either by internal fixation or a second allograft, ORIF generally was attempted but after early failures in femur fractures, these fractures were treated with a second allograft. Using a chart review, we ascertained the frequency of osseous union, complications, and reoperations after the treatment of fractured intercalary allografts. Followup was at a mean of 101 months (range, 24-260 months); of the original 135

Erythropoietin, but not the correction of anemia alone, protects from chronic kidney allograft injury.

PubMed

Cassis, Paola; Gallon, Lorenzo; Benigni, Ariela; Mister, Marilena; Pezzotta, Anna; Solini, Samantha; Gagliardini, Elena; Cugini, Daniela; Abbate, Mauro; Aiello, Sistiana; Rocchetta, Federica; Scudeletti, Pierangela; Perico, Norberto; Noris, Marina; Remuzzi, Giuseppe

2012-05-01

Anemia can contribute to chronic allograft injury by limiting oxygen delivery to tissues, particularly in the tubulointerstitium. To determine mechanisms by which erythropoietin (EPO) prevents chronic allograft injury we utilized a rat model of full MHC-mismatched kidney transplantation (Wistar Furth donor and Lewis recipients) with removal of the native kidneys. EPO treatment entirely corrected post-transplant anemia. Control rats developed progressive proteinuria and graft dysfunction, tubulointerstitial damage, inflammatory cell infiltration, and glomerulosclerosis, all prevented by EPO. Normalization of post-transplant hemoglobin levels by blood transfusions, however, had no impact on chronic allograft injury, indicating that EPO-mediated graft protection went beyond the correction of anemia. Compared to syngeneic grafts, control allografts had loss of peritubular capillaries, higher tubular apoptosis, tubular and glomerular oxidative injury, and reduced expression of podocyte nephrin; all prevented by EPO treatment. The effects of EPO were associated with preservation of intragraft expression of angiogenic factors, upregulation of the anti-apoptotic factor p-Akt in tubuli, and increased expression of Bcl-2. Inhibition of p-Akt by Wortmannin partially antagonized the effect of EPO on allograft injury and tubular apoptosis, and prevented EPO-induced Bcl-2 upregulation. Thus non-erythropoietic derivatives of EPO may be useful to prevent chronic renal allograft injury.

CMV mismatch does not affect patient and graft survival in UK renal transplant recipients.

PubMed

Johnson, Rachel J; Clatworthy, Menna R; Birch, Rhiannon; Hammad, Abdul; Bradley, J Andrew

2009-07-15

Cytomegalovirus (CMV) is one of the major infections encountered posttransplantation. UK Guidelines (2003) recommend CMV prophylaxis or screening with preemptive treatment for all high risk recipients. Studies predating the widespread use of CMV prophylaxis have shown that CMV seronegative recipients (R-) receiving a renal allograft from a CMV seropositive donor (D+) have worse outcomes than those avoiding primary CMV infection. Therefore, it has been suggested that CMV matching should be a part of the UK national deceased donor kidney allocation scheme. We examined patient and allograft survival according to donor and recipient CMV serostatus in 10,190 UK adult and pediatric deceased donor renal transplant recipients transplanted between 2000 and 2007. We also ascertained CMV prophylaxis strategies in all UK renal transplant units. Twenty-one of the 22 UK renal transplant centers used prophylactic oral valganciclovir for 3 months posttransplant in the D+R- transplants, having done so for a median of 4 years. Unadjusted data showed that D+R+ rather than D+R- transplants had the lowest patient and allograft survivals at 3 years posttransplant. However, after adjustment for donor age, there was no significant effect of donor and recipient CMV serostatus on allograft or patient survival. These findings suggest that in an era where CMV prophylaxis is used routinely in D+R- transplants, the previously noted adverse effects of primary CMV infection on allograft and patient survival can be avoided (perhaps through a reduction in the incidence and/or severity of primary CMV infection), without using a CMV-matching allocation scheme.

History of osteochondral allograft transplantation.

PubMed

Nikolaou, V S; Giannoudis, P V

2017-07-01

Osteochondral defects or injuries represent the most challenging entities to treat, especially when occur to young and active patients. For centuries, it has been recognized that such defects are almost impossible to treat. However, surgeons have never stopped the effort to develop reliable methods to restore articular cartilage and salvage the endangered joint function. Osteochondral allograft transplantation in human was first introduced by Eric Lexer in 1908. Since that era, several pioneers have been worked in the field of osteochondral allotransplantation, presenting and developing the basic research, the methodology and the surgical techniques. Herein we present in brief, the history and the early clinical results of osteochondral allograft transplantation in human. Copyright © 2017 Elsevier Ltd. All rights reserved.

Recent Advances in Allograft Vasculopathy

PubMed Central

Merola, Jonathan; Jane-Wit, Daniel D.; Pober, Jordan S.

2017-01-01

Purpose of review Despite considerable advances in controlling acute rejection, the longevity of cardiac and renal allografts remains significantly limited by chronic rejection in the form of allograft vasculopathy (AV). This review discusses recently reported mechanistic insights of AV pathogenesis as well recent clinical evaluations of new therapeutic approaches. Recent findings Although adaptive immunity is the major driver of AV, natural killer cells mediate vasculopathic changes in a transplanted mouse heart following treatment with donor-specific antibody (DSA). However, NK cells may also dampen chronic inflammatory responses by killing donor-derived tissue-resident CD4 T cells that provide help to host B cells, the source of DSA. DSA may directly contribute to vascular inflammation by inducing intracellular signaling cascades that upregulate leukocyte adhesion molecules, facilitating recruitment of neutrophils and monocytes. DSA-mediated complement activation additionally enhances endothelial alloimmunogenicity through activation of non-canonical NF-κB signaling. New clinical studies evaluating mTOR and proteasome inhibitors to target these pathways have been reported. Summary AV is a pathology resultant from several innate and adaptive alloimmune responses. Mechanistic insights from preclinical studies have identified agents that are currently being investigated in clinical trials. PMID:27898462

Renal cell carcinoma in a cat with polycystic kidney disease undergoing renal transplantation.

PubMed

Adams, Daniel J; Demchur, Jolie A; Aronson, Lillian R

2018-01-01

A 10-year-old spayed female American Shorthair cat underwent renal transplantation due to worsening chronic kidney disease secondary to polycystic kidney disease. During transplantation, the right kidney grossly appeared to be more diseased than the left and was firmly adhered to the surrounding tissues. An intraoperative fine-needle aspirate of the right native kidney revealed inflammatory cells but no evidence of neoplasia. To create space for the allograft, a right nephrectomy was performed. Following nephrectomy, the right native kidney was submitted for biopsy. Biopsy results revealed a renal cell carcinoma. Although the cat initially recovered well from surgery, delayed graft function was a concern in the early postoperative period. Significant azotemia persisted and the cat began to have diarrhea. Erythematous skin lesions developed in the perineal and inguinal regions, which were suspected to be secondary to thromboembolic disease based on histopathology. The cat's clinical status continued to decline with development of signs of sepsis, followed by marked obtundation with uncontrollable seizures. Given the postoperative diagnosis of renal cell carcinoma and the cat's progressively declining clinical status, humane euthanasia was elected. This case is the first to document renal cell carcinoma in a cat with polycystic kidney disease. An association of the two diseases has been reported in the human literature, but such a link has yet to be described in veterinary medicine. Given the association reported in the human literature, a plausible relationship between polycystic kidney disease and renal cell carcinoma in cats merits further investigation.

ANTIBACTERIAL ACTIVITY OF BONE ALLOGRAFTS: COMPARISON OF A NEW VANCOMYCIN-TETHERED ALLOGRAFT WITH ALLOGRAFT LOADED WITH ADSORBED VANCOMYCIN

PubMed Central

Ketonis, Constantinos; Barr, Stephanie; Shapiro, Irving M.; Parvizi, Javad; Adams, Christopher S.; Hickok, Noreen J.

2010-01-01

Bacterial contamination of bone allograft is a significant complication of orthopaedic surgery. To address this issue, we have engineered a method for covalently modifying bone allograft tissue with the antibiotic vancomycin. The goal of this investigation was to compare the biocidal properties of this new allograft material with those of vancomycin physisorbed onto graft material. The duration of antibiotic release from the vancomycin-modified allograft matrix was determined and no elution was observed. In contrast, the adsorbed antibiotic showed a peak elution at 24 h that then decreased over several days. We next used an S. aureus disk diffusion assay to measure the activity of the eluted vancomycin. Again we found that no active antibiotic was eluted from the covalently–modified allograft. Similarly, when the vancomycin-modified allograft morsel was used in the assay, no measurable elution was observed; amounts of antibiotic released from the adsorbed samples inhibited S. aureus growth for 4-7 days. Probably the most telling property of the allograft was that after two weeks, the tethered-allograft was able to resist bacterial colonization. Unlike the elution system in which vancomycin was depleted over the course of days-weeks, the antibiotic on the allograft was stably bound even after 300 days, while its biocidal activity remained undiminished for 60 days. This finding was in stark contrast to the antibiotic impregnated allograft which was readily colonized by bacteria. Finally we chose to evaluate three indicators of cell function: expression of a key transcription factor, expression of selected transcripts, and assessment of cell morphology. Since the tethered antibiotic appeared to have little or no effect on any of these activities, it was concluded that the stable, tethered antibiotic prevented bacterial infection while not modifying bone cell function. PMID:21035576

Allograft dendritic cell p40 homodimers activate donor-reactive memory CD8+ T cells

PubMed Central

Tsuda, Hidetoshi; Su, Charles A.; Tanaka, Toshiaki; Ayasoufi, Katayoun; Min, Booki; Valujskikh, Anna; Fairchild, Robert L.

2018-01-01

Recipient endogenous memory T cells with donor reactivity pose an important barrier to successful transplantation and costimulatory blockade–induced graft tolerance. Longer ischemic storage times prior to organ transplantation increase early posttransplant inflammation and negatively impact early graft function and long-term graft outcome. Little is known about the mechanisms enhancing endogenous memory T cell activation to mediate tissue injury within the increased inflammatory environment of allografts subjected to prolonged cold ischemic storage (CIS). Endogenous memory CD4+ and CD8+ T cell activation is markedly increased within complete MHC-mismatched cardiac allografts subjected to prolonged versus minimal CIS, and the memory CD8+ T cells directly mediate CTLA-4Ig–resistant allograft rejection. Memory CD8+ T cell activation within allografts subjected to prolonged CIS requires memory CD4+ T cell stimulation of graft DCs to produce p40 homodimers, but not IL-12 p40/p35 heterodimers. Targeting p40 abrogates memory CD8+ T cell proliferation within the allografts and their ability to mediate CTLA-4Ig–resistant allograft rejection. These findings indicate a critical role for memory CD4+ T cell–graft DC interactions to increase the intensity of endogenous memory CD8+ T cell activation needed to mediate rejection of higher-risk allografts subjected to increased CIS. PMID:29467328

Role of Magnetic Resonance Elastography as a Noninvasive Measurement Tool of Fibrosis in a Renal Allograft: A Case Report.

PubMed

Kim, J K; Yuen, D A; Leung, G; Jothy, S; Zaltzman, J; Ramesh Prasad, G V; Prabhudesai, V; Mnatzakanian, G; Kirpalani, A

2017-09-01

A major reason for poor long-term kidney transplant outcomes is the development of chronic allograft injury, characterized by interstitial fibrosis and tubular atrophy. Currently, an invasive biopsy that samples only <1% of the kidney is the gold standard for detecting kidney allograft fibrosis. We report the use of magnetic resonance elastography (MRE) to quantify tissue stiffness as a noninvasive and whole-kidney measurement tool of allograft fibrosis in a kidney transplant patient at 2 time points. The MRE whole-kidney stiffness values reflected the changes in fibrosis of the kidney allograft as assessed by histologic examination. To our knowledge, this technique is the first observation of change over time in MRE-derived whole-kidney stiffness in an allograft that is consistent with changes in histology-derived fibrosis scores in a single patient. Copyright © 2017 Elsevier Inc. All rights reserved.

Influence of preformed donor-specific antibodies and C4d on early liver allograft function.

PubMed

Perera, M T; Silva, M A; Murphy, N; Briggs, D; Mirza, D F; Neil, D A H

2013-12-01

INTRODUCTION. The impact of preformed donor-specific antibodies (DSA) is incompletely understood in liver transplantation. The incidence and impact of preformed DSA on early post liver transplant were assessed and these were correlated with compliment fragment C4d on allograft biopsy. METHODS. Pretransplant serum from 41 consecutive liver transplant recipients (brain dead donors; DBD = 27 and cardiac death donors; DCD = 14) were tested for class-specific anti-human leukocyte antigen (HLA) and compared against donor HLA types. Liver biopsies were taken during cold storage (t-1) and post-reperfusion (t0) stained with C4d and graded for preservation-reperfusion injury (PRI). RESULTS. Of the 41 recipients, 8 (20%) had anti-HLA class I/II antibodies pretransplant, 3 (7%) were confirmed preformed DSA; classes I and II (n=1) and class I only (n=2). No biopsies showed definite evidence of antibody-mediated rejection. Graft biopsies in overall showed only mild PRI with ischemic hepatocyte C4d pattern similar in both positive and negative DSA patients. One DSA-positive (33%) compared with four DSA-negative patients (10%) had significant early graft dysfunction; severe PRI causing graft loss from primary nonfunction was seen only in DSA-negative group. Allograft biopsy of preformed DSA-positive patient demonstrated only minimal PRI; however, no identifiable cause could be attributed to graft dysfunction other than preformed DSA. CONCLUSION. Preformed DSA are present in 5-10% liver transplant recipients. There is no association between anti-HLA DSA and PRI and C4d, but preformed DSA may cause early morbidity. Larger studies on the impact of DSA with optimization of C4d techniques are required.

Sterilization with electron beam irradiation influences the biomechanical properties and the early remodeling of tendon allografts for reconstruction of the anterior cruciate ligament (ACL).

PubMed

Schmidt, Tanja; Hoburg, Arnd; Broziat, Christine; Smith, Mark D; Gohs, Uwe; Pruss, Axel; Scheffler, Sven

2012-08-01

Although allografts for anterior cruciate ligament (ACL) replacement have shown advantages compared to autografts, their use is limited due to the risk of disease transmission and the limitations of available sterilization methods. Gamma sterilization has shown detrimental effects on graft properties at the high doses required for sufficient pathogen inactivation. In our previous in vitro study on human patellar tendon allografts, Electron beam (Ebeam) irradiation showed less detrimental effects compared to gamma sterilization (Hoburg et al. in Am J Sports Med 38(6):1134-1140, 2010). To investigate the biological healing and restoration of the mechanical properties of a 34 kGy Ebeam treated tendon allograft twenty-four sheep underwent ACL replacement with either a 34 kGy Ebeam treated allograft or a non-sterilized fresh frozen allograft. Biomechanical testing of stiffness, ultimate failure load and AP-laxity as well as histological analysis to investigate cell, vessel and myofibroblast-density were performed after 6 and 12 weeks. Native sheep ACL and hamstring tendons (HAT, each n = 9) served as controls. The results of a previous study analyzing the remodeling of fresh frozen allografts (n = 12) and autografts (Auto, n = 18) with the same study design were also included in the analysis. Statistics were performed using Mann-Whitney U test followed by Bonferroni-Holm correction. Results showed significantly decreased biomechanical properties during the early remodeling period in Ebeam treated grafts and this was accompanied with an increased remodeling activity. There was no recovery of biomechanical function from 6 to 12 weeks in this group in contrast to the results observed in fresh frozen allografts and autografts. Therefore, high dose Ebeam irradiation investigated in this paper cannot be recommended for soft tissue allograft sterilization.

Atypical cells in a voided urine cytology specimen in a renal transplant recipient.

PubMed

Lu, Miao; Ho, Julie; Azordegan, Nazila; Perry, Anamarija M; Gibson, Ian W; Baker, Patricia

2017-01-01

Voided urine is routinely collected from renal transplant patients to screen for polyomavirus. In rare cases, atypical lymphoid cells can be detected in voided urine and raise the suspicion of post-transplant lymphoproliferative disorder (PTLD). However, further immunohistochemistry of the cell block and flow cytometry is frequently limited by the low cellularity and poor preservation of voided urine. Therefore, PTLD of the renal allograft is usually diagnosed from tissue biopsy or nephrectomy specimens. Herein, we report a rare case of atypical cells in a voided urine cytology specimen from a kidney transplant recipient. Needle core biopsy of the renal allograft showed monomorphic PTLD. Diagn. Cytopathol. 2017;45:69-72. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Mast cell phenotypes in the allograft after lung transplantation.

PubMed

Banga, Amit; Han, Yingchun; Wang, Xiaofeng; Hsieh, Fred H

2016-07-01

The burden of mast cell (MC) infiltration and their phenotypes, MC-tryptase (MCT ) and MC-tryptase/chymase (MCTC ), after lung transplantation (LT) has not been evaluated in human studies. We reviewed 20 transbronchial lung biopsy (TBLB) specimen from patients with early normal allograft (<6 months post-LT, n=5), late normal allograft (>6 months, n=5), A2 or worse acute cellular rejection (ACR, n=5), and chronic lung allograft dysfunction (CLAD, n=5). Slides were immunostained for tryptase and chymase. Total MC, MCT , MCTC and MCTC to-MCT ratio were compared between the four groups using a generalized linear mixed model. Irrespective of clinicopathologic diagnosis, MC burden tends to increase with time (r(2) =.56, P=.009). MCTC phenotype was significantly increased in the CLAD group (8.2±4.9 cells per HPF) in comparison with the other three groups (early normal: 1.6±1.7, P=.0026; late normal: 2.5±2.3, P=.048; ACR: 2.7±3.5, P=.021). Further, the ratio of MCTC to MCT was significantly increased in CLAD group as compared to the other three groups (P<.001 for all comparisons). The burden of MC may increase in the allograft as function of time. Patients with CLAD have an increased relative and absolute burden of MCTC phenotype MC. Future studies are needed to confirm these findings and evaluate the potential pathologic role of MCTC in allograft dysfunction. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Hair Follicle Dermal Sheath Derived Cells Improve Islet Allograft Survival without Systemic Immunosuppression

PubMed Central

Wang, Xiaojie; Hao, Jianqiang; Leung, Gigi; Breitkopf, Trisia; Wang, Eddy; Kwong, Nicole; Akhoundsadegh, Noushin; Warnock, Garth L.; Shapiro, Jerry; McElwee, Kevin J.

2015-01-01

Immunosuppressive drugs successfully prevent rejection of islet allografts in the treatment of type I diabetes. However, the drugs also suppress systemic immunity increasing the risk of opportunistic infection and cancer development in allograft recipients. In this study, we investigated a new treatment for autoimmune diabetes using naturally immune privileged, hair follicle derived, autologous cells to provide localized immune protection of islet allotransplants. Islets from Balb/c mouse donors were cotransplanted with syngeneic hair follicle dermal sheath cup cells (DSCC, group 1) or fibroblasts (FB, group 2) under the kidney capsule of immune-competent, streptozotocin induced, diabetic C57BL/6 recipients. Group 1 allografts survived significantly longer than group 2 (32.2 ± 12.2 versus 14.1 ± 3.3 days, P < 0.001) without administration of any systemic immunosuppressive agents. DSCC reduced T cell activation in the renal lymph node, prevented graft infiltrates, modulated inflammatory chemokine and cytokine profiles, and preserved better beta cell function in the islet allografts, but no systemic immunosuppression was observed. In summary, DSCC prolong islet allograft survival without systemic immunosuppression by local modulation of alloimmune responses, enhancing of beta cell survival, and promoting of graft revascularization. This novel finding demonstrates the capacity of easily accessible hair follicle cells to be used as local immunosuppression agents in islet transplantation. PMID:26000314

Immunological tolerance induced by galectin-1 in rat allogeneic renal transplantation.

PubMed

Xu, Gaosi; Tu, Weiping; Xu, Chengyun

2010-06-01

The existed literatures indicated that galectin-1 has anti-inflammatory effects and plays a pivotal role in autoimmune diseases. Present study was to identify the roles of galectin-1 in acute animal renal allograft rejection. Rat acute rejection models were erected by allogeneic renal transplantation. Galectin-1 injection was performed in different concentrations in renal recipients post-transplantation. Recipient survivals, CD8+ T cell proliferation, production of IFN-gamma, levels of serum CD30, enzyme-linked immunoabsorbent spot assay (ELISPOT) and immunohistochemistry were observed or tested 7days after renal transplantation. Galectin-1 injection can prolong the recipient animal survival, reduce the serum levels of IFN-gamma, soluble CD30, percentage of CD8+ T cell subset, CD8+ T cell-mediated cytotoxicity, and IFN-gamma ELISPOT frequency for allograft recipients. The therapeutic effects of galectin-1 injection on recipient rats were dose-dependent. Galectin-1 plays an important role in CD8+ T cell-mediated renal rejection by inducing immunological tolerance. Copyright 2010 Elsevier B.V. All rights reserved.

Recipient Myd88 Deficiency Promotes Spontaneous Resolution of Kidney Allograft Rejection

PubMed Central

Lerret, Nadine M.; Li, Ting; Wang, Jiao-Jing; Kang, Hee-Kap; Wang, Sheng; Wang, Xueqiong; Jie, Chunfa; Kanwar, Yashpal S.; Abecassis, Michael M.

2015-01-01

The myeloid differentiation protein 88 (MyD88) adapter protein is an important mediator of kidney allograft rejection, yet the precise role of MyD88 signaling in directing the host immune response toward the development of kidney allograft rejection remains unclear. Using a stringent mouse model of allogeneic kidney transplantation, we demonstrated that acute allograft rejection occurred equally in MyD88-sufficient (wild-type [WT]) and MyD88−/− recipients. However, MyD88 deficiency resulted in spontaneous diminution of graft infiltrating effector cells, including CD11b−Gr-1+ cells and activated CD8 T cells, as well as subsequent restoration of near-normal renal graft function, leading to long-term kidney allograft acceptance. Compared with T cells from WT recipients, T cells from MyD88−/− recipients failed to mount a robust recall response upon donor antigen restimulation in mixed lymphocyte cultures ex vivo. Notably, exogenous IL-6 restored the proliferation rate of T cells, particularly CD8 T cells, from MyD88−/− recipients to the proliferation rate of cells from WT recipients. Furthermore, MyD88−/− T cells exhibited diminished expression of chemokine receptors, specifically CCR4 and CXCR3, and the impaired ability to accumulate in the kidney allografts despite an otherwise MyD88-sufficient environment. These results provide a mechanism linking the lack of intrinsic MyD88 signaling in T cells to the effective control of the rejection response that results in spontaneous resolution of acute rejection and long-term graft protection. PMID:25788530

Splicing alterations in human renal allografts: detection of a new splice variant of protein kinase Par1/Emk1 whose expression is associated with an increase of inflammation in protocol biopsies of transplanted patients.

PubMed

Hueso, Miguel; Beltran, Violeta; Moreso, Francesc; Ciriero, Eva; Fulladosa, Xavier; Grinyó, Josep Maria; Serón, Daniel; Navarro, Estanis

2004-05-24

Protein kinase Emk1/Par1 (GenBank accession no. X97630) has been identified as a regulator of the immune system homeostasis. Since immunological factors are critical for the development of chronic allograft nephropathy (CAN), we reasoned that expression of Par1/Emk1 could be altered in kidney allografts undergoing CAN. In this paper, we have analysed the association among renal allograft lesions and expression of Par1/Emk1, studied by RT-PCR on total RNA from 51 protocol biopsies of transplanted kidneys, five normal kidneys, and five dysfunctional allografts. The most significant result obtained has been the detection of alterations in the normal pattern of alternative splicing of the Par1/Emk1 transcript, alterations that included loss of expression of constitutively expressed isoforms, and the inclusion of a cryptic exon to generate a new Emk1 isoform (Emk1C). Expression of Emk1C was associated with an increase in the extension of the interstitial infiltrate (0.88+/-0.33 in Emk1C([+]) vs. 0.41+/-0.50 in Emk1C([-]); P<0.011), and with a trend to display higher interstitial scarring (0.66+/-0.70 vs. 0.29+/-0.52; P=0.09) in protocol biopsies when evaluated according to the Banff schema. Moreover, a higher mean arterial pressure (MAP) was also observed (110+/-11 vs. 99+/-11 mm Hg; P=0.012). From these results we propose that Par1/Emk1 could have a role in the development of CAN in kidney allografts.

Ischemic acute kidney injury and klotho in renal transplantation.

PubMed

Panah, Fatemeh; Ghorbanihaghjo, Amir; Argani, Hassan; Asadi Zarmehri, Maryam; Nazari Soltan Ahmad, Saeed

2018-05-01

Post-transplant ischemic acute kidney injury (AKI), secondary to ischemia reperfusion injury (IRI), is a major problem influencing on the short and long term graft and patient survival. Many molecular and cellular modifications are observed during IRI, for example, tissue damage result production of reactive oxygen species (ROS), cytokines, chemokines, and leukocytes recruitment which are activated by NF-κB (nuclear factor kappa B) signaling pathway. Therefore, inhibiting these processes can significantly protect renal parenchyma from tissue damage. Klotho protein, mainly produced in distal convoluted tubules (DCT), is an anti-senescence protein. There is increasing evidence to confirm a relationship between Klotho levels and renal allograft function. Many studies have also demonstrated that expression of the Klotho gene would be down regulated with IRI, so it will be used as an early biomarker for acute kidney injury after renal transplantation. Other studies suggest that Klotho may have a renoprotective effect for attenuating of kidney injury. In this review, we will discuss pathophysiology of IRI-induced acute kidney injury and its relation with klotho level in renal transplantation procedure. Copyright © 2018 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Renal transplantation in systemic lupus erythematosus: outcome and prognostic factors in 50 cases from a single centre.

PubMed

Cairoli, Ernesto; Sanchez-Marcos, Carolina; Espinosa, Gerard; Glucksmann, Constanza; Ercilla, Guadalupe; Oppenheimer, Federico; Cervera, Ricard

2014-01-01

End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). To analyze the outcome and prognostic factors of renal transplantation in patients with ESRD due to SLE from January 1986 to December 2013 in a single center. Fifty renal transplantations were performed in 40 SLE patients (32 female (80%), mean age at transplantation 36±10.4 years). The most frequent lupus nephropathy was type IV (72.2%). Graft failure occurred in a total of 15 (30%) transplantations and the causes of graft failure were chronic allograft nephropathy (n=12), acute rejection (n=2), and chronic humoral rejection (1). The death-censored graft survival rates were 93.9% at 1 year, 81.5% at 5 years, and 67.6% at the end of study. The presence of deceased donor allograft (P=0.007) and positive anti-HCV antibodies (P=0.001) negatively influence the survival of the renal transplant. The patient survival rate was 91.4% at the end of the study. Recurrence of lupus nephritis in renal allograft was observed in one patient. Renal transplantation is a good alternative for renal replacement therapy in patients with SLE. In our cohort, the presence of anti-HCV antibodies and the type of donor source were related to the development of graft failure.

Renal Transplantation in Systemic Lupus Erythematosus: Outcome and Prognostic Factors in 50 Cases from a Single Centre

PubMed Central

Cairoli, Ernesto; Sanchez-Marcos, Carolina; Espinosa, Gerard; Glucksmann, Constanza; Ercilla, Guadalupe; Oppenheimer, Federico; Cervera, Ricard

2014-01-01

Background. End-stage renal disease (ESRD) is an important cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Objectives. To analyze the outcome and prognostic factors of renal transplantation in patients with ESRD due to SLE from January 1986 to December 2013 in a single center. Results. Fifty renal transplantations were performed in 40 SLE patients (32 female (80%), mean age at transplantation 36 ± 10.4 years). The most frequent lupus nephropathy was type IV (72.2%). Graft failure occurred in a total of 15 (30%) transplantations and the causes of graft failure were chronic allograft nephropathy (n = 12), acute rejection (n = 2), and chronic humoral rejection (1). The death-censored graft survival rates were 93.9% at 1 year, 81.5% at 5 years, and 67.6% at the end of study. The presence of deceased donor allograft (P = 0.007) and positive anti-HCV antibodies (P = 0.001) negatively influence the survival of the renal transplant. The patient survival rate was 91.4% at the end of the study. Recurrence of lupus nephritis in renal allograft was observed in one patient. Conclusion. Renal transplantation is a good alternative for renal replacement therapy in patients with SLE. In our cohort, the presence of anti-HCV antibodies and the type of donor source were related to the development of graft failure. PMID:25013800

Timing of Pregnancy After Kidney Transplantation and Risk of Allograft Failure.

PubMed

Rose, C; Gill, J; Zalunardo, N; Johnston, O; Mehrotra, A; Gill, J S

2016-08-01

The optimal timing of pregnancy after kidney transplantation remains uncertain. We determined the risk of allograft failure among women who became pregnant within the first 3 posttransplant years. Among 21 814 women aged 15-45 years who received a first kidney-only transplant between 1990 and 2010 captured in the United States Renal Data System, n = 729 pregnancies were identified using Medicare claims. The probability of allograft failure from any cause including death (ACGL) at 1, 3, and 5 years after pregnancy was 9.6%, 25.9%, and 36.6%. In multivariate analyses, pregnancy in the first posttransplant year was associated with an increased risk of ACGL (hazard ratio [HR]: 1.18; 95% confidence interval [CI] 1.00, 1.40) and death censored graft loss (DCGL) (HR:1.25; 95% CI 1.04, 1.50), while pregnancy in the second posttransplant year was associated with an increased risk of DCGL (HR: 1.26; 95% CI 1.06, 1.50). Pregnancy in the third posttransplant year was not associated with an increased risk of ACGL or DCGL. These findings demonstrate a higher incidence of allograft failure after pregnancy than previously reported and that the increased risk of allograft failure extends to pregnancies in the second posttransplant year. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Early renal dysfunction after contrast media administration despite prophylactic hydration.

PubMed

Burchardt, Pawel; Guzik, Przemyslaw; Tabaczewski, Piotr; Synowiec, Tomasz; Bogdan, Monika; Faner, Paula; Chmielarz-Sobocińska, Anna; Palasz, Anna

2013-06-01

The actual incidence of renal dysfunction after contrast media administration seems to be underestimated, especially in the context of epidemiological data. There are only few data concerning the monitoring of impaired kidney function within a few hours after iodine contrast medium application. Hence, the purpose of this study is to observe the incidence of early renal function deterioration within 12-18 h after administration of iodine contrast media in patients scheduled for elective coronary angiography, who were intravenously and orally hydrated. In addition, the project aims to reclassify the contrast induced nephropathy phenomenon, by identification of early markers of renal dysfunction. Morphology, electrolytes, blood urea nitrogen (BUN), creatinine, low-density lipoprotein cholesterol, triglycerides, high-density lipoprotein, and total cholesterol levels were assessed with the use of typical laboratory techniques in 319 patients referred for coronary angiography. We demonstrated that early deterioration of renal function in patients 12-18 h after administration of contrast during imaging tests (even when appropriate prophylactic hydration was used), may occurred just as an increase (or no change) of serum creatinine level and BUN level and a decrease of creatinine clearance and glomerular filtration rate. Depending on the parameter, the phenomenon can be found in 13-28 % of all respondents. Early renal function impairment defined as above was almost 2 and 2.22 × 10(3) times (respectively) more frequently observed in our study than contrast induced nephropathy defined by current definitions.

Early impact of robot-assisted partial nephrectomy on renal function as assessed by renal scintigraphy.

PubMed

Luciani, Lorenzo G; Chiodini, Stefano; Donner, Davide; Cai, Tommaso; Vattovani, Valentino; Tiscione, Daniele; Giusti, Guido; Proietti, Silvia; Chierichetti, Franca; Malossini, Gianni

2016-06-01

To measure the early impact of robot-assisted partial nephrectomy (RAPN) on renal function as assessed by renal scan (Tc 99m-DTPA), addressing the issue of risk factors for ischemic damage to the kidney. All patients undergoing RAPN for cT1 renal masses between June 2013 and May 2014 were included in this prospective study. Renal function as expressed by glomerular filtration rate (GFR) was assessed by Technetium 99m-diethylenetriaminepentaacetic acid (Tc 99m-DTPA) renal scan preoperatively and postoperatively at 1 month in every patient. A multivariable analysis was used for the determination of independent factors predictive of GFR decrease of the operated kidney. Overall, 32 patients underwent RAPN in the time interval. Median tumor size, blood loss, and ischemia time were 4 cm, 200 mL, and 24 min, respectively. Two grade III complications occurred (postoperative bleeding in the renal fossa, urinoma). The GFR of the operated kidney decreased significantly from 51.7 ± 15.1 mL/min per 1.73 m(2) preoperatively to 40, 12 ± 12.4 mL/min per 1.73 m(2) 1 month postoperatively (p = 0.001) with a decrease of 22.4 %. On multivariable analysis, only tumor size (p = 0.05) was a predictor of GFR decrease of the operated kidney. Robotic-assisted partial nephrectomy had a detectable impact on early renal function in a series of relatively large tumors and prevailing intermediate nephrometric risk. A mean decrease of 22 % of GFR as assessed by renal scan in the operated kidney was found at 1 month postoperatively. In multivariable analysis, tumor size only was a significant predictor of renal function loss.

Mechanisms of filtration failure during postischemic injury of the human kidney. A study of the reperfused renal allograft.

PubMed

Alejandro, V; Scandling, J D; Sibley, R K; Dafoe, D; Alfrey, E; Deen, W; Myers, B D

1995-02-01

Postischemic filtration failure in experimental animals results primarily from depression of the transcapillary hydraulic pressure difference (delta P), a quantity that cannot be determined in humans. To circumvent this limitation we determined the GFR and each of its remaining determinants in transplanted kidneys. Findings in 12 allografts that exhibited subsequent normofiltration (group 1) were compared with those in 11 allografts that exhibited persistent hypofiltration (group 2). Determinations were made intraoperatively in the exposed graft after 1-3 h of reperfusion. GFR (6 +/- 2 vs 29 +/- 5 ml/min) and renal plasma flow by Doppler flow meter (140 +/- 30 vs 315 +/- 49 ml/min) were significantly lower in group 2 than group 1. Morphometric analysis of glomeruli obtained by biopsy and a structural hydrodynamic model of viscous flow revealed the glomerular ultrafiltration coefficient to be similar, averaging 3.5 +/- 0.6 and 3.1 +/- 0.2 ml/(min.mmHg) in group 2 vs 1, respectively. Corresponding values for plasma oncotic pressure were also similar, averaging 19 +/- 1 vs 21 +/- 1 mmHg. We next used a mathematical model of glomerular ultrafiltration and a sensitivity analysis to calculate the prevailing range for delta P from the foregoing measured quantities. This revealed delta P to vary from only 20-21 mmHg in group 2 vs 34-45 mmHg in group 1 (P < 0.001). Further morphometric analysis revealed the diameters of Bowman's space and tubular lumens, as well as the percentage of tubular cells that were necrotic or devoid of brush border, to be similar in the two groups. We thus conclude (a) that delta P depression is the predominant cause of hypofiltration in this form of postischemic injury; and (b) that afferent vasoconstriction rather than tubular obstruction is the proximate cause of the delta P depression.

Captopril in hypertension after renal transplantation.

PubMed Central

Chan, M. K.; Sweny, P.; El Nahas, A. M.; Farrington, K.; Fernando, O. N.; Moorhead, J. F.

1984-01-01

Eight hypertensive renal allograft recipients who had received captopril are presented. Captopril in a maximal daily dose of 250 mg enabled the withdrawal of large doses of beta-blocking agents and vasodilators. Blood pressure was satisfactorily controlled in all except one. No adverse side effects were observed other than the 'first dose' effect which resulted in transient anuria in one patient. Captopril appears to be a useful agent in the management of severe hypertension after renal transplantation. PMID:6369287

Renal transplantation in patients with hepatitis C virus antibody. A long national experience

PubMed Central

Morales, Jose María; Marcén, Roberto; Andres, Amado; Domínguez-Gil, Beatriz; Campistol, Josep María; Gallego, Roberto; Gutierrez, Alex; Gentil, Miguel Angel; Oppenheimer, Federico; Samaniego, María Luz; Muñoz-Robles, Jorge; Serón, Daniel

2010-01-01

Background. Renal transplantation is the best therapy for patients with hepatitis C virus (HCV) infection with end-stage renal disease. Patient and graft survival are lower in the long term compared with HCV-negative patients. The current study evaluated the results of renal transplantation in Spain in a long period (1990–2002), focusing on graft failure. Methods. Data on the Spanish Chronic Allograft Nephropathy Study Group including 4304 renal transplant recipients, 587 of them with HCV antibody, were used to estimate graft and patient survival at 4 years with multivariate Cox models. Results. Among recipients alive with graft function 1 year post-transplant, the 4-year graft survival was 92.8% in the whole group; this was significantly better in HCV-negative vs HCV-positive patients (94.4% vs 89.5%, P < 0.005). Notably, HCV patients showed more acute rejection, a higher degree of proteinuria accompanied by a diminution of renal function, more graft biopsies and lesions of de novo glomerulonephritis and transplant glomerulopathy. Serum creatinine and proteinuria at 1 year, acute rejection, HCV positivity and systolic blood pressure were independent risk factors for graft loss. Patient survival was 96.3% in the whole group, showing a significant difference between HCV-negative vs HCV-positive patients (96.6% vs 94.5%, P < 0.05). Serum creatinine and diastolic blood pressure at 1 year, HCV positivity and recipient age were independent risk factors for patient death. Conclusions. Renal transplantation is an effective therapy for HCV-positive patients with good survival but inferior than results obtained in HCV-negative patients in the short term. Notably, HCV-associated renal damage appears early with proteinuria, elevated serum creatinine showing chronic allograft nephropathy, transplant glomerulopathy and, less frequently, HCV-associated de novo glomerulonephritis. We suggest that HCV infection should be recognized as a true risk factor for graft failure, and

Angiotensin converting enzyme genotype and chronic allograft nephropathy in protocol biopsies.

PubMed

Hueso, Miguel; Alía, Pedro; Moreso, Francesc; Beltrán-Sastre, Violeta; Riera, Luis; González, Carlota; Navarro, Miguel Angel; Grinyó, Josep Maria; Navarro, Estanis; Serón, Daniel

2004-08-01

Genotype DD of the angiotensin-converting enzyme (ACE) is not associated with an increased incidence of native renal diseases, although it could modulate progression to renal failure in patients who already display chronic lesions. Because its role in renal allograft degeneration is not well characterized, whether ACE genotype was associated with the prevalence of chronic allograft nephropathy (CAN) was studied, in a group of protocol biopsies from 180 patients, or with the incidence of CAN in 152 patients with at least two sequential biopsies. As a control group, ACE genotype was also studied in 41 donors and 72 healthy subjects. For analyzing the influence of ACE genotype in graft survival, patients were grouped into six categories (II-normal biopsy, ID-normal, DD-normal, II-CAN, ID-CAN and DD-CAN). Finally, relative renal ACE mRNA levels were measured in 67 cases by real-time PCR using the delta threshold cycle method. ACE-DD genotype was more frequent in patients who received a transplant than in control subjects (43.3% versus 30.1%, P = 0.026), but prevalence (DD = 42.7% versus non-DD = 42.2%) or incidence (DD = 24.6% versus non-DD = 29.9%) of CAN was not different regarding recipient ACE genotype. Furthermore, patients with the ACE-DD genotype and CAN had the poorest graft survival (II-normal = 100%, ID-normal = 91%, DD-normal = 84%, II-CAN = 100%, ID-CAN = 66%, and DD-CAN = 36%; P = 0.034) and higher ACE mRNA levels than non-DD and CAN (DD = -3.36 +/- 2.35 versus non-DD = -5.65 +/- 1.72-fold in ACE copies; P = 0.012). It is concluded that ACE-DD genotype is not associated with an increased prevalence or incidence of CAN but is actually associated with higher ACE mRNA levels and poorer graft survival in patients who already display CAN.

Biomarker for early renal microvascular and diabetic kidney diseases.

PubMed

Futrakul, Narisa; Futrakul, Prasit

2017-11-01

Recognition of early stage of diabetic kidney disease, under common practice using biomarkers, namely microalbuminuria, serum creatinine level above 1 mg/dL and accepted definition of diabetic kidney disease associated with creatinine clearance value below 60 mL/min/1.73 m 2 , is unlikely. This would lead to delay treatment associated with therapeutic resistance to vasodilator due to a defective vascular homoeostasis. Other alternative biomarkers related to the state of microalbuminuria is not sensitive to screen for early diabetic kidney disease (stages I, II). In this regard, a better diagnostic markers to serve for this purpose are creatinine clearance, fractional excretion of magnesium (FE Mg), cystatin C. Recently, renal microvascular disease and renal ischemia have been demonstrated to correlate indirectly with the development of diabetic kidney disease and its function. Among these are angiogenic and anti-angiogenic factors, namely VEGF, VEGF receptors, angiopoietins and endostatin. With respect to therapeutic prevention, implementation of treatment at early stage of diabetic and nondiabetic kidney disease is able to restore renal perfusion and function.

Lipidomics comparing DCD and DBD liver allografts uncovers lysophospholipids elevated in recipients undergoing early allograft dysfunction.

PubMed

Xu, Jin; Casas-Ferreira, Ana M; Ma, Yun; Sen, Arundhuti; Kim, Min; Proitsi, Petroula; Shkodra, Maltina; Tena, Maria; Srinivasan, Parthi; Heaton, Nigel; Jassem, Wayel; Legido-Quigley, Cristina

2015-12-04

Finding specific biomarkers of liver damage in clinical evaluations could increase the pool of available organs for transplantation. Lipids are key regulators in cell necrosis and hence this study hypothesised that lipid levels could be altered in organs suffering severe ischemia. Matched pre- and post-transplant biopsies from donation after circulatory death (DCD, n = 36, mean warm ischemia time = 2 min) and donation after brain death (DBD, n = 76, warm ischemia time = none) were collected. Lipidomic discovery and multivariate analysis (MVA) were applied. Afterwards, univariate analysis and clinical associations were conducted for selected lipids differentiating between these two groups. MVA grouped DCD vs. DBD (p = 6.20 × 10(-12)) and 12 phospholipids were selected for intact lipid measurements. Two lysophosphatidylcholines, LysoPC (16:0) and LysoPC (18:0), showed higher levels in DCD at pre-transplantation (q < 0.01). Lysophosphatidylcholines were associated with aspartate aminotransferase (AST) 14-day post-transplantation (q < 0.05) and were more abundant in recipients undergoing early allograft dysfunction (EAD) (p < 0.05). A receiver-operating characteristics (ROC) curve combining both lipid levels predicted EAD with 82% accuracy. These findings suggest that LysoPC (16:0) and LysoPC (18:0) might have a role in signalling liver tissue damage due to warm ischemia before transplantation.

Estimation of total glomerular number in stable renal transplants.

PubMed

Fulladosa, Xavier; Moreso, Francesc; Narváez, Jose A; Grinyó, Josep M; Serón, Daniel

2003-10-01

Glomerular number (N(g)) is considered a major determinant of renal function and outcome. In the dog, it has been shown that Ng can be estimated with reasonable precision in vivo by means of a renal biopsy and magnetic resonance imaging (MRI). Thus, this method was applied to study anatomoclinical correlations in stable human renal transplants. Thirty-nine stable renal transplants were included. A protocol renal allograft biopsy was done at 4 mo. Biopsies were evaluated according to Banff criteria. Glomerular volume fraction (Vv(glom/cortex)) was measured by means of a point-counting method, and mean glomerular volume (V(g)) was estimated by means of Weibel and Gomez (V(g)-W&G) and maximal profile area (V(g)-MPA) methods. MRI was used to estimate renal cortical volume (V(cortex)). N(g) was calculated as (Vv(glom/cortex) x V(cortex))/V(g). GFR was estimated by the inulin clearance. Ten age-matched donor biopsies served as controls for V(g). Histologic diagnosis was as follows: normal (n = 20), borderline (n = 7), acute rejection (n = 1), and chronic allograft nephropathy (n = 11). Vv(glom/cortex) was 3.4 +/- 1.1%, V(cortex) was 167 +/- 46 cm(3), V(g)-W&G was 3.2 +/- 1.2 x 10(6) micro m(3), and V(g)-MPA was 3.3 +/- 1.0 x 10(6) micro m(3). V(g)-W&G in donor and recipient biopsies was not different (3.6 +/- 1.1 versus 3.2 +/- 1.2 x 10(6) micro m(3)). Total glomerular number estimated by means of V(g)-W&G (N(g)-W&G) was 0.73 +/- 0.33 x 10(6) and by V(g)-MPA (N(g)-MPA) was 0.74 +/- 0.31 x 10(6). A positive correlation between GFR and N(g)-W&G (r = 0.47, P = 0.002) was observed. Furthermore, the older the donor, the higher V(g)-W&G (r = 0.37, P = 0.01) and the lower N(g)-W&G (r = -0.40, P = 0.01). Total glomerular number can be estimated in stable renal allografts by means of a renal biopsy and MRI. Our data show that N(g) depends on donor age and positively correlates with GFR.

Endogenous Memory CD8 T Cells Directly Mediate Cardiac Allograft Rejection

PubMed Central

Su, C. A.; Iida, S.; Abe, T.; Fairchild, R. L.

2014-01-01

Differences in levels of environmentally induced memory T cells that cross-react with donor MHC molecules are postulated to account for the efficacy of allograft tolerance inducing strategies in rodents versus their failure in nonhuman primates and human transplant patients. Strategies to study the impact of donor-reactive memory T cells on allografts in rodents have relied on the pre-transplant induction of memory T cells cross-reactive with donor allogeneic MHC molecules through recipient viral infection, priming directly with donor antigen, or adoptive transfer of donor-antigen primed memory T cells. Each approach accelerates allograft rejection and confers resistance to tolerance induction, but also biases the T cell repertoire to strong donor-reactivity. The ability of endogenous memory T cells within unprimed mice to directly reject an allograft is unknown. Here we show a direct association between increased duration of cold ischemic allograft storage and numbers and enhanced functions of early graft infiltrating endogenous CD8 memory T cells. These T cells directly mediate rejection of allografts subjected to prolonged ischemia and this rejection is resistant to costimulatory blockade. These findings recapitulate the clinically significant impact of endogenous memory T cells with donor reactivity in a mouse transplant model in the absence of prior recipient priming. PMID:24502272

An update on renal involvement in hemophagocytic syndrome (macrophage activation syndrome).

PubMed

Esmaili, Haydarali; Mostafidi, Elmira; Mehramuz, Bahareh; Ardalan, Mohammadreza; Mohajel-Shoja, Mohammadali

2016-01-01

Hemophagocytic syndrome (HPS) is mainly characterized by massive infiltration of bone marrow by activated macrophages and often presents with pancytopenia. Thrombotic microangiopathy (TMA) is also present with thrombocytopenia and renal involvement. Both conditions could coexist with each other and complicate the condition. Directory of Open Access Journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science with keywords relevant to; Hemophagocytic syndrome, macrophage activation syndrome, interferon-gamma and thrombotic microangiopathy, have been searched. Viral infection, rheumatologic disease and malignancies are the main underlying causes for secondary HPS. calcineurin inhibitors and viral infections are also the main underlying causes of TMA in transplant recipients. In this review, we discussed a 39-year-old male who presented with pancytopenia and renal allograft dysfunction. With the diagnosis of HPS induced TMA his renal condition and pancytopenia improved after receiving intravenous immunoglobulin (IVIG) and plasmapheresis therapy. HPS is an increasingly recognized disorder in the realm of different medical specialties. Renal involvement complicates the clinical picture of the disease, and this condition even is more complex in renal transplant recipients. We should consider the possibility of HPS in any renal transplant recipient with pancytopenia and allograft dysfunction. The combination of HPS with TMA future increases the complexity of the situation.

An update on renal involvement in hemophagocytic syndrome (macrophage activation syndrome)

PubMed Central

Esmaili, Haydarali; Mostafidi, Elmira; Mehramuz, Bahareh; Ardalan, Mohammadreza; Mohajel-Shoja, Mohammadali

2016-01-01

Context: Hemophagocytic syndrome (HPS) is mainly characterized by massive infiltration of bone marrow by activated macrophages and often presents with pancytopenia. Thrombotic microangiopathy (TMA) is also present with thrombocytopenia and renal involvement. Both conditions could coexist with each other and complicate the condition. Evidence Acquisition: Directory of Open Access Journals (DOAJ), EMBASE, Google Scholar, PubMed, EBSCO, and Web of Science with keywords relevant to; Hemophagocytic syndrome, macrophage activation syndrome, interferon-gamma and thrombotic microangiopathy, have been searched. Results: Viral infection, rheumatologic disease and malignancies are the main underlying causes for secondary HPS. calcineurin inhibitors and viral infections are also the main underlying causes of TMA in transplant recipients. In this review, we discussed a 39-year-old male who presented with pancytopenia and renal allograft dysfunction. With the diagnosis of HPS induced TMA his renal condition and pancytopenia improved after receiving intravenous immunoglobulin (IVIG) and plasmapheresis therapy. Conclusions: HPS is an increasingly recognized disorder in the realm of different medical specialties. Renal involvement complicates the clinical picture of the disease, and this condition even is more complex in renal transplant recipients. We should consider the possibility of HPS in any renal transplant recipient with pancytopenia and allograft dysfunction. The combination of HPS with TMA future increases the complexity of the situation. PMID:27047804

New insights into saccular development and vascular formation in lung allografts under the renal capsule

PubMed Central

Vu, Thiennu H.; Alemayehu, Yemisrach; Werb, Zena

2009-01-01

The study of distal lung morphogenesis and vascular development would be greatly facilitated by an in vitro or ex vivo experimental model. In this study we show that the growth of mouse embryonic day 12.5 lung rudiments implanted underneath the kidney capsules of syngeneic or immunodeficient hosts follows closely lung development in utero. The epithelium develops extensively with both proximal and distal differentiation to the saccular stage. The vasculature also develops extensively. Large blood vessels accompany large airways and capillaries develop within the saccular walls. Interestingly, vessels in the lung grafts develop from endothelial progenitor cells endogenous to the explants and host vessels do not vascularize the grafts independently. This suggests that embryonic lungs possess mechanisms to prevent the inappropriate ingrowth of surrounding vessels. However, vessels in the lung grafts do connect to host vessels, showing that embryonic lungs have the ability to stimulate host angiogenesis and recruit host vessel connections. These data support the hypothesis that the lung vasculature develops by both vasculogenic and angiogenic processes: a vascular network develops in situ in lung mesenchyme, which is then connected to angiogenic processes from central vessels. The lung renal capsule allograft is thus an excellent model to study the development of the pulmonary vasculature and of late fetal lung development that requires a functional blood supply. PMID:12591600

Renal Allograft Survival in Nonhuman Primates Infused with Donor Antigen-Pulsed Autologous Regulatory Dendritic Cells

PubMed Central

Ezzelarab, M.B.; Raich-Regue, D.; Lu, L.; Zahorchak, A.F.; Perez-Gutierrez, A.; Humar, A.; Wijkstrom, M.; Minervini, M.; Wiseman, R.W.; Cooper, D.K.C.; Morelli, A.E.; Thomson, A.W.

