Science.gov

Sample records for early renal allograft

  1. Intragraft vascular occlusive sickle crisis with early renal allograft loss in occult sickle cell trait.

    PubMed

    Kim, Lisa; Garfinkel, Marc R; Chang, Anthony; Kadambi, Pradeep V; Meehan, Shane M

    2011-07-01

    Early renal allograft failure due to sickle cell trait is rare. We present clinical and pathologic findings in 2 cases of early renal allograft failure associated with renal vein thrombosis and extensive erythrocyte sickling. Hemoglobin AS was identified in retrospect. In case 1, a 41-year-old female recipient of a deceased donor renal transplant developed abdominal pain and acute allograft failure on day 16, necessitating immediate nephrectomy. In case 2, the transplanted kidney in a 58-year-old female recipient was noted to be mottled blue within minutes of reperfusion. At 24 hours, the patient was oliguric; and the graft was removed. Transplant nephrectomies had diffuse enlargement with diffuse, nonhemorrhagic, cortical, and medullary necrosis. Extensive sickle vascular occlusion was evident in renal vein branches; interlobar, interlobular, and arcuate veins; vasa recta; and peritubular capillaries. The renal arteries had sickle vascular occlusion in case 1. Glomeruli had only focal sickle vascular occlusion. The erythrocytes in sickle vascular occlusion had abundant cytoplasmic filaments by electron microscopy. Acute rejection was not identified in either case. Protein C and S levels, factor V Leiden, and lupus anticoagulant assays were within normal limits. Hemoglobin analysis revealed hemoglobin S of 21.8% and 25.6%, respectively. Renal allograft necrosis with intragraft sickle crisis, characterized by extensive vascular occlusive erythrocyte sickling and prominent renal vein thrombosis, was observed in 2 patients with sickle cell trait. Occult sickle cell trait may be a risk factor for early renal allograft loss. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Xenon treatment attenuates early renal allograft injury associated with prolonged hypothermic storage in rats.

    PubMed

    Zhao, Hailin; Yoshida, Akira; Xiao, Wei; Ologunde, Rele; O'Dea, Kieran P; Takata, Masao; Tralau-Stewart, Catherine; George, Andrew J T; Ma, Daqing

    2013-10-01

    Prolonged hypothermic storage elicits severe ischemia-reperfusion injury (IRI) to renal grafts, contributing to delayed graft function (DGF) and episodes of acute immune rejection and shortened graft survival. Organoprotective strategies are therefore needed for improving long-term transplant outcome. The aim of this study is to investigate the renoprotective effect of xenon on early allograft injury associated with prolonged hypothermic storage. Xenon exposure enhanced the expression of heat-shock protein 70 (HSP-70) and heme oxygenase 1 (HO-1) and promoted cell survival after hypothermia-hypoxia insult in human proximal tubular (HK-2) cells, which was abolished by HSP-70 or HO-1 siRNA. In the brown Norway to Lewis rat renal transplantation, xenon administered to donor or recipient decreased the renal tubular cell death, inflammation, and MHC II expression, while delayed graft function (DGF) was therefore reduced. Pathological changes associated with acute rejection, including T-cell, macrophage, and fibroblast infiltration, were also decreased with xenon treatment. Donors or recipients treated with xenon in combination with cyclosporin A had prolonged renal allograft survival. Xenon protects allografts against delayed graft function, attenuates acute immune rejection, and enhances graft survival after prolonged hypothermic storage. Furthermore, xenon works additively with cyclosporin A to preserve post-transplant renal function.

  3. Detection of urinary biomarkers for early diagnosis of acute renal allograft rejection by proteomic analysis.

    PubMed

    Jia, Xiongfei; Gan, Chengjun; Xiao, Ke; He, Weifeng; Zhang, Tao; Huang, Cibing; Wu, Xiongfei; Luo, Gaoxing; Wang, Xiaojuan; Hu, Jie; Tan, Jiangling; Zhang, Xiaorong; Larsen, Peter Mose; Wu, Jun

    2009-06-01

    Acute allograft rejection has been recognized as a major impediment to improved success in renal transplantation. Timely detection and control of rejection are very important for the improvement in long-term renal allograft survival. Thus, biomarkers for early diagnosis of acute rejection are required urgently to clinical medication. This study seeks to search for such biomarker candidates by comparing patients' pre-treatment urinary protein profiling with their post-treatment urinary protein profiling. A total of 15 significantly and consistently down-regulated protein candidates were identified. Among them, alpha-1-antichymotrypsin precursor (AACT), tumor rejection antigen gp96 (GP96) and Zn-Alpha-2-Glycoprotein (ZAG) were selected for further analysis. The results indicated that Western Blot assay of AACT, GP96 and ZAG had advanced the diagnosis time of acute renal rejection by 3 days, compared with current standard clinical observation and laboratory examination. Furthermore, the double-blind detection revealed that the accuracy, sensitivity and specificity of the diagnosis of acute renal rejection of AACT, GP96 and ZAG were 66.67%/100%/60%, 83.33%/100%/80% and 66.67%/100%/60%, respectively, and 100%/100%/100% in combination. In conclusion, urinary protein AACT, GP96 and ZAG could be a set of potential biomarkers for early non-invasive diagnosis of the acute rejection after renal transplantation. Copyright © 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Mucormycosis (zygomycosis) of renal allograft

    PubMed Central

    Gupta, Krishan L.; Joshi, Kusum; Kohli, Harbir S.; Jha, Vivekanand; Sakhuja, Vinay

    2012-01-01

    Fungal infection is relatively common among renal transplant recipients from developing countries. Mucormycosis, also known as zygomycosis, is one of the most serious fungal infections in these patients. The most common of presentation is rhino-cerebral. Isolated involvement of a renal allograft is very rare. A thorough search of literature and our medical records yielded a total of 24 cases with mucormycosis of the transplanted kidney. There was an association with cytomegalovirus (CMV) infection and anti-rejection treatment in these patients and most of these transplants were performed in the developing countries from unrelated donors. The outcome was very poor with an early mortality in 13 (54.5%) patients. Renal allograft mucormycosis is a relatively rare and potentially fatal complication following renal transplantation. Early diagnosis, graft nephrectomy and appropriate antifungal therapy may result in an improved prognosis for these patients. PMID:26069793

  5. 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

  6. 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

  7. Early Focal Segmental Glomerulosclerosis as a Cause of Renal Allograft Primary Nonfunction

    PubMed Central

    Griffin, Emma J.; Thomson, Peter C.; Kipgen, David; Clancy, Marc; Daly, Conal

    2013-01-01

    Background. Primary focal segmental glomerulosclerosis (FSGS) is one of the commonest causes of glomerular disease and if left untreated will often progress to established renal failure. In many cases the best treatment option is renal transplantation; however primary FSGS may rapidly recur in renal allografts and may contribute to delayed graft function. We present a case of primary nonfunction in a renal allograft due to biopsy-proven FSGS. Case Report. A 32-year-old man presented with serum albumin of 22 g/L, proteinuria quantified at 12 g/L, and marked peripheral oedema. Renal biopsy demonstrated tip-variant FSGS. Despite treatment, the patient developed progressive renal dysfunction and was commenced on haemodialysis. Cadaveric renal transplantation was undertaken; however this was complicated by primary nonfunction. Renal biopsies failed to demonstrate evidence of acute rejection but did demonstrate clear evidence of FSGS. The patient was treated to no avail. Discussion. Primary renal allograft nonfunction following transplantation is often due to acute kidney injury or acute rejection. Recurrent FSGS is recognised as a phenomenon that drives allograft dysfunction but is not traditionally associated with primary nonfunction. This case highlights FSGS as a potentially aggressive process that, once active in the allograft, may prove refractory to targeted treatment. Preemptive therapies in patients deemed to be at high risk of recurrent disease may be appropriate and should be considered. PMID:23781382

  8. Evaluation of renal allografts function early after transplantation using intravoxel incoherent motion and arterial spin labeling MRI.

    PubMed

    Ren, Tao; Wen, Cheng-Long; Chen, Li-Hua; Xie, Shuang-Shuang; Cheng, Yue; Fu, Ying-Xin; Oesingmann, Niels; de Oliveira, Andre; Zuo, Pan-Li; Yin, Jian-Zhong; Xia, Shuang; Shen, Wen

    2016-09-01

    To evaluate renal allografts function early after transplantation using intravoxel incoherent motion (IVIM) and arterial spin labeling (ASL) MRI. This prospective study was approved by the local ethics committee, and written informed consent was obtained from all participants. A total of 82 participants with 62 renal allograft recipients (2-4weeks after kidney transplantation) and 20 volunteers were enrolled to be scanned using IVIM and ASL MRI on a 3.0T MR scanner. Recipients were divided into two groups with either normal or impaired function according to the estimated glomerular filtration rate (eGFR) with a threshold of 60ml/min/1.73m(2). The apparent diffusion coefficient (ADC) of pure diffusion (ADCslow), the ADC of pseudodiffusion (ADCfast), perfusion fraction (PF), and renal blood flow (RBF) of cortex were compared among three groups. The correlation of ADCslow, ADCfast, PF and RBF with eGFR was evaluated. The receiver operating characteristic (ROC) curve and binary logistic regression analyses were performed to assess the diagnostic efficiency of using IVIM and ASL parameters to discriminate allografts with impaired function from normal function. P<0.05 was considered statistically significant. In allografts with normal function, no significant difference of mean cortical ADCslow, ADCfast, and PF was found compared with healthy controls (P>0.05). Cortical RBF in allografts with normal function was statistically lower than that of healthy controls (P<0.001). Mean cortical ADCslow, ADCfast, PF and RBF were lower for allografts with impaired function than that with normal function (P<0.05). Mean cortical ADCslow, ADCfast, PF and RBF showed a positive correlation with eGFR (all P<0.01) for recipients. The combination of IVIM and ASL MRI showed a higher area under the ROC curve (AUC) (0.865) than that of ASL MRI alone (P=0.02). Combined IVIM and ASL MRI can better evaluate the diffusion and perfusion properties for allografts early after kidney transplantation

  9. Glomerular enlargement assessed by paired donor and early protocol renal allograft biopsies.

    PubMed

    Alperovich, Gabriela; Maldonado, Rafael; Moreso, Francesc; Fulladosa, Xavier; Grinyó, Josep M; Serón, Daniel

    2004-04-01

    The aim of the study was to evaluate the evolution of glomerular volume 4 months after transplantation. Mean glomerular volume (Vg) was estimated according to the Weibel and Gomez method in a donor and a protocol biopsy done at 139 +/- 58 d in 41 stable grafts. Biopsies were also evaluated according to the Banff schema. Vg increased after transplantation from 4.1 +/- 1.4 to 5.1 +/- 2.4 x 10(6) micro3 (p=0.02). In patients with chronic allograft nephropathy in the protocol biopsy (n=14), the Vg enlargement was -0.3 +/-x 10(6) micro3 while in patients without chronic allograft nephropathy (n=27), glomerular enlargement was 1.6 +/- 2.1 x 10(6) micro3 (p=0.01). There was a negative association between glomerular volume in the donor biopsy and glomerular enlargement after transplantation (R=- 0.34, p=0.03). Multivariate regression analysis confirmed that Vg in the donor biopsy and chronic allograft nephropathy in the protocol biopsy were independent predictors of glomerular enlargement after transplantation (R=0.48, p=0.01). Moreover, Vg in the protocol biopsy correlated with creatinine clearance at the time of biopsy (R=0.38, p=0.01). Glomeruli enlarge after transplantation and glomerular volume after 4 months correlates with creatinine clearance, suggesting that glomerular enlargement is a necessary condition for renal adaptation to the recipient. Glomerular enlargement is impaired in patients with chronic allograft nephropathy.

  10. 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.

  11. [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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. Functional MRI detects perfusion impairment in renal allografts with delayed graft function.

    PubMed

    Hueper, Katja; Gueler, Faikah; Bräsen, Jan Hinrich; Gutberlet, Marcel; Jang, Mi-Sun; Lehner, Frank; Richter, Nicolas; Hanke, Nils; Peperhove, Matti; Martirosian, Petros; Tewes, Susanne; Vo Chieu, Van Dai; Großhennig, Anika; Haller, Hermann; Wacker, Frank; Gwinner, Wilfried; Hartung, Dagmar

    2015-06-15

    Delayed graft function (DGF) after kidney transplantation is not uncommon, and it is associated with long-term allograft impairment. Our aim was to compare renal perfusion changes measured with noninvasive functional MRI in patients early after kidney transplantation to renal function and allograft histology in biopsy samples. Forty-six patients underwent MRI 4-11 days after transplantation. Contrast-free MRI renal perfusion images were acquired using an arterial spin labeling technique. Renal function was assessed by estimated glomerular filtration rate (eGFR), and renal biopsies were performed when indicated within 5 days of MRI. Twenty-six of 46 patients had DGF. Of these, nine patients had acute rejection (including borderline), and eight had other changes (e.g., tubular injury or glomerulosclerosis). Renal perfusion was significantly lower in the DGF group compared with the group with good allograft function (231 ± 15 vs. 331 ± 15 ml·min(-1)·100 g(-1), P < 0.001). Living donor allografts exhibited significantly higher perfusion values compared with deceased donor allografts (P < 0.001). Renal perfusion significantly correlated with eGFR (r = 0.64, P < 0.001), resistance index (r = -0.57, P < 0.001), and cold ischemia time (r = -0.48, P < 0.01). Furthermore, renal perfusion impairment early after transplantation predicted inferior renal outcome and graft loss. In conclusion, noninvasive functional MRI detects renal perfusion impairment early after kidney transplantation in patients with DGF. Copyright © 2015 the American Physiological Society.

  17. Targeting Sirtuin-1 prolongs murine renal allograft survival and function

    PubMed Central

    Levine, Matthew H.; Wang, Zhonglin; Xiao, Haiyan; Jiao, Jing; Wang, Liqing; Bhatti, Tricia R.; Hancock, Wayne W.; Beier, Ulf H.

    2016-01-01

    Current immunosuppressive medications used after transplantation have significant toxicities. Foxp3+ T-regulatory (Treg) cells can prevent allograft rejection without compromising protective host immunity. Interestingly, inhibiting the class III histone/protein deacetylase Sirtuin-1 can augment Foxp3+ Treg suppressive function through increasing Foxp3 acetylation. Here we determined whether Sirtuin-1 targeting can stabilize biological allograft function. BALB/c kidney allografts were transplanted into C57BL/6 recipients with a CD4-conditional deletion of Sirtuin-1 (Sirt1fl/flCD4cre) or mice treated with a Sirtuin-1 specific inhibitor (EX-527), and the native kidneys removed. Blood chemistries and hematocrit were followed weekly. Sirt1fl/flCD4cre recipients showed markedly longer survival and improved kidney function. Sirt1fl/flCD4cre recipients exhibited donor specific tolerance, accepted BALB/c, but rejected third-party C3H cardiac allografts. C57BL/6 recipients of BALB/c renal allografts that were treated with EX-527 showed improved survival and renal function at 1, but not 10 mg/kg/day. Pharmacologic inhibition of Sirtuin-1 also improved renal allograft survival and function with dosing effects having relevance to outcome. Thus, inhibiting Sirtuin-1 can be a useful asset in controlling T-cell mediated rejection. However, effects on non-T cells that could adversely affect allograft survival and function merit consideration. PMID:27083279

  18. Expression of GSK-3β in renal allograft tissue and its significance in pathogenesis of chronic allograft dysfunction.

    PubMed

    Yan, Qiang; Wang, Baoyao; Sui, Weiguo; Zou, Guimian; Chen, Huaizhou; Xie, Shenping; Zou, Hequn

    2012-01-13

    To explore the expression of Glycogen synthase kinase 3 beta (GSK-3β) in renal allograft tissue and its significance in the pathogenesis of chronic allograft dysfunction. Renal allograft biopsy was performed in all of the renal allograft recipients with proteinuria or increased serum creatinine level who came into our hospital from January 2007 to December 2009. Among them 28 cases was diagnosed as chronic allograft dysfunction based on pahtological observation, including 21 males with a mean age of 45 ± 10 years old and 7 females with a mean age of 42 ± 9 years old. The time from kidney transplantation to biopsy were 1-9 (3.5) years. Their serum creatinine level were 206 ± 122 umol/L. Immunohistochemical assay and computer-assisted genuine color image analysis system (imagepro-plus 6.0) were used to detect the expression of GSK-3β in the renal allografts of 28 cases of recipients with chronic allograft dysfunction. Mean area and mean integrated optical density of GSK-3β expression were calculated. The relationship between expression level of GSK-3β and either the grade of inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft was analyzed. Five specimens of healthy renal tissue were used as controls. The expression level of the GSK-3β was significantly increased in the renal allograft tissue of recipients with chronic allograft dysfunction, compared to normal renal tissues, and GSK-3β expression became stronger along with the increasing of the grade of either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy in renal allograft tissue. There might be a positive correlation between either inflammatory cell infiltration or interstitial fibrosis/tubular atrophy and high GSK-3β expression in renal allograft tissue. The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/9924478946162998.

  19. 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.

  20. Treatment options for renal cell carcinoma in renal allografts: a case series from a single institution.

    PubMed

    Swords, Darden C; Al-Geizawi, Samer M; Farney, Alan C; Rogers, Jeffrey; Burkart, John M; Assimos, Dean G; Stratta, Robert J

    2013-01-01

    Renal cell carcinoma (RCC) is more common in renal transplant and dialysis patients than the general population. However, RCC in transplanted kidneys is rare, and treatment has previously consisted of nephrectomy with a return to dialysis. There has been recent interest in nephron-sparing procedures as a treatment option for RCC in allograft kidneys in an effort to retain allograft function. Four patients with RCC in allograft kidneys were treated with nephrectomy, partial nephrectomy, or radiofrequency ablation. All of the patients are without evidence of recurrence of RCC after treatment. We found nephron-sparing procedures to be reasonable initial options in managing incidental RCCs diagnosed in functioning allografts to maintain an improved quality of life and avoid immediate dialysis compared with radical nephrectomy of a functioning allograft. However, in non-functioning renal allografts, radical nephrectomy may allow for a higher chance of cure without the loss of transplant function. Consequently, radical nephrectomy should be utilized whenever the allograft is non-functioning and the patient's surgical risk is not prohibitive. © 2013 John Wiley & Sons A/S.

  1. 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.

  2. 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

  3. Nocturnal polyuria and saluresis in renal allograft recipients.

    PubMed Central

    Chan, M K; Varghese, Z; Fernando, O N; Moorhead, J F

    1980-01-01

    The evolution of nocturnal polyuria and saluresis in renal allograft recipients was studied by comparing the day to night (D:N) ratios of urine volume and sodium excretion in 15 patients who had undergone transplantation less than one year previously (recent-transplant group) with those in 11 patients who had undergone transplantation at least one year previously. Eleven patients with chronic renal failure and 12 normal subjects served as controls. Patients in the recent-transplant group had significantly lower D:N ratios of urine volume and sodium excretion than the patients who had undergone transplantation at least a year before, while the ratios in this last group did not differ significantly from those in the normal subjects. Nocturnal polyuria and saluresis gradually subsided in five patients studied for three months. Chronic renal failure and uraemic autonomic neuropathy were unlikely causes of the nocturia. The patients in the recent-transplant group had significantly lower D:N ratios of urine volume than the controls with chronic renal failure, and the mean Valsalva ratio in eight of them was not significantly different from that in the normal subjects. An undue sensitivity of renal allografts to postural influences was proposed. PMID:6986946

  4. 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

  5. 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

  6. Assessment of the relationship between ACE I/D gene polymorphism and renal allograft survival.

    PubMed

    Yang, Chun-Hua; Lu, Yi; Chen, Xue-Xia; Xian, Wen-Feng; Tu, Wei-Feng; Li, Hong-Yan

    2015-12-01

    The relationship between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and renal allograft survival after renal transplantation from the published reports are still debatable. This study was performed to evaluate the relationship between the ACE I/D gene polymorphism and renal allograft survival after renal transplantation using meta-analysis. Eligible studies were identified from PubMed and Cochrane Library on 1 November 2014, and eligible studies were recruited and synthesized using a meta-analysis methodology. Twelve investigations were included in this meta-analysis for the assessment of the relationship between the ACE I/D gene polymorphism and renal allograft survival. In this meta-analysis, the ACE I/D gene polymorphism was not associated with renal allograft survival after renal transplantation for overall populations, Caucasians, Brazilians and Africans. Interestingly, the ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. ACE D allele and DD genotype were associated with renal allograft survival after renal transplantation in the Asian population. However, more studies should be performed to confirm this association. © The Author(s) 2015.

  7. Effect of a stable prostacyclin analogue on canine renal allograft rejection.

    PubMed Central

    Tobimatsu, M; Ueda, Y; Toyoda, K; Saito, S; Konomi, K

    1987-01-01

    The effect of OP-41483 (Ono Pharmaceutical Co., Osaka, Japan), a stable prostacyclin analogue, on canine renal allograft rejection was investigated. Administration for 4 days after transplantation significantly increased renal cortical blood flow and urine output when compared with untreated dogs with renal allografts. Serum creatinine levels remained relatively low during postoperative days 1-4. Mean animal survival time was prolonged. Vascular lesions and mononuclear cell infiltration were greatly diminished in biopsy specimens removed on day 4. This stable prostacyclin analogue provided a degree of protection against canine renal allograft rejection. Images Figs. 1A and B. PMID:3545109

  8. 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.

  9. 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.

  10. 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.

  11. Spleen tyrosine kinase contributes to acute renal allograft rejection in the rat

    PubMed Central

    Ramessur Chandran, Sharmila; Tesch, Greg H; Han, Yingjie; Woodman, Naomi; Mulley, William R; Kanellis, John; Blease, Kate; Ma, Frank Y; Nikolic-Paterson, David J

    2015-01-01

    Kidney allografts induce strong T-cell and antibody responses which mediate acute rejection. Spleen tyrosine kinase (Syk) is expressed by most leucocytes, except mature T cells, and is involved in intracellular signalling following activation of the Fcγ-receptor, B-cell receptor and some integrins. A role for Syk signalling has been established in antibody-dependent native kidney disease, but little is known of Syk in acute renal allograft rejection. Sprague–Dawley rats underwent bilateral nephrectomy and received an orthotopic Wistar renal allograft. Recipient rats were treated with a Syk inhibitor (CC0482417, 30 mg/kg/bid), or vehicle, from 1 h before surgery until being killed 5 days later. Vehicle-treated recipients developed severe allograft failure with marked histologic damage in association with dense leucocyte infiltration (T cells, macrophages, neutrophils and NK cells) and deposition of IgM, IgG and C3. Immunostaining identified Syk expression by many infiltrating leucocytes. CC0482417 treatment significantly improved allograft function and reduced histologic damage, although allograft injury was still clearly evident. CC0482417 failed to prevent T-cell infiltration and activation within the allograft. However, CC0482417 significantly attenuated acute tubular necrosis, infiltration of macrophages and neutrophils and thrombosis of peritubular capillaries. In conclusion, this study identifies a role for Syk in acute renal allograft rejection. Syk inhibition may be a useful addition to T-cell-based immunotherapy in renal transplantation. PMID:25529862

  12. Renal denervation in a patient with Alport syndrome and rejected renal allograft.

    PubMed

    Raju, Narayana; Lloyd, Vincent; Yalagudri, Sachin; Das, Bharati; Ravikishore, A G

    2015-12-01

    Renal denervation is a new intervention to treat resistant hypertension. By applying radiofrequency (RF) to renal arteries, sympathetic nerves in adventitia layer of vascular wall can be denervated. Sympathetic hyperactivity is an important contributory factor in hypertension of hemodialysis patients. Hyperactive sympathetic nervous system aggravates hypertension and it can cause complications like left ventricular hypertrophy, heart failure, arrhythmias and atherogenesis. Our report illustrates the use of renal denervation using conventional RF catheter for uncontrolled hypertension in a patient with Alport syndrome and rejected renal allograft. Progressive and sustained reduction of blood pressure was obtained post-procedure and at 24 months follow-up with antihypertensives decreased from 6 to 2 per day, thereby demonstrating the safety, feasibility, and efficacy of the procedure. There are some reports available on the usefulness of this technique in hemodialysis patients; however, there are no studies of renal denervation in patients with Alport syndrome and failed allograft situation. Copyright © 2015 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.

  13. Non-invasive evaluation of stable renal allograft function using point shear-wave elastography.

    PubMed

    Kim, Bom Jun; Kim, Chan Kyo; Park, Jung Jae

    2018-01-01

    To investigate the feasibility of point shear-wave elastography (SWE) in evaluating patients with stable renal allograft function who underwent protocol biopsies. 95 patients with stable renal allograft function that underwent ultrasound-guided biopsies at predefined time points (10 days or 1 year after transplantation) were enrolled. Ultrasound and point SWE examinations were performed immediately before protocol biopsies. Patients were categorized into two groups: subclinical rejection (SCR) and non-SCR. Tissue elasticity (kPa) on SWE was measured in the cortex of all renal allografts. SCR was pathologically confirmed in 34 patients. Tissue elasticity of the SCR group (31.0 kPa) was significantly greater than that of the non-SCR group (24.5 kPa) (=0.016), while resistive index value did not show a significant difference between the two groups (p = 0.112). Tissue elasticity in renal allografts demonstrated significantly moderate negative correlation with estimated glomerular filtration rate (correlation coefficient = -0.604, p < 0.001). Tissue elasticity was not independent factor for SCR prediction on multivariate analysis. As a non-invasive tool, point SWE appears feasible in distinguishing between patients with SCR and without SCR in stable functioning renal allografts. Moreover, it may demonstrate the functional state of renal allografts. Advances in knowledge: On point SWE, SCR has greater tissue elasticity than non-SCR.

