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Familial Mediterranean Fever Is Associated With Increased Mortality After Kidney Transplantation-A 19 Years' Single Center Experience.

Wed, 09/20/2017 - 12:45
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Familial Mediterranean Fever Is Associated With Increased Mortality After Kidney Transplantation-A 19 Years' Single Center Experience.

Transplantation. 2017 Oct;101(10):2621-2626

Authors: Green H, Lichtenberg S, Rahamimov R, Livneh A, Chagnac A, Mor E, Rozen-Zvi B

Abstract
BACKGROUND: Current data regarding the outcome of kidney transplantation in patients with familial Mediterranean fever (FMF) who reach end-stage renal disease (ESRD) due to reactive amyloidosis A (AA) are scarce and inconclusive.
METHODS: The outcomes of 20 patients with FMF and biopsy-proven AA amyloidosis that were transplanted between 1995 and 2014 were compared with 82 control patients (32 with diabetes mellitus and 50 with nondiabetic kidney disease). Major outcome data included overall patient and graft survivals.
RESULTS: During a mean overall follow-up of 116.6 ± 67.5 months 11 patients (55%) with FMF died versus 26 patients (31%) in the control group. Median time of death for patients with FMF was 61 months (range, 16-81) after transplantation. Estimated 5-year, 10-year, and actuarial 15-year overall patients survival rates were 73%, 45%, and 39%, respectively, for patients with FMF, versus 84%, 68% and 63%, respectively, for the control group (P = 0.028). FMF was associated with more than twofold increased risk for death after transplantation, and with a threefold increased risk for hospitalization because of infections during the first year. Infections and cardiovascular disease were the cause of death in the majority of patients with FMF. Overall graft survival was similar between the groups. Recurrence of AA amyloidosis was diagnosed in 2 patients during the first year after transplantation.
CONCLUSIONS: FMF is associated with increased risk of mortality after kidney transplantation.

PMID: 28926523 [PubMed - in process]

Sequential and urgent coronary artery bypass surgery followed by kidney transplantation in a highly sensitized patient with unstable angina.

Wed, 09/20/2017 - 12:45
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Sequential and urgent coronary artery bypass surgery followed by kidney transplantation in a highly sensitized patient with unstable angina.

Transplantation. 2017 Sep 18;:

Authors: Yao H, Smilovitch M, Cerere R, Sandal S, Paraskevas S, Baran D, Helena Calixto Fernandes M, Loong Saw C, Tchervenkov J, Cantarovich M

PMID: 28926377 [PubMed - as supplied by publisher]

Early effects of renal replacement therapy on cardiovascular comorbidity in children with end-stage kidney disease: findings from the 4C-T Study.

Wed, 09/20/2017 - 12:45
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Early effects of renal replacement therapy on cardiovascular comorbidity in children with end-stage kidney disease: findings from the 4C-T Study.

Transplantation. 2017 Sep 18;:

Authors: Schmidt BMW, Sugianto RI, Thurn D, Azukaitis K, Bayazit AK, Canpolat N, Eroglu AG, Caliskan S, Doyon A, Duzova A, Karagoz T, Anarat A, Deveci M, Mir S, Ranchin B, Shroff R, Baskin E, Litwin M, Özcakar ZB, Büscher R, Soylemezoglu O, Dusek J, Kemper M, Matteucci MC, Habbig S, Laube G, Wühl E, Querfeld U, Sander A, Schaefer F, Melk A, 4C Study Consortium

Abstract
BACKGROUND: The early impact of renal transplantation on subclinical cardiovascular measures in pediatric patients has not been widely investigated. This analysis is performed for pediatric patients participating in the prospective 4C study and focuses on the early effects of RRT modality on cardiovascular comorbidity in patients receiving a preemptive transplant or started on dialysis.
METHODS: We compared measures indicating subclinical cardiovascular organ damage (aortal pulse wave velocity, carotid intima media thickness, left ventricular mass index) and evaluated cardiovascular risk factors in 166 pediatric patients before and 6 to 18 months after start of RRT (n=76 transplantation, n=90 dialysis).
RESULTS: RRT modality had a significant impact on the change in arterial structure and function: compared to dialysis treatment, transplantation was independently associated with decreases in pulse wave velocity (ß=-0.67; p<0.001) and intima media thickness (ß=-0.40; p=0.008). Independent of RRT modality, an increase in pulse wave velocity was associated with an increase in diastolic blood pressure (ß=0.31; p<0.001). Increasing intima media thickness was associated with a larger increase in body mass index (ß=0.26; p=0.003) and the use of antihypertensive agents after RRT (ß=0.41; p=0.007). Changes in left ventricular mass index were associated with changes in systolic blood pressure (ß=1.47; p=0.01).
CONCLUSIONS: In comparison with initiating dialysis, preemptive transplantation prevented further deterioration of the subclinical vascular organ damage early after transplantation. Classical cardiovascular risk factors such as hypertension and obesity are of major importance for the development of cardiovascular organ damage after renal transplantation.

