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Analysis of common polymorphisms within NR1I2 and NR1I3 genes and tacrolimus dose-adjusted concentration in stable kidney transplant recipients.

Sat, 08/05/2017 - 12:45
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Analysis of common polymorphisms within NR1I2 and NR1I3 genes and tacrolimus dose-adjusted concentration in stable kidney transplant recipients.

Pharmacogenet Genomics. 2017 Aug 02;:

Authors: Kurzawski M, Malinowski D, Dziewanowski K, Droździk M

Abstract
OBJECTIVES: Several genetic factors were identified to be responsible for interidividual variability in tacrolimus (TAC) pharmacokinetics, with the predominant role of CYP3A5 and CYP3A4 polymorphisms. In this study, genetic variants of NR1I2 and NR1I3 nuclear receptors (responsible for the regulation of drug-metabolizing enzymes and transporters at the transcriptional level) were evaluated for their potential association with altered TAC concentrations.
MATERIALS AND METHODS: Two hundred and forty White kidney transplant patients were genotyped for five single-nucleotide polymorphisms (rs3814055, rs6785049, rs2276707, rs2307424, and rs2307418) in NR1I2 and NR1I3 genes. Genetic data were analyzed in relation to TAC dose-adjusted trough concentration measured 6 months after transplantation (unadjusted and adjusted for patient's CYP3A5 expresser status).
RESULTS: There were significant differences in TAC concentrations between patients with different NR1I2 rs3814055:C>T genotypes (mean values: 121.3 ng/ml mg/kg in major CC homozygotes, 169.6 ng/ml mg/kg in CT heterozygotes, and 186.0 ng/ml mg/kg in patients homozygous for the minor T allele) that remained significant after excluding CYP3A5 expressers from analysis. The TAC dose administered to minor T allele carriers (CT or TT genotype) was significantly lower (~22%) compared with CC homozygotes. For all the other loci analyzed, no significant associations were noted.
CONCLUSION: Our results support the previous data on the functionality of NR1I2 rs3814055 single-nucleotide polymorphism that points to its association with interindividual differences in activity and inducibility of a broad range of drug-metabolizing enzymes and drug transporters.

PMID: 28777242 [PubMed - as supplied by publisher]

ROLE OF DE NOVO DONOR-SPECIFIC ANTI-HLA ANTIBODIES IN KIDNEY GRAFT FAILURE: A CASE-CONTROL STUDY.

Sat, 08/05/2017 - 12:45
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ROLE OF DE NOVO DONOR-SPECIFIC ANTI-HLA ANTIBODIES IN KIDNEY GRAFT FAILURE: A CASE-CONTROL STUDY.

HLA. 2017 Aug 04;:

Authors: Castro A, Malheiro J, Tafulo S, Dias L, Martins S, Fonseca I, Beirão I, Castro-Henriques A, Cabrita A

Abstract
The role of de novo donor-specific anti-HLA antibodies (dnDSA) within the pathways leading to graft failure remains not fully understood. We investigated 56 patients who were transplanted between 2002-2014 with kidney graft failure (cases), for a possible association of development of dnDSA with graft failure. The 56 patients with failed transplants were matched with 56 patients with a functioning graft at present for the variables deceased or living donor, transplant number, transplant year, recipient age and gender, donor age and gender, dialysis vintage time, transplant induction therapy. All patients had at least one serum collected 1 year before failure (in cases) or end of follow-up (in controls). Cases and controls were very well-matched in several baseline characteristics. Post-transplant anti-HLA antibodies were found in 84% of cases and only 36% of controls (P<0.001), with 54% of cases and 16% of controls (P<0.001) having dnDSA at time of detection. Chronic active antibody-mediated rejection was significantly more common (P<0.001) in patients with dnDSA (61% vs. 12%), in 53 (47%) patients that had at least 1 graft biopsy performed during follow-up. dnDSA was a significant risk factor (OR=6.06; P=0.003) for graft failure in a multivariable conditional logistic regression model. dnDSA as a time-dependent variable, was also an independent predictor (HR=2.46; P=0.002) of graft failure in a multivariable Cox regression analysis. In both statistical approaches, only dnDSA-II (OR=11.90; P=0.006) (HR=2.30; P=0.014) was significantly associated with graft failure. Post-transplant dnDSA was clearly associated with graft loss, particularly if against HLA class II antigens. dnDSA detection should be a tool for post-transplant monitoring of kidney graft recipients, allowing for the identification of those with a higher risk of graft failure.

