Skip directly to content

PubMed Kidney Transplant

Subscribe to PubMed Kidney Transplant feed PubMed Kidney Transplant
NCBI: db=pubmed; Term=kidney transplant
Updated: 1 hour 40 min ago

Preeclampsia and Long-term Renal Function in Women Who Underwent Kidney Transplantation.

Fri, 12/08/2017 - 13:45

Preeclampsia and Long-term Renal Function in Women Who Underwent Kidney Transplantation.

Obstet Gynecol. 2017 Dec 04;:

Authors: Vannevel V, Claes K, Baud D, Vial Y, Golshayan D, Yoon EW, Hodges R, Le Nepveu A, Kerr PG, Kennedy C, Higgins M, Resch E, Klaritsch P, Van Mieghem T

Abstract
OBJECTIVE: Preeclampsia often complicates pregnancies after maternal kidney transplantation. We aimed to assess whether preeclampsia is associated with kidney function decline either during the pregnancy or in the long term.
METHODS: We performed an international multicenter retrospective cohort study. Renal function at conception, pregnancy outcomes, and short- and long-term graft outcomes were collected for women who were pregnant after renal transplantation and had transplant and obstetric care at the participating centers. In women who had multiple pregnancies during the study period, only the last pregnancy was included. Univariate and multivariable analyses were performed.
RESULTS: We retrieved pregnancy outcomes and long-term renal outcomes for 52 women. Chronic hypertension was present at baseline in 27%. Mean estimated glomerular filtration rate (GFR) at start of pregnancy was 52.4±17.5 mL/min/1.73 m. Mean estimated GFR at delivery was 47.6±21.6 mL/min/1.73 m, which was significantly lower than at conception (P=.03). Twenty women (38%) developed preeclampsia. In multivariable analysis, women who developed preeclampsia had a 10.7-mL/min/1.73 m higher drop in estimated GFR between conception and delivery than women who did not develop preeclampsia (P=.02). Long-term estimated GFR follow-up was obtained at a median of 5.8 years (range 1.3-27.5 years). Mean estimated GFR at last follow-up was 38±23 mL/kg/1.73 m. Seventeen women (33%) experienced graft loss over the follow-up period. Incidence of graft loss was similar in women with and without preeclampsia in their last pregnancy (30% and 34%, respectively; P=.99). In multivariable analysis, the decrease in estimated GFR between conception and last follow-up was similar in women who experienced preeclampsia during pregnancy and those who did not (difference -2.69 mL/min/1.73 m, P=.65).
CONCLUSION: Preeclampsia commonly complicates pregnancies after renal transplantation but is not associated with long-term renal dysfunction or graft loss.

PMID: 29215520 [PubMed - as supplied by publisher]

Variation in Practice Patterns for Listing Patients for Renal Transplantation in the United Kingdom: a National Survey.

Fri, 12/08/2017 - 13:45

Variation in Practice Patterns for Listing Patients for Renal Transplantation in the United Kingdom: a National Survey.

Transplantation. 2017 Dec 05;:

Authors: Pruthi R, Tonkin-Crine S, Calestani M, Leydon G, Eyles C, Oniscu GC, Tomson C, Bradley A, Forsythe JL, Bradley C, Cairns J, Dudley C, Watson C, Draper H, Johnson R, Metcalfe W, Fogarty D, Ravanan R, Roderick PJ, ATTOM Investigators

Abstract
INTRODUCTION: Despite the availability of guidelines for the evaluation of candidates for renal transplantation, variation in access to transplantation exists. This national survey investigates whether centre variation exists in the assessment of patients for renal transplantation in the UK.
METHODS: An online survey, informed by qualitative interviews, was distributed to all UK renal centres. This survey examined centre approaches to chronic kidney disease service provision, transplant recipient assessment, education provision and wait-listing decision making processes. Centre re-evaluation policies for patients already listed and priorities for future development were also examined.
RESULTS: All 71 renal centres responded. Of these, 83% reviewed predialysis patients in a low clearance clinic. In 26% of centres transplantation was not discussed as a treatment option with all patients. Fourteen centres reported having a dedicated transplant assessment clinic whilst 28% did not have a formal assessment protocol. Age was an exclusion criterion for listing in 3 centers, all of which had a cut off at 75 years. 83% of centres excluded patients with a high BMI. Cardiac investigations were risk-stratified in 90% of centres. Surgical involvement varied with 11% of centres listing patients without formal surgical review. There was no formal protocol in place to re-evaluate listed patients in 62% of centres.
CONCLUSIONS: There is wide variation in UK practice patterns for listing patients for renal transplantation, though its impact on access to transplantation is unclear. The extent to which centre-specific and patient-specific factors affect access to transplantation requires further analysis in a prospective cohort of patients.

PMID: 29215463 [PubMed - as supplied by publisher]

Influence of Blood Pressure and Calcineurin Inhibitors on Kidney Function After Heart or Liver Transplantation.