2017-01-01

Systemic administration of autologous regulatory dendritic cells (DCreg; unpulsed or pulsed with donor antigen [Ag]), prolongs allograft survival and promotes transplant tolerance in rodents. Here, we demonstrate that nonhuman primate (NHP) monocyte-derived DCreg pre-loaded with cell membrane vesicles from allogeneic PBMC, induce T cell hyporesponsiveness to donor alloAg in vitro. These donor alloAg-pulsed autologous DCreg (1.4–3.6 x 106/kg) were administered intravenously, one day before MHC-mismatched renal transplantation to rhesus monkeys treated with costimulation blockade (cytotoxic T lymphocyte Ag 4 [CTLA4] Ig) and tapered rapamycin. Prolongation of graft median survival time from 39.5 days (no DCreg infusion; n=6 historical controls) and 29 days with control unpulsed DCreg (n=2), to 56 days with donor Ag-pulsed DCreg (n=5), was associated with evidence of modulated host CD4+ and CD8+ T cell responses to donor Ag and attenuation of systemic IL-17 production. Circulating anti-donor antibody (Ab) was not detected until CTLA4Ig withdrawal. One monkey treated with donor Ag-pulsed DCreg rejected its graft in association with progressively elevated anti-donor Ab, 525 days post-transplant (160 days after withdrawal of immunosuppression). These findings indicate a modest but not statistically significant beneficial effect of donor Ag-pulsed autologous DCreg infusion on NHP graft survival when administered with a minimal immunosuppressive drug regimen. PMID:28009481

Proteomic signatures in plasma during early acute renal allograft rejection.

PubMed

Freue, Gabriela V Cohen; Sasaki, Mayu; Meredith, Anna; Günther, Oliver P; Bergman, Axel; Takhar, Mandeep; Mui, Alice; Balshaw, Robert F; Ng, Raymond T; Opushneva, Nina; Hollander, Zsuzsanna; Li, Guiyun; Borchers, Christoph H; Wilson-McManus, Janet; McManus, Bruce M; Keown, Paul A; McMaster, W Robert

2010-09-01

Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR). Plasma samples were depleted of the 14 most abundant plasma proteins to enhance detection sensitivity. A total of 18 plasma proteins that encompassed processes related to inflammation, complement activation, blood coagulation, and wound repair exhibited significantly different relative concentrations between patient cohorts with and without BCAR (p value <0.05). Twelve proteins with a fold-change >or=1.15 were selected for diagnostic purposes: seven were increased (titin, lipopolysaccharide-binding protein, peptidase inhibitor 16, complement factor D, mannose-binding lectin, protein Z-dependent protease and beta(2)-microglobulin) and five were decreased (kininogen-1, afamin, serine protease inhibitor, phosphatidylcholine-sterol acyltransferase, and sex hormone-binding globulin) in patients with BCAR. The first three principal components of these proteins showed clear separation of cohorts with and without BCAR. Performance improved with the inclusion of sequential proteins, reaching a primary asymptote after the first three (titin, kininogen-1, and lipopolysaccharide-binding protein). Longitudinal monitoring over the first 3 months post-transplant based on ratios of these three proteins showed clear discrimination between the two patient cohorts at time of rejection. The score then declined to baseline following treatment and resolution of the rejection episode and remained comparable between cases and

Proteomic Signatures in Plasma during Early Acute Renal Allograft Rejection*

PubMed Central

Freue, Gabriela V. Cohen; Sasaki, Mayu; Meredith, Anna; Günther, Oliver P.; Bergman, Axel; Takhar, Mandeep; Mui, Alice; Balshaw, Robert F.; Ng, Raymond T.; Opushneva, Nina; Hollander, Zsuzsanna; Li, Guiyun; Borchers, Christoph H.; Wilson-McManus, Janet; McManus, Bruce M.; Keown, Paul A.; McMaster, W. Robert

2010-01-01

Acute graft rejection is an important clinical problem in renal transplantation and an adverse predictor for long term graft survival. Plasma biomarkers may offer an important option for post-transplant monitoring and permit timely and effective therapeutic intervention to minimize graft damage. This case-control discovery study (n = 32) used isobaric tagging for relative and absolute protein quantification (iTRAQ) technology to quantitate plasma protein relative concentrations in precise cohorts of patients with and without biopsy-confirmed acute rejection (BCAR). Plasma samples were depleted of the 14 most abundant plasma proteins to enhance detection sensitivity. A total of 18 plasma proteins that encompassed processes related to inflammation, complement activation, blood coagulation, and wound repair exhibited significantly different relative concentrations between patient cohorts with and without BCAR (p value <0.05). Twelve proteins with a fold-change ≥1.15 were selected for diagnostic purposes: seven were increased (titin, lipopolysaccharide-binding protein, peptidase inhibitor 16, complement factor D, mannose-binding lectin, protein Z-dependent protease and β2-microglobulin) and five were decreased (kininogen-1, afamin, serine protease inhibitor, phosphatidylcholine-sterol acyltransferase, and sex hormone-binding globulin) in patients with BCAR. The first three principal components of these proteins showed clear separation of cohorts with and without BCAR. Performance improved with the inclusion of sequential proteins, reaching a primary asymptote after the first three (titin, kininogen-1, and lipopolysaccharide-binding protein). Longitudinal monitoring over the first 3 months post-transplant based on ratios of these three proteins showed clear discrimination between the two patient cohorts at time of rejection. The score then declined to baseline following treatment and resolution of the rejection episode and remained comparable between cases and

Raman-based detection of hydroxyethyl starch in kidney allograft biopsies as a potential marker of allograft quality in kidney transplant recipients

NASA Astrophysics Data System (ADS)

Vuiblet, Vincent; Fere, Michael; Bankole, Ezechiel; Wynckel, Alain; Gobinet, Cyril; Birembaut, Philippe; Piot, Olivier; Rieu, Philippe

2016-09-01

In brain-dead donor resuscitation, hydroxyethyl starch (HES) use has been associated with presence of osmotic-nephrosis-like lesions in kidney transplant recipients. Our aim was to determine whether the presence of HES in protocol renal graft biopsies at three months (M3) after transplantation is associated with renal graft quality. According to the HES administered to the donor during the procurement procedure, two groups of patients were defined according graft exposition to HES: HES group, (N = 20) and control group (N = 6). Detection and relative quantification of HES was performed by Raman spectroscopy microimaging on M3 protocol renal graft biopsies. Statistical analyses were used to investigate the association between Raman data and graft characteristics. HES spectral signal was revealed negative in the control group, whereas it was positive in 40% of biopsies from the HES group. In the HES group, a stronger HES signal was associated with a lower risk of graft failure measured by the Kidney Donor Risk Index (KDRI) and was correlated with the allograft kidney function. Thus, HES accumulation in donor kidney, as probed by Raman biophotonic technique, is correlated with the quality of donor kidney and consequently the graft renal function and graft survival.

Optimising the use of mTOR inhibitors in renal transplantation.

PubMed

Russ, Graeme R

2013-11-20

Renal transplantation is the treatment of choice for end-stage renal failure. Although advances in immunosuppression have led to improvements in short-term outcomes, graft survival beyond 5 to 10 years has not improved. One of the major causes of late renal allograft failure is chronic allograft nephropathy, a component of which is nephrotoxicity from the use of calcineurin inhibitors (CNIs). In addition, premature patient death is a major limitation of renal transplantation and the major causes are cancer, cardiovascular disease and infection. CNI-free immunosuppressive regimens based on mammalian target of rapamycin (mTOR) inhibitors have been trial led over the last few years and have defined the rational use of these agents. Conversion from a CNI-based to an mTOR-inhibitor-based regimen has been successful at improving renal function for a number of years after conversion, although long-term survival outcomes are still awaited. The studies suggest that the safest and most effective time to convert is between 1 and 6 months after transplant. In addition, mTOR-inhibitor-based regimens have been shown to be associated with lower rates of post-transplant malignancy and less cytomegalovirus infection, which may add further to the appeal of this approach.

Surgical Anatomy and Microvascular Surgical Technique Relevant to Experimental Renal Transplant in Rat Employing Aortic and Inferior Venacaval Conduits.

PubMed

Shrestha, Badri Man; Haylor, John

2017-11-15

Rat models of renal transplant are used to investigate immunologic processes and responses to therapeutic agents before their translation into routine clinical practice. In this study, we have described details of rat surgical anatomy and our experiences with the microvascular surgical technique relevant to renal transplant by employing donor inferior vena cava and aortic conduits. For this study, 175 rats (151 Lewis and 24 Fisher) were used to establish the Fisher-Lewis rat model of chronic allograft injury at our institution. Anatomic and technical details were recorded during the period of training and establishment of the model. A final group of 12 transplanted rats were studied for an average duration of 51 weeks for the Lewis-to-Lewis isografts (5 rats) and 42 weeks for the Fisher-to-Lewis allografts (7 rats). Functional measurements and histology confirmed the diagnosis of chronic allograft injury. Mastering the anatomic details and microvascular surgical techniques can lead to the successful establishment of an experimental renal transplant model.

Risk of Infection After Allograft Anterior Cruciate Ligament Reconstruction: Are Nonprocessed Allografts More Likely to Get Infected? A Cohort Study of Over 10,000 Allografts.

PubMed

Yu, Anthony; Prentice, Heather A; Burfeind, William E; Funahashi, Tadashi; Maletis, Gregory B

2018-03-01

Allograft tissue is frequently used in anterior cruciate ligament reconstruction (ACLR). It is often irradiated and/or chemically processed to decrease the risk of disease transmission, but some tissue is aseptically harvested without further processing. Irradiated and chemically processed allograft tissue appears to have a higher risk of revision, but whether this processing decreases the risk of infection is not clear. To determine the incidence of deep surgical site infection after ACLR with allograft in a large community-based sample and to evaluate the association of allograft processing and the risk of deep infection. Cohort study; Level of evidence, 3. The authors conducted a cohort study using the Kaiser Permanente Anterior Cruciate Ligament Reconstruction Registry. Primary isolated unilateral ACLR with allograft were identified from February 1, 2005 to September 30, 2015. Ninety-day postoperative deep infections were identified via an electronic screening algorithm and then validated through chart review. Logistic regression was used to evaluate the likelihood of 90-day postoperative deep infection per allograft processing method: processed (graft treated chemically and/or irradiated) or nonprocessed (graft not irradiated or chemically processed). Of 10,190 allograft cases, 8425 (82.7%) received a processed allograft, and 1765 (17.3%) received a nonprocessed allograft. There were 15 (0.15%) deep infections during the study period: 4 (26.7%) coagulase-negative Staphylococcus, 4 (26.7%) methicillin-sensitive Staphylococcus aureus, 1 (6.7%) Peptostreptococcus micros, and 6 (40.0%) with no growth. There was no difference in the likelihood for 90-day deep infection for processed versus nonprocessed allografts (odds ratio = 1.36, 95% CI = 0.31-6.04). The overall incidence of deep infection after ACLR with allograft tissue was very low (0.15%), suggesting that the methods currently employed by tissue banks to minimize the risk of infection are effective. In this

Fas/Fas Ligand pathways gene polymorphisms in pediatric renal allograft rejection.

PubMed

Fadel, Fatina I; Elshamaa, Manal F; Salah, Ahmed; Nabhan, Marwa; Rasheed, Maha; Kamel, Solaf; Kandil, Dina; Thabet, Eman H

2016-07-01

An essential milestone in pediatric transplantation is to find noninvasive biomarkers to monitor acute rejection (AR). In this retrospective (Case-control) study, we examined the role of Fas -670A/G and Fas Ligand (FasL) -843C/T gene polymorphisms in allograft nephropathy in pediatric renal transplant recipients. In 47 pediatric kidney transplant recipients and 20 healthy controls, Fas -670A/G and FasL -843C/T gene polymorphisms as well as serum soluble Fas Ligand level (sFasL) were measured. Serum sFasL levels were significantly higher in transplant recipients children than that in controls (548.25±298.64pg/ml vs 143.17±44.55pg/ml, p=0.0001). There was no significant difference between patients with AR and those without AR in regards to serum sFasL levels (567.70±279.87pg/ml vs 507.85±342.80pg/ml, p=0.56). Fas -670A/G genotypes or alleles were not significantly different between controls and transplant recipients and among transplant recipients with and without AR. (P>0.05 for all). FasL -843C/T genotypes were not different between transplant recipients and controls and among transplant recipients with and without AR (P>0.05 for all). However, Frequency of C allele in transplant patients was significantly higher than that in the control group (44.68% vs 25%, P=0.03). FasL -843C/T alleles were significantly different between patients with and without AR (P=0.03). The percentages of C allele were higher in children with AR (58.82% vs 36.67%). We found that serum FasL and serum creatinine were variables that were independently associated with AR. This study suggests that FasL gene polymorphisms in peripheral blood might be accurate in detecting cellular AR. Copyright © 2016 Elsevier B.V. All rights reserved.

Protective effects of FTY720 on chronic allograft nephropathy by reducing late lymphocytic infiltration.

PubMed

Wang, Minghui; Liu, Shanying; Ouyang, Nengtai; Song, Erwei; Lutz, Jens; Heemann, Uwe

2004-09-01

Lymphocytic infiltration is obvious throughout early and late stages of chronic allograft nephropathy. Early infiltrating lymphocytes are involved in initial insults to kidney allografts, but the contribution of late infiltration to long-term allograft attrition is still controversial. Early application of FTY720 reduced the number of graft infiltrating lymphocytes, and inhibited acute rejection. The present study investigated the potential of FTY720 to reduce the number of infiltrating lymphocytes even at a late stage, and, thus, slow the pace of chronic allograft nephropathy. Fisher (F344) rat kidneys were orthotopically transplanted into Lewis recipients with an initial 10-day course of cyclosporine A (1.5 mg/kg/day). FTY720, at a dose of 0.5 mg/kg/day, or vehicle was administered to recipients either from weeks 12 to 24 or from 20 to 24 after transplantation. Animals were harvested 24 weeks after transplantation for histologic, immunohistologic, and molecular analysis. FTY720, either initiated at 12 or 20 weeks after transplantation, reduced urinary protein excretion, and significantly ameliorated glomerulosclerosis, interstitial fibrosis, tubular atrophy, and intimal proliferation of graft arteries at 24 weeks after transplantation. Furthermore FTY720 markedly suppressed lymphocyte infiltration and decreased mRNA levels of interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta), and platelet-derived growth factor-B (PDGF-B) but enhanced the number of apoptotic cells in grafts. FTY720 ameliorated chronic allograft nephropathy even at advanced stages. Furthermore, our data suggest that this effect was achieved by a reduction of graft infiltrating lymphocytes.

Ankle bipolar fresh osteochondral allograft survivorship and integration: transplanted tissue genetic typing and phenotypic characteristics.

PubMed

Neri, Simona; Vannini, Francesca; Desando, Giovanna; Grigolo, Brunella; Ruffilli, Alberto; Buda, Roberto; Facchini, Andrea; Giannini, Sandro

2013-10-16

Fresh osteochondral allografts represent a treatment option for early ankle posttraumatic arthritis. Transplanted cartilage survivorship, integration, and colonization by recipient cells have not been fully investigated. The aim of this study was to evaluate the ability of recipient cells to colonize the allograft cartilage and to assess allograft cell phenotype. Seventeen ankle allograft samples were studied. Retrieved allograft cartilage DNA from fifteen cases was compared with recipient and donor constitutional DNA by genotyping. In addition, gene expression was evaluated on six allograft cartilage samples by means of real-time reverse transcription-polymerase chain reaction. Histology and immunohistochemistry were performed to support molecular observations. Of fifteen genotyped allografts, ten completely matched to the host, three matched to the donor, and two showed a mixed profile. Gene expression analysis showed that grafted cartilage expressed cartilage-specific markers. The rare persistence of donor cells and the prevailing presence of host DNA in retrieved ankle allografts suggest the ingrowth of recipient cells into the allograft cartilage, presumably migrating from the subchondral bone, in accordance with morphological findings. The expression of chondrogenic markers in some of the samples argues for the acquisition of a chondrocyte-like phenotype by these cells. To our knowledge, this is the first report describing the colonization of ankle allograft cartilage by host cells showing the acquisition of a chondrocyte-like phenotype.

Outcome of renal replacement treatment in patients with diabetes mellitus.

PubMed Central

McMillan, M A; Briggs, J D; Junor, B J

1990-01-01

OBJECTIVE--To compare the outcome of renal replacement treatment in patients with diabetes mellitus and in non-diabetic patients with end stage renal failure. DESIGN--Retrospective comparison of cases and matched controls. SETTING--Renal unit, Western Infirmary, Glasgow, providing both dialysis and renal transplantation. PATIENTS--82 Diabetic patients starting renal replacement treatment between 1979 and 1988, compared with 82 matched non-diabetic controls with renal failure and 39 different matched controls undergoing renal transplantation. MAIN OUTCOME MEASURES--Patient characteristics, history of smoking, prevalence of left ventricular hypertrophy and myocardial ischaemia at start of renal replacement treatment; survival of patients with renal replacement treatment and of patients and allografts with renal transplantation. RESULTS--The overall survival of the diabetic patients during the treatment was 83%, 59%, and 50% at one, three, and five years. Survival was significantly poorer in the diabetic patients than the controls (p less than 0.001). Particularly adverse features for outcome at the start of treatment were increasing age (p less than 0.01) and current cigarette smoking (relative risk (95% confidence interval) 2.28 (0.93 to 4.84), p less than 0.05). Deaths were mainly from cardiac and vascular causes. The incidence of peritonitis in patients on continuous ambulatory peritoneal dialysis was the same in diabetic patients and controls (49% in each group remained free of peritonitis after one year), and the survival of renal allografts was not significantly worse in diabetic patients (p less than 0.5). CONCLUSIONS--Renal replacement treatment may give good results in diabetic patients, although the outlook remains less favourable than for non-diabetic patients because of coexistent, progressive vascular disease, which is more severe in older patients. PMID:2207427

Deaths from occlusive arterial disease in renal allograft recipients.

PubMed

Ibels, L S; Stewart, J H; Mahony, J F; Sheil, A G

1974-08-31

In a series of 325 recipients of cadaveric renal transplants sudden occlusive arterial disease was found to be responsible for 12% of deaths. Acute myocardial infarction (9%) occurred 25 times more than expected in the normal population and cerebral thrombosis (3%) 300 times more. The greatest loss was in the initial three-month period after transplantation. Patients with renal failure due to essential hypertension were especially at risk, accounting for six of the 12 deaths.

Cost effectiveness of meniscal allograft for torn discoid lateral meniscus in young women.

PubMed

Ramme, Austin J; Strauss, Eric J; Jazrawi, Laith; Gold, Heather T

2016-09-01

A discoid meniscus is more prone to tears than a normal meniscus. Patients with a torn discoid lateral meniscus are at increased risk for early onset osteoarthritis requiring total knee arthroplasty (TKA). Optimal management for this condition is controversial given the up-front cost difference between the two treatment options: the more expensive meniscal allograft transplantation compared with standard partial meniscectomy. We hypothesize that meniscal allograft transplantation following excision of a torn discoid lateral meniscus is more cost-effective compared with partial meniscectomy alone because allografts will extend the time to TKA. A decision analytic Markov model was created to compare the cost effectiveness of two treatments for symptomatic, torn discoid lateral meniscus: meniscal allograft and partial meniscectomy. Probability estimates and event rates were derived from the scientific literature, and costs and benefits were discounted by 3%. One-way sensitivity analyses were performed to test model robustness. Over 25 years, the partial meniscectomy strategy cost $10,430, whereas meniscal allograft cost on average $4040 more, at $14,470. Partial meniscectomy postponed TKA an average of 12.5 years, compared with 17.30 years for meniscal allograft, an increase of 4.8 years. Allograft cost $842 per-year-gained in time to TKA. Meniscal allografts have been shown to reduce pain and improve function in patients with discoid lateral meniscus tears. Though more costly, meniscal allografts may be more effective than partial meniscectomy in delaying TKA in this model. Additional future long term clinical studies will provide more insight into optimal surgical options.

Serial protocol biopsies to quantify the progression of chronic transplant nephropathy in stable renal allografts.

PubMed

Moreso, F; Lopez, M; Vallejos, A; Giordani, C; Riera, L; Fulladosa, X; Hueso, M; Alsina, J; Grinyó, J M; Serón, D

2001-05-01

To evaluate the utility of intimal thickness and interstitial width as a primary efficacy variable in the design of clinical trials aimed to modify the natural history of chronic allograft nephropathy. A donor and a 4-month protocol biopsy were evaluated in 40 stable grafts according to the Banff schema. In 27 patients, a second protocol biopsy was done at 1 yr. Arterial intimal volume fraction (Vvintima/artery) and cortical interstitial volume fraction (Vvinterstitium/cortex) were estimated with a point counting technique. Chronic Banff scores increased during follow-up, while acute scores reached its peak at 4 months. Vvintima/artery and Vvinterstitium/cortex significantly increased at 4 months, but not at 1 yr. Vvintima/artery at 4 months correlated with donor Vvintima/artery (r = 0.57, p < 0.001), histocompatibility (r = 0.38, p = 0.01) and serum cholesterol (r = 0.31, p = 0.047). Vvinterstitium/cortex at 4 months correlated with recipient body surface area (r = 0.44, p = 0.004) and delayed graft function (p = 0.016). Power calculations showed that Vvintima/artery and Vvinterstitium/cortex allow an important reduction in minimum sample size of a hypothetical trial aimed to prevent chronic allograft nephropathy. Intimal thickening and interstitial widening progresses rapidly during the first 4 months after transplantation and slowly thereafter. These parameters can be considered as a primary efficacy variable in trials aimed to prevent chronic allograft nephropathy.

PRINS Long Noncoding RNA Involved in IP-10-Mediated Allograft Rejection in Rat Kidney Transplant.

PubMed

Zou, X-F; Song, B; Duan, J-H; Hu, Z-D; Cui, Z-L; Yang, T

2018-06-01

Previously, high levels of CXCR3+ T-cell recruitment was demonstrated in the prolonged ischemia-accelerated acute allograft rejection in rat kidney transplant. In the present study, the effect of chemokine IP-10 was investigated and the expression of chemokine-related PRINS (Psoriasis susceptibility-related RNA gene induced by stress) lncRNA determined in the allografts subjected to ischemia. F344-to-Lewis rat kidney transplantation was performed, and renal grafts were stored for 2 hours or 16 hours. Samples were removed at 24 hours and 7 days after operation. Cellular infiltration was determined with the use of immunohistochemistry, and messenger RNA expression was assessed with the use of real-time polymerase chain reaction. The 16-hour-ischemia kidney displayed acute tubule damage and up-regulation of PRINS lncRNA expression. On day 7, IP-10 expression and CD3-positive T cells were increased in allografts compared with control samples, which were inhibited by the IP-10 antibody treatment accompanied by reduced serum creatinine. These observations provide evidence for IP-10 in a regulatory role in cold ischemia-elicited acute allograft rejection and in PRINS lncRNA expression. Our data enhance the understanding of the mechanism underlying between prolonged ischemia and acute rejection. Copyright © 2018 Elsevier Inc. All rights reserved.

Scabies in a bilateral hand allograft recipient: An additional mimicker of acute skin rejection in vascularized composite allotransplantation.

PubMed

Kanitakis, Jean; Morelon, Emmanuel

2017-06-01

Vascularized composite tissue allografts include skin, which frequently undergoes, in the early post-graft period, acute rejections. The diagnosis of acute rejection may be difficult as it can be mimicked by several dermatoses. We present a bilateral hand allograft recipient who developed, 16.5 years post-graft, cutaneous lesions raising suspicion about rejection. Physical examination and skin biopsy were diagnostic of scabies. This ectoparasitosis should be added in the list of dermatoses that can mimic allograft rejection in vascular composite allografts. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Personal experience with the procurement of 132 liver allografts

PubMed Central

Yanaga, K.; Tzakis, A.G.; Starzl, T.E.

2010-01-01

A single donor surgeon's experience procuring the livers from 132 donors is described. Thirty-seven grafts (28.9%) had hepatic arterial anomalies, 19 (14.4%) of which required arterial reconstruction prior to transplantation. Of the 121 grafts evaluated for early function, 103 grafts (85.2%) functioned well, whereas 14 grafts (11.6%) functioned poorly and 4 grafts (3.3%) failed to function at all. The variables associated with less than optimal function of the graft consisted of donor age (P < 0.05), duration of donor's stay in the intensive care unit (P < 0.005), abnormal graft appearance (P < 0.05), and such recipient problems as vascular thromboses during or immediately following transplantation (P < 0.005). A new preservation fluid, University of Wisconsin solution, allowed safe and longer cold storage of the liver allograft than did Euro-Collins' solution (P < 0.0001). A parameter of liver allograft viability, which is simple and predictive of allograft function prior to the actual transplant procedure, is urgently needed. PMID:2803485

Immunephenotype of glomerular and interstitial infiltrating cells in protocol renal allograft biopsies and histological diagnosis.

PubMed

Moreso, F; Seron, D; O'Valle, F; Ibernon, M; Gomà, M; Hueso, M; Cruzado, J M; Bestard, O; Duarte, V; del Moral, R García; Grinyó, J M

2007-12-01

Patients with a protocol renal allograft biopsy simultaneously displaying interstitial fibrosis/tubular atrophy (IF/TA) and subclinical rejection (SCR) have a shortened graft survival than patients with a normal biopsy, or with a biopsy only displaying IF/TA or SCR. The poor outcome of these patients could be related with a more severe inflammation. We evaluate the immunophenotype of infiltrating cells in these diagnostic categories. Nonexhausted paraffin blocks from protocol biopsies done during the first year were stained with anti-CD45, CD3, CD20, CD68 and CD15 monoclonal antibodies. Glomerular and interstitial positive cells were counted. C4d deposition in peritubular capillaries was evaluated. Histological diagnoses were: normal (n = 80), SCR (n = 17), IF/TA (n = 42) and IF/TA + SCR (n = 17). Only interstitial CD20 positive cells were significantly increased in patients displaying IF/TA + SCR; normal (137 +/- 117), SCR (202 +/- 145), IF/TA (208 +/- 151) and IF/TA + SCR (307 +/- 180 cells/mm(2)), p < 0.01. The proportion of biopsies displaying C4d deposition was not different among groups. The upper tertile of CD20 positive interstitial cells was associated with a decreased death-censored graft survival (relative risk: 3.01, 95% confidence interval: 1.23-7.35; p = 0.015). These data suggest that B-cell interstitial infiltrates are associated with histological damage and outcome, but do not distinguish whether these infiltrates were the cause or the consequence of chronic tubulo-interstitial damage.

Renal Allograft Survival in Nonhuman Primates Infused With Donor Antigen-Pulsed Autologous Regulatory Dendritic Cells.

PubMed

Ezzelarab, M B; Raich-Regue, D; Lu, L; Zahorchak, A F; Perez-Gutierrez, A; Humar, A; Wijkstrom, M; Minervini, M; Wiseman, R W; Cooper, D K C; Morelli, A E; Thomson, A W

2017-06-01

Systemic administration of autologous regulatory dendritic cells (DCreg; unpulsed or pulsed with donor antigen [Ag]), prolongs allograft survival and promotes transplant tolerance in rodents. Here, we demonstrate that nonhuman primate (NHP) monocyte-derived DCreg preloaded with cell membrane vesicles from allogeneic peripheral blood mononuclear cells induce T cell hyporesponsiveness to donor alloantigen (alloAg) in vitro. These donor alloAg-pulsed autologous DCreg (1.4-3.6 × 10 6 /kg) were administered intravenously, 1 day before MHC-mismatched renal transplantation to rhesus monkeys treated with costimulation blockade (cytotoxic T lymphocyte Ag 4 immunoglobulin [CTLA4] Ig) and tapered rapamycin. Prolongation of graft median survival time from 39.5 days (no DCreg infusion; n = 6 historical controls) and 29 days with control unpulsed DCreg (n = 2), to 56 days with donor Ag-pulsed DCreg (n = 5) was associated with evidence of modulated host CD4 + and CD8 + T cell responses to donor Ag and attenuation of systemic IL-17 production. Circulating anti-donor antibody (Ab) was not detected until CTLA4 Ig withdrawal. One monkey treated with donor Ag-pulsed DCreg rejected its graft in association with progressively elevated anti-donor Ab, 525 days posttransplant (160 days after withdrawal of immunosuppression). These findings indicate a modest but not statistically significant beneficial effect of donor Ag-pulsed autologous DCreg infusion on NHP graft survival when administered with a minimal immunosuppressive drug regimen. © 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

Osteochondral allograft.

PubMed

Torrie, Arissa M; Kesler, William W; Elkin, Joshua; Gallo, Robert A

2015-12-01

Over the past decade, osteochondral allograft transplantation has soared in popularity. Advances in storage techniques have demonstrated improved chondrocyte viability at longer intervals and allowed for potential of increased graft availability. Recent studies have stratified outcomes according to location and etiology of the chondral or osteochondral defect. Unipolar lesions generally have favorable outcomes with promising 10-year survival rates. Though those undergoing osteochondral allograft transplantation often require reoperation, patient satisfaction remains high.

Inability to determine tissue health is main indication of allograft use in intermediate extent burns.

PubMed

Fletcher, John L; Cancio, Leopoldo C; Sinha, Indranil; Leung, Kai P; Renz, Evan M; Chan, Rodney K

2015-12-01

Cutaneous allograft is commonly used in the early coverage of excised burns when autograft is unavailable. However, allograft is also applied in intermediate-extent burns (25-50%), during cases in which it is possible to autograft. In this population, there is a paucity of data on the indications for allograft use. This study explores the indications for allograft usage in moderate size burns. Under an IRB-approved protocol, patients admitted to our burn unit between March 2003 and December 2010 were identified through a review of the burn registry. Data on allograft use, total burn surface area, operation performed, operative intent, number of operations, intensive care unit length of stay, and overall length of stay were collected and analyzed. Data are presented as means±standard deviations, except where noted. In the study period, 146 patients received allograft during their acute hospitalization. Twenty-five percent of allograft recipients sustained intermediate-extent burns. Patients with intermediate-extent burns received allograft later in their hospitalization than those with large-extent (50-75% TBSA) burns (6.8 days vs. 3.4 days, p=0.01). Allografted patients with intermediate-extent burns underwent more operations (10.8 vs. 6.1, p=0.002) and had longer hospitalizations (78.3 days vs. 40.9 days, p<0.001) than non-allografted patients, when controlled for TBSA. Clinical rationale for placement of allograft in this population included autograft failure, uncertain depth of excision, lack of autograft donor site, and wound complexity. When uncertain depth of excision was the indication, allograft was universally applied onto the face. In half of allografted intermediate-extent burn patients the inability to identify a viable recipient bed was the ultimate reason for allograft use. Unlike large body surface area burns, allograft skin use in intermediate-extent injury occurs later in the hospitalization and is driven by the inability to determine wound bed

Radioprotection provides functional mechanics but delays healing of irradiated tendon allografts after ACL reconstruction in sheep.

PubMed

Seto, Aaron U; Culp, Brian M; Gatt, Charles J; Dunn, Michael

2013-12-01

Successful protection of tissue properties against ionizing radiation effects could allow its use for terminal sterilization of musculoskeletal allografts. In this study we functionally evaluate Achilles tendon allografts processed with a previously developed radioprotective treatment based on (1-ethyl-3-(3-dimethylaminopropyl)carbodiimide) crosslinking and free radical scavenging using ascorbate and riboflavin, for ovine anterior cruciate ligament reconstruction. Arthroscopic anterior cruciate ligament (ACL) reconstruction was performed using double looped allografts, while comparing radioprotected irradiated and fresh frozen allografts after 12 and 24 weeks post-implantation, and to control irradiated grafts after 12 weeks. Radioprotection was successful at preserving early subfailure mechanical properties comparable to fresh frozen allografts. Twelve week graft stiffness and anterior-tibial (A-T) translation for radioprotected and fresh frozen allografts were comparable at 30 % of native stiffness, and 4.6 and 5 times native A-T translation, respectively. Fresh frozen allograft possessed the greatest 24 week peak load at 840 N and stiffness at 177 N/mm. Histological evidence suggested a delay in tendon to bone healing for radioprotected allografts, which was reflected in mechanical properties. There was no evidence that radioprotective treatment inhibited intra-articular graft healing. This specific radioprotective method cannot be recommended for ACL reconstruction allografts, and data suggest that future efforts to improve allograft sterilization procedures should focus on modifying or eliminating the pre-crosslinking procedure.

Effect of intraoperative transesophageal Doppler-guided fluid therapy versus central venous pressure-guided fluid therapy on renal allograft outcome in patients undergoing living donor renal transplant surgery: a comparative study.

PubMed

Srivastava, Divya; Sahu, Sandeep; Chandra, Abhilash; Tiwari, Tanmay; Kumar, Sanjay; Singh, P K

2015-12-01

Transesophageal Doppler (TED)-guided intraoperative fluid therapy has shown to noninvasively optimize intravascular volume and reduce postoperative morbidity. The aim of this study was to compare the effects of Doppler-guided intraoperative fluid administration and central venous pressure (CVP)-guided fluid therapy on renal allograft outcome and postoperative complications. A prospective nonrandomized active controlled study was conducted on end-stage renal disease patients scheduled for living donor renal transplant surgery. 110 patients received intraoperative fluid guided by corrected flow time (FTc) and variation in stroke volume values obtained by continuous TED monitoring. Data of 104 patients in whom intraoperative fluid administration was guided by CVP values were retrospectively obtained for a control. The amount of intraoperative fluid given in the study group (12.20 ± 4.24 ml/kg/h) was significantly lower than in the controls (22.21 ± 4.67 ml/kg/h). The amount of colloid used was also significantly less and fewer recipients were seen to require colloid (69 vs 85%). The mean arterial pressures were comparable throughout. CVP reached was 7.18 ± 3.17 mmHg in the study group. It was significantly higher in the controls (13.42 ± 3.12 mmHg). The postoperative graft function and rate of dysfunction were comparable. Side-effects like postoperative dyspnoea (4.8 vs 0%) and tissue edema (9.6 vs 2.7%) were higher in the controls. FTc-guided intraoperative fluid therapy achieved the same rate of immediate graft function as CVP-guided fluid therapy but used a significantly less amount of fluid. The incidence of postoperative complications related to fluid overload was also reduced. The use of TED may replace invasive central line insertions in the future.

Liver microRNA profile of induced allograft tolerance

PubMed Central

Vitalone, Matthew James; Wai, Liang; Fujiki, Masato; Lau, Audrey H.; Littau, Erik; Esquivel, Carlos; Martinez, Olivia M.; Krams, Sheri M.

2016-01-01

Introduction Although the liver is less immunogenic than other solid organs, most liver transplant recipients receive lifelong immunosuppression. In both experimental models and clinical transplantation, total Lymphoid Irradiation (TLI) has been shown to induce allograft tolerance. Our goal was to identify the microRNAs (miRNAs) expressed in tolerant liver allograft recipients in an experimental model of TLI-induced tolerance. Methods To identify the miRNAs associated with TLI-induced tolerance we examined syngeneic recipients (Lewis→Lewis) and allogeneic recipients (DA→Lewis) of orthotropic liver transplants that received post-transplant TLI, allogeneic recipients that were not treated post-transplantation and experienced acute rejection, and native DA livers. QPCR miRNA array cards were used to profile liver grafts. Results We identified 12 miRNAs that were specifically and significantly increased during acute rejection. In early tolerance, 33 miRNAs were altered compared to syngeneic livers, with 80% of the miRNAs increased. In established tolerance 42 miRNAs were altered. In addition, miR-142-5p and miR-181a demonstrated increased expression in tolerant livers (both early and established tolerance) as compared to syngeneic livers. A principal component analysis of all miRNAs assayed, demonstrated a profile in established tolerance that was closely related to that seen in syngeneic livers. Conclusions The miRNA profile of established tolerant allografts is very similar to syngeneic grafts suggesting tolerance may be a return to an immunological state of quiescence. PMID:26950716

Early changes in the apparent diffusion coefficient and MMP-9 expression of a cervical carcinoma U14 allograft model following irradiation.

PubMed

Huang, Yecai; Huang, Jianming; Feng, Mei; Ren, Jing; Mi, Kun; Cheng, Jia; Song, Bing; Lang, Jinyi

2017-12-01

A cervical carcinoma allograft model was designed to assess the correlation between early changes in the apparent diffusion coefficient (ADC) values on diffusion-weighted magnetic resonance imaging (DW-MRI) and the expression of matrix metalloproteinase-9 (MMP-9) in tumors. BALB/c mice with U14 tumor allografts on the right rear flank were irradiated with a single 20 Gy dose. All tumor-bearing mice were subjected to DW-MRI, followed by calculation of the ADC values and characterization of the T1 and T2 relaxation time constants. Pre- and post-irradiation ADC values were compared with the tumor volume, and the immunohistochemical staining of MMP-9 and hematoxylin-eosin (HE) staining of tumor allografts. However, no correlations between the pre-treatment ADC values and changes in tumor volumes following irradiation were observed. Notably, the mean ADC value was significantly higher in the irradiated tumors (0.756±0.102×10 -3 mm 2 /sec) as compared with those in the untreated tumors (0.501±0.052×10 -3 mm 2 /sec; P=0.002; r=0.682). Additionally, immunohistochemical staining demonstrated that MMP-9 expression in the irradiated tumors was significantly increased. The mean ADC value was significantly higher in the irradiated tumors with high MMP-9 expression levels (0.815±0.112×10 -3 mm 2 /sec), as compared with in the untreated tumors with low MMP-9 expression levels (0.631±0.068×10 -3 mm 2 /sec). Quantitative analysis determined that the ADC values were correlated with MMP-9 expression (r=0.752; P=0.003). Combined, these results suggest that radiation-induced increases in MMP-9 expression levels may be responsible for early changes in the mean ADC value and the response to irradiation in cervical carcinoma.

The evolving role of alemtuzumab (Campath-1H) in renal transplantation

PubMed Central

Pham, Phuong-Thu T; Lipshutz, Gerald S; Pham, Phuong-Truc T; Kawahji, Joseph; Singer, Jennifer S; Pham, Phuong-Chi T

2009-01-01

The introduction of new immunosuppressive agents into clinical transplantation in the 1990s has resulted in excellent short-term graft survival. Nonetheless, extended long-term graft outcomes have not been achieved due in part to the nephrotoxic effects of calcineurin inhibitors (CNIs) and the adverse effects of steroid on cardiovascular disease risk factors. Induction therapy with lymphocyte depleting antibodies has originally been introduced into renal transplantation to provide intense immunosuppression in the early post-transplant period to prevent allograft rejection. Over the past half decade, induction therapy with both non-lymphocyte depleting (basiliximab and daclizumab) and lymphocyte-depleting antibodies (antithymocyte antibodies, OKT3, alemtuzumab) has increasingly been utilized in steroid or CNI sparing protocols in the early postoperative period. Alemtuzumab is a humanized monoclonal antibody targeted against CD52 on the surface of circulatory mononuclear cells. The ability of alemtuzumab (Campath-1H) to provide rapid and profound depletion of lymphocytes from the peripheral blood has sparked interest in the use of this agent as induction therapy in steroid and/or CNI minimization or avoidance protocols. This article provides an overview of the literarure on the evolving role of alemtuzumab in renal transplantation. PMID:19920920

Autograft versus nonirradiated allograft tissue for anterior cruciate ligament reconstruction: a systematic review.

PubMed

Mariscalco, Michael W; Magnussen, Robert A; Mehta, Divyesh; Hewett, Timothy E; Flanigan, David C; Kaeding, Christopher C

2014-02-01

physical examination findings, and all studies reported patient-reported outcome scores. This review demonstrated no statistically significant difference between autografts and nonirradiated allografts in any outcome measure. No significant differences were found in graft failure rate, postoperative laxity, or patient-reported outcome scores when comparing ACLR with autografts to nonirradiated allografts in this systematic review. These findings apply to patients in their late 20s and early 30s. Caution is advised when considering extrapolation of these findings to younger, more active cohorts.

Desensitization protocol enabling pediatric crossmatch-positive renal transplantation: successful HLA-antibody-incompatible renal transplantation of two highly sensitized children.

PubMed

Adamusiak, Anna M; Stojanovic, Jelena; Shaw, Olivia; Vaughan, Robert; Sebire, Neil J; Drage, Martin; Kessaris, Nicos; Marks, Stephen D; Mamode, Nizam

2017-02-01

Renal transplantation improves quality of life (QoL) and survival in children requiring renal replacement therapy (RRT). Sensitization with development of a broad-spectrum of anti-HLA antibodies as a result of previous transplantation or after receiving blood products is an increasing problem. There are no published reports of desensitization protocols in children allowing renal transplantation from HLA-antibody-incompatible living donors. We adopted our well-established adult desensitization protocol for this purpose and undertook HLA antibody-incompatible living donor renal transplants in two children: a 14-year-old girl and a 13-year-old boy. After 2 and 1.5 years of follow-up, respectively, both patients have stable renal allograft function despite a rise in donor-specific antibodies in one case. HLA-incompatible transplantation should be considered in selected cases for sensitized children.

Dendritic Cells in Kidney Transplant Biopsy Samples Are Associated with T Cell Infiltration and Poor Allograft Survival

PubMed Central

De Serres, Sacha A.; Safa, Kassem; Bijol, Vanesa; Ueno, Takuya; Onozato, Maristela L.; Iafrate, A. John; Herter, Jan M.; Lichtman, Andrew H.; Mayadas, Tanya N.; Guleria, Indira; Rennke, Helmut G.; Najafian, Nader; Chandraker, Anil

2015-01-01

Progress in long-term renal allograft survival continues to lag behind the progress in short-term transplant outcomes. Dendritic cells are the most efficient antigen-presenting cells, but surprisingly little attention has been paid to their presence in transplanted kidneys. We used dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin as a marker of dendritic cells in 105 allograft biopsy samples from 105 kidney transplant recipients. High dendritic cell density was associated with poor allograft survival independent of clinical variables. Moreover, high dendritic cell density correlated with greater T cell proliferation and poor outcomes in patients with high total inflammation scores, including inflammation in areas of tubular atrophy. We then explored the association between dendritic cells and histologic variables associated with poor prognosis. Multivariate analysis revealed an independent association between the densities of dendritic cells and T cells. In biopsy samples with high dendritic cell density, electron microscopy showed direct physical contact between infiltrating lymphocytes and cells that have the ultrastructural morphologic characteristics of dendritic cells. The origin of graft dendritic cells was sought in nine sex-mismatched recipients using XY fluorescence in situ hybridization. Whereas donor dendritic cells predominated initially, the majority of dendritic cells in late allograft biopsy samples were of recipient origin. Our data highlight the prognostic value of dendritic cell density in allograft biopsy samples, suggest a new role for these cells in shaping graft inflammation, and provide a rationale for targeting dendritic cell recruitment to promote long-term allograft survival. PMID:25855773

Sclerotherapy with tetracycline for hydroceles in renal transplant patients.

PubMed

Sankari, B R; Boullier, J A; Garvin, P J; Parra, R O

1992-10-01

A total of 17 patients with hydroceles following renal transplantation underwent sclerotherapy with tetracycline hydrochloride (10 ml. of a 5% solution of tetracycline in 1% lidocaine). A successful outcome was obtained in 15 patients (88%). Post-sclerotherapy hydrocelectomy was necessary in 2 patients (12%). No major complications (testicular loss, scrotal abscess or necrosis) occurred in any patient. Pain at injection was the only adverse effect. Tetracycline sclerotherapy for hydroceles appears to be an effective and safe procedure in the renal transplant population. We recommend this procedure as the initial treatment modality for hydroceles in patients with a renal allograft.

Identification of a B cell signature associated with renal transplant tolerance in humans

PubMed Central

Newell, Kenneth A.; Asare, Adam; Kirk, Allan D.; Gisler, Trang D.; Bourcier, Kasia; Suthanthiran, Manikkam; Burlingham, William J.; Marks, William H.; Sanz, Ignacio; Lechler, Robert I.; Hernandez-Fuentes, Maria P.; Turka, Laurence A.; Seyfert-Margolis, Vicki L.

2010-01-01

Establishing long-term allograft acceptance without the requirement for continuous immunosuppression, a condition known as allograft tolerance, is a highly desirable therapeutic goal in solid organ transplantation. Determining which recipients would benefit from withdrawal or minimization of immunosuppression would be greatly facilitated by biomarkers predictive of tolerance. In this study, we identified the largest reported cohort to our knowledge of tolerant renal transplant recipients, as defined by stable graft function and receiving no immunosuppression for more than 1 year, and compared their gene expression profiles and peripheral blood lymphocyte subsets with those of subjects with stable graft function who are receiving immunosuppressive drugs as well as healthy controls. In addition to being associated with clinical and phenotypic parameters, renal allograft tolerance was strongly associated with a B cell signature using several assays. Tolerant subjects showed increased expression of multiple B cell differentiation genes, and a set of just 3 of these genes distinguished tolerant from nontolerant recipients in a unique test set of samples. This B cell signature was associated with upregulation of CD20 mRNA in urine sediment cells and elevated numbers of peripheral blood naive and transitional B cells in tolerant participants compared with those receiving immunosuppression. These results point to a critical role for B cells in regulating alloimmunity and provide a candidate set of genes for wider-scale screening of renal transplant recipients. PMID:20501946

Detection of occupational lead nephropathy using early renal markers.

PubMed

Kumar, B D; Krishnaswamy, K

1995-01-01

Automotive use of leaded gasoline continues to be an important source of occupational exposure to lead in India and other countries. The present study assessed the renal function and markers of early renal damage of 22 mechanics at three automobile garages. Urinary N-acetyl-3-D-glucosaminidase activity and beta-2-microglobulin levels were significantly increased in auto garage mechanics with blood leads of 30-69 micrograms/dL. A significant correlation was observed between blood lead levels and urinary N-acetyl-3-D-glucosaminidase activity but not with urine beta-2-microglobulin levels. A marginal impairment in creatinine clearance was not statistically significant. Urinary N-acetyl-3-D-glucosaminidase activity offers a sensitive monitor of blood lead and renal tubular injury.

IL-1 Receptor Signaling on Graft Parenchymal Cells Regulates Memory and De Novo Donor-Reactive CD8 T Cell Responses to Cardiac Allografts.

PubMed

Iida, Shoichi; Tsuda, Hidetoshi; Tanaka, Toshiaki; Kish, Danielle D; Abe, Toyofumi; Su, Charles A; Abe, Ryo; Tanabe, Kazunari; Valujskikh, Anna; Baldwin, William M; Fairchild, Robert L

2016-03-15

Reperfusion of organ allografts induces a potent inflammatory response that directs rapid memory T cell, neutrophil, and macrophage graft infiltration and their activation to express functions mediating graft tissue injury. The role of cardiac allograft IL-1 receptor (IL-1R) signaling in this early inflammation and the downstream primary alloimmune response was investigated. When compared with complete MHC-mismatched wild-type cardiac allografts, IL-1R(-/-) allografts had marked decreases in endogenous memory CD8 T cell and neutrophil infiltration and expression of proinflammatory mediators at early times after transplant, whereas endogenous memory CD4 T cell and macrophage infiltration was not decreased. IL-1R(-/-) allograft recipients also had marked decreases in de novo donor-reactive CD8, but not CD4, T cell development to IFN-γ-producing cells. CD8 T cell-mediated rejection of IL-1R(-/-) cardiac allografts took 3 wk longer than wild-type allografts. Cardiac allografts from reciprocal bone marrow reconstituted IL-1R(-/-)/wild-type chimeric donors indicated that IL-1R signaling on graft nonhematopoietic-derived, but not bone marrow-derived, cells is required for the potent donor-reactive memory and primary CD8 T cell alloimmune responses observed in response to wild-type allografts. These studies implicate IL-1R-mediated signals by allograft parenchymal cells in generating the stimuli-provoking development and elicitation of optimal alloimmune responses to the grafts. Copyright © 2016 by The American Association of Immunologists, Inc.

Expanded criteria donor and donation after circulatory death renal allografts in the West of Scotland: Their place in the kidney allocation process.

PubMed

Hesse, Kerrick; Aitken, Emma; Clancy, Marc; Vesey, Alex

2016-06-01

Due to the rising disparity between demand and availability, organs from expanded criteria donors (ECD) and donors after determination of circulatory death (DCD) are increasingly used. The purpose of this study was to report outcomes in recipients of ECD and DCD renal allografts from a single centre. A retrospective analysis from a single centre for all renal transplants performed between 2001 and 2010 inclusive was undertaken. SCD (standard criteria donor) and ECD organs were compared, as were DCD and DBD (donation after determination of brain stem death) organs. Baseline data and predefined standard transplant outcomes were collected and compared using appropriate statistical tests. P < 0.05 was defined as significant. 729 renal transplants were performed. Comparing ECD to SCD organs, there was a significant difference in graft survival between groups (logrank for trend, p = 0.032) with ECD organs doing worse than SCD organs. Short-term outcomes showed a similar disparity with a higher 1-year post-transplant creatinine and delayed graft function (DGF) rate in ECD grafts. Nevertheless, outcomes were still clinically acceptable. When comparing DCD to DBD organs, no such differences were apparent, with DCD organs appearing to perform at least as well as DBD organs. In our cohort, unlike some previous studies, DGF rates were similar in both DCD and DBD groups. Although ECD organs perform less well than SCD organs, outcomes are still acceptable and our results support their continuing use. When considering DCD organs, our data support the view that they should no longer be necessarily regarded as marginal grafts. Our low DGF rates are perhaps explained by local factors contributing to a short CIT. Copyright © 2014 Royal College of Surgeons of Edinburgh (Scottish charity number SC005317) and Royal College of Surgeons in Ireland. Published by Elsevier Ltd. All rights reserved.

