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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
LETTER TO THE EDITOR  
Year : 2019  |  Volume : 30  |  Issue : 1  |  Page : 270-272
Cincinnati protocol is not suitable for Indian patients with antibody mediated renal allograft rejection


1 Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Pathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Renal Transplant Surgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India

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Date of Submission04-Jun-2018
Date of Acceptance04-Jul-2018
Date of Web Publication26-Feb-2019
 

How to cite this article:
Sethi J, Ramachandran R, Kumar V, Rathi M, Kohli H S, Nada R, Sharma A, Gupta KL. Cincinnati protocol is not suitable for Indian patients with antibody mediated renal allograft rejection. Saudi J Kidney Dis Transpl 2019;30:270-2

How to cite this URL:
Sethi J, Ramachandran R, Kumar V, Rathi M, Kohli H S, Nada R, Sharma A, Gupta KL. Cincinnati protocol is not suitable for Indian patients with antibody mediated renal allograft rejection. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Mar 26];30:270-2. Available from: http://www.sjkdt.org/text.asp?2019/30/1/270/252927


To the Editor,

We present our experience of treating acute antibody-mediated rejection (ABMR) with a combination of proteosome inhibitor (bortezomib), plasmapheresis, and rituximab (cincinnati protocol).[1] The results were disappointing with serious infections and allograft loss in the majority of our patients. We recorded patient and graft survival of 80% and 20%, respectively, at six months following therapy. A reasonable explanation for inferior graft survival in our patients could be attributed to the life-threatening infections which prompted to the withdrawal of maintenance immunosuppression and advanced renal dysfunction at diagnosis.

We used the combination therapy of rituximab, bortezomib, plasmapheresis in five patients of ABMR [Table 1]. Therapy consisted of a combination of bortezomib, rituximab, and plasmapheresis. Plasmapheresis (1.5 plasma volumes) was performed on day 1, 4,8, and 11 with albumin replacement, bortezomib was given at a dose of 1.3 mg/m2 intravenous (i.v.) after each plasmapheresis session and rituximab (375 mg/m2) was given i.v. on day 1. Starting in 2015, we treated five consecutive patients with ABMR according to the Banff criteria[2] with this protocol and followed these patients for two years. Mean age was 33 years (range 24–43), median serum creatinine at the time of diagnosis of ABMR was 3 mg/dL (range 1.6–3.4) and ABMR was diagnosed at a median of 36 months (3–72) posttransplant. All the five patients had C4d positive ABMR. However, donor-specific antibody (DSA) could not be done in our patients due to logistic issues. Four out of five patients (80%) treated with anti-rejection therapy developed serious life-threatening infections within six months of therapy for which maintenance immunosuppression had to be stopped and one out of five patients expired (20%). The first patient was admitted three months post rejection therapy with cytomegalovirus (CMV) and acinetobacter pneumonia and succumbed to her illness. The second patient presented with disseminated CMV and pneumocystis pneumonia one month posttherapy. Third patient developed pulmonary nocardiosis, whereas the 4th patient developed disseminated mucormycosis (pulmonary, naso-orbital). Fifth patient had a functioning graft 24 months after treatment. First four patients with infections posttherapy returned to chronic dialysis therapy within six months after diagnosis of ABMR. Drawbacks of our study included the lack of a control group and unavailability of DSA in our patients.
Table 1: Clinical profile and posttherapy complications in patients treated with Cincinnati protocol.

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Walsh et al[1] presented their initial experience with proteasome inhibitor-based combination therapy and showed a successful reversal of ABMR and elimination of DSA in both the patients. Waiser et al[3] compared combination therapy of rituximab, bortezomib, plasmapheresis, and high-dose IV immunoglobulins (IVIG) in 10 patients with identical regimen without rituximab in 11 patients. They showed similar graft survival in both arms. However, 70% of patients receiving combination therapy developed infections. Our results were consistent with Waiser et al who also showed an increased risk of infections with combination therapy.[3] Based on our experience, we later adopted IVIG and plasmapheresis-based therapy for primary ABMR and stopped using combination based therapy. To conclude, combination based therapy for ABMR is not suitable for our patients due to serious life-threatening infections and more research is needed to better preserve graft function without increasing the risk of infections in our patient population.

Conflict of interest:

None declared.



 
   References Top

1.
Walsh RC, Everly JJ, Brailey P, et al. Proteasome inhibitor-based primary therapy for antibody-mediated renal allograft rejection. Transplantation 2010;89:277-84.  Back to cited text no. 1
    
2.
Haas M. The revised (2013) Banff classification for antibody-mediated rejection of renal allografts: Update, difficulties, and future considerations. Am J Transplant 2016;16: 1352-7.  Back to cited text no. 2
    
3.
Waiser J, Duerr M, Schönemann C, et al. Rituximab in combination with bortezomib, plasmapheresis, and high-dose IVIG to treat antibody-mediated renal allograft rejection. Transplant Direct 2016;2:e91.  Back to cited text no. 3
    

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Correspondence Address:
Krishan Lal Gupta
Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh
India
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PMID: 30804297

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