PMID: 28776960 [PubMed - as supplied by publisher]

Sleeve Gastrectomy After Liver Transplantation: Feasibility and Outcomes.

Sat, 08/05/2017 - 12:45
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Sleeve Gastrectomy After Liver Transplantation: Feasibility and Outcomes.

Obes Surg. 2017 Aug 03;:

Authors: Osseis M, Lazzati A, Salloum C, Gavara CG, Compagnon P, Feray C, Lim C, Azoulay D

Abstract
BACKGROUND: Knowledge regarding the feasibility and safety of sleeve gastrectomy (SG) in obese liver transplant recipients is scarce. We report our experience of sleeve gastrectomy following liver transplantation (LT).
METHODS: All patients who had undergone LT and subsequently underwent SG at our institution were retrospectively reviewed. Surgical outcomes, liver and kidney function tests, outcomes of obesity-related comorbidities, and excess weight loss were analyzed.
RESULTS: Between May 2008 and February 2015, six consecutive patients underwent SG after LT. Three procedures (50%) were performed totally by laparoscopy, and three by upfront laparotomy for concomitant incisional hernia complex repair. Within the first 30 days, one complication occurred: early gastric fistula that required multiple endoscopic procedures and re-intervention, followed by death 19 months after SG due to multi-organ failure. Another patient had one late complication: chronic infection on a parietal mesh successfully controlled by mesh removal. Excess weight loss averaged 76% at 2 years with a median BMI of 28 (21-39) kg/m(2). Median follow-up was 37.2 months (range 13-101 months). Median length of stay was 9 days (range: 6-81 days).
CONCLUSIONS: SG is technically feasible after LT and resulted in weight loss without adversely affecting graft function and immunosuppression. However, morbidity and mortality are high.

PMID: 28776154 [PubMed - as supplied by publisher]

Clinical Outcome of Rituximab and Intravenous Immunoglobulin Combination Therapy in Kidney Transplant Recipients with Chronic Active Antibody-Mediated Rejection.

Sat, 08/05/2017 - 12:45
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Clinical Outcome of Rituximab and Intravenous Immunoglobulin Combination Therapy in Kidney Transplant Recipients with Chronic Active Antibody-Mediated Rejection.

Ann Transplant. 2017 Aug 04;22:468-474

Authors: Ban TH, Yu JH, Chung BH, Choi BS, Park CW, Kim YS, Yang CW

Abstract
BACKGROUND We previously reported that rituximab (RIT) and intravenous immunoglobulin (IVIg) combination therapy is effective in deterring the progression of chronic active antibody-mediated rejection (CAMR), but that report was based on the assessment of a small number of cases for a short period. MATERIAL AND METHODS Forty-three patients with CAMR were recruited during the study period after 2010. The patients were divided into high (n=17, 39.5%) and low proteinuria groups (n=26, 60.5%) based on spot urine protein-to-creatinine ratio of > or <3.5 g/g. We compared clinical outcomes between the two groups in terms of allograft survival rate, decrease in estimated glomerular filtration rate (ΔeGFR), change in proteinuria level, and infectious complications. We also evaluated the risk factors of allograft failure. RESULTS The 3-year allograft survival rate after combination treatment was 60.5% overall, but was higher in the low proteinuria group than in the high proteinuria group (69.2% versus 47.1%; log rank p<0.05). The combination treatment reduced the eGFR slope in both groups, and this effect was more definite in the low proteinuria group. No significant differences in the amount of proteinuria and infectious complication rate were found between the two groups. Proteinuria and eGFR at treatment were independent predictive factors of allograft failure (p<0.01 and p<0.001, respectively). CONCLUSIONS RIT and IVIg combination therapy was effective in reducing the progression of CAMR, and this effect was more definite in the patients with low proteinuria.

PMID: 28775248 [PubMed - in process]

Disseminated cryptococcal infection in a patient who had kidney transplant: discrepancy between clinical symptoms and microbiological findings.

Sat, 08/05/2017 - 12:45
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Disseminated cryptococcal infection in a patient who had kidney transplant: discrepancy between clinical symptoms and microbiological findings.

BMJ Case Rep. 2017 Aug 03;2017:

Authors: Dahdal S, Kalicki R, Von Steiger N, Sendi P

Abstract
A 29-year-old man complained of a 2-day history of frontal headache and new-onset fever but no other symptoms. Two months prior to admission, he underwent his third kidney transplantation. Clinical and laboratory examinations were unremarkable. Brain MRI showed a meningeal irritation consistent with viral meningitis. A diagnosis of cryptococcal meningitis and fungaemia was made after detection of a remarkably high and visible load of Cryptococcus neoformans in the cerebrospinal fluid.

