Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year

AJT - Early Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year

This study examined outcomes beyond 1 year in eculizumab-treated (EC) positive crossmatch kidney transplants (+XMKTx) compared to a historical control group. +XMKTx received desensitization with either plasma exchange (PE) alone (N = 48) or PE and EC (N = 30). EC, given for at least 1 month, was continued in the setting of persistently high DSA (B flow cytometric crossmatch [BFXM] >200) including: 4 weeks (n = 14); 9 weeks (n = 6), 6 months (n = 2), and 12 months (n = 8). All patients had at least 2 years follow-up. The incidence of acute clinical ABMR was lower in the EC group than controls (6.7% vs. 43.8% p < 0.01). Death-censored allograft survival was similar between groups. Chronic ABMR was the main cause of graft loss. On 1-year protocol biopsies, no differences were noted between EC and controls including: cg score >0, 26.7% versus 31.9% (p = 0.62), ptc score ≥ 2, 60.0% versus 60.0% (p = 1.00), or C4d + , 33.8% versus 13.5% (p = 0.08). A persistently high BFXM in EC-treated patients was associated with cg score >0 at 1 year, while EC appeared to protect against cg if the BFXM remained low. We conclude that despite decreasing acute clinical ABMR rates, EC treatment does not prevent chronic ABMR in recipients with persistently high BFXM after +XMKTx.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.13168

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Daclizumab Versus Rabbit Antithymocyte Globulin in High-Risk Renal Transplants: Five-Year Follow-up of a Randomized Study.

AJT Daclizumab Versus Rabbit Antithymocyte Globulin in High-Risk Renal Transplants: Five-Year Follow-up of a Randomized Study.

• Hellemans R, Hazzan M, Durand D, et al. 
• Daclizumab Versus Rabbit Antithymocyte Globulin in High-Risk Renal Transplants: Five-Year Follow-up of a Randomized Study. [JOURNAL ARTICLE]
• Am J Transplant 2015 Feb 23.

We previously reported a randomized controlled trial in which 227 de novo deceased-donor kidney transplant recipients were randomized to rabbit antithymocyte (rATG, Thymoglobulin) or daclizumab if they were considered to be at high immunological risk, defined as high panel reactive antibodies (PRA), loss of a first kidney graft through rejection within 2 years of transplantation, or third or fourth transplantation. Patients treated with rATG had lower incidences of biopsy-proven acute rejection (BPAR) and steroid-resistant rejection at 1 year. Patients were followed to 5 years posttransplant in an observational study; findings are described here. Treatment with rATG was associated with a lower rate of BPAR at 5 years (14.2% vs. 26.0% with daclizumab; p = 0.035). Only one rATG-treated patient (0.9%) and one daclizumab-treated patient (1.0%) developed BPAR after 1 year. Five-year graft and patient survival rates, and renal function, were similar between the two groups. Overall graft survival at 5 years was significantly higher in patients without BPAR (81.0% vs. 54.8%; p < 0.001). In conclusion, rATG is superior to daclizumab for the prevention of BPAR among high-immunological-risk renal transplant recipients. Overall graft survival at 5 years was approximately 70% with either induction therapy, which compares favorably to low-risk cohorts.

http://www.unboundmedicine.com/medline/citation/25707875/Daclizumab_Versus_Rabbit_Antithymocyte_Globulin_in_High_Risk_Renal_Transplants:_Five_Year_Follow_up_of_a_Randomized_Study_

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Rotavirus in Organ Transplantation: Drug-Virus-Host Interactions