PMID: 28926375 [PubMed - as supplied by publisher]

Excellent outcomes in combined liver-kidney transplantation: Impact of KDPI and delayed kidney transplantation.

Wed, 09/20/2017 - 12:45
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Excellent outcomes in combined liver-kidney transplantation: Impact of KDPI and delayed kidney transplantation.

Liver Transpl. 2017 Sep 19;:

Authors: Ekser B, Mangus RS, Kubal CA, Powelson JA, Fridell JA, Goggins WC

Abstract
The positive impact of delayed kidney transplantation (KT) on patient survival for combined liver-KT (CLKT) has already been demonstrated by our group. The purpose of this study is to identify whether the quality of the kidneys (based on KDPI) or the delayed approach KT contributes to improved patient survival. 130 CLKT were performed between 2002-2015; 69 with simultaneous KT (Group S) and 61 with delayed KT (Group D) (performed as a second operation with a mean cold ischemia time [CIT] of 50±15h). All patients were categorized according to the KDPI score; 1-33%, 34-66%, and 67-99%. Recipient and donor characteristics were comparable within Groups S and D. Transplant outcomes were comparable within Groups S and D, including liver and kidney CIT, warm ischemia time, and delayed graft function. Lower KDPI kidneys (<34%) were associated with increased patient survival in both groups. Combination of delayed KT and KDPI 1-33% resulted in 100% patient survival at 3-years. These results support that delayed KT in CLKT improves patient survival. The combination of delayed KT and low KDPI offers excellent patient survival up to 3-years. Improved outcomes in the delayed KT group including high KDPI kidneys supports expansion of the donor pool with the use of more ECD and DCD kidneys. This article is protected by copyright. All rights reserved.

PMID: 28926173 [PubMed - as supplied by publisher]

Recurrence of IgA nephropathy after kidney transplantation in steroid continuation versus early steroid-withdrawal regimens: a retrospective analysis of the UNOS/OPTN database.

Wed, 09/20/2017 - 12:45
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Recurrence of IgA nephropathy after kidney transplantation in steroid continuation versus early steroid-withdrawal regimens: a retrospective analysis of the UNOS/OPTN database.

Transpl Int. 2017 Sep 19;:

Authors: Leeaphorn N, Garg N, Khankin EV, Cardarelli F, Pavlakis M

Abstract
In the past 20 years, there has been an increase in use of steroid-withdrawal regimens in kidney transplantation. However, steroid withdrawal may be associated with an increased risk of recurrent IgA nephropathy (IgAN). Using UNOS/OPTN data, we analyzed adult patients with ESRD due to IgAN who received their first kidney transplant between 2000 and 2014. For the primary outcome, we used a competing risk analysis to compare the cumulative incidence of graft loss due to IgAN recurrence between early steroid-withdrawal (ESW) and steroid continuation groups. The secondary outcomes were patient survival and death-censored graft survival (DCGS). A total of 9690 recipients were included (2831 in ESW group and 6859 in steroid continuation group). 1238 recipients experienced graft loss, of which 191 (15.43%) were due to IgAN recurrence. In multivariable analysis, steroid use was associated with a decreased risk of recurrence (subdistribution hazard ratio 0.666, 95% CI 0.482-0.921; p=0.014). Patient survival and DCGS were not different between the two groups. In the U.S., ESW in transplant for ESRD due to IgAN is associated with a higher risk of graft loss due to disease recurrence. Future prospective studies are warranted to further address which patients with IgAN would benefit from steroid continuation. This article is protected by copyright. All rights reserved.

PMID: 28926143 [PubMed - as supplied by publisher]

Clostridium difficile Infection in Intestinal Transplant Recipients.

Wed, 09/20/2017 - 12:45
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Clostridium difficile Infection in Intestinal Transplant Recipients.

