Friday, December 20, 2013

Clinical outcomes among renal transplant recipients with pre-transplant weakly reactive donor-specific antibodies

Clinical Transplantation Clinical outcomes among renal transplant recipients with pre-transplant weakly reactive donor-specific antibodies

Abstract

Background

Alloantibody can lead to antibody-mediated rejection and graft loss in renal transplantation, necessitating an assessment of cross-match compatibility. Within the past decade, more specific solid phase assays of alloantibody have been widely adopted, allowing virtual cross-matching based on unacceptable antigens, the threshold of which is determined by individual centers.

Methods

We examined the clinical outcomes of 482 patients transplanted 2007–2009 in a single center, focusing on 30 patients with weakly reactive donor-specific antibody (DSA) determined prospectively prior to renal transplant.

Results

Compared with patients without DSA, patients with weakly reactive DSA do not have increased rates of antibody-mediated rejection, cellular rejection, or graft loss despite conventional immunosuppression utilization.

Conclusions

Using the screening methodology and immunosuppression regimen, we have applied to the patients with weak DSA allows them to be transplanted with equivalent outcomes as those without DSA, despite the overall higher risk characteristics of the patients in the weak DSA group.




http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12289

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Alberto Reino Buelvas
Médico Internista Nefrólogo
Hospital San Vicente de Paul
Grupo Trasplantes Renales
Director Médico Unidad Renal

Thursday, December 12, 2013

The role of mycophenolate mofetil in kidney transplantation revisited

Transplantation Reviews The role of mycophenolate mofetil in kidney transplantation revisited

Abstract: Since its regulatory approval in 1995, mycophenolate mofetil (MMF) has largely replaced azathioprine (AZA) as the anti-metabolite immunosuppressive of choice in kidney transplantation. While the initial industry-sponsored clinical trials suggested strong reductions in the incidence of acute rejection in the first six months post transplantation, long-term follow-up studies have failed to demonstrate a similar degree of benefit in overall graft and patient survival. In addition, several subsequent studies have raised questions on the potential attenuating effects of calcineurin inhibitor choice on MMF efficacy when compared to AZA. This review will revisit the question of whether the available evidence continues to support the superiority of MMF over AZA in kidney transplantation outcomes while comprehensively reviewing the available evidence from clinical trial data, systematic reviews, and registry studies.


http://www.transplantationreviews.com/article/S0955-470X(13)00112-2/abstract?rss=yes

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Alberto Reino Buelvas
Médico Internista Nefrólogo
Hospital San Vicente de Paul
Grupo Trasplantes Renales
Director Médico Unidad Renal

Sunday, December 8, 2013

Desensitization for prevention of chronic antibody-mediated rejection after kidney transplantation

Clinical Transplantation Desensitization for prevention of chronic antibody-mediated rejection after kidney transplantation

Abstract

Chronic antibody-mediated rejection (C-AMR) is the most important and leading cause of graft loss after kidney transplantation. Although it is well known that chronic renal allograft dysfunction or failure is caused by various immunological or non-immunological factors, donor-specific anti-human leukocyte antigen antibodies (DSAs) are considered to be the most detrimental to graft survival and could cause C-AMR. Despite the use of intensive treatment for C-AMR, outcomes have not always been promising. Recently, prevention, rather than treatment, of C-AMR has been attempted, and this approach appears to be a more effective option for reducing the incidence of C-AMR and, ultimately, improving long-term survival. To prevent C-AMR, removal of antibodies, inactivation of antibodies, and prevention of antibody production after kidney transplantation are essential. Preconditioning treatment including plasmapheresis, intravenous immunoglobulin, and rituximab injection seems the most effective of current desensitization protocols. In this minireview, we will focus on the prevention of C-AMR through desensitization and improving long-term graft survival.




http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12260

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Alberto Reino Buelvas
Médico Internista Nefrólogo
Hospital San Vicente de Paul
Grupo Trasplantes Renales
Director Médico Unidad Renal

Outcome of tonsillectomy for recurrent IgA nephropathy after kidney transplantation

Clinical Transplantation Outcome of tonsillectomy for recurrent IgA nephropathy after kidney transplantation

Abstract

Since 2007, we have performed tonsillectomies for patients with recurrent immunoglobulin A nephropathy (IgAN) after kidney transplantation. Seven patients with primary IgAN showed biopsy-proven recurrent IgAN after living-donor kidney transplantation. They had persistent proteinuria or hematuria for an average of 40.3 months, and tonsillectomy was performed, on average, 75.6 months after kidney transplantation. In six patients with observation periods of more than one yr, good remission of urinary findings was observed after tonsillectomy. We classified the seven patients into three types of renal injury based on histological findings: severe, moderate, and mild. Two patients classified with severe renal injury at the time of tonsillectomy had other problems, such as refractory hypertension and bilateral sinusitis. They followed a rapidly progressive clinical course. One case already had moderate histological renal injury. He demonstrated prompt amelioration of urinary findings after tonsillectomy but immediate deviation from remission of proteinuria and hematuria. In the four cases presenting mild renal injury at tonsillectomy, the improved urinary findings and serum creatinine value after tonsillectomy have persisted. In conclusion, tonsillectomy may be a favorable treatment for cases of mild-grade IgAN. However, other treatments such as antihypertensive agents and diet therapy may be necessary in other grades.