Fri, 12/08/2017 - 13:45

Influence of Blood Pressure and Calcineurin Inhibitors on Kidney Function After Heart or Liver Transplantation.

Transplantation. 2017 Dec 05;:

Authors: Morath C, Opelz G, Döhler B, Zeier M, Süsal C

Abstract
BACKGROUND: Chronic kidney disease is common after heart or liver transplantation, with calcineurin inhibitors (CNI) considered the key contributor. A possible influence of posttransplant blood pressure has not been extensively examined.
METHODS: Data from adult recipients of a first heart or liver transplant were analyzed regarding the relationship between blood pressure at year 1, renal function at year 5, and CNI therapy.
RESULTS: Whereas we confirmed the well-known detrimental effect of increased 1-year systolic blood pressure on 5-year kidney graft survival, heart or liver graft survival were not affected. However, among 2,534 heart transplant recipients with good renal function at year 1, increasing systolic blood pressure at year 1 was associated with higher rates of poor renal function at year 5 posttransplant. This association was confirmed on multivariate analysis overall (odds ratio [OR] 1.25 per 20 mmHg increment, P<0.001) and within subgroups. Similar results were observed in 1,822 liver transplant recipients (OR 1.35, P<0.001). Neither the type of CNI nor CNI dose or trough level at year 1 showed a significant association with kidney function at year 5.
CONCLUSIONS: One-year blood pressure was identified as the major modifiable risk factor associated with deteriorating kidney function between years 1 to 5 after heart or liver transplantation.

PMID: 29215461 [PubMed - as supplied by publisher]

Complete B Cell Deficiency Reduces Allograft Inflammation and Intragraft Macrophages a Rat Kidney Transplant Model.

Fri, 12/08/2017 - 13:45

Complete B Cell Deficiency Reduces Allograft Inflammation and Intragraft Macrophages a Rat Kidney Transplant Model.

Transplantation. 2017 Dec 05;:

Authors: Panzer SE, Wilson NA, Verhoven BM, Xiang D, Rubinstein CD, Redfield RR, Zhong W, Reese SR

Abstract
BACKGROUND: Increasingly it is being appreciated that B cells have broad roles beyond the humoral response, and are able to contribute to and regulate inflammation. The specific role of B cells in the pathogenesis of early allograft inflammation remains unclear.
METHODS: To address this question, we generated B cell deficient Lewis rats via CRISPR technology. In a full mismatch transplant model, kidneys from Brown Norway donors were transplanted into B cell deficient Lewis recipients (B) or wild type Lewis recipients. T cell mediated rejection was attenuated with cyclosporine.
RESULTS: Renal inflammation was reduced at 1 week after transplant (Banff scores for interstitial inflammation, microvascular inflammation, glomerulitis, and C4d) in allografts from B recipients. The reduction in interstitial inflammation was predominantly due to a decline in graft infiltrating macrophages. Intragraft T cell numbers remained unchanged. In addition, B cell deficiency was associated with increased T regulatory cells and reduced splenic T follicular helper cells at baseline; and significantly increased intragraft and splenic IL-10 mRNA levels after transplant. In vitro, B and wild type splenic T cells produced similar levels of IFN-γ in response to T cell specific activation.
CONCLUSIONS: B cell deficiency in this model produced an anti-inflammatory phenotype with a shift towards regulatory T cell populations, production of anti-inflammatory cytokines (IL-10), and a reduction in allograft inflammation. These findings define a role for B cells to influence the cell populations and mediators involved in the pathogenesis of early allograft inflammation.

PMID: 29215459 [PubMed - as supplied by publisher]

Recurrence of renal cell cancer after renal transplantation in a multicenter French cohort.

Fri, 12/08/2017 - 13:45

Recurrence of renal cell cancer after renal transplantation in a multicenter French cohort.

Transplantation. 2017 Dec 05;:

Authors: Cognard N, Anglicheau D, Gatault P, Girerd S, Essig M, Hurault de Ligny B, Le Meur Y, Le Roy F, Garrouste C, Thierry A, Colosio C, Rivalan J, Sayegh J, Choukroun G, Moulin B, Caillard S