Transpl Int. 2017 Sep 19;:

Authors: Goldenberg V, Berbel A, Camargo JF, Simkins J

Abstract
Clostridium difficile infection (CDI) is a common complication among solid organ transplant (SOT) recipients with an estimated incidence of 7-31% for lung recipients, 8-15% for heart, 3-19% for liver, 9% for intestinal, 4-16% for kidney and 2-8% for pancreas-kidney recipients (1) and it is associated with increased mortality (2). There is limited data on CDI in intestinal transplant (ITx) recipients. This is a retrospective study that was conducted at Jackson Memorial Hospital, a 1558-licensed bed tertiary care teaching hospital. Our study was approved by the Institutional Review Board of University of Miami. This article is protected by copyright. All rights reserved.

PMID: 28926130 [PubMed - as supplied by publisher]

Laparoscopic-Assisted Resection for Advanced Colorectal Cancer in Solid Organ Transplant Recipients.

Wed, 09/20/2017 - 12:45
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Laparoscopic-Assisted Resection for Advanced Colorectal Cancer in Solid Organ Transplant Recipients.

J Invest Surg. 2017 Sep 19;:1-8

Authors: Xia ZN, Hou R, Zhu W, Yao R, Lu Z, Qiu HZ, Lin GL

Abstract
AIM: To evaluate the feasibility, short- and long-term outcomes, and safety of laparoscopic resection for advanced colorectal cancer (CRC) in solid organ transplant recipients.
METHODS: Between September 2001 and April 2016, five patients who underwent laparoscopic-assisted resection for CRC after solid organ transplantation were included in this study. Their clinical data were retrospectively analyzed with regard to patient demographics, immunosuppressive therapy, tumor characteristics, surgical outcomes, and follow-up data.
RESULTS: Four kidney and one heart transplant recipients were included. Laparoscopic-assisted low anterior resection was performed in four patients with rectal or rectosigmoid junction cancer, and sigmoidectomy was done in one with sigmoid colon cancer. One kidney transplant patient received a protective loop transverse colostomy. All resections achieved complete tumor removal with tumor-free margins and total mesorectal excision, with an average number of 14 lymph nodes harvested. Most tumors were in stage III (n = 3), one was in stage II, and one in stage IV. The mean duration of surgery, intraoperative blood loss, and postoperative hospital stay were 144 min, 105 mL, and 8.8 days, respectively. No major complications occurred and graft function stayed well. During a mean follow-up period of 62 months, two patients developed metastasis and died eventually.
CONCLUSION: Laparoscopic resection for advanced CRC in organ transplant recipients is technically feasible and therapeutically safe, and seems to have the advantages of few postoperative complications, short recovery time, and acceptable oncological outcomes.

PMID: 28925783 [PubMed - as supplied by publisher]

Lower Tacrolimus Exposure and Time in Therapeutic Range Increase the Risk of De Novo Donor-Specific Antibodies in the First Year of Kidney Transplantation.

Wed, 09/20/2017 - 12:45
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Lower Tacrolimus Exposure and Time in Therapeutic Range Increase the Risk of De Novo Donor-Specific Antibodies in the First Year of Kidney Transplantation.

Am J Transplant. 2017 Sep 19;:

Authors: Davis S, Gralla J, Klem P, Tong S, Wedermyer G, Freed B, Wiseman A, Cooper JE

Abstract
De novo donor-specific antibodies (dnDSA) have been associated with reduced graft survival. Tacrolimus (TAC)-based regimens are the most common immunosuppression used in in clinical practice today, yet an optimal therapeutic dose to prevent dnDSA has not been established. We evaluated mean TAC C0 and TAC time in therapeutic range for the risk of dnDSA in a cohort of 538 patients in the first year of kidney transplant. A mean TAC C0 < 8 ng/ml was associated with dnDSA by 6 months (OR 2.51, 95% CI 1.32-4.79, p=0.005) and by 12 months (OR 2.32, 95% CI 1.30-4.15, p=0.004) and there was a graded increase in risk with lower mean TAC C0 . TAC time in therapeutic range of < 60% was associated with dnDSA (OR 2.05, 95% CI 1.28-3.30, p=0.003) and acute rejection (HR 4.18, 95% CI 2.31-7.58, p<0.001) by 12 months and death-censored graft loss by 5 years (HR 3.12, 95% CI 1.53-6.37, p=0.002). TAC minimization may come at a cost of higher rates of dnDSA and TAC time in therapeutic range may be a valuable strategy to stratify patients at increased risk of adverse outcomes. This article is protected by copyright. All rights reserved.