PMID: 28775082 [PubMed - in process]

C-Terminal Fibroblast Growth Factor 23, Iron Deficiency, and Mortality in Renal Transplant Recipients.

Sat, 08/05/2017 - 12:45
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C-Terminal Fibroblast Growth Factor 23, Iron Deficiency, and Mortality in Renal Transplant Recipients.

J Am Soc Nephrol. 2017 Aug 03;:

Authors: Eisenga MF, van Londen M, Leaf DE, Nolte IM, Navis G, Bakker SJL, de Borst MH, Gaillard CAJM

Abstract
Iron deficiency (ID) is independently associated with an increased risk of death in renal transplant recipients (RTRs). ID promotes production and cleavage of intact fibroblast growth factor 23 (iFGF23) into C-terminal fibroblast growth factor 23 (cFGF23), elevated levels of which are also prospectively associated with adverse outcomes. We hypothesized that in RTRs, the relationship between ID and mortality is mediated by FGF23. We measured plasma iFGF23 and cFGF23 levels in 700 stable RTRs at a median of 5.4 years after transplant. RTRs with ID had median (interquartile range) cFGF23 concentrations higher than those of RTRs without ID (223 [131-361] versus 124 [88-180] RU/ml; P<0.001), whereas iFGF23 concentrations were similar between groups. In multivariable-adjusted Cox regression analyses, ID associated with increased mortality (81 events; hazard ratio, 1.95; 95% confidence interval, 1.22 to 3.10; P<0.01). However, this association lost significance after additional adjustment for cFGF23 levels (hazard ratio, 1.45; 95% confidence interval, 0.87 to 2.51; P=0.15). In further mediation analysis, cFGF23 explained 46% of the association between ID and mortality, whereas iFGF23 did not mediate this association. In conclusion, we found that cFGF23 levels are increased in iron-deficient RTRs and that the underlying biologic process driving production and cleavage of iFGF23, or alternatively the increased level of cFGF23 fragments, probably is an important mediator of the association between ID and mortality. Our results underline the strong relationship between iron and FGF23 physiology, and provide a potential mechanism explaining the relationship between ID and adverse outcome in RTRs.

PMID: 28774998 [PubMed - as supplied by publisher]

Therapeutic apheresis in kidney AB0 incompatible transplantation.

Sat, 08/05/2017 - 12:45
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Therapeutic apheresis in kidney AB0 incompatible transplantation.

Transfus Apher Sci. 2017 Jul 10;:

Authors: Parolo A, Silvestre C, Neri F, Rigotti P, Furian L

Abstract
Desensitization strategies to safely perform ABO incompatible living donor kidney transplantations are various and still evolving. Given the successful outcome of the majority of the approaches, the current trend is focused on a minimization of treatments. Based on this consideration, the evolution at a single Center of the desensitization protocol is herein described. Starting from 2010, 58 AB0 incompatible living donor kidney transplantations were performed at the University-Hospital of Padua. Over the years, the initial desensitization strategy with rituximab single-dose induction, pre-and post-transplant plasmapheresis and CMV-specific immunoglobulin administration has been shifted to a minimized approach, omitting post-transplant antibody removal in 25 cases. The results of such reduction in post-transplant antibody removal did not affect the outcome of AB0-incompatible kidney transplants, with a reduction in costs and hospitalization.

PMID: 28774827 [PubMed - as supplied by publisher]

[Thrombotic microangiopathy and cancer].

Sat, 08/05/2017 - 12:45
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[Thrombotic microangiopathy and cancer].

Nephrol Ther. 2017 Jul 31;:

Authors: Kheder El-Fekih R, Deltombe C, Izzedine H

Abstract
Thrombotic microangiopathy (TMA) is a group of disorders characterized by mechanical hemolytic anemia with thrombocytopenia and an ischemic organic lesion of variable and potentially fatal importance affecting mostly the kidneys and the brain with histologically a disseminated and occlusive microvasculopathy. The incidence of TMA represents 15% of acute kidney failure in oncological setting, largely due to the introduction of anti-angiogenic agents over the past decade. It may be more rarely related to cancer itself. The iatrogenic TMA can be classified into 2 types: The type I, secondary to chemotherapy (mitomycinC, gemcitabine), exposes to a chronic dose-dependent renal injury as well as an increase in morbidity and mortality; iatrogenic type II, secondary to anti-angiogenic agents', results in a dose-independent renal involvement and renal functional recovery is usual when the drug is discontinued. There is no randomized controlled trial to establish EBM-type management in TMA support. However, complement activation pathways and regulatory factors analyses allowed us to understand the mechanisms of endothelial lesions. As a result, the current trend includes the use of immunosuppressive agents in recurrent or plasmapheresis-refractory MAT.