Abstract
BACKGROUND: Renal cancer accounts for 3% of adult malignancies; renal cell carcinoma (RCC) represents 80% of all renal cancers, and is characterized by late recurrences. Recurrences after kidney transplantation are associated with a high mortality rate. We aimed to determine if recurrences are linked to tumor characteristics and to delays between diagnosis and transplantation.
METHODS: We retrospectively analyzed data from French kidney-transplanted patients with medical histories of pre-transplant renal cancer, focusing on the most common histological subtypes: clear cell and papillary cancers. Characteristics of the tumors, patients, and kidney transplantations were documented, and posttransplant patient survival was analyzed.
RESULTS: Of 143 patients, 13 experienced cancer recurrence after kidney transplantation. The mean delay in recurrence was 3±2.3 years posttransplantation, and the cumulative incidences of recurrence were 7.7% at 5 years and 14.9% at 10 years. The risk of recurrence was higher in patients with clear cell RCC (13% vs. 0%, p=0.015). There was no correlation between posttransplant recurrence and the interval before transplantation. Factors associated with a higher risk of cancer recurrence were histological clear cell RCC (p=0.025), tumor stage pT2 (p=0.002) and Fuhrman grade IV (p<0.001). Recurrences were associated with a high mortality rate; 76.9% of patients with recurrences had died by the end of the follow-up period.
CONCLUSIONS: Recurrences of clear cell RCC are not uncommon after kidney transplantation, and are associated with very poor prognoses. These results should be considered before listing patients with a history of renal cancer for transplantation.

PMID: 29215458 [PubMed - as supplied by publisher]

Direct and indirect costs incurred by Australian living kidney donors.

Fri, 12/08/2017 - 13:45

Direct and indirect costs incurred by Australian living kidney donors.

Nephrology (Carlton). 2017 Dec 07;:

Authors: Barnieh L, Kanellis J, McDonald S, Arnold J, Sontrop JM, Cuerden M, Klarenbach S, Garg AX, Boudville N, Donor Nephrectomy Outcomes Research (DONOR) Network

Abstract
AIM: To describe the direct and indirect costs incurred by Australian living kidney donors.
METHODS: We studied 55 living kidney donors from 3 centres in Perth, Australia and 1 centre in Melbourne, Australia (2010-2014); 49 donors provided information on expenses incurred during the donor evaluation period and up to 3 months after donation. We used a micro-costing approach to measure and value the units of resources consumed. Expenses were grouped as direct costs (ground and air travel, accommodation, and prescription medications) and indirect costs (lost wages and lost productivity). We standardized costs to the year 2016 in Australian dollars.
RESULTS: The most common direct costs were for ground travel (100%), parking (76%), and post-donation pain medications or antibiotics (73%). The highest direct costs were for air travel (median $1,986 [3 donors]) and ground travel (median $459 [49 donors]). Donors also reported lost wages (median $9,891 [37 donors]). The inability to perform household activities or care for dependants were reported by 32 (65%) and 23 (47%) donors. Total direct costs averaged $1,682 per donor (median $806 among 49 donors). Total indirect costs averaged $7,249 per donor (median $7,273 among 49 donors). Total direct and indirect costs averaged $8,932 per donor (median $7,963 among 49 donors).
CONCLUSION: Many Australian living kidney donors incur substantial costs during the donation process. Our findings inform the continued development of policies and programs designed to minimize costs incurred by living kidney donors.

PMID: 29215180 [PubMed - as supplied by publisher]

The Risk in Living Kidney Donation.

Fri, 12/08/2017 - 13:45

The Risk in Living Kidney Donation.

Camb Q Healthc Ethics. 2018 Jan;27(1):29-35

Authors: Glannon W

Abstract
This article examines two questions. (1) If prospective living kidney donors knew of the lifetime risk of end-stage renal disease (ESRD) in their remaining kidney, then would they be as willing to give it up? and (2) What should transplant organizations and physicians be telling those who express an interest in donating a kidney about risk? Based on the principle that prospective donors must be fully informed of the risk, I raise the issue of a possible obstacle to closing the gap between the availability and need of transplantable kidneys. Some strategies are offered to address this problem.

PMID: 29214959 [PubMed - in process]

Sulfasalazine induces mitochondrial dysfunction and renal injury.

Fri, 12/08/2017 - 13:45

Sulfasalazine induces mitochondrial dysfunction and renal injury.

Ren Fail. 2017 Nov;39(1):745-753

Authors: Niknahad H, Heidari R, Mohammadzadeh R, Ommati MM, Khodaei F, Azarpira N, Abdoli N, Zarei M, Asadi B, Rasti M, Shirazi Yeganeh B, Taheri V, Saeedi A, Najibi A

Abstract
Sulfasalazine is a commonly used drug for the treatment of rheumatoid arthritis and inflammatory bowel disease. There are several cases of renal injury encompass sulfasalazine administration in humans. The mechanism of sulfasalazine adverse effects toward kidneys is obscure. Oxidative stress and its consequences seem to play a role in the sulfasalazine-induced renal injury. The current investigation was designed to investigate the effect of sulfasalazine on kidney mitochondria. Rats received sulfasalazine (400 and 600 mg/kg/day, oral) for 14 consecutive days. Afterward, kidney mitochondria were isolated and assessed. Sulfasalazine-induced renal injury was biochemically evident by the increase in serum blood urea nitrogen (BUN), gamma-glutamyl transferase (γ-GT), and creatinine (Cr). Histopathological presentations of the kidney in sulfasalazine-treated animals revealed by interstitial inflammation, tubular atrophy, and tissue necrosis. Markers of oxidative stress including an increase in reactive oxygen species (ROS) and lipid peroxidation (LPO), a defect in tissue antioxidant capacity, and glutathione (GSH) depletion were also detected in the kidney of sulfasalazine-treated groups. Decreased mitochondrial succinate dehydrogenase activity (SDA), mitochondrial depolarization, mitochondrial GSH depletion, increase in mitochondrial ROS, LPO, and mitochondrial swelling were also evident in sulfasalazine-treated groups. Current data suggested that oxidative stress and mitochondrial injury might be involved in the mechanism of sulfasalazine-induced renal injury.