PMID: 28925597 [PubMed - as supplied by publisher]

A kidney offer acceptance decision tool to inform the decision to accept an offer or wait for a better kidney.

Wed, 09/20/2017 - 12:45
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A kidney offer acceptance decision tool to inform the decision to accept an offer or wait for a better kidney.

Am J Transplant. 2017 Sep 19;:

Authors: Wey A, Salkowski N, Kremers WK, Schaffhausen CR, Kasiske BL, Israni AK, Snyder JJ

Abstract
We developed a kidney offer acceptance decision tool to predict the probability of graft survival and patient survival for first-time kidney-alone candidates after an offer is accepted or declined, and we characterized the effect of restricting the donor pool with a maximum acceptable kidney donor profile index (KDPI). For accepted offers, Cox proportional hazards models estimated these probabilities using transplanted kidneys. For declined offers, these probabilities were estimated by considering the experience of similar candidates who declined offers and the probability that declining would lead to these outcomes. We randomly selected 5000 declined offers and estimated these probabilities 3 years post-offer had the offers been accepted or declined. Predicted outcomes for declined offers were well calibrated (< 3% error) with good predictive accuracy (AUC: graft survival, 0.69; patient survival, 0.69). Had the offers been accepted, the probabilities of graft survival and patient survival were typically higher. However, these advantages attenuated or disappeared with higher KDPI, candidate priority, and local donor supply. Donor pool restrictions were associated with worse 3-year outcomes, especially for candidates with high allocation priority. The kidney offer acceptance decision tool could inform offer acceptance by characterizing the potential risk-benefit tradeoff associated with accepting or declining an offer. This article is protected by copyright. All rights reserved.

PMID: 28925596 [PubMed - as supplied by publisher]

Endothelial precursor cell crossmatch using Tie-2-enriched spleen cells.

Wed, 09/20/2017 - 12:45
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Endothelial precursor cell crossmatch using Tie-2-enriched spleen cells.

Clin Transplant. 2017 Sep 19;:

Authors: Daniel V, Süsal C, Scherer S, Tran H, Gombos P, Trojan K, Sadeghi M, Morath C, Opelz G

Abstract
BACKGROUND: Non-HLA-antibodies against human endothelial progenitor cells (EPC) in pre-transplant recipient serum can have a deleterious influence on the graft. EPC enriched from peripheral blood have been commonly used for EPC crossmatching. In the present study, we describe crossmatches using EPC enriched from fresh or frozen-thawed spleen cell preparations, thereby widening the sample source for deceased-donor crossmatching and retrospective studies.
METHODS: EPC crossmatches were performed retrospectively using spleen cells and the flow cytometric XM-ONE crossmatch test kit.
RESULTS: Healthy controls (n=28) showed no IgG antibodies against EPC. When sera of 11 random dialysis patients were studied, 2 patients (18%) exhibited IgG EPC antibodies. When pre-transplant sera of 20 kidney graft recipients with good long-term graft outcome (serum creatinine 1.0±0.2 mg/dl measured 2463±324 days post-transplant) were investigated using frozen-thawed and then separated Tie-2-enriched spleen cells of the original transplant donor, 3 patients (15%) had pre-transplant IgG EPC antibodies. When pre-transplant sera of 5 patients with intra-operative graft loss were studied employing the original donor spleen cells, 4 (80%) patients showed IgG EPC antibodies.
CONCLUSIONS: Crossmatches with spleen cell-derived EPC using the XM-ONE assay are technically possible. Our very preliminary experience suggests clinical relevance. This article is protected by copyright. All rights reserved.

PMID: 28925558 [PubMed - as supplied by publisher]

When and how can nephrologists treat hepatitis C virus infection in dialysis patients?

Wed, 09/20/2017 - 12:45
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When and how can nephrologists treat hepatitis C virus infection in dialysis patients?