PMID: 28774729 [PubMed - as supplied by publisher]

A comparative study on the efficacy of a retrograde perfusion technique and an antegrade perfusion technique for donor kidney recovery in transplantation in pigs.

Sat, 08/05/2017 - 12:45
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A comparative study on the efficacy of a retrograde perfusion technique and an antegrade perfusion technique for donor kidney recovery in transplantation in pigs.

BMC Surg. 2017 Aug 03;17(1):88

Authors: Han X, Zhu X, Li T, Li Y, Shan H, Zhang P, He B

Abstract
BACKGROUND: Donor organ shortage is a significant problem in kidney transplantation. Improvement of perfusion techniques can increase the number of available organs. The aim of this study is to investigate the efficiency and safety of retrograde perfusion (RP) of kidney grafts during organ recovery after transplantation in pigs.
METHODS: Ten pigs were divided into two groups, six in the study group for the RP technique and four in the control group for standard antegrade perfusion (AP). The left kidney was removed and perfused by the RP or AP method according to the study group. The perfused left kidney was auto-transplanted to the right groin location. The right kidney was removed and perfused in the same manner and then stored at 4 °C for 24 h prior to histopathological analysis. Data in both groups were observed and recorded.
RESULTS: All kidneys perfused by both the RP and AP methods were satisfactory in appearance. All grafts showed diuresis from the first postoperative day onward. On postoperative day 7, the mean serum creatinine (Scr) and blood urea nitrogen (BUN) levels were 174 ± 9.7 ìmol/L and 27.7 ± 2.5 mg/dL in the RP group, and they were 168 ± 13.7 ìmol/L and 26.5 ± 4.3 mg/dL, respectively, in the AP group (p = 0.483 for Scr and p = 0.646 for BUN). The mean peak Scr levels in the RP group (570 ìmol/L) and the AP group (530 ìmol/L) were similar. All pigs survived with adequate renal function throughout the study period. There was minimal interstitial and tubular edema, and there was endothelial cell swelling in some specimens before revascularization in both groups. At postoperative day 7, the auto-transplanted kidneys showed normal glomerular and tubular structure with little interstitial edema and inflammatory cell infiltration in the grafts. No differences were identified between the two groups. Under electron microscopy, the tubular epithelial cells, glomeruli, and glomerular capillary endothelium of the grafts appeared normal in both groups after 24 h in cold storage.
CONCLUSIONS: Kidney grafts in pigs perfused by RP had normal function after transplantation compared with the AP control group. Therefore,retrograde perfusion is potentially an efficient, safe kidney perfusion method for organ recovery.

PMID: 28774335 [PubMed - in process]

Antidepressant medication use before and after kidney transplant: implications for outcomes - A retrospective study.

Sat, 08/05/2017 - 12:45
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Antidepressant medication use before and after kidney transplant: implications for outcomes - A retrospective study.

Transpl Int. 2017 Aug 03;:

Authors: Lentine KL, Naik AS, Ouseph R, Zhang Z, Axelrod DA, Segev DL, Dharnidharka VR, Brennan DC, Randall H, Gadi R, Lam NN, Hess GP, Kasiske BL, Schnitzler MA

Abstract
We examined a novel database wherein national US transplant registry identifiers were linked to records from a large pharmaceutical claims warehouse (2008-2015) to characterize antidepressant use before and after kidney transplantation, and associations [adjusted hazard ratio (aHR) 95% CI] with death and graft failure. Among 72 054 recipients, 12.6% filled antidepressant medications in the year before transplant, and use was more common among women and patients who were white, unemployed, and had limited functional status. Pre-transplant antidepressant use was associated with 39% higher 1-year mortality (aHR 1.39, 95% CI 1.18-1.64) and 15% higher all-cause graft loss risk (aHR 1.15, 95% CI 1.02-1.30). More than 50% of patients who filled antidepressants pre-transplant continued fill post-transplant. Antidepressant use in the first year after transplant was associated with twofold higher risk of death (aHR 1.94, 95% CI 1.60-2.35), 38% higher risk of death-censored graft failure, and 61% higher risk of all-cause graft failure in the subsequent year. Pre-listing antidepressant use was also associated with increased mortality, but transplantation conferred a survival benefit regardless of prelisting antidepressant use status. While associations may in part reflect underlying behaviors or comorbidities, kidney transplant candidates and recipients treated with antidepressant medications should be monitored and supported to reduce the risk of adverse outcomes.

