Inosine Monophosphate Dehydrogenase Polymorphisms and Renal Allograft Outcome
Background: Interindividual variation in inosine monophosphate dehydrogenase (IMPDH) enzyme activity and adverse effects caused by mycophenolate mofetil (MMF) inhibition may be genetically determined, and if so, transplant recipients should receive personalized dosing regimens of MMF, which would maximize efficacy and minimize toxicity. Some studies have demonstrated a relationship between the single nucleotide polymorphism and the risk of acute rejection with IMPDH I variants rs2278293 and rs2278294 and IMPDH II variant rs11706052, whereas others have failed to exhibit an effect. The aim of this work was to investigate the influence of these polymorphisms on acute rejection rates, graft survival and function, and MMF doses in a large cohort of patients. Methods: A random sample of 1040 recipients from the Collaborative Transplant Study DNA bank was genotyped for the variants IMPDH I rs2278293 and rs2278294 and IMPDH II rs11706052. Results: The presence of the T (rs2278293) and G alleles (rs2278294) in the IMPDH I variants and carriage of the G allele (rs11706052) in the IMPDH II variant did not increase the risk of rejection or affect graft function by 1 year after transplantation. There was no association with MMF dose tolerated at 1 year. Furthermore, these polymorphisms did not impact graft or patient survival at 5 years. Conclusion: This study represents the largest cohort of patients with the longest follow-up to date and does not support previous evidence for an association between these IMPDH variants and renal allograft rejection and graft survival.
Showing posts with label Renal Allograft Rejection. Show all posts
Showing posts with label Renal Allograft Rejection. Show all posts
Sunday, September 16, 2012
Wednesday, October 19, 2011
Thymoglobulin Versus Basiliximab Induction Therapy for Simultaneous Kidney-Pancreas Transplantation: Impact on Rejection, Graft Function, and Long-Term Outcome
Thymoglobulin Versus Basiliximab Induction Therapy for Simultaneous Kidney-Pancreas Transplantation: Impact on Rejection, Graft Function, and Long-Term Outcome: Background. Thymoglobulin (ATG) and basiliximab induction therapies are used by the majority of centers for pancreas transplantation today. Although both strategies have different mechanisms, there is a paucity of studies comparing them. We compared the efficacy and side effects of both methods in simultaneous pancreas-kidney (SPK) transplantation.
Methods. We analyzed 128 SPKs at our institution between January 2001 and August 2008. Forty-nine patients received basiliximab (40 mg), whereas 79 patients had ATG (5 mg/kg). Graft function, complications, rejection, and survival rates were analyzed.
Methods. We analyzed 128 SPKs at our institution between January 2001 and August 2008. Forty-nine patients received basiliximab (40 mg), whereas 79 patients had ATG (5 mg/kg). Graft function, complications, rejection, and survival rates were analyzed.
Friday, September 9, 2011
Validation of Urinary CXCL10 As a Marker of Borderline, Subclinical, and Clinical Tubulitis
Validation of Urinary CXCL10 As a Marker of Borderline, Subclinical, and Clinical Tubulitis: Background. Renal allograft injury secondary to subclinical and clinical tubulitis remains an important cause of allograft fibrosis and loss despite modern immunosuppression. The goal of this study was to validate the previously reported use of urinary CXCL10 (interferon-[gamma]-induced protein of 10 kDa) as a noninvasive marker of tubulitis in an independent clinical cohort.
Methods. Urine samples (n=102) from 91 patients with protocol or indication biopsies were assayed for urinary CXCL10 using ELISA. The groups analyzed were as follows: normal histology (n=22); interstitial fibrosis and tubular atrophy (IFTA) (n=20); IFTA and borderline tubulitis (n=13); borderline (n=13), subclinical (n=17); and clinical tubulitis (n=17) without IFTA.
Methods. Urine samples (n=102) from 91 patients with protocol or indication biopsies were assayed for urinary CXCL10 using ELISA. The groups analyzed were as follows: normal histology (n=22); interstitial fibrosis and tubular atrophy (IFTA) (n=20); IFTA and borderline tubulitis (n=13); borderline (n=13), subclinical (n=17); and clinical tubulitis (n=17) without IFTA.
Friday, June 3, 2011
Antibody-Mediated Rejection After Alemtuzumab Induction: Incidence, Risk Factors, and Predictors of Poor Outcome
Antibody-Mediated Rejection After Alemtuzumab Induction: Incidence, Risk Factors, and Predictors of Poor Outcome: "Background. Antibody-mediated rejection (AMR) is associated with allograft loss. Identification of factors associated with poor outcome has not been extensively studied.