Semin Dial. 2017 Sep 18;:

Authors: Davis MI, Chute DF, Chung RT, Sise ME

Abstract
Hepatitis C virus (HCV) infection, a major cause of end-stage liver disease, is a common comorbidity in patients on dialysis and causes increased morbidity and mortality. Historically HCV has been extremely difficult to cure with interferon and ribavirin-based therapies, which are also associated with significant side effects, and few dialysis patients ever received HCV treatment. However, in the last 4 years, interferon-free direct-acting antiviral therapies have been approved, and several combinations have been studied in dialysis patients. A recently approved, pan-genotypic, direct-acting antiviral regimen, glecaprevir and pibrentasvir, may simplify prescribing. The simplicity of these new therapies, with few side effects, makes it possible for nephrologists to treat HCV infection in their patients on dialysis. We review the workflow and motivation behind nephrology-led management of HCV infection. We highlight the importance of identifying which patients need referral to a hepatologist or HCV specialist prior to treatment and which can be managed by their nephrologist. Nephrologist involvement would lead to improved access to treatment and ensure that appropriate patients are referred for HCV treatment. In this paper, we review the background of HCV infection, its effect on dialysis patients, and impact on kidney transplantation. In addition, we outline the therapy options for each genotype of HCV, and we discuss the benefits and barriers to nephrology-led HCV treatment.

PMID: 28925068 [PubMed - as supplied by publisher]

Do the Benefits of Transplant Tourism Amongst Nigerian Patients Outweigh the Risks? A Single-Center Experience.

Wed, 09/20/2017 - 12:45
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Do the Benefits of Transplant Tourism Amongst Nigerian Patients Outweigh the Risks? A Single-Center Experience.

Int J Organ Transplant Med. 2017;8(3):132-139

Authors: Amira CO, Bello BT

Abstract
BACKGROUND: Transplant tourism (TT) is the term used to describe travel outside one's country of abode for the sole purpose of obtaining organ transplantation services.
OBJECTIVE: This study describes the characteristics and outcomes of kidney transplant tourists who were followed up in our institution.
METHODS: A retrospective study was conducted on patients who underwent kidney transplantation outside the country and were followed up in our institution from 2007 to 2015.
RESULTS: 26 patients were followed up; 19 (73%) were males. The mean±SD age of patients was 40.5±10.3 years. The majority (n=20) of the transplantations were carried out in India. Living-unrelated transplants were most common (54%). Complications encountered were infections in 11 (42%) patients, new-onset diabetes after transplantation in 9 (35%), chronic allograft nephropathy in 8 (31%), biopsy-proven acute rejections in 3 (12%), and primary non-function in 2 (8%). 1-year graft survival was 81% and 1-year patient survival was 85%.
CONCLUSION: Kidney transplant tourism is still common among Nigerian patients with end-stage renal disease. Short-term graft and patient survival rates were poorer than values recommended for living kidney transplants. We therefore advise that TT should be discouraged in Nigeria, given the availability of transplantation services in the country, and also in line with international efforts to curb the practice.

PMID: 28924461 [PubMed]

Recent Progress in Cell Therapy in Solid Organ Transplantation.

Wed, 09/20/2017 - 12:45
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Recent Progress in Cell Therapy in Solid Organ Transplantation.

Int J Organ Transplant Med. 2017;8(3):125-131

Authors: Garakani R, Saidi RF

Abstract
There has been ample of preclinical and animal studies showing efficacy and safety of using various cells, such as stem cells or T regulatory cells, after transplantation for tissue repair, immunosuppression or tolerance induction. However, there has been a significant progress recently using cell therapy in solid organ transplantation in small clinical trials. Recent results have been promising and using cell therapy in solid organ transplantation seems feasible and safe. However, there are more hurdles to overcome such as dose and timing of the infusions. Current studies mainly focused on live donor kidney transplantation. Expansion of current regimes to other organs and deceased donor transplantation would be crucial.

PMID: 28924460 [PubMed]

Coloduodenovesical Fistula After Simultaneous Pancreas-Kidney Transplant: Case Report and Review of the Literature.

Wed, 09/20/2017 - 12:45
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Coloduodenovesical Fistula After Simultaneous Pancreas-Kidney Transplant: Case Report and Review of the Literature.