Is It Worthwhile Treating Occluded Cold Stored Venous Allografts by Thrombolysis?

PubMed

Balaz, P; Wohlfahrt, P; Rokosny, S; Maly, S; Bjorck, M

2016-09-01

Thrombolysis has been reported to be suboptimal in occluded vein grafts and cryopreserved allografts, and there are no data on the efficacy of thrombolysis in occluded cold stored venous allografts. The aim was to evaluate early outcomes, secondary patency and limb salvage rates of thrombolysed cold stored venous allograft bypasses and to compare the outcomes with thrombolysis of autologous bypasses. This was a single center study of consecutive patients with acute and non-acute limb ischemia between September 1, 2000, and January 1, 2014, with occlusion of cold stored venous allografts, and between January 1, 2012, and January 1, 2014, with occlusion of autologous bypass who received intra-arterial thrombolytic therapy. Sixty-one patients with occlusion of an infrainguinal bypass using a cold stored venous allograft (n = 35) or an autologous bypass (n = 26) underwent percutaneous intra-arterial thrombolytic therapy. The median duration of thrombolysis was 20 h (IQR 18-24) with no difference between the groups (p = .14). The median follow up was 18.5 months (IQR 11.0-52.0). Secondary patency rates of thrombolysed bypass at 6 and 12 months were 44 ± 9% and 32 ± 9% in patients with a venous allograft bypass and 46 ± 10% and 22 ± 8% with an autologous bypass, with no difference between groups (p = .40). Limb salvage rates at 1, 6, and 12 months after thrombolysis in the venous allograft group were 83 ± 7%, 72 ± 8% and 63 ± 9%, and in the autologous group 91 ± 6%, 76 ± 9%, and 65 ± 13%, with no difference between groups (p = .69). Long-term results of thrombolysis of venous allograft bypasses are similar to those of autologous bypasses. Occluded cold stored venous allograft can be successfully re-opened in most cases with a favorable effect on limb salvage. Copyright © 2016 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

The Risk of Transplant Failure With HLA Mismatch in First Adult Kidney Allografts From Deceased Donors.

PubMed

Williams, Robert C; Opelz, Gerhard; McGarvey, Chelsea J; Weil, E Jennifer; Chakkera, Harini A

2016-05-01

Since the beginning of the technology, there has been active debate about the role of human leucocyte antigen (HLA) matching in kidney allograft survival. Recent studies have reported diminishing importance of HLA matching, which have, in turn, been challenged by reports that suggest the continuing importance of these loci. Given the controversies, we examined the effect of HLA compatibility on kidney allograft survival by studying all first adult kidney transplants in the United States from a deceased donor. Using the United Network for Organ Sharing data, we identified first deceased donor kidney transplants between October 1, 1987, and December 31, 2013. Recipients were classified by their number of HLA mismatches. Cox multivariate regression analyses adjusting for recipient and donor transplant characteristics were performed to determine the impact of HLA compatibility on kidney allograft survival. Study cohort included 189 141 first adult kidney alone transplants, with a total of 994 558 years of kidney allograft follow-up time. Analyses adjusted for recipient and donor characteristics demonstrated a 13% higher risk (hazard ratio, 1.13; 95% confidence interval, 1.06-1.21) with 1 mismatch and a 64% higher risk (hazard ratio, 1.64, 95% confidence interval, 1.56-1.73) with 6 mismatches. Dividing the mismatch categories into 27 ordered permutations, and testing their 57 within mismatch category differences, demonstrated that all but 1 were equal, independent of locus. A significant linear relationship of hazard ratios was associated with HLA mismatch and affects allograft survival even during the recent periods of increasing success in renal transplantation.

Orthotopic Transplantation of Achilles Tendon Allograft in Rats

PubMed Central

Aynardi, Michael; Zahoor, Talal; Mitchell, Reed; Loube, Jeffrey; Feltham, Tyler; Manandhar, Lumanti; Paudel, Sharada; Schon, Lew; Zhang, Zijun

2018-01-01

The biology and function of orthotopic transplantation of Achilles tendon allograft are unknown. Particularly, the revitalization of Achilles allograft is a clinical concern. Achilles allografts were harvested from donor rats and stored at −80 °C. Subcutaneous adipose tissue was harvested from the would-be allograft recipient rats for isolation of mesenchymal stem cells (MSCs). MSCs were cultured with growth differentiation factor-5 (GDF-5) and applied onto Achilles allografts on the day of transplantation. After the native Achilles tendon was resected from the left hind limb of the rats, Achilles allograft, with or without autologous MSCs, was implanted and sutured with calf muscles proximally and calcaneus distally. Animal gait was recorded presurgery and postsurgery weekly. The animals were sacrificed at week 4, and the transplanted Achilles allografts were collected for biomechanical testing and histology. The operated limbs had altered gait. By week 4, the paw print intensity, stance time, and duty cycle (percentage of the stance phase in a step cycle) of the reconstructed limbs were mostly recovered to the baselines recorded before surgery. Maximum load of failure was not different between Achilles allografts, with or without MSCs, and the native tendons. The Achilles allograft supplemented with MSCs had higher cellularity than the Achilles allograft without MSCs. Deposition of fine collagen (type III) fibers was active in Achilles allograft, with or without MSCs, but it was more evenly distributed in the allografts that were incubated with MSCs. In conclusion, orthotopically transplanted Achilles allograft healed with host tissues, regained strength, and largely restored Achilles function in 4 wk in rats. It is therefore a viable option for the reconstruction of a large Achilles tendon defect. Supplementation of MSCs improved repopulation of Achilles allograft, but large animal models, with long-term follow up and cell tracking, may be required to fully

Nonoperative management of blunt renal trauma: Is routine early follow-up imaging necessary?

PubMed Central

Malcolm, John B; Derweesh, Ithaar H; Mehrazin, Reza; DiBlasio, Christopher J; Vance, David D; Joshi, Salil; Wake, Robert W; Gold, Robert

2008-01-01

Background There is no consensus on the role of routine follow-up imaging during nonoperative management of blunt renal trauma. We reviewed our experience with nonoperative management of blunt renal injuries in order to evaluate the utility of routine early follow-up imaging. Methods We reviewed all cases of blunt renal injury admitted for nonoperative management at our institution between 1/2002 and 1/2006. Data were compiled from chart review, and clinical outcomes were correlated with CT imaging results. Results 207 patients were identified (210 renal units). American Association for the Surgery of Trauma (AAST) grades I, II, III, IV, and V were assigned to 35 (16%), 66 (31%), 81 (39%), 26 (13%), and 2 (1%) renal units, respectively. 177 (84%) renal units underwent routine follow-up imaging 24–48 hours after admission. In three cases of grade IV renal injury, a ureteral stent was placed after serial imaging demonstrated persistent extravasation. In no other cases did follow-up imaging independently alter clinical management. There were no urologic complications among cases for which follow-up imaging was not obtained. Conclusion Routine follow-up imaging is unnecessary for blunt renal injuries of grades I-III. Grade IV renovascular injuries can be followed clinically without routine early follow-up imaging, but urine extravasation necessitates serial imaging to guide management decisions. The volume of grade V renal injuries in this study is not sufficient to support or contest the need for routine follow-up imaging. PMID:18768088

Regulatory dendritic cell infusion prolongs kidney allograft survival in non-human primates

PubMed Central

Ezzelarab, M.; Zahorchak, A.F.; Lu, L.; Morelli, A.E.; Chalasani, G.; Demetris, A.J.; Lakkis, F.G.; Wijkstrom, M.; Murase, N.; Humar, A.; Shapiro, R.; Cooper, D.K.C.; Thomson, A.W.

2014-01-01

We examined the influence of regulatory dendritic cells (DCreg), generated from cytokine-mobilized donor blood monocytes in vitamin D3 and IL-10, on renal allograft survival in a clinically-relevant rhesus macaque model. DCreg expressed low MHC class II and costimulatory molecules, but comparatively high levels of programmed death ligand-1 (B7-H1), and were resistant to pro-inflammatory cytokine-induced maturation. They were infused intravenously (3.5–10×106/kg), together with the B7-CD28 costimulation blocking agent CTLA4Ig, 7 days before renal transplantation. CTLA4Ig was given for up to 8 weeks and rapamycin, started on day −2, was maintained with tapering of blood levels until full withdrawal at 6 months. Median graft survival time was 39.5 days in control monkeys (no DC infusion; n=6) and 113.5 days (p< 0.05) in DCreg-treated animals (n=6). No adverse events were associated with DCreg infusion, and there was no evidence of induction of host sensitization based on circulating donor-specific alloantibody levels. Immunologic monitoring also revealed regulation of donor-reactive memory CD95+ T cells and reduced memory/regulatory T cell ratios in DCreg-treated monkeys compared with controls. Termination allograft histology showed moderate combined T cell- and Ab-mediated rejection in both groups. These findings justify further pre-clinical evaluation of DCreg therapy and their therapeutic potential in organ transplantation. PMID:23758811

Early aspirin use and the development of cardiac allograft vasculopathy.

PubMed

Kim, Miae; Bergmark, Brian A; Zelniker, Thomas A; Mehra, Mandeep R; Stewart, Garrick C; Page, Deborah S; Woodcome, Erica L; Smallwood, Jennifer A; Gabardi, Steven; Givertz, Michael M

2017-12-01

Cardiac allograft vasculopathy (CAV) remains a leading cause of morbidity and mortality after orthotopic heart transplantation (OHT). Little is known about the influence of aspirin on clinical expression of CAV. We followed 120 patients with OHT at a single center for a median of 7 years and categorized them by the presence or absence of early aspirin therapy post-transplant (aspirin treatment ≥6 months in the first year). The association between aspirin use and time to the primary end-point of angiographic moderate or severe CAV (International Society for Heart and Lung Transplantation grade ≥2) was investigated. Propensity scores for aspirin treatment were estimated using boosting models and applied by inverse probability of treatment weighting (IPTW). Despite a preponderance of risk factors for CAV among patients receiving aspirin (male sex, ischemic heart disease as the etiology of heart failure, and smoking), aspirin therapy was associated with a lower rate of moderate or severe CAV at 5 years. Event-free survival was 95.9% for patients exposed to aspirin compared with 79.6% for patients without aspirin exposure (log-rank p = 0.005). IPTW-weighted Cox regression revealed a powerful inverse association between aspirin use and moderate to severe CAV (adjusted hazard ratio 0.13; 95% confidence interval 0.03-0.59), which was directionally consistent for CAV of any severity (adjusted hazard ratio 0.50; 95% confidence interval 0.23-1.08). This propensity score-based comparative observational analysis suggests that early aspirin exposure may be associated with a reduced risk of development of moderate to severe CAV. These findings warrant prospective validation in controlled investigations. Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

[Vascular trombosis of renal graft: 9 cases].

PubMed

Kaaroud, Hayet; Béji, Soumaya; Ben Hamida, Fethi; Rais, Lamia; Ben Abdallah, Taieb; El Younsi, Fethi; Ben Moussa, Fatma; Abderrahim, Ezzedine; Bardi, Rafika; Ayed, Khaled; Chebil, Mohamed; Kheder, Adel

2008-04-01

Allograft renal thrombosis can occur in 1 to 6% of cases. Many predisposing factors has been identified especially alteration of coagulation. We analyzed in this study frequency and predisposing factors of renal graft thrombosis. We report a retrospective study including 319 renal transplant recipients. Nine patients (2.8%) presented veinous graft thrombosis in 5 cases and arterial thombosis in 4 cases. There were 6 men and 3 women aged of 30.6 years meanly (10-56) which developed the thrombosis 6 days (1-48) after the transplantation. All patients were detransplanted after 16.2 days and 1 patient died. Thrombosis constitute an important cause of graft loss. A perfect surgical technic and prophylactic treatment in high risk patients are necessary to reduce this complication.

Donor-Derived Regulatory Dendritic Cell Infusion Maintains Donor-Reactive CD4+CTLA4hi T Cells in Non-Human Primate Renal Allograft Recipients Treated with CD28 Co-Stimulation Blockade.

PubMed

Ezzelarab, Mohamed B; Lu, Lien; Shufesky, William F; Morelli, Adrian E; Thomson, Angus W

2018-01-01

Donor-derived regulatory dendritic cell (DCreg) infusion before transplantation, significantly prolongs renal allograft survival in non-human primates. This is associated with enhanced expression of the immunoregulatory molecules cytotoxic T-lymphocyte-associated antigen (Ag) 4 (CTLA4) and programmed cell death protein 1 (PD1) by host donor-reactive T cells. In rodents and humans, CD28 co-stimulatory pathway blockade with the fusion protein CTLA4:Ig (CTLA4Ig) is associated with reduced differentiation and development of regulatory T cells (Treg). We hypothesized that upregulation of CTLA4 by donor-reactive CD4 + T cells in DCreg-infused recipients treated with CTLA4Ig, might be associated with higher incidences of donor-reactive CD4 + T cells with a Treg phenotype. In normal rhesus monkeys, allo-stimulated CD4 + CTLA4 hi , but not CD4 + CTLA4 med/lo T cells exhibited a regulatory phenotype, irrespective of PD1 expression. CTLA4Ig significantly reduced the incidence of CD4 + CTLA4 hi , but not CD4 + CTLA4 med/lo T cells following allo-stimulation, associated with a significant reduction in the CD4 + CTLA4 hi /CD4 + CTLA4 med/lo T cell ratio. In CTLA4Ig-treated renal allograft recipient monkeys, there was a marked reduction in circulating donor-reactive CD4 + CTLA4 hi T cells. In contrast, in CTLA4Ig-treated monkeys with DCreg infusion, no such reduction was observed. In parallel, the donor-reactive CD4 + CTLA4 hi /CD4 + CTLA4 med/lo T cell ratio was reduced significantly in graft recipients without DCreg infusion, but increased in those given DCreg. These observations suggest that pre-transplant DCreg infusion promotes and maintains donor-reactive CD4 + CTLA4 hi T cells with a regulatory phenotype after transplantation, even in the presence of CD28 co-stimulation blockade.

[Pedal bypass using venous allograft].

PubMed

Pluháčková, H; Staffa, R; Konečný, Z; Kříž, Z; Vlachovský, R

Pedal or distal crural bypass surgery for limb salvage is a method with very good long-term results. For patients in whom a suitable autologous venous graft is not available, the use of a venous allograft is an alternative procedure. A 68 years old man with ischaemic disease of lower extremities and gangrene of the left foot was admitted to our Centre in August 2014. He underwent percutaneous transluminal angioplasty of crural arteries of his left lower extremity. This, however, failed to improve peripheral circulation. The patient was then indicated for pedal or distal crural vascular reconstruction. Since no suitable autologous vein was available, distal bypass surgery using a donor graft remained the only option for limb salvage. Amputation of the toes on the left foot due to gangrene was necessary. Subsequently, femoro-pedal bypass to the left common plantar artery was performed using a great saphenous vein allograft. The post-operative course was without complications, the pedal bypass was patent and toe amputation was with good healing. The patient remained in follow-up care. A good outcome of vascular reconstruction with an allograft depends on the availability of a suitable allograft and good patient compliance with post-operative care. In the case presented here, the pedal bypass grafting by means of an allograft helped to save the patients limb. pedal bypass venous allograft limb salvage.

Characterization of skin allograft use in thermal injury.

PubMed

Fletcher, John L; Caterson, E J; Hale, Robert G; Cancio, Leopoldo C; Renz, Evan M; Chan, Rodney K

2013-01-01

This study provides objective data on the practice of allograft usage in severely burned patients. Furthermore, gaps in our knowledge are identified, and areas for further research are delineated. Using an institutional review board-approved protocol, active duty military patients injured while deployed in support of overseas contingency operations and treated at our burn center between March 2003 and December 2010 were identified. Their electronic medical records were reviewed for allograft use, TBSA burned, injury severity score, anatomic distribution of burns, operative burden, length of stay, transfusions, and outcome. Among 844 patients, 112 (13.3%) received allograft and 732 (86.7%) did not. The amount of allograft used per patient varied and was not normally distributed (median, 23.5; interquartile range, 69.5). Patients received allograft skin an average of 12.75 times during their admission. Allografted patients sustained severe burns (μ, 53.8% TBSA); most were transfused (71.2%) and grafted frequently, averaging every 7.45 days. Most commonly, allograft was placed on the extremities (66.5%) followed by the trunk (44.2%); however, the vast majority of allografted patients also had concomitant burns of the head (91.1%) and hands (87.5%). All-cause mortality among the allografted patients was 19.1%. In conclusion, allograft is commonly used in the surgical treatment of severe burns. Although there are no anatomic limitations to allograft placement, there are distinct patterns of use. Given the role of allograft in the acute management of large burns, there is need for further investigation of its effect on mortality, morbidity, and antigenicity.

Regulatory dendritic cell infusion prolongs kidney allograft survival in nonhuman primates.

PubMed

Ezzelarab, M B; Zahorchak, A F; Lu, L; Morelli, A E; Chalasani, G; Demetris, A J; Lakkis, F G; Wijkstrom, M; Murase, N; Humar, A; Shapiro, R; Cooper, D K C; Thomson, A W

2013-08-01

We examined the influence of regulatory dendritic cells (DCreg), generated from cytokine-mobilized donor blood monocytes in vitamin D3 and IL-10, on renal allograft survival in a clinically relevant rhesus macaque model. DCreg expressed low MHC class II and costimulatory molecules, but comparatively high levels of programmed death ligand-1 (B7-H1), and were resistant to pro-inflammatory cytokine-induced maturation. They were infused intravenously (3.5-10 × 10(6) /kg), together with the B7-CD28 costimulation blocking agent CTLA4Ig, 7 days before renal transplantation. CTLA4Ig was given for up to 8 weeks and rapamycin, started on Day -2, was maintained with tapering of blood levels until full withdrawal at 6 months. Median graft survival time was 39.5 days in control monkeys (no DC infusion; n = 6) and 113.5 days (p < 0.05) in DCreg-treated animals (n = 6). No adverse events were associated with DCreg infusion, and there was no evidence of induction of host sensitization based on circulating donor-specific alloantibody levels. Immunologic monitoring also revealed regulation of donor-reactive memory CD95(+) T cells and reduced memory/regulatory T cell ratios in DCreg-treated monkeys compared with controls. Termination allograft histology showed moderate combined T cell- and Ab-mediated rejection in both groups. These findings justify further preclinical evaluation of DCreg therapy and their therapeutic potential in organ transplantation. © Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.

Biomarkers-a potential route for improved diagnosis and management of ongoing renal damage.

PubMed

Oberbauer, R

2008-12-01

Currently, the identification and validation of biomarkers of kidney injury is among the top priorities of many diagnostic biotechnology companies as well as academic research institutes. Specifically, in renal transplantation, validated biomarkers of tissue injury with good discriminatory power between the various renal compartments and the underlying pathophysiology are desired, because sequential allograft biopsies are limited in number and cannot be used as a screening tool. Given the high demands on these markers, it is not surprising that none of those currently under evaluation has been thoroughly validated for a specific entity. Published biomarker candidates for early tubular damage include neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-18, soluble CD30, perforin, and granzyme B. Recently, C4d flow panel reactive antibodies were evaluated as biomarkers for humoral alloimmune responses. Additional biomarkers such as FOXP3 and kidney injury molecule 1 have been studied in the maintenance phase of renal transplantation. Given the complex prerequisites, it is not surprising that no biomarker panel has been sufficiently validated for clinical use. However, in the near future a biomarker for use as an indicator of renal tubule cell injury will be available. Troponin T or transaminase of the kidney may then at least be used to differentiate between functional renal failure (equivalent to a rise in creatinine) and intrinsic kidney injury.

Allograft-prosthetic composite reverse total shoulder arthroplasty for reconstruction of proximal humerus tumor resections.

PubMed

King, Joseph J; Nystrom, Lukas M; Reimer, Nickolas B; Gibbs, C Parker; Scarborough, Mark T; Wright, Thomas W

2016-01-01

Proximal humerus reconstructions after resection of tumors are challenging. Early success of the reverse shoulder arthroplasty for reconstructions has recently been reported. The reverse allograft-prosthetic composite offers the advantage of improved glenohumeral stability compared with hemiarthroplasty for proximal humeral reconstructions as it uses the deltoid for stability. This article describes the technique for treating proximal humeral tumors, including preoperative planning, biopsy principles, resection pearls, soft tissue tensioning, and specifics about reconstruction using the reverse allograft-prosthetic composite. Two cases are presented along with the functional outcomes with use of this technique. Biomechanical considerations during reconstruction are reviewed, including techniques to improve the deltoid compression force. Reported instability rates are less with reverse shoulder arthroplasty reconstruction as opposed to hemiarthroplasty or total shoulder arthroplasty reconstructions of tumor resections. Reported functional outcomes are promising for the reverse allograft-prosthetic composite reconstructions, although complications are reported. Reverse allograft-prosthetic composites are a promising option for proximal humeral reconstructions, although nonunion of the allograft-host bone junction continues to be a challenge for this technique. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Interleukin (IL)-1 Receptor Signaling on Graft Parenchymal Cells Regulates Memory and De Novo Donor-Reactive CD8 T Cell Responses to Cardiac Allografts1

PubMed Central

Iida, Shoichi; Tsuda, Hidetoshi; Tanaka, Toshiaki; Kish, Danielle D.; Abe, Toyofumi; Su, Charles A.; Abe, Ryo; Tanabe, Kazunari; Valujskikh, Anna; Baldwin, William M.; Fairchild, Robert L.

2016-01-01

Reperfusion of organ allografts induces a potent inflammatory response that directs rapid memory T cell, neutrophil and macrophage graft infiltration and their activation to express functions mediating graft tissue injury. The role of cardiac allograft IL-1 receptor signaling in this early inflammation and the downstream primary alloimmune response was investigated. When compared to complete MHC-mismatched wild type cardiac allografts, IL-1R−/− allografts had marked decreases in endogenous memory CD8 T cell and neutrophil infiltration and expression of proinflammatory mediators at early times after transplant whereas endogenous memory CD4 T cell and macrophage infiltration was not decreased. IL-1R−/− allograft recipients also had marked decreases in de novo donor-reactive CD8, but not CD4, T cell development to IFN-γ-producing cells. CD8 T cell-mediated rejection of IL-1R−/− cardiac allografts took 3 weeks longer than wild type allografts. Cardiac allografts from reciprocal bone marrow reconstituted IL-1R−/−/wild type chimeric donors indicated that IL-1R signaling on graft non-hematopoietic-derived, but not bone marrow-derived, cells is required for the potent donor-reactive memory and primary CD8 T cell alloimmune responses observed in response to wild type allografts. These studies implicate IL-1R-mediated signals by allograft parenchymal cells in generating the stimuli provoking development and elicitation of optimal alloimmune responses to the grafts. PMID:26856697

Remodeling of ACL Allografts is Inhibited by Peracetic Acid Sterilization

PubMed Central

Gonnermann, Johannes; Kamp, Julia; Przybilla, Dorothea; Pruss, Axel

2008-01-01

Sterilization of allografts for anterior cruciate ligament (ACL) reconstruction has become an important prerequisite to prevent disease transmission. However, current sterilization techniques impair the biological or mechanical properties of such treated grafts. Peracetic acid (PAA) has been successfully used to sterilize bone allografts without these disadvantages and does not impair the mechanical properties of soft tissue grafts in vitro. We asked whether PAA sterilization would influence recellularization, restoration of crimp length and pattern, and revascularization of ACL grafts during early healing. We used an in vivo sheep model for open ACL reconstruction. We also correlated the histologic findings with the restoration of anteroposterior stability and structural properties during load-to-failure testing. PAA slowed remodeling activity at 6 and 12 weeks compared to nonsterilized allografts and autografts. The mechanical properties of PAA grafts were also reduced compared to these control groups at both time points. We conclude PAA sterilization currently should not be used to sterilize soft tissue grafts typically used in ACL reconstruction. PMID:18491201

Allograft replacement for absent native tissue.

PubMed

Chaudhury, Salma; Wanivenhaus, Florian; Fox, Alice J; Warren, Russell F; Doyle, Maureen; Rodeo, Scott A

2013-03-01

Structural instability due to poor soft tissue quality often requires augmentation. Allografts are important biological substitutes that are used for the symptomatic patient in the reconstruction of deficient ligaments, tendons, menisci, and osteochondral defects. Interest in the clinical application of allografts has arisen from the demand to obtain stable anatomy with restoration of function and protection against additional injury, particularly for high-demand patients who participate in sports. Traditionally, allografts were employed to reinforce weakened tissue. However, they can also be employed to substitute deficient or functionally absent tissue, particularly in the sports medicine setting. This article presents a series of 6 cases that utilized allografts to restore functionally deficient anatomic architecture, rather than just simply augmenting the degenerated or damaged native tissue. Detailed discussions are presented of the use of allografts as a successful treatment strategy to replace functionally weakened tissue, often after failed primary repairs.

Allograft Replacement for Absent Native Tissue

PubMed Central

Chaudhury, Salma; Wanivenhaus, Florian; Fox, Alice J.; Warren, Russell F.; Doyle, Maureen; Rodeo, Scott A.

2013-01-01

Context: Structural instability due to poor soft tissue quality often requires augmentation. Allografts are important biological substitutes that are used for the symptomatic patient in the reconstruction of deficient ligaments, tendons, menisci, and osteochondral defects. Interest in the clinical application of allografts has arisen from the demand to obtain stable anatomy with restoration of function and protection against additional injury, particularly for high-demand patients who participate in sports. Traditionally, allografts were employed to reinforce weakened tissue. However, they can also be employed to substitute deficient or functionally absent tissue, particularly in the sports medicine setting. Objective: This article presents a series of 6 cases that utilized allografts to restore functionally deficient anatomic architecture, rather than just simply augmenting the degenerated or damaged native tissue. Detailed discussions are presented of the use of allografts as a successful treatment strategy to replace functionally weakened tissue, often after failed primary repairs. PMID:24427387

Allografts for Ligament Reconstruction: Where Are We Now?

PubMed

Wydra, Frank B; York, Philip J; Johnson, Christopher R; Silvestri, Lorenzo

The use of musculoskeletal allografts by orthopedic surgeons continues to rise. The process of procuring and sterilizing allografts is evolving with much consideration to limiting the spread of infectious diseases and preserving tissue integrity. Research involving the application of allografts, particularly for ligament repair, is quite active, necessitating an update for the practicing orthopedist. Avoiding donor site morbidities is one of the most commonly cited advantages of allografts over autografts. There is controversy amongst studies for allografts in terms of their biological incorporation and clinical outcomes compared to autografts. This article focuses on reviewing the most current literature and usage of allograft tissue for ligamentous reconstruction amongst orthopedic surgeons today. It includes an in-depth analysis of the current processing, handling, and safety standards employed today, in addition to the advantages and disadvantages of allograft use.

Proton Pump Inhibitors Independently Protect Against Early Allograft Injury or Chronic Rejection After Lung Transplantation.

PubMed

Lo, Wai-Kit; Goldberg, Hilary J; Boukedes, Steve; Burakoff, Robert; Chan, Walter W

2018-02-01

Acid reflux has been associated with poor outcomes following lung transplantation. Unlike surgical fundoplication, the role of noninvasive, pharmacologic acid suppression remains uncertain. To assess the relationship between post-transplant acid suppression with proton pump inhibitors (PPI) or histamine-2 receptor antagonists (H2RA) and onset of early allograft injury or chronic rejection following lung transplantation. This was a retrospective cohort study of lung transplant recipients at a tertiary center in 2007-2014. Patients with pre-transplant antireflux surgery were excluded. Time-to-event analysis using the Cox proportional hazards model was applied to assess acid suppression therapy and onset of acute or chronic rejection, defined histologically and clinically. Subgroup analyses were performed to assess PPI versus H2RA use. A total of 188 subjects (60% men, mean age 54, follow-up 554 person-years) met inclusion criteria. During follow-up, 115 subjects (61.5%) developed rejection, with all-cause mortality of 27.6%. On univariate analyses, acid suppression and BMI, but not other patient demographics, were associated with rejection. The Kaplan-Meier curve demonstrated decreased rejection with use of acid suppression therapy (log-rank p = 0.03). On multivariate analyses, acid suppression (HR 0.39, p = 0.04) and lower BMI (HR 0.67, p = 0.04) were independently predicted against rejection. Subgroup analyses demonstrated that persistent PPI use was more protective than H2RA or no antireflux medications. Post-lung transplant exposure to persistent PPI therapy results in the greatest protection against rejection in lung transplant recipients, independent of other clinical predictors including BMI, suggesting that PPI may have antireflux or anti-inflammatory effects in enhancing allograft protection.

Early Subretinal Allograft Rejection Is Characterized by Innate Immune Activity.

PubMed

Kennelly, Kevin P; Holmes, Toby M; Wallace, Deborah M; O'Farrelly, Cliona; Keegan, David J

2017-06-09

Successful subretinal transplantation is limited by considerable early graft loss despite pharmacological suppression of adaptive immunity. We postulated that early innate immune activity is a dominant factor in determining graft survival and chose a nonimmunosuppressed mouse model of retinal pigment epithelial (RPE) cell transplantation to explore this. Expression of almost all measured cytokines by DH01 RPE cells increased significantly following graft preparation, and the neutrophil chemoattractant KC/GRO/CINC was most significantly increased. Subretinal allografts of DH01 cells (C57BL/10 origin) into healthy, nonimmunosuppressed C57BL/6 murine eyes were harvested and fixed at 1, 3, 7, and 28 days postoperatively and subsequently cryosectioned and stained. Graft cells were detected using SV40 large T antigen (SV40T) immunolabeling and apoptosis/necrosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Sections were also immunolabeled for macrophage (CD11b and F4/80), neutrophil (Gr1 Ly-6G), and T-lymphocyte (CD3-ɛ) infiltration. Images captured with an Olympus FV1000 confocal microscope were analyzed using the Imaris software. The proportion of the subretinal bolus comprising graft cells (SV40T+) was significantly (p < 0.001) reduced between postoperative day (POD) 3 (90 ± 4%) and POD 7 (20 ± 7%). CD11b+, F4/80+, and Gr1 Ly-6G+ cells increased significantly (p < 0.05) from POD 1 and predominated over SV40T+ cells by POD 7. Colabeling confocal microscopic analysis demonstrated graft engulfment by neutrophils and macrophages at POD 7, and reconstruction of z-stacked confocal images confirmed SV40T inside Gr1 Ly-6G+ cells. Expression of CD3-ɛ was low and did not differ significantly between time points. By POD 28, no graft cells were detectable and few inflammatory cells remained. These studies reveal, for the first time, a critical role for innate immune mechanisms early in subretinal graft rejection. The future success

A biomechanical cadaveric study comparing superior capsule reconstruction using fascia lata allograft with human dermal allograft for irreparable rotator cuff tear.

PubMed

Mihata, Teruhisa; Bui, Christopher N H; Akeda, Masaki; Cavagnaro, Matthew A; Kuenzler, Michael; Peterson, Alexander B; McGarry, Michelle H; Itami, Yasuo; Limpisvasti, Orr; Neo, Masashi; Lee, Thay Q

2017-12-01

Biomechanical and clinical success of the superior capsule reconstruction (SCR) using fascia lata (FL) grafts has been reported. In the United States, human dermal (HD) allograft has been used successfully for SCRs; however, the biomechanical characteristics have not been reported. Eight cadaveric shoulders were tested in 5 conditions: (1) intact; (2) irreparable supraspinatus tear; (3) SCR using FL allograft with anterior and posterior suturing; (4) SCR using HD allograft with anterior and posterior suturing; and (5) SCR using HD allograft with posterior suturing. Rotational range of motion, superior translation, glenohumeral joint force, and subacromial contact were measured at 0°, 30°, and 60° of glenohumeral abduction in the scapular plane. Graft dimensions before and after testing were also recorded. Biomechanical parameters were compared using a repeated-measures analysis of variance with Tukey post hoc test, and graft dimensions were compared using a Student t-test (P < .05). Irreparable supraspinatus tear significantly increased superior translation, superior glenohumeral joint force, and subacromial contact pressure, which were completely restored with the SCR FL allografts. Both SCR HD allograft repairs partially restored superior translation and completely restored subacromial contact and superior glenohumeral joint force. The HD allografts significantly elongated by 15% during testing, whereas the FL allograft lengths were unchanged. Single-layered HD SCR allografts partially restored superior glenohumeral stability, whereas FL allograft SCR completely restored the superior glenohumeral stability. This may be due to the greater flexibility of the HD allograft, and the SCR procedure used was developed on the basis of FL grafts. Published by Elsevier Inc.

Inflammatory macrophage-associated 3-gene signature predicts subclinical allograft injury and graft survival.

PubMed

Azad, Tej D; Donato, Michele; Heylen, Line; Liu, Andrew B; Shen-Orr, Shai S; Sweeney, Timothy E; Maltzman, Jonathan Scott; Naesens, Maarten; Khatri, Purvesh

2018-01-25

Late allograft failure is characterized by cumulative subclinical insults manifesting over many years. Although immunomodulatory therapies targeting host T cells have improved short-term survival rates, rates of chronic allograft loss remain high. We hypothesized that other immune cell types may drive subclinical injury, ultimately leading to graft failure. We collected whole-genome transcriptome profiles from 15 independent cohorts composed of 1,697 biopsy samples to assess the association of an inflammatory macrophage polarization-specific gene signature with subclinical injury. We applied penalized regression to a subset of the data sets and identified a 3-gene inflammatory macrophage-derived signature. We validated discriminatory power of the 3-gene signature in 3 independent renal transplant data sets with mean AUC of 0.91. In a longitudinal cohort, the 3-gene signature strongly correlated with extent of injury and accurately predicted progression of subclinical injury 18 months before clinical manifestation. The 3-gene signature also stratified patients at high risk of graft failure as soon as 15 days after biopsy. We found that the 3-gene signature also distinguished acute rejection (AR) accurately in 3 heart transplant data sets but not in lung transplant. Overall, we identified a parsimonious signature capable of diagnosing AR, recognizing subclinical injury, and risk-stratifying renal transplant patients. Our results strongly suggest that inflammatory macrophages may be a viable therapeutic target to improve long-term outcomes for organ transplantation patients.

[Early detection, prevention and management of renal failure in liver transplantation].

PubMed

Castells, Lluís; Baliellas, Carme; Bilbao, Itxarone; Cantarell, Carme; Cruzado, Josep Maria; Esforzado, Núria; García-Valdecasas, Juan Carlos; Lladó, Laura; Rimola, Antoni; Serón, Daniel; Oppenheimer, Federico

2014-10-01

Renal failure is a frequent complication in liver transplant recipients and is associated with increased morbidity and mortality. A variety of risk factors for the development of renal failure in the pre- and post-transplantation periods have been described, as well as at the time of surgery. To reduce the negative impact of renal failure in this population, an active approach is required for the identification of those patients with risk factors, the implementation of preventive strategies, and the early detection of progressive deterioration of renal function. Based on published evidence and on clinical experience, this document presents a series of recommendations on monitoring RF in LT recipients, as well as on the prevention and management of acute and chronic renal failure after LT and referral of these patients to the nephrologist. In addition, this document also provides an update of the various immunosuppressive regimens tested in this population for the prevention and control of post-transplantation deterioration of renal function. Copyright © 2013 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

Dual growth factor delivery from biofunctionalized allografts: Sequential VEGF and BMP-2 release to stimulate allograft remodeling.

PubMed

Sharmin, Farzana; McDermott, Casey; Lieberman, Jay; Sanjay, Archana; Khan, Yusuf

2017-05-01

Autografts have been shown to stimulate osteogenesis, osteoclastogenesis, and angiogenesis, and subsequent rapid graft incorporation. Large structural allografts, however, suffer from limited new bone formation and remodeling, both of which are directly associated with clinical failure due to non-unions, late graft fractures, and infections, making it a priority to improve large structural allograft healing. We have previously shown the osteogenic ability of a polymer-coated allograft that delivers bone morphogenetic protein-2 both in vitro and in vivo through both burst release and sustained release kinetics. In this study, we have demonstrated largely sequential delivery of bone morphogenetic protein-2 and vascular endothelial growth factor from the same coated allograft. Release data showed that loading both growth factors onto a polymeric coating with two different techniques resulted in short-term (95% release within 2 weeks) and long-term (95% release within 5 weeks) delivery kinetics. We have also demonstrated how released VEGF, traditionally associated with angiogenesis, can also provide a stimulus for allograft remodeling via resorption. Bone marrow derived mononuclear cells were co-cultured with VEGF released from the coated allograft and showed a statistically significant (p < 0.05) and dose dependent increase in the number of tartrate-resistant acid phosphatase-positive multinucleated osteoclasts. Functionality of these osteoclasts was assessed quantitatively and qualitatively by evaluating resorption pit area from both osteo-assay plates and harvested bone. Data indicated a statistically significant higher resorption area from the cells exposed to VEGF released from the allografts over controls (p < 0.05). These results indicate that by using different loading protocols temporal control can be achieved when delivering multiple growth factors from a polymer-coated allograft. Further, released VEGF can also stimulate osteoclastogenesis that may

Outcomes of kidney transplantation in Alport syndrome compared with other forms of renal disease.

PubMed

Kelly, Yvelynne P; Patil, Anish; Wallis, Luke; Murray, Susan; Kant, Saumitra; Kaballo, Mohammed A; Casserly, Liam; Doyle, Brendan; Dorman, Anthony; O'Kelly, Patrick; Conlon, Peter J

2017-11-01

Alport syndrome is an inherited renal disease characterized by hematuria, renal failure, hearing loss and a lamellated glomerular basement membrane. Patients with Alport syndrome who undergo renal transplantation have been shown to have patient and graft survival rates similar to or better than those of patients with other renal diseases. In this national case series, based in Beaumont Hospital Dublin, we studied the cohort of patients who underwent renal transplantation over the past 33 years, recorded prospectively in the Irish Renal Transplant Registry, and categorized them according to the presence or absence of Alport syndrome. The main outcomes assessed were patient and renal allograft survival. Fifty-one patients diagnosed with Alport syndrome in Beaumont Hospital received 62 transplants between 1982 and 2014. The comparison group of non-Alport patients comprised 3430 patients for 3865 transplants. Twenty-year Alport patient survival rate was 70.2%, compared to 44.8% for patients with other renal diseases (p = .01). Factors associated with patient survival included younger age at transplantation as well as differences in recipient sex, donor age, cold ischemia time, and episodes of acute rejection. Twenty-year graft survival was 46.8% for patients with Alport syndrome compared to 30.2% for those with non-Alport disease (p = .11). Adjusting for baseline differences between the groups, patients with end-stage kidney disease (ESKD) due to Alport syndrome have similar patient and graft survival to those with other causes of ESKD. This indicates that early diagnosis and management can lead to favorable outcomes for this patient cohort.

Infiltration of Macrophages Correlates with Severity of Allograft Rejection and Outcome in Human Kidney Transplantation.

PubMed

Bergler, Tobias; Jung, Bettina; Bourier, Felix; Kühne, Louisa; Banas, Miriam C; Rümmele, Petra; Wurm, Simone; Banas, Bernhard

2016-01-01

Despite substantial progress in recent years, graft survival beyond the first year still requires improvement. Since modern immunosuppression addresses mainly T-cell activation and proliferation, we studied macrophage infiltration into the allografts of 103 kidney transplant recipients during acute antibody and T-cell mediated rejection. Macrophage infiltration was correlated with both graft function and graft survival until month 36 after transplantation. Macrophage infiltration was significantly elevated in antibody-mediated and T-cell mediated rejection, but not in kidneys with established IFTA. Treatment of rejection with steroids was less successful in patients with more prominent macrophage infiltration into the allografts. Macrophage infiltration was accompanied by increased cell proliferation as well as antigen presentation. With regard to the compartmental distribution severity of T-cell-mediated rejection was correlated to the amount of CD68+ cells especially in the peritubular and perivascular compartment, whereas biopsies with ABMR showed mainly peritubular CD68 infiltration. Furthermore, severity of macrophage infiltration was a valid predictor of resulting creatinine values two weeks as well as two and three years after renal transplantation as illustrated by multivariate analysis. Additionally performed ROC curve analysis showed that magnitude of macrophage infiltration (below vs. above the median) was a valid predictor for the necessity to restart dialysis. Having additionally stratified biopsies in accordance to the magnitude of macrophage infiltration, differential CD68+ cell infiltration was reflected by striking differences in overall graft survival. The differences in acute allograft rejection have not only been reflected by different magnitudes of macrophage infiltration, but also by compartment-specific infiltration pattern and subsequent impact on resulting allograft function as well as need for dialysis initiation. There is a robust

Infiltration of Macrophages Correlates with Severity of Allograft Rejection and Outcome in Human Kidney Transplantation

PubMed Central

Bourier, Felix; Kühne, Louisa; Banas, Miriam C.; Rümmele, Petra; Wurm, Simone; Banas, Bernhard

2016-01-01

Objective Despite substantial progress in recent years, graft survival beyond the first year still requires improvement. Since modern immunosuppression addresses mainly T-cell activation and proliferation, we studied macrophage infiltration into the allografts of 103 kidney transplant recipients during acute antibody and T-cell mediated rejection. Macrophage infiltration was correlated with both graft function and graft survival until month 36 after transplantation. Results Macrophage infiltration was significantly elevated in antibody-mediated and T-cell mediated rejection, but not in kidneys with established IFTA. Treatment of rejection with steroids was less successful in patients with more prominent macrophage infiltration into the allografts. Macrophage infiltration was accompanied by increased cell proliferation as well as antigen presentation. With regard to the compartmental distribution severity of T-cell-mediated rejection was correlated to the amount of CD68+ cells especially in the peritubular and perivascular compartment, whereas biopsies with ABMR showed mainly peritubular CD68 infiltration. Furthermore, severity of macrophage infiltration was a valid predictor of resulting creatinine values two weeks as well as two and three years after renal transplantation as illustrated by multivariate analysis. Additionally performed ROC curve analysis showed that magnitude of macrophage infiltration (below vs. above the median) was a valid predictor for the necessity to restart dialysis. Having additionally stratified biopsies in accordance to the magnitude of macrophage infiltration, differential CD68+ cell infiltration was reflected by striking differences in overall graft survival. Conclusion The differences in acute allograft rejection have not only been reflected by different magnitudes of macrophage infiltration, but also by compartment-specific infiltration pattern and subsequent impact on resulting allograft function as well as need for dialysis

Early outcomes of liver transplants in patients receiving organs from hypernatremic donors.

PubMed

Khosravi, Mohammad Bagher; Firoozifar, Mohammad; Ghaffaripour, Sina; Sahmeddini, Mohammad Ali; Eghbal, Mohammad Hossien

2013-12-01

Uncorrected hypernatremia in organ donors has been associated with poor graft or patient survival during liver transplants. However, recent studies have found no association between the donor serum sodium and transplant outcome. This study sought to show the negative effect donor hypernatremia has on initial liver allograft function. This is the first study to investigate international normalized ratio and renal factors of patients with normal and those with hypernatremic donor livers. This study was conducted at the Shiraz Transplant Research Center in Shiraz, Iran, between May 2009, and July 2011. Four hundred seven consecutive adult orthotopic liver transplants were performed at the University of Shiraz Medical Center. There were 93 donors in the group with hypernatremia with terminal serum sodium of 155 mEq/L or greater (group 1), and 314 with terminal serum sodium less than 155 mEq/L (group 2). Posttransplant data after 5 days showed that aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and kidney function did not differ between the groups. Hypernatremia is the most important complication after brain death. Previous studies have suggested donor hypernatremia results in a greater incidence of early postoperative graft dysfunction in liver transplant and is considered one of the extended criteria donor. However, in recent years, this hypothesis has been questioned. Our study shows no difference between patients' initial results of liver and kidney functioning with normal and hypernatremic donor livers. This is the first study to investigate international normalized ratio as a fundamental factor in defining early allograft dysfunction and renal factors between patients with normal and hypernatremic donor's livers.

The capacities of earthworms to heal wounds and to destroy allografts are modified by polychlorinated biphenyls (PCB).

PubMed

Cooper, E L; Roch, P

1992-07-01

Earthworms (Lumbricus terrestris) were maintained at 15 degrees C and exposed on filter paper to 10 micrograms/cm2 of the polychlorinated biphenyl (PCB) Aroclor 1254 for 5 days prior to surgical treatments which consisted of wounds, autografts, and allografts. At 1 day after surgery, we observed a higher percentage of healing defects and a significantly greater number of early signs of allograft rejection in exposed worms. Observations for 25 days post-transplantation revealed no response to autografts, but an acceleration of the allograft rejection process in exposed earthworms. We postulate that Aroclor modified host coelomocytes and/or their interactions associated with antigen recognition and inflammation.

Cytokines in single layer amnion allografts compared to multilayer amnion/chorion allografts for wound healing.

PubMed

Koob, Thomas J; Lim, Jeremy J; Zabek, Nicole; Massee, Michelle

2015-07-01

Human amniotic membrane allografts have proven effective at improving healing of cutaneous wounds. The mechanism of action for these therapeutic effects is poorly understood but is thought to involve the resident growth factors present in near term amniotic tissue. To determine the relative cytokine contribution of the amnion and chorion in amniotic allografts, the content of 18 cytokines involved in wound healing were measured in samples of PURION® Processed dehydrated amnion, chorion, and amnion/chorion membrane (dHACM) grafts by multiplex enzyme-linked immunosorbent assay array. Both amnion and chorion contained similar amounts of each factor when normalized per dry weight; however, when calculated per surface area of tissue applied to a wound, amnion contained on average only 25% as much of each factor as the chorion. Therefore, an allograft containing both amnion and chorion would contain four to five times more cytokine than a single layer amnion allograft alone. Both single layer amnion and multilayer allografts containing amnion and chorion are currently marketed for wound repair. To examine the role of tissue processing technique in cytokine retention, cytokine contents in representative dehydrated single layer wound care products were measured. The results demonstrated that cytokine content varied significantly among the allografts tested, and that PURION® Processed single layer amnion grafts contained more cytokines than other single layer products. These results suggest that PURION® Processed dHACM contains substantially more cytokines than single layer amnion products, and therefore dHACM may be more effective at delivering growth factors to a healing wound than amnion alone. © 2014 Wiley Periodicals, Inc.

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction.

PubMed

Iglesias, Jose; Frank, Elliot; Mehandru, Sushil; Davis, John M; Levine, Jerrold S

2013-07-13

Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction.

Predictors of renal recovery in patients with pre-orthotopic liver transplant (OLT) renal dysfunction

PubMed Central

2013-01-01

Background Renal dysfunction occurs commonly in patients awaiting orthotopic liver transplantation (OLT) for end-stage liver disease. The use of simultaneous liver-kidney transplantation has increased in the MELD scoring era. As patients may recover renal function after OLT, identifying factors predictive of renal recovery is a critical issue, especially given the scarcity of available organs. Methods Employing the UNOS database, we sought to identify donor- and patient-related predictors of renal recovery among 1720 patients with pre-OLT renal dysfunction and transplanted from 1989 to 2005. Recovery of renal function post-OLT was defined as a composite endpoint of serum creatinine (SCr) ≤1.5 mg/dL at discharge and survival ≥29 days. Pre-OLT renal dysfunction was defined as any of the following: SCr ≥2 mg/dL at any time while awaiting OLT or need for renal replacement therapy (RRT) at the time of registration and/or OLT. Results Independent predictors of recovery of renal function post-OLT were absence of hepatic allograft dysfunction, transplantation during MELD era, recipient female sex, decreased donor age, decreased recipient ALT at time of OLT, decreased recipient body mass index at registration, use of anti-thymocyte globulin as induction therapy, and longer wait time from registration. Contrary to popular belief, a requirement for RRT, even for prolonged periods in excess of 8 weeks, was not an independent predictor of failure to recover renal function post-OLT. Conclusion These data indicate that the duration of renal dysfunction, even among those requiring RRT, is a poor way to discriminate reversible from irreversible renal dysfunction. PMID:23849513

[Renal decapsulation for the treatment of anuria : A "forgotten" treatment from the early 20th century].

PubMed

Dräger, D L; Protzel, C; Hakenberg, O W

2017-01-01

In the early 20th century, Harrison first performed renal decapsulation in anuric children with scarlet fever and observed improvement in renal function postoperatively. The pathophysiological explanation was seen in intraparenchymal renal pressure due to edema which was improved by surgical decapsulation. The technique of decapsulation was simple excision after incision and blunt dissection of the renal parenchyma. Renal decapsulation then became a procedure commonly used for many indications in inflammatory renal conditions; indications were renal angioneurosis, hydronephrosis, toxic, bacterial and chronic nephritis, renal abscess and even eclampsia. With the beginning of the antibiotic era, renal decapsulation became obsolete and has disappeared from the urological spectrum completely.