PMID: 29214868 [PubMed - in process]

Multi-center Performance Evaluations of Tacrolimus and Cyclosporine Electrochemiluminescence Immunoassays in the Asia-Pacific Region.

Fri, 12/08/2017 - 13:45

Multi-center Performance Evaluations of Tacrolimus and Cyclosporine Electrochemiluminescence Immunoassays in the Asia-Pacific Region.

Ann Lab Med. 2018 Mar;38(2):85-94

Authors: Qin X, Rui J, Xia Y, Mu H, Song SH, Raja Aziddin RE, Miles G, Sun Y, Chun S

Abstract
BACKGROUND: The immunosuppressant drugs (ISDs), tacrolimus and cyclosporine, are vital for solid organ transplant patients to prevent rejection. However, toxicity is a concern, and absorption is highly variable across patients; therefore, ISD levels need to be precisely monitored. In the Asia-Pacific (APAC) region, tacrolimus and cyclosporine concentrations are typically measured using immunoassays. The objective of this study was to assess the analytical performance of Roche Elecsystacrolimus and cyclosporinee electrochemiluminescence immunoassays (ECLIAs).
METHODS: This evaluation was performed in seven centers across China, South Korea, and Malaysia. Imprecision (repeatability and reproducibility), assay accuracy, and lot-to-lot reagent variability were tested. The Elecsys ECLIAs were compared with commercially available immunoassays (Architect, Dimension, and Viva-E systems) using whole blood samples from patients with various transplant types (kidney, liver, heart, and bone marrow).
RESULTS: Coefficients of variation for repeatability and reproducibility were ≤5.4% and ≤12.4%, respectively, for the tacrolimus ECLIA, and ≤5.1% and ≤7.3%, respectively, for the cyclosporine ECLIA. Method comparisons of the tacrolimus ECLIA with Architect, Dimension, and Viva-E systems yielded slope values of 1.01, 1.14, and 0.897, respectively. The cyclosporine ECLIA showed even closer agreements with the Architect, Dimension, and Viva-E systems (slope values of 1.04, 1.04, and 1.09, respectively). No major differences were observed among the different transplant types.
CONCLUSIONS: The tacrolimus and cyclosporine ECLIAs demonstrated excellent precision and close agreement with other immunoassays tested. These results show that both assays are suitable for ISD monitoring in an APAC population across a range of different transplant types.

PMID: 29214751 [PubMed - in process]

Increased Serum Level of IGF-1 Correlates With Better Cognitive Status in End-Stage Renal Disease Patients Undergoing Hemodialysis.

Fri, 12/08/2017 - 13:45

Increased Serum Level of IGF-1 Correlates With Better Cognitive Status in End-Stage Renal Disease Patients Undergoing Hemodialysis.

Ther Apher Dial. 2017 Dec 07;:

Authors: Prelevic V, Radunovic D, Antunovic T, Ratkovic M, Gligorovic-Bahranovic N, Gledovic B, Vujosevic S, Nedovic-Vukovic M, Basic-Jukic N

Abstract
Prevalence of cognitive function decline in end stage renal disease (ESRD) patients undergoing hemodialysis is higher than in the general population. We analyzed risk factors for cognitive function decline in those patients. This study included 93 ESRD patients undergoing hemodialysis two or three times a week in three centers for hemodialysis in Montenegro. The cognitive status of patients was assessed using the mini mental score examination (MMSE) test. All 93 patients have been divided into three groups according to the results of MMSE. Patients in the first group had severe cognitive impairment and MMSE score below 17 (26.88%), patients in the second group with MMSE score 18-23 had moderate cognitive impairment (40.86%) and third group of patients have MMSE >24 and no cognitive impairment (32.26%). There were no significant differences between groups for gender, smoking habits and level of parathyroid hormone. Level of schooling was significantly different between groups of patients (P < 0.001). Laboratory markers observed in this study with significant differences between groups were: IGF 1, IGFBP 3, erythrocytes and hemoglobin (P < 0.001, P = 0.004, P < 0.001, P = 0.002, respectively). IGF 1 proved to be of great importance for evaluating cognitive status in our study. This marker was statistically different between groups (P < 0.001) and Tukey post hoc analysis showed significant differences between all three groups (first and second group P = 0.045, second and third group P = 0.015, first and third group P < 0.001). Our data suggest that IGF 1 can be considered as novel biomarker for assessment of cognitive functioning in CKD patients, which can be of huge clinical importance.