Transplant Proc. 2017 Oct;49(8):1960-1962

Authors: Rahnemai-Azar AA, Penna M, Morrison SD, Rayhill SC, Sibulesky L, Muczynski KA, Bakthavatsalam R

Abstract
BACKGROUND: Complicated diverticulitis after transplantation occurs in as many as 3.5% of cases and carries a 25% mortality rate. Diagnosis of complicated diverticulitis in this population can be challenging because of abnormal presentations caused by immunosuppression. Only 4 cases of fistulization after kidney transplantation are described in the literature; none occurred after simultaneous pancreas-kidney transplant.
METHODS: We present a first case of a coloduodenovesical fistula in a patient 9 years after simultaneous pancreas-kidney transplant. The patient presented with intermittent episodes of elevated creatinine and recurrent urinary tract infection. The presence of fistula was strongly suspected in cystoscopy, but, despite extensive investigation, a fistula tract could not be identified.
RESULTS: The patient ultimately underwent surgical exploration for positive cystoscopy examination, continuation of urinary complaints, and presence of multiple colonic diverticula in computed tomography scan. At surgical exploration, a fistula track was identified between the sigmoid colon and duodenal stump of the pancreas allograft. Subsequently, sigmoidectomy, bladder repair, and enteric conversion of the pancreas transplant were performed.
CONCLUSIONS: Complications of diverticulitis should be considered in organ transplant recipients presenting with recurrent urinary infection and elevated creatinine, and surgical exploration might be indicated even if unable to well-define the fistula tract.

PMID: 28923655 [PubMed - in process]

Orthotopic Kidney Transplantation in the Rat With the Use of a Sleeve Arterial Anastomosis Method and a Modified Stenting Technique for Renal Veins.

Wed, 09/20/2017 - 12:45
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Orthotopic Kidney Transplantation in the Rat With the Use of a Sleeve Arterial Anastomosis Method and a Modified Stenting Technique for Renal Veins.

Transplant Proc. 2017 Oct;49(8):1942-1946

Authors: Jin ZD, Xue LN, Peng LS

Abstract
BACKGROUND: We describe a simple and reliable orthotopic kidney transplantation method in rats with the use of sleeve arterial anastomosis and a modified stenting technique for anastomosis of the renal vein (RV).
METHODS: Male Fischer and Lewis rats were used as kidney donors and recipients, respectively, and their left kidneys were harvested in situ. In the control rats (n = 30), the renal artery (RA) and RV anastomoses were performed end-to-end with interrupted sutures by means of the conventional technique. In the experimental animals (n = 30), revascularization of the RA was fashioned end-in-end with the use of a modified sleeve anastomosis, the RV was anastomosed end-to-end with the use of a modified stenting technique and interrupted sutures, and the ureter was anastomosed with the use of the end-to-end interrupted suture technique.
RESULTS: The arterial anastomosis time in the control group was 8.52 ± 1.1 minutes, and that in the experimental group was 4.7 ± 0.6 minutes (P < .05). The venous anastomosis time in the experimental group was 9.2 ± 1.3 minutes, which also was less than in the control group (11.19 ± 0.78 minutes; P < .05). The warm ischemia time decreased from 26.8 ± 1.3 minutes in the control group to 20.7 ± 0.5 minutes in the experimental group (P < .05). The success rate of 93% at 21 days after grafting was identical in the experimental and control groups.
CONCLUSIONS: We developed a modified model of orthotopic kidney transplantation that can significantly reduce the warm ischemia time.

PMID: 28923652 [PubMed - in process]

Does Renal Tubular Injury-Induced Local Tissue Hypoxia Involve Post-Transplantation Erythrocytosis?

Wed, 09/20/2017 - 12:45
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Does Renal Tubular Injury-Induced Local Tissue Hypoxia Involve Post-Transplantation Erythrocytosis?

Transplant Proc. 2017 Oct;49(8):1930-1934

Authors: Unal A, Ata S, Karakurkcu C, Ciraci MZ, Kocyigit I, Sipahioglu MH, B Tokgoz, Oymak O

Abstract
BACKGROUND: The pathogenesis of post-transplantation erythrocytosis (PTE) is not well understood and appears to be multifactorial. Our hypothesis in this study was that several factors, including toxicity of calcineurin inhibitor, immunologic factors, and chronic allograft nephropathy, can trigger local tissue hypoxia in peritubular interstitium, which is where production of erythropoietin (EPO) takes place. This local interstitial tissue hypoxia can cause an increase in renal EPO production, which induces the development of PTE.
METHODS: This cross-sectional study included 15 renal transplant recipients, in whom polycythemia developed after kidney transplantation, with elevated hematocrit level to >51%. Forty-eight age- and gender-matched renal transplant recipients with normal hematocrit level were included as the renal transplant control group. In addition, 13 age- and gender-matched healthy subjects were also included as the healthy control group. We used urine hypoxia-inducible factor-2 alpha (HIF-2α) levels to evaluate whether there is local tissue hypoxia in renal allograft. HIF-2α levels were measured by double antibody sandwich enzyme-linked immunosorbent assay (ELISA). Serum EPO and insulin-like growth factor-1 (IGF-1) levels were also measured.
RESULTS: HIF-2α levels were significantly lower in the polycythemia group than the other two groups, but there was no significant difference between the healthy control group and the renal transplant control group with regard to HIF-2α levels. There was no significant difference among the 3 study groups in terms of levels of serum EPO and IGF-1.
CONCLUSION: Local tissue hypoxia in renal allograft does not seem to play an important role in the development of PTE.