Knee salvage procedures: The indications, techniques and outcomes of large osteochondral allografts

PubMed Central

Chui, Karen; Jeys, Lee; Snow, Martyn

2015-01-01

The overall incidence of osteochondral defect in the general population is estimated to be 15 to 30 per 100000 people. These lesions can become symptomatic causing pain, swelling and decreased function of the knee, and may eventually progress to osteoarthritis. In the young and active population, partial or total knee arthroplasty (TKA) is rarely the treatment of choice due to risk of early failure. Osteochondral allograft transplantation has been demonstrated to be a safe and effective treatment of large osteochondral and chondral defects of the knee in appropriately selected patients. The treatment reduces pain, improves function and is a viable limb salvage procedure for patients, especially young and active patients for whom TKA is not recommended. Either large dowels generated with commercially available equipment or free hand shell allografts can be implanted in more posterior lesions. Current recommendations for fresh allografts stored at 4C advise implantation within 21-28 d of procurement for optimum chondrocyte viability, following screening and testing protocols. Higher rates of successful allograft transplantation are observed in younger patients, unipolar lesions, normal or corrected malalignment, and defects that are treated within 12 mo of symptom onset. Patients with bipolar lesions, uncorrectable malalignment, advanced osteoarthritis, and those over 40 tend to have less favourable outcomes. PMID:25893177

Diagnostic value of quantitative contrast-enhanced ultrasound (CEUS) for early detection of renal hyperperfusion in diabetic kidney disease.

PubMed

Wang, Ling; Wu, Jian; Cheng, Jia-Fen; Liu, Xin-Ying; Ma, Fang; Guo, Le-Hang; Xu, Jun-Mei; Wu, Tianfu; Mohan, Chandra; Peng, Ai; Xu, Hui-Xiong; Song, Ya-Xiang

2015-12-01

To investigate the diagnostic value of quantitative contrast-enhanced ultrasound (CEUS) for early detection of renal hyperperfusion in diabetic kidney disease (DKD). 55 DKD patients with estimated glomerular filtration rate (eGFR) >30 ml/min/1.73 m(2) and 26 normal controls (NCs) were enrolled. Clinical data was well documented. Blood samples were drawn for evaluation of renal function including blood urea nitrogen (BUN), serum creatinine (SCr) and serum uric acid (SUA), and urine samples were assayed for total protein quantification, and various microprotein markers. According to eGFR level, DKD patients were divided into early-stage DKD (eGFR ≥90 ml/min/1.73 m(2), n = 18) and middle-stage DKD (eGFR 30-90 ml/min/1.73 m(2), n = 37). Based on urinary microalbumin/creatinine ratio (MALB/UCR), early-stage DKD patients were further classified into two groups: MALB/UCR <10 g/mol (n = 11) and MALB/UCR ≥10 g/mol (n = 7). Then, CEUS was performed to observe the real-time renal perfusion, and low acoustic power contrast-specific imaging was used for quantitative analysis. The renal perfusion images of CEUS were well developed successively. The corresponding perfusion curves based on echo-power signals in time series were constructed. Quantitative analysis showed that area under the descending curve (AUC2) was significantly increased in early-stage DKD compared to middle-stage DKD (p < 0.05), but AUC showed no significant difference. Further comparison between different MALB/UCR levels of early-stage DKD showed that patients with MALB/UCR ≥10 g/mol had significantly increased levels of AUC, AUC2 and proteinuria than patients with low MALB/UCR (p < 0.05). Also, high MALB/UCR DKD patients had increased proteinuria but similar eGFR compared to low MALB/UCR patients. Renal microvascular hyperperfusion may be responsible for overt proteinuria until decline of renal filtration in DKD. AUC2 could be an early and sensitive marker for early renal injury and renal microvascular

A cost-effective method for femoral head allograft procurement for spinal arthrodesis: an alternative to commercially available allograft.

PubMed

Brown, Desmond A; Mallory, Grant W; Higgins, Dominique M; Abdulaziz, Mohammed; Huddleston, Paul M; Nassr, Ahmad; Fogelson, Jeremy L; Clarke, Michelle J

2014-07-01

A cost-effective procurement process for harvesting, storing, and using femoral head allografts is described. A brief review of the literature on the use of these allografts and a discussion of costs are provided. To describe a cost-effective method for the harvesting, storage, and use of femoral heads from patients undergoing total hip arthroplasty at our institution as a source of allograft bone. Spine fusion surgery uses a large proportion of commercially available bone grafts and bone substitutes. As the number of such surgical procedures performed in the United States continues to rise, these materials are at a historically high level of demand, which is projected to continue. Iliac crest bone autograft has historically been the standard of care, although this may be losing favor due to potential donor site morbidity. Although many substitutes are effective in promoting arthrodesis, their use is limited because of cost. Femoral heads are harvested under sterile conditions during total hip arthroplasty. The patient is tested per Food and Drug Administration regulations, and the tissue sample is cultured. The tissue is frozen and quarantined for a 6-month minimum pending repeat testing of donors and subsequently released for use. The relative cost-effectiveness of this tissue as a source of allograft bone is discussed. The average femoral head allograft is 54 to 56 mm in diameter and yields 50 cm of bone graft, with an average cost of US $435 for processing of the tissue resulting in a cost of US $8.70 per cm of allograft produced. Average production costs are significantly lower than those for other commonly available commercial bone grafts and substitutes. Femoral head allograft is a cost-effective alternative to commercially available allografts and bone substitutes. The method of procurement, storage, and use described could be adopted by other institutions in an effort to mitigate cost and increase supply. N/A.

Impact of early screening for reflux in siblings on the detection of renal damage.

PubMed

Houle, Anne-Marie; Cheikhelard, Alaa; Barrieras, Diego; Rivest, Marie-Christine; Gaudreault, Valérie

2004-07-01

To assess the impact of screening siblings after detecting significant vesico-ureteric reflux (VUR) and renal scarring, as such screening might identify patients with VUR before urinary tract infections develop, but might also detect clinically insignificant VUR. We used a previously reported screening protocol to assess the clinical characteristics of patients, including the incidence of renal scarring, and their siblings, and compared the results. In all, 123 children were screened and 44 (36%) had VUR on voiding cystography. The median (range) age at screening was 9 (1-90) months. The grades of VUR detected were < III in 61% and > or = III in 39%; VUR was bilateral in 48%. In all, 37 siblings with VUR were assessed by ultrasonography; 70% were normal, including 12 (32%) children with VUR of grade > or = III. When used, renal scintigraphy was normal in 74% of siblings, vs 18% of index patients. However, when screened after 2 years old, siblings had twice the risk of already having renal damage on renal scintigraphy (P = 0.04). Early screening (< or = 2 years) appears to be more protective for avoiding renal damage than screening older patients. Thus we propose early screening in asymptomatic siblings to detect VUR before it becomes clinically significant.

WT1 controls antagonistic FGF and BMP-pSMAD pathways in early renal progenitors.

PubMed

Motamedi, Fariba Jian; Badro, Danielle A; Clarkson, Michael; Lecca, M Rita; Bradford, Stephen T; Buske, Fabian A; Saar, Kathrin; Hübner, Norbert; Brändli, André W; Schedl, Andreas

2014-07-17

Kidney organogenesis requires the tight control of proliferation, differentiation and apoptosis of renal progenitor cells. How the balance between these cellular decisions is achieved remains elusive. The Wilms' tumour suppressor Wt1 is required for progenitor survival, but the molecular cause for renal agenesis in mutants is poorly understood. Here we demonstrate that lack of Wt1 abolishes fibroblast growth factor (FGF) and induces BMP/pSMAD signalling within the metanephric mesenchyme. Addition of recombinant FGFs or inhibition of pSMAD signalling rescues progenitor cell apoptosis induced by the loss of Wt1. We further show that recombinant BMP4, but not BMP7, induces an apoptotic response within the early kidney that can be suppressed by simultaneous addition of FGFs. These data reveal a hitherto unknown sensitivity of early renal progenitors to pSMAD signalling, establishes FGF and pSMAD signalling as antagonistic forces in early kidney development and places WT1 as a key regulator of pro-survival FGF signalling pathway genes.

Intragraft expression of the IL-10 gene is up-regulated in renal protocol biopsies with early interstitial fibrosis, tubular atrophy, and subclinical rejection.

PubMed

Hueso, Miguel; Navarro, Estanis; Moreso, Francesc; O'Valle, Francisco; Pérez-Riba, Mercè; Del Moral, Raimundo García; Grinyó, Josep M; Serón, Daniel

2010-04-01

Grafts with subclinical rejection associated with interstitial fibrosis and tubular atrophy (SCR+IF/TA) show poorer survival than grafts with subclinical rejection without IF/TA (SCR). Aiming to detect differences among SCR+IF/TA and SCR, we immunophenotyped the inflammatory infiltrate (CD45, CD3, CD20, CD68) and used a low-density array to determine levels of T(H)1 (interleukin IL-2, IL-3, gamma-interferon, tumor necrosis factor-alpha, lymphotoxin-alpha, lymphotoxin-beta, granulocyte-macrophage colony-stimulating factor) and T(H)2 (IL-4, IL-5, IL-6, IL-10, and IL-13) transcripts as well as of IL-2R (as marker for T-cell activation) in 31 protocol biopsies of renal allografts. Here we show that grafts with early IF/TA and SCR can be distinguished from grafts with SCR on the basis of the activation of IL-10 gene expression and of an increased infiltration by B-lymphocytes in a cellular context in which the degree of T-cell activation is similar in both groups of biopsies, as demonstrated by equivalent levels of IL-2R mRNA. These results suggest that the up-regulation of the IL-10 gene expression, as well as an increased proportion of B-lymphocytes in the inflammatory infiltrates, might be useful as markers of early chronic lesions in grafts with SCR.

Intragraft Expression of the IL-10 Gene Is Up-Regulated in Renal Protocol Biopsies with Early Interstitial Fibrosis, Tubular Atrophy, and Subclinical Rejection

PubMed Central

Hueso, Miguel; Navarro, Estanis; Moreso, Francesc; O'Valle, Francisco; Pérez-Riba, Mercè; del Moral, Raimundo García; Grinyó, Josep M.; Serón, Daniel

2010-01-01

Grafts with subclinical rejection associated with interstitial fibrosis and tubular atrophy (SCR+IF/TA) show poorer survival than grafts with subclinical rejection without IF/TA (SCR). Aiming to detect differences among SCR+IF/TA and SCR, we immunophenotyped the inflammatory infiltrate (CD45, CD3, CD20, CD68) and used a low-density array to determine levels of TH1 (interleukin IL-2, IL-3, γ-interferon, tumor necrosis factor-α, lymphotoxin-α, lymphotoxin-β, granulocyte-macrophage colony-stimulating factor) and TH2 (IL-4, IL-5, IL-6, IL-10, and IL-13) transcripts as well as of IL-2R (as marker for T-cell activation) in 31 protocol biopsies of renal allografts. Here we show that grafts with early IF/TA and SCR can be distinguished from grafts with SCR on the basis of the activation of IL-10 gene expression and of an increased infiltration by B-lymphocytes in a cellular context in which the degree of T-cell activation is similar in both groups of biopsies, as demonstrated by equivalent levels of IL-2R mRNA. These results suggest that the up-regulation of the IL-10 gene expression, as well as an increased proportion of B-lymphocytes in the inflammatory infiltrates, might be useful as markers of early chronic lesions in grafts with SCR. PMID:20150436

Improvement in late renal allograft survival between 1990 and 2002 in Spain: results from a multicentre case-control study.

PubMed

Moreso, Francesc; Alonso, Angel; Gentil, Miguel A; González-Molina, Miguel; Capdevila, Lluis; Marcén, Roberto; Pascual, Julio; Serón, Daniel

2010-09-01

Epidemiological studies have failed to show an improvement in graft survival beyond 1 year after kidney transplantation possibly because of an increased number of expanded donors and older recipients. Thus, we performed a case-control study matching patients transplanted in different eras by donor and recipient characteristics. We considered renal transplant recipients included in the database of the Spanish Chronic Allograft Dysfunction Study Group in 1990, 1994, 1998 and 2002 (n = 4842). We matched patients from these cohorts considering the following variables: donor and recipient age, cause of donor death, hepatitis C virus, panel reactive antibodies and re-transplantation. We identified a total of 896 patients distributed in four cohorts of 224 matched patients. Between 1990 and 2002, the use of cyclosporin decreased (96%, 94%, 80% and 23% respectively, P = 0.001), while the use of tacrolimus increased (0%, 1%, 15% and 63% respectively, P = 0.001) and the prevalence of acute rejection decreased (46%, 37.9%, 20.6% and 15.8% respectively, P < 0.001). One-year serum creatinine was 1.63 +/- 0.66, 1.64 +/- 0.70, 1.44 +/- 0.52 and 1.38 +/- 0.75 respectively, P = 0.001. Graft survival beyond the first year between 1990 and 2002 significantly improved while patient survival did not. Transplant outcome has improved between 1990 and 2002 when donors and recipients of similar characteristics are compared.

Successful immunosuppressant-free heterotopic transplantation of tracheal allografts in the pig.

PubMed

De Wolf, Julien; Brieu, Mathias; Zawadzki, Christophe; Ung, Alexandre; Kipnis, Eric; Jashari, Ramadan; Hubert, Thomas; Fayoux, Pierre; Mariette, Christophe; Copin, Marie-Christine; Wurtz, Alain

2017-08-01

It has been demonstrated that both heterotopic and orthotopic transplants of epithelium-denuded cryopreserved tracheal allografts are feasible in immunosuppressant-free rabbits. Validation of these results in large animals is required before considering clinical applications. We evaluated the viability, immune tolerance and strain properties of such tracheal allografts heterotopically transplanted in a pig model. Ten tracheal segments, 5 short (5 rings) and 5 long (10 rings), were obtained from male Landrace pigs. The tracheal segments were surgically denuded of their epithelium, then cryopreserved and stored in a tissue bank for 33 to 232 days. After thawing, tracheal segments stented with a silicone tube were wrapped in the omentum in 2 groups of 5 female recipients. The animals did not receive any immunosuppressive drugs. The animals were euthanized from Day 6 to Day 90 in both groups. An effective revascularization of allografts regardless of length was observed. Lymphocyte infiltrate was shown in the early postoperative period and became non-significant after 30 days. Allografts displayed high levels of neoangiogenesis and viable cartilage rings with islets of calcification. Biomechanical measurements demonstrated strain properties similar to those of a fresh tracheal segment from Day 58. Our results demonstrate the acceptability and satisfactory stiffness of epithelium-denuded cryopreserved tracheal allografts implanted in the omentum, despite the absence of immunosuppressive drugs. Since the omentum has the capability to reach the tracheal region, this approach should be investigated in the setting of orthotopic transplants in a pig model before considering clinical applications. © The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

Disseminated Cryptococcosis presenting as cellulitis in a renal transplant recipient.

PubMed

Chaya, Ramachandraiah; Padmanabhan, Srinivasan; Anandaswamy, Venugopal; Moin, Aumir

2013-01-15

Cellulitis is an unusual presentation of cryptococcal infection in renal allograft recipients. In such patients, disseminated cryptococcal infection can result in significant morbidity and mortality. Patients are often treated with antibiotics before a definitive diagnosis is made, delaying appropriate therapy. We describe the case of a 43-year-old post renal transplant recipient presenting with fever and swelling in the right thigh. On physical examination, the patient was found to have features suggestive of cellulitis with minimal slurring of speech. Material obtained from incision and drainage of the wound showed yeast cells resembling Cryptococcus spp. Blood culture and cerebrospinal fluid culture were also found to have growth of Cryptococcus neoformans. He received treatment with amphotericin B 6 mg/kg daily intravenously for two weeks, then continued with fluconazole 400 mg daily for three months. The patient showed a remarkable improvement. There was no recurrence of cryptococcosis after four months of follow-up. The diagnosis of disseminated cryptococcosis should be considered in differential diagnosis of cellulitis among non HIV immunocompromised hosts. A high clinical suspicion and early initiation of therapy is needed to recognize and treat patients effectively.

Stability of renal allograft recipients after conversion from cyclosporine to azathioprine.

PubMed

Carpenter, C B; Milford, E L; Kirkman, R L; Strom, T B; Lazarus, J M; Tilney, N L

1985-08-01

Forty-eight patients with stable renal function after allotransplantation have been converted from CsA/prednisone to azathioprine/prednisone to assess the short- and long-term effects upon renal function. Virtually all patients show an initial improvement in serum creatinine levels. Three patients developed chronic renal failure after 12 to 21 months, and three died of pneumonia 7, 12, and 19 months later. The mean serum creatinine level at latest follow-up (seven to 36 months) was 2.5 +/- 1.5 mg/dL for all 48 patients. Of interest, a control group of 21 patients not converted to azathioprine had serum creatinine levels of 2.5 +/- 0.8 mg/dL, over a follow-up period of five to 25 months. It is not immediately apparent that either group will have a superior overall outcome, although patients on azathioprine seem to have more of a risk for graft loss. More data are needed with various dosage schedules, and with randomized controls.

Chronic Lung Allograft Dysfunction: A Systematic Review of Mechanisms.

PubMed

Royer, Pierre-Joseph; Olivera-Botello, Gustavo; Koutsokera, Angela; Aubert, John-David; Bernasconi, Eric; Tissot, Adrien; Pison, Christophe; Nicod, Laurent; Boissel, Jean-Pierre; Magnan, Antoine

2016-09-01

Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. Chronic lung allograft dysfunction manifests as bronchiolitis obliterans syndrome or the recently described restrictive allograft syndrome. Although numerous risk factors have been identified so far, the physiopathological mechanisms of CLAD remain poorly understood. We investigate here the immune mechanisms involved in the development of CLAD after lung transplantation. We explore the innate or adaptive immune reactions induced by the allograft itself or by the environment and how they lead to allograft dysfunction. Because current literature suggests bronchiolitis obliterans syndrome and restrictive allograft syndrome as 2 distinct entities, we focus on the specific factors behind one or the other syndromes. Chronic lung allograft dysfunction is a multifactorial disease that remains irreversible and unpredictable so far. We thus finally discuss the potential of systems-biology approach to predict its occurrence and to better understand its underlying mechanisms.

Structural allograft reconstruction of the foot and ankle after tumor resections.

PubMed

Ayerza, M A; Piuzzi, N S; Aponte-Tinao, L A; Farfalli, G L; Muscolo, D L

2016-08-01

Structural allografts have been used to correct deformities or to fill bone defects secondary to tumor excisions, trauma, osteochondral lesions, or intercalary arthrodesis. However, the quality of published evidence supporting the use of allograft transplantation in foot and ankle surgery has been reported as fair. The purpose of this study was to report the overall survival of structural allograft in the foot and ankle after tumor resection, and the survival according to the type of allograft and the complication rates in the medium to long term. From January 1989 to June 2011, 44 structural allograft reconstructions of the foot and ankle were performed in 42 patients (28 men and 14 women) due to musculoskeletal tumor resections. Mean age at presentation was 27 years. Mean follow-up was 53 months. Demographic data, diagnosis, site of the neoplasm, operations performed, operative complications, outcomes after surgery, date of last follow-up evaluation, and local recurrences were reviewed for all patients. Regarding the type of 44 allograft reconstructions, 16 were hemicylindrical allografts (HA), 12 intercalary allografts (IA), 10 osteoarticular allografts (OA), and 6 were total calcaneal allograft (CA). The overall allograft survival rate, as calculated with the Kaplan-Meier method, at 5 and 10 years was 79 % (95 % CI 64-93 %). When allocated by type of allograft reconstruction the specific allograft survival at 5 and 10 years was: 83 % for CA, 80 % for HA, 77 % for OA, and 75 % for IA. The complications rate for this series was 36 % including: articular failure, local recurrence, infection, fracture and nonunion. This study showed that structural allograft reconstruction in the foot and ankle after tumor resection may be durable with a 79 % survival rate at 5 and 10 years. The two types of allografts that showed better survival rate were hemicylindrical allografts (80 %) and calcaneus allografts (83 %). The highest complication rates occurred

Allograft materials in phalloplasty: a comparative analysis.

PubMed

Solomon, Mark P; Komlo, Caroline; Defrain, Molly

2013-09-01

Allograft use has increased recently with the rising use of allograft materials in breast surgery. There are few data that compare the performance of the various allograft materials in this application, despite marketing efforts by the manufacturers to present one allograft material as superior to another. Phalloplasty is a procedure that uses allografts for penis girth augmentation. Preparation of these grafts differs with each manufacturer. We report our experience with 3 different types of allografts for this procedure. This allows for the comparison of these materials in their performance with a single model. Forty-seven patients who underwent penis girth enhancement with allograft material were reviewed. All patients underwent circumferential grafting to the shaft of the penis at the level of Buck's fascia. Graft materials included AlloDerm (n = 9), Belladerm (n = 20), and Repriza (n = 21). Charts were reviewed for material type, presence and type of infection, wound exposure, and graft loss with attention to the type of allograft material that was used. Follow-up ranged from 1 to 120 months with an average of 11.25 months. Infection, defined as an open wound with graft exposure, occurred in 20 (42%) of 47 patients. Of these, graft exposure only occurred in 17 (36%) patients, whereas 3 (6%) patients sustained total graft loss. Graft exposure or loss occurred in 3 patients who had AlloDerm, 9 patients with Belladerm, and 8 patients with Repriza. No patients with AlloDerm sustained graft loss, whereas 2 patients with Belladerm and 1 patient with Repriza sustained graft loss. There were no statistical differences among these graft types with regard to infection or graft loss. Three different brands of allograft material were used in 1 surgical procedure and followed up for their performance with regard to exposure and infection. In this model, there is no difference in the rate of infection in these materials despite their different methods of preparation

PTH promotes allograft integration in a calvarial bone defect

PubMed Central

Sheyn, Dmitriy; Yakubovich, Doron Cohn; Kallai, Ilan; Su, Susan; Da, Xiaoyu; Pelled, Gadi; Tawackoli, Wafa; Cook-Weins, Galen; Schwarz, Edward M.; Gazit, Dan; Gazit, Zulma

2013-01-01

Allografts may be useful in craniofacial bone repair, although they often fail to integrate with the host bone. We hypothesized that intermittent administration of parathyroid hormone (PTH) would enhance mesenchymal stem cell recruitment and differentiation, resulting in allograft osseointegration in cranial membranous bones. Calvarial bone defects were created in transgenic mice, in which luciferase is expressed under the control of the osteocalcin promoter. The mice were given implants of allografts with or without daily PTH treatment. Bioluminescence imaging (BLI) was performed to monitor host osteprogenitor differentiation at the implantation site. Bone formation was evaluated with the aid of fluorescence imaging (FLI) and micro–computed tomography (μCT) as well as histological analyses. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the expression of key osteogenic and angiogenic genes. Osteoprogenitor differentiation, as detected by BLI, in mice treated with an allograft implant and PTH was over 2-fold higher than those in mice treated with an allograft implant without PTH. FLI also demonstrated that the bone mineralization process in PTH-treated allografts was significantly higher than that in untreated allografts. The μCT scans revealed a significant increase in bone formation in Allograft + PTH–treated mice comparing to Allograft + PBS treated mice. The osteogenic genes osteocalcin (Oc/Bglap) and integrin binding sialoprotein (Ibsp) were upregulated in the Allograft + PTH–treated animals. In summary, PTH treatment enhances osteoprogenitor differentiation and augments bone formation around structural allografts. The precise mechanism is not clear, but we show that infiltration pattern of mast cells, associated with the formation of fibrotic tissue, in the defect site is significantly affected by the PTH treatment. PMID:24131143

PTH promotes allograft integration in a calvarial bone defect.

PubMed

Sheyn, Dmitriy; Cohn Yakubovich, Doron; Kallai, Ilan; Su, Susan; Da, Xiaoyu; Pelled, Gadi; Tawackoli, Wafa; Cook-Weins, Galen; Schwarz, Edward M; Gazit, Dan; Gazit, Zulma

2013-12-02

Allografts may be useful in craniofacial bone repair, although they often fail to integrate with the host bone. We hypothesized that intermittent administration of parathyroid hormone (PTH) would enhance mesenchymal stem cell recruitment and differentiation, resulting in allograft osseointegration in cranial membranous bones. Calvarial bone defects were created in transgenic mice, in which luciferase is expressed under the control of the osteocalcin promoter. The mice were given implants of allografts with or without daily PTH treatment. Bioluminescence imaging (BLI) was performed to monitor host osteprogenitor differentiation at the implantation site. Bone formation was evaluated with the aid of fluorescence imaging (FLI) and microcomputed tomography (μCT) as well as histological analyses. Reverse transcription polymerase chain reaction (RT-PCR) was performed to evaluate the expression of key osteogenic and angiogenic genes. Osteoprogenitor differentiation, as detected by BLI, in mice treated with an allograft implant and PTH was over 2-fold higher than those in mice treated with an allograft implant without PTH. FLI also demonstrated that the bone mineralization process in PTH-treated allografts was significantly higher than that in untreated allografts. The μCT scans revealed a significant increase in bone formation in allograft + PTH treated mice comparing to allograft + PBS treated mice. The osteogenic genes osteocalcin (Oc/Bglap) and integrin binding sialoprotein (Ibsp) were upregulated in the allograft + PTH treated animals. In summary, PTH treatment enhances osteoprogenitor differentiation and augments bone formation around structural allografts. The precise mechanism is not clear, but we show that infiltration pattern of mast cells, associated with the formation of fibrotic tissue, in the defect site is significantly affected by the PTH treatment.

CMV allograft pancreatitis: diagnosis, treatment, and histological features.

PubMed

Klassen, D K; Drachenberg, C B; Papadimitriou, J C; Cangro, C B; Fink, J C; Bartlett, S T; Weir, M R

2000-05-15

Cytomegalovirus (CMV) infection is a common problem in solid organ transplant recipients. CMV infection of pancreas allografts is not, however, well described. We report the clinical presentation, histologic findings, treatment, and outcome in four patients with CMV allograft pancreatitis. These patients presented 18 weeks to 44 months after transplantation with elevated serum amylase and lipase and were suspected to have acute rejection. Percutaneous pancreas allograft biopsy specimens showed evidence of tissue invasive CMV infection. One patient had simultaneous CMV infection and acute rejection. Prolonged treatment with ganciclovir resulted in clinical and histologic resolution of the CMV disease. Rejection was successfully treated. Primary CMV infection in seronegative recipients seemed to be a risk factor. Three patients maintain normal allograft function; one patient lost function due to chronic rejection. The histology of tissue-invasive CMV pancreas allograft infection and its differentiation from acute rejection is described. Prompt diagnosis and prolonged therapy with antiviral agents can result in maintenance of allograft function.

Transitional epithelial lesions of the ureter in renal transplant rejection.

PubMed

Katz, J P; Greenstein, S M; Hakki, A; Miller, A; Katz, S M; Simonian, S

1988-04-01

The spectrum of ureteric lesions of human renal allografts, long attributed exclusively to postsurgical complications such as ischemia, has recently been shown to include the types of rejection seen in the kidney. Since the rejected ureter also exhibits transitional epithelial lesions that may impact on renal and ureteral function, we studied, by light, immunohistochemical, immunofluorescent, and electron microscopic techniques, ureters of 65 irreversibly rejected kidneys. Seven unused cadaver kidneys served as controls. Urothelial lesions, noticed in 57 of 65 ureters (88%), ranged from minimal basal vacuolization to complete sloughing with or without necrosis of the epithelial lining. Epithelial exfoliation was noticed in 31 cases (54.4%), and basal vacuolization, severe enough to produce cleavage of the epithelial junctions and thus create bullae, was noticed in 21 cases (36.8%). Immunofluorescent and immunoperoxidase stains, performed in 16 cases, were all positive for immunoglobulins but yielded varied results ranging from granular to linear staining, particularly in the region of the basal cells and the basement membrane. Electron microscopic findings confirmed the light microscopic alterations. By contrast, control ureters showed no lesions. Urothelial ureteric lesions might impede ureteral functions and result in obstruction or infection, thus compounding the consequences of renal allograft rejection. Moreover, elucidation of the pathophysiology of the process will advance the understanding of various cutaneous and transitional epithelial autoimmune conditions.

Donor-Derived Regulatory Dendritic Cell Infusion Maintains Donor-Reactive CD4+CTLA4hi T Cells in Non-Human Primate Renal Allograft Recipients Treated with CD28 Co-Stimulation Blockade

PubMed Central

Ezzelarab, Mohamed B.; Lu, Lien; Shufesky, William F.; Morelli, Adrian E.; Thomson, Angus W.

2018-01-01

Donor-derived regulatory dendritic cell (DCreg) infusion before transplantation, significantly prolongs renal allograft survival in non-human primates. This is associated with enhanced expression of the immunoregulatory molecules cytotoxic T-lymphocyte-associated antigen (Ag) 4 (CTLA4) and programmed cell death protein 1 (PD1) by host donor-reactive T cells. In rodents and humans, CD28 co-stimulatory pathway blockade with the fusion protein CTLA4:Ig (CTLA4Ig) is associated with reduced differentiation and development of regulatory T cells (Treg). We hypothesized that upregulation of CTLA4 by donor-reactive CD4+ T cells in DCreg-infused recipients treated with CTLA4Ig, might be associated with higher incidences of donor-reactive CD4+ T cells with a Treg phenotype. In normal rhesus monkeys, allo-stimulated CD4+CTLA4hi, but not CD4+CTLA4med/lo T cells exhibited a regulatory phenotype, irrespective of PD1 expression. CTLA4Ig significantly reduced the incidence of CD4+CTLA4hi, but not CD4+CTLA4med/lo T cells following allo-stimulation, associated with a significant reduction in the CD4+CTLA4hi/CD4+CTLA4med/lo T cell ratio. In CTLA4Ig-treated renal allograft recipient monkeys, there was a marked reduction in circulating donor-reactive CD4+CTLA4hi T cells. In contrast, in CTLA4Ig-treated monkeys with DCreg infusion, no such reduction was observed. In parallel, the donor-reactive CD4+CTLA4hi/CD4+CTLA4med/lo T cell ratio was reduced significantly in graft recipients without DCreg infusion, but increased in those given DCreg. These observations suggest that pre-transplant DCreg infusion promotes and maintains donor-reactive CD4+CTLA4hi T cells with a regulatory phenotype after transplantation, even in the presence of CD28 co-stimulation blockade. PMID:29520267

Autograft versus Allograft for Cervical Spinal Fusion

PubMed Central

Brodke, Darrel S.; Youssef, Jim A.; Meisel, Hans-Jörg; Dettori, Joseph R.; Park, Jong-Beom; Yoon, S. Tim; Wang, Jeffrey C.

2017-01-01

Study Design Systematic review. Objective To compare the effectiveness and safety between iliac crest bone graft (ICBG), non-ICBG autologous bone, and allograft in cervical spine fusion. To avoid problems at the donor site, various allograft materials have been used as a substitute for autograft. However, there are still questions as to the comparative effectiveness and safety of cadaver allograft compared with autologous ICBG. Methods A systematic search of multiple major medical reference databases was conducted to identify studies evaluating spinal fusion in patients with cervical degenerative disk disease using ICBG compared with non-ICBG autograft or allograft or non-ICBG autograft compared with allograft in the cervical spine. Radiographic fusion, patient-reported outcomes, and functional outcomes were the primary outcomes of interest. Adverse events were evaluated for safety. Results The search identified 13 comparative studies that met our inclusion criteria: 2 prospective cohort studies and 11 retrospective cohort studies. Twelve cohort studies compared allograft with ICBG autograft during anterior cervical fusion and demonstrated with a low evidence level of support that there are no differences in fusion percentages, pain scores, or functional results. There was insufficient evidence comparing patients receiving allograft with non-ICBG autograft for fusion, pain, revision, and functional and safety outcomes. No publications directly comparing non-ICBG autograft with ICBG were found. Conclusion Although the available literature suggests ICBG and allograft may have similar effectiveness in terms of fusion rates, pain scores, and functional outcomes following anterior cervical fusion, there are too many limitations in the available literature to draw any significant conclusions. No individual study provided greater than class III evidence, and when evaluating the overall body of literature, no conclusion had better than low evidence support. A prospective

Resistive index and chronic allograft nephropathy evaluated in protocol biopsies as predictors of graft outcome.

PubMed

Vallejos, Augusto; Alperovich, Gabriela; Moreso, Francesc; Cañas, Concepcion; de Lama, M Eugenia; Gomà, Montserrat; Fulladosa, Xavier; Carrera, Marta; Hueso, Miguel; Grinyó, Josep M; Serón, Daniel

2005-11-01

The presence of chronic allograft nephropathy (CAN) in protocol biopsies is negatively associated with graft survival. Although recent studies have indicated that the resistive index (RI) is a predictor of graft failure, it does not correlate with CAN in stable grafts. We therefore studied the relationship between RI and CAN and examined the predictive value of both parameters on graft outcome. Included were patients transplanted between 1997 and 2002 and who had protocol biopsies and RI determinations. Renal lesions were blindly evaluated according to Banff 97 criteria. Mean glomerular volume, cortical interstitial volume fraction and intimal arterial volume fraction were estimated using a point counting technique. RI was determined before biopsy in at least two different renal locations. The outcome variable was defined as graft failure or a 30% serum creatinine increase between protocol biopsy and last follow-up. Eighty-seven patients were included. RI correlated with recipient age (R = 0.52, P < 0.0001), diastolic blood pressure (R = -0.36, P = 0.0006), pulse pressure index (R = 0.27, P = 0.009) and g-score for histological glomerulitis (rho = 0.30, P = 0.0054), but there were no correlations between RI and chronic Banff scores or any morphometric parameter. The presence of CAN (relative risk, 3.5; 95% confidence interval 1.2-10.2; P = 0.02) but not RI was associated with the outcome variable. RI was associated with surrogate measures of vascular compliance such as recipient age and pulse pressure index but not with chronic allograft damage, even when it was evaluated by histomorphometry. Our results indicate that histology may be superior to RI in predicting graft function deterioration, at least in patients with stable renal function.

Tanshinol suppresses cardiac allograft rejection in a murine model.

PubMed

Lu, Chuanjian; Zeng, Yu-Qun; Liu, Huazhen; Xie, Qingfeng; Xu, Shengmei; Tu, Kangsheng; Dou, Changwei; Dai, Zhenhua

2017-02-01

Achieving long-term cardiac allograft survival without continuous immunosuppression is highly desired in organ transplantation. Studies have shown that Salvia miltiorrhiza, an herb also known as danshen, improves microcirculation and is highly effective in treating coronary heart disease. Our objective is to determine whether tanshinol, an ingredient of danshen, improves cardiac allograft survival. Fully vascularized heterotopic heart transplantation was performed using BALB/c mice as donors and C57BL/6 mice as recipients, which were then treated with tanshinol and rapamycin. CD4 + FoxP3 + regulatory T cells (Tregs) were quantified by flow analyses, whereas CCL22 was measured by real-time polymerase chain reaction and Western blotting. We found that tanshinol significantly delayed cardiac allograft rejection. It promoted long-term allograft survival induced by rapamycin, a mammalian target-of-rapamycin (mTOR) inhibitor. Tanshinol increased CD4 + FoxP3 + Treg numbers in cardiac allografts, but not spleens and lymph nodes, of recipient mice by enhancing chemokine CCL22 expression in cardiac allografts, especially cardiac dendritic cells. In contrast, rapamycin increased Treg numbers in both lymphoid organs and allografts, suggesting that it generally expands Tregs. Moreover, Tregs induced by rapamycin plus tanshinol were more potent in suppressing T-cell proliferation in vitro than those from untreated recipients. Neutralizing CCL22 hindered CD4 + FoxP3 + Treg migration to cardiac allografts and reversed long-term allograft survival induced by tanshinol plus rapamycin. Tanshinol suppresses cardiac allograft rejection by recruiting CD4 + FoxP3 + Tregs to the graft, whereas rapamycin does so via expanding the Tregs. Thus, tanshinol cooperates with rapamycin to further extend cardiac allograft survival. Copyright © 2016 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

Posttransplant soluble CD30 as a predictor of acute renal allograft rejection.

PubMed

Kamali, Koosha; Abbasi, Mohammad Amin; Farokhi, Babak; Abbasi, Ata; Fallah, Parvane; Seifee, Mohammad Hasan; Ghadimi, Naime; Rezaie, Alireza R

2009-12-01

Recent results have indicated that high prerenal and postrenal transplant soluble CD30 levels may be associated with an increased acute rejection and graft loss. The aim of this study was to evaluate the feasibility of using serum sCD30 as a marker for predicting acute graft rejection. In this prospective study,we analyzed clinical data of 80 patients, whose pretransplant and posttransplant serum levels of sCD30 were detected by enzyme-linked immunoassay. Eight patients developed acute rejection, 7 patients showed delayed graft function, and 65 recipients experienced an uncomplicated course group. The patients were followed for 12 months, and there were no deaths. Preoperative sCD30 levels of 3 groups were 96.2 -/+ 32.5, 80.2 -/+ 28.3, and 76.8 -/+ 29.8 U/mL (P = .28). After transplant, a significant decrease in the sCD30 level was detected in 3 groups on day 14 posttransplant (P < .001), while sCD30 levels of acute rejection group remained significantly higher than delayed graft function and nonrejecting patients (28.3 -/+ 5.2, 22.1 -/+ 3.2, and 19.8 -/+ 4.7 U/mL) (P = .02). Positive panel reactive antibody was not statistically different among groups (P = .05). Also, hemodialysis did not affect sCD30 levels (P = .05). Receiver operating characteristic curve demonstrated that the sCD30 level on day 14 posttransplant could discriminate patients who subsequently suffered acute allograft rejection (area under receiver operating characteristic curve, 0.95). According to receiver operating characteristic curve, 20 U/mL may be the optimal operational cutoff level to predict impending graft rejection (specificity 93.8%, sensitivity 83.3%). Measurement of the soluble CD30 level on day 14 after transplant might offer a noninvasive means for recognizing patients at risk of acute graft rejection during the early posttransplant period.

Induction of tolerance and prolongation of islet allograft survival by syngeneic hematopoietic stem cell transplantation in mice.

PubMed

Yang, Shi-feng; Xue, Wu-jun; Lu, Wan-hong; Xie, Li-yi; Yin, Ai-ping; Zheng, Jin; Sun, Ji-ping; Li, Yang

2015-10-01

Syngeneic or autologous hematopoietic stem cells transplantation (HSCT) has been proposed to treat autoimmune diseases because of its immunosuppressive and immunomodulatory effects, which can also contribute to posttransplant antirejection therapy. In this study, we explored the tolerogenic effect of syngeneic HSCT on prolonging islet allograft survival. C57BL/6 mice received syngeneic HSCT plus preconditioning with sublethal irradiation. Then islets of BALB/c mice were transplanted into the renal subcapsular of C57BL/6 mice after chemically induced into diabetes. HSCT mice exhibited improved islet allograft survival and increased serum insulin compared to control mice. Islet allografts of HSCT mice displayed lower level lymphocyte infiltration and stronger insulin staining than control mice. T cells of HSCT mice proliferated poorly in response to allogeneic splenocytes compared to control mice. Mice appeared reversed interferon-γ (IFN-γ)/interleukin-4 (IL-4) ratio to a Th2 immune deviation after syngeneic HSCT. The percentage of CD8(+) T cells was lower, while percentage of CD4(+)CD25(+)Foxp3(+) T regulatory cells (Tregs) was higher in HSCT mice than control mice. HSCT mice showed higher percentage of CTLA-4(+) T cells and expression of CTLA-4 mRNA than control mice. Targeting of CTLA-4 by intraperitoneal injection of anti-CTLA-4 mAb abrogated the effect of syngeneic HSCT on prolonging islet allograft survival, inhibiting activity of T cells in response to alloantigen, promoting Th1 to Th2 immune deviation and up regulating CD4(+)CD25(+)Foxp3(+) Tregs. Syngeneic HSCT plus preconditioning of sublethal irradiation induces tolerance and improves islet allograft survival in fully mismatched mice model. Th1 to Th2 immune deviation, increased CD4(+)CD25(+)Foxp3(+) Tregs and up-regulation of CTLA-4 maybe contribute to the tolerogenic effect induced by syngeneic HSCT. Copyright © 2015 Elsevier B.V. All rights reserved.

Early statin use is an independent predictor of long-term graft survival.

PubMed

Moreso, Francesc; Calvo, Natividad; Pascual, Julio; Anaya, Fernando; Jiménez, Carlos; Del Castillo, Domingo; Sánchez-Plumed, Jaime; Serón, Daniel

2010-06-01

Background. Statin use in renal transplantation has been associated with a lower risk of patient death but not with an improvement of graft functional survival. The aim of this study is to evaluate the effect of statin use in graft survival, death-censored graft survival and patient survival using the data recorded on the Spanish Late Allograft Dysfunction Study Group.Patients and methods. Patients receiving a renal allograft in Spain in 1990, 1994, 1998 and 2002 were considered. Since the mean follow-up in the 2002 cohort was 3 years, statin use was analysed considering its introduction during the first year or during the initial 2 years after transplantation. Univariate and multivariate Cox regression analyses with a propensity score for statin use were employed to analyse graft survival, death-censored graft survival and patient survival.Results. In the 4682 evaluated patients, the early statin use after transplantation significantly increased from 1990 to 2002 (12.7%, 27.9%, 47.7% and 53.0%, P < 0.001). Statin use during the first year was not associated with graft or patient survival. Statin use during the initial 2 years was associated with a lower risk of graft failure (relative risk [RR] = 0.741 and 95% confidence interval [CI] = 0.635-0.866, P < 0.001) and patient death (RR = 0.806 and 95% CI = 0.656-0.989, P = 0.039). Death-censored graft survival was not associated with statin use during the initial 2 years.Conclusion. The early introduction of statin treatment after transplantation is associated with a significant decrease in late graft failure due to a risk reduction in patient death.

Early statin use is an independent predictor of long-term graft survival

PubMed Central

Moreso, Francesc; Calvo, Natividad; Pascual, Julio; Anaya, Fernando; Jiménez, Carlos; del Castillo, Domingo; Sánchez-Plumed, Jaime; Serón, Daniel

2010-01-01

Background. Statin use in renal transplantation has been associated with a lower risk of patient death but not with an improvement of graft functional survival. The aim of this study is to evaluate the effect of statin use in graft survival, death-censored graft survival and patient survival using the data recorded on the Spanish Late Allograft Dysfunction Study Group. Patients and methods. Patients receiving a renal allograft in Spain in 1990, 1994, 1998 and 2002 were considered. Since the mean follow-up in the 2002 cohort was 3 years, statin use was analysed considering its introduction during the first year or during the initial 2 years after transplantation. Univariate and multivariate Cox regression analyses with a propensity score for statin use were employed to analyse graft survival, death-censored graft survival and patient survival. Results. In the 4682 evaluated patients, the early statin use after transplantation significantly increased from 1990 to 2002 (12.7%, 27.9%, 47.7% and 53.0%, P < 0.001). Statin use during the first year was not associated with graft or patient survival. Statin use during the initial 2 years was associated with a lower risk of graft failure (relative risk [RR] = 0.741 and 95% confidence interval [CI] = 0.635–0.866, P < 0.001) and patient death (RR = 0.806 and 95% CI = 0.656–0.989, P = 0.039). Death-censored graft survival was not associated with statin use during the initial 2 years. Conclusion. The early introduction of statin treatment after transplantation is associated with a significant decrease in late graft failure due to a risk reduction in patient death. PMID:20508861

Acellular Nerve Allografts in Peripheral Nerve Regeneration: A Comparative Study

PubMed Central

Moore, Amy M.; MacEwan, Matthew; Santosa, Katherine B.; Chenard, Kristofer E.; Ray, Wilson Z.; Hunter, Daniel A.; Mackinnon, Susan E.; Johnson, Philip J.

2011-01-01

Background Processed nerve allografts offer a promising alternative to nerve autografts in the surgical management of peripheral nerve injuries where short deficits exist. Methods Three established models of acellular nerve allograft (cold-preserved, detergent-processed, and AxoGen® -processed nerve allografts) were compared to nerve isografts and silicone nerve guidance conduits in a 14 mm rat sciatic nerve defect. Results All acellular nerve grafts were superior to silicone nerve conduits in support of nerve regeneration. Detergent-processed allografts were similar to isografts at 6 weeks post-operatively, while AxoGen®-processed and cold-preserved allografts supported significantly fewer regenerating nerve fibers. Measurement of muscle force confirmed that detergent-processed allografts promoted isograft-equivalent levels of motor recovery 16 weeks post-operatively. All acellular allografts promoted greater amounts of motor recovery compared to silicone conduits. Conclusions These findings provide evidence that differential processing for removal of cellular constituents in preparing acellular nerve allografts affects recovery in vivo. PMID:21660979

Albumin-coated structural lyophilized bone allografts: a clinical report of 10 cases.

PubMed

Klára, Tamás; Csönge, Lajos; Janositz, Gábor; Csernátony, Zoltán; Lacza, Zsombor

2014-03-01

Bone replacement and the use of bone supplementary biological substances have become widespread in clinical practice. Although autografts have excellent properties, their limited availability, difficulties with shaping and donor site morbidity have made allografts a viable and increasingly preferred alternative. The main drawback of allografts is that the preparation destroys osteogenic cells and results in denaturation of osteoinductive proteins. Serum albumin is a well-known constituent of stem cell culture media and we found that lyophilizing albumin onto bone allografts markedly improves stem-cell attachment and bone healing in animal models thus replacing some of the osteoinductive potential. As a first step in the clinical introduction of albumin coated grafts, we aimed to test surgical handling and early incorporation in aseptic revision arthroplasty in humans. We selected patients who needed large structural allografts and the current operation was the last attempt at preserving a moving joint. In a series of 10 cases of hip and knee revision surgery we did not experience any drawbacks of the albumin-coated grafts during handling and implantation. Twelve months radiographic and SPECT-CT follow-up showed that the graft was well received by the host and active remodelling was observed. The lack of graft-related complications and the good 1-year results indicate that controlled trials may be initiated in more common bone grafting indications where long-term effectiveness can be evaluated.

Lineage mapping and characterization of the native progenitor population in cellular allograft.

PubMed

Neman, Josh; Duenas, Vincent; Kowolik, Claudia; Hambrecht, Amanda; Chen, Mike; Jandial, Rahul

2013-02-01

Osteocalcin; and (3) enzyme-linked immunosorbent assays (ELISA) for BMP-2, Osteocalcin, RANKL, Osteoprotegrin, and Osteocalcin. Clonal analysis of cells from cellular allograft was performed utilizing advance lentivirus lineage mapping techniques and massive parallel sequencing. Alizarin Red, Alcian Blue, and Oil red O staining assessed tripotential differentiation capacity. Serial trypsinization of allograft cellular bone matrix yielded approximately 1×105 cells per mL with viability greater than 90%. Cells expressed a panel of 84 MSC-associated genes in a pattern similar to but not identical to pure MSCs; specifically, 59 of 84 genes showed less than a 2.5-fold change in both cell types. Protein analysis showed that cellular allograft -derived cells maintained in nondifferentiation media expressed the early osteo-progenitor markers BMP-2, SMADs, and Runx2. Corresponding flow cytometry data for MSC markers revealed the presence of Stro-1 (49%), CD44 (99%), CD90 (42%), and CD146 (97%). Lineage mapping indicated that 62% of clones persisted and generated progeny through 10 passages, strongly suggesting the presence of bona fide stem cells. Passage 10 clones also exhibited tri-lineage differentiation capacity into osteogenic (Alizarin Red with H&E counterstain), chondrogenic (Alcian Blue), and adipogenic (Oil red O). Cells that did not proliferate through 10 passages presumably differentiated along an osteo-progenitor lineage. These data indicate that cellular allograft (Osteocel Plus) contains a heterogeneous population of cells with most cells demonstrating the capacity for extensive self-renewal and multipotential differentiation, which are hallmarks of stem cells. Whether stem cell-enriched allografts function comparably to autograft will require further studies, and their efficacy in facilitating arthrodesis will depend on randomized clinical studies. Copyright © 2013 Elsevier Inc. All rights reserved.

Relationship between histopathological changes in post partum renal biopsies and renal function tests of African women with early onset pre-eclampsia.

PubMed

Khedun, S M; Naicker, T; Moodley, J

2000-05-01

To improve the diagnostic accuracy of concurrent renal disease in hypertension of pregnancy, biopsy evaluation is essential. In addition, establishing underlying renal disease is important for prognosis on future pregnancies. We therefore designed a study to determine the diagnostic yield of postpartum renal biopsy and the nature and frequency of complications associated with this procedure. Also, to determine relationships, if any, between renal function tests and ultrastructural and histopathological findings. Fifty renal biopsies were performed in the immediate postpartum period in black African women with early onset pre-eclampsia. Each biopsy specimen was placed in a separate container and coded so that sampling was unknown to the electron microscopist. Each biopsy specimen was divided into three parts, and processed and stained for light, fluorescent and transmission electron microscopy using conventional techniques. Renal tissue biopsies were adequate for diagnostic purposes in all cases. There were no complications in any of the 50 patients studied. Ultrastructural examination confirmed the light microscopy findings. In addition the ultrastructural findings showed intramembranous deposits, foot process fusion and mesangial deposits. In 16 patients with normal renal function tests; the biopsies evaluation from these patients showed ultrastructural changes. In the remaining 34 patients with abnormal renal function tests of varying severity; biopsy evaluation from these patients showed both ultrastructural and histopathological changes. Renal biopsy procedure is safe, and ultrastructural and histological findings obtained from postpartum renal biopsies are more informative than the routine renal function tests.

Depletion of CD8 Memory T Cells for Induction of Tolerance of a Previously Transplanted Kidney Allograft

PubMed Central

Koyama, I.; Nadazdin, O.; Boskovic, S.; Ochiai, T.; Smith, R. N.; Sykes, M.; Sogawa, H.; Murakami, T.; Strom, T. B.; Colvin, R. B.; Sachs, D. H.; Benichou, G.; Cosimi, A. B.; Kawai, T.