PMID: 28771882 [PubMed - as supplied by publisher]

Laryngeal abscess formation in an immunosuppressed patient: A case report.

Sat, 08/05/2017 - 12:45
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Laryngeal abscess formation in an immunosuppressed patient: A case report.

Laryngoscope. 2017 Aug 03;:

Authors: Vanhille DL, Blumin JH

Abstract
Prior to the onset of the antibiotic era, laryngeal perichondritis and abscess formation were more frequent complications of systemic infections. We report a case of 54-year-old male who was medically immunosuppressed after kidney transplantation and developed multiple pseudomonas abscesses of his larynx. After failing initial treatment and with worsening signs and symptoms, the patient eventually was treated with a prolonged course of intravenous and oral antibiotics, with resolution of his symptoms and clinical findings. Although this pathophysiology remains uncommon, laryngeal abscess formation should remain in the differential for persistent symptoms, especially in cases of patients on immunosuppression. Laryngoscope, 2017.

PMID: 28771743 [PubMed - as supplied by publisher]

Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype.

Sat, 08/05/2017 - 12:45
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Quantification of transplant-derived circulating cell-free DNA in absence of a donor genotype.

PLoS Comput Biol. 2017 Aug;13(8):e1005629

Authors: Sharon E, Shi H, Kharbanda S, Koh W, Martin LR, Khush KK, Valantine H, Pritchard JK, De Vlaminck I

Abstract
Quantification of cell-free DNA (cfDNA) in circulating blood derived from a transplanted organ is a powerful approach to monitoring post-transplant injury. Genome transplant dynamics (GTD) quantifies donor-derived cfDNA (dd-cfDNA) by taking advantage of single-nucleotide polymorphisms (SNPs) distributed across the genome to discriminate donor and recipient DNA molecules. In its current implementation, GTD requires genotyping of both the transplant recipient and donor. However, in practice, donor genotype information is often unavailable. Here, we address this issue by developing an algorithm that estimates dd-cfDNA levels in the absence of a donor genotype. Our algorithm predicts heart and lung allograft rejection with an accuracy that is similar to conventional GTD. We furthermore refined the algorithm to handle closely related recipients and donors, a scenario that is common in bone marrow and kidney transplantation. We show that it is possible to estimate dd-cfDNA in bone marrow transplant patients that are unrelated or that are siblings of the donors, using a hidden Markov model (HMM) of identity-by-descent (IBD) states along the genome. Last, we demonstrate that comparing dd-cfDNA to the proportion of donor DNA in white blood cells can differentiate between relapse and the onset of graft-versus-host disease (GVHD). These methods alleviate some of the barriers to the implementation of GTD, which will further widen its clinical application.

PMID: 28771616 [PubMed - in process]

Confirmed Transmission of Bacterial or Fungal Infection to Kidney Transplant Recipients from Donated After Cardiac Death (DCD) Donors in China: A Single-Center Analysis.

Sat, 08/05/2017 - 12:45
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Confirmed Transmission of Bacterial or Fungal Infection to Kidney Transplant Recipients from Donated After Cardiac Death (DCD) Donors in China: A Single-Center Analysis.

Med Sci Monit. 2017 Aug 03;23:3770-3779

Authors: Wan Q, Liu H, Ye S, Ye Q

Abstract
BACKGROUND We aimed to investigate blood and urine cultures of donated after cardiac death (DCD) donors and report the cases of confirmed (proven/probable) transmission of bacterial or fungal infection from donors to kidney recipients. MATERIAL AND METHODS Seventy-eight DCD donors between 2010 and 2016 were included. Sixty-one DCD donors underwent blood cultures and 22 episodes of bacteremias developed in 18 donors. Forty-three donors underwent urine cultures and 14 donors experienced 17 episodes of urinary infections. RESULTS Seven of 154 (4.5%) kidney recipients developed confirmed donor-derived bacterial or fungal infections. Inappropriate use of antibiotics in donor was a risk factor for donor-derived infection (p=0.048). The use of FK506 was more frequent in recipients without donor-derived infection than those with donor-derived infection (p=0.033). Recipients with donor-derived infection were associated with higher mortality and graft loss (42.9% and 28.6%, respectively), when compared with those without donor-derived infection (4.8% each). Three kidney recipients with donor-derived infection died; one death was due to multi-organ failure caused by Candida albicans, and two were related to rupture of the renal artery; two of them did not receive appropriate antimicrobial therapy after infection. CONCLUSIONS Our kidney recipients showed high occurrence rates of donor-derived infection. Recipients with donor-derived infection were associated with higher mortality and graft loss than those without donor-derived infection. The majority of recipients with donor-derived infection who died did not receive appropriate antimicrobial therapy after infection.