PMID: 28923650 [PubMed - in process]

Hypothermic Machine Perfusion's Protection on Porcine Kidney Graft Uncovers Greater Akt-Erk Phosphorylation.

Wed, 09/20/2017 - 12:45
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Hypothermic Machine Perfusion's Protection on Porcine Kidney Graft Uncovers Greater Akt-Erk Phosphorylation.

Transplant Proc. 2017 Oct;49(8):1923-1929

Authors: He N, Li JH, Jia JJ, Xu KD, Zhou YF, Jiang L, Lu HH, Yin SY, Xie HY, Zhou L, Zheng SS

Abstract
BACKGROUND: To investigate the potential mechanisms of hypothermic machine perfusion (HMP)'s beneficial effects on kidney graft over static cold storage (SCS) in vitro.
METHODS: Ten kidneys of 5 Bama miniature male pigs were paired into 2 groups: SCS group and HMP group. Preservation solutions were taken at 0, 1, 3, and 6 hours for the measurement of K(+), Na(+), Cl(-), blood urea nitrogen (BUN), creatinine (Cr), and lactate dehydrogenase (LDH) using the standard laboratory methods. Renal cortex were harvested at 6 hours for the following measurement: lactic acid (LD), adenosine triphosphate (ATP), malondialdehyde (MDA), neutrophil accumulation (MPO), interleukin-10 (IL-10), and transforming growth factor-β (TGF-β). Ischemia-induced apoptosis and the protein expression levels of total Akt, phospho-Akt, total Erk, and phospho-Erk were analyzed by Western blotting.
RESULTS: Almost all of the tested metabolites in preservation solutions were reduced with time in the HMP group. Levels of Na(+), Cl(-), BUN, Cr, K(+), and LDH were lower in the HMP group compared with the SCS group, with differences in the first 4 reaching statistical significance. HMP alleviated ATP degradation and LD accumulation, diminished the MDA (P < .05) and MPO (P = .227) levels, and greatly raised IL-10 and TGF-β (P < .05) expression. A marked decrease of proapoptotic and a large increase of antiapoptotic markers (P < .05) along with greatly raised Akt (P < .05) and Erk (P < .01) phosphorylation was observed in the kidney of the HMP group compared with the SCS group.
CONCLUSION: HMP's kidney graft protection involves inhibition of accumulation of toxic metabolites, oxidative damage, and apoptosis along with upregulation of the Akt and Erk signaling pathway.

PMID: 28923649 [PubMed - in process]

Octreotide Ameliorates Renal Ischemia/Reperfusion Injury via Antioxidation and Anti-inflammation.

Wed, 09/20/2017 - 12:45
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Octreotide Ameliorates Renal Ischemia/Reperfusion Injury via Antioxidation and Anti-inflammation.

Transplant Proc. 2017 Oct;49(8):1916-1922

Authors: Xu Z, Zhao K, Han P, Qi X, Zhang W, Niu T

Abstract
Oxidative stress, calcium overload, inflammation, cellular necrosis, and apoptosis are implicated in renal ischemic/reperfusion injury (RIRI). Because octreotide (OCT) is protective in retinal IRI, the effect of OCT on mouse RIRI and the mechanisms involved were investigated. The RIRI model was induced in male C57BL/6 mice, and the mice were then treated with saline or OCT. Serum and kidneys were subjected to periodic acid-Schiff staining, terminal deoxynucleotidyl transferase dUTP nick end labeling assay, enzyme-linked immunosorbent assay, western blotting, and immunohistochemistry. Treatment with OCT restored the renal functions and histologic changes induced by RIRI. The administration of OCT reduced tumor necrosis factor-α and interleukin-6 levels in kidney tissues, protected the kidney from apoptosis, and significantly downregulated the expression of nuclear factor-κB p65. In addition, OCT treatment upregulated the expression of nuclear factor erythroid 2-related factor 2, heme oxygenase-1, and NAD(P)H quinone oxidoreductase 1 and enhanced the renal antioxidant capacity. These results cumulatively indicate that OCT may protect the kidneys against IRI in a mouse model through the regulation of antioxidation and anti-inflammation.

