Cranberrry pas sur que ca marche ....

CLINICAL QUESTION: Are cranberry products (juice, tablets, capsules, and syrup) associated with prevention of urinary tract infections (UTIs) compared with placebo or other treatments? BOTTOM LINE: Cranberry products are not associated with prevention of UTIs. However, lack of association of cranberry products with a reduced incidence of UTIs in clinical trials may be due to lack of participant adherence, lack of sufficient active ingredient in the cranberry product, or lack of sufficient statistical power.
JAMA. 310(13):1395-1396, October 2, 2013.
Jepson, Ruth

Techniques "sensibles" pour détecter les DSA, une perte de chance ?

Influence of test technique on sensitization status of patients on the kidney transplant waiting list.

Gombos P, Opelz G, Scherer S, Morath C, Zeier M, Schemmer P, Süsal C.

Source

Department of Transplantation Immunology, University of Heidelberg, Heidelberg, Germany.

Am J Transplant. 2013 Aug;13(8):2075-82

The exquisitely sensitive single antigen bead (SAB) technique was shown to detect human leukocyte antigen (HLA) antibodies in sera of healthy male blood donors. Such false reactions can have an impact on critical decisions, especially with respect to the determination of unacceptable HLA-antigen mismatches in patients awaiting a kidney transplant. We tested pretransplant sera of 534 patients on the kidney waiting list using complement-dependent cytotoxicity (CDC), enzyme-linked immunosorbent assay (ELISA) and SAB in parallel. Evidence of HLA antibodies was obtained in 5% of patients using CDC, 14% using ELISA, and 81% using SAB. Among patients without history of an immunizing event, 77% showed evidence of HLA antibodies in SAB. In contrast 98% of these patients were negative in ELISA and CDC. In patients without an immunizing event, SAB-detected antibodies reacted not always weakly but with mean fluorescence intensity (MFI) values as high as 14 440. High-MFI-value antibodies were found in some of these patients with HLA specificities that are rather common in general population, consideration of which would lead to unjustified exclusion of potential kidney donors. False SAB reactions can be unveiled by testing with additional antibody assays. Denial of donor kidneys to recipients based on HLA-antibody specificities detected exclusively in the SAB assay is not advisable.

Mieux au début mais pas après, Meier-Kriesch AJT 2004

Long-term renal allograft survival: have we made significant progress or is it time to rethink our analytic and therapeutic strategies?

Meier-Kriesche HU, Schold JD, Kaplan B.

Source

Department of Medicine, University of Florida, Gainesville, FL, USA. meierhu@medicine.ufl.edu

Impressive renal allograft survival improvement between 1988 and 1995 has been described using projections of half-lives based on limited actual follow up. We aimed, now with sufficient follow up available to calculate real half-lives. Real half-lives calculated from Kaplan-Meier curves for the overall population as well as subsets of repeat transplants and African Americans recipients were examined. Real half-lives were substantially shorter than projected half-lives. As a whole, half-lives have improved by about 2 years between 1988 and 1995 as compared to the earlier projected 6 years of improvement. The improvement seems to be driven primarily by the improvement in graft survival of re-transplants. First transplants showed a cumulative increase in graft survival of less than 6 months. Projected half-lives are a risky estimation of long-term survival especially when based on short actual follow up. First transplant survival has only marginally improved during the early years of post transplant follow up while no significant improvement in long-term survival could be detected between 1988 and 1995. Redirection of attention from early endpoints towards the process of long-term graft loss may be necessary to sustain early gains in the long term.

Un contrat d'adhérence ....

Improving Outcomes of Renal Transplant Recipients With Behavioral Adherence Contracts: A Randomized Controlled Trial.

Chisholm-Burns MA, Spivey CA, Graff Zivin J, Lee JK, Sredzinski E, Tolley EA.

Source

University of Tennessee College of Pharmacy, Memphis, TN.

Am J Transplant. 2013 Jul 2. doi: 10.1111/ajt.12341.