  14. Biological mechanism analysis of acute renal allograft rejection: integrated of mRNA and microRNA expression profiles.

    PubMed

    Huang, Shi-Ming; Zhao, Xia; Zhao, Xue-Mei; Wang, Xiao-Ying; Li, Shan-Shan; Zhu, Yu-Hui

    2014-01-01

    Renal transplantation is the preferred method for most patients with end-stage renal disease, however, acute renal allograft rejection is still a major risk factor for recipients leading to renal injury. To improve the early diagnosis and treatment of acute rejection, study on the molecular mechanism of it is urgent. MicroRNA (miRNA) expression profile and mRNA expression profile of acute renal allograft rejection and well-functioning allograft downloaded from ArrayExpress database were applied to identify differentially expressed (DE) miRNAs and DE mRNAs. DE miRNAs targets were predicted by combining five algorithm. By overlapping the DE mRNAs and DE miRNAs targets, common genes were obtained. Differentially co-expressed genes (DCGs) were identified by differential co-expression profile (DCp) and differential co-expression enrichment (DCe) methods in Differentially Co-expressed Genes and Links (DCGL) package. Then, co-expression network of DCGs and the cluster analysis were performed. Functional enrichment analysis for DCGs was undergone. A total of 1270 miRNA targets were predicted and 698 DE mRNAs were obtained. While overlapping miRNA targets and DE mRNAs, 59 common genes were gained. We obtained 103 DCGs and 5 transcription factors (TFs) based on regulatory impact factors (RIF), then built the regulation network of miRNA targets and DE mRNAs. By clustering the co-expression network, 5 modules were obtained. Thereinto, module 1 had the highest degree and module 2 showed the most number of DCGs and common genes. TF CEBPB and several common genes, such as RXRA, BASP1 and AKAP10, were mapped on the co-expression network. C1R showed the highest degree in the network. These genes might be associated with human acute renal allograft rejection. We conducted biological analysis on integration of DE mRNA and DE miRNA in acute renal allograft rejection, displayed gene expression patterns and screened out genes and TFs that may be related to acute renal allograft

  15. Biological mechanism analysis of acute renal allograft rejection: integrated of mRNA and microRNA expression profiles

    PubMed Central

    Huang, Shi-Ming; Zhao, Xia; Zhao, Xue-Mei; Wang, Xiao-Ying; Li, Shan-Shan; Zhu, Yu-Hui

    2014-01-01

    Objectives: Renal transplantation is the preferred method for most patients with end-stage renal disease, however, acute renal allograft rejection is still a major risk factor for recipients leading to renal injury. To improve the early diagnosis and treatment of acute rejection, study on the molecular mechanism of it is urgent. Methods: MicroRNA (miRNA) expression profile and mRNA expression profile of acute renal allograft rejection and well-functioning allograft downloaded from ArrayExpress database were applied to identify differentially expressed (DE) miRNAs and DE mRNAs. DE miRNAs targets were predicted by combining five algorithm. By overlapping the DE mRNAs and DE miRNAs targets, common genes were obtained. Differentially co-expressed genes (DCGs) were identified by differential co-expression profile (DCp) and differential co-expression enrichment (DCe) methods in Differentially Co-expressed Genes and Links (DCGL) package. Then, co-expression network of DCGs and the cluster analysis were performed. Functional enrichment analysis for DCGs was undergone. Results: A total of 1270 miRNA targets were predicted and 698 DE mRNAs were obtained. While overlapping miRNA targets and DE mRNAs, 59 common genes were gained. We obtained 103 DCGs and 5 transcription factors (TFs) based on regulatory impact factors (RIF), then built the regulation network of miRNA targets and DE mRNAs. By clustering the co-expression network, 5 modules were obtained. Thereinto, module 1 had the highest degree and module 2 showed the most number of DCGs and common genes. TF CEBPB and several common genes, such as RXRA, BASP1 and AKAP10, were mapped on the co-expression network. C1R showed the highest degree in the network. These genes might be associated with human acute renal allograft rejection. Conclusions: We conducted biological analysis on integration of DE mRNA and DE miRNA in acute renal allograft rejection, displayed gene expression patterns and screened out genes and TFs that may

  16. 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.

  17. 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.

  18. 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.

  19. Augmenting kidney mass at transplantation abrogates chronic renal allograft injury in rats.

    PubMed

    Mackenzie, H S; Azuma, H; Troy, J L; Rennke, H G; Tilney, N L; Brenner, B M

    1996-03-01

    Conventional renal transplantation, which substitutes a single allograft for two native kidneys, imposes an imbalance between nephron supply and the metabolic and excretory demands of the recipient. This discrepancy, which stimulates hyperfunction and hypertrophy of viable allograft nephrons, may be intensified by nephron loss through ischemia-reperfusion injury or acute rejection episodes occurring soon after transplantation. In other settings where less than 50% of the total renal mass remains, progressive glomerular injury develops through mechanisms associated with compensatory nephron hyperfiltration and hypertrophy. To determine whether responses to nephron loss contribute to chronic injury in renal allografts, nephron supply was restored to near-normal levels by transplanting Lewis recipients with two Fisher 344 kidneys (group 2A) compared with the standard single allograft F344 --> LEW rat model of late renal allograft failure (group 1A). At 20 weeks, indices of injury were observed in 1A but not 2A rats. These indices included proteinuria (1A: 45 +/- 13; 2A: 4.0 +/- 0.29 mg/day) and glomerulosclerosis (1A: 23 +/- 4.9%, 2A: 0.7 +/- 0.3%) (p < .05). Double-allograft recipients maintained near normal renal structure and function, whereas 1A rats showed evidence of compensatory hyperfiltration (single-nephron glomerular filtration rate of 63 +/- 10 versus 44 +/- 2.0 nl/min in 2A rats) and hypertrophy (mean glomerular volume of 2.64 +/- 0.15 versus 1.52 +/- 0.05 microns3 x 10(6) in 2A rats) (p < .05). Thus, we conclude that a major component of late allograft injury is attributable to processes associated with inadequate transplanted renal mass, a finding that has major implications for kidney transplantation biology and policy.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

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

    SciT

    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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. [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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. 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.

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

    SciT

    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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.).

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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.

  16. The Spectrum of Histopathological Changes in the Renal Allograft - a 12 Months Protocol Biopsy Study

    PubMed Central

    Severova-Andreevska, Galina; Grcevska, Ladislava; Petrushevska, Gordana; Cakalaroski, Koco; Sikole, Aleksandar; Stojceva–Taneva, Olivera; Danilovska, Ilina; Ivanovski, Ninoslav

    2018-01-01

    INTRODUCTION: Renal transplantation became a routine and successful medical treatment for Chronic Kidney Disease in the last 30 years all over the world. Introduction of Luminex based Single Antigen Beads (SAB) and recent BANFF consensus of histopathological phenotypes of different forms of rejection enables more precise diagnosis and changes the therapeutic approach. The graft biopsies, protocol or cause, indicated, remain a golden diagnostic tool for clinical follow up of kidney transplant recipients (KTR). AIM: The study aimed to analyse the histopathological changes in renal grafts 12 months after the surgery in KTR with satisfactory kidney function. MATERIAL AND METHODS: A 12-month protocol biopsy study was performed in a cohort of 50 Kidney transplant recipients (42 from living and 8 from deceased donors). Usual work-up for suitable donors and recipients, standard surgical procedure, basic principles of peri and postoperative care and follow up were done in all KTR. Sequential quadruple immunosuppression including induction with Anti-thymocyte globulin (ATG) or Interleukin-2R antagonist (IL-2R), and triple drug maintenance therapy with Calcineurin Inhibitors (CNI), Mycophenolate Mofetil (MMF) and Steroids were prescribed to all pts. Different forms of Glomerulonephritis (16), Hypertension (10), End Stage Renal Disease (13), Hereditary Nephropathies (6), Diabetes (3) and Vesicoureteral Reflux (2) were the underlying diseases. All biopsies were performed under ultrasound guidance. The 16 gauge needles with automated “gun” were used to take 2 cores of tissue. The samples were stained with HE, PAS, Trichrome Masson and Silver and reviewed by the same pathologist. A revised and uploaded BANFF 2013 classification in 6 categories (Cat) was used. RESULTS: Out of 48 biopsies, 15 (31%) were considered as normal, 4 (8%), Borderline (BL-Cat 3), 5 (10%) as Interstitial Fibrosis/Tubular Atrophy (IF/TA-Cat 5), 5 (10%) were classified as non-immunological (Cat 6), 2 as a

  17. Impact of low-level BK polyomavirus viremia on intermediate-term renal allograft function.

    PubMed

    Korth, Johannes; Widera, Marek; Dolff, Sebastian; Guberina, Hana; Bienholz, Anja; Brinkhoff, Alexandra; Anastasiou, Olympia Evdoxia; Kribben, Andreas; Dittmer, Ulf; Verheyen, Jens; Wilde, Benjamin; Witzke, Oliver

    2018-02-01

    BK polyomavirus (BKPyV)-associated nephropathy (PyVAN) is a significant cause of premature renal transplant failure. High-level BKPyV viremia is predictive for PyVAN; however, low-level BKPyV viremia does not necessarily exclude the presence of PyVAN. As data are limited regarding whether or not low-level BKPyV viremia has an effect on intermediate-term graft outcome, this study analyzes the impact of low-level BKPyV viremia on intermediate-term graft function and outcome compared with high-level viremia and non-viremic patients. All renal transplant patients received follow-up examinations at the Department of Nephrology, University Hospital Essen. Patients were screened for BKPyV viremia and stratified into three groups according to their maximum BKPyV load in serum (low-level viremia, high-level viremia, and no viremia). In 142 of 213 (67%) patients, BKPyV was never detected in serum; 42 of 213 (20%) patients were found positive for low-level viremia (≤10 4 copies/mL); and 29 of 213 (13%) patients showed high-level viremia (>10 4 copies/mL). No significant differences regarding transplant function and graft failure were observed between patients without BKPyV viremia (delta estimated glomerular filtration rate [eGFR] +0.1 mL/min [month 1 vs last visit at month 44]) and patients with low-level BKPyV viremia (delta eGFR -1.7 mL/min). In patients with high-level viremia, transplant function was significantly restricted (delta eGFR -6.5 mL/min) compared with low-level viremia until the last visit at 44 ± 9.7 months after transplantation. Although the graft function and graft loss were worse in the high-level viremia group compared with no viremia (eGFR 37 vs 45 mL/min), the difference was not significant. High-level viremia was associated with impaired graft function. In contrast, low-level BKPyV viremia had no significant impact on intermediate-term graft function. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Pre- and post-transplant monitoring of soluble CD30 levels as predictor of acute renal allograft rejection.

    PubMed

    Wang, Dong; Wu, Guo-Jun; Wu, Wei-Zhen; Yang, Shun-Liang; Chen, Jin-Hua; Wang, He; Lin, Wen-Hong; Wang, Qing-Hua; Zeng, Zhang-Xin; Tan, Jian-Ming

    2007-06-01

    Identification of renal graft candidates at high risk of impending acute rejection (AR) and graft loss may be helpful for patient-tailored immunosuppressive regimens and renal graft survival. To investigate the feasibility with soluble CD30 (sCD30) as predictor of AR, sCD30 levels of 70 patients were detected on day 0 pre-transplant and day 1, 3, 5, 7, 10, 14, 21, and 30 post-transplant. AR episodes in 6 months were recorded and then patients were divided into Group AR (n=11) and Group UC (n=59). Results showed that the patients had higher pre-transplant sCD30 levels than healthy people. A significant decrease of sCD30 was observed on the first day post-transplant and continued until day 14 post-transplant. Soluble CD30 presented a stable level from day 14 to 30 post-transplant. Pre-transplant sCD30 levels of Group AR were much higher than those of Group UC (P<0.001). Patients of Group AR also had higher sCD30 levels than those of Group UC on day 1, 3, 5, 7, 10 and 14 (P<0.001). The sCD30 level presented a significantly delayed decrease in the patients of Group AR. Statistical results showed that the highest value of area under ROC curve (0.95) was obtained on day 5 post-transplant, suggesting that sCD30 levels on day 5 are of high predictive value. Therefore, sCD30 level may be a good marker of increased alloreactivity and of significant predictive value. It's necessary to monitor the variation of sCD30 in the early period post-transplant.

  5. 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.

  6. Renal cytokines improve early after bariatric surgery.

    PubMed

    Bueter, M; Dubb, S S; Gill, A; Joannou, L; Ahmed, A; Frankel, A H; Tam, F W K; le Roux, C W

    2010-12-01

    Bariatric surgery has been suggested to improve arterial hypertension and renal function. This prospective controlled observational study aimed to investigate changes in renal inflammation, renal function and arterial blood pressure before and after bariatric surgery. Blood pressure was measured, and urine and blood samples were collected from 34 morbidly obese patients before and 4 weeks after bariatric surgery. Serum levels of cystatin C, creatinine, albumin, cholesterol and C-reactive protein (CRP) were measured, along with urinary cytokine/creatinine ratios for macrophage migration inhibitory factor (MIF), monocyte chemotactic protein (MCP) 1, chemokine ligand (CCL) 18 and CCL-15. Mean(s.e.m.) bodyweight dropped from 124·1(2·6) to 114·8(2·4) kg (P < 0·001) and mean arterial blood pressure decreased from 105·7(1·8) to 95·5(1·2) mmHg (P < 0·001) in 4 weeks. Systemic and urinary inflammatory markers improved, with a reduction in serum CRP level (P < 0·001), and decreased urinary MIF/creatinine (P < 0·001), MCP-1/creatinine (P < 0·001) and CCL-18/creatinine (P = 0·003) ratios. In contrast, urinary CCL-15/creatinine ratios did not change and the glomerular filtration rate, measured by serum cystatin C, was unchanged (P = 0·615). Surgically induced weight loss contributed to a decrease in blood pressure and markers of renal inflammation. The reduced levels of CRP and urinary cytokines suggest that bariatric surgery attenuates systemic and renal inflammatory status. Copyright © 2010 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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

  13. [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.

  14. Optical metabolic imaging measures early drug response in an allograft murine breast cancer model (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Sharick, Joe T.; Cook, Rebecca S.; Skala, Melissa C.

    2017-02-01

    Previous work has shown that cellular-level Optical Metabolic Imaging (OMI) of organoids derived from human breast cancer cell-line xenografts accurately and rapidly predicts in vivo response to therapy. To validate OMI as a predictive measure of treatment response in an immune-competent model, we used the polyomavirus middle-T (PyVmT) transgenic mouse breast cancer model. The PyVmT model includes intra-tumoral heterogeneity and a complex tumor microenvironment that can influence treatment responses. Three-dimensional organoids generated from primary PyVmT tumor tissue were treated with a chemotherapy (paclitaxel) and a PI3K inhibitor (XL147), each alone or in combination. Cellular subpopulations of response were measured using the OMI Index, a composite endpoint of metabolic response comprised of the optical redox ratio (ratio of the fluorescence intensities of metabolic co-enzymes NAD(P)H to FAD) as well as the fluorescence lifetimes of NAD(P)H and FAD. Combination treatment significantly decreased the OMI Index of PyVmT tumor organoids (p<0.0001) and in vivo tumors (p<0.0001) versus controls. Subpopulation analyses revealed a homogeneous response to combined therapy in both cultured organoids and in vivo tumors, while single agent treatment with XL147 alone or paclitaxel alone elicited heterogeneous responses in organoids. Tumor volume decreased with combination treatment through treatment day 30. These results indicate that OMI of organoids generated from PyVmT tumors can accurately reflect drug response in heterogeneous allografts with both innate and adaptive immunity. Thus, this method is promising for use in humans to predict long-term treatment responses accurately and rapidly, and could aid in clinical treatment planning.

  15. 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.

  16. 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.

  17. Hyperimmunoglobulin prophylaxis, monitoring and preemptive ganciclovir treatment eliminate the risk of CMV infection to improve patient and renal allograft survival.

    PubMed

    Schneeberger, H; Aydemir, S; Müller, R; Illner, W D; Pfeiffer, M; Theodorakis, J; Zanker, B; Land, W

    2000-01-01

    This study was designed to investigate whether the introduction of ganciclovir to clinical use for anti-CMV treatment changes the risk of CMV infection in renal transplant patients. A total of 1545 cases who had received cadaveric renal transplants were divided into two groups: group 1 (n = 721) was made up of patients who received their transplants within 6 years before the introduction (1991) of ganciclovir and group 2 (n = 824), of individuals transplanted thereafter. Patient and graft survival of CMV D+/R- patients was uni- and multivariately compared with non-CMV D+/R- patients. In CMV D+/R- patients in group 1, survival was significantly lower, and their relative risk for graft loss was 1.32-fold (P = 0.0483) that of non-CMV D+/R- patients. In group 2 patient and graft survival was identical regardless of whether the patients were at risk for CMV infection or not. The risk of CMV infection can be eliminated by hyperimmunoglobulin prophylaxis, CMV monitoring and preemptive ganciclovir treatment in renal transplant patients.

  18. 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.

  19. 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.

  20. Donor age and delayed graft function as predictors of renal allograft survival in rejection-free patients.

    PubMed

    Moreso, F; Serón, D; Gil-Vernet, S; Riera, L; Fulladosa, X; Ramos, R; Alsina, J; Grinyó, J M

    1999-04-01

    Transplant recipients of kidneys harvested from old donors have a high incidence of delayed graft function (DGF) and a poor graft outcome. This result is partly explained by the increased incidence of acute rejection in patients suffering from DGF. However, the long-term impact of donor age and DGF in rejection free renal transplants is not well established. The aim of the present work is to evaluate the impact of donor age and DGF on long-term outcome in renal transplants with or without acute rejection. We review all cadaveric kidney transplants performed in our centre between April 1984 and December 1995 treated with a cyclosporin-based immunosuppression. Five hundred and ninety-five patients were included. The overall incidence of DGF was 29.1%, and this event was associated with an increased donor age and cold ischaemia time. Univariate and multivariate analysis showed that graft loss was associated with acute rejection (relative risk (RR) 2.24, 95% confidence interval (CI) 1.62-3.01); DGF (RR 1.83, 95% CI 1.32-2.54); donors >50 years (RR 1.65, 95% CI 1.13-2.38); and retransplantation (RR 1.52, 95% CI 1.01-2.31). In rejection-free patients there were two independent predictors of graft failure: donor >50 years (RR 2.40, 95% CI 1.45-4.01); and DGF (RR 2.42, 95% CI 1.53-3.84). Regardless of the presence of acute rejection, delayed graft function amplifies the detrimental effect of advanced donor age on long-term graft outcome.

  1. Effect of N-Acetylcysteine Pretreatment of Deceased Organ Donors on Renal Allograft Function: A Randomized Controlled Trial

    PubMed Central

    Orban, Jean-Christophe; Quintard, Hervé; Cassuto, Elisabeth; Jambou, Patrick; Samat-Long, Corine; Ichai, Carole

    2015-01-01

    Background Antioxidant donor pretreatment is one of the pharmacologic strategy proposed to prevent renal ischemia-reperfusion injuries and delayed graft function (DGF). The aim of the study was to investigate whether a donor pretreatment with N-acetylcysteine (NAC) reduces the incidence of DGF in adult human kidney transplant recipients. Methods In this randomized, open-label, monocenter trial, 160 deceased heart-beating donors were allowed to perform 236 renal transplantations from September 2005 to December 2010. Donors were randomized to receive, in a single-blind controlled fashion, 600 mg of intravenous NAC 1 hr before and 2 hr after cerebral angiography performed to confirm brain death. Primary endpoint was DGF defined by the need for at least one dialysis session within the first week or a serum creatinine level greater than 200 μmol/L at day 7 after kidney transplantation. Results The incidence of DGF was similar between donors pretreated with or without NAC (39/118; 33% vs. 30/118; 25.4%; P = 0.19). Requirement for at least one dialysis session was not different between the NAC and No NAC groups (17/118; 14.4% vs. 14/118; 11.8%, P = 0.56). The two groups had comparable serum creatinine levels, estimated glomerular filtration rates, and daily urine output at days 1, 7, 15, and 30 after kidney transplantation as well as at hospital discharge. No difference in recipient mortality nor in 1-year kidney graft survival was observed. Conclusion Donor pretreatment with NAC does not improve delayed graft function after kidney transplantation. PMID:25250647

  2. De Novo Collapsing Glomerulopathy in Renal Allograft in Association with BK Virus Nephropathy in a Child and Stabilization of Renal Function by Elimination of Viremia.

    PubMed

    Gera, D N; Shah, M K; Ghodela, V A; Kute, V B; Trivedi, H L

    2017-01-01

    Well-recognized association between HIV 1 infection and collapsing glomerulopathy (CG) raises the possibility that intrarenal infection by other viruses may also contribute to the development of this lesion in native or post-transplant kidneys. There is evidence in literature about association of these lesions with cytomegalovirus, Epstein-Barr virus, hepatitis C virus, and parvovirus B19 infections. Here, we present a case report of post-transplant BK virus nephropathy in a male child who was found to have CG in subsequent biopsy 2 months later. His renal function and proteinuria were stabilized on elimination of viremia.

  3. Intravascular ultrasound of the proximal left anterior descending artery is sufficient to detect early cardiac allograft vasculopathy.

    PubMed

    Floré, Vincent; Brown, Adam J; Pettit, Stephen J; West, Nick E J; Lewis, Clive; Parameshwar, Jayan; Hoole, Stephen P

    2018-02-01

    Cardiac allograft vasculopathy (CAV) can be detected early with intravascular ultrasound (IVUS), but there is limited information on the most efficient imaging protocol. Coronary angiography and IVUS of the three coronary arteries were performed. Volumetric IVUS analysis was performed, and a Stanford grade determined for each vessel. Eighteen patients were included 18 (range 12-24) months after transplantation. Angiographic CAV severity ranged from none (CAV0) to mild (CAV1), whereas IVUS CAV severity ranged from none (Stanford grade I) to severe (grade IV). Maximal intimal thickness measured with IVUS was significantly greater in the LAD (0.84 ± 0.48 mm) than in the LCX (0.46 ± 0.32 mm) or the RCA (0.53 ± 0.41 mm, P = .005). Diagnostic accuracy of IVUS in the left anterior descending artery was 100% (18 of 18 Stanford grades matched the patient's highest overall Stanford grade), 66% in the right coronary artery (12 of 18), and 56% in the left circumflex artery (11 of 18). The minimal required length of left anterior descending artery pullbacks to attain 100% accuracy was 36 mm (range 3-36 mm) distal from the guide catheter ostium. These data suggest that focal IVUS imaging of the proximal LAD followed by volumetric analysis may suffice when screening for transplant vasculopathy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. Chronic Antibody-Mediated Rejection in Nonhuman Primate Renal Allografts: Validation of Human Histological and Molecular Phenotypes.

    PubMed

    Adam, B A; Smith, R N; Rosales, I A; Matsunami, M; Afzali, B; Oura, T; Cosimi, A B; Kawai, T; Colvin, R B; Mengel, M

    2017-11-01

    Molecular testing represents a promising adjunct for the diagnosis of antibody-mediated rejection (AMR). Here, we apply a novel gene expression platform in sequential formalin-fixed paraffin-embedded samples from nonhuman primate (NHP) renal transplants. We analyzed 34 previously described gene transcripts related to AMR in humans in 197 archival NHP samples, including 102 from recipients that developed chronic AMR, 80 from recipients without AMR, and 15 normal native nephrectomies. Three endothelial genes (VWF, DARC, and CAV1), derived from 10-fold cross-validation receiver operating characteristic curve analysis, demonstrated excellent discrimination between AMR and non-AMR samples (area under the curve = 0.92). This three-gene set correlated with classic features of AMR, including glomerulitis, capillaritis, glomerulopathy, C4d deposition, and DSAs (r = 0.39-0.63, p < 0.001). Principal component analysis confirmed the association between three-gene set expression and AMR and highlighted the ambiguity of v lesions and ptc lesions between AMR and T cell-mediated rejection (TCMR). Elevated three-gene set expression corresponded with the development of immunopathological evidence of rejection and often preceded it. Many recipients demonstrated mixed AMR and TCMR, suggesting that this represents the natural pattern of rejection. These data provide NHP animal model validation of recent updates to the Banff classification including the assessment of molecular markers for diagnosing AMR. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  5. 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.

  6. 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.

  7. Is basiliximab induction, a novel risk factor for new onset diabetes after transplantation for living donor renal allograft recipients?

    PubMed

    Prasad, Narayan; Gurjer, Desraj; Bhadauria, Dharmender; Gupta, Amit; Srivastava, Aneesh; Kaul, Anupama; Jaiswal, Akhilesh; Yadav, Brijesh; Yadav, Subhash; Sharma, Raj K

    2014-04-01

    It was found that, by affecting populations of T lymphocytes and regulatory T cells, basiliximab also indirectly affects pancreatic β-cell function and glucose homeostasis. In this prospective observational study, we included all renal transplant recipients from 1 July 2007 to 31 July 2011. The overall incidence of hyperglycaemia (transient hyperglycaemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and new onset diabetes after transplantation (NODAT)) was compared between patients with and without basiliximab induction. Of the 439 eligible study patients, 105 patients received basiliximab induction and 334 patients did not. Overall hyperglycaemia (transient hyperglycaemia, IFG, IGT and NODAT) was detected in 102/334 (30.5%) patients without induction and 44/105 (41.9%) patients with induction (P = 0.03). Of the 102 patients with hyperglycaemia in patients without basiliximab, 46 (45.1%) patients improved, while only 10 (22.7%) of the 44 patients with basiliximab improved (P = 0.016) at the end of 3 months. Finally, NODAT was observed in 56/334 (16.7%) patients without induction and 102/334 (30.5%) patients with induction. Relative risk of NODAT with basiliximab was 2.3 (95% CI 1.4-3.9) compared to that of patients without induction. Basiliximab and hepatitis C virus infection were independent risk factors for NODAT. Risk of NODAT remained high with basiliximab despite adjusting the acute rejections episodes. Basiliximab induction prevents acute rejection; however, it is associated with increased risk of NODAT. © 2014 Asian Pacific Society of Nephrology.