2013-01-01

Heterologous immunologic memory has been considered a potent barrier to tolerance induction in primates. Induction of such tolerance for a previously transplanted organ may be more difficult, because specific memory cells can be induced and activated by a transplanted organ. In the current study, we attempted to induce tolerance to a previously transplanted kidney allograft in nonhuman primates. The conditioning regimen consisted of low dose total body irradiation, thymic irradiation, antithymocyte globulin, and anti- CD154 antibody followed by a brief course of a calcineurin inhibitor. This regimen had been shown to induce mixed chimerism and allograft tolerance when kidney transplantation (KTx) and donor bone marrow transplantation (DBMT) were simultaneously performed. However, the same regimen failed to induce mixed chimerism when delayed DBMT was performed after KTx. We found that significant levels of memory T cells remained after conditioning, despite effective depletion of naïve T cells. By adding humanized anti-CD8 monoclonal antibody (cM-T807), CD8 memory T cells were effectively depleted and these recipients successfully achieved mixed chimerism and tolerance. The current studies provide ‘proof of principle’ that the mixed chimerism approach can induce renal allograft tolerance, even late after organ transplantation if memory T-cell function is adequately controlled. PMID:17286617

Radiation sterilization of tissue allografts: A review.

PubMed

Singh, Rita; Singh, Durgeshwer; Singh, Antaryami

2016-04-28

Tissue substitutes are required in a number of clinical conditions for treatment of injured and diseased tissues. Tissues like bone, skin, amniotic membrane and soft tissues obtained from human donor can be used for repair or reconstruction of the injured part of the body. Allograft tissues from human donor provide an excellent alternative to autografts. However, major concern with the use of allografts is the risk of infectious disease transmission. Therefore, tissue allografts should be sterilized to make them safe for clinical use. Gamma radiation has several advantages and is the most suitable method for sterilization of biological tissues. This review summarizes the use of gamma irradiation technology as an effective method for sterilization of biological tissues and ensuring safety of tissue allografts.

Radiation sterilization of tissue allografts: A review

PubMed Central

Singh, Rita; Singh, Durgeshwer; Singh, Antaryami

2016-01-01

Tissue substitutes are required in a number of clinical conditions for treatment of injured and diseased tissues. Tissues like bone, skin, amniotic membrane and soft tissues obtained from human donor can be used for repair or reconstruction of the injured part of the body. Allograft tissues from human donor provide an excellent alternative to autografts. However, major concern with the use of allografts is the risk of infectious disease transmission. Therefore, tissue allografts should be sterilized to make them safe for clinical use. Gamma radiation has several advantages and is the most suitable method for sterilization of biological tissues. This review summarizes the use of gamma irradiation technology as an effective method for sterilization of biological tissues and ensuring safety of tissue allografts. PMID:27158422

Cryptic B cell response to renal transplantation.

PubMed

Lynch, R J; Silva, I A; Chen, B J; Punch, J D; Cascalho, M; Platt, J L

2013-07-01

Transplantation reliably evokes allo-specific B cell and T cell responses in mice. Yet, human recipients of kidney transplants with normal function usually exhibit little or no antibody specific for the transplant donor during the early weeks and months after transplantation. Indeed, the absence of antidonor antibodies is taken to reflect effective immunosuppressive therapy and to predict a favorable outcome. Whether the absence of donor-specific antibodies reflects absence of a B cell response to the donor, tolerance to the donor or immunity masked by binding of donor-specific antibodies to the graft is not known. To distinguish between these possibilities, we devised a novel ELISPOT, using cultured donor, recipient and third-party fibroblasts as targets. We enumerated donor-specific antibody-secreting cells in the blood of nine renal allograft recipients with normal kidney function before and after transplantation. Although none of the nine subjects had detectable donor-specific antibodies before or after transplantation, all exhibited increases in the frequency of donor-specific antibody-secreting cells eight weeks after transplantation. The responses were directed against the donor HLA-class I antigens. The increase in frequency of donor-specific antibody-secreting cells after renal transplantation indicates that B cells respond specifically to the transplant donor more often than previously thought. © 2013 The Authors. American Journal of Transplantation Published by Wiley Periodicals Inc.

Metabolomics discloses donor liver biomarkers associated with early allograft dysfunction.

PubMed

Cortes, Miriam; Pareja, Eugenia; García-Cañaveras, Juan C; Donato, M Teresa; Montero, Sandra; Mir, Jose; Castell, José V; Lahoz, Agustín

2014-09-01

Early allograft dysfunction (EAD) dramatically influences graft and patient outcome after orthotopic liver transplantation and its incidence is strongly determined by donor liver quality. Nevertheless, objective biomarkers, which can assess graft quality and anticipate organ function, are still lacking. This study aims to investigate whether there is a preoperative donor liver metabolomic biosignature associated with EAD. A comprehensive metabolomic profiling of 124 donor liver biopsies collected before transplantation was performed by mass spectrometry coupled to liquid chromatography. Donor liver grafts were classified into two groups: showing EAD and immediate graft function (IGF). Multivariate data analysis was used to search for the relationship between the metabolomic profiles present in donor livers before transplantation and their function in recipients. A set of liver graft dysfunction-associated biomarkers was identified. Key changes include significantly increased levels of bile acids, lysophospholipids, phospholipids, sphingomyelins and histidine metabolism products, all suggestive of disrupted lipid homeostasis and altered histidine pathway. Based on these biomarkers, a predictive EAD model was built and further evaluated by assessing 24 independent donor livers, yielding 91% sensitivity and 82% specificity. The model was also successfully challenged by evaluating donor livers showing primary non-function (n=4). A metabolomic biosignature that accurately differentiates donor livers, which later showed EAD or IGF, has been deciphered. The remarkable metabolomic differences between donor livers before transplant can relate to their different quality. The proposed metabolomic approach may become a clinical tool for donor liver quality assessment and for anticipating graft function before transplant. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Renal tubular ACE-mediated tubular injury is the major contributor to microalbuminuria in early diabetic nephropathy.

PubMed

Eriguchi, Masahiro; Lin, Mercury; Yamashita, Michifumi; Zhao, Tuantuan V; Khan, Zakir; Bernstein, Ellen A; Gurley, Susan B; Gonzalez-Villalobos, Romer A; Bernstein, Kenneth E; Giani, Jorge F

2018-04-01

Diabetic nephropathy is a major cause of end-stage renal disease in developed countries. While angiotensin-converting enzyme (ACE) inhibitors are used to treat diabetic nephropathy, how intrarenal ACE contributes to diabetic renal injury is uncertain. Here, two mouse models with different patterns of renal ACE expression were studied to determine the specific contribution of tubular vs. glomerular ACE to early diabetic nephropathy: it-ACE mice, which make endothelial ACE but lack ACE expression by renal tubular epithelium, and ACE 3/9 mice, which lack endothelial ACE and only express renal ACE in tubular epithelial cells. The absence of endothelial ACE normalized the glomerular filtration rate and endothelial injury in diabetic ACE 3/9 mice. However, these mice developed tubular injury and albuminuria and displayed low renal levels of megalin that were similar to those observed in diabetic wild-type mice. In diabetic it-ACE mice, despite hyperfiltration, the absence of renal tubular ACE greatly reduced tubulointerstitial injury and albuminuria and increased renal megalin expression compared with diabetic wild-type and diabetic ACE 3/9 mice. These findings demonstrate that endothelial ACE is a central regulator of the glomerular filtration rate while tubular ACE is a key player in the development of tubular injury and albuminuria. These data suggest that tubular injury, rather than hyperfiltration, is the main cause of microalbuminuria in early diabetic nephropathy.

Allograft-prosthesis composites after bone tumor resection at the proximal tibia.

PubMed

Biau, David Jean; Dumaine, Valérie; Babinet, Antoine; Tomeno, Bernard; Anract, Philippe

2007-03-01

The survival of irradiated allograft-prosthesis composites at the proximal tibia is mostly unknown. However, allograft-prosthesis composites have proved beneficial at other reconstruction sites. We presumed allograft-prosthesis composites at the proximal tibia would improve survival and facilitate reattachment of the extensor mechanism compared with that of conventional (megaprostheses) reconstructions. We retrospectively reviewed 26 patients who underwent resection of proximal tibia tumors followed by reconstruction with allo-graft-prosthesis composites. Patients received Guepar massive custom-made fully constrained prostheses. Allografts were sterilized with gamma radiation, and the stems were cemented into the allograft and host bone. The minimum followup was 6 months (median, 128 months; range, 6-195 months). Fourteen patients had one or more components removed. The median allograft-prosthesis composite survival was 102 months (95% confidence interval, 64.2-infinity). Of the 26 allografts, seven fractured, six showed signs of partial resorption, and six had infections develop. Seven allografts showed signs of fusion with the host bone. Six extensor mechanism reconstructions failed. Allograft-prosthesis composites sterilized by gamma radiation yielded poor results for proximal tibial reconstruction as complications and failures were common. We do not recommend irradiated allograft-prosthesis composites for proximal tibia reconstruction.

A case of rhabdomyolysis after kidney transplantation successfully managed with intensive continuous dialysis.

PubMed

Shahbazov, Rauf; Fox, Michael; Alejo, Jennifer L; Anjum, Malik A; Azari, Feredun; Doyle, Alden; Agarwal, Avinash; Brayman, Kenneth L

2018-04-01

Rhabdomyolysis is characterized by muscle cell death which can result in acute kidney injury from pigment nephropathy. We present a patient who developed rhabdomyolysis immediately after deceased donor kidney transplantation surgery and was managed with continuous renal replacement therapy that resulted in successful salvage of the kidney allograft. Patients who develop acute kidney failure requiring renal replacement therapy generally have a poor prognosis. It is worth noting that while continuous veno-venous hemofiltration (CVVHF) offers greater volume support and continuous clearance compared to hemodialysis (HD), recent studies have demonstrated no clinically significant improvement in clinical outcome between the two. Perhaps CVVHF is a better modality compared to HD in this setting to prevent further insult from pigment nephropathy to an allograft. A combination of early diagnosis and intensive continuous renal replacement therapy can be used for allograft salvage in a patient with rhabdomyolysis in the immediate post-kidney transplant period.

Cytokines in the regulation of allograft rejection.

PubMed

Huber, C; Irschick, E

1988-01-01

Stimulation of T lymphocytes with alloantigen leads to release of both IL-2 and IFN-gamma. IL-2 enhances clonal expansion of alloantigen-activated T cells. This permits it to overcome acquired allograft tolerance which, at the efferent limb of the cellular immune response, is caused by reduced clone size of donor-specific cytotoxic lymphocyte precursor cells. Cells exhibiting a low constitutive expression of class I MHC antigenes are refractory to lysis by cytotoxic T cells. This second type of tolerance located at the level of the allogeneic target cells can be easily broken by exogenous IFN-gamma, which increases the density of class I MHC antigens. There is suggestive evidence for enhanced endogenous production of lymphokines during rejection of cardiac allografts in mice and men. Rejection episodes are also associated with increased expression of class I and elevated frequency of class II MHC antigen-positive cells in the cardiac transplants. Whereas early immune recognition of histoincompatible grafts is primarily related to the presence of genetic barriers between donor and recipient, the further amplification of alloreactivity is driven by the release of antigen-unspecific lymphokines. Production of endogenous lymphokines can be modified by a variety of means: methylprednisone, ciclosporin and specific antibodies against lymphokines or their receptors represent effective inhibitors of this amplification mechanism which can finally lead to irreversible graft damage. It is well established in clinical experience that infectious complications subsequent to allografting may precipitate rejection or graft-vs.-host disease. Our finding of increased endogenous IFN-gamma levels during infections, in particular in those caused by cytomegalovirus, provides an explanation for this association.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of serum sCD30 in renal transplantation patients with and without acute rejection.

PubMed

Cervelli, C; Fontecchio, G; Scimitarra, M; Azzarone, R; Famulari, A; Pisani, F; Battistoni, C; Di Iulio, B; Fracassi, D; Scarnecchia, M A; Papola, F

2009-05-01

Despite new immunosuppressive approaches, acute rejection episodes (ARE) are still a major cause of early kidney dysfunction with a negative impact on long-term allograft survival. Noninvasive markers able to identify renal ARE earlier than creatinine measurement include sCD30. We sought to establish whether circulating levels of sCD30 in pretransplantation and posttransplantation periods were of clinical relevance to avoid graft damage. Quantitative detection of serum sCD30 was performed using an enzyme-linked immunosorbent assay. Our results demonstrated that the mean concentrations of sCD30 were significantly higher in the sera of renal transplant recipients with ARE (30.04 U/mL) and in uremic patients on the waiting list (37.7 U/mL) compared with healthy controls (HC; 9.44 U/mL), but not nonrejecting patients (12.01 U/mL). Statistical analysis revealed a strong association between high sCD30 levels in posttransplantation sera and ARE risk. This study suggested that sCD30 levels were a reliable predictor of ARE among deceased-donor kidney recipients.

Belatacept: a novel biologic for maintenance immunosuppression after renal transplantation.

PubMed

Martin, Spencer T; Tichy, Eric M; Gabardi, Steven

2011-04-01

In the past decade, the availability of new immunosuppressive maintenance therapies for use in solid organ transplantation has remained limited. Patients and clinicians have relied on immunosuppressive drugs that require a significant amount of therapeutic monitoring and are associated with a variety of adverse effects that affect both quality of life and allograft function. Belatacept is an investigational intravenous biologic agent for long-term use in renal transplant recipients. The costimulatory pathway (signal 2) of T-cell activation and proliferation is produced by stimulation of the T-cell surface marker, CD28, and is essential to the immune system's cellular response and ability to recognize an allograft as foreign. Belatacept is a potent antagonist of B7-1 (CD80) and B7-2 (CD86) ligands present on antigen-presenting cells that are responsible for activation of CD28. Recent phase III trials describe various dosing strategies of belatacept versus a standard cyclosporine protocol in recipients of both living- and deceased-donor renal transplants, as well as in patients receiving kidneys transplanted from extended-criteria donors. Compared with cyclosporine, belatacept has been shown to be noninferior in both patient and allograft survival rates. However, the rate of biopsy-proven acute cellular rejection occurred more frequently in the belatacept groups. Also, compared with standard calcineurin-based regimens, the risk of posttransplant lymphoproliferative disorder is increased in patients receiving belatacept, with the greatest risk in transplant recipients who are Epstein-Barr virus seronegative before transplantation. However, this investigational immunosuppressive agent may avert common adverse effects experienced with standard immunosuppressive protocols including renal dysfunction, metabolic disorders, neurotoxicities, glucose abnormalities, and cosmetic effects. More data on the long-term risks of belatacept are needed to better define its role as

Musculoskeletal allograft risks and recalls in the United States.

PubMed

Mroz, Thomas E; Joyce, Michael J; Steinmetz, Michael P; Lieberman, Isador H; Wang, Jeffrey C

2008-10-01

There have been several improvements to the US tissue banking industry over the past decade. Tissue banks had limited active government regulation until 1993, at which time the US Food and Drug Administration began regulatory oversight because of reports of disease transmission from allograft tissues. Reports in recent years of disease transmission associated with the use of allografts have further raised concerns about the safety of such implants. A retrospective review of allograft recall data was performed to analyze allograft recall by tissue type, reason, and year during the period from January 1994 to June 30, 2007. During the study period, more than 96.5% of all allograft tissues recalled were musculoskeletal. The reasons underlying recent musculoskeletal tissue recalls include insufficient or improper donor evaluation, contamination, recipient infection, and positive serologic tests. Infectious disease transmission following allograft implantation may occur if potential donors are not adequately evaluated or screened serologically during the prerecovery phase and if the implant is not sterilized before implantation.

Effects of early overnutrition on the renal response to Ang II and expression of RAAS components in rat renal tissue.

PubMed

Granado, M; Amor, S; Fernández, N; Carreño-Tarragona, G; Iglesias-Cruz, M C; Martín-Carro, B; Monge, L; García-Villalón, A L

2017-10-01

The aim of this study was to analyze the effects of early overnutrition (EON) on the expression of the renin angiotensin aldosterone system (RAAS) components in renal cortex, renal arteries and renal perivascular adipose tissue (PVAT), as well as the vascular response of renal arteries to Angiotensin II (Ang II). On birth day litters were adjusted to twelve (L12-control) or three (L3-overfed) pups per mother. Half of the animals were sacrificed at weaning (21 days old) and the other half at 5 months of age. Ang II-induced vasoconstriction of renal artery segments increased in young overfed rats and decreased in adult overfed rats. EON decreased the gene expression of angiotensinogen (Agt), Ang II receptors AT1 and AT2 and eNOS in renal arteries of young rats, while it increased the mRNA levels of AT-2 and ET-1 in adult rats. In renal PVAT EON up-regulated the gene expression of COX-2 and TNF-α in young rats and the mRNA levels of renin receptor both in young and in adult rats. On the contrary, Ang II receptors mRNA levels were downregulated at both ages. Renal cortex of overfed rats showed increased gene expression of Agt in adult rats and of AT1 in young rats. However the mRNA levels of AT1 were decreased in the renal cortex of overfed adult rats. EON is associated with alterations in the vascular response of renal arteries to Ang II and changes in the gene expression of RAAS components in renal tissue. Copyright © 2017 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Loss of Myeloid Related Protein-8/14 Exacerbates Cardiac Allograft Rejection

PubMed Central

Shimizu, Koichi; Libby, Peter; Rocha, Viviane Z.; Folco, Eduardo J.; Shubiki, Rica; Grabie, Nir; Jang, Sunyoung; Lichtman, Andrew H.; Shimizu, Ayako; Hogg, Nancy; Simon, Daniel I.; Mitchell, Richard N.; Croce, Kevin

2011-01-01

Background The calcium-binding proteins myeloid-related protein (MRP)-8 (S100A8) and MRP-14 (S100A9) form MRP-8/14 heterodimers (S100A8/A9, calprotectin) that regulate myeloid cell function and inflammatory responses, and serve as early serum markers for monitoring acute allograft rejection. Despite functioning as a pro-inflammatory mediator, the pathophysiological role of MRP-8/14 complexes in cardiovascular disease is incompletely defined. This study investigated the role of MRP-8/14 in cardiac allograft rejection using MRP-14-deficient mice (MRP14-/-) that lack MRP-8/14 complexes. Methods and Results We examined parenchymal rejection (PR) after major histocompatibility complex (MHC) class II allomismatched cardiac transplantation (bm12 donor heart and B6 recipients) in wild-type (WT) and MRP14-/- recipients. Allograft survival averaged 5.9 ± 2.9 weeks (n=10) in MRP14-/- recipients, compared to > 12 weeks (n = 15, p < 0.0001) in WT recipients. Two weeks after transplantation, allografts in MRP14-/- recipients had significantly higher PR scores (2.8 ± 0.8, n=8) than did WT recipients (0.8 ± 0.8, n=12, p<0.0001). Compared to WT recipients, allografts in MRP14-/- recipients had significantly increased T-cell and macrophage infiltration, as well as increased mRNA levels of IFN-γ and IFN-γ–associated chemokines (CXCL9, CXCL10, and CXCL11), IL-6, and IL-17, with significantly higher levels of Th17 cells. MRP14-/- recipients also had significantly more lymphocytes in the adjacent paraaortic lymph nodes than did WT recipients (cell number per lymph node: 23.7 ± 0.7 × 105 for MRP14-/- vs. 6.0 ± 0.2 × 105 for WT, p < 0.0001). The dendritic cells (DCs) of the MRP14-/- recipients of bm12 hearts expressed significantly higher levels of the co-stimulatory molecules CD80 and CD86 than did those of WT recipients 2 weeks after transplantation. Mixed leukocyte reactions using allo-EC-primed MRP14-/- DCs resulted in significantly higher antigen-presenting function than

Skin allograft and vascularized composite allograft: potential for long-term efficacy in the context of lymphatic modulation.

PubMed

Rinkinen, Jacob; Selley, Ryan; Agarwal, Shailesh; Loder, Shawn; Levi, Benjamin

2014-01-01

Tissue transplantation restores form and function in burn patients. The treatment of burn injuries is influenced by severity, location, and the percentage of total body surface area. There have been a number of different techniques developed to temporize and repair the destroyed tissue. However, in patients with large wound burden, sufficient donor site tissue may not be available for autograft harvesting. Such extensive burns necessitate other temporary and permanent options for wound coverage such as skin or vascularized composite allografts (VCA). Rejection of these tissues presents an ongoing problem which is currently managed using a host of systemic immunosuppressive medications. This article discusses the mechanism behind the innate and adaptive immune systems rejection of the allografts. By understanding these pathways, various techniques using immunomodulatory protocols have led to increased allograft survival. However, our primary interest lies in the initial recognition of the graft. We tailor this article to have a specific emphasis on lymphatic modulation as a potential adjunctive therapy. Reviews of the studies evaluating the effect of lymph node modulation on graft survival are described with future implications to allograft transplant research.

Case Series With Histopathologic and Radiographic Analyses Following Failure of Fresh Osteochondral Allografts of the Talus.

PubMed

Pomajzl, Ryan Joseph; Baker, Erin Ann; Baker, Kevin Charles; Fleischer, Mackenzie Marie; Salisbury, Meagan R; Phillips, Dylan M; Fortin, Paul Thomas

2016-09-01

Fresh osteochondral allografting of the talus is one treatment option for large chondral defects. Following positive early term results, failure rates of up to 35% have been reported. A retrieval study was performed to characterize failed talar allografts. Failed fresh osteochondral allografts of the talus were retrieved on revision. Cases of deep infection were excluded. After tissue fixation, samples were decalcified, embedded, and stained with Safranin-O/Fast Green, osteocalcin, tumor necrosis factor alpha (TNF-α), CD4, CD8, and CD68. Slides were graded according to the modified Mankin scoring system or severity scale. Medical record review was performed. Eight allografts (7 patients) were retrieved from patients, following an average term of implantation of 31 months (range, 12-58). There were 3 types of allografts in this series (hemidome, n=5; segmental, n=2; bipolar, n=1). Reasons for transplantation were post-traumatic arthritis or osteonecrosis; reasons for revision were graft failure/collapse, nonunion, progressive arthritis, and/or pain. Prior to revision, all grafts exhibited collapse and subchondral lucencies. At the graft host interface, Safranin-O staining demonstrated substantial loss of sulfated glycosaminoglycans, Osteocalcin immunostaning was nearly absent, CD68 (indicating osteoclast activity) was predominantly exhibited, and CD4+ helper T cells as well as CD8+ cytotoxic T cells and NK cells-cell types commonly implicated in allogeneic organ transplant rejection-were found in high concentrations. TNF-α was present throughout the graft. A histopathologic analysis of 8 retrieved, failed talar allografts was performed. Graft failure appeared to be primarily biologic, with an extensive loss of viable cartilaginous and osseous tissue at the graft-host interface. This study provides the first evidence of a potential CD4+ and CD8+ lymphocyte-mediated failure mechanism in fresh osteochondral allografts that were revised following collapse. Level IV

Dengue virus infection in renal allograft recipients: a case series during 2010 outbreak.

PubMed

Prasad, N; Bhadauria, D; Sharma, R K; Gupta, A; Kaul, A; Srivastava, A

2012-04-01

Dengue virus infection is an emerging global threat caused by Arbovirus, a virus from Flaviridiae family, which is transmitted by mosquitoes, Aedes aegypti and Aedes albopictus. Renal transplant recipients who live in the endemic zones of dengue infection or who travel to an endemic zone could be at risk of this infection. Despite multiple epidemics and a high case fatality rate in the Southeast Asian region, only a few cases of dengue infection in renal transplant recipients have been reported. Here, we report a case series of 8 dengue viral infection in renal transplant recipients. Of the 8 patients, 3 developed dengue hemorrhagic shock syndrome and died. © 2011 John Wiley & Sons A/S.

Early onset primary pulmonary cryptococcosis in a renal transplant patient.

PubMed

Tarai, B; Kher, V; Kotru, P; Sabhikhi, A; Barman, P; Rattan, A

2010-01-01

We report a case of primary pulmonary cryptococcosis in a post-renal transplant patient. A 65-year-old male renal transplant patient was admitted to the hospital with a low grade fever of 1 month, radiologically mimicking tuberculosis (TB). Broncho-alveolar fluid (BAL) shows capsulated yeast, and Cryptococcus neoformans was grown on culture supported by cytology and histopathological examination. Cryptococcal antigen was positive (32-fold) in serum and was negative in cerebrospinal fluid (CSF). The patient was given amphotericin B and 5-flucytosine and clinical improvement was seen on a weekly follow up. The serum cryptococcal antigen test might contribute to the early detection and treatment of pulmonary cryptococcosis. The results of antifungal susceptibility were aid in selecting the drug of choice for treatment.

Renal impairment and heart failure with preserved ejection fraction early post-myocardial infarction

PubMed Central

Jorapur, Vinod; Lamas, Gervasio A; Sadowski, Zygmunt P; Reynolds, Harmony R; Carvalho, Antonio C; Buller, Christopher E; Rankin, James M; Renkin, Jean; Steg, Philippe Gabriel; White, Harvey D; Vozzi, Carlos; Balcells, Eduardo; Ragosta, Michael; Martin, C Edwin; Srinivas, Vankeepuram S; Wharton III, William W; Abramsky, Staci; Mon, Ana C; Kronsberg, Shari S; Hochman, Judith S

2010-01-01

AIM: To study if impaired renal function is associated with increased risk of peri-infarct heart failure (HF) in patients with preserved ejection fraction (EF). METHODS: Patients with occluded infarct-related arteries (IRAs) between 1 to 28 d after myocardial infarction (MI) were grouped into chronic kidney disease (CKD) stages based on estimated glomerular filtration rate (eGFR). Rates of early post-MI HF were compared among eGFR groups. Logistic regression was used to explore independent predictors of HF. RESULTS: Reduced eGFR was present in 71.1% of 2160 patients, with significant renal impairment (eGFR < 60 mL/min every 1.73 m2) in 14.8%. The prevalence of HF was higher with worsening renal function: 15.5%, 17.8% and 29.4% in patients with CKD stages 1, 2 and 3 or 4, respectively (P < 0.0001), despite a small absolute difference in mean EF across eGFR groups: 48.2 ± 10.0, 47.9 ± 11.3 and 46.2 ± 12.1, respectively (P = 0.02). The prevalence of HF was again higher with worsening renal function among patients with preserved EF: 10.1%, 13.6% and 23.6% (P < 0.0001), but this relationship was not significant among patients with depressed EF: 27.1%, 26.2% and 37.9% (P = 0.071). Moreover, eGFR was an independent correlate of HF in patients with preserved EF (P = 0.003) but not in patients with depressed EF (P = 0.181). CONCLUSION: A significant proportion of post-MI patients with occluded IRAs have impaired renal function. Impaired renal function was associated with an increased rate of early post-MI HF, the association being strongest in patients with preserved EF. These findings have implications for management of peri-infarct HF. PMID:20885993

The safety of bone allografts used in dentistry: a review.

PubMed

Holtzclaw, Dan; Toscano, Nicholas; Eisenlohr, Lisa; Callan, Don

2008-09-01

Recent media reports concerning "stolen body parts" have shaken the public's trust in the safety of and the use of ethical practices involving human allografts. The authors provide a comprehensive review of the safety aspects of human bone allografts. The authors reviewed U.S. government regulations, industry standards, independent industry association guidelines, company guidelines and scientific articles related to the use of human bone allografts in the practice of dentistry published in the English language. The use of human bone allografts in the practice of dentistry involves the steps of procurement, processing, use and tracking. Rigorous donor screening and aseptic proprietary processing programs have rendered the use of human bone allografts safe and effective as a treatment option. When purchasing human bone allografts for the practice of dentistry, one should choose products accredited by the American Association of Tissue Banks for meeting uniformly high safety and quality control measures. Knowledge of human bone allograft procurement, processing, use and tracking procedures may allow dental clinicians to better educate their patients and address concerns about this valuable treatment option.

Renal excretion of ingested gastrografin: clinical relevance in early postoperative treatment of patients who have undergone gastric surgery.

PubMed

Sohn, Kyung-Myung; Lee, Sung-Yong; Kwon, Oh-Han

2002-05-01

We performed this study to evaluate the clinical relevance of renal excretion of ingested Gastrografin (methylglucamine diatrizoate) revealed on CT in the early treatment of patients who have undergone gastric surgery. Unenhanced abdominal CT was performed before and then 1 hr to 1 hr 30 min after Gastrografin ingestion in 30 patients 7 days after gastric surgery and in 19 healthy adults who served as the control group. CT scans were reviewed for the opacification of the renal collecting system or urinary bladder after Gastrografin ingestion, a finding that represents renal excretion of the ingested contrast medium. In the control group, four (21 %) of the 19 healthy adults showed renal excretion of ingested Gastrografin visualized as opacification of the urinary tract on CT scans obtained 1 hr to 1 hr 30 min after ingestion of the substance. Renal excretion of the ingested Gastrografin was seen in 19 (63%) of the 30 patients, a significantly larger percentage than in the control group (z score, p < 0.01). No patient showed either radiologic or clinical evidence of leakage from the anastomotic site. Renal excretion of ingested Gastrografin is frequently visualized on CT in patients without anastomotic leakage during the early postoperative period after gastric surgery, and this phenomenon is not rare, even in healthy adults. Therefore, renal excretion seen on CT should not be regarded as a sign of anastomotic leakage in early postoperative patients.

Multiple Osteochondral Allograft Transplantation with Concomitant Tibial Tubercle Osteotomy for Multifocal Chondral Disease of the Knee.

PubMed

Cotter, Eric J; Waterman, Brian R; Kelly, Mick P; Wang, Kevin C; Frank, Rachel M; Cole, Brian J

2017-08-01

Symptomatic patellofemoral chondral lesions are a challenging clinical entity, as these defects may result from persistent lateral patellar maltracking or repetitive microtrauma. Anteromedializing tibial tubercle osteotomy has been shown to be an effective strategy for primary and adjunctive treatment of focal or diffuse patellofemoral disease to improve the biomechanical loading environment. Similarly, osteochondral allograft transplantation has proven efficacy in physiologically young, high-demand patients with condylar or patellofemoral lesions, particularly without early arthritic progression. The authors present the surgical management of a young athlete with symptomatic tricompartmental focal chondral defects with fresh osteochondral allograft transplantation and anteromedializing tibial tubercle osteotomy.

Unique molecular changes in kidney allografts after simultaneous liver-kidney compared with solitary kidney transplantation.

PubMed

Taner, Timucin; Park, Walter D; Stegall, Mark D

2017-05-01

Kidney allografts transplanted simultaneously with liver allografts from the same donor are known to be immunologically privileged. This is especially evident in recipients with high levels of donor-specific anti-HLA antibodies. Here we investigated the mechanisms of liver's protective impact using gene expression in the kidney allograft. Select solitary kidney transplant or simultaneous liver-kidney transplant recipients were retrospectively reviewed and separated into four groups: 16 cross-match negative kidney transplants, 15 cross-match positive kidney transplants, 12 cross-match negative simultaneous liver-kidney transplants, and nine cross-match-positive simultaneous liver-kidney transplants. Surveillance biopsies of cross-match-positive kidney transplants had increased expression of genes associated with donor-specific antigens, inflammation, and endothelial cell activation compared to cross-match-negative kidney transplants. These changes were not found in cross-match-positive simultaneous liver-kidney transplant biopsies when compared to cross-match-negative simultaneous liver-kidney transplants. In addition, simultaneously transplanting a liver markedly increased renal expression of genes associated with tissue integrity/metabolism, regardless of the cross-match status. While the expression of inflammatory gene sets in cross-match-positive simultaneous liver-kidney transplants was not completely reduced to the level of cross-match-negative kidney transplants, the downstream effects of donor-specific anti-HLA antibodies were blocked. Thus, simultaneous liver-kidney transplants can have a profound impact on the kidney allograft, not only by decreasing inflammation and avoiding endothelial cell activation in cross-match-positive recipients, but also by increasing processes associated with tissue integrity/metabolism by unknown mechanisms. Copyright © 2017 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Primary Cytomegalovirus Infection Causing Guillain-Barré Syndrome in a Living Renal Allograft Recipient

PubMed Central

Israel, Ezra

2017-01-01

Guillain-Barré Syndrome (GBS) is a common acute autoimmune polyneuropathy in adults. There have been few reported cases of Guillain-Barré Syndrome associated with active cytomegalovirus (CMV) infection in renal transplant recipients. Here we present a case of active CMV viremia inducing Guillain-Barré Syndrome in a renal transplant recipient. We discuss the treatment regimen utilized. Furthermore, we performed a review of the literature and discuss the cases of CMV induced GBS in renal transplant recipients. PMID:29348962

Determination of residual dimethylsulfoxide in cryopreserved cardiovascular allografts.

PubMed

Díaz Rodríguez, R; Van Hoeck, B; De Gelas, S; Blancke, F; Ngakam, R; Bogaerts, K; Jashari, R

2017-06-01

Dimethylsulfoxide (DMSO) is a solvent which protects the structure of allografts during the cryopreservation and thawing process. However, several toxic effects of DMSO in patients after transplantation of cryopreserved allografts have been described. The aim of this study is to determine the residual DMSO in the cardiovascular allografts after thawing and preparation of cryopreserved allografts for clinical application following guidelines of the European Pharmacopoeia for DMSO detection. Four types of EHB allografts (aortic valve-AV, pulmonary valve-PV, descending thoracic aorta-DA, and femoral artery-FA) are cryopreserved using as cryoprotecting solution a 10% of DMSO in medium 199. Sampling is carried out after thawing, after DMSO dilution and after delay of 30 min from final dilution (estimated delay until allograft implantation). After progressive thawing in sterile water bath at 37-42 °C (duration of about 20 min), DMSO dilution is carried out by adding consecutively 33, 66 and 200 mL of saline. Finally, tissues are transferred into 200 mL of a new physiologic solution. Allograft samples are analysed for determination of the residual DSMO concentration using a validated Gas Chromatography analysis. Femoral arteries showed the most important DMSO reduction after the estimated delay: 92.97% of decrease in the cryoprotectant final amount while a final reduction of 72.30, 72.04 and 76.29% in DMSO content for AV, PV and DA, was found, respectively. The residual DMSO in the allografts at the moment of implantation represents a final dose of 1.95, 1.06, 1.74 and 0.26 mg kg -1 in AV, PV, DA and FA, respectively, for men, and 2.43, 1.33, 2.17 and 0.33 mg kg -1 for same tissues for women (average weight of 75 kg in men, and 60 kg in women). These results are seriously below the maximum recommended dose of 1 g DMSO kg -1 (Regan et al. in Transfusion 50:2670-2675, 2010) of weight of the patient guaranteeing the safety and quality of allografts.

Serum creatinine detection by a conducting-polymer-based electrochemical sensor to identify allograft dysfunction.

PubMed

Wei, Fang; Cheng, Scott; Korin, Yael; Reed, Elaine F; Gjertson, David; Ho, Chih-ming; Gritsch, H Albin; Veale, Jeffrey

2012-09-18

Kidney transplant recipients who have abnormally high creatinine levels in their blood often have allograft dysfunction secondary to rejection. Creatinine has become the preferred marker for renal dysfunction and is readily available in hospital clinical settings. We developed a rapid and accurate polymer-based electrochemical point-of-care (POC) assay for creatinine detection from whole blood to identify allograft dysfunction. The creatinine concentrations of 19 blood samples from transplant recipients were measured directly from clinical serum samples by the conducting polymer-based electrochemical (EC) sensor arrays. These measurements were compared to the traditional clinical laboratory assay. The time required for detection was <5 min from sample loading. Sensitivity of the detection was found to be 0.46 mg/dL of creatinine with only 40 μL sample in the creatinine concentration range of 0 mg/dL to 11.33 mg/dL. Signal levels that were detected electrochemically correlated closely with the creatinine blood concentration detected by the UCLA Ronald Reagan Medical Center traditional clinical laboratory assay (correlation coefficient = 0.94). This work is encouraging for the development of a rapid and accurate POC device for measuring creatinine levels in whole blood.

Fresh-frozen Complete Extensor Mechanism Allograft versus Autograft Reconstruction in Rabbits

PubMed Central

Chen, Guanyin; Zhang, Hongtao; Ma, Qiong; Zhao, Jian; Zhang, Yinglong; Fan, Qingyu; Ma, Baoan

2016-01-01

Different clinical results have been reported in the repair of extensor mechanism disruption using fresh-frozen complete extensor mechanism (CEM) allograft, creating a need for a better understanding of fresh-frozen CME allograft reconstruction. Here, we perform histological and biomechanical analyses of fresh-frozen CEM allograft or autograft reconstruction in an in vivo rabbit model. Our histological results show complete incorporation of the quadriceps tendon into the host tissues, patellar survival and total integration of the allograft tibia, with relatively fewer osteocytes, into the host tibia. Vascularity and cellularity are reduced and delayed in the allograft but exhibit similar distributions to those in the autograft. The infrapatellar fat pad provides the main blood supply, and the lowest cellularity is observed in the patellar tendon close to the tibia in both the allograft and autograft. The biomechanical properties of the junction of quadriceps tendon and host tissues and those of the allograft patellar tendon are completely and considerably restored, respectively. Therefore, fresh-frozen CEM allograft reconstruction is viable, but the distal patellar tendon and the tibial block may be the weak links of the reconstruction. These findings provide new insight into the use of allograft in repairing disruption of the extensor mechanism. PMID:26911538

Fresh-frozen Complete Extensor Mechanism Allograft versus Autograft Reconstruction in Rabbits.

PubMed

Chen, Guanyin; Zhang, Hongtao; Ma, Qiong; Zhao, Jian; Zhang, Yinglong; Fan, Qingyu; Ma, Baoan

2016-02-25

Different clinical results have been reported in the repair of extensor mechanism disruption using fresh-frozen complete extensor mechanism (CEM) allograft, creating a need for a better understanding of fresh-frozen CME allograft reconstruction. Here, we perform histological and biomechanical analyses of fresh-frozen CEM allograft or autograft reconstruction in an in vivo rabbit model. Our histological results show complete incorporation of the quadriceps tendon into the host tissues, patellar survival and total integration of the allograft tibia, with relatively fewer osteocytes, into the host tibia. Vascularity and cellularity are reduced and delayed in the allograft but exhibit similar distributions to those in the autograft. The infrapatellar fat pad provides the main blood supply, and the lowest cellularity is observed in the patellar tendon close to the tibia in both the allograft and autograft. The biomechanical properties of the junction of quadriceps tendon and host tissues and those of the allograft patellar tendon are completely and considerably restored, respectively. Therefore, fresh-frozen CEM allograft reconstruction is viable, but the distal patellar tendon and the tibial block may be the weak links of the reconstruction. These findings provide new insight into the use of allograft in repairing disruption of the extensor mechanism.

Micro-organisms isolated from cadaveric samples of allograft musculoskeletal tissue.

PubMed

Varettas, Kerry

2013-12-01

Allograft musculoskeletal tissue is commonly used in orthopaedic surgical procedures. Cadaveric donors of musculoskeletal tissue supply multiple allografts such as tendons, ligaments and bone. The microbiology laboratory of the South Eastern Area Laboratory Services (SEALS, Australia) has cultured cadaveric allograft musculoskeletal tissue samples for bacterial and fungal isolates since 2006. This study will retrospectively review the micro-organisms isolated over a 6-year period, 2006-2011. Swab and tissue samples were received for bioburden testing and were inoculated onto agar and/or broth culture media. Growth was obtained from 25.1 % of cadaveric allograft musculoskeletal tissue samples received. The predominant organisms isolated were coagulase-negative staphylococci and coliforms, with the heaviest bioburden recovered from the hemipelvis. The rate of bacterial and fungal isolates from cadaveric allograft musculoskeletal tissue samples is higher than that from living donors. The type of organism isolated may influence the suitability of the allograft for transplant.

Bone allograft banking in South Australia.

PubMed

Campbell, D G; Oakeshott, R D

1995-12-01

The South Australian Bone Bank had expanded to meet an increased demand for allograft bone. During a 5 year period from 1988 to 1992, 2361 allografts were harvested from 2146 living donors and 30 cadaveric donors. The allografts were screened by contemporary banking techniques which include a social history, donor serum tests for HIV-1, HIV-2, hepatitis B and C, syphilis serology, graft microbiology and histology. Grafts were irradiated with 25 kGy. The majority of grafts were used for arthroplasty or spinal surgery and 99 were used for tumour reconstruction. Of the donated grafts 336 were rejected by the bank. One donor was HIV-positive and two had false positive screens. There were seven donors with positive serology for hepatitis B, eight for hepatitis C and nine for syphilis. Twenty-seven grafts had positive cultures. Bone transplantation is the most frequent non-haematogenous allograft in South Australia and probably nationally. The low incidence of infectious viral disease in the donor population combined with an aggressive discard policy has ensured relative safety of the grafts. The frequency of graft rejection was similar to other bone banks but the incidence of HIV was lower.

Anterior cruciate ligament allograft transplantation in dogs.

PubMed

Vasseur, P B; Stevenson, S; Gregory, C R; Rodrigo, J J; Pauli, S; Heitter, D; Sharkey, N

1991-08-01

The biomechanical and clinical performance of bone-ligament-bone anterior cruciate ligament (ACL) allografts was studied in eight dogs. Allografts were collected from skeletally mature, healthy dogs using aseptic technique, and stored at -70 degrees for three to five weeks before implantation. The allografts were size-matched to the recipient dogs using ACL length and then rigidly fixed in position with interference screws and Kirschner wires. Three dogs regained a normal gait, and their grafts sustained breaking loads that were 25%, 41%, and 59% of controls. Partial or complete graft failure occurred in the other five dogs at some point in the study. Four had intraligamentous rupture and one had an avulsion fracture of the femoral attachment site. Joint-fluid cytology was normal in all eight dogs. Histologic examination showed persistent lymphoplasmacytic infiltrate. Eventually the allograft cores were incorporated in the host bed. Hyperplasia and fibrosis of the synovial membrane were diffuse and persisted as focal accumulations of mononuclear inflammatory cells.

TECHNIQUES FOR COMBINED PROCUREMENT OF HEARTS AND KIDNEYS WITH SATISFACTORY EARLY FUNCTION OF RENAL ALLOGRAFTS

PubMed Central

Shaw, Byers W.; Rosenthal, J. Thomas; Griffith, Bartley F.; Haresty, Robert L.; Broznik, Brian; Hakala, Thomas; Bahnson, Henry T.; Starzl, Thomas E.

2009-01-01

SUMMARY Methods for combination of donor nephrectomy with donor cardiectomy are outlined. The satisfactory early function of 29 of 34 transplanted kidneys harvested with these techniques supports their wider application and should encourage their wider acceptance. PMID:6351307

Tendon allograft sterilized by peracetic acid/ethanol combined with gamma irradiation.

PubMed

Zhou, Mo; Zhang, Naili; Liu, Xiaoming; Li, Youchen; Zhang, Yumin; Wang, Xusheng; Li, Baoming; Li, Baoxing

2014-07-01

Research and clinical applications have demonstrated that the effects of tendon allografts are comparable to those of autografts when reconstructing injured tendons or ligaments, but allograft safety remains problematic. Sterilisation could eliminate or decrease the possibility of disease transmission, but current methods seldom achieve satisfactory sterilisation without affecting the mechanical properties of the tendon. Peracetic acid-ethanol in combination with low-dose gamma irradiation (PE-R) would inactivate potential deleterious microorganisms without affecting mechanical and biocompatible properties of tendon allograft. Controlled laboratory design. HIV, PPV, PRV and BVDV inactivation was evaluated. After verifying viral inactivation, the treated tendon allografts were characterised by optical microscopy, scanning electron microscopy and tensile testing, and the cytocompatibility was assessed with an MTT assay and by subcutaneous implantation. Effective and efficient inactivation of HIV, PPV, PRV and BVDV was observed. Histological structure and ultrastructure were unchanged in the treated tendon allograft, which also exhibited comparable biomechanical properties and good biocompatibility. The preliminary results confirmed our hypothesis and demonstrated that the PE-R tendon allograft has significant potential as an alternative to ligament/tendon reconstruction. Tendon allografts have been extensively used in ligament reconstruction and tendon repair. However, current sterilisation methods have various shortcomings, so PE-R has been proposed. This study suggests that PE-R tendon allograft has great potential as an alternative for ligament/tendon reconstruction. Sterilisation has been a great concern for tendon allografts. However, most sterilisation methods cannot inactivate viruses and bacteria without impairing the mechanical properties of the tendon allograft. Peracetic acid/ethanol with gamma irradiation can effectively inactivate viruses and bacteria

Cytomegalovirus cultured from different major leukocyte subpopulations: association with clinical features in CMV immunoglobulin G-positive renal allograft recipients.

PubMed

Schäfer, P; Tenschert, W; Cremaschi, L; Schröter, M; Gutensohn, K; Laufs, R

2000-08-01

Cytomegalovirus (CMV) cultured from peripheral blood mononuclear cells (PBMCs) was shown to be associated more closely with clinical manifestations than infectious CMV in polymorphonuclear leukocytes (PMNLs) of renal allograft recipients with secondary CMV infection. Shell vial culture was carried out with ficoll-purified PBMCs and PMNLs of 71 CMV IgG-positive patients after kidney transplantation. Thirty-six patients experienced active CMV infections. Of these, 17 developed clinical symptoms. The diagnostic value of PMNLs and PBMCs viremia was determined in comparison to pp65 antigenemia, leukoDNAemia, plasma DNAemia, and detection of cytomegalic endothelial cells. In both PMNLs and PBMCs (with or without detectable endothelial cells), frequencies and levels of viremia were significantly higher among symptomatic patients. Regarding the occurrence of clinical CMV manifestations, the sensitivity of culture from PMNLs and from PBMCs fractions was 100%. Viremia in PBMCs, however, was far more specific (94%) than in PMNLs (74%). Cutoff values established previously for pp65 antigenemia and leukoDNAemia, standard markers in the laboratory, had similar specificity (96% each) to PBMCs viremia, but were less sensitive (88% each). Plasma DNA-emia was both less sensitive (82%) and less specific (69%) than PBMCs viremia. Detection of endothelemia showed maximal specificity (100%), but inferior sensitivity (47%). All patients had PBMCs viremia before the onset of symptoms. In conclusion, infectious CMV present in PBMCs may prove to be a determinant of clinical CMV manifestations in seropositive immunocompromised individuals. Factors involved in PBMCs tropism may help to understand the pathogenetic mechanisms of CMV dissemination in this group of patients. Copyright 2000 Wiley-Liss, Inc.

Is Euro-Collins better than ringer lactate in live related donor renal transplantation?

PubMed

Prasad, G Siva; Ninan, Chacko N; Devasia, Antony; Gnanaraj, Lionel; Kekre, Nitin S; Gopalakrishnan, Ganesh

2007-07-01

Euro-Collins and University of Wisconsin are preferred solutions in cadaveric renal transplantation. There are no guidelines regarding the perfusion fluids in live donor renal transplantation. We studied whether Euro-Collins was better than Ringer lactate in terms of protecting allograft function. A double-blind permuted randomized trial comparing Euro-Collins and Ringer lactate was performed on 100 patients undergoing live related donor renal transplantation. Outcome variable was serum creatinine. Age, sex, donor nephrectomy and ischemia times, kidney temperature, time of first appearance of urine was not significantly different in both the groups. Fall in serum creatinine was significantly more in Euro-Collins than Ringer lactate in the first postoperative week (P-<0.05). The time to reach nadir creatinine was 4.97 days in Euro-Collins and 7.75 days in the Ringer lactate group (P-0.088). Serum creatinine was significantly lower in the Euro-Collins group till six months, thereafter it equalized with Ringer lactate. When individual parameters were analyzed for time to nadir creatinine, only the cold ischemia time of > 80 min was found to be significant (P-0.024). Twelve kidneys in Euro-Collins and 17 in the Ringer lactate group had cold ischemia times of >/=80 min and time to nadir creatinine was 4.33 +/-3.74 and 12.76+/- 12.68 days (P-0.035). Renal function normalized rapidly when Euro-Collins was used. Cold ischemia time of >/= 80 min was the most important factor affecting the graft function and perfusing with Euro-Collins could protect the allograft.

Combined use of rapamycin and leflunomide in prevention of acute cardiac allografts rejection in rats.

PubMed

Sun, Yan; Chen, Xi; Zhao, Jiabin; Zou, Xiaoming; Li, Gang; Li, Xiaolin; Shen, Bin; Sun, Shibo

2012-08-01

This study aimed to evaluate the role of combined use of rapamycin and leflunomide(Lef) on the prevention of acute allograft rejection in rats. After cardiac transplantations, rats were randomly divided into untreated group, rapamycin group, Lef group and rapamycin+Lef group. The drugs were given by gavage from day 0 to day 9 after transplantations. Graft survival time was observed. Some grafts were harvested for histopathological investigation on day 10 after transplantations. The levels of CD(4)(+) and CD(8)(+) T lymphocytes and the concentrations of interleukin 2(IL-2) and interferon (IFN)γ in peripheral blood were examined on day 10 after transplantations. At the same time, the body weight, the hepatic function, renal function and the haemoglobin of the recipients were also examined. The graft survival time of untreated group was 7.14 ± 1.07 days. Rapamycin group was 11.14 ± 1.35 days. Lef group was 11.29 ± 1.80 days. While in rapamycin+Lef group, the graft survival time was prolonged to 13.86 ± 1.57 days(P<0.05). Histological changes of the allografts in rapamycin+Lef group were much milder than either of the two single drug groups. The absolute number and the percentage of CD(4)(+) T lymphocytes in peripheral blood in rapamycin+Lef group were lower than those of rapamycin or Lef group on day 10 after transplantations(P<0.05), while the percentage of CD(8)(+) T lymphocytes in rapamycin+Lef group was higher than that of rapamycin or Lef group(P<0.05). The absolute number of CD(8)(+) T lymphocytes was not significantly different among rapamycin group, Lef group and rapamycin+Lef group. The levels of IL-2 and IFN-γ in rapamycin+Lef group were significantly lower than that of rapamycin group or Lef group(P<0.05). The body weight, the hepatic function, renal function and the haemoglobin were not significantly different among rapamycin group, Lef group and rapamycin+Lef group (P>0.05). Combined use of rapamycin and Lef had better effect on the prevention of

Cryopreserved Cadaveric Arterial Allograft for Arterial Reconstruction in Patients with Prosthetic Infection.