PMID: 29214734 [PubMed - as supplied by publisher]

Pharmacologic Complement Inhibition in Clinical Transplantation.

Fri, 12/08/2017 - 13:45

Pharmacologic Complement Inhibition in Clinical Transplantation.

Curr Transplant Rep. 2017;4(2):91-100

Authors: Tatapudi VS, Montgomery RA

Abstract
Purpose of Review: Over the past two decades, significant strides made in our understanding of the etiology of antibody-mediated rejection (AMR) in transplantation have put the complement system in the spotlight. Here, we review recent progress made in the field of pharmacologic complement inhibition in clinical transplantation and aim to understand the impact of this therapeutic approach on outcomes in transplant recipients.
Recent Findings: Encouraged by the success of agents targeting the complement cascade in disorders of unrestrained complement activation like paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), investigators are testing the safety and efficacy of pharmacologic complement blockade in mitigating allograft injury in conditions ranging from AMR to recurrent post-transplant aHUS, C3 glomerulopathies and antiphospholipid anti-body syndrome (APS). A recent prospective study demonstrated the efficacy of terminal complement inhibition with eculizumab in the prevention of acute AMR in human leukocyte antigen (HLA)-incompatible living donor renal transplant recipients. C1 esterase inhibitor (C1-INH) was well tolerated in two recent studies in the treatment of AMR and was associated with improved renal allograft function.
Summary: Pharmacologic complement inhibition is emerging as valuable therapeutic tool, especially in the management of highly sensitized renal transplant recipients. Novel and promising agents that target various elements in the complement cascade are in development. Graphical Abstractᅟ.

PMID: 29214126 [PubMed]

Clinical Indices Can Standardize and Monitor Pediatric Care: A Novel Mechanism to Improve Quality and Safety.

Fri, 12/08/2017 - 13:45

Clinical Indices Can Standardize and Monitor Pediatric Care: A Novel Mechanism to Improve Quality and Safety.

J Pediatr. 2017 Dec 04;:

Authors: Crandall W, Davis JT, Dotson J, Elmaraghy C, Fetzer M, Hayes D, Horwitz E, Kogon A, Olshefski R, Patel H, Brilli RJ

Abstract
OBJECTIVE: The Cancer Care Index (CCI), a single metric that sums the number of undesirable patient events in a given time frame (either preventable harm events or missed opportunities to provide optimal care), resulted in a 42% improvement in performance. Our objective was to test the index concept in other service lines to determine whether similar performance improvement occurred.
STUDY DESIGN: Care indices were developed and introduced in 3 additional service lines: Nephrology (Chronic Kidney Disease Care Index; CKDCI), Pulmonology (Lung Transplantation Care Index; LTCI), and Otolaryngology (Tracheostomy Care Index; TCI). After reaching agreement on specific harms to be avoided and elements of optimal care that should be reliably delivered, these items were compiled into indices that were updated monthly. Reports included each element individually and the total for all elements. Baseline performance was calculated retrospectively for the previous year.
RESULTS: Significant improvement in performance occurred in each program following implementation of the clinical indices. The CKDCI was decreased by 63.2% (P < .001), the LTCI was decreased by 89.5% (P < .001), and the TCI was decreased by 53.0% (P < .001). Surveyed staff indicated satisfaction with use of the metric.
CONCLUSIONS: Clinical indices are useful for evaluating and managing the overall reliability of a program's ability to deliver optimal care, and are associated with improved clinical performance and satisfaction by service line staff when incorporated into a program's operation.

PMID: 29212624 [PubMed - as supplied by publisher]

Exploring the use of tablet computer-based electronic data capture system to assess patient reported measures among patients with chronic kidney disease: a pilot study.

Fri, 12/08/2017 - 13:45

Exploring the use of tablet computer-based electronic data capture system to assess patient reported measures among patients with chronic kidney disease: a pilot study.

BMC Nephrol. 2017 Dec 06;18(1):356

Authors: Wong D, Cao S, Ford H, Richardson C, Belenko D, Tang E, Ugenti L, Warsmann E, Sissons A, Kulandaivelu Y, Edwards N, Novak M, Li M, Mucsi I