  8. 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.

  9. 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.

  10. 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.

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

    SciT

    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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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.

  19. 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

  20. 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.

  1. Urine protein profiling identified alpha-1-microglobulin and haptoglobin as biomarkers for early diagnosis of acute allograft rejection following kidney transplantation.

    PubMed

    Stubendorff, Beatrice; Finke, Stephanie; Walter, Martina; Kniemeyer, Olaf; von Eggeling, Ferdinand; Gruschwitz, Torsten; Steiner, Thomas; Ott, Undine; Wolf, Gunter; Wunderlich, Heiko; Junker, Kerstin

    2014-12-01

    Early diagnosis of acute rejection and effective immunosuppressive therapy lead to improvement in graft survival following kidney transplantation. In this study, we aimed to establish a urinary protein profile suitable to distinguish between patients with rejection and stable graft function and to predict acute rejection based on postoperatively collected urine samples. A further objective was to identify candidate proteins for the use as biomarkers in clinical practice. Urine samples of 116 kidney recipients were included. Rejection was proven by biopsy (n = 58), and stable transplant function was monitored for at least 2 years (n = 58). Postoperative urine samples were collected between 3rd and 10th day following transplantation. Urinary protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry. Protein identification and validation were performed using multiplex fluorescence 2DE, peptide mass fingerprinting and enzyme-linked immunosorbent assay. A protein profile including four mass peaks differentiated acute rejection from stable transplants at the time point of rejection and at the postoperative state with 73 % sensitivity and 88 % specificity. Alpha-1-microglobulin (A1MG) and Haptoglobin (Hp) were identified as putative rejection biomarkers. Protein levels were significantly higher in postoperative urine from patients with rejection (A1MG 29.13 vs. 22.06 μg/ml, p = 0.001; Hp 628.34 vs. 248.57 ng/ml, p = 0.003). The combination of both proteins enabled the diagnosis of early rejection with 85 % sensitivity and 80 % specificity. Protein profiling using mass spectrometry is suitable for noninvasive detection of rejection-specific changes following kidney transplantation. A specific protein profile enables the prediction of early acute allograft rejection in the immediate postoperative period. A1MG and Hp appear to be reliable rejection biomarkers.

  2. 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.

  3. 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

  4. 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.

  5. 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.

  6. Limitation on the use of amiloride in early renal failure.

    PubMed

    Knauf, H; Reuter, K; Mutschler, E

    1985-01-01

    The effect of a single oral dose of 10 mg amiloride was studied on urinary excretion of Na+, K+, Ca++ and Mg++ in healthy subjects and in patients with varying degrees of renal impairment. Amiloride produced a moderate diuresis and sodium excretion, and a slight calciuresis. Urinary excretion of potassium was significantly reduced as compared to the controls. Despite its diuretic and natriuretic effects, amiloride did not change the excretion of Mg++ as compared to the pretreatment period. When the creatinine clearance was below 50 ml/min, the net excretion of Na+ and Ca++ was drastically reduced. However, K+ retention and neutrality of Mg++ excretion were maintained down to end-stage renal disease. In the healthy volunteers the mean elimination half-life of amiloride was 20 h, and it rose to about 100 h in end-stage renal disease. This was because about 3/4 of native amiloride was eliminated through the kidney. Nonrenal elimination of amiloride was calculated to amount to only 1/4 of the total elimination. Therefore, the anticaliuretic amiloride is a valuable comedication in subjects with normal kidney function to prevent K+ and Mg++ loss. However, its use is hazardous if plasma creatinine is raised.

  7. 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.

  8. 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

  9. 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.

  10. 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

  11. 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

  12. MicroRNA-146b-5p Identified in Porcine Liver Donation Model is Associated with Early Allograft Dysfunction in Human Liver Transplantation

    PubMed Central

    Li, Cheukfai; Zhao, Qiang; Zhang, Wei; Chen, Maogen; Ju, Weiqiang; Wu, Linwei; Han, Ming; Ma, Yi; Zhu, Xiaofeng; Wang, Dongping; Guo, Zhiyong; He, Xiaoshun

    2017-01-01

    Background Poor transplant outcome was observed in donation after brain death followed by circulatory death (DBCD), since the donor organs suffered both cytokine storm of brain death and warm ischemia injury. MicroRNAs (miRNAs) have emerged as promising disease biomarkers, so we sought to establish a miRNA signature of porcine DBCD and verify the findings in human liver transplantation. Material/Methods MiRNA expression was determined with miRNA sequencing in 3 types of the porcine model of organ donation, including donation after brain death (DBD) group, donation after circulatory death (DCD) group, and DBCD group. Bioinformatics analysis was performed to reveal the potential regulatory behavior of target miRNA. Human liver graft biopsy samples after reperfusion detected by fluorescence in situ hybridization were used to verify the expression of target miRNA. Results We compared miRNA expression profiles of the 3 donation types. The porcine liver graft miR-146b was significantly increased and selected in the DBCD group versus in the DBD and DCD groups. The donor liver expression of human miR-146b-5p, which is homologous to porcine miR-146b, was further examined in 42 cases of human liver transplantations. High expression of miR-146b-5p successfully predicted the post-transplant early allograft dysfunction (EAD) with the area under the ROC curve (AUC) 0.759 (P=0.004). Conclusions Our results revealed the miRNA signature of DBCD liver grafts for the first time. The miR-146b-5p may have important clinical implications for monitoring liver graft function and predicating transplant outcomes. PMID:29227984

  13. The Association Between Renin-Angiotensin System Blockade and Long-term Outcomes in Renal Transplant Recipients: The Wisconsin Allograft Recipient Database (WisARD).

    PubMed

    Shin, Jung-Im; Palta, Mari; Djamali, Arjang; Kaufman, Dixon B; Astor, Brad C

    2016-07-01

    Renin-angiotensin system (RAS) blockade reduces mortality in the general population and among non-dialysis-dependent patients with chronic kidney disease. The RAS blockade also decreases proteinuria and protects renal function in non-transplant patients with chronic kidney disease. It remains controversial, however, whether this translates to improved patient or graft survival among transplant recipients. We analyzed 2684 primary kidney transplant recipients at the University of Wisconsin in 1994 to 2010 who had a functioning graft at 6 months after transplantation. We assessed the association of RAS blockade with patient and graft survival using time-dependent Cox and marginal structural models. Three hundred seventy-seven deaths and 329 graft failures before death (638 total graft losses) occurred during a median of 5.4 years of follow-up. The RAS blockade was associated with an adjusted-hazard ratio of 0.63 (95% confidence interval, 0.53-0.75) for total graft loss, 0.69 (0.55-0.86) for death, and 0.62 (0.49-0.78) for death-censored graft failure. The associations of RAS blockade with a lower risk of total graft loss and mortality were stronger with more severe proteinuria. The RAS blockade was associated with a 2-fold higher risk of hyperkalemia. Our findings suggest RAS blockade is associated with better patient and graft survival in renal transplant recipients.

  14. [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.

  15. 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

  16. 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

  17. Lin28 sustains early renal progenitors and induces Wilms tumor

    PubMed Central

    Urbach, Achia; Yermalovich, Alena; Zhang, Jin; Spina, Catherine S.; Zhu, Hao; Perez-Atayde, Antonio R.; Shukrun, Rachel; Charlton, Jocelyn; Sebire, Neil; Mifsud, William; Dekel, Benjamin; Pritchard-Jones, Kathy; Daley, George Q.

    2014-01-01

    Wilms Tumor, the most common pediatric kidney cancer, evolves from the failure of terminal differentiation of the embryonic kidney. Here we show that overexpression of the heterochronic regulator Lin28 during kidney development in mice markedly expands nephrogenic progenitors by blocking their final wave of differentiation, ultimately resulting in a pathology highly reminiscent of Wilms tumor. Using lineage-specific promoters to target Lin28 to specific cell types, we observed Wilms tumor only when Lin28 is aberrantly expressed in multiple derivatives of the intermediate mesoderm, implicating the cell of origin as a multipotential renal progenitor. We show that withdrawal of Lin28 expression reverts tumorigenesis and markedly expands the numbers of glomerulus-like structures and that tumor formation is suppressed by enforced expression of Let-7 microRNA. Finally, we demonstrate overexpression of the LIN28B paralog in a significant percentage of human Wilms tumor. Our data thus implicate the Lin28/Let-7 pathway in kidney development and tumorigenesis. PMID:24732380

  18. 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

  19. 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

  20. 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.

  1. 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.

  2. Graft extrusion in both the coronal and sagittal planes is greater after medial compared with lateral meniscus allograft transplantation but is unrelated to early clinical outcomes.

    PubMed

    Lee, Dae-Hee; Lee, Chang-Rack; Jeon, Jin-Ho; Kim, Kyung-Ah; Bin, Seong-Il

    2015-01-01

    Graft extrusion after meniscus allograft transplantation (MAT) may be affected by horn fixation, which differs between medial and lateral MAT. Few studies have compared graft extrusion, especially sagittal extrusion, after medial and lateral MAT. In patients undergoing medial and lateral MAT, graft extrusion is likely similar and not correlated with postoperative Lysholm scores. Cohort study; Level of evidence, 2. Meniscus graft extrusion in the coronal and sagittal planes was compared in 51 knees undergoing medial MAT and 84 undergoing lateral MAT. Distances from the anterior and posterior articular cartilage margins to the anterior (anterior cartilage meniscus distance [ACMD]) and posterior (posterior cartilage meniscus distance [PCMD]) horns, respectively, were assessed on immediate postoperative magnetic resonance imaging and compared in patients undergoing medial and lateral MAT. Correlations between coronal and sagittal graft extrusion and between extrusion and the Lysholm score were compared in the 2 groups. In the coronal plane, mean absolute (4.3 vs 2.7 mm, respectively; P<.001) and relative (39% vs 21%, respectively; P<.001) graft extrusions were significantly greater for medial than lateral MAT. In the sagittal plane, mean absolute and relative ACMD and PCMD values were significantly greater for medial than lateral MAT (P<.001 each). For both medial and lateral MAT, mean absolute and relative ACMDs were significantly larger than PCMDs (P<.001 each). Graft extrusion>3 mm in the coronal plane was significantly more frequent in the medial (78%) than in the lateral (35%) MAT group. In the sagittal plane, the frequencies of ACMDs (72% vs 39%, respectively) and PCMDs (23% vs 4%, respectively) >3 mm were also significantly greater in the medial than in the lateral MAT group. Coronal and sagittal extrusions were not correlated with postoperative Lysholm scores for both medial and lateral MAT. The amount and incidence of graft extrusion were greater after medial

  3. 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.

  4. 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.

  5. Renal Tumors: Technical Success and Early Clinical Experience with Radiofrequency Ablation of 18 Tumors

    SciT

    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

  6. 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.

  7. 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.

  8. Can zero-hour cortical biopsy predict early graft outcomes after living donor renal transplantation?

    PubMed

    Rathore, Ranjeet Singh; Mehta, Nisarg; Mehta, Sony Bhaskar; Babu, Manas; Bansal, Devesh; Pillai, Biju S; Sam, Mohan P; Krishnamoorthy, Hariharan

    2017-11-01

    The aim of this study was to identify relevance of subclinical pathological findings in the kidneys of living donors and correlate these with early graft renal function. This was a prospective study on 84 living donor kidney transplant recipients over a period of two years. In all the donors, cortical wedge biopsy was taken and sent for assessment of glomerular, mesangial, and tubule status. The graft function of patients with normal histology was compared with those of abnormal histological findings at one, three, and six months, and one year post-surgery. Most abnormal histological findings were of mild degree. Glomerulosclerosis (GS, 25%), interstitial fibrosis (IF, 13%), acute tubular necrosis (ATN 5%), and focal tubal atrophy (FTA, 5%) were the commonly observed pathological findings in zero-hour biopsies. Only those donors who had histological changes of IF and ATN showed progressive deterioration of renal function at one month, three months, six months, and one year post-transplantation. In donors with other histological changes, no significant effect on graft function was observed. Zero-hour cortical biopsy gave us an idea of the general status of the donor kidney and presence or absence of subclinical pathological lesions. A mild degree of subclinical and pathological findings on zero-hour biopsy did not affect early graft renal function in living donor kidney transplantation. Zero-hour cortical biopsy could also help in discriminating donor-derived lesions from de novo alterations in the kidney that could happen subsequently.

  9. 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

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

  2. 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.

  3. Fetal bilateral renal agenesis, phocomelia, and single umbilical artery associated with cocaine abuse in early pregnancy.

    PubMed

    Kashiwagi, Maki; Chaoui, Rabih; Stallmach, Thomas; Hürlimann, Sandra; Lauper, Urs; Hebisch, Gundula

    2003-11-01

    Maternal cocaine abuse in pregnancy is associated with complications such as intrauterine growth retardation, abruptio placentae, and preterm delivery. We report what is, to our knowledge, the first published observation of fetal bilateral renal agenesis associated with a vascular disruption syndrome comprising upper limb reduction defect and a single umbilical artery following maternal cocaine abuse in early pregnancy. This constellation in a fetus aborted at 18 weeks extends the spectrum of complications possibly associated with cocaine abuse in pregnancy. Copyright 2003 Wiley-Liss, Inc.

  4. Practical recommendations for the early use of m-TOR inhibitors (sirolimus) in renal transplantation.

    PubMed

    Campistol, Josep M; Cockwell, Paul; Diekmann, Fritz; Donati, Donato; Guirado, Luis; Herlenius, Gustaf; Mousa, Dujanah; Pratschke, Johann; San Millán, Juan Carlos Ruiz

    2009-07-01

    m-TOR inhibitors (e.g. sirolimus) are well-tolerated immunosuppressants used in renal transplantation for prophylaxis of organ rejection, and are associated with long-term graft survival. Early use of sirolimus is often advocated by clinicians, but this may be associated with a number of side-effects including impaired wound-healing, lymphoceles and delayed graft function. As transplant clinicians with experience in the use of sirolimus, we believe such side-effects can be limited by tailored clinical management. We present recommendations based on published literature and our clinical experience. Furthermore, guidance is provided on sirolimus use during surgery, both at transplantation and for subsequent operations.

  5. Hypertension in kidney transplantation is associated with an early renal nerve sprouting

    PubMed Central

    Rovella, Valentina; Borri, Filippo; Anemona, Lucia; Giannini, Elena; Giacobbi, Erica; Saggini, Andrea; Palmieri, Giampiero; Anselmo, Alessandro; Bove, Pierluigi; Melino, Gerry; Valentina, Guardini; Tesauro, Manfredi; Gabriele, D’Urso; Di Daniele, Nicola

    2017-01-01

    Abstract Background. Normalization of arterial pressure occurs in just a few patients with hypertensive chronic kidney disease undergoing kidney transplantation. Hypertension in kidney transplant recipients may be related to multiple factors. We aimed to assess whether hypertension in kidney-transplanted patients may be linked to reinnervation of renal arteries of the transplanted kidney. Methods. We investigated renal arteries innervation from native and transplanted kidneys in three patients 5 months, 2 years and 11 years after transplantation, respectively. Four transplanted kidneys from non-hypertensive patients on immunosuppressive treatment without evidence of hypertensive arteriolar damage were used as controls. Results. Evidence of nerve sprouting was observed as early as 5 months following transplantation, probably originated from ganglions of recipient patient located near the arterial anastomosis and was associated with mild hypertensive arteriolar damage. Regeneration of periadventitial nerves was already complete 2 years after transplantation. Nerve density tended to reach values observed in native kidney arteries and was associated with hypertension-related arteriolar lesions in transplanted kidneys. Control kidneys, albeit on an immunosuppressive regimen, presented only a modest regeneration of sympathetic nerves. Conclusions. Our results suggest that the considerable increase in sympathetic nerves, as found in patients with severe arterial damage, may be correlated to hypertension rather than to immunosuppressive therapy, thus providing a morphological basis for hypertension recurrence despite renal denervation. PMID:28498963

  6. Preoperative determinant of early postoperative renal function following radical cystectomy and intestinal urinary diversion.

    PubMed

    Gondo, Tatsuo; Ohno, Yoshio; Nakashima, Jun; Hashimoto, Takeshi; Nakagami, Yoshihiro; Tachibana, Masaaki

    2017-02-01

    To identify preoperative factors correlated with postoperative early renal function in patients who had undergone radical cystectomy (RC) and intestinal urinary diversion. We retrospectively identified 201 consecutive bladder cancer patients without distant metastasis who had undergone RC at our institution between 2003 and 2012. The estimated glomerular filtration rate (eGFR) was calculated using the modified Chronic Kidney Disease Epidemiology equation before RC and 3 months following RC. Univariate and stepwise multiple linear regression analyses were applied to estimate postoperative renal function and to identify significant preoperative predictors of postoperative renal function. Patients who had undergone intestinal urinary diversion and were available for the collection of follow-up data (n = 164) were eligible for the present study. Median preoperative and postoperative eGFRs were 69.7 (interquartile range [IQR] 56.3-78.0) and 70.7 (IQR 57.3-78.1), respectively. In univariate analyses, age, preoperative proteinuria, thickness of abdominal subcutaneous fat tissue (TSF), preoperative serum creatinine level, preoperative eGFR, and urinary diversion type were significantly associated with postoperative eGFR. In a stepwise multiple linear regression analysis, preoperative eGFR, age, and TSF were significant factors for predicting postoperative eGFR (p < 0.001, p = 0.02, and p = 0.046, respectively). The estimated postoperative eGFRs correlated well with the actual postoperative eGFRs (r = 0.65, p < 0.001). Preoperative eGFR, age, and TSF were independent preoperative factors for determining postoperative renal function in patients who had undergone RC and intestinal urinary diversion. These results may be used for patient counseling before surgery, including the planning of perioperative chemotherapy administration.

  7. 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.

  8. Outcome of Early Initiation of Peritoneal Dialysis in Patients with End-Stage Renal Failure

    PubMed Central

    Oh, Kook-Hwan; Hwang, Young-Hwan; Cho, Jung-Hwa; Kim, Mira; Ju, Kyung Don; Joo, Kwon Wook; Kim, Dong Ki; Kim, Yon Su; Ahn, Curie

    2012-01-01

    Recent studies reported that early initiation of hemodialysis may increase mortality. However, studies that assessed the influence of early initiation of peritoneal dialysis (PD) yielded controversial results. In the present study, we evaluated the prognosis of early initiation of PD on the various outcomes of end stage renal failure patients by using propensity-score matching methods. Incident PD patients (n = 491) who started PD at SNU Hospital were enrolled. The patients were divided into 'early starters (n = 244)' and 'late starters (n = 247)' on the basis of the estimated glomerular filtration rate (eGFR) at the start of dialysis. The calculated propensity-score was used for one-to-one matching. After propensity-score-based matching (n = 136, for each group), no significant differences were observed in terms of all-cause mortality (P = 0.17), technique failure (P = 0.62), cardiovascular event (P = 0.96) and composite event (P = 0.86) between the early and late starters. Stratification analysis in the propensity-score quartiles (n = 491) exhibited no trend toward better or poorer survival in terms of all-cause mortality. In conclusion, early commencement of PD does not reduce the mortality risk and other outcomes. Although the recent guidelines suggest that initiation of dialysis at higher eGFR, physicians should not determine the time to initiate PD therapy simply rely on the eGFR alone. PMID:22323864

  9. Small Renal Masses in Close Proximity to the Collecting System and Renal Sinus Are Enriched for Malignancy and High Fuhrman Grade and Should Be Considered for Early Intervention.

    PubMed

    Correa, Andres F; Toussi, Amir; Amin, Milon; Hrebinko, Ronald L; Gayed, Bishoy A; Parwani, Anil V; Maranchie, Jodi K

    2018-02-05

    Recent reports show a correlation between renal tumor radiographic characteristics and pathologic features. We hypothesize that a more central location within the relatively hypoxic renal medulla might confer a more aggressive tumor phenotype. To test this, radiographic tumor characteristics were compared with tumor grade and histology. We retrospectively reviewed renal masses <4 cm in diameter that underwent resection between 2008 and 2013. Tumor location was recorded using standard R.E.N.A.L. Nephrometry Score. Multivariate logistic regression was performed to compare independent anatomic features with incidence of malignancy and high nuclear grade. A total of 334 renal tumors had information available for analysis. Univariate analysis showed that increasing endophycity and proximity to the collecting system (<4 mm) were predictors of malignancy and high-grade features. In multivariate analysis, proximity to the collecting system <4 mm remained the as the only anatomical variable predictive of malignancy (odds ratio [OR], 3.58; 95% confidence interval [CI], 1.06-12.05; P = .04) and high nuclear grade (OR, 2.81; 95% CI, 1.44-5.51; P = .003). Malignancy and high tumor grade occur with much greater frequency when tumors are located deep in the kidney, in close proximity to the collecting system and renal sinus. Ninety-six percent of small renal masses in this region were cancers and nearly half were Fuhrman Grade 3 or 4, suggesting that these small centrally located tumors should be targeted for early intervention. Copyright © 2018 Elsevier Inc. All rights reserved.

  10. Early administration of tolvaptan preserves renal function in elderly patients with acute decompensated heart failure.

    PubMed

    Kimura, Kazuhiro; Momose, Tomoyasu; Hasegawa, Tomoya; Morita, Takehiro; Misawa, Takuo; Motoki, Hirohiko; Izawa, Atsushi; Ikeda, Uichi

    2016-05-01

    Loop diuretics used in the treatment of heart failure often induce renal impairment. This study was conducted in order to evaluate the renal protective effect of adding tolvaptan (TLV), compared to increasing the furosemide (FRM) dose, for the treatment of acute decompensated heart failure (ADHF) in a real-world elderly patient population. This randomized controlled trial enrolled 52 consecutive hospitalized patients (age 83.4±9.6 years) with ADHF. The patients were assigned alternately to either the TLV group (TLV plus conventional treatment, n=26) or the FRM group (increasing the dose of FRM, n=26). TLV was administered within 24h from admission. The incidence of worsening renal function (WRF) within 7 days from admission was significantly lower in the TLV group (26.9% vs. 57.7%, p=0.025). Furthermore, the rates of occurrence of persistent and late-onset (≥5 days from admission) WRF were significantly lower in the TLV group. Persistent and late-onset WRF were significantly associated with a higher incidence of cardiac death or readmission for worsening heart failure in the 90 days following discharge, compared to transient and early-onset WRF, respectively. Early administration of TLV, compared to increased FRM dosage, reduces the incidence of WRF in real-world elderly ADHF patients. In addition, it reduces the occurrence of 'worse' WRF-persistent and late-onset WRF-which are associated with increased rates of cardiac death or readmission for worsening heart failure in the 90 days after discharge. Copyright © 2015 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.

  11. 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.

  12. 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.

  13. Early serum creatinine changes and outcomes in patients admitted for acute heart failure: the cardio-renal syndrome revisited.

    PubMed

    Núñez, Julio; Garcia, Sergio; Núñez, Eduardo; Bonanad, Clara; Bodí, Vicent; Miñana, Gema; Santas, Enrique; Escribano, David; Bayes-Genis, Antonio; Pascual-Figal, Domingo; Chorro, Francisco J; Sanchis, Juan

    2017-08-01

    The changes in renal function that occurred in patients with acute decompensated heart failure (ADHF) are prevalent, and have multifactorial etiology and dissimilar prognosis. To what extent the prognostic role of such changes may vary according to the presence of renal insufficiency at admission is not clear. Accordingly, we sought to determine whether early creatinine changes (ΔCr) (admission to 48-72 hours) had an effect on 1-year mortality relative to the presence of renal insufficiency at admission. We included 705 consecutive patients admitted with the diagnosis of ADHF. Admission renal insufficiency was defined as serum creatinine ≥1.4mg/dl (A-RI cr ) or estimated glomerular filtration rate <60ml/min/1.73m 2 (A-RI GFR ). Appropriate survival regression techniques were used. The mean age was 72.9±11.4 years and 51.2% were males. Patients with admission renal insufficiency (24.7% and 42.8% for A-RIcr and A-RIGFR, respectively) had higher prevalence of extreme values in ΔCr in either direction (increasing/decreasing). At 1-year follow-up, 114 (16.2%) deaths were registered. The multivariable analysis showed a significant interaction between admission renal insufficiency and ΔCr ( p=0.004 and p=0.019 for A-RIcr and A-RIGFR, respectively). In the presence of renal insufficiency, the continuum of ΔCr followed a positive and almost linear relationship with mortality risk. Conversely, in patients without renal insufficiency, those changes adopted a 'J-shape' trajectory with increased mortality at both ends of the curve distribution. In patients with ADHF the effect of ΔCr on 1-year mortality varied according to its magnitude and the presence of admission renal insufficiency. There was a graded-association with mortality when renal insufficiency was present on admission.

  14. [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.

  15. The unsuitability of implantable Doppler probes for the early detection of renal vascular complications – a porcine model for prevention of renal transplant loss

    PubMed Central

    Jespersen, Bente; Møldrup, Ulla; Keller, Anna K.

