Improved renal function after kidney transplantation is associated with heme oxygenase-1 polymorphism

Heme oxygenase-1 (HO-1) has a microsatellite polymorphism based on the number of guanosine-thymidine nucleotide repeats (GT) repeats that regulates expression levels and could have an impact on organ survival post-injury. We correlated HO-1 polymorphism with renal graft function. The HO-1 gene was sequenced (N = 181), and the allelic repeats were divided into subclasses: short repeats (S) (< 27 repeats) and long repeats (L) (>= 27 repeats). A total of 47.5% of the donors carried the S allele. The allograft function was statistically improved six months, two and three yr after transplantation in patients receiving kidneys from donors with an S allele. For the recipients carrying the S allele (50.3%), the allograft function was also better throughout the follow-up, but reached statistical significance only three yr after transplantation (p = 0.04). Considering only those patients who had chronic allograft nephropathy (CAN; 74 of 181), allograft function was also better in donors and in recipients carrying the S allele, two and three yr after transplantation (p = 0.03). Recipients of kidney transplantation from donors carrying the S allele presented better function even in the presence of CAN.

Methods of Analysis for Peritubular Capillaritis and Glomerulitis in Acute Renal Rejection: Capillaritis in Management of Routine Diagnosis

Glomerulitis and peritubular capillaritis have been recognized as important lesions in acute renal rejection (AR). We studied glomerulitis and peritubular capillaritis in AR by 2 methods and investigated associations with C4d, type/grade of AR, and allograft survival time. Glomerulitis was measured according to Banff scores (glomerulitis by Banff Method [gBM]) and by counting the number of intraglomerular inflammatory cells (glomerulitis by Quantitative Method [gQM]). Capillaritis was classified by the Banff scoring system (peritubular capillaritis by Banff Method [ptcBM]) and by counting the number of cells in peritubular capillaries in 10 high-power fields (hpf; peritubular capillaritis by Quantitative Method [ptcQM]). These quantitative analyses were performed in an attempt to improve our understanding of the role played by glomerulitis and capillaritis in AR. The g0 + g1 group (gBM) associated with negative C4d (P = .02). In peritubular capillaritis, a larger number of cells per 10 hpf in peritubular capillaries (ptcQM) were observed in positive C4d cases (P = .03). The group g2 + g3 (gBM) correlated with graft loss (P = .01). Peritubular capillaritis was not significantly related to graft survival time. Our study showed that the Banff scoring system is the best method to study glomerulitis and observed that the evaluation of capillaritis in routine biopsies is difficult and additional studies are required for a better understanding of its meaning in AR biopsy specimens of renal allografts.

Low-Level Laser Therapy Decreases Renal Interstitial Fibrosis

Objective: the purpose of this study was to investigate the effect of low-level laser therapy (LLLT) on chronic kidney disease (CKD) in a model of unilateral ureteral obstruction (UUO). Background data: Regardless of the etiology, CKD involves progressive widespread tissue fibrosis, tubular atrophy, and loss of kidney function. This process also occurs in kidney allograft. At present, effective therapies for this condition are lacking. We investigated the effects of LLLT on the interstitial fibrosis that occurs after experimental UUO in rats. Methods: The occluded kidney of half of the 32 Wistar rats that underwent UUO received a single intraoperative dose of LLLT (AlGaAs laser, 780 nm, 22.5 J/cm(2), 30mW, 0.75W/cm(2), 30 sec on each of nine points). After 14 days, renal fibrosis was assessed by Sirius red staining under polarized light. Immunohistochemical analyses quantitated the renal tissue cells that expressed fibroblast (FSP-1) and myofibroblast (alpha-SMA) markers. Reverse transcriptase polymerase chain reaction (RT-PCR) was performed to determine the mRNA expression of interleukin (IL)-6, monocyte chemotactic protein-1 (MCP-1), transforming growth factor (TGF)-beta 1 and Smad3. Results: The UUO and LLLT animals had less fibrosis than the UUO animals, as well having decreased expression inflammatory and pro-fibrotic markers. Conclusions: For the first time, we showed that LLLT had a protective effect regarding renal interstitial fibrosis. It is conceivable that by attenuating inflammation, LLLT can prevent tubular activation and transdifferentiation, which are the two processes that mainly drive the renal fibrosis of the UUO model.

The impact of pretransplant donor-specific antibodies on graft outcome in renal transplantation: a six-year follow-up study

OBJECTIVE: The significance of pretransplant, donor-specific antibodies on long-term patient outcomes is a subject of debate. This study evaluated the impact and the presence or absence of donor-specific antibodies after kidney transplantation on short-and long-term graft outcomes. METHODS: We analyzed the frequency and dynamics of pretransplant donor-specific antibodies following renal transplantation from a randomized trial that was conducted from 2002 to 2004 and correlated these findings with patient outcomes through 2009. Transplants were performed against a complement-dependent T-and B-negative crossmatch. Pre- and posttransplant sera were available from 94 of the 118 patients (80%). Antibodies were detected using a solid-phase (Luminex (R)), single-bead assay, and all tests were performed simultaneously. RESULTS: Sixteen patients exhibited pretransplant donor-specific antibodies, but only 3 of these patients (19%) developed antibody-mediated rejection and 2 of them experienced early graft losses. Excluding these 2 losses, 6 of 14 patients exhibited donor-specific antibodies at the final follow-up exam, whereas 8 of these patients (57%) exhibited complete clearance of the donor-specific antibodies. Five other patients developed "de novo'' posttransplant donor-specific antibodies. Death-censored graft survival was similar in patients with pretransplant donor-specific and non-donor-specific antibodies after a mean follow-up period of 70 months. CONCLUSION: Pretransplant donor-specific antibodies with a negative complement-dependent cytotoxicity crossmatch are associated with a risk for the development of antibody-mediated rejection, although survival rates are similar when patients transpose the first months after receiving the graft. Our data also suggest that early posttransplant donor-specific antibody monitoring should increase knowledge of antibody dynamics and their impact on long-term graft outcome.