Abstract
BACKGROUND: Collecting patient reported outcome measures (PROMs) via computer-based electronic data capture system may improve feasibility and facilitate implementation in clinical care. We report our initial experience about the acceptability of touch-screen tablet computer-based, self-administered questionnaires among patients with chronic kidney disease (CKD), including stage 5 CKD treated with renal replacement therapies (RRT) (either dialysis or transplant).
METHODS: We enrolled a convenience sample of patients with stage 4 and 5 CKD (including patients on dialysis or after kidney transplant) in a single-centre, cross-sectional pilot study. Participants completed validated questionnaires programmed on an electronic data capture system (DADOS, Techna Inc., Toronto) on tablet computers. The primary objective was to evaluate the acceptability and feasibility of using tablet-based electronic data capture in patients with CKD. Descriptive statistics, Fischer's exact test and multivariable logistic regression models were used for data analysis.
RESULTS: One hundred and twenty one patients (55% male, mean age (± SD) of 58 (±14) years, 49% Caucasian) participated in the study. Ninety-two percent of the respondents indicated that the computer tablet was acceptable and 79% of the participants required no or minimal help for completing the questionnaires. Acceptance of tablets was lower among patients 70 years or older (75% vs. 95%; p = 0.011) and with little previous computer experience (81% vs. 96%; p = 0.05). Furthermore, a greater level of assistance was more frequently required by patients who were older (45% vs. 15%; p = 0.009), had lower level of education (33% vs. 14%; p = 0.027), low health literacy (79% vs. 12%; p = 0.027), and little previous experience with computers (52% vs. 10%; p = 0.027).
CONCLUSIONS: Tablet computer-based electronic data capture to administer PROMs was acceptable and feasible for most respondents and could therefore be used to systematically assess PROMs among patients with CKD. Special consideration should focus on elderly patients with little previous computer experience, since they may require more assistance with completion.

PMID: 29212466 [PubMed - in process]

Impact of complement component 3/4/5 single nucleotide polymorphisms on renal transplant recipients with antibody-mediated rejection.

Fri, 12/08/2017 - 13:45

Impact of complement component 3/4/5 single nucleotide polymorphisms on renal transplant recipients with antibody-mediated rejection.

Oncotarget. 2017 Nov 07;8(55):94539-94553

Authors: Wang Z, Yang H, Guo M, Han Z, Tao J, Chen H, Ge Y, Wang K, Tan R, Wei JF, Gu M

Abstract
Antibody-mediated rejection (ABMR) is an important risk of allograft dysfunction in kidney transplantation. The complement system is considered to be associated with the generation of alloreative antibodies and donor-specific antibodies. However, the association of complement single nucleotide polymorphisms (SNPs) with ABMR still remained unclear. Blood samples of 199 renal transplant recipients containing 68 with ABMR and 131 with stable graft function were collected, and analyzed by next-generation sequencing with an established gene panel. High quality readout was obtained in 18 C3 SNPs, 9 C4 SNPs and 22 C5 SNPs. Concerning C3 gene polymorphisms, after being adjusted with age, sex and immunosuppressive protocols, rs10411506 and rs2230205 were found to be statistically associated with ABMR in dominant model (rs10411506: OR=2.73, 95% CIs: 1.16, 6.68, P=0.028; rs2230205: OR=2.52, 95% CIs: 1.07, 5.92, P=0.034); rs10411506, rs2230205 and rs2230201 were found different in HET model (rs10411506: OR=3.05, 95% CIs: 1.22, 7.64, P=0.017; rs2230205: OR=2.90, 95% CIs: 1.20, 7.00, P=0.018; rs2230201: OR=2.41, 95% CIs: 1.03, 5.64, P=0.042). The linkage analysis showed relatively high linkage disequilibrium among these SNPs. In addition, no significant correlation was found between C4 SNPs, or C5 SNPs, and the development of ABMR. Our study firstly identified the two SNPs (rs10411506 and rs2230205) in C3 gene were statistically correlated with ABMR in kidney transplantation. These findings may have implications for the diagnosis and prevention of ABMR.

PMID: 29212248 [PubMed]

Bone marrow-derived mesenchymal stem cells ameliorate nephrosis through repair of impaired podocytes.

Fri, 12/08/2017 - 13:45
Related Articles

Bone marrow-derived mesenchymal stem cells ameliorate nephrosis through repair of impaired podocytes.

Clin Invest Med. 2017 Feb 19;40(1):E13-E24

Authors: Chen Y, Chen J, Wan J, Gao N, Cui J, You D, Zou Z

Abstract
PURPOSE: The purpose of this study was to investigate the effects of bone marrow-derived mesenchymal stem cells (BMSC) on podocytes of puromycin amino nuclear glucoside (PAN) -induced nephrosis in mice.
METHODS: Mice were randomly divided into Control, PAN and BMSC groups. Mice were injected with PAN (0.5 mg/g weight) via the tail vein. The 24-h urinary protein was obtained after modelling, and urinary protein excretion was determined. The blood and kidney specimens were isolated after the tenth day of modelling. Blood samples were collected for measuring serum creatinine (SCr) and blood urea nitrogen (BUN). A sample of kidney was taken for observing pathological changes through hematoxylin-eosin staining and electron microscopy, and the rest of the kidney was used for detecting the protein and mRNA expression of nephrin, CD2AP, synaptopodin, TRPC6 by real-time quantitative PCR, Western-blot and immunohistochemistry.
RESULTS: After PAN injection, podocyte foot process fusion was detected by electron microscopy, and the 24 h urinary protein excretion increased compared with control mice on days 3, 7 and 10 post-PAN injection (P.