The objective of this randomized controlled trial was to assess the effects of a 1-year behavioral contract intervention on immunosuppressant therapy (IST) adherence and healthcare utilizations and costs among adult renal transplant recipients (RTRs). The sample included adult RTRs who were at least 1 year posttransplant, taking tacrolimus or cyclosporine and served by a specialty pharmacy. Pharmacy refill records were used to measure adherence and monthly questionnaires were used to measure healthcare utilizations. Direct medical costs were estimated using the 2009 Medicare Expenditure Panel Survey. Adherence was analyzed using the GLM procedure and the MIXED procedure of SAS. Rate ratios and 95% confidence intervals were estimated to quantify the rate of utilizing healthcare services relative to treatment assignment. One hundred fifty RTRs were enrolled in the study. Intervention group RTRs (n = 76) had higher adherence than control group RTRs (n = 74) over the study period (p < 0.01). And 76.1% of the intervention group compared with 42.7% of the control group was not hospitalized during the 1-year study period (RR = 1.785; 95% CI: 1.314, 2.425), resulting in cost savings. Thus, evidence supports using behavioral contracts as an effective adherence intervention that may improve healthcare outcomes and lower costs.

Rejet aiguë cellulaire > rejet humoral > inflammation > impact sur la durée de vie du greffon

Kidney Allograft Survival After Acute Rejection, the Value of Follow-Up Biopsies.

El Ters M, Grande JP, Keddis MT, Rodrigo E, Chopra B, Dean PG, Stegall MD, Cosio FG.

Source

Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN.

Am J Transplant. 2013 Jul 19. doi: 10.1111/ajt.12370. [Epub ahead of print]

Kidney allografts are frequently lost due to alloimmunity. Still, the impact of early acute rejection (AR) on long-term graft survival is debated. We examined this relationship focusing on graft histology post-AR and assessing specific causes of graft loss. Included are 797 recipients without anti-donor antibodies (DSA) at transplant who had 1 year protocol biopsies. 15.2% of recipients had AR diagnosed by protocol or clinical biopsies. Compared to no-AR, all histologic types of AR led to abnormal histology in 1 and 2 years protocol biopsies, including more fibrosis + inflammation (6.3% vs. 21.9%), moderate/severe fibrosis (7.7% vs. 13.5%) and transplant glomerulopathy (1.4% vs. 8.3%, all p < 0.0001). AR were associated with reduced graft survival (HR = 3.07 (1.92-4.94), p < 0.0001). However, only those AR episodes followed by abnormal histology led to reduced graft survival. Early AR related to more late alloimmune-mediated graft losses, particularly transplant glomerulopathy (31% of losses). Related to this outcome, recipients with AR were more likely to have new DSA class II 1 year posttransplant (no-AR, 11.1%; AR, 21.2%, p = 0.039). In DSA negative recipients, early AR often leads to persistent graft inflammation and increases the risk of new DSA II production. Both of these post-AR events are associated with increased risk of graft loss.

AMR, apoptose et complément

Polyreactive Antibodies Developing Amidst Humoral Rejection of Human Kidney Grafts Bind Apoptotic Cells and Activate Complement.

1. Porcheray F, Fraser JW, Gao B, McColl A, Devito J, Dargon I, Helou Y, Wong W, 
   Girouard TC, Saidman SL, Colvin RB, Palmisano A, Maggiore U, Vaglio A, Smith RN, 
   Zorn E.

1. Transplant Center, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
2. Am J Transplant. 2013 Aug 6. doi: 10.1111/ajt.12394.

Antibody mediated rejection (AMR) is associated with a variety of graft-reactive antibodies following kidney transplant. To characterize these antibodies, we immortalized 107 B cell clones from a patient with AMR. In a previous study, we showed that six clones were reacting to multiple self-antigens as well as to HLA and MICA for two of them, thus displaying a pattern of polyreactivity. We show here that all six polyreactive clones also reacted to apoptotic but not viable cells. More generally we observed a nearly perfect overlap between polyreactivity and reactivity to apoptotic cells. Functionally, polyreactive antibodies can activate complement, resulting in the deposition of C3d and C4d at the surface of target cells. Testing the serum of 88 kidney transplant recipients revealed a significantly higher IgG reactivity to apoptotic cells in AMR patients than in patients with stable graft function. Moreover, total IgG purified from AMR patients had increased complement activating properties compared to IgG from non-AMR patients. Overall, our studies show the development of polyreactive antibodies cross-reactive to apoptotic cells during AMR. Further studies are now warranted to determine their contribution to the detection of C4d in graft biopsies as well as their role in the pathophysiology of AMR.