    2017-01-01

    Background Vascular occlusion is a rare, but serious complication after kidney transplantation often resulting in graft loss. We therefore aimed to develop an experimental porcine model for stepwise reduction of the renal venous blood flow and to compare an implantable Doppler probe and microdialysis for fast detection of vascular occlusion. Methods In 20 pigs, implantable Doppler probes were placed on the renal artery and vein and a microdialysis catheter was placed in the renal cortex. An arterial flowprobe served as gold standard. Following two-hour baseline measurements, the pigs were randomised to stepwise venous occlusion, complete venous occlusion, complete arterial occlusion or controls. Results All parameters were stable through baseline measurements. Glutamate and lactate measured by microdialysis increased significantly (p = 0.02 and p = 0.03 respectively) 30 minutes after a 2/3 (66%) reduction in renal blood flow. The implantable Doppler probe was not able to detect flow changes until there was total venous occlusion. Microdialysis detected changes in local metabolism after both arterial and venous occlusion; the implantable Doppler probe could only detect vascular occlusions on the vessel it was placed. Conclusions We developed a new model for stepwise renal venous blood flow occlusion. Furthermore, the first comparison of the implantable Doppler probe and microdialysis for detection of renal vascular occlusions was made. The implantable Doppler probe could only detect flow changes after a complete occlusion, whereas microdialysis detected changes earlier, and could detect both arterial and venous occlusion. Based on these results, the implantable Doppler probe for early detection of vascular occlusions cannot be recommended. PMID:28542429

  16. Cardiovascular Disease Outcomes Related to Early Stage Renal Impairment Following Liver Transplantation.

    PubMed

    VanWagner, Lisa B; Montag, Samantha; Zhao, Lihui; Allen, Norrina B; Lloyd-Jones, Donald M; Das, Arighno; Skaro, Anton I; Hohmann, Samuel; Friedewald, John J; Levitsky, Josh

    2018-03-20

    In the general population, even mild renal disease is associated with increased cardiovascular (CV) complications. Whether this is true in liver transplant recipients (LTR) is unknown. This was a retrospective cohort study of 671 LTR (2002-2012) from a large urban tertiary care center and 37,322 LTR using Vizient hospitalization data linked to the United Network for Organ Sharing. The MDRD4 equation estimated GFR (eGFR). Outcomes were 1-year CV complications (death/hospitalization from myocardial infarction, heart failure, atrial fibrillation, cardiac arrest, pulmonary embolism or stroke) and mortality. Latent mixture modeling identified trajectories in eGFR in the first LT year in the 671 patients. Mean(SD) eGFR was 72.1(45.7) ml/min/1.73m. Six distinct eGFR trajectories were identified in the local cohort (n=671): qualitatively Normal-Slow Decrease (4% of cohort), Normal-Rapid Decrease (4%), Mild-Stable (18%), Mild-Slow Decrease (35%), Moderate-Stable (30%), and Severe-Stable (9%). In multivariable analyses adjusted for confounders and baseline eGFR, the greatest odds of 1-year CV complications were in the Normal-Rapid Decrease group (OR, 95% CI: 10.6, 3.0-36.9). Among the national cohort, each 5-unit lower eGFR at LT was associated with a 2% and 5% higher hazard of all-cause and CV-mortality, respectively (p<0.0001) independent of multiple confounders. Even mild renal disease at the time of LT is a risk factor for posttransplant all-cause and CV mortality. More rapid declines in eGFR soon after LT correlate with risk of adverse CV outcomes, highlighting the need to study whether early renal preservation interventions also reduce CV complications.

  17. 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

  18. Procalcitonin for the early prediction of renal parenchymal involvement in children with UTI: preliminary results.

    PubMed

    Kotoula, Aggeliki; Gardikis, Stefanos; Tsalkidis, Aggelos; Mantadakis, Elpis; Zissimopoulos, Athanassios; Kambouri, Katerina; Deftereos, Savvas; Tripsianis, Gregorios; Manolas, Konstantinos; Chatzimichael, Athanassios; Vaos, George

    2009-01-01

    In order to establish the most reliable marker for distinguishing urinary tract infections (UTI) with and without renal parenchymal involvement (RPI), we recorded the clinical features and admission leukocyte count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and serum procalcitonin (PCT) in 57 children (including 43 girls) aged 2-108 months admitted with a first episode of UTI. RPI was evaluated by Tc-99m dimercaptosuccinic acid (DMSA) scintigraphy within 7 days of admission. To establish cut-off points for ESR, CRP, and PCT, we used receiver operating characteristics curves and compared the area under the curve for ESR, CRP, and PCT. Twenty-seven children were diagnosed as having RPI based on positive renal scintigraphy. A body temperature of >38 degrees C, a history of diarrhea, and poor oral intake were more common in patients with RPI. ESR, CRP, and PCT, but not leukocyte count, were significantly higher in patients with RPI (P < 0.001). PCT was more sensitive and specific for the diagnosis of upper versus lower UTI than ESR and CRP. Using a cut-off value of 0.85 ng/ml, PCT had the best performance, with sensitivity, specificity, and positive and negative predictive values of 89%, 97%, 96%, and 91% respectively. Serum PCT is a better marker than ESR, CRP, and leukocyte count for the early prediction of RPI in children with a first episode of UTI.

  19. Early renal function recovery and long-term graft survival in kidney transplantation.

    PubMed

    Wan, Susan S; Cantarovich, Marcelo; Mucsi, Istvan; Baran, Dana; Paraskevas, Steven; Tchervenkov, Jean

    2016-05-01

    Following kidney transplantation (KTx), renal function improves gradually until a baseline eGFR is achieved. Whether or not a recipient achieves the best-predicted eGFR after KTx may have important implications for immediate patient management, as well as for long-term graft survival. The aim of this cohort study was to calculate the renal function recovery (RFR) based on recipient and donor eGFR and to evaluate the association between RFR and long-term death-censored graft failure (DCGF). We studied 790 KTx recipients between January 1990 and August 2014. The last donor SCr prior to organ procurement was used to estimate donor GFR. Recipient eGFR was calculated using the average of the best three SCr values observed during the first 3 months post-KTx. RFR was defined as the ratio of recipient eGFR to half the donor eGFR. 53% of recipients had an RFR ≥1. There were 127 death-censored graft failures (16%). Recipients with an RFR ≥1 had less DCGF compared with those with an RFR <1 (HR 0.56; 95% CI 0.37-0.85; P = 0.006). Transplant era, acute rejection, ECD and DGF were also significant determinants of graft failure. Early recovery of predicted eGFR based on donor eGFR is associated with less DCGF after KTx. © 2016 Steunstichting ESOT.

  20. 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

  1. EARLY DIAGNOSIS IN POST RENAL TRANSPLANT OPPORTUNISTIC INFECTIONS: A FRESH LOOK.

    PubMed

    Chopra, G S; Narula, A S; Reddy, P S; Bhardwaj, J R

    1999-04-01

    A total of 86 renal transplant patients who were transplanted with live related donor (LRD) and live unrelated donor (LURD) kidneys were studied for opportunistic infections. Immune diagnosis of Toxoplasma, Cytomegalovirus (CMV), Herpes-simplex virus type II (HSV-2), Aspergillosis and Tuberculosis was carried out in these patients along with sputum examination, CSF studies and biopsy of lymphnode and other tissues in few cases. A high degree of Toxoplasma, CMV & HSV-2 positivity was seen in transplanted patients. However sensitivity of serological diagnosis of tuberculos was found to be low with standard criteria, which increased significantly when modified criteria were used. It is concluded that regular immunological monitoring should be carried out in transplanted patients so as to reach an early diagnosis and management of opportunistic infections.

  2. Development of a neural network for early detection of renal osteodystrophy

    NASA Astrophysics Data System (ADS)

    Cheng, Shirley N.; Chan, Heang-Ping; Adler, Ronald; Niklason, Loren T.; Chang, Chair-Li

    1991-07-01

    Bone erosion presenting as subperiosteal resorption on the phalanges of the hand is an early manifestation of hyperparathyroidism associated with chronic renal failure. At present, the diagnosis is made by trained radiologists through visual inspection of hand radiographs. In this study, a neural network is being developed to assess the feasibility of computer-aided detection of these changes. A two-pass approach is adopted. The digitized image is first compressed by a Laplacian pyramid compact code. The first neural network locates the region of interest using vertical projections along the phalanges and then the horizontal projections across the phalanges. A second neural network is used to classify texture variations of trabecular patterns in the region using a concurrence matrix as the input to a two-dimensional sensor layer to detect the degree of associated osteopenia. Preliminary results demonstrate the feasibility of this approach.

  3. Renal function improvement in liver transplant recipients after early everolimus conversion: A clinical practice cohort study in Spain.

    PubMed

    Bilbao, Itxarone; Salcedo, Magdalena; Gómez, Miguel Angel; Jimenez, Carlos; Castroagudín, Javier; Fabregat, Joan; Almohalla, Carolina; Herrero, Ignacio; Cuervas-Mons, Valentín; Otero, Alejandra; Rubín, Angel; Miras, Manuel; Rodrigo, Juan; Serrano, Trinidad; Crespo, Gonzalo; De la Mata, Manuel; Bustamante, Javier; Gonzalez-Dieguez, M Luisa; Moreno, Antonia; Narvaez, Isidoro; Guilera, Magda

    2015-08-01

    A national, multicenter, retrospective study was conducted to assess the results obtained for liver transplant recipients with conversion to everolimus in daily practice. The study included 477 recipients (481 transplantations). Indications for conversion to everolimus were renal dysfunction (32.6% of cases), hepatocellular carcinoma (HCC; 30.2%; prophylactic treatment for 68.9%), and de novo malignancy (29.7%). The median time from transplantation to conversion to everolimus was 68.7 months for de novo malignancy, 23.8 months for renal dysfunction, and 7.1 months for HCC and other indications. During the first year of treatment, mean everolimus trough levels were 5.4 (standard deviation [SD], 2.7) ng/mL and doses remained stable (1.5 mg/day) from the first month after conversion. An everolimus monotherapy regimen was followed by 28.5% of patients at 12 months. Patients with renal dysfunction showed a glomerular filtration rate (4-variable Modification of Diet in Renal Disease) increase of 10.9 mL (baseline mean, 45.8 [SD, 25.3] versus 57.6 [SD, 27.6] mL/minute/1.73 m(2) ) at 3 months after everolimus initiation (P < 0.001), and 6.8 mL at 12 months. Improvement in renal function was higher in patients with early conversion (<1 year). Adverse events were the primary reason for discontinuation in 11.2% of cases. The probability of survival at 3 years after conversion to everolimus was 83.0%, 71.1%, and 59.5% for the renal dysfunction, de novo malignancy, and HCC groups, respectively. Everolimus is a viable option for the treatment of renal dysfunction, and earlier conversion is associated with better recovery of renal function. Prospective studies are needed to confirm advantages in patients with malignancy. © 2015 American Association for the Study of Liver Diseases.

  4. [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.

  5. 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.

  6. Baroreflex control of renal sympathetic nerve activity in early heart failure assessed by the sequence method

    PubMed Central

    Lataro, Renata Maria; Silva, Luiz Eduardo Virgilio; Silva, Carlos Alberto Aguiar; Salgado, Helio Cesar

    2017-01-01

    Key points The integrity of the baroreflex control of sympathetic activity in heart failure (HF) remains under debate.We proposed the use of the sequence method to assess the baroreflex control of renal sympathetic nerve activity (RSNA).The sequence method assesses the spontaneous arterial pressure (AP) fluctuations and their related changes in heart rate (or other efferent responses), providing the sensitivity and the effectiveness of the baroreflex. Effectiveness refers to the fraction of spontaneous AP changes that elicits baroreflex‐mediated variations in the efferent response.Using three different approaches, we showed that the baroreflex sensitivity between AP and RSNA is not altered in early HF rats. However, the sequence method provided evidence that the effectiveness of baroreflex in changing RSNA in response to AP changes is markedly decreased in HF.The results help us better understand the baroreflex control of the sympathetic nerve activity. Abstract In heart failure (HF), the reflex control of the heart rate is known to be markedly impaired; however, the baroreceptor control of the sympathetic drive remains under debate. Applying the sequence method to a series of arterial pressure (AP) and renal sympathetic nerve activity (RSNA), we demonstrated a clear dysfunction in the baroreflex control of sympathetic activity in rats with early HF. We analysed the baroreflex control of the sympathetic drive using three different approaches: AP vs. RSNA curve, cross‐spectral analysis and sequence method between AP and RSNA. The sequence method also provides the baroreflex effectiveness index (BEI), which represents the percentage of AP ramps that actually produce a reflex response. The methods were applied to control rats and rats with HF induced by myocardial infarction. None of the methods employed to assess the sympathetic baroreflex gain were able to detect any differences between the control and the HF group. However, rats with HF exhibited a lower BEI

  7. 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.

  8. Effect of alendronate on early bone loss of renal transplant recipients.

    PubMed

    Abediazar, S; Nakhjavani, M R

    2011-03-01

    Renal transplant recipients (RTRs) are at risk of developing osteoporosis and osteopenia due to underlying renal osteodystrophy, hypophosphatemia, and immunosuppression. This process occurs more frequently in the first year after renal transplantation (RTX), resulting in eventual bone loss and fractures. The purpose of this study was to evaluate the effect of low-dose alendronate to prevent early bone loss after RTX. We prospectively studied 43 successful RTR including 22 men and 21-women with a mean overall age of 39.16±11.73 years, mean body mass index of 23.6±3.73, and mean dialysis duration of 25.73±17.67 months. We matched them based on age and sex: the alendronate-treated group received vitamin D (Vit D) during the study plus 30 mg alendronate weekly from 1 month after RTX. The control group only received Vit D. We measured serum calcium, phosphate, alkaline phosphatase, blood urea, creatinine, and intact parathyroid hormone (iPTH) at the pretransplant baseline and monthly thereafter as well as BMD of the lumbar spine, femur, and radius pretransplant baseline versus 3 and 6 months after RTX. At 6 month after RTX, the lumbar BMD in the alendronate group increased significantly from 0.819±0.11 to 0.863±0.14 (P<.01), while it decreased in the control group from 0.897±0.17 to 0.817±0.16 (P<.001). There was also a significant increase in radius BMD (P<.001) and a nonsignificant increase in femoral BMD in the alendronate versus a significant decrease of femoral and radius BMD (P<.001) in the control group at 6 months. Upon multivariate analysis, there was a significant correlation between alendronate and spine BMD (r=.45, P<.001) but no linear regression between age, sex, BMI, dialysis duration of or iPTH with femoral, spine, or radius BMD changes at month 6. Low-dose alendronate was significantly useful to mitigate fast bone loss and increase BMD immediately after RTX. Copyright © 2011. Published by Elsevier Inc.

  9. Urinary podocalyxin, the novel biomarker for detecting early renal change in obesity.

    PubMed

    Suwanpen, Chayanut; Nouanthong, Phonethipsavanh; Jaruvongvanich, Veeravich; Pongpirul, Krit; Pongpirul, Wannarat Amornnimit; Leelahavanichkul, Asada; Kanjanabuch, Talerngsak

    2016-02-01

    The prevalence of obesity is increasing during the past decade along with obesity-related glomerulopathy (ORG), glomeruli injury due to the obesity. The major pathogenesis of ORG is the shedding of podocytes from the glomerular cell barrier into urine. Podocalyxin (PCX), a main surface antigen of podocyte, correlates well with glomerulosclerosis progression and glomerular injury severity, and might be a potential biomarker for early renal alteration in obesity. In addition, vascular endothelial growth factor (VEGF) and alpha-smooth muscle actin (α-SMA) also play a role in promoting glomerulosclerosis. The aim of this study was to explore whether obese subjects without other diseases excrete more PCX-positive (PCX+) cells than non-obese individuals, in comparison with urine protein-creatinine ratio (UPCR) and glomerular filtration rate (GFR) as traditional renal markers. Moreover, the effect of body mass index (BMI) on urinary VEGF, PCX or α-SMA positive cells was also investigated. Forty-eight obese and 13 non-obese adults were included. Exfoliated cells from fresh first void morning urine were harvested, stained with PCX, VEGF, and α-SMA antibody, and quantified by flow cytometry. Correlation between interested urinary biomarkers (cells positive for PCX, VEGF plus PCX and α-SMA), UPCR and GFR with BMI and metabolic risk factors were analyzed. Obese patients had significantly higher PCX+ cells than non-obese [0.62 (0.00-13.13) vs. 0.15 (0.00-0.72) cells/ml × mg cr, p < 0.05]. There was no significant difference in GFR and UPCR between the groups. Of interest, BMI demonstrated a correlation with PCX+ cells (r = 0.343, p = 0.008) and cells positive for PCX plus VEGF (r = 0.374, p = 0.004). Obese subjects without other diseases and with normal UPCR and GFR showed evidence of renal alteration through the detection of a higher number of PCX+ cells. Increasing BMI also resulted in higher number of PCX+ cells.

  10. Impact of occult renal impairment on early and late outcomes following coronary artery bypass grafting.

    PubMed

    Marui, Akira; Okabayashi, Hitoshi; Komiya, Tatsuhiko; Tanaka, Shiro; Furukawa, Yutaka; Kita, Toru; Kimura, Takeshi; Sakata, Ryuzo

    2013-10-01

    High serum creatinine is considered an independent risk factor for poor outcomes following coronary artery bypass grafting (CABG). However, the impact of occult renal impairment (ORI), defined as an impaired glomerular filtration rate (GFR) with a normal serum creatinine (SCr) level, remains unclear. Thus, we sought to investigate the impact of ORI on outcomes after CABG. Among patients undergoing their first percutaneous coronary intervention (PCI) or CABG enrolled in the CREDO-Kyoto Registry (a registry of first-time PCI and CABG patients in Japan), 1842 patients with normal SCr levels undergoing CABG were enrolled in the study. Patients were divided into two groups based on preoperative estimated GFR calculated by the Cockcroft-Gault equation: 1339 patients with estimated GFR of ≥ 60 ml/min/1.73 m(2) (normal group) and 503 with estimated GFR of <60 ml/min/1.73 m(2) (ORI group). Preoperative estimated GFR differed between the groups (51.3 ± 6.6 vs 85.8 ± 23.0 ml/min/1.73 m(2), P < 0.01). ORI was associated with high in-hospital mortality (3.2 vs 1.0%, P < 0.01) and need for dialysis (2.0 vs 0.2%, P < 0.01). In terms of long-term outcomes, ORI was associated with high mortality compared with the normal (hazard ratio [95% confidence interval]: 1.72 [1.16-2.54], P < 0.01) and high incidence of composite cardiovascular events (death, stroke or myocardial infarction: 1.53 [1.16-2.02], P < 0.01). ORI was an independent risk factor for early and late death as well as cardiovascular events in patients undergoing CABG with normal SCr levels. A more accurate evaluation of renal function through a combination of SCr and estimated GFR is needed in patients with normal SCr levels.

  11. 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.

  12. 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.

  13. Increased plasma Kidney Injury Molecule-1 suggests early progressive renal decline in non-proteinuric patients with Type 1 diabetes

    PubMed Central

    Nowak, Natalia; Skupien, Jan; Niewczas, Monika A.; Yamanouchi, Masayuki; Major, Melissa; Croall, Stephanie; Smiles, Adam; Warram, James H.; Bonventre, Joseph V.; Krolewski, Andrzej S.

    2015-01-01

    Progressively decreasing glomerular filtration rate (GFR), or renal decline, is seen in patients with type 1 diabetes (T1D) and normoalbuminuria or microalbuminuria. Here we examined the associations of kidney injury molecule-1 (KIM-1) in plasma and urine with the risk of renal decline and determine whether those associations are independent of markers of glomerular damage. The study group comprised patients with T1D from the 2nd Joslin Kidney Study of which 259 had normoalbuminuria and 203 had microalbuminuria. Serial measurements over 4 to 10 years of follow-up (median 8 years) of serum creatinine and cystatin C were used jointly to estimate eGFRcr-cys slopes and time of onset of CKD stage 3 or higher. Baseline urinary excretion of IgG2 and albumin were used as markers of glomerular damage, and urinary excretion of KIM-1 and its plasma concentration were used as markers of proximal tubular damage. All patients had normal renal function at baseline. During follow-up, renal decline (eGFRcr-cys loss 3.3% or more per year) developed in 96 patients and 62 progressed to CKD stage 3. For both outcomes, the risk rose with increasing baseline levels of plasma KIM-1. In multivariable models, elevated baseline plasma KIM-1 was strongly associated with risk of early progressive renal decline, regardless of baseline clinical characteristics, serum TNFR1 or markers of glomerular damage. Thus, damage to proximal tubules may play an independent role in the development of early progressive renal decline in non-proteinuric patients with T1D. PMID:26509588

  14. Combined osteochondral allograft and meniscal allograft transplantation: a survivorship analysis.

    PubMed

    Getgood, Alan; Gelber, Jonathon; Gortz, Simon; De Young, Alison; Bugbee, William

    2015-04-01

    The efficacy of meniscal allograft transplantation (MAT) and osteochondral allografting (OCA) as individual treatment modalities for select applications is well established. MAT and OCA are considered symbiotic procedures due to a complementary spectrum of indications and reciprocal contraindications. However, few outcomes of concomitant MAT and OCA have been reported. This study is a retrospective review of patients who received simultaneous MAT and OCA between 1983 and 2011. Forty-eight (twenty-nine male: nineteen female) patients with a median age of 35.8 years (15-66) received combined MAT and OCA procedures between 1983 and 2011. Forty-three patients had received previous surgery with a median of 3 procedures (1-11 procedures). The underlying diagnosis was trauma (tibial plateau fracture) in 33 % with osteoarthritis predominating in 54.2 % of cases. Thirty-one patients received a lateral meniscus, 16 received a medial meniscus and one patient received bilateral MAT. The median number of OCAs was two per patient (1-5 grafts), with a median graft area of 15 cm(2) (0.7-41 cm(2)). There were 21 unipolar, 24 bipolar (tibiofemoral) and three multifocal lesions. Thirty-six MATs constituted a compound tibial plateau OCA with native meniscus attached. At follow-up, failure was defined as any procedure resulting in removal or revision of one or more of the grafts. Patients completed the modified Merle d'Aubigné and Postel (18-point) scale, Knee Society Function (KS-F) score, and subjective International Knee Documentation Committee (IKDC) scores. Patient satisfaction was also captured. Twenty-six of 48 patients (54.2 %) required reoperation, but only 11 patients (22.9 %) were noted to have failed (10 MAT and 11 OCA). The mean time to failure was 3.2 years (95 % CI 1.5-4.9 years) and 2.7 years (95 % CI 1.3-4.2 years) for MAT and OCA, respectively. The 5-year survivorship was 78 and 73 % for MAT and OCA respectively, and 69 and 68 % at 10 years. Six of

  15. 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

  16. 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)

  17. Cidofovir inhibits polyomavirus BK replication in human renal tubular cells downstream of viral early gene expression.

    PubMed

    Bernhoff, E; Gutteberg, T J; Sandvik, K; Hirsch, H H; Rinaldo, C H

    2008-07-01

    The human polyomavirus BK (BKV) causes nephropathy and hemorrhagic cystitis in kidney and bone marrow transplant patients, respectively. The anti-viral cidofovir (CDV) has been used in small case series but the effects on BKV replication are unclear, since polyomaviruses do not encode viral DNA polymerases. We investigated the effects of CDV on BKV(Dunlop) replication in primary human renal proximal tubule epithelial cells (RPTECs). CDV inhibited the generation of viral progeny in a dose-dependent manner yielding a 90% reduction at 40 microg/mL. Early steps such as receptor binding and entry seemed unaffected. Initial large T-antigen transcription and expression were also unaffected, but subsequent intra-cellular BKV DNA replication was reduced by >90%. Late viral mRNA and corresponding protein levels were also 90% reduced. In uninfected RPTECs, CDV 40 microg/mL reduced cellular DNA replication and metabolic activity by 7% and 11% in BrdU and WST-1 assays, respectively. BKV infection increased DNA replication to 142% and metabolic activity to 116%, respectively, which were reduced by CDV 40 microg/mL to levels of uninfected untreated RPTECs. Our results show that CDV inhibits BKV DNA replication downstream of large T-antigen expression and involves significant host cell toxicity. This should be considered in current treatment and drug development.

  18. 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.

  19. 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

  20. 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.

  1. [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.

  2. Impact of occult renal impairment on early and late outcomes following coronary artery bypass grafting

    PubMed Central

    Marui, Akira; Okabayashi, Hitoshi; Komiya, Tatsuhiko; Tanaka, Shiro; Furukawa, Yutaka; Kita, Toru; Kimura, Takeshi; Sakata, Ryuzo

    2013-01-01

    OBJECTIVES High serum creatinine is considered an independent risk factor for poor outcomes following coronary artery bypass grafting (CABG). However, the impact of occult renal impairment (ORI), defined as an impaired glomerular filtration rate (GFR) with a normal serum creatinine (SCr) level, remains unclear. Thus, we sought to investigate the impact of ORI on outcomes after CABG. METHODS Among patients undergoing their first percutaneous coronary intervention (PCI) or CABG enrolled in the CREDO-Kyoto Registry (a registry of first-time PCI and CABG patients in Japan), 1842 patients with normal SCr levels undergoing CABG were enrolled in the study. Patients were divided into two groups based on preoperative estimated GFR calculated by the Cockcroft–Gault equation: 1339 patients with estimated GFR of ≥60 ml/min/1.73 m2 (normal group) and 503 with estimated GFR of <60 ml/min/1.73 m2 (ORI group). RESULTS Preoperative estimated GFR differed between the groups (51.3 ± 6.6 vs 85.8 ± 23.0 ml/min/1.73 m2, P < 0.01). ORI was associated with high in-hospital mortality (3.2 vs 1.0%, P < 0.01) and need for dialysis (2.0 vs 0.2%, P < 0.01). In terms of long-term outcomes, ORI was associated with high mortality compared with the normal (hazard ratio [95% confidence interval]: 1.72 [1.16–2.54], P < 0.01) and high incidence of composite cardiovascular events (death, stroke or myocardial infarction: 1.53 [1.16–2.02], P < 0.01). CONCLUSIONS ORI was an independent risk factor for early and late death as well as cardiovascular events in patients undergoing CABG with normal SCr levels. A more accurate evaluation of renal function through a combination of SCr and estimated GFR is needed in patients with normal SCr levels. PMID:23793709

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. Clinical role of early dynamic FDG-PET/CT for the evaluation of renal cell carcinoma.