PubMed

Lejay, Anne; Delay, Charline; Girsowicz, Elie; Chenesseau, Bettina; Bonnin, Emilie; Ghariani, Mohamed-Zied; Thaveau, Fabien; Georg, Yannick; Geny, Bernard; Chakfe, Nabil

2017-11-01

The aim of this study was to report outcomes of cryopreserved arterial allografts used as a vascular substitute in the setting of prosthetic material infection. A retrospective analysis of prospectively collected data was conducted including all consecutive interventions performed with cryopreserved arterial allografts used for vascular reconstruction in the setting of prosthetic material infection between January 2005 and December 2014. Five year outcomes included allograft related re-interventions, survival, primary patency, and limb salvage rates. Fifty-three procedures were performed using cryopreserved allografts for vascular prosthetic infection: 25 procedures (47%) were performed at aorto-iliac level (Group 1) and 28 procedures (53%) at peripheral level (Group 2). The mean follow-up was 52 months. Five year allograft related re-intervention was 55% in Group 1 (6 allograft ruptures and 5 allograft aneurysm degenerations) and 33% in Group 2 (2 allograft ruptures and 7 allograft aneurysm degenerations). Five year survival was 40% and 68%, primary patency was 89% and 59% and limb salvage was 100% and 89% for Group 1 and 2 respectively. Use of cryopreserved arterial allografts provides acceptable results but is tempered by suboptimal 5 year outcomes with high re-intervention rates. Copyright © 2017 European Society for Vascular Surgery. Published by Elsevier Ltd. All rights reserved.

Early ultrasonographic evaluation of tumor thrombus level during sunitinib therapy for renal cell carcinoma.

PubMed

Sano, Futoshi; Fusayasu, Syusei; Otake, Shinji; Yamanaka, Hiroyuki; Tatenuma, Tomoyuki; Sakata, Ryoko; Makiyama, Kazuhide; Nakaigawa, Noboru; Yao, Masahiro; Kubota, Yoshinobu

2013-10-01

A 72-year-old man presenting with a 14-cm left renal mass, an inferior vena cava (IVC) tumor thrombus, and pulmonary metastases underwent renal mass biopsy that revealed clear cell renal cell carcinoma. Because of metastases and the extent of the tumor thrombus, sunitinib was administered, which resulted in a marked reduction in the tumor thrombus (from level III to level II after 11 weeks of treatment). Ultrasonography, preceding computed tomography, showed a slight shrinkage of the tumor thrombus level in the first 2 weeks. Therefore, ultrasound may be advantageous to monitor the IVC tumor thrombus level during the early phase of targeted therapy.

Host-Pathogen Interactions and Chronic Lung Allograft Dysfunction.

PubMed

Belperio, John; Palmer, Scott M; Weigt, S Sam

2017-09-01

Lung transplantation is now considered to be a therapeutic option for patients with advanced-stage lung diseases. Unfortunately, due to post-transplant complications, both infectious and noninfectious, it is only a treatment and not a cure. Infections (e.g., bacterial, viral, and fungal) in the immunosuppressed lung transplant recipient are a common cause of mortality post transplant. Infections have more recently been explored as factors contributing to the risk of chronic lung allograft dysfunction (CLAD). Each major class of infection-(1) bacterial (Staphylococcus aureus and Pseudomonas aeruginosa); (2) viral (cytomegalovirus and community-acquired respiratory viruses); and (3) fungal (Aspergillus)-has been associated with the development of CLAD. Mechanistically, the microbe seems to be interacting with the allograft cells, stimulating the induction of chemokines, which recruit recipient leukocytes to the graft. The recipient leukocyte interactions with the microbe further up-regulate chemokines, amplifying the influx of allograft-infiltrating mononuclear cells. These events can promote recipient leukocytes to interact with the allograft, triggering an alloresponse and graft dysfunction. Overall, interactions between the microbe-allograft-host immune system alters chemokine production, which, in part, plays a role in the pathobiology of CLAD and mortality due to CLAD.

Primary Cardiac Allograft Dysfunction-Validation of a Clinical Definition.

PubMed

Dronavalli, Vamsidhar B; Rogers, Chris A; Banner, Nicholas R

2015-09-01

Heart transplantation is an established treatment for advanced heart failure. Primary allograft dysfunction (PGD) is reported in up to 40% of transplants and is associated with a poor outcome. As part of Heart Evaluation and Retrieval for Transplantation study, an investigation of the assessment of donor hearts for transplantation, we proposed a clinical definition for cardiac PGD comprising severely impaired systolic function affecting one or both ventricles accompanied by hypotension, low cardiac output, and high filling pressures occurring in the first 72 hours (in the absence of hyper acute rejection and technical surgical factors, such as cardiac tamponade). Here, we examine the prospective application of this definition to 290 heart transplants. We compared the clinical outcome of PGD and non-PGD cases. Ninety-four of 290 transplants developed PGD (32.4%). Inotrope use (score) was higher in the PGD group at 24, 48, and 72 hours after transplantation (P < 0.01). In the PGD group, there was a greater requirement for, intra-aortic balloon pump (50% vs 15%, P < 0.01), mechanical support (27% vs 0%, P < 0.01), and renal replacement therapy (61% vs 26%, P < 0.01). Intensive care stay was longer for recipients with PGD (median 14 vs 5 days, P < 0.01) and early mortality was higher (37% vs 4% at 30 days, 42% vs 8% at 1 year, P < 0.01). In conclusion, our definition of PGD could be applied in a national multicenter study, and the cases it defined had more frequent complications and higher mortality.

Pancreas allograft biopsies in the management of pancreas transplant recipients: histopathologic review and clinical correlations.

PubMed

Gaber, Lillian W

2007-08-01

Pancreas transplantation has become a therapeutic option for patients with type 1 diabetes mellitus who are in end-stage renal failure. It also is indicated for a subset of nonuremic, insulin-dependent diabetics who experience extreme difficulties in maintaining proper glucose homeostasis by insulin therapy that compromises their productivity and safety. To provide a review of the literature and expert experiences for understanding the histologic findings in pancreas transplantation. The published literature between 1990 and 2005 was reviewed for this report. Additionally, personal files of the author were used, along with biopsy slides that were used for figures. Pancreas transplantation reestablishes the physiologic state of insulin secretion, and pancreas transplant recipients are able to maintain a state of long-term euglycemia and are less likely to be exposed to hyperglycemia and its systemic complications. Key to the success of transplantation is the scrupulous management and close monitoring of the pancreas transplant recipients. To that end, histologic evaluation of pancreas allografts assumed a pivotal role in management of pancreas allograft dysfunction episodes, and in some centers surveillance biopsies are used to monitor immunologically high-risk situations.

APOL1 Genotype and Kidney Transplantation Outcomes From Deceased African American Donors.

PubMed

Freedman, Barry I; Pastan, Stephen O; Israni, Ajay K; Schladt, David; Julian, Bruce A; Gautreaux, Michael D; Hauptfeld, Vera; Bray, Robert A; Gebel, Howard M; Kirk, Allan D; Gaston, Robert S; Rogers, Jeffrey; Farney, Alan C; Orlando, Giuseppe; Stratta, Robert J; Mohan, Sumit; Ma, Lijun; Langefeld, Carl D; Bowden, Donald W; Hicks, Pamela J; Palmer, Nicholette D; Palanisamy, Amudha; Reeves-Daniel, Amber M; Brown, W Mark; Divers, Jasmin

2016-01-01

Two apolipoprotein L1 gene (APOL1) renal-risk variants in donors and African American (AA) recipient race are associated with worse allograft survival in deceased-donor kidney transplantation (DDKT) from AA donors. To detect other factors impacting allograft survival from deceased AA kidney donors, APOL1 renal-risk variants were genotyped in additional AA kidney donors. The APOL1 genotypes were linked to outcomes in 478 newly analyzed DDKTs in the Scientific Registry of Transplant Recipients. Multivariate analyses accounting for recipient age, sex, race, panel-reactive antibody level, HLA match, cold ischemia time, donor age, and expanded criteria donation were performed. These 478 transplantations and 675 DDKTs from a prior report were jointly analyzed. Fully adjusted analyses limited to the new 478 DDKTs replicated shorter renal allograft survival in recipients of APOL1 2-renal-risk-variant kidneys (hazard ratio [HR], 2.00; P = 0.03). Combined analysis of 1153 DDKTs from AA donors revealed donor APOL1 high-risk genotype (HR, 2.05; P = 3 × 10), older donor age (HR, 1.18; P = 0.05), and younger recipient age (HR, 0.70; P = 0.001) adversely impacted allograft survival. Although prolonged allograft survival was seen in many recipients of APOL1 2-renal-risk-variant kidneys, follow-up serum creatinine concentrations were higher than that in recipients of 0/1 APOL1 renal-risk-variant kidneys. A competing risk analysis revealed that APOL1 impacted renal allograft survival, but not recipient survival. Interactions between donor age and APOL1 genotype on renal allograft survival were nonsignificant. Shorter renal allograft survival is reproducibly observed after DDKT from APOL1 2-renal-risk-variant donors. Younger recipient age and older donor age have independent adverse effects on renal allograft survival.

Intraoperative culture positive allograft bone and subsequent postoperative infections: a retrospective review.

PubMed

Sims, Laura; Kulyk, Paul; Woo, Allan

2017-04-01

Obtaining intraoperative cultures of allograft bone just before use in orthopedic procedures is standard practice in many centres; however, the association between positive cultures and subsequent surgical infections is unknown. Our study had 3 goals: to determine the prevalence of positive intraoperative allograft culture and subsequent infection; to determine if, in cases of subsequent infection, organisms isolated at reoperation were the same as those cultured from the allograft at the time of the index procedure; and to assess the costs associated with performing intraoperative allograft cultures. In this retrospective case series, we obtained data on patients receiving allograft bone between 2009 and 2012. Patients receiving allograft with positive cultures were reviewed to identify cases of significant infection. Organisms isolated at reoperation were compared with the allograft culture taken at the time of implantation, and we performed a cost assessment. Of the 996 allograft bone grafts used, 43 (4.3%) had positive intraoperative cultures and significant postoperative infections developed in 2, requiring reoperation. Antibiotics based on culture results were prescribed in 24% of cases. Organisms cultured at the time of reoperation differed from those isolated initially. The cost of performing 996 allograft cultures was $169 320. This series suggests that rates of positive intraoperative bone allograft culture are low, and subsequent infection is rare. In cases of postoperative infection, primary allograft culture and secondary tissue cultures isolated different organisms. Costs associated with performing cultures are high. Eliminating initial culture testing could save $42 500 per year in our health region.

Intraoperative culture positive allograft bone and subsequent postoperative infections: a retrospective review

PubMed Central

Sims, Laura; Kulyk, Paul; Woo, Allan

2017-01-01

Background Obtaining intraoperative cultures of allograft bone just before use in orthopedic procedures is standard practice in many centres; however, the association between positive cultures and subsequent surgical infections is unknown. Our study had 3 goals: to determine the prevalence of positive intraoperative allograft culture and subsequent infection; to determine if, in cases of subsequent infection, organisms isolated at reoperation were the same as those cultured from the allograft at the time of the index procedure; and to assess the costs associated with performing intraoperative allograft cultures. Methods In this retrospective case series, we obtained data on patients receiving allograft bone between 2009 and 2012. Patients receiving allograft with positive cultures were reviewed to identify cases of significant infection. Organisms isolated at reoperation were compared with the allograft culture taken at the time of implantation, and we performed a cost assessment. Results Of the 996 allograft bone grafts used, 43 (4.3%) had positive intraoperative cultures and significant postoperative infections developed in 2, requiring reoperation. Antibiotics based on culture results were prescribed in 24% of cases. Organisms cultured at the time of reoperation differed from those isolated initially. The cost of performing 996 allograft cultures was $169 320. Conclusion This series suggests that rates of positive intraoperative bone allograft culture are low, and subsequent infection is rare. In cases of postoperative infection, primary allograft culture and secondary tissue cultures isolated different organisms. Costs associated with performing cultures are high. Eliminating initial culture testing could save $42 500 per year in our health region. PMID:28234217

Antiangiogenic treatment diminishes renal injury and dysfunction via regulation of local AKT in early experimental diabetes.

PubMed

Bai, Xiaoyan; Li, Xiao; Tian, Jianwei; Zhou, Zhanmei

2014-01-01

In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser⁴⁷³-AKT, phosphorylated Thr³⁰⁸-AKT, nephrin, angiotensin II (Ang II), angiotensin type II receptor 1 (ATR1) were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr³⁰⁸-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr³⁰⁸-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr³⁰⁸-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr³⁰⁸-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr³⁰⁸-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the interstitial fibrosis

Antiangiogenic Treatment Diminishes Renal Injury and Dysfunction via Regulation of Local AKT in Early Experimental Diabetes

PubMed Central

Zhou, Zhanmei

2014-01-01

In view of increased vascular endothelial growth factor-A (VEGF-A) expression and renal dysfunction in early diabetes, we designed a study to test whether VEGF-A inhibition can prevent early renal injury and dysfunction. We investigated the relationship and mechanism between VEGF-A and AKT regulation. In vitro, VEGF-A small interfering RNA (siRNA) and AKT inhibitor MK-2206 were employed to podocytes and NRK-52 cells cultured in high glucose (30 mM). In vivo, the antiangiogenic drug endostatin was administered in 12 week-old streptozotocin-induced male Sprague Dawley rats. The levels of VEGF-A, AKT, phosphorylated Ser473-AKT, phosphorylated Thr308-AKT, nephrin, angiotensin II (Ang II), angiotensin type II receptor 1 (ATR1) were examined using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemistry. Interactions between phosphorylated Thr308-AKT and either nephrin in podocytes or Ang II in renal tubules were studied, respectively, using confocal immunofluorescence microscopy and immunoprecipitation. Silencing VEGF-A in podocytes upregulated phosphorylated Thr308-AKT and nephrin. Silencing VEGF-A in NRK-52E cells upregulated phosphorylated Thr308-AKT while downregulated Ang II and ATR1. MK-2206 enhanced VEGF-A expression in both podocytes and NRK-52E cells by inhibiting AKT activities. In diabetic rat kidneys, VEGF-A was upregulated and phosphorylated Thr308-AKT colocalized with either nephrin in podocytes or Ang II in renal tubules. With the endostatin treatment, the level of VEGF-A decreased while phosphorylated Thr308-AKT increased in both glomeruli and renal tubules. Treatment with endostatin upregulated nephrin in podocytes while downregulated Ang II and AT1R in renal tubules. Glomerular mesangial expansion was attenuated by the endostatin treatment, however, differences did not reach statistical significance. Endostatin ameliorated the interstitial fibrosis, urine albumin excretion rate

Renal Tumors: Technical Success and Early Clinical Experience with Radiofrequency Ablation of 18 Tumors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sabharwal, Rohan, E-mail: rohan50000@yahoo.com; Vladica, Philip

2006-04-15

Purpose. To evaluate the feasibility, safety, and technical efficacy of image-guided radiofrequency ablation (RFA) for the treatment of small peripheral renal tumors and to report our early results with this treatment modality. Methods. Twenty-two RFA sessions for 18 tumors were performed in 11 patients with renal tumors. Indications included coexistent morbidity, high surgical or anesthetic risk, solitary kidney, and hereditary predisposition to renal cell carcinoma. Ten patients had CT-guided percutaneous RFA performed on an outpatient basis. One patient had open intraoperative ultrasound-guided RFA. Technical success was defined as elimination of areas that enhanced at imaging within the entire tumor. Withmore » the exception of one patient with renal insufficiency who required gadolinium-enhanced MRI, the remaining patients underwent contrast-enhanced CT for post-treatment follow-up assessment. Follow-up was performed after 2-4 weeks and then at 3, 6, 12 months, and every 12 months thereafter. Results. Fourteen (78%) of 18 tumors were successfully ablated with one session. Three of the remaining four tumors required two sessions for successful ablation. One tumor will require a third session for areas of persistent enhancement. Mean patient age was 72.82 {+-} 10.43 years. Mean tumor size was 1.95 {+-} 0.79 cm. Mean follow-up time was 10.91 months. All procedures were performed without any major complications. Conclusions. Our early experience with percutaneous image-guided radiofrequency ablation demonstrates it to be a feasible, safe, noninvasive, and effective treatment of small peripheral renal tumors.« less

Tolerance to Vascularized Composite Allografts in Canine Mixed Hematopoietic Chimeras

PubMed Central

Mathes, David W.; Hwang, Billanna; Graves, Scott S.; Edwards, James; Chang, Jeff; Storer, Barry E.; Butts-Miwongtum, Tiffany; Sale, George E.; Nash, Richard A.; Storb, Rainer.

2012-01-01

Background Mixed donor-host chimerism, established through hematopoietic cell transplantation (HCT), is a highly reproducible strategy for the induction of tolerance towards solid organs. Here, we ask whether a nonmyeloablative conditioning regimen establishing mixed donor-host chimerism leads to tolerance of highly antigenic vascularized composite allografts. Methods Stable mixed chimerism was established in dogs given a sublethal dose (1–2 Gy) total body irradiation before and a short course of immunosuppression after dog leukocyte antigen-identical marrow transplantation. Vascularized composite allografts from marrow donors were performed after a median of 36 (range 4-54) months after HCT. Results All marrow recipients maintained mixed donor-host hematopoietic chimerism and accepted composite tissue grafts for periods ranging between 52 and 90 weeks; in turn, marrow donors rejected vascularized composite allografts from their respective marrow recipients within 18–29 days. Biopsies of muscle and skin of vascularized composite allografts from mixed chimeras showed few infiltrating cells compared to extensive infiltrates in biopsies of vascularized composite allografts from marrow donors. Elevated levels of CD3+ FoxP3+ T-regulatory cells were found in skin and muscle of vascularized composite allografts of mixed chimeras compared to normal tissues. In mixed chimeras, increased numbers of T-regulatory cells were found in draining compared to non-draining lymph nodes of vascularized composite allografts. Conclusion These data suggest that nonmyeloablative HCT may form the basis for future clinical applications of solid organ transplantation and that T-regulatory cells may function towards maintenance of the vascularized composite allograft. PMID:22082819

[Ureterostomy cytomegalovirus infection presenting as stoma ulceration in a kidney allograft receptor: a case report].

PubMed

Rico, J E; Cardona, X; Rodelo, J; Reino, A; Arias, L F; Arbeláez, M

2008-06-01

Cytomegalovirus (CMV) is the most common viral infection affecting transplant patients, but urinary tract involvement has been rare. Only a few cases of symptomatic ureteritis have been reported in renal transplant recipients. In previous reports the presentation of CMV ureteritis is obstructive nephropathy, often in the absence of systemic illness, or rarely it may also mimic allograft rejection with minimal obstructive symptoms. We describe an additional case of CMV ureteritis in a patient with cutaneous ureterostomy. The unusual clinical presentation with urinary infection symptoms and ureterostomy stoma ulceration constitute a very particular presentation. The increasing report cases with CMV ureteritis suggest an increase of this post-transplant complication.

Early life stress sensitizes the renal and systemic sympathetic system in rats.

PubMed

Loria, Analia S; Brands, Michael W; Pollock, David M; Pollock, Jennifer S

2013-08-01

We hypothesized that maternal separation (MS), an early life stress model, induces a sensitization of the sympathetic system. To test this hypothesis, we evaluated the renal and systemic sympathetic system in 12- to 14-wk-old male control or MS rats with the following parameters: 1) effect of renal denervation on conscious renal filtration capacity, 2) norepinephrine (NE) content in key organs involved in blood pressure control, and 3) acute systemic pressor responses to adrenergic stimulation or ganglion blockade. MS was performed by separating pups from their mothers for 3 h/day from day 2 to 14; controls were nonhandled littermates. Glomerular filtration rate (GFR) was examined in renal denervated (DnX; within 2 wk) or sham rats using I¹²⁵-iothalamate plasma clearance. MS-DnX rats showed significantly increased GFR compared with MS-SHAM rats (3.8 ± 0.4 vs. 2.4 ± 0.2 ml/min, respectively, P < 0.05), whereas DnX had no effect in controls, indicating that renal nerves regulate GFR in MS rats. NE content was significantly increased in organ tissues from MS rats (P < 0.05, n = 6-8), suggesting a sensitization of the renal and systemic sympathetic system. Conscious MS rats displayed a significantly greater increase in mean arterial pressure (MAP) in response to NE (2 μg/kg ip) and a greater reduction in MAP in response to mecamylamine (2 mg/kg ip, P < 0.05, n = 4) monitored by telemetry, indicating that MS rats exhibit exaggerated responses to sympathetic stimulation. In conclusion, these data indicate that MS sensitizes the renal and systemic sympathetic system ultimately impairing blood pressure regulation.

Revitalization of biostatic tissue allografts: new perspectives in tissue transplantology.

PubMed

Olender, E; Uhrynowska-Tyszkiewicz, I; Kaminski, A

2011-10-01

Biostatic (nonvital) tissue allografts have been used for temporary replacement as well as to trigger, stimulate, and ensure space for the regeneration of a recipient's own tissues. Examples of biostatic allografts routinely used in clinic are bone, tendons, skin, and amniotic membrane. A characteristic feature of biostatic allografts is the lack of living cells. In the recipient's body, biostatic allografts function as scaffolds as well as sources of growth, differentiation, and chemotactic factors. After implantation, recipient cells migrate onto the graft, colonize it, and initiate synthesis of extracellular matrix, thereby regenerating the structure of the lost or damaged tissue. The allograft gradually degrades before being remodeled and substituted by the recipient's new tissue. However, this process is not always effective due to a lack of reaction by recipient cells. New concepts have proposed seeding recipient cells onto the allograft prior to implantation, that is, biostatic allografts that are revitalized ex vivo. The aim of this presentation was to review scientific publications to provide essential information on the revitalization of biostatic allografts, as a rising trend in tissue transplantology. Biostatic allografts show the following advantages: they are human-derived, nontoxic, biocompatible, and, in some cases, already display the desired shape. The process of introducing cells into the biostatic graft is described as "revitalization." The cells used in the process are recipient autologous elements that are either differentiated or progenitor elements. Cells are seeded onto the graft directly after retrieval or after propagation in culture. Revitalized biostatic allografts can be used orthotopically for the regeneration of the same tissue they have been retrieved from or heterotopically wherein the graft retrieved from a different tissue is used as a carrier for cells typical for the tissue to be regenerated. Examples of orthotopic use include

Factors Predicting Meniscal Allograft Transplantation Failure

PubMed Central

Parkinson, Ben; Smith, Nicholas; Asplin, Laura; Thompson, Peter; Spalding, Tim

2016-01-01

Background: Meniscal allograft transplantation (MAT) is performed to improve symptoms and function in patients with a meniscal-deficient compartment of the knee. Numerous studies have shown a consistent improvement in patient-reported outcomes, but high failure rates have been reported by some studies. The typical patients undergoing MAT often have multiple other pathologies that require treatment at the time of surgery. The factors that predict failure of a meniscal allograft within this complex patient group are not clearly defined. Purpose: To determine predictors of MAT failure in a large series to refine the indications for surgery and better inform future patients. Study Design: Cohort study; Level of evidence, 3. Methods: All patients undergoing MAT at a single institution between May 2005 and May 2014 with a minimum of 1-year follow-up were prospectively evaluated and included in this study. Failure was defined as removal of the allograft, revision transplantation, or conversion to a joint replacement. Patients were grouped according to the articular cartilage status at the time of the index surgery: group 1, intact or partial-thickness chondral loss; group 2, full-thickness chondral loss 1 condyle; and group 3, full-thickness chondral loss both condyles. The Cox proportional hazards model was used to determine significant predictors of failure, independently of other factors. Kaplan-Meier survival curves were produced for overall survival and significant predictors of failure in the Cox proportional hazards model. Results: There were 125 consecutive MATs performed, with 1 patient lost to follow-up. The median follow-up was 3 years (range, 1-10 years). The 5-year graft survival for the entire cohort was 82% (group 1, 97%; group 2, 82%; group 3, 62%). The probability of failure in group 1 was 85% lower (95% CI, 13%-97%) than in group 3 at any time. The probability of failure with lateral allografts was 76% lower (95% CI, 16%-89%) than medial allografts at

Urine biomarkers informative of human kidney allograft rejection and tolerance.

PubMed

Nissaisorakarn, Voravech; Lee, John Richard; Lubetzky, Michelle; Suthanthiran, Manikkam

2018-05-01

We developed urinary cell messenger RNA (mRNA) profiling to monitor in vivo status of human kidney allografts based on our conceptualization that the kidney allograft may function as an in vivo flow cell sorter allowing access of graft infiltrating cells to the glomerular ultrafiltrate and that interrogation of urinary cells is informative of allograft status. For the profiling urinary cells, we developed a two-step preamplification enhanced real-time quantitative PCR (RT-QPCR) assays with a customized amplicon; preamplification compensating for the low RNA yield from urine and the customized amplicon facilitating absolute quantification of mRNA and overcoming the inherent limitations of relative quantification widely used in RT-QPCR assays. Herein, we review our discovery and validation of urinary cell mRNAs as noninvasive biomarkers prognostic and diagnostic of acute cellular rejection (ACR) in kidney allografts. We summarize our results reflecting the utility of urinary cell mRNA profiling for predicting reversal of ACR with anti-rejection therapy; differential diagnosis of kidney allograft dysfunction; and noninvasive diagnosis and prognosis of BK virus nephropathy. Messenger RNA profiles associated with human kidney allograft tolerance are also summarized in this review. Altogether, data supporting the idea that urinary cell mRNA profiles are informative of kidney allograft status and tolerance are reviewed in this report. Copyright © 2018. Published by Elsevier Inc.

21 CFR 862.1163 - Cardiac allograft gene expression profiling test system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cardiac allograft gene expression profiling test... Chemistry Test Systems § 862.1163 Cardiac allograft gene expression profiling test system. (a) Identification. A cardiac allograft gene expression profiling test system is a device that measures the...

Early superoxide scavenging accelerates renal microvascular rarefaction and damage in the stenotic kidney.

PubMed

Kelsen, Silvia; He, Xiaochen; Chade, Alejandro R

2012-08-15

Renal artery stenosis (RAS), the main cause of chronic renovascular disease (RVD), is associated with significant oxidative stress. Chronic RVD induces renal injury partly by promoting renal microvascular (MV) damage and blunting MV repair in the stenotic kidney. We tested the hypothesis that superoxide anion plays a pivotal role in MV dysfunction, reduction of MV density, and progression of renal injury in the stenotic kidney. RAS was induced in 14 domestic pigs and observed for 6 wk. Seven RAS pigs were chronically treated with the superoxide dismutase mimetic tempol (RAS+T) to reduce oxidative stress. Single-kidney hemodynamics and function were quantified in vivo using multidetector computer tomography (CT) and renal MV density was quantified ex vivo using micro-CT. Expression of angiogenic, inflammatory, and apoptotic factors was measured in renal tissue, and renal apoptosis and fibrosis were quantified in tissue sections. The degree of RAS and blood pressure were similarly increased in RAS and RAS+T. Renal blood flow (RBF) and glomerular filtration rate (GFR) were reduced in the stenotic kidney (280.1 ± 36.8 and 34.2 ± 3.1 ml/min, P < 0.05 vs. control). RAS+T kidneys showed preserved GFR (58.5 ± 6.3 ml/min, P = not significant vs. control) but a similar decreases in RBF (293.6 ± 85.2 ml/min) and further decreases in MV density compared with RAS. These changes were accompanied by blunted angiogenic signaling and increased apoptosis and fibrosis in the stenotic kidney of RAS+T compared with RAS. The current study shows that tempol administration provided limited protection to the stenotic kidney. Despite preserved GFR, renal perfusion was not improved by tempol, and MV density was further reduced compared with untreated RAS, associated with increased renal apoptosis and fibrosis. These results suggest that a tight balance of the renal redox status is necessary for a normal MV repair response to injury, at least at the early stage of RVD, and raise caution

Early superoxide scavenging accelerates renal microvascular rarefaction and damage in the stenotic kidney

PubMed Central

Kelsen, Silvia; He, Xiaochen

2012-01-01

Renal artery stenosis (RAS), the main cause of chronic renovascular disease (RVD), is associated with significant oxidative stress. Chronic RVD induces renal injury partly by promoting renal microvascular (MV) damage and blunting MV repair in the stenotic kidney. We tested the hypothesis that superoxide anion plays a pivotal role in MV dysfunction, reduction of MV density, and progression of renal injury in the stenotic kidney. RAS was induced in 14 domestic pigs and observed for 6 wk. Seven RAS pigs were chronically treated with the superoxide dismutase mimetic tempol (RAS+T) to reduce oxidative stress. Single-kidney hemodynamics and function were quantified in vivo using multidetector computer tomography (CT) and renal MV density was quantified ex vivo using micro-CT. Expression of angiogenic, inflammatory, and apoptotic factors was measured in renal tissue, and renal apoptosis and fibrosis were quantified in tissue sections. The degree of RAS and blood pressure were similarly increased in RAS and RAS+T. Renal blood flow (RBF) and glomerular filtration rate (GFR) were reduced in the stenotic kidney (280.1 ± 36.8 and 34.2 ± 3.1 ml/min, P < 0.05 vs. control). RAS+T kidneys showed preserved GFR (58.5 ± 6.3 ml/min, P = not significant vs. control) but a similar decreases in RBF (293.6 ± 85.2 ml/min) and further decreases in MV density compared with RAS. These changes were accompanied by blunted angiogenic signaling and increased apoptosis and fibrosis in the stenotic kidney of RAS+T compared with RAS. The current study shows that tempol administration provided limited protection to the stenotic kidney. Despite preserved GFR, renal perfusion was not improved by tempol, and MV density was further reduced compared with untreated RAS, associated with increased renal apoptosis and fibrosis. These results suggest that a tight balance of the renal redox status is necessary for a normal MV repair response to injury, at least at the early stage of RVD, and raise caution

Nutritional status and body composition in patients early after renal transplantation.

PubMed

Netto, M C A S; Alves-Filho, G; Mazzali, M

2012-10-01

After renal transplantation recovery in nutritional status occurs during the first year. We assessed the changes in nutritional status after transplantation in 145 transplant recipients (94 males, 51 females). Patients were evaluated immediately after renal transplant (baseline data) and at 6 months' follow-up. Analysis included body mass index (BMI), body composition (skin fold and arm circumference), and estimated body composition (calculated percent of fat, arm circumference, arm muscle circumference, and arm muscle area). Other data obtained from medical records included renal function (MDRD) serum albumin and lipid profile. At baseline evaluation (21 ± 15 days posttransplant), mean BMI was 23.9 ± 3.9 kg/m(2), serum albumin was 3.7 ± 0.7 g/dL, and lipid profile showed (cholesterol 158.5 ± 52.7 mg% and triglycerides 135.9 ± 91.8 mg%. Body composition analysis showed better adaptation of muscle mass in females [AC (91 ± 10.2 × 98 ± 14.6; male × female, P < .05) arm muscle circumference (92.6 ± 1.4 × 102.3% ± 2.9%, male × female, P < .05) and arm muscle area (87.1 ± 22.3 × 105.5% ± 25.9%, male × female, P < .05)]. Body fat was above the recommended levels in 80% of patients, especially females. After 6 months we divided the groups according to BMI, observing better renal function in the normal weight group compared with obese subjects (60 ± 17.2 × 39.5 ± 19.8 mL/min MDRD, P < .05), despite comparable estimated glomerular filtration rate at baseline. The nutritional assessment of patients with end-stage renal disease early after renal transplantation, showed inadequate body composition, with increased fat and reduced lean body mass. The lower glomerular filtration rate after 6 months may be attributed to relatively inadequate renal mass or to obesity-induced hyperfiltration. Copyright © 2012 Elsevier Inc. All rights reserved.

Short-term survival in renal transplantation from brain-death donors: focusing on recipients with diabetes background.

PubMed

Nakhjavani, Manoochehr; Ghaemi, Fatemeh; Ravaghi, Hamid; Aghighi, Mohammad; Ghaemi, Farahnaz

2014-05-06

Our aim was to evaluate short term survival rates in renal transplant recipients from deceased donors, while focusing on recipients with diabetes mellitus background. This is a longitudinal follow-up study based on national registry of recipients in Ministry of Health and Medical Education in Iran from 2010-11. Five hundred fifty-five recipients, 226 (40.8%) females and 328 (59.2%) males, were included in the study. Mean (± SD) age of the recipients was 39 ± 14 years. Of donors 18.4% were females and 81.6% were males. Age of the donors was 33 ± 14 years. All allograft recipients from deceased donors enrolled in the study. Short-term graft survival (1 year) was determined. Data regarding age, gender, background disease and cold ischemic time of recipients and donors were collected from the organ procurement units. Allografts were functioning in 499 (90.1%) of recipients after one year. Of recipients 38 (6.9%) died and rejection of transplanted kidney occurred in 17 (3.1%) cases. So, in 55 (9.9%) cases, allografts were not functioning. There were significant relationships between short term graft survival of donors' gender, age of recipients, cold ischemic time and level of clearance of creatinine of recipients. In addition to cold ischemic time, graft survival can be affected by recipients' age. There are some other considerations and implications regarding the short term graft survival in renal transplantation from cadaver donors which are discussed in this paper.

Allografts with autogenous platelet-rich plasma for tibial defect reconstruction: a rabbit study.

PubMed

Nather, Aziz; Wong, Keng Lin; David, Vikram; Pereira, Barry P

2012-12-01

To evaluate the effect of autogenous platelet-rich plasma (PRP) for fresh-frozen allografts in tibial defect reconstruction in rabbits. 40 adult New Zealand white rabbits underwent tibial defect reconstruction with autografts (n=12), allografts without PRP (n=12), or allografts with PRP (n=12) and were observed for 12, 16, and 24 weeks (4 for each period). Tibias of the remaining 4 rabbits were used as donor allografts, and the remaining allografts were procured from recipient rabbits. A 1.5- cm cortical segment of the tibia was osteotomised, and then fixed with a 9-hole mini-compression plate and 2 cerclage wires. Allografts were stripped off the periosteum and soft tissues and medullary contents, and then stored in a freezer at -80 ºC. All allografts were deep frozen for at least 4 weeks before transplantation. 7 ml of whole blood was drawn to prepare 1 ml of PRP. The PRP was then mixed with 1.0 ml of human thrombin to form a platelet gel. The PRP gel was then packed into the medullary canal of the allograft and applied on the cortical surface before tibial defect reconstruction. Rabbits were sacrificed at 12, 16, and 24 weeks. The specimens were assessed for bone union at host-graft junctions and for bone resorption, new bone formation, callus encasement, and viable osteocyte counts. There were 4 specimens in each group at each observation period. Osteoid bridging the gap at host-graft junctions was noted in all specimens in the autograft and allograft-with-PRP groups at week 12 and in the allograft-without-PRP group at week 24. Bone union in allografts without PRP was delayed. All indices for biological incorporation (resorption index, new bone formation index, callus encasement index, and viable osteocyte count) were significantly greater in the autograft than allograft-without-PRP groups, except for the resorption index at week 24, whereas the differences were not significant between the autograft and allograft-with-PRP groups. The differences between the 2

Role of airway epithelial injury in murine orthotopic tracheal allograft rejection.

PubMed

Kuo, Elbert; Bharat, Ankit; Shih, Jennifer; Street, Tyler; Norris, Jenyi; Liu, Wei; Parks, William; Walter, Michael; Patterson, G Alexander; Mohanakumar, T

2006-10-01

Murine tracheal transplantation is a model used to study bronchiolitis obliterans syndrome, a major cause of morbidity and mortality after lung transplantation. Unlike murine heterotopic tracheal transplants, orthotopic transplantation does not cause luminal obliteration despite major histocompatibility antigen mismatch. Repopulation of the tracheal allografts with recipient-derived epithelium confers protection against luminal obliteration. The purpose of this study was to determine whether (1) orthotopic tracheal transplantation showed signs of allograft rejection, and (2) airway epithelial cell injury promoted orthotopic tracheal allograft rejection. Forty isogeneic (C57BL/6 to C57BL/6) and 40 allogeneic (BALB/c to C57BL/6) orthotopic tracheal transplants were performed. Damage to airway epithelial cells was induced by Sendai viral (SdV) infection and tracheal transplantation into non-reepithelializing matrix metalloproteinase-7 knockout (MMP7-KO) recipient mice. Percent fibrosis and lamina propria to cartilage ratio were calculated with computer assistance on harvested allografts. Allografts showed significantly more intramural fibrosis compared with isografts at 30, 60, and 180 days after transplant without luminal occlusion. Tracheal allografts infected with SdV showed an increase in fibrosis and lamina propria to cartilage ratio compared with noninfected controls. Allografts retrieved from MMP7-KO recipients also showed a significant increase in fibrosis and lamina propria to cartilage ratio. Although orthotopic tracheal transplantation does not cause luminal obliteration, it results in increased fibrosis in allografts. Damage to the respiratory epithelium by viral infection or defective reepithelialization after transplant as seen in MMP7-KO recipient mice leads to changes consistent with chronic allograft rejection, suggesting a role for epithelial injury in bronchiolitis obliterans syndrome development.

Supply of human allograft tissue in Canada.

PubMed

Lakey, Jonathan R T; Mirbolooki, Mohammadreza; Rogers, Christina; Mohr, Jim

2007-01-01

There is relatively little known about the supply for allograft tissues in Canada. The major aim of this study is to quantify the current or "Known Supply" of human allograft tissue (bone, tendons, soft tissue, cardiovascular, ocular and skin) from known tissue banks in Canada, to estimate the "Unknown Supply" of human allograft tissue available to Canadian users from other sources, and to investigate the nature and source of these tissue products. Two surveys were developed; one for tissue banks processing one or more tissue types and the other specific to eye banks. Thirty nine sites were initially identified as potential tissue bank respondent sites. Of the 39 sites, 29 sites indicated that they were interested in participating or would consider completing the survey. A survey package and a self-addressed courier envelope were couriered to each of 29 sites. A three week response time was indicated. The project consultants conducted telephone and email follow-up for incomplete data. Unknown supply was estimated by 5 methods. Twenty-eight of 29 sites (97%) completed and returned surveys. Over the past year, respondents reported a total of 5,691 donors (1,550 living and 4,141 cadaveric donors). Including cancellous ground bone, there were 10,729 tissue products produced by the respondent banks. Of these, 71% were produced by accredited banks and 32% were ocular tissues. Total predicted shortfall of allograft tissues was 31,860-66,481 grafts. Through estimating Current supply, and compiling additional qualitative information, this study has provided a snapshot of the current Canadian supply and shortfall of allograft tissue grafts.

Clinical experience with induction therapy in renal transplantation.

PubMed

Muntean, Adriana; Lucan, Mihai; Barbos, Adrian; Elec, Alina; Iacob, Gheorghita; Loga, Luminita; Dican, Lucia

2013-01-01

Acute rejection (AR) is a major determinant of renal allograft survival. The incorporation of new immunosuppressive agents explains the improvement seen in the results of transplantation in recent years. To assess the optimal immunosuppression regimen according to the immunological risk of renal transplant patients. We performed a retrospective study of 977 consecutive patients transplanted in our institution between January 2000 and December 2011. Recipients were classified according to the immunological risk (high, intermediate and low) and the type of induction therapy received. We evaluated the incidence of early acute rejection (eAR) and late acute rejection (lAR) and their influence on graft and patients survival in relation to the immunological risk and induction regimen used. The incidence of eAR was 5.4%, 6.4% and 1.4% in relation with the immunological risk, high, intermediate and low respectively. The most commonly used induction immunosuppression was rabbit antithymocyte globulin (ATG), followed by methylprednisolone and basiliximab. No statistical difference was found between the incidence of eAR according to the type of induction therapy and immunological risk. The graft survival was significantly better for the cases without eAR at 1 year (98.6% versus 94.4%, p=0.019), and 3 years (94.9% versus 88.9%, p=0.056). The patients survival was significantly better for those without eAR at 1 year after transplant (95.7% vs. 88.9%, p=0.051), 3 years (93.1% vs. 83.3%, p=0.008) and 5 years (92.2% vs. 79.6%, p=0.001). The incidence of lAR was between 0 and 7.1% according to the induction therapy, lacking any statistical significance (p=0.450). Tailoring the induction immunosuppression according to the immunological risk reduces the incidence of early acute rejection.

Clinical experience with induction therapy in renal transplantation

PubMed Central

MUNTEAN, ADRIANA; LUCAN, MIHAI; BARBOS, ADRIAN; ELEC, ALINA; IACOB, GHEORGHITA; LOGA, LUMINITA; DICAN, LUCIA

2013-01-01

Introduction Acute rejection (AR) is a major determinant of renal allograft survival. The incorporation of new immunosuppressive agents explains the improvement seen in the results of transplantation in recent years. Objective To assess the optimal immunosuppression regimen according to the immunological risk of renal transplant patients. Method We performed a retrospective study of 977 consecutive patients transplanted in our institution between January 2000 and December 2011. Recipients were classified according to the immunological risk (high, intermediate and low) and the type of induction therapy received. We evaluated the incidence of early acute rejection (eAR) and late acute rejection (lAR) and their influence on graft and patients survival in relation to the immunological risk and induction regimen used. Results The incidence of eAR was 5.4%, 6.4% and 1.4% in relation with the immunological risk, high, intermediate and low respectively. The most commonly used induction immunosuppression was rabbit antithymocyte globulin (ATG), followed by methylprednisolone and basiliximab. No statistical difference was found between the incidence of eAR according to the type of induction therapy and immunological risk. The graft survival was significantly better for the cases without eAR at 1 year (98.6% versus 94.4%, p=0.019), and 3 years (94.9% versus 88.9%, p=0.056). The patients survival was significantly better for those without eAR at 1 year after transplant (95.7% vs. 88.9%, p=0.051), 3 years (93.1% vs. 83.3%, p=0.008) and 5 years (92.2% vs. 79.6%, p=0.001). The incidence of lAR was between 0 and 7.1% according to the induction therapy, lacking any statistical significance (p=0.450). Conclusion Tailoring the induction immunosuppression according to the immunological risk reduces the incidence of early acute rejection. PMID:26527980

Differential role of afferent and efferent renal nerves in the maintenance of early- and late-phase Dahl S hypertension

PubMed Central

Foss, Jason D.; Fink, Gregory D.

2015-01-01

Clinical data suggest that renal denervation (RDNX) may be an effective treatment for human hypertension; however, it is unclear whether this therapeutic effect is due to ablation of afferent or efferent renal nerves. We have previously shown that RDNX lowers arterial pressure in hypertensive Dahl salt-sensitive (S) rats to a similar degree observed in clinical trials. In addition, we have recently developed a method for selective ablation of afferent renal nerves (renal-CAP). In the present study, we tested the hypothesis that the antihypertensive effect of RDNX in the Dahl S rat is due to ablation of afferent renal nerves by comparing the effect of complete RDNX to renal-CAP during two phases of hypertension in the Dahl S rat. In the early phase, rats underwent treatment after 3 wk of high-NaCl feeding when mean arterial pressure (MAP) was ∼140 mmHg. In the late phase, rats underwent treatment after 9 wk of high NaCl feeding, when MAP was ∼170 mmHg. RDNX reduced MAP ∼10 mmHg compared with sham surgery in both the early and late phase, whereas renal-CAP had no antihypertensive effect. These results suggest that, in the Dahl S rat, the antihypertensive effect of RDNX is not dependent on pretreatment arterial pressure, nor is it due to ablation of afferent renal nerves. PMID:26661098

Non-invasive quantification of collagen turnover in renal transplant recipients

PubMed Central

Brix, Susanne; Karsdal, Morten Asser; Seelen, Marc A.; van Goor, Harry; Bakker, Stephan J. L.; Olinga, Peter; Mutsaers, Henricus A. M.; Genovese, Federica

2017-01-01

Kidney allograft failure due to chronic injury/rejection remains the main cause of graft loss in renal transplant recipients (RTR). Here, we investigated whether specific biomarkers of extracellular matrix (ECM) turnover are associated with allograft function and chronic kidney disease (CKD) stage in RTR. Seventy-eight patients who attended the University Medical Center Groningen for a routine check-up after kidney transplantation were enrolled in the study. Plasma and/or 24h-urine samples were collected and specific matrix-metalloproteinase-generated neo-epitope fragments of collagens were measured by enzyme-linked immunosorbent assay. Our results demonstrated that urinary levels of C3M, a marker for collagen type III degradation, correlated with estimated glomerular filtration rate (eGFR; r = 0.58, p<0.0001), with lower levels detected in the urine of patients with advanced CKD. In addition, plasma levels of Pro-C6, a marker for collagen type VI formation, significantly increased with disease progression and correlated with eGFR (r = -0.72, p<0.0001). Conversely, plasma C3M and urinary Pro-C6 levels showed no correlation with renal function. We identified two neo-epitope biomarkers of tissue turnover associated with ECM remodeling and fibrosis that can stratify patients by CKD stage. This is as promising first step towards non-invasive monitoring of ECM turnover in the kidneys. PMID:28430784

[The clinical use of cryopreserved human skin allografts for transplantation].

PubMed

Martínez-Flores, Francisco; Chacón-Gómez, María; Madinaveitia-Villanueva, Juan Antonio; Barrera-Lopez, Araceli; Aguirre-Cruz, Lucinda; Querevalu-Murillo, Walter

2015-01-01

The biological recovery of human skin allografts is the gold standard for preservation in Skin Banks. However, there is no worldwide consensus about specific allocation criteria for preserved human skin allografts with living cells. A report is presented on the results of 5 years of experience of using human skin allografts in burned patient in the Skin and Tissue Bank at the "Instituto Nacional de Rehabilitacion" The human skin allografts were obtained from multi-organ donors. processed and preserved at -80 °C for 12 months. Allocation criteria were performed according to blood type match, clinical history, and burned body surface. Up to now, the Skin and Tissue Bank at 'Instituto Nacional de Rehabilitacion" has processed and recovered 125,000 cm(2) of human skin allografts. It has performed 34 surgical implants on 21 burned patients. The average of burn body surface was 59.2%. More than two-thirds (67.7%) of recipients of skin allografts were matched of the same to type blood of the donor, and 66.6% survived after 126 days hospital stay. It is proposed to consider recipient's blood group as allocation criteria to assign tissue; and use human skin allografts on patiens affected with burns over 30% of body surface (according the "rule of the 9"). Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.

Validity and reliability of a novel immunosuppressive adverse effects scoring system in renal transplant recipients.

PubMed

Meaney, Calvin J; Arabi, Ziad; Venuto, Rocco C; Consiglio, Joseph D; Wilding, Gregory E; Tornatore, Kathleen M

2014-06-12

After renal transplantation, many patients experience adverse effects from maintenance immunosuppressive drugs. When these adverse effects occur, patient adherence with immunosuppression may be reduced and impact allograft survival. If these adverse effects could be prospectively monitored in an objective manner and possibly prevented, adherence to immunosuppressive regimens could be optimized and allograft survival improved. Prospective, standardized clinical approaches to assess immunosuppressive adverse effects by health care providers are limited. Therefore, we developed and evaluated the application, reliability and validity of a novel adverse effects scoring system in renal transplant recipients receiving calcineurin inhibitor (cyclosporine or tacrolimus) and mycophenolic acid based immunosuppressive therapy. The scoring system included 18 non-renal adverse effects organized into gastrointestinal, central nervous system and aesthetic domains developed by a multidisciplinary physician group. Nephrologists employed this standardized adverse effect evaluation in stable renal transplant patients using physical exam, review of systems, recent laboratory results, and medication adherence assessment during a clinic visit. Stable renal transplant recipients in two clinical studies were evaluated and received immunosuppressive regimens comprised of either cyclosporine or tacrolimus with mycophenolic acid. Face, content, and construct validity were assessed to document these adverse effect evaluations. Inter-rater reliability was determined using the Kappa statistic and intra-class correlation. A total of 58 renal transplant recipients were assessed using the adverse effects scoring system confirming face validity. Nephrologists (subject matter experts) rated the 18 adverse effects as: 3.1 ± 0.75 out of 4 (maximum) regarding clinical importance to verify content validity. The adverse effects scoring system distinguished 1.75-fold increased gastrointestinal adverse

Expression of decoy receptor 3 in kidneys is associated with allograft survival after kidney transplant rejection.

PubMed

Weng, Shuo-Chun; Shu, Kuo-Hsiung; Wu, Ming-Ju; Wen, Mei-Chin; Hsieh, Shie-Liang; Chen, Nien-Jung; Tarng, Der-Cherng

2015-09-03

Decoy receptor 3 (DcR3) expression in kidneys has been shown to predict progression of chronic kidney disease. We prospectively investigated a cohort comprising 96 renal transplant recipients (RTRs) undergoing graft kidney biopsies. Computer-assisted quantitative immunohistochemical staining value of DcR3 in renal tubular epithelial cells (RTECs) was used to determine the predictive role of DcR3 in kidney disease progression. The primary end point was doubling of serum creatinine and/or graft failure. A multivariate Cox proportional hazards model was used to assess the risk of DcR3 expression in rejected kidney grafts toward the renal end point. In total, RTRs with kidney allograft rejection were evaluated and the median follow-up was 30.9 months. The greater expression of DcR3 immunoreactivity in RTECs was correlated with a higher rate of the histopathological concordance of acute T cell-mediated rejection. Compared with 65 non-progressors, 31 progressors had higher DcR3 expression (HDE) regardless of the traditional risk factors. Cox regression analysis showed HDE was significantly associated with the risk of renal end point with a hazard ratio of 3.19 (95% confidence interval, 1.40 to 7.27; P = 0.006) after adjusting for other variables. In repetitive biopsies, HDE in tissue showed rapid kidney disease progression due to persistent inflammation.

IgA-dominant extracapillary proliferative glomerulonephritis following E.coli sepsis in a renal transplant recipient.

PubMed

Basic-Jukic, Nikolina; Coric, Marijana; Kastelan, Zeljko

2018-05-29

Postinfective glomerulonephritis (PIGN) generally occurs in association with staphylococcal infection. We present the first reported case of IgA-dominant PIGN after E.coli infection in a renal-transplant recipient. A 65-year-old patient with stable allograft function and E. coli urosepsis was treated with ciprofloxacin for 2 weeks with excellent response. One week later he developed proteinuria 16 g/day. Renal biopsy finding revealed IgA-dominant PIGN. He received steroid pulses and intravenous imunoglobulins without effect and had started with hemodialysis. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

A review of the evidence for use of thymoglobulin induction in renal transplantation.