Methods. We retrospectively studied 469 patients who received a negative crossmatch renal transplant with alemtuzumab induction. Forty-eight of 469 (10.2%) patients were treated for AMR. Thirty of 48 (62.5%) of the cases fulfilled the Banff criteria for definite AMR, whereas 18 of 48 (37.5%) were categorized as suspicious for AMR (tissue injury with C4d staining or donor-specific antibodies [DSAbs]). Sensitization, high human leukocyte antigen, and -DR mismatch were risk factors for the development of AMR (P=0.0016, 0.001, and 0.012, respectively).
Methods. We retrospectively studied 469 patients who received a negative crossmatch renal transplant with alemtuzumab induction. Forty-eight of 469 (10.2%) patients were treated for AMR. Thirty of 48 (62.5%) of the cases fulfilled the Banff criteria for definite AMR, whereas 18 of 48 (37.5%) were categorized as suspicious for AMR (tissue injury with C4d staining or donor-specific antibodies [DSAbs]). Sensitization, high human leukocyte antigen, and -DR mismatch were risk factors for the development of AMR (P=0.0016, 0.001, and 0.012, respectively).
Thursday, May 5, 2011
Inferior Kidney Allograft Outcomes in Patients With De Novo Donor-Specific Antibodies Are Due to Acute Rejection Episodes
Inferior Kidney Allograft Outcomes in Patients With De Novo Donor-Specific Antibodies Are Due to Acute Rejection Episodes: "Background. Donor-specific antibodies (DSAs) after kidney transplantation have been associated with poor graft outcomes in multiple studies. However, these studies have generally used stored sera or a single cross sectional screening test to identify patients with DSA. We evaluated the effectiveness of a prospective DSA screening protocol in identifying kidney and kidney/pancreas recipients at risk for poor graft outcomes.
Wednesday, April 20, 2011
A Systematic Review and Meta-Analysis of Rituximab in Antibody-mediated Renal Allograft Rejection
A Systematic Review and Meta-Analysis of Rituximab in Antibody-mediated Renal Allograft Rejection: "
Background: The standard treatment of antibody-mediated rejection (AMR) consists of antilymphocyte antibody, intravenous immunoglobulin, and plasmapheresis. This treatment is associated with a high rate of resistance and refractory AMR. Recent interest has focused on use of rituximab (RTX), a chimeric anti-CD20 monoclonal antibody.
Objective: We conducted a systematic review and meta-analysis of studies of RTX in AMR of the renal allograft.
Methods: Combining two comprehensive search themes (AMR and RTX), we searched electronic databases from 1969 through 2010, supplemented by a manual review of abstracts from nephrology and transplant meetings, and reference lists of review articles. All studies evaluating explicit response of patients with AMR to RTX were included. The outcome was pooled odds ratio (OR) of response to RTX.
Results: A total of 114 studies were identified, 94 of which were excluded on initial screening. Analysis of the 10 studies (249 patients) showed an OR of 3.16 (95% CI: 1.75–5.70) for response to RTX. Reported adverse effects included BK virus nephropathy, cytomegalovirus (CMV) viremia, pneumonia, herpes zoster, and septic shock.
Conclusion: This study suggests that RTX is a reasonable therapeutic option in the treatment of AMR. Further randomized studies are necessary to establish its efficacy and safety.
"
Background: The standard treatment of antibody-mediated rejection (AMR) consists of antilymphocyte antibody, intravenous immunoglobulin, and plasmapheresis. This treatment is associated with a high rate of resistance and refractory AMR. Recent interest has focused on use of rituximab (RTX), a chimeric anti-CD20 monoclonal antibody.
Objective: We conducted a systematic review and meta-analysis of studies of RTX in AMR of the renal allograft.
Methods: Combining two comprehensive search themes (AMR and RTX), we searched electronic databases from 1969 through 2010, supplemented by a manual review of abstracts from nephrology and transplant meetings, and reference lists of review articles. All studies evaluating explicit response of patients with AMR to RTX were included. The outcome was pooled odds ratio (OR) of response to RTX.
Results: A total of 114 studies were identified, 94 of which were excluded on initial screening. Analysis of the 10 studies (249 patients) showed an OR of 3.16 (95% CI: 1.75–5.70) for response to RTX. Reported adverse effects included BK virus nephropathy, cytomegalovirus (CMV) viremia, pneumonia, herpes zoster, and septic shock.
Conclusion: This study suggests that RTX is a reasonable therapeutic option in the treatment of AMR. Further randomized studies are necessary to establish its efficacy and safety.
"
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