    PubMed

    Nakajima, Reiko; Abe, Koichiro; Kondo, Tsunenori; Tanabe, Kazunari; Sakai, Shuji

    2016-06-01

    We studied the usefulness of early dynamic (ED) and whole-body (WB) FDG-PET/CT for the evaluation of renal cell carcinoma (RCC). One hundred patients with 107 tumours underwent kidney ED and WB FDG-PET/CT. We visually and semiquantitatively evaluated the FDG accumulation in RCCs in the ED and WB phases, and compared the accumulation values with regard to histological type (clear cell carcinoma [CCC] vs. non-clear cell carcinoma [N-CCC]), the TNM stage (high stage [3-4] vs. low stage [1-2]), the Fuhrman grade (high grade [3-4] vs. low grade [1-2]) and presence versus absence of venous (V) and lymphatic (Ly) invasion. In the ED phase, visual evaluation revealed no significant differences in FDG accumulation in terms of each item. However, the maximum standardized uptake value and tumour-to-normal tissue ratios were significantly higher in the CCCs compared to the N-CCCs (p < 0.001). In the WB phase, in contrast, significantly higher FDG accumulation (p < 0.001) was found in RCCs with a higher TNM stage, higher Furman grade, and the presence of V and Ly invasion in both the visual and the semiquantitative evaluations. ED and WB FDG-PET/CT is a useful tool for the evaluation of RCCs. • ED and WB FDG-PET/ CT helps to assess patients with RCC • ED FDG-PET/CT enabled differentiation between CCC and N-CCC • FDG accumulation in the WB phase reflects tumour aggressiveness • Management of RCC is improved by ED and WB FDG-PET/CT.

  9. Management of early renal anaemia: diagnostic work-up, iron therapy, epoetin therapy.

    PubMed

    Van Wyck, D B

    2000-01-01

    Effective management of early anaemia in the course of chronic renal insufficiency requires the following: (i) implementing an efficient diagnostic strategy to exclude common contributing factors; (ii) initiating epoetin therapy for the majority of patients; for and (iii) ensuring adequate iron supply erythropoiesis. Diagnostic inquiry is warranted whenever the haemoglobin concentration is below the normal range adjusted for age and gender. The most efficient diagnostic approach is to assume erythropoietin deficiency, exclude iron deficiency, and pursue further diagnostic tests only when red-cell indices are abnormal or when leukopenia or thrombocytopenia are also present. Macrocytosis should prompt an inquiry into alcoholism, B12 deficiency, or folate deficiency. Microcytosis suggests iron deficiency or thalassaemia. Associated cytopenias raise the possibility of alcohol toxicity, pernicious anaemia, malignancy, or myelodysplastic syndrome. Epoetin therapy is warranted whenever the haemoglobin concentration has fallen below 10.0 g/dl. To initiate therapy prior to dialysis, epoetin should be administered at an average dose of 100 IU/kg/week (80-120 IU/kg/week, 50-150 IU/kg/ week) by subcutaneous injection. Haemoglobin concentration should be monitored every 2 weeks and the epoetin dose adjusted by increments or decrements of 25% to maintain a rate of rise of haemoglobin concentration of 0.2-0.6 g/dl (0.3 0.6 g/dl/week, 0.2-0.5 g/dl/week). When the target range is achieved, the dose of epoetin should be continually adjusted to maintain a stable haemoglobin concentration. Transferrin saturation and ferritin concentration should be monitored monthly, and sufficient iron provided to maintain transferrin saturation above 20%. The lower the haemoglobin concentration, the greater the likelihood that future intravenous iron will be required. Oral iron supplements should be avoided, since they are costly, ineffective, and troublesome to patients. Finally, a blunted

  10. 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.

  11. 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

  12. Early audit of renal complications in a new cardiac surgery service in Australia.

    PubMed

    Bolsin, Stephen N; Stow, Peter; Bucknell, Sarah

    2004-09-01

    To assess the incidence of renal failure in a cardiac surgery service commencing in Australia. Prospective data collection and retrospective database analysis. A tertiary referral, university teaching hospital in the state of Victoria, Australia. The first 502 patients undergoing cardiac surgery in this institution from commencement of the service. The overall rate of renal failure was low in comparison to other studies at 0.2% (95% CI 0.04-1.3%). The rate of postoperative renal dysfunction was also low at 4.2% (95% CI 2.7-6.5%). The safety of the new service with respect to this complication of cardiac surgery was good when compared with published data. However the lack of uniform definitions of renal failure following cardiac surgery make comparisons between studies difficult. Uniform reporting of this complication would facilitate comparisons between units and quality assurance activities in this field.

  13. Staphylococcus aureus Sepsis Induces Early Renal Mitochondrial DNA Repair and Mitochondrial Biogenesis in Mice

    PubMed Central

    Bartz, Raquel R.; Fu, Ping; Suliman, Hagir B.; Crowley, Stephen D.; MacGarvey, Nancy Chou; Welty-Wolf, Karen; Piantadosi, Claude A.

    2014-01-01

    Acute kidney injury (AKI) contributes to the high morbidity and mortality of multi-system organ failure in sepsis. However, recovery of renal function after sepsis-induced AKI suggests active repair of energy-producing pathways. Here, we tested the hypothesis in mice that Staphyloccocus aureus sepsis damages mitochondrial DNA (mtDNA) in the kidney and activates mtDNA repair and mitochondrial biogenesis. Sepsis was induced in wild-type C57Bl/6J and Cox-8 Gfp-tagged mitochondrial-reporter mice via intraperitoneal fibrin clots embedded with S. aureus. Kidneys from surviving mice were harvested at time zero (control), 24, or 48 hours after infection and evaluated for renal inflammation, oxidative stress markers, mtDNA content, and mitochondrial biogenesis markers, and OGG1 and UDG mitochondrial DNA repair enzymes. We examined the kidneys of the mitochondrial reporter mice for changes in staining density and distribution. S. aureus sepsis induced sharp amplification of renal Tnf, Il-10, and Ngal mRNAs with decreased renal mtDNA content and increased tubular and glomerular cell death and accumulation of protein carbonyls and 8-OHdG. Subsequently, mtDNA repair and mitochondrial biogenesis was evidenced by elevated OGG1 levels and significant increases in NRF-1, NRF-2, and mtTFA expression. Overall, renal mitochondrial mass, tracked by citrate synthase mRNA and protein, increased in parallel with changes in mitochondrial GFP-fluorescence especially in proximal tubules in the renal cortex and medulla. Sub-lethal S. aureus sepsis thus induces widespread renal mitochondrial damage that triggers the induction of the renal mtDNA repair protein, OGG1, and mitochondrial biogenesis as a conspicuous resolution mechanism after systemic bacterial infection. PMID:24988481

  14. Early plasma exchange improves outcome in PR3-ANCA-positive renal vasculitis.

    PubMed

    Gregersen, Jon W; Kristensen, Tilde; Krag, Søren R P; Birn, Henrik; Ivarsen, Per

    2012-01-01

    Plasma exchange (PE) has been shown to improve renal outcome in anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV) and severe renal failure; however the effect of PE in AAV with moderate renal impairment is controversial. A single-centre, retrospective one-year follow-up study, including patients with renal AAV and eGFR <60 ml/min/1.73 m2. Since 2007, all patients with renal AAV and eGFR <60 ml/min/1.73 m2 had PE in addition to induction therapy with cyclophosphamide and prednisolone. Patients admitted from 1999 to 2007 that did not receive PE served as controls. The primary outcome was the combination of death, end-stage renal disease, and relapses after one year. A significant reduction in the primary endpoint was observed following the addition of PE (25% vs. 43%, p=0.04). Furthermore, a greater improvement in renal function after one year was observed among surviving PE treated patients not on dialysis (ΔeGFR 36.1 vs. 19.7 ml/min, p=0.03). There was a significant reduction in serious adverse events in the PE treated group (4% vs. 30%, p=0.02) despite no differences in types and doses of induction immunosuppressive therapy. The advantageous effect of PE was related to the presence of anti-proteinase3 (PR3)-antibodies and also evident among patients with plasma creatinine less than 500 μM. This study suggests the use of PE in addition to standard induction treatment with cyclophosphamide and glucocorticoids to patients with renal PR3-AAV and an estimated-GFR <60 ml/min/1.73m2.

  15. 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.

  16. Homocysteine and the C677T Gene Polymorphism of Its Key Metabolic Enzyme MTHFR Are Risk Factors of Early Renal Damage in Hypertension in a Chinese Han Population

    PubMed Central

    Yun, Lin; Xu, Rui; Li, Guohua; Yao, Yucai; Li, Jiamin; Cong, Dehong; Xu, Xingshun; Zhang, Lihua

    2015-01-01

    Abstract The combined hyperhomocysteinemia condition is a feature of the Chinese hypertensive population. This study used the case-control method to investigate the association between plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme, 5, 10-methylenetetrahydrofolate reductase (MTHFR), and early renal damage in a hypertensive Chinese Han population. A total of 379 adult essential hypertensive patients were selected as the study subjects. The personal information, clinical indicators, and the C677T gene polymorphism of MTHFR were texted. This study used the urine microalbumin/urine creatinine ratio (UACR) as a grouping basis: the hypertension without renal damage group (NRD group) and the hypertension combined with early renal damage group (ERD group). Early renal damage in the Chinese hypertensive population was associated with body weight, systolic pressure, diastolic pressure, urea nitrogen, serum creatinine, cystatin C, uric acid, aldosterone, and glomerular filtration rate. The homocysteine level and the UACR in the TT genotype group were higher than those in the CC genotype group. The binary logistic regression analysis results showed that after sex and age were adjusted, the MTHFR C677T gene polymorphism was correlated with early renal damage in hypertension in both the recessive model and in the additive model. Plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme MTHFR might be independent risk factors of early renal damage in the hypertensive Chinese Han population. PMID:26717388

  17. Homocysteine and the C677T Gene Polymorphism of Its Key Metabolic Enzyme MTHFR Are Risk Factors of Early Renal Damage in Hypertension in a Chinese Han Population.

    PubMed

    Yun, Lin; Xu, Rui; Li, Guohua; Yao, Yucai; Li, Jiamin; Cong, Dehong; Xu, Xingshun; Zhang, Lihua

    2015-12-01

    The combined hyperhomocysteinemia condition is a feature of the Chinese hypertensive population. This study used the case-control method to investigate the association between plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme, 5, 10-methylenetetrahydrofolate reductase (MTHFR), and early renal damage in a hypertensive Chinese Han population.A total of 379 adult essential hypertensive patients were selected as the study subjects. The personal information, clinical indicators, and the C677T gene polymorphism of MTHFR were texted. This study used the urine microalbumin/urine creatinine ratio (UACR) as a grouping basis: the hypertension without renal damage group (NRD group) and the hypertension combined with early renal damage group (ERD group).Early renal damage in the Chinese hypertensive population was associated with body weight, systolic pressure, diastolic pressure, urea nitrogen, serum creatinine, cystatin C, uric acid, aldosterone, and glomerular filtration rate. The homocysteine level and the UACR in the TT genotype group were higher than those in the CC genotype group. The binary logistic regression analysis results showed that after sex and age were adjusted, the MTHFR C677T gene polymorphism was correlated with early renal damage in hypertension in both the recessive model and in the additive model.Plasma homocysteine and the C677T gene polymorphism of its key metabolic enzyme MTHFR might be independent risk factors of early renal damage in the hypertensive Chinese Han population.

  18. 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

  19. 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

  20. Urinary NGAL and hematic ADMA levels: an early sign of cardio-renal syndrome in young adults born preterm?

    PubMed

    Bassareo, Pier Paolo; Fanos, Vassilios; Mussap, Michele; Flore, Giovanna; Noto, Antonio; Puddu, Melania; Saba, Luca; Mercuro, Giuseppe

    2013-10-01

    Prematurity at birth is a known risk factor for the development of an early chronic renal disease. Urinary neutrophil gelatinase-associated lipocalin (NGAL) is a well established biomarker of kidney injury, while high blood levels of asymmetric dimethylarginine (ADMA) are associated with the future development of adverse cardiovascular events and cardiac death. (1) to verify the presence of statistically significant differences between urinary NGAL and hematic ADMA levels in young adults born preterm at extremely low birth weight (<1000 g; ex-ELBW) and those of a control group of healthy adults born at term (C) (2) to seek correlations between NGAL and ADMA levels, which would indicate the presence of an early cardio-renal involvement in ex-ELBW. Twelve ex-ELBW subjects (six males and six female, mean age: 23.9 ± 3.2 years) were compared with 12 C (six males and six female). Urinary NGAL and hematic ADMA levels were assessed. Urinary NGAL levels were higher in ex- ELBW subjects compared to C (p < 0.05), as well as hematic ADMA concentrations (p < 0.05). A statistically significant correlation was found between urinary NGAL and ADMA (r = -0.60, p < 0.04). Our preliminary findings support the hypothesis that in ex-ELBW subjects the development of an early chronic kidney disease contributes towards inducing an increase in the atherosclerotic process and in the risk of future adverse cardiovascular events.

  1. 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.

  2. Cutting-Balloon Angioplasty in Transplant Renal Artery Stenosis as First-Line Treatment in the Early Postoperative Period

    SciT

    Ucar, Adem, E-mail: ucaradem@yahoo.com; Yahyayev, Aghakishi, E-mail: aghakishi@yahoo.com; Bakkaloglu, Huseyin, E-mail: drhuseyin@yahoo.com

    2011-02-15

    Percutaneous transluminal angioplasty has been successfully used for the treatment of transplant renal artery stenosis (RAS). Cutting-balloon angioplasty (CBA) is being used as a second option in pressure-resistant stenosis. It is thought that CBA is less traumatic and therefore restenosis occurs less frequently than in conventional angioplasty. This case report describes the unusual use of a cutting balloon in transplant RAS as a first option in the early postoperative period. Long-term follow-up data are also presented.

  3. 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

  4. 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.

  5. Renal arteriography

    MedlinePlus

    Renal angiogram; Angiography - kidney; Renal angiography; Renal artery stenosis - arteriography ... an artery by a blood clot Renal artery stenosis Renal cell cancer Angiomyolipomas (noncancerous tumors of the ...

  6. Purinergic receptors contribute to early mesangial cell transformation and renal vessel hypertrophy during angiotensin II-induced hypertension

    PubMed Central

    Graciano, Miguel L.; Nishiyama, Akira; Jackson, Keith; Seth, Dale M.; Ortiz, Rudy M.; Prieto-Carrasquero, Minolfa C.; Kobori, Hiroyuki; Navar, L. Gabriel

    2008-01-01

    Chronic ANG II infusions lead to increases in intrarenal ANG II levels, hypertension, and tissue injury. Increased blood pressure also elicits increases in renal interstitial fluid (RIF) ATP concentrations that stimulate cell proliferation. We evaluated the contribution of purinergic receptor activation to ANG II-induced renal injury in rats by treating with clopidogrel, a P2Y12 receptor blocker, or with PPADS, a nonselective P2 receptor blocker. α-Actin expression in mesangial cells, afferent arteriolar wall thickness (AAWT), cortical cell proliferation, and macrophage infiltration were used as early markers of renal injury. Clopidogrel and PPADS did not alter blood pressure, renin or kidney ANG II content. α-Actin expression increased from control of 0.6 ± 0.4% of mesangial area to 6.3 ± 1.9% in ANG II-infused rats and this response was prevented by clopidogrel (0.4 ± 0.2%) and PPADS. The increase in AAWT from 4.7 ± 0.1 to 6.0 ± 0.1 mm in ANG II rats was also prevented by clopidogrel (4.8 ± 0.1 mm) and PPADS. ANG II infusion led to interstitial macrophage infiltration (105 ± 16 vs. 62 ± 4 cell/mm2) and tubular proliferation (71 ± 15 vs. 20 ± 4 cell/mm2) and these effects were prevented by clopidogrel (52 ± 4 and 36 ± 3 cell/mm2) and PPADS. RIF ATP levels were higher in ANG II-infused rats than in control rats (11.8 ± 1.9 vs. 5.6 ± 0.6 nmol/l, P < 0.05). The results suggest that activation of vascular and glomerular purinergic P2 receptors may contribute to the mesangial cell transformation, renal inflammation, and vascular hypertrophy observed in ANG II-dependent hypertension. PMID:17989111

  7. Microalbuminuria and early renal response to lethal dose Shiga toxin type 2 in rats.

    PubMed

    Ochoa, Federico; Oltra, Gisela; Gerhardt, Elizabeth; Hermes, Ricardo; Cohen, Lilian; Damiano, Alicia E; Ibarra, Cristina; Lago, Nestor R; Zotta, Elsa

    2012-01-01

    In Argentina, hemolytic uremic syndrome (HUS) constitutes the most frequent cause of acute renal failure in children. Approximately 2%-4% of patients die during the acute phase, and one-third of the 96% who survive are at risk of chronic renal sequelae. Little information is available about the direct effect of Shiga toxin type 2 (Stx2) on the onset of proteinuria and the evolution of toxin-mediated glomerular or tubular injury. In this work, rats were injected intraperitoneally with recombinant Escherichia coli culture supernatant containing Stx2 (sStx2; 20 μg/kg body weight) to induce HUS. Functional, immunoblotting, and immunohistochemistry studies were carried out to determine alterations in slit diaphragm proteins and the proximal tubule endocytic system at 48 hours post-inoculation. We detected a significant increase in microalbuminuria, without changes in the proteinuria values compared to the control rats. In immunoperoxidase studies, the renal tubules and glomerular mesangium showed an increased expression of transforming growth factor β(1)(TGF-β(1)). The expression of megalin was decreased by immunoperoxidase and the cytoplasm showed a granular pattern of megalin expression by immunofluorescence techniques. Western blot analysis performed in the renal cortex from sStx2-treated and control rats using anti-nephrin and anti-podocalyxin antibodies showed a decreased expression of these proteins. We suggest that the alterations in slit diaphragm proteins and megalin expression could be related to the development of microalbuminuria in response to lethal doses of Stx2.

  8. Inhibition of Reticulon-1A-Mediated Endoplasmic Reticulum Stress in Early AKI Attenuates Renal Fibrosis Development.

    PubMed

    Fan, Ying; Xiao, Wenzhen; Lee, Kyung; Salem, Fadi; Wen, Jiejun; He, Li; Zhang, Jing; Fei, Yang; Cheng, Dongsheng; Bao, Hongda; Liu, Yumei; Lin, Fujun; Jiang, Gengru; Guo, Zhiyong; Wang, Niansong; He, John Cijiang

    2017-07-01

    Several animal studies have shown an important role for endoplasmic reticulum (ER) stress in AKI, whereas human studies are lacking. We recently reported that Reticulon-1A (RTN1A) is a key mediator of ER stress and kidney cell injury. Here, we investigated whether modulation of RTN1A expression during AKI contributes to the progression to CKD. In a retrospective study of 51 patients with AKI, increased expression of RTN1A and other ER stress markers were associated with the severity of kidney injury and with progression to CKD. In an inducible tubular cell-specific RTN1A-knockdown mouse model subjected to folic acid nephropathy (FAN) or aristolochic acid nephropathy, reduction of RTN1A expression during the initial stage of AKI attenuated ER stress and kidney cell injury in early stages and renal fibrosis development in later stages. Treatment of wild-type mice with tauroursodeoxycholic acid, an inhibitor of ER stress, after the induction of kidney injury with FA facilitated renoprotection similar to that observed in RTN1A-knockdown mice. Conversely, in transgenic mice with inducible tubular cell-specific overexpression of RTN1A subjected to FAN, induction of RTN1A overexpression aggravated ER stress and renal injury at the early stage and renal fibrosis at the late stage of FAN. Together, our human and mouse data suggest that the RTN1A-mediated ER stress response may be an important determinant in the severity of AKI and maladaptive repair that may promote progression to CKD. Copyright © 2017 by the American Society of Nephrology.

  9. 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

  10. 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

  11. [Early results with a monorail-stent-balloon device for endovascular treatment of renal artery stenosis].

    PubMed

    Müller-Hülsbeck, S; Jahnke, T; Grimm, J; Behm, C; Hilbert, C; Frahm, C; Biederer, J; Brossmann, J; Heller, M

    2002-03-01

    To evaluate the technical feasibility of a new monorail-stent-balloon device for treatment of renal artery stenosis (RAS). During a study period of 18 months, 38 patients with proven RAS in 41 cases (hypertension n = 36, renal insufficiency n = 13) and indication for stenting (calicified ostial lesions n = 35, insufficient PTA n = 4, dissection n = 2) were enrolled into this prospective evaluation. Pre-mounted stents (Rx-Herculink(TM) 5 mm = 13, 6 mm = 34, 7 mm = 1) were implanted a transfemoral (n = 35) or transbrachial approach (n = 6). Mean grade and lengths of stenosis measured were 88 % plus minus 10 and 9 mm plus minus 5. Renal stent implantation was technically successful in all cases (100 %). In 7 cases a second stent had to be implanted to cover the entire lesion. The transstenotic pressure drop decreased from 88 mmHg plus minus 10 before to 1 mmHg plus minus 1.8 after the procedure. Remaining stenosis measured 0.7 % plus minus 4.2. Serum creatine levels decreased from 1.9 mm/dl to 1.5 mg/dl (n. s.), blood pressure decreased from 178/94 mmHg to 148/79 mmHg (p < 0.0001) after the intervention. Primary and secondary patency rates at 6 months were 72 % (Standard Error 9.8 %) and 77 (% (Standard Error 9.2 %), respectively. With the used monorail-stend-balloon device a technically easy, secure and exact renal stent placement is guaranteed, patency rates are similar to those described in the current literature.

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. Serial detection of Epstein-Barr virus DNA in sera and peripheral blood leukocyte samples of pediatric renal allograft recipients with persistent mononucleosis-like symptoms defines patients at risk to develop post-transplant lymphoproliferative disease.

    PubMed

    Campe, Hartmut; Jaeger, Gundula; Abou-Ajram, Claudia; Nitschko, Hans; Griebel, Martin; Montoya, Carmen; Klare, Bernd; Koszinowski, Ulrich

    2003-02-01

    We tested blood samples of 25 pediatric renal transplant recipients for Epstein-Barr virus (EBV) DNA load by quantitative polymerase chain reaction (PCR). Eleven of these transplant recipients showed clinical persistent mononucleosis-like symptoms years after transplantation (Tx). A quantitation of EBV DNA by PCR in peripheral blood lymphocyte (PBL) and serum samples revealed variable EBV DNA titers. The majority of EBV PCR results in samples of the 14 asymptomatic transplant recipients was repeatedly below detection limit. In contrast, patients with mononucleosis-like symptoms showed persistent EBV genome titers over a period of 6 months, ranging from 75 to 18 750 copies/10 000 PBL and from 680 to 335 000 copies/mL serum, respectively. One child suffering from this mononucleosis-like condition developed an EBV-associated Burkitt-like lymphoma 29 months after Tx. Whereas clinical and histological investigations did not indicate a post-transplant lymphoproliferative disorder (PTLD) until tumor detection, EBV titers in PBL and serum had been high for at least 8 months. We propose that pediatric transplant recipients who show both, recurrent mononucleosis-like symptoms and a sustained high EBV genome load, are at increased risk for severe EBV-related post-transplant complications.

  17. 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

  18. 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.

  19. 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

  20. Induction treatment with rabbit antithymocyte globulin versus basiliximab in renal transplant recipients with planned early steroid withdrawal.

    PubMed

    Martin, Spencer T; Roberts, Keri L; Malek, Sayeed K; Tullius, Stefan G; Vadivel, Nidyanandh; De Serres, Sacha; Grafals, Monica; Elsanjak, Abdelaziz; Filkins, Beth Anne; Chandraker, Anil; Gabardi, Steven

    2011-06-01

    To compare the safety and efficacy of rabbit antithymocyte globulin (r-ATG) with basiliximab in renal transplant recipients for whom an early steroid withdrawal (ESW) regimen was planned. Single-center, retrospective, cohort study. Tertiary care medical center, including inpatient hospital stays and outpatient nephrology clinics. Ninety-nine consecutive adult recipients of living- or deceased-donor renal transplants between January 1, 2004, and December 31, 2007, in whom ESW was planned and who received either r-ATG or basiliximab; patients receiving an extended-criteria kidney donation or a donation after cardiac death were excluded. All patients received mycophenolate mofetil and tacrolimus as maintenance therapy with planned ESW. Induction therapy was either r-ATG 1.5 mg/kg/day for 4 days (68 patients) or basiliximab 20 mg on postoperative days 0 and 4 (31 patients). The primary composite end point of biopsy-proven acute rejection (BPAR), graft loss, and death occurred in 6 patients (9%) and 9 patients (29%) in the r-ATG and basiliximab groups at 1 year after transplantation, respectively (p=0.01), with rates of 7% (5/68 patients) and 26% (8/31 patients) for BPAR (p=0.02), 0% and 3% (1/31 patients) for graft loss (p=0.31), and 2% (1/68 patients) and 0% for patient death (p>0.99). Average time to first BPAR was significantly longer in the r-ATG group (mean ± SD 151.4 ± 82.9 vs 53.6 ± 68.4 days, p<0.01). Kidney function at 12 months was similar between the two groups. Rabbit-ATG was associated with a lower frequency and delayed onset of BPAR compared with basiliximab in renal transplant recipients who received an ESW regimen.