PMID: 28218578 [PubMed - indexed for MEDLINE]

So Many Possibilities: Lung Nodules in a Transplant Recipient.

Fri, 12/08/2017 - 13:45
Related Articles

So Many Possibilities: Lung Nodules in a Transplant Recipient.

Am J Med. 2017 May;130(5):534-536

Authors: Sfeir M, Douglass E, Soave R

PMID: 28082166 [PubMed - indexed for MEDLINE]

Association of high HLA-E expression during acute cellular rejection and numbers of HLA class I leader peptide mismatches with reduced renal allograft survival.

Fri, 12/08/2017 - 13:45
Related Articles

Association of high HLA-E expression during acute cellular rejection and numbers of HLA class I leader peptide mismatches with reduced renal allograft survival.

Immunobiology. 2017 Mar;222(3):536-543

Authors: Guberina H, Rebmann V, Wagner B, da Silva Nardi F, Dziallas P, Dolff S, Bienholz A, Wohlschlaeger J, Bankfalvi A, Heinemann FM, Witzke O, Zoet YM, Claas FH, Horn PA, Kribben A, Doxiadis II

Abstract
Non-classical Human Leukocyte Antigen (HLA)-E preferentially presents leader peptides derived from classical HLA-class I molecules. HLA-E can trigger opposed immune responses by interacting with inhibitory NKG2A or by activating NKG2C receptors on NK and T-cells. We studied the impact of HLA-E on renal allograft survival during acute cellular rejection. HLA-E expression was up-regulated in acute cellular rejection (ACR) biopsies (n=12) compared to biopsies from 13 renal allografts with no rejection-signs. HLA-E up-regulation was correlated with numbers of HLA-class I leader peptide mismatches (p=0.04). CD8+ and CD56+ infiltrating cells correlated with HLA-E expression (p<0.0001 and p=0.0009, respectively). Activating NKG2C receptor dominated on effector cells in biopsies and peripheral blood during ACR potentially allowing HLA-E-mediated immune activation. Moreover, HLA-E expression correlated with deterioration in renal allograft function (p<0.008) and reduced allograft survival (p=0.002). Our findings provide evidence that during renal allograft rejection HLA-E along with high numbers of mismatched HLA-class I leader peptides might represent additional targets for immune-activating responses.

PMID: 27871782 [PubMed - indexed for MEDLINE]

Risk factors for severe clinical events in male and female patients with Fabry disease treated with agalsidase beta enzyme replacement therapy: Data from the Fabry Registry.

Fri, 12/08/2017 - 13:45
Related Articles

Risk factors for severe clinical events in male and female patients with Fabry disease treated with agalsidase beta enzyme replacement therapy: Data from the Fabry Registry.

Mol Genet Metab. 2016 Sep;119(1-2):151-9

Authors: Hopkin RJ, Cabrera G, Charrow J, Lemay R, Martins AM, Mauer M, Ortiz A, Patel MR, Sims K, Waldek S, Warnock DG, Wilcox WR

Abstract
BACKGROUND: Fabry disease, an X-linked lysosomal storage disorder, causes intracellular accumulation of glycosphingolipids leading to progressive renal, cardiovascular, and cerebrovascular disease, and premature death.
METHODS: This longitudinal Fabry Registry study analyzed data from patients with Fabry disease to determine the incidence and type of severe clinical events following initiation of enzyme replacement therapy (ERT) with agalsidase beta, as well as risk factors associated with occurrence of these events. Severe events assessed included chronic dialysis, renal transplantation, cardiac events, stroke, and death.
RESULTS: The analyses included 969 male and 442 female Fabry patients. The mean age at first agalsidase beta infusion was 35 and 44, and median treatment follow-up 4.3years and 3.2years, respectively. Among males, cardiac events were the most common on-ERT events, followed by renal, stroke, and non-cardiac death. Among females, cardiac events were also most common followed by stroke and renal events. Patients with on-ERT events had significantly more advanced cardiac and renal disease at baseline as compared with patients without on-ERT events. Severe events were also associated with older age at ERT initiation (males and females), a history of pre-ERT events (females; approaching statistical significance in males), and a higher urinary protein/creatinine ratio (females). Approximately 65% of patients with pre-ERT events did not experience subsequent on-ERT events. Of patients without pre-ERT events, most (84% of males, 92% of females) remained event-free.
CONCLUSIONS: Patients with on-ERT severe events had more advanced Fabry organ involvement at baseline than those without such events and patients who initiated ERT at a younger age had less residual risk of on-ERT events. The observed patterns of residual risk may aid clinicians in multidisciplinary monitoring of male and female patients with Fabry disease receiving ERT, and in determining the need for administration of adjunctive therapies.