PMID: 28771455 [PubMed - in process]

Trends in Deceased Donor Kidney Availability and Utilization in the Kingdom of Saudi Arabia.

Sat, 08/05/2017 - 12:45
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Trends in Deceased Donor Kidney Availability and Utilization in the Kingdom of Saudi Arabia.

Exp Clin Transplant. 2017 Aug;15(4):381-386

Authors: Hejaili F, Attar B, Shaheen FAM

Abstract
OBJECTIVES: We investigated trends in deceased donor kidney availability and utilization in Saudi Arabia, wait list changes, and recipient characteristics.
MATERIALS AND METHODS: Ten-year registry data from the Saudi Center for Organ Transplantation were analyzed, including consent/discard rates, numbers of kidneys from deceased donors versus expanded criteria and standard criteria donors, wait list characteristics, dialysis characteristics, and causes of chronic kidney disease.
RESULTS: Annual mean number of deceased donor transplants remained almost constant over the 10-year period (mean of 129). Use of kidneys from expanded criteria donors increased (from 16%-28%), which was associated with higher frequency of delayed graft function (36.2% vs 16%; P = .002) and acute rejection (5.4% vs 19.6%; P = .001) versus kidneys from standard criteria donors. Donor consent rate (34%) and cold ischemic time (12.3 hours) remained constant. Numbers of patients on wait lists remained fairly constant (mean of 2825), although those on dialysis on wait lists decreased from 24% to 17% (P < .0001). Overall wait list numbers remained level or even dropped despite increased patients on dialysis (from 7%-10% annually). Between 2008 and 2016, prevalence of patients > 65 and > 75 years rose by 4.2% and 2.4% and prevalence of diabetes mellitus in patients on dialysis increased by 59.2%. Of kidneys consented in 2016, 14.7% were not recovered, mainly because of sudden cardiac arrest (60%). Of total transplanted kidneys, proportion from deceased donors decreased from 51% (2008-2010) to 22.1% (2014-2016). Only 13% of recipients were older than 55 years, although they comprised 25% of the dialysis population, with patients < 18 years (comprising 2.2% of the dialysis population) receiving 15% of kidneys.
CONCLUSIONS: Deceased donor transplants remained almost constant; however, their proportion of total transplanted kidneys decreased, while transplants with extended criteria kidneys increased. Wait list totals decreased, with relatively less elderly patients and more children being transplanted.

PMID: 28771117 [PubMed - in process]

Osteopontin at the Crossroads of Inflammation and Tumor Progression.

Sat, 08/05/2017 - 12:45
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Osteopontin at the Crossroads of Inflammation and Tumor Progression.

Mediators Inflamm. 2017;2017:4049098

Authors: Castello LM, Raineri D, Salmi L, Clemente N, Vaschetto R, Quaglia M, Garzaro M, Gentilli S, Navalesi P, Cantaluppi V, Dianzani U, Aspesi A, Chiocchetti A

Abstract
Complex interactions between tumor and host cells regulate systemic tumor dissemination, a process that begins early at the primary tumor site and goes on until tumor cells detach themselves from the tumor mass and start migrating into the blood or lymphatic vessels. Metastatic cells colonize the target organs and are capable of surviving and growing at distant sites. In this context, osteopontin (OPN) appears to be a key determinant of the crosstalk between cancer cells and the host microenvironment, which in turn modulates immune evasion. OPN is overexpressed in several human carcinomas and has been implicated in inflammation, tumor progression, and metastasis. Thus, it represents one of the most attracting targets for cancer therapy. Within the tumor mass, OPN is secreted in various forms either by the tumor itself or by stroma cells, and it can exert either pro- or antitumorigenic effects according to the cell type and tumor microenvironment. Thus, targeting OPN for therapeutic purposes needs to take into account the heterogeneous functions of the multiple OPN forms with regard to cancer formation and progression. In this review, we will describe the role of systemic, tumor-derived, and stroma-derived OPN, highlighting its pivotal role at the crossroads of inflammation and tumor progression.

PMID: 28769537 [PubMed - in process]

Internet and social network users' profiles in Renal Transplant Recipients in France.

Sat, 08/05/2017 - 12:45
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Internet and social network users' profiles in Renal Transplant Recipients in France.