Le rein induirait une tolérance, greffe coeur + rein chez le porc

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Induction of Cardiac Allograft Tolerance Across a Full MHC Barrier in Miniature Swine by Donor Kidney Cotransplantation

M. L. Madariaga, S. G. Michel, M. Tasaki, V. Villani, G. M. La Muraglia II, S. Sihag, J. Gottschall, E. A. Farkash, A. Shimizu, J. S. Allan, D. H. Sachs, K. Yamada and J. C. Madsen

Am J Transpl 22 AUG 2013 | DOI: 10.1111/ajt.12423

We have previously shown that tolerance of kidney allografts across a full major histocompatibility complex (MHC) barrier can be induced in miniature swine by a 12-day course of high-dose tacrolimus. However, that treatment did not prolong survival of heart allografts across the same barrier. We have now tested the effect of cotransplanting an allogeneic heart and kidney from the same MHC-mismatched donor using the same treatment regimen. Heart allografts (n = 3) or heart plus kidney allografts (n = 5) were transplanted into MHC-mismatched recipients treated with high-dose tacrolimus for 12 days. As expected, all isolated heart allografts rejected by postoperative day 40. In contrast, heart and kidney allografts survived for >200 days with no evidence of rejection on serial cardiac biopsies. Heart/kidney recipients lost donor-specific responsiveness in cell-mediated lympholysis and mixed-lymphocyte reaction assays, were free of alloantibody and exhibited prolonged survival of donor, but not third-party skin grafts. Late (>100 days) removal of the kidney allografts did not cause acute rejection of the heart allografts (n = 2) and did not abrogate donor-specific unresponsiveness in vitro. While kidney-induced cardiac allograft tolerance (KICAT) has previously been demonstrated across a Class I disparity, these data demonstrate that this phenomenon can also be observed across the more clinically relevant full MHC mismatch. Elucidating the renal element(s) responsible for KICAT could provide mechanistic information relevant to the induction of tolerance in recipients of isolated heart allografts as well as other tolerance-resistant organs.

Approximately 100,000 individuals in the United States currently await kidney transplantation, and 400,000 individuals live with end-stage kidney disease requiring hemodialysis. The creation of a transplantable graft to permanently replace kidneyfunction would address donor organ shortage and the morbidity associated with immunosuppression. Such abioengineered graft must have the kidney's architecture and function and permit perfusion, filtration, secretion, absorption and drainage of urine. We decellularized rat, porcine and human kidneys by detergent perfusion, yielding acellular scaffolds with vascular, cortical and medullary architecture, a collecting system and ureters. To regenerate functional tissue, we seeded rat kidney scaffolds with epithelial and endothelial cells and perfused these cell-seeded constructs in a whole-organ bioreactor. The resulting grafts produced rudimentary urine in vitro when perfused through their intrinsic vascular bed. When transplanted in an orthotopic position in rat, the grafts were perfused by the recipient's circulation and produced urine through the ureteral conduit in vivo.

Nat Med. 2013 Apr 14. doi: 10.1038/nm.3154. [Epub ahead of print]

Regeneration and experimental orthotopic transplantation of a bioengineered kidney.

Song JJ, Guyette JP, Gilpin SE, Gonzalez G, Vacanti JP, Ott HC.

Source

1] Center for Regenerative Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Harvard Medical School, Boston, Massachusetts, USA.

Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis

Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk.

Nat Med. 2013 Apr 7. doi: 10.1038/nm.3145. [Epub ahead of print]

Koeth RA, Wang Z, Levison BS, Buffa JA, Org E, Sheehy BT, Britt EB, Fu X, Wu Y, Li L, Smith JD, Didonato JA, Chen J, Li H, Wu GD, Lewis JD, Warrier M, Brown JM, Krauss RM, Tang WH, Bushman FD, Lusis AJ, Hazen SL.

Source

1] Department of Cellular & Molecular Medicine, Cleveland Clinic, Cleveland, Ohio, USA. [2] Center for Cardiovascular Diagnostics & Prevention, Cleveland Clinic, Cleveland, Ohio, USA.