AJT - Early Rotavirus in Organ Transplantation: Drug-Virus-Host Interactions

Although rotavirus is usually recognized as the most common etiology of diarrhea in young children, it can in fact cause severe diseases in organ transplantation recipients irrespective of pediatric or adult patients. This comprehensive literature analysis revealed 200 cases of rotavirus infection with 8 related deaths in the setting of organ transplantation been recorded. Based on published cohort studies, an average incidence of 3% (187 infections out of 6176 organ recipients) was estimated. Rotavirus infection often causes severe gastroenteritis complications and occasionally contributes to acute cellular rejection in these patients. Immunosuppressive agents, universally used after organ transplantation to prevent organ rejection, conceivably play an important role in such a severe pathogenesis. Interestingly, rotavirus can in turn affect the absorption and metabolism of particular immunosuppressive medications via several distinct mechanisms. Even though rotaviral enteritis is self-limiting in general, infected transplantation patients are usually treated with intensive care, rehydration and replacement of nutrition, as well as applying preventive strategies. This article aims to properly assess the clinical impact of rotavirus infection in the setting of organ transplantation and to disseminate the interactions among the virus, host and immunosuppressive medications.

http://onlinelibrary.wiley.com/resolve/doi?DOI=10.1111%2Fajt.13135

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Complement Inhibition in HLA-Incompatible Kidney Transplants: Persisting Antibody-Mediated Injury Despite Marked Decrease of Clinical ABMR.

AJT Complement Inhibition in HLA-Incompatible Kidney Transplants: Persisting Antibody-Mediated Injury Despite Marked Decrease of Clinical ABMR.

• Loupy A, Viglietti D, Mengel M 
• Complement Inhibition in HLA-Incompatible Kidney Transplants: Persisting Antibody-Mediated Injury Despite Marked Decrease of Clinical ABMR. [EDITORIAL]
• Am J Transplant 2015 Mar 2.

http://www.unboundmedicine.com/medline/citation/25731892/Complement_Inhibition_in_HLA_Incompatible_Kidney_Transplants:_Persisting_Antibody_Mediated_Injury_Despite_Marked_Decrease_of_Clinical_ABMR_

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year.

AJT Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year.

• Cornell LD, Schinstock CA, Gandhi MJ, et al. 
• Positive Crossmatch Kidney Transplant Recipients Treated With Eculizumab: Outcomes Beyond 1 Year. [JOURNAL ARTICLE]
• Am J Transplant 2015 Mar 2.

This study examined outcomes beyond 1 year in eculizumab-treated (EC) positive crossmatch kidney transplants (+XMKTx) compared to a historical control group. +XMKTx received desensitization with either plasma exchange (PE) alone (N = 48) or PE and EC (N = 30). EC, given for at least 1 month, was continued in the setting of persistently high DSA (B flow cytometric crossmatch [BFXM] >200) including: 4 weeks (n = 14); 9 weeks (n = 6), 6 months (n = 2), and 12 months (n = 8). All patients had at least 2 years follow-up. The incidence of acute clinical ABMR was lower in the EC group than controls (6.7% vs. 43.8% p < 0.01). Death-censored allograft survival was similar between groups. Chronic ABMR was the main cause of graft loss. On 1-year protocol biopsies, no differences were noted between EC and controls including: cg score >0, 26.7% versus 31.9% (p = 0.62), ptc score ≥ 2, 60.0% versus 60.0% (p = 1.00), or C4d + , 33.8% versus 13.5% (p = 0.08). A persistently high BFXM in EC-treated patients was associated with cg score >0 at 1 year, while EC appeared to protect against cg if the BFXM remained low. We conclude that despite decreasing acute clinical ABMR rates, EC treatment does not prevent chronic ABMR in recipients with persistently high BFXM after +XMKTx.

http://www.unboundmedicine.com/medline/citation/25731800/Positive_Crossmatch_Kidney_Transplant_Recipients_Treated_With_Eculizumab:_Outcomes_Beyond_1_Year_

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Alberto Reino Buelvas 

Médico Internista Nefrólogo

I'm sharing "A randomized trial of icatibant in ACE-inhibitor-induced angioedema."

New England Journal of Medicine 2015 Jan 29; 372 (5) : 418-25. A randomized trial of icatibant in ACE-inhibitor-induced angioedema. Murat Baş, Jens Greve, Klaus Stelter, Miriam Havel, Ulrich Strassen, Nicole Rotter, Johannes Veit, Beate Schossow, Alexander Hapfelmeier, Victoria Kehl, Georg Kojda, Thomas K Hoffmann PMID: 25629740

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Alberto Reino Buelvas