  1. Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy

    PubMed Central

    Rodríguez-Peña, Ana B.; Fuentes-Calvo, Isabel; Docherty, Neil G.; Arévalo, Miguel; Grande, María T.; Eleno, Nélida; Pérez-Barriocanal, Fernando; López-Novoa, José M.

    2014-01-01

    Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis. PMID:25101263

  2. Effect of angiotensin II and small GTPase Ras signaling pathway inhibition on early renal changes in a murine model of obstructive nephropathy.

    PubMed

    Rodríguez-Peña, Ana B; Fuentes-Calvo, Isabel; Docherty, Neil G; Arévalo, Miguel; Grande, María T; Eleno, Nélida; Pérez-Barriocanal, Fernando; López-Novoa, José M

    2014-01-01

    Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis.

  3. 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

  4. 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

  5. The early history of dialysis for chronic renal failure in the United States: a view from Seattle.

    PubMed

    Blagg, Christopher R

    2007-03-01

    Forty-seven years have passed since the first patient started treatment for chronic renal failure by repeated hemodialysis (HD) at the University of Washington Hospital in Seattle in March 1960, and some 34 years have elapsed since the United States Congress passed legislation creating the Medicare End-Stage Renal Disease Program. Many nephrologists practicing today are unfamiliar with the history of the clinical and political developments that occurred during the 13 years between these 2 dates and that led to dialysis as we know it today in this country. This review briefly describes these events. Clinical developments following introduction of the Teflon shunt by Belding Scribner and Wayne Quinton included empirical observations leading to better understanding of HD and patient management, out-of-hospital dialysis by nurses, bioethical discussions of the problems of patient selection, home HD, improved dialysis technology, intermittent peritoneal dialysis, including automated equipment for home use and an effective peritoneal access catheter, the arteriovenous fistula for more reliable blood access, dialyzer reuse, the first for-profit dialysis units, understanding of many of the complications of treatment, the first considerations of dialysis adequacy, early development of other technologies, and more frequent HD. Political developments began less than 3 years after the first Seattle patient began dialysis, but it took another 10 years of intermittent activities before Congress acted on legislation to provide almost universal Medicare entitlement to patients with chronic kidney disease requiring dialysis or kidney transplantation.

  6. Prognostic Importance of Early Worsening Renal Function Following Initiation of Angiotensin Converting Enzyme Inhibitor Therapy in Patients with Cardiac Dysfunction

    PubMed Central

    Testani, Jeffrey M.; Kimmel, Stephen E.; Dries, Daniel L.; Coca, Steven G.

    2011-01-01

    Background Worsening renal function (WRF) in the setting of heart failure has been associated with increased mortality. However, it is unclear if this decreased survival is a direct result of the reduction in glomerular filtration rate (GFR) or if the mechanism underlying the deterioration in GFR is driving prognosis. Given that WRF in the setting of angiotensin converting enzyme inhibitor (ACE-I) initiation is likely mechanistically distinct from spontaneously occurring WRF, we sought to investigate the relative early WRF associated mortality rates in subjects randomized to ACE-I or placebo. Methods and Results Subjects in the Studies Of Left Ventricular Dysfunction limited data set were studied (6,377 patients). The interaction between early WRF (decrease in estimated GFR ≥20% at 14 days), randomization to enalapril, and mortality was the primary endpoint. In the overall population, early WRF was associated with increased mortality (adjusted HR=1.2, 95% CI 1.0–1.4, p=0.037). When analysis was restricted to the placebo group, this association strengthened (adjusted HR=1.4, 95% CI 1.1–1.8, p=0.004). However, in the enalapril group, early WRF had no adverse prognostic significance (adjusted HR=1.0, 95% CI 0.8–1.3, p=1.0, p interaction=0.09). In patients that continued study drug despite early WRF, a survival advantage remained with enalapril therapy (adjusted HR=0.66, 95% CI 0.5–0.9, p=0.018). Conclusions These data support the notion that the mechanism underlying WRF is important in determining its prognostic significance. Specifically, early WRF in the setting of ACE-I initiation appears to represent a benign event which is not associated with a loss of benefit from continued ACE-I therapy. PMID:21903907

  7. Radiation sterilization of skin allograft

    NASA Astrophysics Data System (ADS)

    Kairiyama, E.; Horak, C.; Spinosa, M.; Pachado, J.; Schwint, O.

    2009-07-01

    In the treatment of burns or accidental loss of skin, cadaveric skin allografts provide an alternative to temporarily cover a wounded area. The skin bank facility is indispensable for burn care. The first human skin bank was established in Argentina in 1989; later, 3 more banks were established. A careful donor selection is carried out according to the national regulation in order to prevent transmissible diseases. As cadaveric human skin is naturally highly contaminated, a final sterilization is necessary to reach a sterility assurance level (SAL) of 10 -6. The sterilization dose for 106 batches of processed human skin was determined on the basis of the Code of Practice for the Radiation Sterilization of Tissue Allografts: Requirements for Validation and Routine Control (2004) and ISO 11137-2 (2006). They ranged from 17.6 to 33.4 kGy for bioburdens of >10-162.700 CFU/100 cm 2. The presence of Gram negative bacteria was checked for each produced batch. From the analysis of the experimental results, it was observed that the bioburden range was very wide and consequently the estimated sterilization doses too. If this is the case, the determination of a tissue-specific dose per production batch is necessary to achieve a specified requirement of SAL. Otherwise if the dose of 25 kGy is preselected, a standardized method for substantiation of this dose should be done to confirm the radiation sterilization process.

  8. Uric acid lowering to prevent kidney function loss in diabetes: the preventing early renal function loss (PERL) allopurinol study.

    PubMed

    Maahs, David M; Caramori, Luiza; Cherney, David Z I; Galecki, Andrzej T; Gao, Chuanyun; Jalal, Diana; Perkins, Bruce A; Pop-Busui, Rodica; Rossing, Peter; Mauer, Michael; Doria, Alessandro

    2013-08-01

    Diabetic kidney disease causes significant morbidity and mortality among people with type 1 diabetes (T1D). Intensive glucose and blood pressure control have thus far failed to adequately curb this problem and therefore a major need for novel treatment approaches exists. Multiple observations link serum uric acid levels to kidney disease development and progression in diabetes and strongly argue that uric acid lowering should be tested as one such novel intervention. A pilot of such a trial, using allopurinol, is currently being conducted by the Preventing Early Renal Function Loss (PERL) Consortium. Although the PERL trial targets T1D individuals at highest risk of kidney function decline, the use of allopurinol as a renoprotective agent may also be relevant to a larger segment of the population with diabetes. As allopurinol is inexpensive and safe, it could be cost-effective even for relatively low-risk patients, pending the completion of appropriate trials at earlier stages.

  9. 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.

  10. Pre-End-Stage Renal Disease Care and Early Survival among Incident Dialysis Patients in the US Military Health System.

    PubMed

    Nee, Robert; Fisher, Evan; Yuan, Christina M; Agodoa, Lawrence Y; Abbott, Kevin C

    2017-01-01

    Previous reports showed an increased early mortality after chronic dialysis initiation among the end-stage renal disease (ESRD) population. We hypothesized that ESRD patients in the Military Health System (MHS) would have greater access to pre-ESRD care and hence better survival rates during this early high-risk period. In this retrospective cohort study, using the US Renal Data System database, we identified 1,256,640 patients initiated on chronic dialysis from January 2, 2004 through December 31, 2014, from which a bootstrap sample of 3,984 non-MHS incident dialysis patients were compared with 996 MHS patients. We assessed care by a nephrologist and dietitian, erythropoietin administration, and vascular access use at dialysis initiation as well as all-cause mortality as outcome variables. MHS patients were significantly more likely to have had pre-ESRD nephrology care (adjusted OR [aOR] 2.9; 95% CI 2.3-3.7) and arteriovenous fistula used at dialysis initiation (aOR 2.2; 95% CI 1.7-2.7). Crude mortality rates peaked between the 4th and the 8th week for both cohorts but were reduced among MHS patients. The baseline adjusted Cox model showed significantly lower death rates among MHS vs. non-MHS patients at 6, 9, and 12 months. This survival advantage among MHS patients was attenuated after further adjustment for pre-ESRD nephrology care and dialysis vascular access. MHS patients had improved survival within the first 12 months compared to the general ESRD population, which may be explained in part by differences in pre-ESRD nephrology care and vascular access types. © 2017 S. Karger AG, Basel.

  11. Extending the benefits of early mobility to critically ill patients undergoing continuous renal replacement therapy: the Michigan experience.

    PubMed

    Talley, Cheryl L; Wonnacott, Robert O; Schuette, Janice K; Jamieson, Jill; Heung, Michael

    2013-01-01

    Evidence to support improved outcomes with early ambulation is strong in medical literature. Yet, critically ill continuous renal replacement therapy (CRRT) patients remain tethered to their beds by devices delivering supportive therapy. The University of Michigan Adult CRRT Committee identified this deficiency and sought to change it. There was no guidance in the literature to support mobilizing this population; therefore, we reviewed literature from devices with similar technological profiles. Revision of our institutional mobility protocol for the CRRT population included a simple safety acronym, ASK. The acronym addresses appropriate candidacy; secured, appropriate access; and potential device and patient complications as a memorable aid to help nursing staff determine whether their CRRT patients are candidates for early mobility. After implementing our CRRT mobility standard, a preliminary study of 109 CRRT patients and a review of incident reports related to CRRT demonstrated no significant adverse patient events or falls and no access complications related to mobility. This deliberate intervention allows CRRT patients to safely engage in mobility activities to improve this population's outcomes. A simple mobility protocol and safety acronym partnered with strong clinical leadership has permitted the University of Michigan to add CRRT patients to the body of early mobility literature.

  12. 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

  13. 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.

  14. Polar orientation of renal grafts within the proximal seal zone affects risk of early type IA endoleaks after chimney endovascular aneurysm repair.

    PubMed

    Tran, Kenneth; Ullery, Brant W; Itoga, Nathan; Lee, Jason T

    2018-04-01

    The objective of this study was to describe the polar orientation of renal chimney grafts within the proximal seal zone and to determine whether graft orientation is associated with early type IA endoleak or renal graft compression after chimney endovascular aneurysm repair (ch-EVAR). Patients who underwent ch-EVAR with at least one renal chimney graft from 2009 to 2015 were included in this analysis. Centerline three-dimensional reconstructions were used to analyze postoperative computed tomography scans. The 12-o'clock polar position was set at the takeoff of the superior mesenteric artery. Relative polar positions of chimney grafts were recorded at the level of the renal artery ostium, at the mid-seal zone, and at the proximal edge of the graft fabric. Early type IA endoleaks were defined as evidence of a perigraft flow channel within the proximal seal zone. There were 62 consecutive patients who underwent ch-EVAR (35 double renal, 27 single renal) for juxtarenal abdominal aortic aneurysms with a mean follow-up of 31.2 months; 18 (29%) early type IA "gutter" endoleaks were identified. During follow-up, the majority of these (n = 13; 72%) resolved without intervention, whereas two patients required reintervention (3.3%). Estimated renal graft patency was 88.9% at 60 months. Left renal chimney grafts were most commonly at the 3-o'clock position (51.1%) at the ostium, traversing posteriorly to the 5- to 7-o'clock positions (55.5%) at the fabric edge. Right renal chimney grafts started most commonly at the 9-o'clock position (n = 17; 33.3%) and tended to traverse both anteriorly (11 to 1 o'clock; 39.2%) and posteriorly (5 to 7 o'clock; 29.4%) at the fabric edge. In the polar plane, the majority of renal chimney grafts (n = 83; 85.6%) traversed <90 degrees before reaching the proximal fabric edge. Grafts that traversed >90 degrees were independently associated with early type IA endoleaks (odds ratio, 11.5; 95% confidence interval, 2.1-64.8) even after

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. Early detection of endothelial injury and dysfunction in conjunction with correction of hemodynamic maladjustment can effectively restore renal function in type 2 diabetic nephropathy.

    PubMed

    Futrakul, Narisa; Butthep, Punnee; Vongthavarawat, Varaphon; Futrakul, Prasit; Sirisalipoch, Sasitorn; Chaivatanarat, Tawatchai; Suwanwalaikorn, Sompongse

    2006-01-01

    This paper was aimed to investigate (1) the early marker of endothelial injury in type 2 diabetes, (2) the intrarenal hemodynamics and renal function, and (3) the therapeutic strategy aiming to restore renal function. Fifty patients (35 normoalbuminuric and 15 albuminuric type 2 diabetes) were examined. Blood was collected for determination of circulating vascular endothelial cells (CEC) and the serum was prepared for determination of transforming growth factor beta (TGFbeta), ratio of CEC/TGFbeta, and soluble vascular cell adhesion molecule. Intrarenal hemodynamics and renal function were also assessed. The results showed that increased number of circulating EC, elevated TGFbeta and depleted ratio of CEC/TGFbeta were significantly observed. Intrarenal hemodynamic study revealed a hemodynamic maladjustment characterized by preferential constriction of the efferent arteriole, intraglomerular hypertension and reduction in peritubular capillary flow. It was concluded that early marker of endothelial injury is reflected by increasing number of CEC. Such markers correlate with the glomerular endothelial dysfunction associated with hemodynamic maladjustment. Early detection of endothelial injury and appropriate correction of hemodynamic maladjustment by multidrug vasodilators can effectively restore renal function in type 2 diabetic nephropathy.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. Association between markers of endothelial dysfunction and early signs of renal dysfunction in pediatric obesity and type 1 diabetes.

    PubMed

    Marcovecchio, M L; de Giorgis, T; Di Giovanni, I; Chiavaroli, V; Chiarelli, F; Mohn, A

    2017-06-01

    To evaluate whether circulating markers of endothelial dysfunction, such as intercellular adhesion molecule-1 (ICAM-1) and myeloperoxidase (MPO), are increased in youth with obesity and in those with type 1 diabetes (T1D) at similar levels, and whether their levels are associated with markers of renal function. A total of 60 obese youth [M/F: 30/30, age: 12.5 ± 2.8 yr; body mass index (BMI) z-score: 2.26 ± 0.46], 30 with T1D (M/F: 15/15; age: 12.9 ± 2.4 yr; BMI z-score: 0.45 ± 0.77), and 30 healthy controls (M/F: 15/15, age: 12.4 ± 3.3 yr, BMI z-score: -0.25 ± 0.56) were recruited. Anthropometric measurements were assessed and a blood sample was collected to measure ICAM-1, MPO, creatinine, cystatin C and lipid levels. A 24-h urine collection was obtained for assessing albumin excretion rate (AER). Levels of ICAM-1 and MPO were significantly higher in obese [ICAM-1: 0.606 (0.460-1.033) µg/mL; MPO: 136.6 (69.7-220.8) ng/mL] and T1D children [ICAM-1: 0.729 (0.507-0.990) µg/mL; MPO: 139.5 (51.0-321.3) ng/mL] compared with control children [ICAM-1: 0.395 (0.272-0.596) µg/mL MPO: 41.3 (39.7-106.9) ng/mL], whereas no significant difference was found between T1D and obese children. BMI z-score was significantly associated with ICAM-1 (β = 0.21, p = 0.02) and MPO (β = 0.41, p < 0.001). A statistically significant association was also found between ICAM-1 and markers of renal function (AER: β = 0.21, p = 0.03; e-GFR: β = 0.19, p = 0.04), after adjusting for BMI. Obese children have increased markers of endothelial dysfunction and early signs of renal damage, similarly to children with T1D, confirming obesity to be a cardiovascular risk factor as T1D. The association between ICAM-1 with e-GFR and AER confirm the known the association between general endothelial and renal dysfunction. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. Early Gains in Renal Function Following Implantation of HeartMate II Left Ventricular Assist Devices May Not Persist to One Year.

    PubMed

    Hasin, Tal; Grupper, Avishay; Dillon, John J; Maleszewski, Joseph J; Li, Zhuo; Topilsky, Yan; Frantz, Robert P; Edwards, Brooks S; Pereira, Naveen L; Maltais, Simon; Stulak, John M; Joyce, Lyle; Daly, Richard; Park, Soon J; Kushwaha, Sudhir S

    Renal function improves early after left ventricular assist device (LVAD) implantation but later decline has been observed. We sought to determine the occurrence and evaluate possible causes for this decline. In 62 consecutive patients with HeartMateII LVAD with available calculated glomerular filtration rate (GFR, ml/min/1.73 m) 1 year after implant, GFR was assessed repeatedly and possible predictors for decline from 3 to 12 months were investigated. Post-mortem renal specimens for patients supported with an LVAD were evaluated. GFR 54.5 ± 19.5 at admission increased to 66.4 ± 22.3 preoperatively and to 79.2 ± 30.1 ~1 month after implantation. Subsequently at ~3 months GFR declined to 74.7 ± 25.4, at ~6 months to 68.8 ± 23.1, and ~1 year after implant to 63.9 ± 17.7. Glomerular filtration rate at 1 year was significantly lower (p < 0.0001, p < 0.0001, p = 0.005) than GFR 1, 3, and 6 months after implant. Early rise in GFR after surgery was not associated with late decline. Shorter bypass time (β = -0.09, p = 0.048) and higher albumin 3 months after LVAD (β = 14.4, p = 0.025) were significantly associated with less later decline in GFR. Arteriosclerosis was identified in autopsy renal specimens. In conclusion, early gains in renal function after LVAD implant are not sustained in many patients. Patient, device, and operative factors may influence long-term renal function in these patients.

  15. 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.

  16. Post-Transplant Blood Transfusions and Pediatric Renal Allograft Outcomes

    PubMed Central

    Verghese, Priya; Gillingham, Kristen; Matas, Arthur; Chinnakotla, Srinath; Chavers, Blanche

    2016-01-01

    The association of blood transfusions with graft survival after pediatric kidney transplant (KTx) is unclear. We retrospectively analyzed blood transfusions post-KTx and subsequent outcomes. Between 1984 and 2013, 482 children (<18 years of age) underwent KTx at our center. Recipient demographics, outcomes and transfusion data were collected. Cox regression with post-KTx blood transfusion as a time-dependent covariate was performed to model the impact of blood transfusion on outcomes. Of the 208 (44%) that were transfused, 39% had transfusion <1 month post-KTx; 48% > 12 months. Transfused and non-transfused recipients were not significantly different. In univariate and multivariate analyses, there was no difference between transfused and non-transfused recipient patient survival; antibody-mediated and acute cellular rejection, and donor-specific antibody (DSA) free survival. Transfusions <1 month post-KTx did not impact death-censored graft survival (DCGS) (p=NS). Patients transfused >12 months post-KTx had significantly lower 12 month estimated glomerular filtration rate (eGFR) (compared to non-transfused) and worse subsequent DCGS. Post-KTx blood transfusions have increased in pediatric KTx over time but have no negative association with rejection or DSA production. DCGS is unaffected by transfusion within first month. Transfusions after the first year occur in patients with more advanced chronic kidney disease and are associated with significantly worse DCGS. PMID:27712016

  17. Post-transplant blood transfusions and pediatric renal allograft outcomes.

    PubMed

    Verghese, Priya; Gillingham, Kristen; Matas, Arthur; Chinnakotla, Srinath; Chavers, Blanche

    2016-11-01

    The association of blood transfusions with GS after pediatric KTx is unclear. We retrospectively analyzed blood transfusions post-KTx and subsequent outcomes. Between 1984 and 2013, 482 children (<18 years of age) underwent KTx at our center. Recipient demographics, outcomes and transfusion data were collected. Cox regression with post-KTx blood transfusion as a time-dependent covariate was performed to model the impact of blood transfusion on outcomes. Of the 208 (44%) that were transfused, 39% had transfusion <1 month post-KTx; 48% >12 months. Transfused and non-transfused recipients were not significantly different. In univariate and multivariate analyses, there was no difference between transfused and non-transfused recipient patient survival, antibody-mediated and ACR, and DSA free survival. Transfusions <1 month post-KTx did not impact DCGS (P=NS). Patients transfused >12 months post-KTx had significantly lower 12 month eGFR (compared to non-transfused) and worse subsequent DCGS. Post-KTx blood transfusions have increased in pediatric KTx over time but have no negative association with rejection or DSA production. DCGS is unaffected by transfusion within first month. Transfusions after the first year occur in patients with more advanced chronic kidney disease and are associated with significantly worse DCGS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Urinary Netrin-1: A New Biomarker for the Early Diagnosis of Renal Damage in Obese Children.

    PubMed

    Övünç Hacıhamdioğlu, Duygu; Hacıhamdioğlu, Bülent; Altun, Demet; Müftüoğlu, Tuba; Karademir, Ferhan; Süleymanoğlu, Selami

    2016-09-01

    Urinary netrin-1 is a new marker to demonstrate early tubular damage. The aim of this study was to determine whether urinary netrin-1 is increased in obese children. A total of 68 normoalbuminuric and normotensive obese patients and 65 controls were included in the study. Urine samples were collected for assessment of urinary phosphorus, sodium, potassium, creatinine, albumin, and netrin-1. Blood samples were collected for measurements of fasting glucose, insulin, lipid, phosphorus, sodium, potassium, and creatinine levels. Homeostatic model assessment insulin resistance index was calculated. Gender and age were similar between obese and control groups (12.01±3.03 vs. 11.7±3.2 years, p=0.568 and 33 vs. 35 girls, p=0.543, respectively). Obese patients had significantly higher netrin-1 excretion than the controls (841.68±673.17 vs. 228.94±137.25 pg/mg creatinine, p=0.000). Urinary netrin-1 level was significantly higher in obese subjects with insulin resistance compared to those without insulin resistance (1142±1181 vs. 604.9±589.91 pg/mg creatinine, p=0.001). In normotensive and normoalbuminuric obese children, urinary netrin-1 level can increase before onset of albuminuria. Urinary netrin-1 excretion appears to be affected predominantly by insulin resistance and hyperinsulinemia. Urinary netrin-1 may be a new biomarker for determining early tubular injury in obese children.

  19. Caudal migration and proliferation of renal progenitors regulates early nephron segment size in zebrafish.

    PubMed

    Naylor, Richard W; Dodd, Rachel C; Davidson, Alan J

    2016-10-19

    The nephron is the functional unit of the kidney and is divided into distinct proximal and distal segments. The factors determining nephron segment size are not fully understood. In zebrafish, the embryonic kidney has long been thought to differentiate in situ into two proximal tubule segments and two distal tubule segments (distal early; DE, and distal late; DL) with little involvement of cell movement. Here, we overturn this notion by performing lineage-labelling experiments that reveal extensive caudal movement of the proximal and DE segments and a concomitant compaction of the DL segment as it fuses with the cloaca. Laser-mediated severing of the tubule, such that the DE and DL are disconnected or that the DL and cloaca do not fuse, results in a reduction in tubule cell proliferation and significantly shortens the DE segment while the caudal movement of the DL is unaffected. These results suggest that the DL mechanically pulls the more proximal segments, thereby driving both their caudal extension and their proliferation. Together, these data provide new insights into early nephron morphogenesis and demonstrate the importance of cell movement and proliferation in determining initial nephron segment size.

  20. 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

  1. Formation of immunochemical advanced glycosylation end products precedes and correlates with early manifestations of renal and retinal disease in diabetes.

    PubMed

    Beisswenger, P J; Makita, Z; Curphey, T J; Moore, L L; Jean, S; Brinck-Johnsen, T; Bucala, R; Vlassara, H

    1995-07-01

    Elevated levels of advanced glycosylation end products (AGEs) have been found in multiple tissues in association with diabetic vascular complications and during the microalbuminuric phase of diabetic nephropathy. In this study, we have used an AGE-specific enzyme-linked immunosorbent assay (ELISA) to measure skin AGEs to determine whether elevated levels can be detected before the onset of overt microangiopathy. Subjects with type I diabetes (n = 48) were graded for the degree of nephropathy (normal [23], microalbuminuria [12], or macroalbuminuria [12]) and retinopathy (none [13], background [20], or proliferative [15]). Subgroups with a premicroalbuminuric phase of albumin excretion (< or = 28 mg/24 h, n = 27) or with the earliest stages of retinopathy (n = 27) were identified. A significant increase in tissue AGEs was found as urinary albumin increased during the premicroalbuminuric phase of nephropathy even when the data were adjusted for age and duration of diabetes (P = 0.005). Immunoreactive AGEs also increased as normal renal status advanced to microalbuminuria and macroalbuminuria (P = 0.0001 across groups). Significant elevation of AGEs was also found in association with the earliest stages of clinically evident retinopathy (early background versus minimal grades). In addition, higher AGE levels were found in subjects with proliferative retinopathy when compared with those with less severe retinopathy (P < 0.004 across groups). In contrast, no significant differences were found in tissue AGE levels between groups with or without early retinopathy based on pentosidine or fluorescent AGE measurements, although fluorescent AGEs correlated with albumin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. VHL and HIF-1α: gene variations and prognosis in early-stage clear cell renal cell carcinoma.

    PubMed

    Lessi, Francesca; Mazzanti, Chiara Maria; Tomei, Sara; Di Cristofano, Claudio; Minervini, Andrea; Menicagli, Michele; Apollo, Alessandro; Masieri, Lorenzo; Collecchi, Paola; Minervini, Riccardo; Carini, Marco; Bevilacqua, Generoso

    2014-03-01

    Von Hipple-Lindau gene (VHL) inactivation represents the most frequent abnormality in clear cell renal cell carcinoma (ccRCC). Hypoxia-inducible factor-1α (HIF-1α) expression is regulated by O2 level. In normal O2 conditions, VHL binds HIF-1α and allows HIF-1α proteasomal degradation. A single-nucleotide polymorphism (SNP) has been found located in the oxygen-dependent degradation domain at codon 582 (C1772T, rs11549465, Pro582Ser). In hypoxia, VHL/HIF-1α interaction is abolished and HIF-1α activates target genes in the nucleus. This study analyzes the impact of genetic alterations and protein expression of VHL and the C1772T SNP of HIF-1α gene (HIF-1α) on prognosis in early-stage ccRCC (pT1a, pT1b, and pT2). Mutational analysis of the entire VHL sequence and the genotyping of HIF-1α C1772T SNP were performed together with VHL promoter methylation analysis and loss of heterozygosis (LOH) analysis at (3p25) locus. Data obtained were correlated with VHL and HIF-1α protein expression and with tumor-specific survival (TSS). VHL mutations, methylation status, and LOH were detected in 51, 11, and 12% of cases, respectively. Our results support the association between biallelic alterations and/or VHL silencing with a worse TSS. Moreover, we found a significant association between the HIF-1α C1772C genotype and a worse TSS. The same association was found when testing the presence of HIF-1α protein in the nucleus. Our results highlight the role of VHL/HIF-1α pathway in RCC and support the molecular heterogeneity of early-stage ccRCC. More important, we show the involvement of HIF-1α C1772T SNP in ccRCC progression.