PubMed

Gaber, A Osama; Knight, R J; Patel, S; Gaber, L W

2010-06-01

Depleting antilymphocyte, or antithymocyte antibodies, have long been an integral part of induction regimens and continue today to be used in the management of patients at risk of early rejection or those in whom the introduction of calcineurins or other immune suppressants must be delayed. Registry data demonstrate that the most commonly used depleting antibody, rabbit anti-human thymocyte globulin (rATG), is associated with improved outcomes following renal transplantation in high-risk patients, particularly in conjunction with steroid-avoidance regimens. Two prospective randomized trials in high-risk renal allograft patients have also demonstrated an advantage of r-ATG induction compared to the nondepleting interleukin receptor (IL2RA) antibodies. In low-immunologic-risk patients, however, r-ATG induction and IL2RA induction appear to be equivalent in terms of rejection prophylaxis and long-term function. Other studies have shown that sequential rATG-containing regimens were superior to no induction and allowed for successful late introduction of calcineurin inhibitors. The side effect profile of the depleting antibody included increased incidence of fever, hematologic abnormalities, cytomegalovirus infections when prophylaxis was not employed, and in some studies, increased incidence of posttransplant lymphoproliferative disease. This review describes the evidence supporting the use of depleting ATGs in kidney transplantation.

Autograft versus Allograft for Cervical Spinal Fusion: A Systematic Review.

PubMed

Tuchman, Alexander; Brodke, Darrel S; Youssef, Jim A; Meisel, Hans-Jörg; Dettori, Joseph R; Park, Jong-Beom; Yoon, S Tim; Wang, Jeffrey C

2017-02-01

Systematic review. To compare the effectiveness and safety between iliac crest bone graft (ICBG), non-ICBG autologous bone, and allograft in cervical spine fusion. To avoid problems at the donor site, various allograft materials have been used as a substitute for autograft. However, there are still questions as to the comparative effectiveness and safety of cadaver allograft compared with autologous ICBG. A systematic search of multiple major medical reference databases was conducted to identify studies evaluating spinal fusion in patients with cervical degenerative disk disease using ICBG compared with non-ICBG autograft or allograft or non-ICBG autograft compared with allograft in the cervical spine. Radiographic fusion, patient-reported outcomes, and functional outcomes were the primary outcomes of interest. Adverse events were evaluated for safety. The search identified 13 comparative studies that met our inclusion criteria: 2 prospective cohort studies and 11 retrospective cohort studies. Twelve cohort studies compared allograft with ICBG autograft during anterior cervical fusion and demonstrated with a low evidence level of support that there are no differences in fusion percentages, pain scores, or functional results. There was insufficient evidence comparing patients receiving allograft with non-ICBG autograft for fusion, pain, revision, and functional and safety outcomes. No publications directly comparing non-ICBG autograft with ICBG were found. Although the available literature suggests ICBG and allograft may have similar effectiveness in terms of fusion rates, pain scores, and functional outcomes following anterior cervical fusion, there are too many limitations in the available literature to draw any significant conclusions. No individual study provided greater than class III evidence, and when evaluating the overall body of literature, no conclusion had better than low evidence support. A prospective randomized trial with adequate sample size to

Assessment of renal perfusion with contrast-enhanced ultrasound: Preliminary results in early diabetic nephropathies.

PubMed

Dong, Yi; Wang, Wen-Ping; Lin, Pan; Fan, Peili; Mao, Feng

2016-01-01

We performed a prospective study to evaluate the value of contrast-enhanced ultrasound (CEUS) in quantitative evaluation of renal cortex perfusion in patients suspected of early diabetic nephropathies (DN), with the estimated GFR (MDRD equation) as the gold standard. The study protocol was approved by the hospital review board; each patient gave written informed consent. Our study included 46 cases (21 males and 25 females, mean age 55.6 ± 4.14 years) of clinical confirmed early DN patients. After intravenous bolus injection of 1 ml sulfur hexafluoride microbubbles of ultrasound contrast agent, real time CEUS of renal cortex was performed successively using a 2-5 MHz convex probe. Time-intensity curves (TICs) and quantitative indexes were created with Qlab software. Receiver operating characteristic (ROC) curves were used to predict the diagnostic criteria of CEUS quantitative indexes, and their diagnostic efficiencies were compared with resistance index (RI) and peak systolic velocity (PSV) of renal segmental arteries by chi square test. Our control group included forty-five healthy volunteers. Difference was considered statistically significant with P <  0.05. Changes of area under curve (AUC), derived peak intensity (DPI) were statistically significant (P <  0.05). DPI less than 12 and AUC greater than 1400 had high utility in DN, with 71.7% and 67.3% sensitivity, 77.8% and 80.0% specificity. These results were significantly better than those obtained with RI and PSV which had no significant difference in early stage of DN (P > 0.05). CEUS might be helpful to improve early diagnosis of DN by quantitative analyses. AUC and DPI might be valuable quantitative indexes.

Fresh Osteochondral Allograft Versus Autograft: Twelve-Month Results in Isolated Canine Knee Defects.

PubMed

McCarty, Eric C; Fader, Ryan R; Mitchell, Justin J; Glenn, R Edward; Potter, Hollis G; Spindler, Kurt P

2016-09-01

Osteochondral autografts and allografts have been widely used in the treatment of isolated grade 4 articular cartilage lesions of the knee. However, there is a paucity of literature regarding the basic science investigating the direct comparison between fresh osteochondral allografts to autografts. At 12 months, fresh osteochondral allografts are equal to autografts with respect to function, bony incorporation into host bone, and chondrocyte viability. Controlled laboratory study. Eight adult mongrel dogs underwent bilateral hindlimb osteochondral graft implantation in the knee after creation of an acute Outerbridge grade 4 cartilage defect. One hindlimb of each dog knee received an autograft, and the contralateral knee received an allograft. All dogs were sacrificed at 12 months. Graft analysis included gross examination, radiographs, magnetic resonance imaging (MRI), biomechanical testing, and histology. MRI demonstrated excellent bony incorporation of both autografts and allografts, except for 1 allograft that revealed partial incorporation. Histologic examination of cartilage showed intact hyaline appearance for both autografts and allografts, with fibrocartilage at the host-graft interface of both. Biomechanical testing demonstrated no significant difference between allografts and autografts (P = .76). Furthermore, no significant difference was observed between allografts and the native cartilage with biomechanical testing (P = .84). After 12 months from time of implantation, fresh osteochondral allograft tissue and autograft tissue in this study were not statistically different with respect to biomechanical properties, gross morphology, bony incorporation, or overall histologic characteristics. When compared with the previously reported 6-month incorporation rates, there was improved allograft and autograft incorporation at 12 months. With no significant differences in gross examination, radiographs, MRI, biomechanical testing, or histology in the canine

Local Expression of Indoleamine 2,3 Dioxygenase in Syngeneic Fibroblasts Significantly Prolongs Survival of an Engineered Three-Dimensional Islet Allograft

PubMed Central

Jalili, Reza B.; Forouzandeh, Farshad; Rezakhanlou, Alireza Moeen; Hartwell, Ryan; Medina, Abelardo; Warnock, Garth L.; Larijani, Bagher; Ghahary, Aziz

2010-01-01

OBJECTIVE The requirement of systemic immunosuppression after islet transplantation is of significant concern and a major drawback to clinical islet transplantation. Here, we introduce a novel composite three-dimensional islet graft equipped with a local immunosuppressive system that prevents islet allograft rejection without systemic antirejection agents. In this composite graft, expression of indoleamine 2,3 dioxygenase (IDO), a tryptophan-degrading enzyme, in syngeneic fibroblasts provides a low-tryptophan microenvironment within which T-cells cannot proliferate and infiltrate islets. RESEARCH DESIGN AND METHODS Composite three-dimensional islet grafts were engineered by embedding allogeneic mouse islets and adenoviral-transduced IDO–expressing syngeneic fibroblasts within collagen gel matrix. These grafts were then transplanted into renal subcapsular space of streptozotocin diabetic immunocompetent mice. The viability, function, and criteria for graft take were then determined in the graft recipient mice. RESULTS IDO-expressing grafts survived significantly longer than controls (41.2 ± 1.64 vs. 12.9 ± 0.73 days; P < 0.001) without administration of systemic immunesuppressive agents. Local expression of IDO suppressed effector T-cells at the graft site, induced a Th2 immune response shift, generated an anti-inflammatory cytokine profile, delayed alloantibody production, and increased number of regulatory T-cells in draining lymph nodes, which resulted in antigen-specific impairment of T-cell priming. CONCLUSIONS Local IDO expression prevents cellular and humoral alloimmune responses against islets and significantly prolongs islet allograft survival without systemic antirejection treatments. This promising finding proves the potent local immunosuppressive activity of IDO in islet allografts and sets the stage for development of a long-lasting nonrejectable islet allograft using stable IDO induction in bystander fibroblasts. PMID:20522587

Assessing the metabolic effects of calcineurin inhibitors in renal transplant recipients by urine metabolic profiling.

PubMed

Diémé, Binta; Halimi, Jean Michel; Emond, Patrick; Büchler, Matthias; Nadal-Desbarat, Lydie; Blasco, Hélène; Le Guellec, Chantal

2014-07-27

Biomarkers that can predict graft function and/or renal side effects of calcineurin inhibitors (CNI) at each stage of treatment in kidney transplantation are still lacking. We report the first untargeted GC-MS-based metabolomic study on urines of renal transplant patients. This approach would bring insight in biomarkers useable for graft function monitoring. All consecutive patients receiving a kidney allograft in our transplantation department over a 6-month period were prospectively included and followed up for 12 months. We collected urine samples on the seventh day (D7) after transplantation, then at month 3 (M3) and month 12 (M12), and obtained mass-spectrometry-based urinary metabolic profiles. Multivariate analyses were conducted to compare metabolic profiles at the 3 different periods and to assess potential differences between cyclosporine and tacrolimus. Differences in metabolic signatures were also assessed according to graft function at D7 and renal function at M3 and M12. The urinary metabolic patterns varied over time in cyclosporine- and tacrolimus-treated patients and were somewhat different at D7, M3, and M12 between the 2 treatment groups. Principal metabolites that differed, regardless of the treatment used, were mainly sugars, inositol, and hippuric acid. Interestingly, among tacrolimus-treated patients, different metabolic signatures were found between patients with immediate or delayed graft function at D7. Urinary metabolomics represents a noninvasive way of monitoring immunosuppressive therapy in renal transplant patients. Although it is too early to consider it as a biomarker of CNI-induced injury or graft function, metabolomics appears a promising evaluation tool in this area.

Low-grade albuminuria reduction with angiotensin II type 1 receptor blocker in renal transplant recipients.

PubMed

Uchida, Junji; Machida, Yuichi; Iwai, Tomoaki; Iguchi, Taro; Kamada, Yoshiko; Naganuma, Toshihide; Kumada, Norihiko; Kim, Taku; Kawashima, Hidenori; Nakatani, Tatsuya

2011-01-01

Microalbuminuria, defined as urine albumin to urine creatinine ratio of 30 to <300 mg/g, is an established risk factor for cardiovascular morbidity and mortality in the general population. Low-grade albuminuria (<30 mg/g) is considered a marker for subclinical vascular damage that predisposes to future cardiovascular diseases and death. Lowering urinary albumin excretion reduces the risk of cardiovascular disease. Our study was designed to evaluate the influence of angiotensin II type 1 receptor blocker (ARB) in normotensive renal transplant recipients with low-grade albuminuria. Our 6-month prospective observation study used a randomized control and open-label design as we examined the effects of an ARB (valsartan) on blood pressure, urinary albumin excretion, hematocrit, serum potassium and estimated glomerular filtration rate (eGFR) in normotensive recipients with allografts of more than 1 year. A total of 35 renal transplant recipients were enrolled in this study. Patients were randomly assigned to 2 groups: ARB group (n=18), receiving 40-80 mg valsartan daily for 6 months, and the control group (n=17). In the ARB group, urine albumin excretion was significantly reduced from 25.9 ± 19.1 mg/g to 12.0 ± 9.6 mg/g at 6 months after administration. eGFR decreased slightly at 6 months after administration. However, no patients undergoing treatment for adverse effects required discontinuation of ARB. This study reveals that ARB is safe and reduces low-grade albuminuria in normotensive renal transplant recipients. Thus, early treatment of ARB in recipients with low-grade albuminuria may prevent cardiovascular disease after renal transplantation.

The inferior impact of antibody-mediated rejection on the clinical outcome of kidney allografts that develop de novo thrombotic microangiopathy.

PubMed

Wu, Kaiyin; Budde, Klemens; Schmidt, Danilo; Neumayer, Hans-Hellmut; Lehner, Lukas; Bamoulid, Jamal; Rudolph, Birgit

2016-02-01

Antibody-mediated rejection (AMR) can induce and develop thrombotic microangiopathy (TMA) in renal allografts. A definitive AMR (dAMR) co-presents three diagnostic features. A suspicious AMR (sAMR) is designated when one of the three features is missing. Thirty-two TMA cases overlapping with AMR (AMR+ TMA) were studied, which involved 14 cases of sAMR+ TMA and 18 cases of dAMR+ TMA. Thirty TMA cases free of AMR features (AMR- TMA) were enrolled as control group. The ratio of complete response to treatment was similar between AMR- TMA and AMR+ TMA group (23.3% vs. 12.5%, p = 0.33), or between sAMR+ TMA and dAMR+ TMA group (14.3% vs. 11.1%, p = 0.79). At eight yr post-transplantation, the death-censored graft survival (DCGS) rate of AMR- TMA group was 62.8%, which was significantly higher than 28.0% of AMR+ TMA group (p = 0.01), but similar between sAMR+ TMA and dAMR+ TMA group (30.0% vs. 26.7%, p = 0.92). Overall, the intimal arteritis and the broad HLA (Human leukocyte antigens) mismatches were closely associated with over time renal allograft failure. The AMR+ TMA has inferior long-term graft survival, but grafts with sAMR+ TMA or dAMR+ TMA have similar characteristics and clinical courses. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage

PubMed Central

Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C.; Khadayate, Sanjay; Mas, Valeria R.; Nitsch, Dorothea D.; Wang, Zhen; Norman, Jill T.; Wilcox, Christopher S.; Wheeler, David C.; Leiper, James

2015-01-01

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule–specific Ddah1 knockout (Ddah1PT−/−) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1PT−/− mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. PMID:25855779

Reduced Renal Methylarginine Metabolism Protects against Progressive Kidney Damage.

PubMed

Tomlinson, James A P; Caplin, Ben; Boruc, Olga; Bruce-Cobbold, Claire; Cutillas, Pedro; Dormann, Dirk; Faull, Peter; Grossman, Rebecca C; Khadayate, Sanjay; Mas, Valeria R; Nitsch, Dorothea D; Wang, Zhen; Norman, Jill T; Wilcox, Christopher S; Wheeler, David C; Leiper, James

2015-12-01

Nitric oxide (NO) production is diminished in many patients with cardiovascular and renal disease. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthesis, and elevated plasma levels of ADMA are associated with poor outcomes. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) is a methylarginine-metabolizing enzyme that reduces ADMA levels. We reported previously that a DDAH1 gene variant associated with increased renal DDAH1 mRNA transcription and lower plasma ADMA levels, but counterintuitively, a steeper rate of renal function decline. Here, we test the hypothesis that reduced renal-specific ADMA metabolism protects against progressive renal damage. Renal DDAH1 is expressed predominately within the proximal tubule. A novel proximal tubule-specific Ddah1 knockout (Ddah1(PT-/-)) mouse demonstrated tubular cell accumulation of ADMA and lower NO concentrations, but unaltered plasma ADMA concentrations. Ddah1(PT-/-) mice were protected from reduced kidney tissue mass, collagen deposition, and profibrotic cytokine expression in two independent renal injury models: folate nephropathy and unilateral ureteric obstruction. Furthermore, a study of two independent kidney transplant cohorts revealed higher levels of human renal allograft methylarginine-metabolizing enzyme gene expression associated with steeper function decline. We also report an association among DDAH1 expression, NO activity, and uromodulin expression supported by data from both animal and human studies, raising the possibility that kidney DDAH1 expression exacerbates renal injury through uromodulin-related mechanisms. Together, these data demonstrate that reduced renal tubular ADMA metabolism protects against progressive kidney function decline. Thus, circulating ADMA may be an imprecise marker of renal methylarginine metabolism, and therapeutic ADMA reduction may even be deleterious to kidney function. Copyright © 2015 by the American Society of Nephrology.

Early Renal Involvement in a Girl with Classic Fabry Disease.

PubMed

Perretta, Fernando; Antongiovanni, Norberto; Jaurretche, Sebastián

2017-01-01

Fabry disease is an X-linked lysosomal storage disorder resulting from the deficiency or absence of the enzyme alpha galactosidase A; this defect leads to the systemic accumulation of globotriaosylceramide and its metabolites. Organic involvement in men is well known, but in women it is controversial, mainly due to the random X-chromosome inactivation in each of their cells (Lyon hypothesis). This would explain why women (heterozygotes) present a wide variability in the severity of their phenotype. The manifestations are multisystemic and begin in early childhood, reaching a severe compromise in adulthood. Typical acroparesthesia in hands and feet, gastrointestinal symptoms, angiokeratomas, dyshidrosis, hearing loss, arrhythmias, hypertrophic cardiomyopathy, cerebrovascular accidents, and renal failure can be observed. Nephropathy is one of the major complications of Fabry disease. Glomerular and vascular changes are present before progression to overt proteinuria and decreased glomerular filtration rate, even in pediatric patients. A case of incipient renal involvement in a girl with classic Fabry disease is reported.

Calcineurin inhibitor-induced complement system activation via ERK1/2 signalling is inhibited by SOCS-3 in human renal tubule cells.

PubMed

Loeschenberger, Beatrix; Niess, Lea; Würzner, Reinhard; Schwelberger, Hubert; Eder, Iris E; Puhr, Martin; Guenther, Julia; Troppmair, Jakob; Rudnicki, Michael; Neuwirt, Hannes

2018-02-01

One factor that significantly contributes to renal allograft loss is chronic calcineurin inhibitor (CNI) nephrotoxicity (CIN). Among other factors, the complement (C-) system has been proposed to be involved CIN development. Hence, we investigated the impact of CNIs on intracellular signalling and the effects on the C-system in human renal tubule cells. In a qPCR array, CNI treatment upregulated C-factors and downregulated SOCS-3 and the complement inhibitors CD46 and CD55. Additionally, ERK1/-2 was required for these regulations. Following knock-down and overexpression of SOCS-3, we found that SOCS-3 inhibits ERK1/-2 signalling. Finally, we assessed terminal complement complex formation, cell viability and apoptosis. Terminal complement complex formation was induced by CNIs. Cell viability was significantly decreased, whereas apoptosis was increased. Both effects were reversed under complement component-depleted conditions. In vivo, increased ERK1/-2 phosphorylation and SOCS-3 downregulation were observed at the time of transplantation in renal allograft patients who developed a progressive decline of renal function in the follow-up compared to stable patients. The progressive cohort also had lower total C3 levels, suggesting higher complement activity at baseline. In conclusion, our data suggest that SOCS-3 inhibits CNI-induced ERK1/-2 signalling, thereby blunting the negative control of C-system activation. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Detection of early changes in renal function using 99mTc-MAG3 imaging in a murine model of ischemia-reperfusion injury

PubMed Central

Roberts, John; Chen, Bo; Curtis, Lisa M.; Agarwal, Anupam; Sanders, Paul W.; Zinn, Kurt R.

2012-01-01

Accurate determination of renal function in mice is a major impediment to the use of murine models in acute kidney injury. The purpose of this study was to determine whether early changes in renal function could be detected using dynamic gamma camera imaging in a mouse model of ischemia-reperfusion (I/R) injury. C57BL/6 mice (n = 5/group) underwent a right nephrectomy, followed by either 30 min of I/R injury or sham surgery of the remaining kidney. Dynamic renal studies (21 min, 10 s/frame) were conducted before surgery (baseline) and at 5, 24, and 48 h by injection of 99mTc-mercaptoacetyltriglycine (MAG3; ~1.0 mCi/mouse) via the tail vein. The percentage of injected dose (%ID) in the kidney was calculated for each 10-s interval after MAG3 injection, using standard region of interest analyses. A defect in renal function in I/R-treated mice was detected as early as 5 h after surgery compared with sham-treated mice, identified by the increased %ID (at peak) in the I/R-treated kidneys at 100 s (P < 0.01) that remained significantly higher than sham-treated mice for the duration of the scan until 600 s (P < 0.05). At 48 h, the renal scan demonstrated functional renal recovery of the I/R mice and was comparable to sham-treated mice. Our study shows that using dynamic imaging, renal dysfunction can be detected and quantified reliably as early as 5 h after I/R insult, allowing for evaluation of early treatment interventions. PMID:17634403

Risk Factors for Urinary Tract Infections in Renal Allograft Recipients: Experience of a Tertiary Care Center in Hyderabad, South India.

PubMed

Mohan, M V N L R; Neeraja, M; Sudhaharan, S; Raju, S B; Gangadhar, T; Lakshmi, V

2017-01-01

Renal transplantation is an effective and commonly performed procedure for end-stage renal disease. Urinary tract infections are a major cause of morbidity and mortality in renal transplant patients. As data on postrenal transplant urinary tract infections from the Indian subcontinent are limited, the present study was conducted to estimate the burden of urinary tract infections in this vulnerable group of patients. This was a prospective study on patients undergoing renal transplantation in 2014 at our tertiary hospital in South India with a follow-up of 2 years to evaluate the risk factors for urinary tract infections. The prevalence of urinary tract infections was 41.9% with a male preponderance of 76.9%. Mean age of the 31 patients was 32.4 ± 10.2 years (range: 16-55 years). Gram-negative bacilli were the most common isolates with Escherichia coli being the predominant pathogen (53.3%). All the infections occurred within 1 year of transplantation with delayed graft function ( P < 0.001; confidence interval [CI]: 29.0-96.3) and prolonged hospital stay ( P = 0.0281; CI: 42.1-99.6) being the significant risk factors for acquiring urinary tract infections. Carbapenemase production was noted in 33.3% of isolates and all the Gram-negative organisms isolated in the 1 st month of transplantation were carbapenem-resistant (CR) E. coli . The high rate of carbapenem-resistant organisms in the early posttransplant period is a point of concern, especially with cadaver transplants. Infection control practices and catheter care need to be strictly monitored to minimize the risk for UTI in the immediate posttransplant period.

Lipoxygenase products in the urine correlate with renal function and body temperature but not with acute transplant rejection.

PubMed

Reinhold, Stephan W; Scherl, Thomas; Stölcker, Benjamin; Bergler, Tobias; Hoffmann, Ute; Weingart, Christian; Banas, Miriam C; Kollins, Dmitrij; Kammerl, Martin C; Krüger, Bernd; Kaess, Bernhard; Krämer, Bernhard K; Banas, Bernhard

2013-02-01

Acute transplant rejection is the leading cause of graft loss in the first months after kidney transplantation. Lipoxygenase products mediate pro- and anti-inflammatory actions and thus we aimed to correlate the histological reports of renal transplant biopsies with urinary lipoxygenase products concentrations to evaluate their role as a diagnostic marker. This study included a total of 34 kidney transplant recipients: 17 with an acute transplant rejection and 17 controls. LTE4, LTB4, 12-HETE and 15-HETE concentrations were measured by enzyme immunoassay. Urinary lipoxygenase product concentrations were not significantly changed during an acute allograft rejection. Nevertheless, LTB4 concentrations correlated significantly with the body temperature (P ≤ 0.05) 3 months after transplantation, and 12- and 15-HETE concentrations correlated significantly with renal function (P ≤ 0.05) 2 weeks after transplantation. In conclusion, our data show a correlation for LTB4 with the body temperature 3 months after transplantation and urinary 12- and 15-HETE concentrations correlate positively with elevated serum creatinine concentrations but do not predict acute allograft rejection.

Allograft update: the current status of tissue regulation, procurement, processing, and sterilization.

PubMed

McAllister, David R; Joyce, Michael J; Mann, Barton J; Vangsness, C Thomas

2007-12-01

Allografts are commonly used during sports medicine surgical procedures in the United States, and their frequency of use is increasing. Based on surgeon reports, it is estimated that more than 60 000 allografts were used in knee surgeries by members of the American Orthopaedic Society for Sports Medicine in 2005. In the United States, there are governmental agencies and other regulatory bodies involved in the oversight of tissue banks. In 2005, the Food and Drug Administration finalized its requirements for current good tissue practice and has mandated new rules regarding the "manufacture" of allogenic tissue. In response to well-publicized infections associated with the implantation of allograft tissue, some tissue banks have developed methods to sterilize allograft tissue. Although many surgeons have significant concerns about the safety of allografts, the majority believe that sterilized allografts are safe but that the sterilization process negatively affects tissue biology and biomechanics. However, most know very little about the principles of sterilization and the proprietary processes currently used in tissue banking. This article will review the current status of allograft tissue regulation, procurement, processing, and sterilization in the United States.

Significant impact of R.E.N.A.L. nephrometry score on changes in postoperative renal function early after robot-assisted partial nephrectomy.

PubMed

Miyake, Hideaki; Furukawa, Junya; Hinata, Nobuyuki; Muramaki, Mototsugu; Tanaka, Kazushi; Fujisawa, Masato

2015-06-01

Our objective was to evaluate the significance of the R.E.N.A.L. nephrometry score (RNS)--developed to quantitatively evaluate the complexity of renal tumors in a reproducible manner--in perioperative and renal functional outcomes following robot-assisted partial nephrectomy (RAPN). This study assessed 48 consecutive patients with renal tumors who underwent RAPN. Preoperative RNS for each patient was calculated, and its impact on several parameters associated with perioperative outcomes, including postoperative renal function, was investigated with Spearman's rank correlation test. Mean RNS in the 48 patients was 6.8; of these 48 patients, 21 (43.7%), 24 (50.0%), and three (6.3%) were classified into low-, moderate-, and high-complexity groups, respectively. The RNS was significantly correlated with resected tumor weight and postoperative changes in estimated glomerular filtration rate (eGFR) at both 1 and 4 weeks--but not age, body mass index (BMI), preoperative eGFR, operative time, warm ischemia time, estimated blood loss, postoperative complications, or eGFR-- after RAPN. No component of the RNS (R: radius; E: exophytic/endophytic properties; N: nearness of tumor to the collecting system or sinus; A: anterior/posterior; L: location relative to polar lines) alone had a significant impact on postoperative changes in eGFR at 1 and 4 weeks, whereas resected tumor weight was significantly associated with the R and E subcategories. Measurement of total RNS is useful for predicting renal functional outcomes early after RAPN.

Bone allografting in children

NASA Astrophysics Data System (ADS)

Sadovoy, M. A.; Kirilova, I. A.; Podorognaya, V. T.; Matsuk, S. A.; Novoselov, V. P.; Moskalev, A. V.; Bondarenko, A. V.; Afanasev, L. M.; Gubina, E. V.

2017-09-01

A total of 522 patients with benign and intermediate bone tumors of various locations, aged 1 to 15 years, were operated in the period from 1996 to 2016. To diagnose skeleton tumors, we used clinical observation, X-ray, and, if indicated, tomography and tumor site biopsy. In the extensive bone resection, we performed bone reconstruction with the replacement of a defect with an allograft (bone strips, deproteinized and spongy grafts), sometimes in the combination with bone autografting. After segmental resection, the defects were filled with bone strips in the form of matchstick grafts; the allografts were received from the Laboratory for Tissue Preparation and Preservation of the Novosibirsk Research Institute of Traumatology and Orthopedics. According to the X-ray data, a complete reorganization of bone grafts occurred within 1.5 to 3 years. The long-term result was assessed as good.

Successful Renal Transplantation with Desensitization in Highly Sensitized Patients: A Single Center Experience

PubMed Central

Yoon, Hye Eun; Hyoung, Bok Jin; Hwang, Hyeon Seok; Lee, So Young; Jeon, Youn Joo; Song, Joon Chang; Oh, Eun-Jee; Park, Sun Cheol; Choi, Bum Soon; Moon, In Sung; Kim, Yong Soo

2009-01-01

Intravenous immunoglobulin (IVIG) and/or plasmapheresis (PP) are effective in preventing antibody-mediated rejection (AMR) of kidney allografts, but AMR is still a problem. This study reports our experience in living donor renal transplantation in highly sensitized patients. Ten patients with positive crossmatch tests or high levels of panel-reactive antibody (PRA) were included. Eight patients were desensitized with pretransplant PP and low dose IVIG, and two were additionally treated with rituximab. Allograft function, number of acute rejection (AR) episodes, protocol biopsy findings, and the presence of donor-specific antibody (DSA) were evaluated. With PP/IVIG, six out of eight patients showed good graft function without AR episodes. Protocol biopsies revealed no evidence of tissue injury or C4d deposits. Of two patients with AR, one was successfully treated with PP/IVIG, but the other lost graft function due to de novo production of DSA. Thereafter, rituximab was added to PP/IVIG in two cases. Rituximab gradually decreased PRA levels and the percentage of peripheral CD20+ cells. DSA was undetectable and protocol biopsy showed no C4d deposits. The graft function was stable and there were no AR episodes. Conclusively, desensitization using PP/IVIG with or without rituximab increases the likelihood of successful living donor renal transplantation in sensitized recipients. PMID:19194545

"Resuscitation" of marginal liver allografts for transplantation with machine perfusion technology.

PubMed

Graham, Jay A; Guarrera, James V

2014-08-01

As the rate of medically suitable donors remains relatively static worldwide, clinicians have looked to novel methods to meet the ever-growing demand of the liver transplant waiting lists worldwide. Accordingly, the transplant community has explored many strategies to offset this deficit. Advances in technology that target the ex vivo "preservation" period may help increase the donor pool by augmenting the utilization and improving the outcomes of marginal livers. Novel ex vivo techniques such as hypothermic, normothermic, and subnormothermic machine perfusion may be useful to "resuscitate" marginal organs by reducing ischemia/reperfusion injury. Moreover, other preservation techniques such as oxygen persufflation are explored as they may also have a role in improving function of "marginal" liver allografts. Currently, marginal livers are frequently discarded or can relegate the patient to early allograft dysfunction and primary non-function. Bench to bedside advances are rapidly emerging and hold promise for expanding liver transplantation access and improving outcomes. Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Severe adult burn survivors. What information about skin allografts?

PubMed Central

Gaucher, Sonia; Duchange, Nathalie; Jarraya, Mohamed; Magne, Jocelyne; Rochet, Jean-Michel; Stéphanazzi, Jean; Hervé, Christian; Moutel, Grégoire

2013-01-01

Background and objective During the acute phase of a severe burn, surgery is an emergency. In this situation, human skin allografts constitute an effective temporary skin substitute. However, information about the use of human tissue can not be given to the patients because most of the allografted patients are unconscious due to their injury. Objective This study explored the restitution of information on skin donation to patients who have been skin allografted and who have survived their injury. Method A qualitative study was conducted due to the limited number of patients in ability to be interviewed according to our medical and psychological criteria. Results and discussion Twelve patients who had been treated between 2002 and 2008 were interviewed. Our results show that 10 of them ignored that they had received skin allografts. One of the two patients who knew that they had received allografts knew that skin had been harvested from deceased donor. All patients expressed that there is no information that should not be delivered. They also expressed their relief to have had the opportunity to discuss their case and at being informed during their interview. Their own experience impacted their view in favor of organ and tissue donation. PMID:23229877

EMMPRIN expression is involved in the development of interstitial fibrosis and tubular atrophy in human kidney allografts.

PubMed

Kemmner, Stephan; Schulte, Christian; von Weyhern, Claus Hann; Schmidt, Roland; Baumann, Marcus; Heemann, Uwe; Renders, Lutz; Schmaderer, Christoph

2016-03-01

Matrix metalloproteinases (MMP) are involved in the development of interstitial fibrosis and tubular atrophy (IF/TA) in renal disease. The synthesis of MMP is activated by the extracellular matrix metalloproteinases inducer protein (EMMPRIN). To analyze the role of EMMPRIN in IF/TA, we retrospectively detected EMMPRIN expression in specimens of human renal allografts with various levels of IF/TA. Immunohistochemistry was performed to detect EMMPRIN expression. In a retrospective analysis, a total cohort of 50 specimens were divided according to BANFF-classification into four subgroups (0-3): no, mild (≤ 25%), moderate (26-50%), or severe (>50%) IF/TA. Among other parameters, renal function was analyzed and compared to EMMPRIN expression. In 24 of 38 biopsies, we detected positive EMMPRIN staining. All nephrectomy (n = 12) samples were negative for EMMPRIN. Positive staining in the biopsy samples was detectable on the basolateral side of tubular epithelial cells. EMMPRIN staining was negatively correlated with IF/TA (p < 0.001). We found significant differences between the mean EMMPRIN expression in IF/TA groups 0 and 3 (p = 0.021) and groups 1 and 3 (p = 0.004). Furthermore, we found significant correlations between EMMPRIN staining and renal function. Our data suggest that EMMPRIN is involved in the pathophysiology of IF/TA. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The arginine-creatine pathway is disturbed in children and adolescents with renal transplants.

PubMed

Andrade, Fernando; Rodríguez-Soriano, Juan; Prieto, José Angel; Elorz, Javier; Aguirre, Mireia; Ariceta, Gema; Martin, Sergio; Sanjurjo, Pablo; Aldámiz-Echevarría, Luis

2008-08-01

Cardiovascular disease is an important cause of morbidity in recipients of renal transplants. The aim of the present study was to analyze the status of the arginine-creatine pathway in such patients, given the relationship between the arginine metabolism and both renal function and the methionine-homocysteine cycle. Twenty-nine children and adolescents (median age 13, range 6-18 years), who had received a renal allograft 14.5-82.0 months before, were recruited for the study. On immunosuppressive therapy, all patients evidenced an adequate level of renal function. Plasma concentrations of homocysteine and glycine were significantly higher, whereas urinary excretions of guanidinoacetate and creatine were significantly lower than controls. Urinary excretions of guanidinoacetate and creatine correlated positively with creatinine clearance. Urinary excretion of creatine was negatively correlated with plasma concentration of homocysteine. The demonstration of disturbances in the arginine-creatine pathway in patients with well-functioning renal transplants and in absence of chronic renal failure represents a novel finding. We speculate that the low urinary excretion of guanidinoacetate and creatine is probably related to the nephrotoxic effect of immunosuppressive therapy and to defective methylation associated with the presence of hyperhomocysteinemia.

Renal Impairment and Complication After Kidney Transplant at Queen Rania Abdulla Children's Hospital.

PubMed

Almardini, Reham Issa; Salita, Ghazi Mohamad; Farah, Mahdi Qasem; Katatbeh, Issa Ahmad; Al-Rabadi, Katibh

2017-02-01

Kidney transplant is the treatment of choice for end-stage renal disease, but it is not without complications. We review the medical cause of significant renal impairment and complications that developed after kidney transplant in pediatric patients who required hospital admission and intervention and/or who were followed between 2007 and 2016. A retrospective noninterventional chart review study was conducted in pediatric patients who received a kidney transplant and/or followed at the nephrology clinic at Queen Rania Abdulla Children's Hospital between 2007 and 2016. In this study, 101 pediatric patients received a total of 103 transplants. Forty-eight patients (47%) experienced deterioration of kidney function out of a total of 53 episodes of complications; 37 of these episodes occurred early (0-6 mo after transplant), and 26 episodes occurred late. The causes of kidney function deterioration were surgical complications, acute tubular necrosis, cell- or antibody-mediated rejection, diabetes mellitus, urinary leak, recurrence of original disease, and chronic allograft nephropathy. Thirteen patients experienced graft loss; 50% of these losses were secondary to noncompliance to immunosuppressant medication treatment after transplant. A total of six patients died; 2 (23%) of these deaths occurred in the first week after transplant, whereas the other 4 patients died over a period of 10 years. Pediatric kidney transplant is not without complications; however, most of these complications are treatable and reversible. The most serious complications leading to graft loss and death occur early, in the first week after transplant. Improving immunosuppressant compliance after transplant would prevent 50% of graft losses.

Impact of Prophylactic Versus Preemptive Valganciclovir on Long-term Renal Allograft Outcomes

PubMed Central

Spinner, Michael L.; Saab, Georges; Casabar, Ed; Bowman, Lyndsey J.; Storch, Gregory A.; Brennan, Daniel C.

2010-01-01

Background Both prophylactic and preemptive oral valganciclovir therapy are effective for management of cytomegalovirus (CMV) post renal transplantation in the short-term. The long-term effect of either strategy is less well-defined. Methods We analyzed data on 115 adult recipients previously enrolled in a prospective randomized controlled trial of prophylaxis versus preemptive therapy for CMV. The primary outcome was a composite of freedom from acute rejection, graft loss, or death. Secondary outcomes included individual primary outcomes, post-transplant cardiovascular events, new-onset diabetes mellitus after transplant (NODAT), achievement of goal blood pressure, change in body mass index (BMI), interstitial fibrosis/tubular atrophy (IF/TA) and change in renal function. The analysis period was a 48-months post-transplant or date of death/graft loss, whichever was earlier. Results The primary outcome was similar between groups (83% prophylactic versus 81% preemptive, p = 0.754). The secondary outcomes showed similarities between the prophylactic and preemptive groups. Four patients in the prophylactic group (8%) compared to none in the preemptive group (0%) died with a functioning graft, p=0.043. Conclusions Within the limitations of sample size, our data suggest that either strategy for the management of CMV immediately post-transplantation appears effective for patient and graft survival in the long-term. CMV-management is one of many therapeutic strategies incorporated into a renal transplantation protocol which often differs among institutions, and the decision as to which approach to use remains center and resource specific. The increased incidence of death in the prophylactic group requires further investigation. PMID:20555305

Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats.

PubMed

Quesada, Andrés; Vargas, Félix; Montoro-Molina, Sebastián; O'Valle, Francisco; Rodríguez-Martínez, María Dolores; Osuna, Antonio; Prieto, Isabel; Ramírez, Manuel; Wangensteen, Rosemary

2012-01-01

This study analyzes the fluorimetric determination of alanyl- (Ala), glutamyl- (Glu), leucyl-cystinyl- (Cys) and aspartyl-aminopeptidase (AspAp) urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group) received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG), albumin, and neutrophil gelatinase-associated lipocalin (NGAL). Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p<0.011; r(2)>0.259) with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.

Is early removal of prophylactic ureteric stents beneficial in live donor renal transplantation?

PubMed Central

Indu, K. N.; Lakshminarayana, G.; Anil, M.; Rajesh, R.; George, K.; Ginil, K.; Georgy, M.; Nair, B.; Sudhindran, S.; Appu, T.; Unni, V. N.; Sanjeevan, K. V.

2012-01-01

Prophylactic ureteric stenting has been shown to reduce ureteric leaks and collecting system obstruction following renal transplantation and is in widespread use. However, the optimal time for removal of ureteric stents after renal transplantation remains unclear. Aim of this study was to compare the result of early versus late removal of ureteric stents after kidney transplantation of the laparoscopically retrieved live related donor grafts. Eligible patients were live donor kidney transplant recipients with normal urinary tracts. All recipients underwent extravesical Lich–Gregoire ureteroneocystostomy over 4F/160 cm polyurethane double J stents by a uniform technique. They were randomized on seventh postoperative day for early removal of stents on postoperative day 7 (Group I), or for late removal on postoperative day 28 (Group II). The incidence of urinary tract infections, asymptomatic bacteriuria, and urological complications were compared. Between 2007 and 2009, 130 kidney transplants were performed at one centre of which 100 were enrolled for the study, and 50 each were randomized into the two groups. Donor and recipient age, sex, native renal disease, immunosupression, number of rejection episodes, and antirejection therapy were similar in the two groups. The occurrence of symptomatic urinary tract infection during the follow-up period of 6 months was significantly less in the early stent removal group [5 out of 50 (10%) in Group I, vs 50 out of 15 (30%) in Group II, P=0.02]. Asymptomatic bacteriuria was documented in 2 out of 50 (4%) in Group I and 4 out of 50 (8%) in Group II (P=0.3). There was no statistically significant difference in the rate of ureteric leak, ureteric obstruction, or hematuria in the two groups (P=1.0). We conclude that, in kidney transplant recipients of laparoscopically retrieved live donor grafts, early stent removal at the end of first week reduces the incidence of urinary tract infection without increasing the rate of urine

Histologic damage of lung allografts according to magnitude of acute rejection in the re-isotransplant model.

PubMed

Marui, Tsutomu; Iwata, Hisashi; Shirahashi, Koyo; Matsumoto, Shinsuke; Mizuno, Yoshimasa; Matsui, Masafumi; Takemura, Hirofumi

2008-06-01

Graft damage due to acute rejection has been reported as one of the risk factors in the chronic stage of cardiac and renal allografts. This study was designed to elucidate the histologic changes of grafts after ongoing acute allograft rejection was discontinued in models of lung re-isotransplantation. WKAH rat lungs were orthotopically transplanted into F344 recipients. Three days (3A group) and 5 days (5A group) after the first allotransplantation, the grafts were re-isotransplanted back into the WKAH rats (3RA and 5RA groups, respectively). Five days (5I group) after the first isotransplantation, the grafts were re-isotransplanted back into the WKAH rats (5RI group). The grafts were removed 30 and 60 days after re-isotransplantation and assessed histologically. Typical acute allograft rejection developed in the 3A and 5A groups, and the changes were reduced after re-isotransplantation, although they remained significantly greater in the 5RA group than in the 3RA and 5RI groups. For intimal hyperplasia, the graft score 60 days after re-isotransplantation in the 5RA group was significantly higher than in the 5RI and 3RA groups. The changes in airway inflammation were significantly greater in the 5RA group than in the 3RA and 5RI groups at 60 days. Peribronchiolar fibrosis was significantly more frequent in the 5RA and 3RA groups than in the 5RI group. Acute rejection and airway inflammation corresponded to the magnitude of rejection before retransplantation. Significant intimal hyperplasia developed in severe acute rejection, and peribronchiolar fibrosis occurred after the first acute rejection.

Allelic and Epitopic Characterization of Intra-Kidney Allograft Anti-HLA Antibodies at Allograft Nephrectomy.

PubMed

Milongo, D; Kamar, N; Del Bello, A; Guilbeau-Frugier, C; Sallusto, F; Esposito, L; Dörr, G; Blancher, A; Congy-Jolivet, N

2017-02-01

The reasons for the increased incidence of de novo anti-human leukocyte antibody (HLA) donor-specific antibodies (DSAs) observed after kidney allograft nephrectomy are not fully understood. One advocated mechanism suggests that at graft loss, DSAs are not detected in the serum because they are fixed on the nonfunctional transplant; removal of the kidney allows DSAs to then appear in the blood circulation. The aim of our study was to compare anti-HLA antibodies present in the serum and in the graft at the time of an allograft nephrectomy. Using solid-phase assays, anti-HLA antibodies were searched for in the sera of 17 kidney transplant patients undergoing allograft nephrectomy. No anti-HLA antibodies were detected in the graft if they were not also detected in the serum. Eleven of the 12 patients who had DSAs detected in their sera also had DSAs detected in the grafts. Epitopic analysis revealed that most anti-HLA antibodies detected in removed grafts were directed against the donor. In summary, our data show that all anti-HLA antibodies that were detected in grafts were also detected in the sera. These intragraft anti-HLA antibodies are mostly directed against the donor at an epitopic level but not always at an antigenic level. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

[Clinical characteristics and renal uric acid excretion in early-onset gout patients].

PubMed

Li, Q H; Liang, J J; Chen, L X; Mo, Y Q; Wei, X N; Zheng, D H; Dai, L

2018-03-01

Objective: To investigate clinical characteristics and renal uric acid excretion in early-onset gout patients. Methods: Consecutive inpatients with primary gout were recruited between 2013 and 2017. The patients with gout onset younger than 30 were defined as early-onset group while the others were enrolled as control group. Clinical characteristics and uric acid (UA) indicators were compared between two groups. Results: Among 202 recruited patients, the early-onset group included 36 patients (17.8%). Compared with control group, the early-onset group presented more patients with obesity [13 patients (36.1%) vs. 22 patients (13.3%), P< 0.05], significantly higher serum UA level [(634±124)μmol/L vs.(527±169)μmol/L] and glomerular load of UA[(7.2±2.8)mg·min(-1)·1.73m(-2) vs. (4.4±2.2)mg·min(-1)·1.73m(-2)] and estimated glomerular filtration rate (GFR) [(83±21)ml·min(-1)·1.73m(-2) vs. (67±21)ml·min(-1)·1.73m(-2)] (all P< 0.05), lower fractional excretion of UA [4.4% (3.4%,6.1%) vs. 7.2% (5.2%,9.6%), P< 0.05], whereas 24h urinary UA excretion was comparable [(2 788±882)μmol/1.73m(2) vs. (2 645±1 140)μmol/1.73m(2), P= 0.274]. Subgroup analysis of patients without chronic kidney disease showed significantly lower fractional excretion of UA in the early-onset group [4.5%(3.3%,6.1%) vs. 6.7% (5.1%,8.7%), P< 0.05]. Logistic regression analysis showed that obesity ( OR= 3.25) and fractional excretion of UA less than 7% ( OR= 9.01, all P< 0.05) were risk factors of gout early onset. Conclusion: The gout patients with early-onset younger than 30 present high serum and glomerular load of uric acid which might be due to obesity and relative under-excretion of renal uric acid.

Estimating the usage of allograft in the treatment of major burns.

PubMed

Horner, C W M; Atkins, J; Simpson, L; Philp, B; Shelley, O; Dziewulski, P

2011-06-01

To assess the amount of allograft used in the past treatment of major burns and calculate a figure to guide estimation of the quantity of allograft required to treat future patients and aid resource planning. A retrospective observational study. Records of 143 patients treated with major burns at a regional centre, from January 2004 to November 2008 were accessed with biometric data and quantity of allograft used being recorded. This data was used to calculate an allograft index (cm² allograft used/burn surface area (cm²)) (AI) for each patient. 112 of the 143 patients had complete sets of data, of the 112, 89 patients survived the initial stay in hospital. For all data average AI=1.077 ± 0.090. AI varied according to burn % area with burns < 40% requiring 0.490 cm² allo/cm²burn, increasing in a logarithmic fashion (R²=0.995) for burn areas > 40%. The ability to estimate deceased donor skin requirements based on % body surface area affected is important in the care planning for patients with major burns. Our findings of 0.5 cm² allograft/cm² burn for injuries less than 40% TBSA, increasing to 1.82 cm² allograft/cm² burn for injuries up to 80% TBSA can be used for planning purposes for individual services and for burn disaster planning. Copyright © 2010 Elsevier Ltd and ISBI. All rights reserved.

Automatic allograft bone selection through band registration and its application to distal femur.

PubMed

Zhang, Yu; Qiu, Lei; Li, Fengzan; Zhang, Qing; Zhang, Li; Niu, Xiaohui

2017-09-01

Clinical reports suggest that large bone defects could be effectively restored by allograft bone transplantation, where allograft bone selection acts an important role. Besides, there is a huge demand for developing the automatic allograft bone selection methods, as the automatic methods could greatly improve the management efficiency of the large bone banks. Although several automatic methods have been presented to select the most suitable allograft bone from the massive allograft bone bank, these methods still suffer from inaccuracy. In this paper, we propose an effective allograft bone selection method without using the contralateral bones. Firstly, the allograft bone is globally aligned to the recipient bone by surface registration. Then, the global alignment is further refined through band registration. The band, defined as the recipient points within the lifted and lowered cutting planes, could involve more local structure of the defected segment. Therefore, our method could achieve robust alignment and high registration accuracy of the allograft and recipient. Moreover, the existing contour method and surface method could be unified into one framework under our method by adjusting the lift and lower distances of the cutting planes. Finally, our method has been validated on the database of distal femurs. The experimental results indicate that our method outperforms the surface method and contour method.

[Hemolytic anemia caused by graft-versus-host reaction in ABO-nonidentical renal transplants from blood group O donors].

PubMed

Peces, R; Díaz Corte, C; Navascués, R A

2001-01-01

Acute hemolytic anemia is one of the side effects associated with cyclosporin and tacrolimus therapy, and three mechanisms have been described to account for hemolytic anemia in patients receiving these drugs: drug induced hemolysis, autoimmune hemolysis and alloimmune hemolysis resulting from donor lymphocytes derived from the allograft (passenger lymphocyte syndrome). We report four cases of renal transplant recipients who developed alloimmune hemolytic anemia due to minor ABO incompatibility while under treatment with cyclosporin (two) and tacrolimus (two). The anti-erythrocyte antibodies responsible for hemolysis were of the IgG isotype and showed anti-A or anti-B specificity. These findings suggest that the hemolysis could be related to alloantibodies derived from the clonal development of donor B lymphocytes in the recipients (microchimerism). In summary, hemolytic anemia due to ABO-minor incompatibility occurs infrequently after renal transplantation. Risks are higher for patients A, B or AB blood group receiving an O blood group graft under treatment with cyclosporin or tacrolimus. Follow-up of these patients is warranted for the early detection and optimal management may be achieved by reduction of immunosuppression and change to mycophenolate mofetil.

Immunomodulatory Strategies Directed Towards Tolerance of Vascularized Composite Allografts

PubMed Central

Michel, Sebastian G.; Villani, Vincenzo; Muraglia, Glenn M. La; Torabi, Radbeh; Leonard, David A.; Randolph, Mark A.; Colvin, Robert B.; Yamada, Kazuhiko; Madsen, Joren C.; Cetrulo, Curtis L.; Sachs, David H.