BMC Nephrol. 2017 Aug 03;18(1):259

Authors: Mouelhi Y, Alessandrini M, Pauly V, Dussol B, Gentile S

Abstract
BACKGROUND: The use of the Internet for searching and sharing health information and for health care interactions may have a great potential for Renal Transplant Recipients (RTR). This study aims to determine the characteristics associated with Internet and social network use in a representative sample of RTR at the time of their inclusion in the study.
METHODS: Data of this cross-sectional design is retrieved from a longitudinal study conducted in five French kidney transplant centers in 2011, and included Renal Transplant Recipients aged 18 years with a functioning graft for at least 1 year. Measures include demographic characteristics (age, gender, level of education, employment status, living arrangement, having children, invalidity and monthly incomes in the household), psycho-social characteristics measured by the perceived social support questionnaire, and medical characteristics (previous dialysis treatment, duration since transplantation, graft rejection episodes, chronic graft dysfunction, health status and comorbidities: neoplasia for the current transplant, hypertension, diabetes mellitus, smoking status, BMI > 30 kg/m(2) and Charlson Comorbidity Index (CCI)). Polytomous linear regression analysis was performed to describe the Internet and social network users' profiles, using lack of Internet access as the comparison category.
RESULTS: Among the 1416 RTR participating in the study, 20.1% had no Internet access in the household, 29.4% connected to social networks and 50.5% were not connected to social networks. Patients who connected the most to the Internet and social networks were younger, male, without children, employed, with high monthly incomes in the household, without hypertension and having felt a need for an informative or an esteem support.
CONCLUSION: In our study, the majority of RTR were actively using Internet and social networks. Renal transplant units should develop flexible and Web-based sources related to transplant information, which will allow a rapid adaptation to changes in prevalent practice, improve the health of the patients and reflect their preferences.

PMID: 28768480 [PubMed - in process]

[Laparoscopic ureteral reimplantation in the treatment of urinary tract complications after renal transplantation.]

Sat, 08/05/2017 - 12:45
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[Laparoscopic ureteral reimplantation in the treatment of urinary tract complications after renal transplantation.]

Arch Esp Urol. 2017 May;70(4):422-428

Authors: Soto Villalba J, Rosety Rodríguez J, León Delgado C, Ledo Cepero MJ, Parra Serván P, Álvarez-Ossorio Fernández JL

Abstract
OBJECTIVES: Laparoscopic ureteral reconstructive surgery is routinely performed , because it demonstrated efficacy and safety profiles similar to open surgery in expert hands. The most frequent surgical complications after transplant are urological, appearing in up to 12,5% of the cases; they can compromise graft function and mortality. The most frequent ones include ureterovesical anastomosis stenosis (2,5-7,5%) and vesicoureteral reflux (0,4-2,2), which present in up to 80% of the cases.
METHODS: Technical description of the Lich-Gregoire ureteral reimplantation technique in renal transplant patients.
RESULTS: From October 2012 we performed 14 Lich-Gregoire laparoscopic ureteral reimplantations in transplant patients, 9 due to distal ureteral stenosis and 5 for vesicoureteral reflux. There were not open conversions.
CONCLUSIONS: Laparoscopic surgery has evolved much allowing the performance on techniques that we could not think of years ago. Renal transplant patients present frequent postoperative complications, so they benefit of minimally invasive surgery such as endoscopy or laparoscopy. The Lich-Gregoire laparoscopic reimplantation in transplant patients is reproducible in Centers with experience both in laparoscopic surgery and transplantation.

PMID: 28530621 [PubMed - indexed for MEDLINE]

NFATC1 genotypes affect acute rejection and long-term graft function in cyclosporine-treated renal transplant recipients.

Sat, 08/05/2017 - 12:45
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NFATC1 genotypes affect acute rejection and long-term graft function in cyclosporine-treated renal transplant recipients.

Pharmacogenomics. 2017 Mar;18(4):381-392

Authors: Xu Q, Qiu X, Jiao Z, Zhang M, Chen J, Zhong M

Abstract
AIM: To investigate the effects of SNPs in the cyclophilin A/calcineurin/nuclear factor of activated T-cells (NFATs) pathway genes (PPIA, PPP3CB, PPP3R1, NFATC1 and NFATC2) on cyclosporine (CsA) efficacy in renal transplant recipients.
MATERIALS & METHODS: Seventy-six tag SNPs were detected in 155 CsA-treated renal recipients with at least a 5-year follow-up. The associations of SNPs with acute rejection, nephrotoxicity, pneumonia and estimated glomerular filtration rate post transplant were explored.
RESULTS: NFATC1 rs3894049 GC was a risk factor for acute rejection compared with CC carriers (p = 0.0005). NFATC1 rs2280055 TT carriers had a more stable estimated glomerular filtration rate level than CC (p = 0.0004).
CONCLUSION: Detecting NFATC1 polymorphisms could help predict CsA efficacy in renal transplant patients.