  3. 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.

  4. The use of cell cycle arrest biomarkers in the early detection of acute kidney injury. Is this the new renal troponin?

    PubMed

    Ortega, Luis M; Heung, Michael

    2018-04-05

    Acute kidney injury (AKI) has a high prevalence in critical care patients. Early detection might prevent patients from developing chronic kidney disease and requirement for renal replacement therapy. If we compare AKI with acute coronary syndrome, in which an increase in cardiac troponin may trigger early diagnosis and therapeutic intervention, we could extrapolate a similar technique in patients with early AKI without changes in urinary frequency or serum creatinine. The objective is to identify biomarker-positive, creatinine-negative patients that would allow therapeutic interventions to be initiated before finding changes in serum creatinine, preventing kidney damage. Tissue inhibitor of metalloproteinase 2 and insulin-like growth factor binding protein 7 are cell cycle arrest biomarkers that have demonstrated, in recent clinical trials, to have good sensitivity and specificity for early detection of AKI. Other recent studies have shown that the joint use of these biomarkers with serum creatinine and urine production could improve the prognosis of AKI in critical patients. The application of these biomarkers in clinical practice would enable the early identification of patients at risk of AKI, establishing interventions that would improve the survival of renal function. Copyright © 2017 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  5. 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

  6. 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.

  7. 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.

  8. [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.

  9. 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

  10. 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

  11. Delayed treatment of the first febrile urinary tract infection in early childhood increased the risk of renal scarring.

    PubMed

    Karavanaki, Kyriaki A; Soldatou, Alexandra; Koufadaki, Athina Maria; Tsentidis, Charalampos; Haliotis, Fotis A; Stefanidis, Constantinos J

    2017-01-01

    This study evaluated the controversial relationship between the duration of fever before treatment initiation (FBT) for a febrile urinary tract infection (UTI), with renal scarring based on dimercaptosuccinic acid scintigraphy (DMSA) findings. The inpatient records of 148 children under two years of age with a first episode of febrile UTI were analysed. Acute and repeat DMSA findings, and clinical and laboratory parameters were evaluated. Acute DMSA showed that 76 of the 148 children with a febrile UTI had renal lesions: 20 were mild, and 56 were moderate or severe. Repeat DMSA showed renal scarring in 34 patients. The only factors associated with the development of renal scars in the repeat DMSA were FBT of more than 72 hours, the presence and severity of vesicoureteral reflux and increased procalcitonin levels and absolute neutrophil counts. Multiple regression analysis showed that an FBT above 72 hours was the only significant factor that predicted renal scars. Delay in treatment initiation of 72 hours or more was a risk factor for permanent renal scars after the first episode of febrile UTI. Other associated factors were increased procalcitonin and absolute neutrophil count on admission and the presence and severity of vesicouretal reflux. ©2016 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. Up-regulation of Serum MiR-130b-3p Level is Associated with Renal Damage in Early Lupus Nephritis

    NASA Astrophysics Data System (ADS)

    Wang, Wanpeng; Mou, Shan; Wang, Ling; Zhang, Minfang; Shao, Xinghua; Fang, Wei; Lu, Renhua; Qi, Chaojun; Fan, Zhuping; Cao, Qin; Wang, Qin; Fang, Yan; Ni, Zhaohui

    2015-08-01

    Systemic lupus erythematosus (SLE) is a common but severe autoimmune systemic inflammatory disease. Lupus nephritis (LN) is a serious complication of SLE,affecting up to 70% of SLE patients. Circulating microRNAs (miRNA) are emerging as biomarkers for pathological conditions and play significant roles in intercellular communication. In present research, serum samples from healthy control, early and late stage LN patients were used to analyze the expression profile of miRNAs by microarray. Subsequent study demonstrated that miR-130b-3p in serum of patients with early stage LN were significantly up-regulated when compared with healthy controls. In addition,we have also observed that the expression of a large amount of circulating microRNAs significantly decreased in patients with late stage LN. The further analysis found that the expression of serum miR-130b-3p was positively correlated with 24-hour proteinuria and renal chronicity index in patients with early stage LN.Transfection of renal tubular cellline(HK-2)with miR-130b-3p mimics can promote epithelial-mesenchymal transition (EMT). The opposite effects were observed when transfected with miR-130b-3p inhibitors. MiR-130b-3p negatively regulated ERBB2IP expression by directly targeting the 3‧-UTR of ERBB2IP The circulating miR-130b-3p might serve as a biomarker and play an important role in renal damage in early stage LN patients.

  17. Population pharmacokinetic-pharmacodynamic modelling of mycophenolic acid in paediatric renal transplant recipients in the early post-transplant period.

    PubMed

    Dong, Min; Fukuda, Tsuyoshi; Cox, Shareen; de Vries, Marij T; Hooper, David K; Goebel, Jens; Vinks, Alexander A

    2014-11-01

    The purpose of this study was to develop a population pharmacokinetic and pharmacodynamic (PK-PD) model for mycophenolic acid (MPA) in paediatric renal transplant recipients in the early post-transplant period. A total of 214 MPA plasma concentrations-time data points from 24 patients were available for PK model development. In 17 out of a total of 24 patients, inosine monophosphate dehydrogenase (IMPDH) enzyme activity measurements (n = 97) in peripheral blood mononuclear cells were available for PK-PD modelling. The PK-PD model was developed using non-linear mixed effects modelling sequentially by 1) developing a population PK model and 2) incorporating IMPDH activity into a PK-PD model using post hoc Bayesian PK parameter estimates. Covariate analysis included patient demographics, co-medication and clinical laboratory data. Non-parametric bootstrapping and prediction-corrected visual predictive checks were performed to evaluate the final models. A two compartment model with a transit compartment absorption best described MPA PK. A non-linear relationship between dose and MPA exposure was observed and was described by a power function in the model. The final population PK parameter estimates (and their 95% confidence intervals) were CL/F, 22 (14.8, 25.2) l h(-1) 70 kg(-1) ; Vc /F, 45.4 (29.6, 55.6) l; Vp /F, 411 (152.6, 1472.6)l; Q/F, 22.4 (16.0, 32.5) l h(-1) ; Ka , 2.5 (1.45, 4.93) h(-1) . Covariate analysis in the PK study identified body weight to be significantly correlated with CL/F. A simplified inhibitory Emax model adequately described the relationship between MPA concentration and IMPDH activity. The final population PK-PD parameter estimates (and their 95% confidence intervals) were: E0 , 3.45 (2.61, 4.56) nmol h(-1)  mg(-1) protein and EC50 , 1.73 (1.16, 3.01) mg l(-1) . Emax was fixed to 0. There were two African-American patients in our study cohorts and both had low IMPDH baseline activities (E0 ) compared with Caucasian

  18. 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.

  19. [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.

  20. 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.

  1. Early Detection of Postoperative Acute Kidney Injury in Acute Stanford Type A Aortic Dissection With Doppler Renal Resistive Index.

    PubMed

    Qin, Huai; Wu, Haibo; Chen, Yi; Zhang, Nan; Fan, Zhanming

    2017-10-01

    This study aimed to evaluate the early efficiency of Doppler renal resistive index (DRRI) in prediction of acute kidney injury (AKI) after surgery in acute Stanford Type A aortic dissection (AAAD) patients. Sixty-one AAAD patients who planned to receive Sun's surgical management were prospectively enrolled. The DRRI was measured by ultrasonography Doppler on the day before surgery (DRRI pre ), on admission to the intensive care unit (DRRI T0 ), 6 hours after surgery (DRRI T6 ), 24 hours after surgery (DRRI T24 ), and 48 hours after surgery (DRRI T48 ). The maximum DRRI value (DRRI max ) was recorded. The AKI was evaluated according to the classifications of the Acute Kidney Injury Network. The DRRI and serum creatinine (sCr) were compared between the pre- and postoperative time stations, as well as between the AKI and no-AKI groups. Thirty-nine (63.9%) patients suffered from AKI, and 12 (19.6%) patients received dialysis. No significant difference was found in DRRI pre (0.63 ± 0.04 versus 0.65 ± 0.06, P = .059) and sCr pre (84.13 ± 23.77 versus 94.29 ± 51.11, P = .383) between the two groups with and without AKI. Both the DRRI and sCr increased significantly after surgery in the AKI groups (P < .001). However, the DRRI reached its maximum 6 hours after surgery, whereas the sCr reached its maximum after 24 hours. Both the DRRI and sCr improved 48 hours after surgery. The area under the receiver operating characteristic curve for DRRI max (0.864, 95% confidence interval: 0.770-0.957) and DRRI T6 (0.861, 95% confidence interval: 0.766-0.957) was larger than the other three DRRIs measured at different time points. The cutoff value of DRRI max was 0.71, a sensitivity of 76.9% and specificity of 95.5%. Postoperative DRRI predicts the AKI earlier than sCr after AAAD surgery. The best time to detect DRRI was 6 hours after surgery. © 2017 by the American Institute of Ultrasound in Medicine.

  2. 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.

  3. Early Application of High Cut-Off Haemodialysis for de-Novo Myeloma Nephropathy is Associated with Long-Term Dialysis-Independency and Renal Recovery

    PubMed Central

    Khalafallah, Alhossain A.; Loi, Sie Wuong; Love, Sarah; Mohamed, Muhajir; Mace, Rose; Khalil, Ramy; Girgs, Miriam; Raj, Rajesh; Mathew, Mathew

    2013-01-01

    Background Multiple myeloma (MM) is a haematological malignancy associated with kidney injury resulting from cast nephropathy, which can be caused by monoclonal free light chains (FLC). It has been demonstrated that early reduction of FLC can lead to a higher proportion of patients recovering renal function with a better outcome, especially if high cut-off haemodialysis (HCO-HD) combined with chemotherapy is used. Patients and Methods In this study, four cases with MM nephropathy were treated with HCO-HD and chemotherapy at a single institution during the period from August 2009 to August 2011. All of the patients presented with acute renal failure and high serum FLC. All patients underwent a bone marrow biopsy to confirm the diagnosis of MM, according to the WHO criteria. Three patients had de novo MM and one patient had relapsed light chain myeloma disease. All patients underwent HCO-HD concomitantly with specific myeloma therapy once the diagnosis or relapse of MM was established. Results After a medial follow up of 26 months, (range, 13–36) our data showed that all patients had a significant decrease in serum FLC through HCO-HD, proving the effectiveness of HCO-HD in managing MM. De-novo MM patients restored their renal function and achieved low-level FLC early in the treatment and became dialysis-independent. One patient with relapsed myeloma remained dialysis-dependent. Conclusion In summary, our study suggests that in myeloma nephropathy associated with light-chain MM, HCO-HD should be initiated as early as possible. At the same time a specific MM treatment should be initiated to gain control of the disease and salvage the kidneys in order to achieve dialysis-independency. Further randomized trials to confirm our results are warranted. PMID:23350020

  4. Old habits die hard; does early urinary catheter removal affect kidney size, bacteriuria and UTI after renal transplantation?

    PubMed

    Akbari, Roghayeh; Rahmani Firouzi, Sedigheh; Akbarzadeh-Pasha, Abazar

    2017-01-01

    Introduction: Renal transplantation is the treatment of choice in chronic renal failure patients. Objectives: The purpose of this study was to evaluate the impact of urinary catheter removal time on transplanted kidney size and incidence of asymptomatic bacteriuria and urinary tract infections (UTIs). Patients and Methods: This retrospective cohort study evaluated the clinical outcomes of 109 consecutive live donor renal transplant recipients from December 2011 to July 2014. Routine ultrasound examinations were performed on donor's kidney prior to operation and one month later. Kidney volume was calculated. UTI and bacteriuria were evaluated one month later. Patients were divided into two groups based on time of Foley catheter removal (before and after fifth day posttransplantation). Results: In this study 74 males (67.9%) and 35 females (32.1%) were evaluated. Sixty-six patients (57.92%) were in group 1. None of the patients with positive urine culture had UTI but bacteriuria occurred in all of them (21.1%). Bacteriuria time after transplantation and catheter removal was significantly later in group 1 and it was not different in female group but they were later in male group. The mean renal volume increase was positively correlated to renal transplant recipient and donor's age and donor's body mass index (BMI) ( P <0.05). Conclusion: This study showed that the time of catheter removal after kidney transplantation does not affect incidence of UTI but increases the probability of bacteria in men whose catheter was removed within 5 days after transplantation. We also found that the renal volume change is not associated with catheter removal time and bacteriuria.

  5. Denervation (ablation) of nerve terminalis in renal arteries: early results of interventional treatment of arterial hypertension in Poland.

    PubMed

    Bartuś, Krzysztof; Sadowski, Jerzy; Kapelak, Bogusław; Zajdel, Wojciech; Godlewski, Jacek; Bartuś, Stanisław; Bochenek, Maciej; Bartuś, Magdalena; Żmudka, Krzysztof; Sobotka, Paul A

    2013-01-01

    Arterial hypertension is one of the main causes of cardiovascular disease morbidity and overall mortality. To report the single centre experiences with changes in arterial blood pressure (BP) in patients after intra-arterial application of radiofrequency (RF) energy to cause renal sympathetic efferent and somatic afferent nerve and report vascular and kidney safety in a six month follow up. Twenty-eight patients, with hypertension despite medical therapy (median age 52.02 years, range 42-72 years) consented to therapeutic renal nerve ablation. SIMPLICITY RF catheters and generator provided by Ardian (currently Medtronic Inc., USA) were used to perform renal artery angiography and ablation. The mean BP at baseline, and after one month, three months and six months were measured [mm Hg]: systolic 176.6; 162.3 (p = 0.004); 150.6 (p < 0.001); 147.2 (p < 0.001); diastolic 100.2; 90.3 (p < 0.001); 91.79 (p = 0.03); 88.5 (p < 0.001); pulse pressure 76.57; 75.18 (p = NS); 65.80 (p < 0.001); 62.15 (p < 0.001). Neither procedure-related nor therapy-related complications were reported in the six month follow up. In our cohort of patients, intra-arterial renal nerve denervation was not associated with either vascular or renal complications out to six months. Nerve ablation of renal arteries led to significant reduction of mean values of arterial systolic, diastolic BP and significant reduction of pulse pressure. The Polish experience is not significantly different compared to that reported in the Symplicity I and Symplicity II international cohorts. The long term durability of this therapy and its application to earlier stages of hypertension or other disease states will require further investigation.

  6. 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

  7. Humeral Head Reconstruction With Osteochondral Allograft Transplantation.

    PubMed

    Saltzman, Bryan M; Riboh, Jonathan C; Cole, Brian J; Yanke, Adam B

    2015-09-01

    To synthesize, in a systematic review, the available clinical evidence of osteochondral allograft transplants for large osteochondral defects of the humeral head. The Medline, Embase, and Cochrane databases were searched for studies reporting clinical or radiographic outcomes of osteochondral allograft transplantation for humeral head defects. Descriptive statistics were provided for all outcomes. After checking for data normality, we compared postoperative and preoperative values using the Student t test. We included 12 studies (8 case reports and 4 case series) in this review. The study group consisted of 35 patients. The mean age was 35.4 ± 18.1 years; 77% of patients were male patients. Thirty-three patients had large Hill-Sachs lesions due to instability, 1 had an osteochondritis dissecans lesion, and 1 had an iatrogenic lesion after resection of synovial chondromatosis. The mean lesion size was 3 ± 1.4 cm (anteroposterior) by 2.25 ± 0.3 cm (medial-lateral), representing on average 40.5% ± 4.73% of the native articular surface. Of the 35 patients, 3 received a fresh graft, with all others receiving frozen grafts. Twenty-three femoral heads, 10 humeral heads, and 2 sets of osteochondral plugs were used. The mean length of follow-up was 57 months. Significant improvements were seen in forward flexion at 6 months (68° ± 18.1°, P < .001), forward flexion at 12 months (83.42° ± 18.3°, P < .001), and external rotation at 12 months (38.72° ± 18.8°, P < .001). American Shoulder and Elbow Surgeons scores improved by 14 points (P = .02). Radiographic studies at final follow-up showed allograft necrosis in 8.7% of cases, resorption in 36.2%, and glenohumeral arthritic changes in 35.7%. Complication rates were between 20% and 30%, and the reoperation rate was 26.67%. Although only 3 patients received fresh allografts, there were no reports of graft resorption, necrosis, or arthritic changes in these patients. Humeral head allograft-most commonly used in the

  8. A case of severe chlorite poisoning successfully treated with early administration of methylene blue, renal replacement therapy, and red blood cell transfusion: case report.

    PubMed

    Gebhardtova, Andrea; Vavrinec, Peter; Vavrincova-Yaghi, Diana; Seelen, Mark; Dobisova, Anna; Flassikova, Zora; Cikova, Andrea; Henning, Robert H; Yaghi, Aktham

    2014-08-01

    The case of a 55-year-old man who attempted suicide by ingesting <100 mL of 28% sodium chlorite solution is presented. On arrival in the intensive care unit, the patient appeared cyanotic with lowered consciousness and displayed anuria and chocolate brown serum.Initial laboratory tests revealed 40% of methemoglobin. The formation of methemoglobin was effectively treated with methylene blue (10% after 29 hours).To remove the toxin, and because of the anuric acute renal failure, the patient received renal replacement therapy. Despite these therapeutic measures, the patient developed hemolytic anemia and disseminated intravascular coagulation, which were treated with red blood cell transfusion and intermittent hemodialysis. These interventions led to the improvement of his condition and the patient eventually fully recovered. Patient gave written informed consent.This is the third known case of chlorite poisoning that has been reported. Based upon this case, we suggest the management of sodium chlorite poisoning to comprise the early administration of methylene blue, in addition to renal replacement therapy and transfusion of red blood cells.

  9. A Case of Severe Chlorite Poisoning Successfully Treated With Early Administration of Methylene Blue, Renal Replacement Therapy, and Red Blood Cell Transfusion

    PubMed Central

    Gebhardtova, Andrea; Vavrinec, Peter; Vavrincova-Yaghi, Diana; Seelen, Mark; Dobisova, Anna; Flassikova, Zora; Cikova, Andrea; Henning, Robert H.; Yaghi, Aktham

    2014-01-01

    Abstract The case of a 55-year-old man who attempted suicide by ingesting <100 mL of 28% sodium chlorite solution is presented. On arrival in the intensive care unit, the patient appeared cyanotic with lowered consciousness and displayed anuria and chocolate brown serum. Initial laboratory tests revealed 40% of methemoglobin. The formation of methemoglobin was effectively treated with methylene blue (10% after 29 hours). To remove the toxin, and because of the anuric acute renal failure, the patient received renal replacement therapy. Despite these therapeutic measures, the patient developed hemolytic anemia and disseminated intravascular coagulation, which were treated with red blood cell transfusion and intermittent hemodialysis. These interventions led to the improvement of his condition and the patient eventually fully recovered. Patient gave written informed consent. This is the third known case of chlorite poisoning that has been reported. Based upon this case, we suggest the management of sodium chlorite poisoning to comprise the early administration of methylene blue, in addition to renal replacement therapy and transfusion of red blood cells. PMID:25144325

  10. 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.

  11. 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.

  12. 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.

  13. Dietary Sodium Modulation of Aldosterone Activation and Renal Function During the Progression of Experimental Heart Failure Miller: Dietary Sodium and Early Heart Failure

    PubMed Central

    Miller, Wayne L.; Borgeson, Daniel D.; Grantham, J. Aaron; Luchner, Andreas; Redfield, Margaret M.; Burnett, John C.

    2015-01-01

    Aims Aldosterone activation is central to the sodium-fluid retention that marks the progression of heart failure (HF). The actions of dietary sodium restriction, a mainstay in HF management, on cardiorenal and neuroendocrine adaptations during the progression of HF are poorly understood. The study aim was to assess the role of dietary sodium during the progression of experimental HF. Methods and Results Experimental HF was produced in a canine model by rapid right ventricular pacing which evolves from early mild HF to overt, severe HF. Dogs were fed one of three diets: 1) high sodium [250 mEq (5.8 grams) per day, n=6]; 2) standard sodium [58 mEq (1.3 grams) per day, n=6]; and 3) sodium restriction [11 mEq (0.25 grams) per day, n=6]. During the 38 day study hemodynamics, renal function, renin activity (PRA), and aldosterone were measured. Changes in hemodynamics at 38 days were similar in all three groups, as were changes in renal function. Aldosterone activation was demonstrated in all three groups, however, dietary sodium restriction, in contrast to high sodium, resulted in early (10 days) activation of PRA and aldosterone. High sodium demonstrated significant suppression of aldosterone activation over the course of HF progression. Conclusions Excessive dietary sodium restriction particularly in early stage HF results in early aldosterone activation, while normal and excess sodium intake are associated with delayed or suppressed activation. These findings warrant evaluation in humans to determine if dietary sodium manipulation, particularly during early stage HF, may have a significant impact on neuroendocrine disease progression. PMID:25823360

  14. 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.

  15. 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

  16. Reliability of chronic allograft nephropathy diagnosis in sequential protocol biopsies.

    PubMed

    Serón, Daniel; Moreso, Francesc; Fulladosa, Xavier; Hueso, Miguel; Carrera, Marta; Grinyó, Josep M

    2002-02-01

    Chronic allograft nephropathy (CAN) progresses rapidly during the first few months and slowly thereafter. Although the presence of CAN in protocol renal biopsies is a predictor of outcome, the reliability of this diagnosis according to Banff criteria has not been characterized. Renal lesions were evaluated according to the Banff criteria in sequential protocol biopsies performed at 4 and 14 months in 310 biopsies obtained from 155 patients. CAN progressed from 40 to 53% (P=0.001) while serum creatinine remained stable (146 +/- 44 vs. 147 +/- 48 micromol/L, P=NS). Graft survival in patients with and without CAN in the first biopsy was 74 versus 91% (P < 0.05), and in the second biopsy 75 versus 94% (P < 0.05). In 54 patients (35%) no CAN was present in both biopsies, 39 (25%) showed progression to CAN, 19 (12%) showed regression of CAN, and 43 (28%) showed CAN in both biopsies. Graft survival was: 100%, 81.6%, 82.6% and 69.4%, respectively (P < 0.01). Assuming that CAN does not regress and sampling error is normally distributed, we estimated that 25% of biopsies cannot be properly classified. The increase in the incidence of CAN between the 4th and 14th month is lower than the proportion of misclassified biopsies. Thus, monitoring the progression of CAN by means of two sequential biopsies at 4 and 14 months is inaccurate. We suggest that progression of scarring be monitored by means of a donor and a protocol biopsy performed during the first year evaluated with a quantitative approach.

  17. Efficacy of Hydrochlorothiazide and low renal solute feed in Neonatal Central Diabetes Insipidus with transition to Oral Desmopressin in early infancy.

    PubMed

    Abraham, Mary B; Rao, Shripada; Price, Glynis; Choong, Catherine S

    2014-01-01

    The treatment of central diabetes insipidus (DI) with desmopressin in the neonatal period is challenging because of the significant risk of hyponatremia with this agent. The fixed anti-diuresis action of desmopressin and the obligate high fluid intake with milk feeds lead to considerable risk of water intoxication and hyponatremia. To reduce this risk, thiazide diuretics, part of the treatment of nephrogenic DI, were used in conjunction with low renal solute feed and were effective in a single case series of neonatal central DI. We evaluated the efficacy of early treatment of neonatal central DI with hydrochlorothiazide with low solute feed and investigated the clinical indicators for transition to desmopressin during infancy. A retrospective chart review was conducted at Princess Margaret Hospital, Perth of neonates diagnosed with central DI and treated with hydrochlorothiazide, between 2007 and 2013. Four newborns were identified. Mean sNa and mean change in sNa with desmopressin and hydrochlorothiazide treatment were recorded along with episodes of hyponatremia and hypernatremia. Length and weight trajectories during the first 12 months were assessed. The mean change in sNa per day with hydrochlorothiazide and low renal solute feed was 2.5 - 3 mmol/L; on desmopressin treatment, the mean change in sNa was 6.8-7.9 mmol/L. There was one episode of symptomatic hyponatremia with intranasal desmopressin with no episodes of hyponatremia or hypernatremia during treatment with hydrochlorothiazide or following transition to oral desmopressin. Transition to oral desmopressin between 3 to 12 months of age was associated with good control of DI. Following introduction of solids, sNa remained stable but weight gain was slow. This improved following transition to desmopressin in one infant. Hydrochlorothiazide with low renal solute feed is a safe and effective treatment option in neonatal central DI. However, transition to desmopressin should be considered early in infancy

  18. Brachial-ankle pulse wave velocity predicts decline in renal function and cardiovascular events in early stages of chronic kidney disease.