Human leukocyte antigen-G 3 ' untranslated region polymorphisms are associated with better kidney allograft acceptance

Human leukocyte antigen-G (FILA-G) plays a well-recognized role in the modulation of the immune response, and HLA-G expression has been associated with increased graft survival and decreased rejection episodes. To investigate the role of the HLA-G 3' untranslated region (3'UTR) in renal transplantation, we evaluated several polymorphic sites (14-bp Del/Ins +3003T/C, +3010C/G, +3027C/A, +3035C/T, +3142G/C, and +3187A/G) in patients exhibiting or not exhibiting rejection episodes. A total of 104 patients (15 with acute and 48 with chronic rejection, and 41 with no rejection) and 142 healthy individuals were studied. HLA-G 3'UTR was typed by direct sequencing. The +3035C-C genotype was more frequent in patients exhibiting chronic rejection compared with healthy controls, and the +3035C-T genotype was less frequent in chronic rejection compared with patients without rejection (acute plus chronic) or compared with healthy controls. The +3187G-A genotype, in which the A allele is associated with increased mRNA degradation, showed increased frequency in the rejection group (acute plus chronic) when compared with healthy controls. The 14 base pair Deletion/Insertion genotype was marginally increased in patients with acute rejection. This is the first study to show associations among numerous polymorphic sites in the HLA-G 3'UTR in kidney allotransplantation, which may contribute to the understanding of HLA-G post-transcriptional mechanisms. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.

[Renal transplantation - new developments]

Renal transplantation has become an established option for renal replacement therapy in many patients with end stage renal disease. Living donation is a possibility for timely transplantation, hampered in 20 % of all possible donors and recipients byincompatible blood groups. AB0-incompatible renal transplantation overcomes this hurdle with acceptable allograft survival compared to conventional living-donor renal transplantation. During the last 10 years, the number of patients awaiting renal transplantation older than 65 years has nearly doubled. The decision to transplant those patients and their medical treatment is a growing challenge in transplantation. On the other hand donor age is increasing with potential negative consequences for long-term outcome of organ function. Antibody-mediated humoral rejection have been identified lately as an important cause for allograft failure during long-term follow up of renal transplant patients. New immunological methods to detect donor-specific antibodies, like solid-phase assays (Luminex®), have increased the knowledge and understanding of humoral rejection processes. This will lead hopefully to modified immunosuppressive strategies to minimize organ failure due to chronic rejection.

Sirolimus conversion regimen versus continued calcineurin inhibitors in liver allograft recipients: a randomized trial

A large prospective, open-label, randomized trial evaluated conversion from calcineurin inhibitor (CNI)- to sirolimus (SRL)-based immunosuppression for preservation of renal function in liver transplantation patients. Eligible patients received liver allografts 6-144 months previously and maintenance immunosuppression with CNI (cyclosporine or tacrolimus) since early posttransplantation. In total, 607 patients were randomized (2:1) to abrupt conversion (<24 h) from CNI to SRL (n = 393) or CNI continuation for up to 6 years (n = 214). Between-group changes in baseline-adjusted mean Cockcroft-Gault GFR at month 12 (primary efficacy end point) were not significant. The primary safety end point, noninferiority of cumulative rate of graft loss or death at 12 months, was not met (6.6% vs. 5.6% in the SRL and CNI groups, respectively). Rates of death at 12 months were not significantly different, and no true graft losses (e.g. liver transplantation) were observed during the 12-month period. At 52 weeks, SRL conversion was associated with higher rates of biopsy-confirmed acute rejection (p = 0.02) and discontinuations (p < 0.001), primarily for adverse events. Adverse events were consistent with known safety profiles. In conclusion, liver transplantation patients showed no demonstrable benefit 1 year after conversion from CNI- to SRL-based immunosuppression.

Fresh-frozen vs irradiated allograft bone in orthopaedic reconstructive surgery

The use of allograft bone is increasingly common in orthopaedic reconstruction procedures. The optimal method of preparation of allograft bone is subject of great debate. Proponents of fresh-frozen graft cite improved biological and biomechanical characteristics relative to irradiated material, whereas fear of bacterial or viral transmission warrants some to favour irradiated graft. Careful review of the literature is necessary to appreciate the influence of processing techniques on bone quality. Whereas limited clinical trials are available to govern the selection of appropriate bone graft, this review presents the argument favouring the use of fresh-frozen bone allograft as compared to irradiated bone.

Compliance in peritoneal dialysis : a qualitative study of renal nurses

End-stage renal failure is a life-threatening condition, often treated with home-based peritoneal dialysis (PD). PD is a demanding regimen, and the patients who practise it must make numerous lifestyle changes and learn complicated biomedical techniques. In our experience, the renal nurses who provide mostPDeducation frequently express concerns that patient compliance with their teaching is poor. These concerns are mirrored in the renal literature. It has been argued that the perceived failure of health professionals to improve compliance rates with PD regimens is because ‘compliance’ itself has never been adequately conceptualized or defined; thus, it is difficult to operationalize and quantify. This paper examines how a group of Australian renal nurses construct patient compliance with PD therapy. These empirical data illuminate how PD compliance operates in one practice setting; how it is characterized by multiple and often competing energies; and how ultimately it might be pointless to try to tame ‘compliance’ through rigid definitions and measurement, or to rigidly enforce it in PD patients. The energies involved are too fractious and might be better spent, as many of the more experienced nurses in this study argue, in augmenting the energies that do work well together to improve patient outcomes.