2015-01-01

Background Achieving tolerance of vascularized composite allografts (VCAs) would improve the risk-to-benefit ratio in patients who undergo this life-enhancing, though not life-saving, transplant. Kidney co-transplantation along with a short course of high-dose immunosuppression enables tolerance of heart allografts across a full MHC mismatch. In this study, we investigated whether tolerance of VCA across full MHC disparities could be achieved in animals already tolerant of heart and kidney allografts. Methods Miniature swine that were tolerant of heart and/or kidney allografts long-term underwent transplantation of myocutaneous VCA across the same MHC barrier. Prior to VCA transplant, Group 1 (n=3) underwent Class I-mismatched kidney transplantation; Group 2 (n=3) underwent two sequential Class I-mismatched kidney transplantations; Group 3 (n=2) underwent haploidentical MHC-mismatched heart/kidney transplantation; and Group 4 (n=2) underwent full MHC-mismatched heart/kidney transplantation. Results All three animals in Group 1 and two of three animals in Group 2 showed skin rejection ≤85 days; one animal in Group 2 showed prolonged skin survival >200 days. Animals in Groups 3 and 4 showed skin rejection ≤30 days and regained in vitro evidence of donor responsiveness. Conclusion This is the first pre-clinical study in which hearts, kidneys, and VCAs have been transplanted into the same recipient. Despite VCA rejection, tolerance of heart and kidney allografts was maintained. These results suggest that regulatory tolerance of skin is possible but not generally achieved by the same level of immunomodulation that is capable of inducing tolerance of heart and kidney allografts. Achieving tolerance of skin may require additional immunomodulatory therapies. PMID:25757218

Arthroscopic single-bundle anterior cruciate ligament reconstruction with six-strand hamstring tendon allograft versus bone-patellar tendon-bone allograft.

PubMed

Dai, Chengliang; Wang, Fei; Wang, Xiaomeng; Wang, Ruipeng; Wang, Shengjie; Tang, Shiyu

2016-09-01

The aim of this study was to compare the clinical outcomes of arthroscopic single-bundle anterior cruciate ligament (ACL) reconstruction with six-strand hamstring tendon (HT) allograft versus bone-patellar tendon-bone (BPTB) allograft. The prospective randomized controlled trial was included 129 patients. Sixty-nine patients received reconstruction with six-strand HT allografts (HT group), whereas 60 patients with BPTB allografts (BPTB group). Outcome assessment included re-rupture findings, International Knee Documentation Committee (IKDC) scores, Lysholm scores, KT-1000 arthrometer, Lachman test, pivot-shift test, range of motion (ROM) and single-leg hop test. At a mean follow-up of 52 months, 113 patients (HT group, 61 patients; BPTB group, 52 patients) completed a minimum 4-year follow-up. Four patients in HT group and six in BPTB group experienced ACL re-rupture (6.2 vs. 10.3 %) and received revision surgery. Significant between-group differences were observed in KT-1000 outcomes and pivot-shift test 1 (1.2 ± 1.5 vs. 1.8 ± 1.3, p = 0.025; positive rate 6.5 vs. 18.9 %, p = 0.036), 2 (1.1 ± 1.4 vs. 1.6 ± 1.2, p = 0.044; 8.1 vs. 20.7 %, p = 0.039), 4 (1.1 ± 1.5 vs. 1.7 ± 1.4, p = 0.031; 9.7 vs. 25 %, p = 0.012) years postoperatively. The outcomes between the two groups were comparable in terms of IKDC scores, Lysholm scores, Lachman test, ROM and single-leg hop test. Six-strand HT allograft achieved superior anteroposterior and rotational stability after single-bundle ACL reconstruction. It is a reasonable graft substitute for ACL reconstruction. II.

Intragraft Molecular Pathways Associated with Tolerance Induction in Renal Transplantation.

PubMed

Gallon, Lorenzo; Mathew, James M; Bontha, Sai Vineela; Dumur, Catherine I; Dalal, Pranav; Nadimpalli, Lakshmi; Maluf, Daniel G; Shetty, Aneesha A; Ildstad, Suzanne T; Leventhal, Joseph R; Mas, Valeria R

2018-02-01

The modern immunosuppression regimen has greatly improved short-term allograft outcomes but not long-term allograft survival. Complications associated with immunosuppression, specifically nephrotoxicity and infection risk, significantly affect graft and patient survival. Inducing and understanding pathways underlying clinical tolerance after transplantation are, therefore, necessary. We previously showed full donor chimerism and immunosuppression withdrawal in highly mismatched allograft recipients using a bioengineered stem cell product (FCRx). Here, we evaluated the gene expression and microRNA expression profiles in renal biopsy samples from tolerance-induced FCRx recipients, paired donor organs before implant, and subjects under standard immunosuppression (SIS) without rejection and with acute rejection. Unlike allograft samples showing acute rejection, samples from FCRx recipients did not show upregulation of T cell- and B cell-mediated rejection pathways. Gene expression pathways differed slightly between FCRx samples and the paired preimplantation donor organ samples, but most of the functional gene networks overlapped. Notably, compared with SIS samples, FCRx samples showed upregulation of genes involved in pathways, like B cell receptor signaling. Additionally, prediction analysis showed inhibition of proinflammatory regulators and activation of anti-inflammatory pathways in FCRx samples. Furthermore, integrative analyses (microRNA and gene expression profiling from the same biopsy sample) identified the induction of regulators with demonstrated roles in the downregulation of inflammatory pathways and maintenance of tissue homeostasis in tolerance-induced FCRx samples compared with SIS samples. This pilot study highlights the utility of molecular intragraft evaluation of pathways related to FCRx-induced tolerance and the use of integrative analyses for identifying upstream regulators of the affected downstream molecular pathways. Copyright © 2018 by the

[Treatment of an old Achilles tendon rupture with allografts. Report of case series].

PubMed

Matus-Jiménez, J; Martínez-Arredondo, H

2011-01-01

Rupture of Achilles tendon occurs at 2-6 cm from its attachment in the calcaneus; its frequency is estimated at 7-18 cases per 100,000 population in the United States and it occurs more frequently in males. The diagnosis is made clinically and with ultrasound or magnetic resonance imaging and treatment may be divided into acute or late. We present herein the use of allograft to treat patients with ruptures more than six weeks old; several techniques were used depending on the rupture site and the available allograft. Ten plasties were performed in ten patients with ruptures that occurred a mean of 8 months back; early rehabilitation was instituted and weight bearing was allowed at 4 weeks with a brace, which was removed at 12 weeks; patients could run at 12 weeks. Four wound dehiscence complications were reported, which resolved with second intention healing without the need for any other surgery, with good results and patient satisfaction.

Assessment of nerve regeneration across nerve allografts treated with tacrolimus.

PubMed

Haisheng, Han; Songjie, Zuo; Xin, Li

2008-01-01

Although regeneration of nerve allotransplant is a major concern in the clinic, there have been few papers quantitatively assessing functional recovery of animals' nerve allografts in the long term. In this study, functional recovery, histopathological study, and immunohistochemistry changes of rat nerve allograft with FK506 were investigated up to 12 weeks without slaughtering. C57 and SD rats were used for transplantation. The donor's nerve was sliced and transplanted into the recipient. The sciatic nerve was epineurally sutured with 10-0 nylon. In total, 30 models of transplantation were performed and divided into 3 groups that were either treated with FK506 or not. Functional recovery of the grafted nerve was serially assessed by the pin click test, walking track analysis and electrophysiological evaluations. A histopathological study and immunohistochemistry study were done in the all of the models. Nerve allografts treated with FK506 have no immune rejection through 12 weeks. Sensibility had similarly improved in both isografts and allografts. There has been no difference in each graft. Walk track analysis demonstrates significant recovery of motor function of the nerve graft. No histological results of difference were found up to 12 weeks in each graft. In the rodent nerve graft model, FK506 prevented nerve allograft rejection across a major histocompatibility barrier. Sensory recovery seems to be superior to motor function. Nerve isograft and allograft treated with FK506 have no significant difference in function recovery, histopathological result, and immunohistochemistry changes.

Central memory CD8+ T lymphocytes mediate lung allograft acceptance

PubMed Central

Krupnick, Alexander Sasha; Lin, Xue; Li, Wenjun; Higashikubo, Ryuiji; Zinselmeyer, Bernd H.; Hartzler, Hollyce; Toth, Kelsey; Ritter, Jon H.; Berezin, Mikhail Y.; Wang, Steven T.; Miller, Mark J.; Gelman, Andrew E.; Kreisel, Daniel

2014-01-01

Memory T lymphocytes are commonly viewed as a major barrier for long-term survival of organ allografts and are thought to accelerate rejection responses due to their rapid infiltration into allografts, low threshold for activation, and ability to produce inflammatory mediators. Because memory T cells are usually associated with rejection, preclinical protocols have been developed to target this population in transplant recipients. Here, using a murine model, we found that costimulatory blockade–mediated lung allograft acceptance depended on the rapid infiltration of the graft by central memory CD8+ T cells (CD44hiCD62LhiCCR7+). Chemokine receptor signaling and alloantigen recognition were required for trafficking of these memory T cells to lung allografts. Intravital 2-photon imaging revealed that CCR7 expression on CD8+ T cells was critical for formation of stable synapses with antigen-presenting cells, resulting in IFN-γ production, which induced NO and downregulated alloimmune responses. Thus, we describe a critical role for CD8+ central memory T cells in lung allograft acceptance and highlight the need for tailored approaches for tolerance induction in the lung. PMID:24569377

Allograft reconstruction after resection of malignant tumors of the scapula.

PubMed

Mnaymneh, Walid A; Temple, H Thomas; Malinin, Theodore I

2002-12-01

The oncologic and functional outcomes of six patients who had scapular allograft reconstruction after scapulectomy for malignant tumors were reviewed. Five patients had Stage IIB and one patient had Stage IB tumors. Total scapulectomy was done in five patients, and partial scapulectomy (glenoid and neck) was done in one patient. Frozen glycerolized scapular allografts were implanted and fixed with plates and screws. The scapular muscles were reattached to the allograft. Tendon reconstruction to replace the excised muscles was done in two patients. The patients were followed up for an average of 3.8 years (range, 2-6 years). Cosmesis, elbow, and hand function were good in all patients. There were no infections, nonunions, or shoulder dislocations. One patient fractured the body of the allograft after a fall. One patient had local recurrence and had scapulectomy 5 years postoperatively. Two patients died 3 and 5 years postoperatively with lung metastases but with functioning grafts. The mean functional result using the Musculoskeletal Tumor Society functional score was 82 (range, 77-87). In this series, scapular allograft reconstruction restored cosmesis, shoulder stability, and function. Preservation or reconstruction of rotator cuff muscles is recommended.

Imaging mouse lung allograft rejection with 1H MRI

PubMed Central

Guo, Jinbang; Huang, Howard J.; Wang, Xingan; Wang, Wei; Ellison, Henry; Thomen, Robert P.; Gelman, Andrew E.; Woods, Jason C.

2014-01-01

Purpose To demonstrate that longitudinal, non-invasive monitoring via MRI can characterize acute cellular rejection (ACR) in mouse orthotopic lung allografts. Methods Nineteen Balb/c donor to C57BL/6 recipient orthotopic left lung transplants were performed, further divided into control-Ig vs anti-CD4/anti-CD8 treated groups. A two-dimensional multi-slice gradient-echo pulse sequence synchronized with ventilation was used on a small-animal MR scanner to acquire proton images of lung at post-operative days 3, 7 and 14, just before sacrifice. Lung volume and parenchymal signal were measured, and lung compliance was calculated as volume change per pressure difference between high and low pressures. Results Normalized parenchymal signal in the control-Ig allograft increased over time, with statistical significance between day 14 and day 3 post transplantation (0.046→0.789, P < 0.05), despite large inter-mouse variations; this was consistent with histopathologic evidence of rejection. Compliance of the control-Ig allograft decreased significantly over time (0.013→0.003, P < 0.05), but remained constant in mice treated with anti-CD4/anti-CD8 antibodies. Conclusion Lung allograft rejection in individual mice can be monitored by lung parenchymal signal changes and by lung compliance through MRI. Longitudinal imaging can help us better understand the time course of individual lung allograft rejection and response to treatment. PMID:24954886

Imaging mouse lung allograft rejection with (1)H MRI.

PubMed

Guo, Jinbang; Huang, Howard J; Wang, Xingan; Wang, Wei; Ellison, Henry; Thomen, Robert P; Gelman, Andrew E; Woods, Jason C

2015-05-01

To demonstrate that longitudinal, noninvasive monitoring via MRI can characterize acute cellular rejection in mouse orthotopic lung allografts. Nineteen Balb/c donor to C57BL/6 recipient orthotopic left lung transplants were performed, further divided into control-Ig versus anti-CD4/anti-CD8 treated groups. A two-dimensional multislice gradient-echo pulse sequence synchronized with ventilation was used on a small-animal MR scanner to acquire proton images of lung at postoperative days 3, 7, and 14, just before sacrifice. Lung volume and parenchymal signal were measured, and lung compliance was calculated as volume change per pressure difference between high and low pressures. Normalized parenchymal signal in the control-Ig allograft increased over time, with statistical significance between day 14 and day 3 posttransplantation (0.046→0.789; P < 0.05), despite large intermouse variations; this was consistent with histopathologic evidence of rejection. Compliance of the control-Ig allograft decreased significantly over time (0.013→0.003; P < 0.05), but remained constant in mice treated with anti-CD4/anti-CD8 antibodies. Lung allograft rejection in individual mice can be monitored by lung parenchymal signal changes and by lung compliance through MRI. Longitudinal imaging can help us better understand the time course of individual lung allograft rejection and response to treatment. © 2014 Wiley Periodicals, Inc.

Characteristics of long-term live-donor pediatric renal transplant survivors: a single-center experience.

PubMed

El-Husseini, Amr A; Foda, Mohamed A; Osman, Yasser M; Sobh, Mohamed A

2006-05-01

To study the characteristics and the predictors of survival observed in our pediatric live-donor renal transplant recipients with an allograft that functioned for more than 10 yr. One hundred fifteen children underwent renal transplantation between 1976 and 1995. Of these, 30 had functioning allografts for more than 10 yr (range, 11-18). The patients included 18 males and 12 females, with a mean age at transplantation of 13 yr (range, 5-18). Characteristics of the patients, data on graft survival, and determinants of outcome were obtained by reviewing all medical charts. At most recent follow-up (January 2005), the mean daily dose of azathioprine was 1.2 mg/kg (range, 1-2) and that of prednisone was 0.16 mg/kg (range, 0.1-0.2). Mean creatinine clearance was 72 mL/min per 1.73 m(2) (range, 45-112). Acute rejection occurred in 14 (47%) patients. Seven patients had one episode, five had two episodes, and two had three episodes of acute rejection. Three patients (10%) developed malignancy. A substantial proportion of patients (44%) were short, with a height standard deviation score (SDS) less than -1.88, which is below the third percentile for age and gender. One quarter of the patients, more commonly the females, were obese. Other complications included osteoporosis in 16 (53%) patients, avascular bone necrosis in four (13%), post-transplantation diabetes mellitus in three (10%), and hypertension in 18 (60%). Twelve (40%) patients were married and 27% had children post-transplantation. The independent determinants of long-term graft survival were acute rejection and post-transplant hypertension. Despite good renal function, long-term pediatric renal transplant survivors are at risk of significant morbidity. The determinants of long-term graft survival are acute rejection and post-transplant hypertension.

Elevated fibroblast growth factor 23 levels as a cause of early post-renal transplantation hypophosphatemia.

PubMed

Han, S Y; Hwang, E A; Park, S B; Kim, H C; Kim, H T

2012-04-01

Hypophosphatemia is a common complication after renal transplantation. Hyperparathyroidism has long been thought to be the cause, but hypophosphatemia can persist after high parathyroid hormone (PTH) levels normalize. Furthermore, calcitriol levels remain inappropriately low after transplantation, suggesting that mechanisms other than PTH contribute. Fibroblast growth factor 23 (FGF-23) induces phosphaturia, inhibits calcitriol synthesis, and accumulates in chronic kidney disease. We performed prospective study to investigate if FGF-23 early after renal transplantation contributes to hypophosphatemia. We measured FGF-23 levels before and at 1, 2, 4, and 12 weeks after transplantation in 20 renal transplant recipients. Serum creatinine, calcium (Ca), phosphate (Pi), intact PTH (PTH), and 1,25-dihydroxy vitamin D (1,25(OH)(2)VitD) were measured at the same time. FGF-23 levels decreased by 97% at 4 weeks after renal transplantation (PRT) (7,471 ± 11,746 vs 225 ± 295 pg/mL; P < .05) but were still above normal. PTH and Pi levels also decreased significantly after renal transplantation, and Ca and 1,25(OH)(2)VitD slightly increased. PRT hypophosphatemia of <2.5 mg/dL developed in 15 (75%) and 12 (60%) patients at 4 weeks and 12 weeks respectively. Compared with nonhypophosphatemic patients, the levels of FGF-23 of hypophosphatemic patients were higher (303 ± 311 vs 10 ± 6.9 pg/mL; P = .02) at 4 weeks PRT. FGF-23 levels were inversely correlated with Pi (r(2) = 0.406; P = .011); PTH was not independently associated with Pi (r(2) = 0.132; P = .151). FGF-23 levels decrease dramatically after renal transplantation. During the early PRT period, Pi rapidly decreased, suggesting that FGF-23 is cleared by the kidney, but residual FGF-23 may contribute to the PRT hypophosphatemia. FGF-23, but not PTH levels, was independently associated with PRT hypophosphatemia. Copyright © 2012 Elsevier Inc. All rights reserved.

Osteoinductive effect of bone bank allografts on human osteoblasts in culture.

PubMed

de la Piedra, Concepción; Vicario, Carlos; de Acuña, Lucrecia Rodríguez; García-Moreno, Carmen; Traba, Maria Luisa; Arlandis, Santiago; Marco, Fernando; López-Durán, Luis

2008-02-01

Incorporation of a human bone allograft requires osteoclast activity and growth of recipient osteoblasts. The aim of this work was to study the effects produced by autoclavated and -80 degrees C frozen bone allografts on osteoblast proliferation and synthesis of interleukin 6 (IL6), activator of bone resorption, aminoterminal propeptide of procollagen I (PINP), marker of bone matrix formation, and osteoprotegerin (OPG), inhibitor of osteoclast activity and differentiation. Allografts were obtained from human femoral heads. Human osteoblasts were cultured in the presence (problem group) or in the absence (control group) of allografts during 15 days. Allografts produced a decrease in osteoblast proliferation in the first week of the experiment, and an increase in IL6 mRNA, both at 3 h and 2 days, and an increase in the IL6 released to the culture medium the second day of the experiment. We found a decrease in OPG released to the culture on the 2nd and fourth days. These results suggest an increase in bone resorption and a decrease in bone formation in the first week of the experiment. In the second week, allografts produced an increase in osteoblast proliferation and PINP release to the culture medium, indicating an increase in bone formation; an increase in OPG released to the culture medium, which would indicate a decrease in bone resorption; and a decrease in IL6, indicating a decrease in bone resorption stimulation. These results demonstrate that autoclavated and -80 degrees C frozen bone allografts produce in bone environment changes that regulate their own incorporation to the recipient bone.

Can Skin Allograft Occasionally Act as a Permanent Coverage in Deep Burns? A Pilot Study.

PubMed

Rezaei, Ezzatollah; Beiraghi-Toosi, Arash; Ahmadabadi, Ali; Tavousi, Seyed Hassan; Alipour Tabrizi, Arash; Fotuhi, Kazem; Jabbari Nooghabi, Mehdi; Manafi, Amir; Ahmadi Moghadam, Shokoofeh

2017-01-01

Skin allograft is the gold standard of wound coverage in patients with extensive burns; however, it is considered as a temporary wound coverage and rejection of the skin allograft is considered inevitable. In our study, skin allograft as a permanent coverage in deep burns is evaluated. Skin allograft survival was assessed in 38 patients from March 2009 to March 2014, retrospectively. Because of the lack of tissue specimen from the skin donors, patients with long skin allograft survival in whom the gender of donor and recipient of allograft was the same were excluded. Seven cases with skin allograft longevity and opposite gender in donor and recipient were finally enrolled. A polymerase chain reaction (PCR) test on the biopsy specimen from recipients and donors were undertaken. PCR on the biopsy specimen from recipients confirmed those specimens belong to the donors. All patients received allograft from the opposite sex. Two (28.57%) patients received allograft from their first-degree blood relatives, and in one (14.29%) case, the allograft was harvested from an alive individual with no blood relation. The rest were harvested from multiorgan donors. In eight months of follow up, no clinical evidence of graft rejection was noted. Long term persistence of skin allograft in patients is worthy of more attention. Further studies An increase in knowledge of factors influencing this longevity could realize the dream of burn surgeons to achieve a permanent coverage other than autograft for major burn patients.

Incidence of bacterial contamination and predisposing factors during bone and tendon allograft procurement.

PubMed

Terzaghi, Clara; Longo, Alessia; Legnani, Claudio; Bernasconi, Davide Paolo; Faré, Maristella

2015-03-01

The aim of this study was to analyze factors contributing to bacteriological contamination of bone and tendon allograft. Between 2008 and 2011, 2,778 bone and tendon allografts obtained from 196 organ and tissue donors or tissue donors only were retrospectively analysed. Several variables were taken into account: donor type (organ and tissue donors vs. tissue donor), cause of death, time interval between death and tissue procurement, duration of the procurement procedure, type of allografts, number of team members, number of trainees members, associated surgical procedures, positivity to haemoculture, type of procurement. The overall incidence of graft contamination was 23 %. The cause of death, the procurement time, the duration of procurement, the associated surgical procedures were not associated with increased risk of contamination. Significant effect on contamination incidence was observed for the number of staff members performing the procurement. In addition, our study substantiated significantly higher contamination rate among bone allografts than from tendon grafts. According to these observations, in order to minimize the contamination rate of procured musculoskeletal allografts, we recommend appropriate donor selection, use of standard sterile techniques, immediate packaging of each allograft to reduce graft exposure. Allograft procurement should be performed by a small surgical team.

Graft-Derived CCL2 Increases Graft Injury During Antibody-Mediated Rejection of Cardiac Allografts

PubMed Central

Abe, Toyofumi; Su, Charles A.; Iida, Shoichi; Baldwin, William M.; Nonomura, Norio; Takahara, Shiro; Fairchild, Robert L.

2015-01-01

The pathogenic role of macrophages in antibody-mediated rejection (AMR) remains unclear. Monocyte chemoattractant protein-1 (MCP-1/CCL2) is a potent chemotactic factor for monocytes and macrophages. The current studies used a murine model of AMR to investigate the role of graft-derived CCL2 in AMR and how macrophages may participate in antibody-mediated allograft injury. B6.CCR5−/−/CD8−/− recipients rejected MHC-mismatched wild type A/J allografts with high donor-reactive antibody titers and diffuse C4d deposition in the large vessels and myocardial capillaries, features consistent with AMR. In contrast, A/J.CCL2−/− allografts induced low donor-reactive antibody titers and C4d deposition at day 7 post-transplant. Decreased donor-reactive CD4 T cells producing IFN-γ were induced in response to A/J.CCL2−/− vs. wild type allografts. Consequently, A/J.CCL2−/− allograft survival was modestly but significantly longer than A/J allografts. Macrophages purified from wild type allografts expressed high levels of IL-1β and IL-12p40 and this expression and the numbers of classically activated macrophages were markedly reduced in CCL2-deficient allografts on day 7. The results indicate that allograft-derived CCL2 plays an important role in directing classically activated macrophages into allografts during AMR and that macrophages are important contributors to the inflammatory environment mediating graft tissue injury in this pathology, suggesting CCL2 as a therapeutic target for AMR. PMID:25040187

Subclinical rejection in renal transplants is associated with low serum mannose-binding lectin levels.

PubMed

Ibernon, Meritxell; Moreso, Francesc; Serón, Daniel

2011-08-01

Surveillance biopsies have contributed to the understanding of the natural history of renal allograft lesions. Subclinical rejection, defined as the presence of histological lesions, indistinguishable from acute rejection in stable grafts, is associated with progression of interstitial fibrosis and tubular atrophy. The prevalence of subclinical rejection has decreased as more powerful immunosuppressive treatments have been introduced, suggesting that subclinical rejection represents the degree of control of the alloimmune response. However, non-immune factors such as donor age are also associated with the prevalence of subclinical rejection, suggesting that kidneys from older donors are more susceptible to insult and have a reduced capacity for tissue regeneration. Innate immunity has a crucial role in the modulation of the inflammatory response during infection and tissue damage. Mannose-binding lectin (MBL) is an innate immune protein, the polymorphisms of which are associated with infection, low-grade inflammation, diabetes, and cardiovascular disease. However, the relationship between MBL and disease is complex. For example, low MBL level is associated with higher risk for diabetes, whereas in patients with diabetes, high MBL level is associated with more severe renal damage. In renal transplant patients, low MBL levels are associated with an increased prevalence of infection and diabetes, whereas high MBL levels are associated with shortened graft survival. Although MBL is not clearly associated with prevalence of acute rejection, surveillance biopsy studies have shown that low MBL levels are associated with subclinical rejection in kidney and the heart, suggesting that MBL modulates the injury-repair process of the allograft.

Subclinical rejection in renal transplants is associated with low serum mannose-binding lectin levels

PubMed Central

Ibernon, Meritxell; Moreso, Francesc; Serón, Daniel

2011-01-01

Surveillance biopsies have contributed to the understanding of the natural history of renal allograft lesions. Subclinical rejection, defined as the presence of histological lesions, indistinguishable from acute rejection in stable grafts, is associated with progression of interstitial fibrosis and tubular atrophy. The prevalence of subclinical rejection has decreased as more powerful immunosuppressive treatments have been introduced, suggesting that subclinical rejection represents the degree of control of the alloimmune response. However, non-immune factors such as donor age are also associated with the prevalence of subclinical rejection, suggesting that kidneys from older donors are more susceptible to insult and have a reduced capacity for tissue regeneration. Innate immunity has a crucial role in the modulation of the inflammatory response during infection and tissue damage. Mannose-binding lectin (MBL) is an innate immune protein, the polymorphisms of which are associated with infection, low-grade inflammation, diabetes, and cardiovascular disease. However, the relationship between MBL and disease is complex. For example, low MBL level is associated with higher risk for diabetes, whereas in patients with diabetes, high MBL level is associated with more severe renal damage. In renal transplant patients, low MBL levels are associated with an increased prevalence of infection and diabetes, whereas high MBL levels are associated with shortened graft survival. Although MBL is not clearly associated with prevalence of acute rejection, surveillance biopsy studies have shown that low MBL levels are associated with subclinical rejection in kidney and the heart, suggesting that MBL modulates the injury–repair process of the allograft. PMID:25018901

3D perfusion bioreactor-activated porous granules on implant fixation and early bone formation in sheep.

PubMed

Ding, Ming; Henriksen, Susan S; Martinetti, Roberta; Overgaard, Søren

2017-11-01

Early fixation of total joint arthroplasties is crucial for ensuring implant survival. An alternative bone graft material in revision surgery is needed to replace the current gold standard, allograft, seeing that the latter is associated with several disadvantages. The incubation of such a construct in a perfusion bioreactor has been shown to produce viable bone graft materials. This study aimed at producing larger amounts of viable bone graft material (hydroxyapatite 70% and β-tricalcium-phosphate 30%) in a novel perfusion bioreactor. The abilities of the bioreactor-activated graft material to induce early implant fixation were tested in a bilateral implant defect model in sheep, with allograft as the control group. Defects were bilaterally created in the distal femurs of the animals, and titanium implants were inserted. The concentric gaps around the implants were randomly filled with either allograft, granules, granules with bone marrow aspirate or bioreactor-activated graft material. Following an observation time of 6 weeks, early implant fixation and bone formation were assessed by micro-CT scanning, mechanical testing, and histomorphometry. Bone formations were seen in all groups, while no significant differences between groups were found regarding early implant fixation. The microarchitecture of the bone formed by the synthetic graft materials resembled that of allograft. Histomorphometry revealed that allograft induced significantly more bone and less fibrous tissue (p < 0.05). In conclusion, bone formation was observed in all groups, while the bioreactor-activated graft material did not reveal additional effects on early implant fixation comparable to allograft in this model. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2465-2476, 2017. © 2016 Wiley Periodicals, Inc.

The use of the inferior epigastric artery for accessory lower polar artery revascularization in live donor renal transplantation.

PubMed

El-Sherbiny, M; Abou-Elela, A; Morsy, A; Salah, M; Foda, A

2008-01-01

This study describes the surgical technique and outcomes of live donor renal allografts with multiple arteries in which the lower polar artery was anastomosed to the inferior epigastric artery after declamping. Between 1988 and 2004, 477 consecutive live donor renal transplants were performed, including 429 with single and 48 with multiple arteries. Anastomosis of the lower polar artery to the inferior epigastric artery was used for 15 grafts with multiple arteries. Successful revascularization of all areas of the transplanted graft was confirmed by Doppler ultrasonography in most patients and radionuclide renal scanning +/- MRA in some patients. In live donor renal transplantation with multiple arteries, the anastomosis of the lower polar artery to the inferior epigastric artery after declamping avoids prolongation of the ischemia time that occurs with other surgical and microsurgical techniques of intracorporeal and ex vivo surgeries.

Therapeutic lymphangiogenesis ameliorates established acute lung allograft rejection

PubMed Central

Cui, Ye; Liu, Kaifeng; Monzon-Medina, Maria E.; Padera, Robert F.; Wang, Hao; George, Gautam; Toprak, Demet; Abdelnour, Elie; D’Agostino, Emmanuel; Goldberg, Hilary J.; Perrella, Mark A.; Forteza, Rosanna Malbran; Rosas, Ivan O.; Visner, Gary; El-Chemaly, Souheil

2015-01-01

Lung transplantation is the only viable option for patients suffering from otherwise incurable end-stage pulmonary diseases such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. Despite aggressive immunosuppression, acute rejection of the lung allograft occurs in over half of transplant recipients, and the factors that promote lung acceptance are poorly understood. The contribution of lymphatic vessels to transplant pathophysiology remains controversial, and data that directly address the exact roles of lymphatic vessels in lung allograft function and survival are limited. Here, we have shown that there is a marked decline in the density of lymphatic vessels, accompanied by accumulation of low-MW hyaluronan (HA) in mouse orthotopic allografts undergoing rejection. We found that stimulation of lymphangiogenesis with VEGF-C156S, a mutant form of VEGF-C with selective VEGFR-3 binding, alleviates an established rejection response and improves clearance of HA from the lung allograft. Longitudinal analysis of transbronchial biopsies from human lung transplant recipients demonstrated an association between resolution of acute lung rejection and decreased HA in the graft tissue. Taken together, these results indicate that lymphatic vessel formation after lung transplantation mediates HA drainage and suggest that treatments to stimulate lymphangiogenesis have promise for improving graft outcomes. PMID:26485284

Swab or biopsy samples for bioburden testing of allograft musculoskeletal tissue?

PubMed

Varettas, Kerry

2014-12-01

Swab and biopsy samples of allograft musculoskeletal tissue are most commonly collected by tissue banks for bacterial and fungal bioburden testing. An in vitro study was performed using the National Committee for Clinical Laboratory Standards standard 'Quality control of microbiological transport systems' (2003) to validate and evaluate the recovery of six challenge organisms from swab and biopsy samples of allograft musculoskeletal tissue. On average, 8.4 to >100 and 7.2 to >100 % of the inoculum was recovered from swab and biopsy samples respectively. A retrospective review of donor episodes was also performed, consisting of paired swab and biopsy samples received in this laboratory during the period 2001-2012. Samples of allograft femoral heads were collected from living donors during hip operations. From the 3,859 donor episodes received, 21 paired swab and biopsy samples each recovered an isolate, 247 swab samples only and 79 biopsy samples only were culture positive. Low numbers of challenge organisms were recovered from inoculated swab and biopsy samples in the in vitro study and validated their use for bioburden testing of allograft musculoskeletal tissue. Skin commensals were the most common group of organisms isolated during a 12-year retrospective review of paired swab and biopsy samples from living donor allograft femoral heads. Paired swab and biopsy samples are a suitable representative sample of allograft musculoskeletal tissue for bioburden testing.

Scapular allograft reconstruction after total scapulectomy: surgical technique and functional results.

PubMed

Capanna, Rodolfo; Totti, Francesca; Van der Geest, Ingrid C M; Müller, Daniel A

2015-08-01

Scapular allograft reconstruction after total scapulectomy preserving the rotator cuff muscles is an oncologically safe procedure and results in good functional outcome with a low complication rate. The data of 6 patients who underwent scapular allograft reconstruction after a total scapulectomy for tumor resection were retrospectively reviewed. At least 1 of the rotator cuff muscles was preserved and the size-matched scapular allograft fixed to the residual host acromion with a plate and screws. The periscapular muscles and the residual joint capsule were sutured to the corresponding insertions of the allograft. The mean follow-up was 5.5 years (range, 24-175 months). In all patients, a wide surgical margin was achieved. The average functional scores were 20 points for the International Society of Limb Salvage score and 60 points for the American Shoulder and Elbow Surgeons score. Mean active shoulder flexion of 60° (range, 30°-90°) and mean active abduction of 62° (range, 30°-90°) were achieved. During the follow-up, 1 patient (16.6%) had a local recurrence and lung metastasis, whereas the remaining 5 patients (83.3%) were disease free. Two breakages of the osteosynthesis and 2 allograft fractures were observed, necessitating a revision surgery in 2 cases (33.3%). In this series, no infection, allograft resorption, or shoulder instability occurred. Allograft substitution of a completely removed scapula is an oncologically safe procedure, with good functional results, avoiding common complications in prosthetic replacements such as infection and dislocation of the shoulder joint. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Assessment of tissue allograft safety monitoring with administrative healthcare databases: a pilot project using Medicare data.

PubMed

Dhakal, Sanjaya; Burwen, Dale R; Polakowski, Laura L; Zinderman, Craig E; Wise, Robert P

2014-03-01

Assess whether Medicare data are useful for monitoring tissue allograft safety and utilization. We used health care claims (billing) data from 2007 for 35 million fee-for-service Medicare beneficiaries, a predominantly elderly population. Using search terms for transplant-related procedures, we generated lists of ICD-9-CM and CPT(®) codes and assessed the frequency of selected allograft procedures. Step 1 used inpatient data and ICD-9-CM procedure codes. Step 2 added non-institutional provider (e.g., physician) claims, outpatient institutional claims, and CPT codes. We assembled preliminary lists of diagnosis codes for infections after selected allograft procedures. Many ICD-9-CM codes were ambiguous as to whether the procedure involved an allograft. Among 1.3 million persons with a procedure ascertained using the list of ICD-9-CM codes, only 1,886 claims clearly involved an allograft. CPT codes enabled better ascertainment of some allograft procedures (over 17,000 persons had corneal transplants and over 2,700 had allograft skin transplants). For spinal fusion procedures, CPT codes improved specificity for allografts; of nearly 100,000 patients with ICD-9-CM codes for spinal fusions, more than 34,000 had CPT codes indicating allograft use. Monitoring infrequent events (infections) after infrequent exposures (tissue allografts) requires large study populations. A strength of the large Medicare databases is the substantial number of certain allograft procedures. Limitations include lack of clinical detail and donor information. Medicare data can potentially augment passive reporting systems and may be useful for monitoring tissue allograft safety and utilization where codes clearly identify allograft use and coding algorithms can effectively screen for infections.

Acellular dermal matrix allograft. The results of controlled randomized clinical studies.

PubMed

Novaes, Arthur Belém; de Barros, Raquel Rezende Martins

2008-10-01

The aim of this presentation was to discuss the effectiveness of the acellular dermal matrix in root coverage therapy and in alveolar ridge augmentation, based on three controlled randomized clinical trials conducted by our research team (Novaes Jr et al., 2001; Barros et al., 2005; Luczyszyn et al., 2005). The first and second studies highlight the allograft's performance in the treatment of gingival recession. In both studies, clinical parameters were assessed prior to surgery and 6 or 12 months post-surgery. The first one compared the use of the acellular dermal matrix with the subepithelial connective tissue graft and showed 1.83 and 2.10 mm of recession reduction, respectively. Because no statistically significant differences between the groups were observed, it was concluded that the allograft can be used as a substitute for the autograft. In the second study, a new surgical approach was compared to a conventional surgical procedure described by Langer and Langer in 1985. A statistically significant greater recession reduction favoring the test procedure was achieved. The percentage of root coverage was 82.5% and 62.3% for test and control groups. Thus the new technique was considered more suitable for the treatment of gingival recessions with the allograft. Finally, the third study evaluated the allograft as a membrane, associated or not with a resorbable hydroxyapatite in bone regeneration to prevent ridge deformities. In one group the extraction sockets were covered only by the allograft and in the other, the alveoli were also filled with the resorbable hydroxyapatite. After six months, both treatments were able to preserve ridge thickness, considering the pre-operative values. In conclusion, no adverse healing events were noted with the use of allograft in site preservation procedures, and sites treated with the combination of allograft plus resorbable hydroxyapatite showed significantly greater ridge thickness preservation at six months when compared to

Mild zinc deficiency in male and female rats: early postnatal alterations in renal nitric oxide system and morphology.

PubMed

Tomat, Analia Lorena; Veiras, Luciana Cecilia; Aguirre, Sofía; Fasoli, Héctor; Elesgaray, Rosana; Caniffi, Carolina; Costa, María Ángeles; Arranz, Cristina Teresa

2013-03-01

Fetal and postnatal zinc deficiencies induce an increase in arterial blood pressure and impair renal function in male adult rats. We therefore hypothesized that these renal alterations are present in early stages of life and that there are sexual differences in the adaptations to this nutritional injury. The aim was to study the effects of moderate zinc deficiency during fetal life and lactation on renal morphology, oxidative stress, apoptosis, and the nitric oxide system in male and female rats at 21 d of life. Female Wistar rats received low (8 ppm) or control (30 ppm) zinc diets from the beginning of pregnancy to weaning. Glomerulus number, morphology, oxidative stress, apoptotic cells, nitric oxide synthase activity, and protein expression were evaluated in the kidneys of offspring at 21 d. Zinc deficiency decreased the nephron number, induced glomerular hypertrophy, increased oxidative damage, and decreased nitric oxide synthase activity in the male and female rat kidneys. Nitric oxide synthase activity was not affected by inhibitors of the neuronal or inducible isoforms, so nitric oxide was mainly generated by the endothelial isoenzyme. Gender differences were observed in glomerular areas and antioxidant enzyme activities. Zinc deficiency during fetal life and lactation induces an early decrease in renal functional units, associated with a decrease in nitric oxide activity and an increase in oxidative stress, which would contribute to increased arterial blood pressure and renal dysfunction in adulthood. The sexual differences observed in this model may explain the dissimilar development of hypertension and renal diseases in adult life. Copyright © 2013 Elsevier Inc. All rights reserved.

Relationship between red cell distribution width and early renal injury in patients with gestational diabetes mellitus.

PubMed

Cheng, Dong; Zhao, Jiangtao; Jian, Liguo; Ding, Tongbin; Liu, Shichao

2016-09-01

Previous studies found that red cell distribution width was related to adverse cardiovascular events. However, few studies reported the relationship between red cell distribution width and early-stage renal injury in pregnant women with gestational diabetes mellitus. Using a cross-sectional design, 334 pregnant women with gestational diabetes mellitus were enrolled according to the criterion of inclusion and exclusion. Demographic and clinical examination data were collected. Depended on the urine albumin, study population were divided into case group (n = 118) and control group (n = 216). Compared with control group, the case group tend to be higher red cell distribution width level (13.6 ± 0.9 vs.12.5 ± 0.6, p < 0.001). The red cell distribution width was positively associated with albuminuria creatinine ratio (r = 0.567, p < 0.001). Multiple logistic regressions showed that red cell distribution width was still associated with early-stage renal injury after adjusting for many other potential cofounders. Compared with the first quartile, the risk ratio of the second, the third and the fourth quartile were 1.38 (95%CI: 1.06-1.80), 1.57 (95%CI: 1.21-2.97), 2.71 (95%CI: 2.08-3.54), respectively. Besides, systolic blood pressure, estimated glomerular filtration rate, uric acid and blood urea nitrogen were also significantly associated with renal injury in gestational diabetes mellitus patients. The elevated red cell distribution width level might be a predictor of early-stage renal injury in pregnant women with gestational diabetes mellitus. As an easy and routine examination index, red cell distribution width may provide better clinical guidance when combined with other important indices.

Electrocardiographic Characteristics of Potential Organ Donors and Associations with Cardiac Allograft Utilization

PubMed Central

Khush, Kiran K.; Menza, Rebecca; Nguyen, John; Goldstein, Benjamin A.; Zaroff, Jonathan G.; Drew, Barbara J.

2012-01-01

Background Current regulations require that all cardiac allograft offers for transplantation must include an interpreted 12-lead electrocardiogram (ECG). However, little is known about the expected ECG findings in potential organ donors, or the clinical significance of any identified abnormalities in terms of cardiac allograft function and suitability for transplantation. Methods and Results A single experienced reviewer interpreted the first ECG obtained after brainstem herniation in 980 potential organ donors managed by the California Transplant Donor Network from 2002-2007. ECG abnormalities were summarized, and associations between specific ECG findings and cardiac allograft utilization for transplantation were studied. ECG abnormalities were present in 51% of all cases reviewed. The most common abnormalities included voltage criteria for left ventricular hypertrophy (LVH), prolongation of the corrected QT interval (QTc), and repolarization changes (ST/T wave abnormalities). Fifty seven percent of potential cardiac allografts in this cohort were accepted for transplantation. LVH on ECG was a strong predictor of allograft non-utilization. No significant associations were seen between QTc prolongation, repolarization changes and allograft utilization for transplantation, after adjusting for donor clinical variables and echocardiographic findings. Conclusions We have performed the first comprehensive study of ECG findings in potential donors for cardiac transplantation. Many of the common ECG abnormalities seen in organ donors may result from the heightened state of sympathetic activation that occurs after brainstem herniation, and are not associated with allograft utilization for transplantation. PMID:22615333

Estimated Nephron Number of the Donor Kidney: Impact on Allograft Kidney Outcomes.

PubMed

Schachtner, T; Reinke, P

Low birth weights have been associated with a reduction in nephron number with compensatory hypertrophy of existing glomeruli. The impact of donor birth weight as an estimate of nephron number on allograft function, however, has not been examined. We collected donor birth weight, kidney weight, and volume from 91 living kidney donor-recipient pairs before nephrectomy and after 12, 36, and 60 months. Nephron number was calculated from donor birth weight and age. Donor birth weight, kidney weight/body surface area (BSA), and kidney volume showed a moderate positive correlation with allograft estimated glomerular filtration rate (eGFR) at 12 months (P < .05). Donor age showed a negative moderate correlation with allograft eGFR at 12 months (P = .015). The strongest correlation with allograft eGFR was observed for calculated donor kidney nephron number at 12, 36, and 60 months (R, 0.340, 0.305, and 0.476, respectively; P < .05). No impact was observed on allograft daily proteinuria of any investigated marker (P > .05). Recipients of donors with birth weight <2.5 kg had need of a significantly greater number of antihypertensive drugs (P < .05). Calculated nephron number from donor birth weight and age is suggested to be superior to donor kidney weight/BSA and volume regarding allograft function. Calculated nephron number could estimate expected eGFR and guide decision making in cases of impaired allograft function. Copyright © 2017 Elsevier Inc. All rights reserved.

Diagnostic value of plasma and bronchoalveolar lavage samples in acute lung allograft rejection: differential cytology.

PubMed

Speck, Nicole E; Schuurmans, Macé M; Murer, Christian; Benden, Christian; Huber, Lars C

2016-06-21

Diagnosis of acute lung allograft rejection is currently based on transbronchial lung biopsies. Additional methods to detect acute allograft dysfunction derived from plasma and bronchoalveolar lavage samples might facilitate diagnosis and ultimately improve allograft survival. This review article gives an overview of the cell profiles of bronchoalveolar lavage and plasma samples during acute lung allograft rejection. The value of these cells and changes within the pattern of differential cytology to support the diagnosis of acute lung allograft rejection is discussed. Current findings on the topic are highlighted and trends for future research are identified.

Inhibition of the purinergic pathway prolongs mouse lung allograft survival.

PubMed

Liu, Kaifeng; Vergani, Andrea; Zhao, Picheng; Ben Nasr, Moufida; Wu, Xiao; Iken, Khadija; Jiang, Dawei; Su, Xiaofeng; Fotino, Carmen; Fiorina, Paolo; Visner, Gary A

2014-08-01

Lung transplantation has limited survival with current immunosuppression. ATP is released from activated T cells, which act as costimulatory molecules through binding to the purinergic receptor P2XR7. We investigated the role of blocking the ATP/purinergic pathway, primarily P2XR7, using its inhibitor oxidized ATP (oATP) in modulating rejection of mouse lung allografts. Mouse lung transplants were performed using mice with major histocompatibility complex mismatch, BALB/c to C57BL6. Recipients received suramin or oATP, and lung allografts were evaluated 15 to ≥ 60 days after transplantation. Recipients were also treated with oATP after the onset of moderate to severe rejection to determine its ability to rescue lung allografts. Outcomes measures included lung function, histology, thoracic imaging, and allo-immune responses. Blocking purinergic receptors with the nonselective inhibitor suramin or with the P2XR7-selective inhibitor oATP reduced acute rejection and prolonged lung allograft survival for ≥ 60 days with no progression in severity. There were fewer inflammatory cells within lung allografts, less rejection, and improved lung function, which was maintained over time. CD4 and CD8 T cells were reduced within lung allografts with impaired activation with prolonged impairment of CD8 responses. In vitro, oATP reduced CD8 activation of Th1 inflammatory cytokines IFN-γ and TNF-α and cytolytic machinery, granzyme B. Cotreatment with immunosuppressive agents, cyclosporine, rapamycin, or CTLA-4Ig resulted in no additive benefits, and oATP alone resulted in better outcomes than cyclosporine alone. This study illustrates a potential new pathway to target in hopes of prolonging survival of lung transplant recipients.

Can Skin Allograft Occasionally Act as a Permanent Coverage in Deep Burns? A Pilot Study 

PubMed Central

Rezaei, Ezzatollah; Beiraghi-Toosi, Arash; Ahmadabadi, Ali; Tavousi, Seyed Hassan; Alipour Tabrizi, Arash; Fotuhi, Kazem; Jabbari Nooghabi, Mehdi; Manafi, Amir; Ahmadi Moghadam, Shokoofeh

2017-01-01

BACKGROUND Skin allograft is the gold standard of wound coverage in patients with extensive burns; however, it is considered as a temporary wound coverage and rejection of the skin allograft is considered inevitable. In our study, skin allograft as a permanent coverage in deep burns is evaluated. METHODS Skin allograft survival was assessed in 38 patients from March 2009 to March 2014, retrospectively. Because of the lack of tissue specimen from the skin donors, patients with long skin allograft survival in whom the gender of donor and recipient of allograft was the same were excluded. Seven cases with skin allograft longevity and opposite gender in donor and recipient were finally enrolled. A polymerase chain reaction (PCR) test on the biopsy specimen from recipients and donors were undertaken. RESULTS PCR on the biopsy specimen from recipients confirmed those specimens belong to the donors. All patients received allograft from the opposite sex. Two (28.57%) patients received allograft from their first-degree blood relatives, and in one (14.29%) case, the allograft was harvested from an alive individual with no blood relation. The rest were harvested from multiorgan donors. In eight months of follow up, no clinical evidence of graft rejection was noted. CONCLUSION Long term persistence of skin allograft in patients is worthy of more attention. Further studies An increase in knowledge of factors influencing this longevity could realize the dream of burn surgeons to achieve a permanent coverage other than autograft for major burn patients. PMID:28289620

Endothelial dysfunction in hemodialysis patients with failed renal transplants.

PubMed

Gorgulu, Numan; Yelken, Berna; Caliskan, Yasar; Elitok, Ali; Cimen, Arif Oguzhan; Yazici, Halil; Oflaz, Huseyin; Golcuk, Ebru; Ekmekci, Ahmet; Turkmen, Aydin; Yildiz, Alaattin; Sever, Mehmet Sukru

2010-01-01

Endothelial dysfunction (ED) is a common precursor and denominator of cardiovascular events including development of atherosclerosis. In this cross-sectional study, we aimed to investigate ED, measured by coronary flow reserve (CFR) in hemodialysis (nHD) patients who were never transplanted and patients with failed renal transplants restarting hemodialysis (fTx-HD). Forty nHD (24 males, mean age 39 ± 9 yr) and 43 fTx-HD patients (27 males, mean age 36 ± 9 yr) were included in the study. Clinical and biochemical parameters, including high-sensitive C-reactive protein (hs-CRP) levels were determined. Also, CFR measurements were used to evaluate ED. There were no significant differences regarding age, gender, smoking status, systolic and diastolic blood pressure levels, mean duration of HD treatment as well as Kt/V((urea)) values between the two groups. Time spent on dialysis in the nHD group and dialysis duration following failure of renal allograft in the fTx-HD group were similar. Serum creatinine, hemoglobin, hematocrit, calcium and phosphorus levels were similar between the two groups as well. When compared to nHD group, serum total cholesterol (139 ± 3 vs. 154 ± 3 mg/dL, p = 0.045), serum albumin (3.8 ± 0.3 g/dL vs. 4.1 ± 0.2 g/dL, p < 0.0001) and CFR (1.60 ± 0.2 vs. 1.75 ± 0.3, p = 0.028) levels were significantly lower, while serum hs-CRP levels (11 ± 15 mg/L vs. 3 ± 4 mg/L, p = 0.001) were significantly higher in the fTx-HD group. Serum hs-CRP negatively correlated (r = -0254, p = 0.021), while serum albumin positively correlated (r = 0402, p = 0.001) with CFR values. ED is more prominent in fTx-HD than the nHD patients. Inflammation, caused by failed renal allograft can be responsible for this abnormality. © 2009 John Wiley & Sons A/S.

Donor Predictors of Allograft Utilization and Recipient Outcomes after Heart Transplantation

PubMed Central

Khush, Kiran K.; Menza, Rebecca; Nguyen, John; Zaroff, Jonathan G.; Goldstein, Benjamin A.

2013-01-01