    PubMed

    Yoon, Hye Eun; Shin, Dong Il; Kim, Sung Jun; Koh, Eun Sil; Hwang, Hyeon Seok; Chung, Sungjin; Shin, Seok Joon

    2013-01-01

    In this study, we investigated the predictive capacity of the brachial-ankle aortic pulse wave velocity (baPWV), a marker of arterial stiffness, for the decline in renal function and for cardiovascular events in the early stages of chronic kidney disease (CKD). Two hundred forty-one patients who underwent a comprehensive check-up were included and were divided into two groups according to their estimated glomerular filtration rates (eGFR): patients with CKD categories G2, G3a and G3b (30 ≤ eGFR < 90 ml/min/1.73m(2), eGFR < 90 group; n=117) and those with eGFR ≥ 90 ml/min/1.73 m(2) (eGFR ≥ 90 group; n=124). The change in renal function, the eGFR change, was determined by the slope of eGFR against time. We analysed whether baPWV was associated with eGFR change or predicted cardiovascular events. baPWV was independently associated with eGFR change in a multivariate analysis of the total patients (β=-0.011, p=0.011) and remained significantly associated with eGFR change in a subgroup analysis of the eGFR < 90 group (β=-0.015, p=0.035). baPWV was independently associated with cardiovascular events (odds ratio=1.002, p=0.048) in the eGFR < 90 group, but not in the eGFR ≥ 90 group. The receiver operative characteristic curve analysis showed that 1,568 cm/sec was the cut-off value of baPWV for predicting CV events in the eGFR < 90 group (area under curve=0.691, p=0.03) CONCLUSIONS: In patients with early stages of CKD, baPWV was independently associated with the decline in renal function and short-term cardiovascular events.

  19. Early Removal of Double-J Stents Decreases Urinary Tract Infections in Living Donor Renal Transplantation: A Prospective, Randomized Clinical Trial.

    PubMed

    Liu, S; Luo, G; Sun, B; Lu, J; Zu, Q; Yang, S; Zhang, X; Dong, J

    2017-03-01

    The optimal timing for stent removal after renal transplantation remains controversial. This article describes an interim analysis of a randomized, prospective, double-blind trial aimed at detecting differences in urological complications between early ureteral stent removal at 1 week and routine ureteral stent removal at 4 weeks. Between October 2010 and March 2015, 103 patients who underwent living donor renal transplantation at a single center were pre-operatively randomly assigned to the early ureteral stent removal (at 1 week) group or the routine ureteral stent removal (at 4 weeks) group. Urinary symptoms, auxiliary examination results, and obstruction events were recorded during 3 months of follow-up. A cost analysis of both the hospitalization and postoperative periods was discussed. In total, 52 patients in the 1-week stent group and 51 patients in the 4-week stent group were analyzed. No serious adverse events were reported. Three episodes of urinary tract infections (UTIs) occurred in the 1-week stent group, and 18 such episodes were recorded in the 4-week stent group (5.8% vs 29.4%; P = .002). After adjusting for age, sex, ischemia time, renal artery number, body mass index, multiple arteries, and associated medical illness, regression analysis indicated that only stent duration was associated with UTI (OR, 8.791; 95% CI, 1.984-38.943; P = .004). The results of our study demonstrate that ureteral stent removal at 1 week reduces the risk of UTIs compared with routine removal at 4 weeks. Similar effects of ureteral stent removal on complication rates are observed for these two removal times. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. 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.

  1. Early double J stent removal in renal transplant patients to prevent urinary tract infection - systematic review and meta-analysis of randomized controlled trials.

    PubMed

    Yahav, Dafna; Green, Hefziba; Eliakim-Raz, Noa; Mor, Eytan; Husain, Shahid

    2018-04-01

    Ureteral stents are routinely used in renal transplant and are associated with reduced urological complications but increased urinary tract infections (UTIs). There is no agreement on the preferred time to removal of stents after transplantation. We performed a systematic review and meta-analysis of all randomized controlled trials (RCTs) comparing stent duration of <14 days vs > =14 days. Electronic databases were searched to identify RCTs that compared early vs late stent removal. Primary outcome was urinary tract infections. Secondary outcomes included various urological complications. No significant difference in UTI rates was demonstrated between short and long stent duration (relative risk (RR) 0.85, 95% confidence interval (CI) 0.44-1.64), with significant heterogeneity (I 2  = 86%). Sensitivity analysis evaluating studies with low risk of bias for allocation concealment demonstrated statistically significant lower rates of UTI with short stent duration (RR 0.48, 95% CI 0.32-0.71) with no heterogeneity. No significant difference was demonstrated for the outcome of major urological complications (RR 0.72, 95% CI 0.50-1.05), without heterogeneity. Ureteral stenosis rates were significantly lower in the short duration arm (RR 0.42, 95% CI 0.18-0.98). Early removal of ureteral stents after renal transplant may be associated with reduced rates of UTI and ureteral stenosis. Additional RCTs are needed.

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. Early Implementation of Continuous Renal Replacement Therapy Optimizes Casualty Evacuation for Combat-Related Acute Kidney Injury

    DTIC Science & Technology

    2013-08-01

    were Acute Kidney Injury Network (AKIN) 3 and all developed critical hyperkalemia (mean [SD], peak K+ 6.4 [0.4]). The peak plasma creatinine ranged...related acid-base disorders, severe hyperkalemia , and metabolic disorders became apparent. Based on the mounting pressure and internal performance im...with severe hyperkalemia was the most common indication for renal replacement. Validation for critical care evacuation to the Role IV facility mandated a

  8. Histopathology of spleen allograft rejection in miniature swine

    PubMed Central

    Dor, Frank J M F; Gollackner, Bernd; Kuwaki, Kenji; Ko, Dicken S C; Cooper, David K C; Houser, Stuart L

    2005-01-01

    Spleen transplantation (SpTx) has established donor-specific tolerance in rodents, but not in large animals or humans. We report the histopathology of rejection in an established model of SpTx in major histocompatibility complex (MHC)-defined miniature swine. Of the 17 SpTx, rejection was observed in two grafts transplanted into untreated, MHC-matched, minor antigen-disparate recipients (group 1, n = 4), but not in the two that received a 12-day course of cyclosporin A (CyA). Rejection also occurred in five grafts transplanted into fully MHC-disparate recipients (group 2, n = 12), one of which was untreated and four of which received some form of immunosuppressive therapy. One recipient of an MHC class-I-mismatched spleen treated with 12 days of CyA did not show rejection. Following biopsy and/or necropsy, fixed allograft tissue sections were treated with multiple stains, immunohistochemical markers and TUNEL assay. Common features of rejection occurred in grafts from both groups, but with varying time courses. Necrosis developed as early as day 8 in group 2 and day 27 in group 1, ranging from focal fibrinoid necrosis of arteriolar walls and sinusoids to diffuse liquefactive necrosis, usually associated with haemorrhage. Other features of rejection included white pulp expansion by atypical cells and decreased staining of basement membranes and reticular fibres. A doubling of the baseline TUNEL index preceded histologically identifiable rejection. This study establishes histologic guidelines for diagnosing and, perhaps, in future studies, predicting acute rejection of splenic allografts transplanted across known histocompatibility barriers in a large-animal model. PMID:15676033

  9. [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.

  10. Hyperhomocysteinaemia as a potential marker of early renal function decline in middle-aged Asian people without chronic kidney disease.

    PubMed

    Tak, Young Jin; Jeong, Dong Wook; Kim, Yun Jin; Lee, Sang Yeoup; Lee, Jeong Gyu; Song, Sang Heon; Cha, Kwang Soo; Kang, Yang Ho

    2016-02-01

    High levels of serum total homocysteine (tHcy), often observed in chronic kidney disease (CKD) patients, are a risk factor for cardiovascular disease. However, little is known about the relationship between tHcy and renal function in healthy individuals. We examined whether tHcy levels are related to renal function in Asian individuals without CKD. This cross-sectional study examined 2032 subjects, aged 40-64 years. Individuals with kidney diseases or other conditions that could affect tHcy were excluded. Renal function was determined by estimated glomerular filtration rate (eGFR) from levels of serum creatinine (sCr) and cystatin C. Age, tHcy, sCr, and cystatin C of the subjects were 54.1 ± 6.0 years, 9.5 (8.0-11.4) μmol/L, 0.81 ± 0.1 mg/dL, and 0.82 ± 0.1 mg/L, respectively. In a multiple linear regression analysis, tHcy was a significant independent determinant of sCr and cystatin C in men (β = 0.206 and β = 0.282, respectively) and women (β = 0.247 and β = 0.229, respectively). Highest tHcy levels were independently associated with increased cystatin C (>s1.10 mg/L) with an odds ratio (OR) of 5.00 [95% confidence interval (CI) 2.81-8.09] and decreased eGFR (<90 mL/min/1.73 m(2)) with an OR of 1.69 (95% CI 1.36-2.11) compared to tHcy levels in the 1st-3rd quartiles. Higher levels of tHcy are independently associated with sCr and cystatin C elevation. Our study suggests that tHcy levels may be influenced by renal function in Asian populations without CKD. Future studies are needed to define the role of tHcy in renal function.

  11. 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

  12. 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

  13. 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.

  14. 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

  15. Albumin stimulates renal tubular inflammation through an HSP70-TLR4 axis in mice with early diabetic nephropathy

    PubMed Central

    Jheng, Huei-Fen; Tsai, Pei-Jane; Chuang, Yi-Lun; Shen, Yi-Ting; Tai, Ting-An; Chen, Wen-Chung; Chou, Chuan-Kai; Ho, Li-Chun; Tang, Ming-Jer; Lai, Kuei-Tai A.; Sung, Junne-Ming; Tsai, Yau-Sheng

    2015-01-01

    ABSTRACT Increased urinary albumin excretion is not simply an aftermath of glomerular injury, but is also involved in the progression of diabetic nephropathy (DN). Whereas Toll-like receptors (TLRs) are incriminated in the renal inflammation of DN, whether and how albumin is involved in the TLR-related renal inflammatory response remains to be clarified. Here, we showed that both TLR2 and TLR4, one of their putative endogenous ligands [heat shock protein 70 (HSP70)] and nuclear factor-κB promoter activity were markedly elevated in the kidneys of diabetic mice. A deficiency of TLR4 but not of TLR2 alleviated albuminuria, tubulointerstitial fibrosis and inflammation induced by diabetes. The protection against renal injury in diabetic Tlr4−/− mice was associated with reduced tubular injuries and preserved cubilin levels, rather than amelioration of glomerular lesions. In vitro studies revealed that albumin, a stronger inducer than high glucose (HG), induced the release of HSP70 from proximal tubular cells. HSP70 blockade ameliorated albumin-induced inflammatory mediators. HSP70 triggered the production of inflammatory mediators in a TLR4-dependent manner. Moreover, HSP70 inhibition in vivo ameliorated diabetes-induced albuminuria, inflammatory response and tubular injury. Finally, we found that individuals with DN had higher levels of TLR4 and HSP70 in the dilated tubules than non-diabetic controls. Thus, activation of the HSP70-TLR4 axis, stimulated at least in part by albumin, in the tubular cell is a newly identified mechanism associated with induction of tubulointerstitial inflammation and aggravation of pre-existing microalbuminuria in the progression of DN. PMID:26398934

  16. Mechanisms for renal blood flow control early in diabetes as revealed by chronic flow measurement and transfer function analysis.

    PubMed

    Bell, Tracy D; DiBona, Gerald F; Wang, Ying; Brands, Michael W

    2006-08-01

    The purpose of this study was to establish the roles of the myogenic response and the TGF mechanism in renal blood flow (RBF) control at the very earliest stages of diabetes. Mean arterial pressure (MAP) and RBF were measured continuously, 18 h/d, in uninephrectomized control and diabetic rats, and transfer function analysis was used to determine the dynamic autoregulatory efficiency of the renal vasculature. During the control period, MAP averaged 91 +/- 0.5 and 89 +/- 0.4 mmHg, and RBF averaged 8.0 +/- 0.1 and 7.8 +/- 0.1 ml/min in the control and diabetic groups, respectively. Induction of diabetes with streptozotocin caused a marked and progressive increase in RBF in the diabetic rats, averaging 10 +/- 6% above control on day 1 of diabetes and 22 +/- 3 and 34 +/- 1% above control by the end of diabetes weeks 1 and 2. MAP increased approximately 9 mmHg during the 2 wk in the diabetic rats, and renal vascular resistance decreased. Transfer function analysis revealed significant increases in gain to positive values over the frequency ranges of both the TGF and myogenic mechanisms, beginning on day 1 of diabetes and continuing through day 14. These very rapid increases in RBF and transfer function gain suggest that autoregulation is impaired at the very onset of hyperglycemia in streptozotocin-induced type 1 diabetes and may play an important role in the increase in RBF and GFR in diabetes. Together with previous reports of decreases in chronically measured cardiac output and hindquarter blood flow, this suggests that there may be differential effects of diabetes on RBF versus nonrenal BF control.

  17. 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.

  18. Rabbit Trochlear Model of Osteochondral Allograft Transplantation

    PubMed Central

    To, Nhat; Curtiss, Shane; Neu, Corey P; Salgado, Christopher J; Jamali, Amir A

    2011-01-01

    Allografting and autografting of osteochondral tissues is a promising strategy to treat articular cartilage lesions in damaged joints. We developed a new model of fresh osteochondral allografting using the entire rabbit trochlea. The objective of the current study was to demonstrate that this model would achieve reproducible graft–host healing and maintain normal articular cartilage histologic, immunolocalization, and biochemical characteristics after transplantation under diverse storage and transplantation conditions. New Zealand white (n = 8) and Dutch belted (n = 8) rabbits underwent a 2-stage transplantation operation using osteochondral grafts that had been stored for 2 or 4 wk. Trochlear grafts harvested from the left knee were transplanted to the right knee as either autografts or allografts. Grafts were fixed with 22-gauge steel wire or 3-0 nylon suture. Rabbits were euthanized for evaluation at 1, 2, 4, 6, and 12 wk after transplantation. All grafts that remained in vivo for at least 4 wk demonstrated 100% interface healing by microCT. Trabecular bridging was present at the host–graft interface starting at 2 wk after transplantation, with no significant difference in cartilage histology between the various groups. The combined histology scores indicated minimal evidence of osteoarthritis. Immunostaining revealed that superficial zone protein was localized at the surface of all transplants. The rabbit trochlear model met our criteria for a successful model in regard to the ease of the procedure, low rate of surgical complications, relatively large articular cartilage surface area, and amount of host–graft bone interface available for analysis. PMID:22330350

  19. 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

  20. Interaction of melamine and di-(2-ethylhexyl) phthalate exposure on markers of early renal damage in children: The 2011 Taiwan food scandal.

    PubMed

    Wu, Chia-Fang; Hsiung, Chao A; Tsai, Hui-Ju; Tsai, Yi-Chun; Hsieh, Hui-Min; Chen, Bai-Hsiun; Wu, Ming-Tsang

    2018-04-01

    Melamine and phthalate, mainly di-(2-ethylhexyl) phthalate (DEHP), are ubiquitously present in the general environment. We investigated whether urine melamine levels can modify the relationship between DEHP exposure and markers of early renal damage in children. A nationwide health survey for Children aged ≤12 years possibly exposed to phthalates were enrolled between August 2012 and January 2013. They were administered questionnaires to collect details regarding past DEHP exposure to phthalate-tainted foodstuffs. Urine samples were measured melamine levels, phthalate metabolites and biomarkers of renal damage, including urine microalbumin/creatinine ratio (ACR), N-acetyl-beta-d-glucosaminidase (NAG), and β2-microglobulin. The study included 224 children who had a median urine melamine level (μg/mmol creatinine) of 1.61 ranging 0.18-47.42. Positive correlations were found between urine melamine levels and urine ACR as well as urine NAG levels (both Spearman correlation coefficients r = 0.24, n = 224, p < .001). The higher the past DEHP exposure or urine melamine levels, the higher the prevalence of microalbuminuria. An interaction effect was also found between urine melamine levels and past DEHP exposure on urine ACR. Melamine levels may further modify the effect of past DEHP exposure on urine ACR in children. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Promoting effects of potassium dibasic phosphate on early-stage renal carcinogenesis in unilaterally nephrectomized rats treated with N-ethyl-N-hydroxyethylnitrosamine.

    PubMed

    Hiasa, Y; Konishi, N; Nakaoka, S; Nakamura, T; Nishii, K; Ohshima, M

    1992-07-01

    The effects of potassium dibasic phosphate (PDP), potassium aluminum sulfate (PAS) and copper sulfate (CS) on early-stage renal carcinogenesis were investigated in unilaterally nephrectomized male Wistar rats after N-ethyl-N-hydroxyethylnitrosamine (EHEN) administration. After feeding 1,000 ppm EHEN, or basal diet for 2 weeks and removal of the left kidney at week 3, male Wistar rats were divided into 8 groups of 20 rats each. These groups received the following dietary treatments: 50,000 ppm PDP, 50,000 ppm PAS, 5,000 ppm CS or basal diet, respectively, for 18 weeks from weeks 3 to 20. The average numbers of adenomatous hyperplasias counted as preneoplastic lesions in the EHEN with 50,000 ppm PDP group were significantly higher than in the EHEN alone group or the EHEN followed by 50,000 ppm PAS or 5,000 ppm CS group. The treatment with 50,000 ppm PDP induced renal calcification and promoted the development of preneoplastic lesions in unilaterally nephrectomized rats treated with EHEN, but that with 50,000 ppm PAS or 5,000 ppm CS did not.

  2. Vascularized Composite Allografts: Procurement, Allocation, and Implementation.

    PubMed

    Rahmel, Axel

    Vascularized composite allotransplantation is a continuously evolving area of modern transplant medicine. Recently, vascularized composite allografts (VCAs) have been formally classified as 'organs'. In this review, key aspects of VCA procurement are discussed, with a special focus on interaction with the procurement of classical solid organs. In addition, options for a matching and allocation system that ensures VCA donor organs are allocated to the best-suited recipients are looked at. Finally, the different steps needed to promote VCA transplantation in society in general and in the medical community in particular are highlighted.

  3. Prognostic importance of early worsening renal function after initiation of angiotensin-converting enzyme inhibitor therapy in patients with cardiac dysfunction.

    PubMed

    Testani, Jeffrey M; Kimmel, Stephen E; Dries, Daniel L; Coca, Steven G

    2011-11-01

    Worsening renal function (WRF) in the setting of heart failure has been associated with increased mortality. However, it is unclear if this decreased survival is a direct result of the reduction in glomerular filtration rate (GFR) or if the mechanism underlying the deterioration in GFR is driving prognosis. Given that WRF in the setting of angiotensin-converting enzyme inhibitor (ACE-I) initiation is likely mechanistically distinct from spontaneously occurring WRF, we investigated the relative early WRF-associated mortality rates in subjects randomized to ACE-I or placebo. Subjects in the Studies Of Left Ventricular Dysfunction (SOLVD) limited data set (n=6337) were studied. The interaction between early WRF (decrease in estimated GFR ≥20% at 14 days), randomization to enalapril, and mortality was the primary end point. In the overall population, early WRF was associated with increased mortality (adjusted hazard ratio [HR], 1.2; 95% CI, 1.0-1.4; P=0.037). When analysis was restricted to the placebo group, this association strengthened (adjusted HR, 1.4; 95% CI, 1.1-1.8; P=0.004). However, in the enalapril group, early WRF had no adverse prognostic significance (adjusted HR, 1.0; 95% CI, 0.8-1.3; P=1.0; P=0.09 for the interaction). In patients who continued to receive study drug despite early WRF, a survival advantage remained with enalapril therapy (adjusted HR, 0.66; 95% CI, 0.5-0.9; P=0.018). These data support the notion that the mechanism underlying WRF is important in determining its prognostic significance. Specifically, early WRF in the setting of ACE-I initiation appears to represent a benign event that is not associated with a loss of benefit from continued ACE-I therapy.

  4. 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.

  5. Good outcome of brain stem progressive multifocal leukoencephalopathy in an immunosuppressed renal transplant patient: Importance of early detection and rapid immune reconstitution.

    PubMed

    Sauer, Roland; Gölitz, Philipp; Jacobi, Johannes; Schwab, Stefan; Linker, Ralf A; Lee, De-Hyung

    2017-04-15

    Progressive multifocal leukoencephalopathy (PML) is a rare, opportunistic and often fatal disease of the CNS which may occur under immunosuppression in transplant patients. Brain stem PML is associated with a particularly bad prognosis. Here, we present a case of a renal transplant patient treated with mycophenolate mofetil (MMF) and tacrolimus who developed brain stem PML with limb ataxia, dysarthria and dysphagia. Diagnosis was established by typical MRI features and detection of JCV-DNA in the CSF. Immune reconstitution after stopping MMF and tacrolimus led to a complete and sustained remission of symptoms with improvement of the brain stem lesion over a follow-up over 20months. In summary, early detection of PML and consequent treatment may improve neurological outcomes even in brain stem disease with a notorious bad prognosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. [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.

  7. 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.

  8. 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

  9. Early home-based group education to support informed decision-making among patients with end-stage renal disease: a multi-centre randomized controlled trial.

    PubMed

    Massey, Emma K; Gregoor, Peter J H Smak; Nette, Robert W; van den Dorpel, Marinus A; van Kooij, Anthony; Zietse, Robert; Zuidema, Willij C; Timman, Reinier; Busschbach, Jan J; Weimar, Willem

    2016-05-01

    The aim was to test the effectiveness of early home-based group education on knowledge and communication about renal replacement therapy (RRT). We conducted a randomized controlled trial using a cross-over design among 80 end-stage renal disease (ESRD) patients. Between T0 and T1 (weeks 1-4) Group 1 received the intervention and Group 2 received standard care. Between T1 and T2 (weeks 5-8) Group 1 received standard care and Group 2 received the intervention. The intervention was a group education session on RRT options held in the patient's home given by social workers. Patients invited members from their social network to attend. Self-report questionnaires were used at T0, T1 and T2 to measure patients' knowledge and communication, and concepts from the Theory of Planned Behaviour such as attitude. Comparable questionnaires were completed pre-post intervention by 229 attendees. Primary RRT was registered up to 2 years post-intervention. Multilevel linear modelling was used to analyse patient data and paired t-tests for attendee data. Statistically significant increases in the primary targets knowledge and communication were found among patients and attendees after receiving the intervention. The intervention also had a significant effect in increasing positive attitude toward living donation and haemodialysis. Of the 80 participants, 49 underwent RRT during follow-up. Of these, 34 underwent a living donor kidney transplant, of which 22 were pre-emptive. Early home-based group education supports informed decision-making regarding primary RRT for ESRD patients and their social networks and may remove barriers to pre-emptive transplantation. © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

  10. Innate Immune Mechanisms in Transplant Allograft Vasculopathy

    PubMed Central

    Jane-wit, D; Fang, C; Goldstein, DR

    2016-01-01

    Purpose of Review Allograft vasculopathy (AV) is the leading cause of late allograft loss following solid organ transplantation. Ischemia reperfusion injury (IRI) and donor specific antibody (DSA)-induced complement activation confer heightened risk for AV via numerous innate immune mechanisms including MyD88, HMGB1, and complement induced non-canonical NF-kB signaling. Recent Findings The role of MyD88, a signal adaptor downstream of the toll-like receptors (TLR), has been defined in an experimental heart transplant model, which demonstrated that recipient MyD88 enhanced AV. Importantly, triggering receptor on myeloid receptor 1(Trem1), a MyD88 amplifying signal, was present in rejecting human cardiac transplant biopsies and enhanced the development of AV in mice. HMGB1, a nuclear protein that activates TLRs, also enhanced the development of AV. Complement activation elicits assembly of membrane attack complexes (MAC) on endothelial cells which activate non-canonical NF-kB signaling, a novel complement effector pathway that induces pro-inflammatory genes and potentiates endothelial cell mediated alloimmune T cell activation, processes which enhance AV. Summary Innate immune mediators including HMGB1, MyD88, and non-canonical NFκB signaling via complement activation contribute to AV. These pathways represent potential therapeutic targets to reduce AV after solid organ transplantation. PMID:27077602

  11. Association Between Early Helicobacter pylori Eradication and a Lower Risk of Recurrent Complicated Peptic Ulcers in End-Stage Renal Disease Patients

    PubMed Central

    Chang, Shen-Shong; Hu, Hsiao-Yun

    2015-01-01

    Abstract End-stage renal disease (ESRD) patients exhibit an increased incidence of peptic ulcer disease. Helicobacter pylori plays a central role in the development of peptic ulcers. The effect of early H pylori eradication on the recurrence of complicated peptic ulcer disease in ESRD patients remains unclear. The aim of the present study was to explore whether early H pylori eradication therapy in ESRD patients can reduce the risk of recurrent complicated peptic ulcers. We conducted a population-based cohort study and recruited patients with ESRD who had developed peptic ulcers. We categorized patients into early (time lag ≦120 days after peptic ulcer diagnosis) and late H pylori eradication therapy groups. The Cox proportional hazards model was used. The endpoint was based on hospitalization for complicated recurrent peptic ulcers. The early and late H pylori eradication therapy groups consisted of 2406 and 1356 ESRD patients, respectively, in a time lag of 120 days. After adjusting for possible confounders, the early eradication group exhibited a lower rate of complicated recurrent peptic ulcer disease (hazard ratio [HR] = 0.76, 95% confidence interval [CI] = 0.64–0.91, P = 0.003) in a time lag of ≦120 days, but a similar rate of complicated recurrent peptic ulcer disease in time lags of ≦1 year (HR = 0.97, 95% CI 0.79–1.19, P = 0.758) and 2 years (HR = 1.11, 95% CI 0.86–1.44, P = 0.433) compared with the late eradication group. We recommend administering H pylori eradication within 120 days after peptic ulcer diagnosis to H pylori infected ESRD patients who have developed peptic ulcers. PMID:25569660

  12. [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.

  13. 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.

  14. 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.

  15. 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

  16. Renal venogram<