PMID: 28923648 [PubMed - in process]

Simultaneous Kidney-Pancreas Transplantation With an Original "Transverse Pancreas" Technique: Initial 9 Years' Experience With 56 Cases.

Wed, 09/20/2017 - 12:45
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Simultaneous Kidney-Pancreas Transplantation With an Original "Transverse Pancreas" Technique: Initial 9 Years' Experience With 56 Cases.

Transplant Proc. 2017 Oct;49(8):1879-1882

Authors: Paulino J, Martins A, Vigia E, Marcelino P, Nobre AM, Bicho L, Filipe E, Barroso E

Abstract
An innovative technique for pancreas transplantation is described. The main aspect consists of the horizontal positioning of the pancreas, which allows a better venous outflow, thus preventing thrombosis and graft loss. The program of pancreas transplantation in this national reference center for pancreatic and liver surgery was started in 2007; the initial results were considered poor, resulting in the loss of half of the grafts due to venous thrombosis. After analyzing the possible causes, this technique was proposed and successfully implemented, reducing the postoperative complications, particularly the problem of venous thrombosis. A detailed description of the new surgical technique is provided. The main clinical and demographic characteristics of the 56 patients who underwent the surgery are analyzed. The incidence of venous thrombosis was 5.3% (3 patients) and graft loss was 3.5% (2 patients). Due to the good results, this technique became the standard surgery for transplantation of the pancreas in our center. The technique proved to be safe and successful. Due to the unique pancreas graft implantation, we called it "transverse pancreas surgery."

PMID: 28923641 [PubMed - in process]

Associations Among Cardio-Ankle Vascular Index, Carotid Intima-Media Thickness, and Fibroblast Growth Factor-21 Levels in Kidney Transplant Patients.

Wed, 09/20/2017 - 12:45
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Associations Among Cardio-Ankle Vascular Index, Carotid Intima-Media Thickness, and Fibroblast Growth Factor-21 Levels in Kidney Transplant Patients.

Transplant Proc. 2017 Oct;49(8):1791-1796

Authors: Trakarnvanich T, Prommool S, Kurathong S, Teepprasan T, Wang Y

Abstract
BACKGROUND: Cardiovascular disease is the major cause of death in patients with chronic kidney disease, even after renal transplantation. Cardio-ankle vascular index (CAVI) provides an indicator of arterial stiffness, whereas fibroblast growth factor-21 (FGF-21) levels may provide a biomarker for atherosclerotic disease. We investigated the association between CAVI and FGF-21 and their relationships to carotid intima-media thickness (IMT) and other cardiovascular risk factors.
METHODS: This study included 90 renal transplant patients. Data on CAVI, echocardiograms, homocysteine, high-sensitivity C-reactive protein, carotid IMT, FGF-21, and incidence of cardiovascular disease were collected and correlations were analyzed statistically.
RESULTS: The mean CAVI was 7.51 ± 1.69. CAVI was significantly higher in older patients (mean age, 51.54 ± 9.92 vs 42.92 ± 11.20 years, P < .001) and was positively correlated with carotid IMT (r = 0.214, P = .050) and negatively with hemoglobin (r = -0.219, P = .044). There was no association between CAVI and FGF-21 or other parameters. FGF-21 was positively correlated with high-sensitivity C-reactive protein and negatively with renal function. The mean carotid IMT score was 0.57 ± 0.18. Scores were significantly higher in patients >60 years of age, with low cholesterol and high-density lipoprotein and high body mass index. Higher body mass index (P = .013) and carotid IMT (P < .001) were associated with more frequent cardiovascular events. Mean homocysteine levels remained >15 μmol/L and did not differ in those with or those without cardiac events.
CONCLUSIONS: This study demonstrates that cardiovascular risk factors remain after renal transplantation, despite normal arterial stiffness. Close cardiac monitoring and risk-factor modification are therefore recommended, even after successful renal transplantation.

PMID: 28923627 [PubMed - in process]

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