3D Ultrasound imaging--a useful non-invasive tool to detect AV fistulas in transplanted kidneys

BACKGROUND: A precise, non-invasive, non-toxic, repeatable, convenient and inexpensive follow-up of renal transplants, especially following biopsies, is in the interest of nephrologists. Formerly, the rate of biopsies leading to AV fistulas had been underestimated. Imaging procedures suited to a detailed judgement of these vascular malformations are to be assessed. METHODS: Three-dimensional (3D) reconstruction techniques of ultrasound flow-directed and non-flow-directed energy mode pictures were compared with a standard procedure, gadolinium-enhanced nuclear magnetic resonance imaging angiography (MRA) using the phase contrast technique. RESULTS: Using B-mode and conventional duplex information, AV fistulas were localized in the upper pole of the kidney transplant of the index patient. The 3D reconstruction provided information about the exact localization and orientation of the fistula in relation to other vascular structures, and the flow along the fistula. The MRA provided localization and orientation information, but less functional information. Flow-directed and non-flow-directed energy mode pictures could be reconstructed to provide 3D information about vascular malformations in transplanted kidneys. CONCLUSION: In transplanted kidneys, 3D-ultrasound angiography may be equally as effective as MRA in localizing and identifying AV malformations. Advantages of the ultrasound method are that it is cheaper, non-toxic, non-invasive, more widely availability and that it even provides more functional information. Future prospective studies will be necessary to evaluate the two techniques further.

Everolimus-based, calcineurin-inhibitor-free regimen in recipients of de-novo kidney transplants: an open-label, randomised, controlled trial

Non-nephrotoxic immunosuppressive strategies that allow reduction of calcineurin-inhibitor exposure without compromising safety or efficacy remain a goal in kidney transplantation. Immunosuppression based on the mammalian-target-of-rapamycin inhibitor everolimus was assessed as a strategy for elimination of calcineurin-inhibitor exposure and optimisation of renal-graft function while maintaining efficacy.

Effect of donor-specific transfusions on the outcome of renal allografts in the cyclosporine era

Despite the introduction of new immunosuppressive agents, a steady decline of functioning renal allografts after living donation is observed. Thus nonpharmacological strategies to prevent graft loss have to be reconsidered, including donor-specific transfusions (DST). We introduced a cyclosporine-based DST protocol for renal allograft recipients from living-related/unrelated donation. From 1993 to 2003, 200 ml of whole blood, or the respective mononuclear cells from the potential living donor were administered twice to all of our 61 recipient candidates. The transplanted subjects were compared with three groups of patients without DST from the Collaborative Transplant Study (Heidelberg, Germany) during a 6-year period. Six patients were sensitized without delay for a subsequent cadaveric kidney. DST patients had less often treatment for rejection and graft survival was superior compared with subjects from the other Swiss transplant centers (n = 513) or from Western Europe (n = 7024). To diminish the probability that superior results reflect patient selection rather than effects of DST, a 'matched-pair' analysis controlling for relevant factors of transplant outcome was performed. Again, this analysis indicated that recipients with DST had better outcome. Thus, our observation suggests that DST improve the outcome of living kidney transplants even when modern immunosuppressive drugs are prescribed.

Renal allografts with IF/TA display distinct expression profiles of metzincins and related genes

Chronic renal allograft injury is often reflected by interstitial fibrosis (IF) and tubular atrophy (TA) without evidence of specific etiology. In most instances, IF/TA remains an irreversible disorder, representing a major cause of long-term allograft loss. As members of the protease family metzincins and functionally related genes are involved in fibrotic and sclerotic processes of the extracellular matrix (ECM), we hypothesized their deregulation in IF/TA. Gene expression and protein level analyses using allograft biopsies with and without Banff'05 classified IF/TA illustrated their deregulation. Expression profiles of these genes differentiated IF/TA from Banff'05 classified Normal biopsies in three independent microarray studies and demonstrated histological progression of IF/TA I to III. Significant upregulation of matrix metalloprotease-7 (MMP-7) and thrombospondin-2 (THBS-2) in IF/TA biopsies and sera was revealed in two independent patient sets. Furthermore, elevated THBS-2, osteopontin (SPP1) and beta-catenin may play regulatory roles on MMP. Our findings further suggest that deregulated ECM remodeling and possibly epithelial to mesenchymal transition (EMT) are implicated in IF/TA of kidney transplants, and that metzincins and related genes play an important role in these processes. Profiling of these genes may be used to complement IF/TA diagnosis and to disclose IF/TA progression in kidney transplant recipients.