PMID: 28244807 [PubMed - indexed for MEDLINE]

Risk factors for nonmelanoma skin cancer in renal transplant recipients: a case-control study from a reference outpatient clinic in Southeast Brazil.

Sat, 08/05/2017 - 12:45
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Risk factors for nonmelanoma skin cancer in renal transplant recipients: a case-control study from a reference outpatient clinic in Southeast Brazil.

Int J Dermatol. 2017 Feb;56(2):154-160

Authors: Ferreira FR, Ogawa MM, Nascimento LF, Tomimori J

Abstract
BACKGROUND: Nonmelanoma skin cancer (NMSC) is the most common tumor in humans, and its incidence increases among renal transplant recipients (RTRs). The aims of this study were to characterize the RTRs with NMSC, to identify risk factors, and to calculate the probability of this tumor in this population.
METHODS: This was a hospital-based case-control study. Epidemiological and clinical variables were evaluated. Hierarchical logistic regression was used, and a mathematical model was built.
RESULTS: In total, 245 subjects were included. Possible associations were identified using a univariate analysis. Multivariate analysis identified risk factors with respective odds ratios and confidence intervals (95% CI): males 2.5 (1.3-4.7), age over 50 years 5.4 (2.3-12.9), Fitzpatrick's skin phototypes I-III 3.7 (1.6-8.7), occupational sun exposure 4.1 (2.1-8.1), timetable of recreational sun exposure all day 3.0 (1.4-6.1), and duration of transplantation (80 months or more) 3.3 (1.6-6.5). The Hosmer-Lemeshow test and the receiver operating characteristics curve showed a strong fit and accuracy, respectively. The probability of an NMSC ranged from less than 1 to 92.5%.
CONCLUSIONS: This study characterized the RTRs with NMSC and identified risk factors. The multivariate analysis by hierarchical logistic regression proved to be a useful tool and allowed for the determination of the probability of NMSC in this population.

PMID: 28074526 [PubMed - indexed for MEDLINE]

Multicenter evaluation of efficacy and safety of low-dose versus high-dose valganciclovir for prevention of cytomegalovirus disease in donor and recipient positive (D+/R+) renal transplant recipients.

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Multicenter evaluation of efficacy and safety of low-dose versus high-dose valganciclovir for prevention of cytomegalovirus disease in donor and recipient positive (D+/R+) renal transplant recipients.

Transpl Infect Dis. 2016 Dec;18(6):904-912

Authors: Heldenbrand S, Li C, Cross RP, DePiero KA, Dick TB, Ferguson K, Kim M, Newkirk E, Park JM, Sudaria-Kerr J, Tichy EM, Ueda KR, Weng R, Wisniewski J, Gabardi S

Abstract
BACKGROUND: The cytomegalovirus (CMV) donor-positive/recipient-positive (D+/R+) population is the largest proportion of renal transplant recipients (RTR). Guidelines for prevention of CMV in the intermediate-risk D+/R+ population include prophylaxis with valganciclovir (VGCV) 900 mg/day for 3 months. This study is the first head-to-head analysis, to our knowledge, comparing the efficacy and safety CMV prophylaxis of VGCV 450 vs 900 mg/day for 3 months in D+/R+ RTR.
METHODS: A multicenter, retrospective analysis evaluated 478 adult RTR between January 2008 and October 2011. Study participants received VGCV 450 mg/day (Group 1; n=398) or 900 mg/day (Group 2; n=89)×3 months for CMV prophylaxis. All VGCV was adjusted for renal function. All groups included in this study received study-approved induction and maintenance immunosuppression regimens. The primary endpoint was incidence of CMV disease at 12 months.
RESULTS: The rates of graft loss, patient survival, T-cell and/or antibody-mediated rejection, hematological adverse events, opportunistic infections, and early VGCV discontinuation were evaluated. Patient demographics were comparable, but had significant differences in ethnicity and donor type between the groups.
CONCLUSION: The occurrence of CMV disease at 12 months was similar between the groups (3.5% vs 3.4%; P=1.000). Log-rank test found no statistically significant difference in the time to development of CMV between the 2 groups (P=.939).

PMID: 27639246 [PubMed - indexed for MEDLINE]

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