PMID: 27510433 [PubMed - indexed for MEDLINE]

Catabolism of (64)Cu and Cy5.5-labeled human serum albumin in a tumor xenograft model.

Fri, 12/08/2017 - 13:45
Related Articles

Catabolism of (64)Cu and Cy5.5-labeled human serum albumin in a tumor xenograft model.

Amino Acids. 2016 Jul;48(7):1667-75

Authors: Kang CM, Kim H, Koo HJ, Park JW, An GI, Choi JY, Lee KH, Kim BT, Choe YS

Abstract
Human serum albumin (HSA), the most abundant protein in blood plasma, has been used as a drug carrier for the last few decades. Residualizingly radiolabeled serum albumin has been reported to be avidly taken up by tumors of sarcoma-bearing mice and to most likely undergo lysosomal degradation. In this study, we prepared (64)Cu-1,4,7,10-tetraazacyclododecane-N,N',N″,N'″-tetraacetic acid (DOTA) and Cy5.5-conjugated HSA (dual probe), and evaluated its tumor uptake and catabolism. Two dual probes were prepared using different DOTA conjugation sites of HSA (one via Lys residues and the other via the Cys residue). (64)Cu-DOTA-Lys-HSA-Cy5.5 (dual probe-Lys) exhibited higher uptake by RR1022 sarcoma cells in vitro than (64)Cu-DOTA-Cys-HSA-Cy5.5 (dual probe-Cys). In RR1022 tumor-bearing mice, the two dual probes showed a similar level of tumor uptake, but uptake of dual probe-Lys was reduced in the liver and spleen compared to dual probe-Cys, probably because of the presence of a higher number of DOTA molecules in the former. At 24 and 48 h after injection, dual probe-Lys was intact or partially degraded in blood, liver, kidney, and tumor samples, but (64)Cu-DOTA-Lys was observed in the urine using radioactivity detection. Similarly, Cy5.5-Lys was observed in the urine using fluorescence detection. These results indicate that dual probe-Lys may be useful for predicting the catabolic fate of drug-HSA conjugates.

PMID: 27098932 [PubMed - indexed for MEDLINE]

Pharmacokinetic Analysis of Mycophenolate Mofetil and Enteric-Coated Mycophenolate Sodium in Calcineurin Inhibitor-Free Renal Transplant Recipients.

Fri, 12/08/2017 - 13:45
Related Articles

Pharmacokinetic Analysis of Mycophenolate Mofetil and Enteric-Coated Mycophenolate Sodium in Calcineurin Inhibitor-Free Renal Transplant Recipients.

Ther Drug Monit. 2016 Jun;38(3):388-92

Authors: Graff J, Scheuermann EH, Brandhorst G, Oellerich M, Gossmann J

Abstract
BACKGROUND: Considerable interest exists in identifying calcineurin inhibitor (CNI)-free and thus, less-toxic immunosuppressive regimens, with mycophenolic acid (MPA)-based treatments being a suitable approach. Because pharmacokinetic analyses of MPA treatments in stable CNI-free renal transplant recipients are lacking, the authors aimed at comparing the steady-state pharmacokinetic characteristics of MPA in patients on stable treatment with mycophenolate mofetil (MMF) or enteric-coated mycophenolate sodium (EC-MPS) plus prednisone (≤5 mg/d).
METHODS: In the prospective, nonrandomized, open-label study, patients with stable transplant function since ≥6 months received their routine single dose of either MMF (n = 12) or EC-MPS (n = 11). The MPA plasma concentration was recorded over 12 hours. Parameters assessed were predose MPA concentration (C0), postdose minimum and maximum concentration (Cmin and Cmax), time to maximum concentration (Tmax), and area under the concentration-time curve (AUC) for the 12-hours of exposure (AUC0-12).
RESULTS: Baseline characteristics were comparable between both the groups. Consistent with enteric coating, the mean Tmax was significantly longer after the intake of EC-MPS compared with MMF (2.2 versus 0.8 hours; P = 0.0002). The exposure measures Cmin, Cmax, and AUC0-12 were not significantly different despite the higher mean MPA equivalent dose in patients receiving MMF compared with those receiving EC-MPS (85% versus 64% of the recommended single dose, respectively). Exposures as reflected by the median AUC0-12 values were 50.7 and 58.7 mg·h·L with MMF and EC-MPS, respectively (P = 0.340). All patients achieved a target AUC of >30 mg·h·L, and 61% had an AUC of >50 mg·h·L.
CONCLUSIONS: The study provides first results on the steady-state pharmacokinetics of the 2 MPA drugs in CNI-free immunosuppressant regimens. Pharmacokinetic parameters measured in this study under real-life conditions were comparable in patients receiving MMF or EC-MPS.

PMID: 26829599 [PubMed - indexed for MEDLINE]

Pages