http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fctr.12194

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Alberto Reino Buelvas
Médico Internista Nefrólogo
Hospital San Vicente de Paul
Grupo Trasplantes Renales
Director Médico Unidad Renal

Incidence and Predictors of Postoperative Atrial Fibrillation in Kidney Transplant Recipients

Transplantation - Current Issue Incidence and Predictors of Postoperative Atrial Fibrillation in Kidney Transplant Recipients

imageBackground: Postoperative atrial fibrillation (POAF) is a complication of cardiothoracic and noncardiothoracic surgery. Kidney transplant recipients bear several known risk factors and may have a higher incidence of POAF. We retrospectively studied kidney and kidney/liver transplant recipients to estimate their POAF incidence and identify relevant risk factors. We also adapted a clinical score originally designed to predict thromboembolic risk in atrial fibrillation (AF; CHA2DS2-VASc) for assessing transplant patients. Methods: We reviewed the clinical charts of kidney or kidney/liver transplant recipients from January 2005 to December 2008 at St. Orsola University Hospital Kidney Transplant Centre. Patients with and without POAF were compared on a number of clinical, laboratory, and instrumental data. Results: The POAF incidence in kidney transplant recipients was 8.2%. Risk factors for POAF identified in univariate analyses included older recipient age, history of myocardial infarction, history of AF, liver/kidney transplantation, arterial stiffness, atherosclerotic plaques in the aorta or lower limbs, and diabetes mellitus. In a multivariate analysis, age, myocardial infarction history and combined liver/kidney transplantation were significant independent predictors of POAF. The modified CHA2DS2-VASc score proved to have a better predictive validity that the original CHA2DS2-VASc (area under the curve=0.71, 95% confidence interval=0.63–0.79 vs. area under the curve=0.62, 95% confidence interval=0.52–0.73, respectively). Conclusion: AF is a notable complication of kidney, and particularly simultaneous liver/kidney, transplant surgery. Age, previous myocardial infarction, and simultaneous liver/kidney transplant independently predicted POAF. The modified CHA2DS2-VASc score could be useful to predict POAF risk in kidney transplant candidates.


http://journals.lww.com/transplantjournal/Fulltext/2013/12150/Incidence_and_Predictors_of_Postoperative_Atrial.9.aspx

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Alberto Reino Buelvas
Médico Internista Nefrólogo
Hospital San Vicente de Paul
Grupo Trasplantes Renales
Director Médico Unidad Renal

Macrophages Contribute to Cellular But Not Humoral Mechanisms of Acute Rejection in Rat Renal Allografts

Transplantation - Current Issue Macrophages Contribute to Cellular But Not Humoral Mechanisms of Acute Rejection in Rat Renal Allografts

imageBackground: Cells of the monocyte/macrophage lineage have been implicated as effectors in acute allograft rejection based on short-term depletion studies. However, the therapeutic potential of targeting monocyte/macrophages in acute rejection is unknown. We investigated the potential of a c-fms kinase inhibitor (fms-I) in acute renal allograft rejection. Methods: Lewis rats underwent bilateral nephrectomy and received an orthotopic Dark Agouti renal allograft. Recipients received fms-I or vehicle from the time of transplantation until being killed on day 5. Results: Vehicle-treated rats developed severe allograft rejection with massive macrophage and T-cell infiltration. In contrast, fms-I substantially inhibited renal allograft dysfunction and structural damage with abrogation of macrophage and dendritic cell infiltration but had only a minor effect on the T-cell infiltrate. However, fms-I suppressed T-cell activation within the allograft, whereas systemic T- and B-cell activation was not affected. In a longer-term study to assess therapeutic potential, fms-I–treated rats developed severe antibody-mediated rejection on day 8 after transplantation. These transplants exhibited features of antibody-mediated rejection including capillaritis with thrombosis, acute tubular injury, IgG and C4d deposition, and neutrophil infiltration and activation. Interestingly, T-cell activation within these rejecting allografts remained suppressed, indicating separation of T-cell and antibody-mediated rejection. Conclusion: This study demonstrates the ability of c-fms kinase blockade to selectively deplete monocyte/macrophages in acute allograft rejection, although this did not result in significant prolongation of allograft survival. Furthermore, we identify contrasting roles for macrophages in cellular and humoral mechanisms of acute renal allograft rejection.


http://journals.lww.com/transplantjournal/Fulltext/2013/12150/Macrophages_Contribute_to_Cellular_But_Not_Humoral.5.aspx