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Year : 2019  |  Volume : 13  |  Issue : 3  |  Page : 225-227

Successful treatment of isolated vascular arteritis in renal allograft recipients: A treatable new histological entity

1 Department of Nephrology, Gandhi Medical College, Hyderabad, Telangana, India
2 Department of Pathology, Nizams Institute of Medical Sciences, Hyderabad, Telangana, India

Date of Submission27-Dec-2018
Date of Decision01-Feb-2019
Date of Acceptance01-Mar-2019
Date of Web Publication17-Sep-2019

Correspondence Address:
Dr. Manjusha Yadla
Department of Nephrology, Gandhi Medical College, Hyderabad, Telangana
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijot.ijot_86_18

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C4d-negative isolated endarteritis is an entity yet to be recognized as an independent entity in Banff Classification. Pathogenesis and treatment of this entity are not well understood. Although it was identified as an entity similar to T-cell rejection based on the response to T-cell depletion therapies in a large retrospective study, this observation is yet to be supported in molecular experimental studies.

Keywords: C4d negative, isolated endarteritis, plasmapheresis

How to cite this article:
Pradeep K, Yadla M, Harke M. Successful treatment of isolated vascular arteritis in renal allograft recipients: A treatable new histological entity. Indian J Transplant 2019;13:225-7

How to cite this URL:
Pradeep K, Yadla M, Harke M. Successful treatment of isolated vascular arteritis in renal allograft recipients: A treatable new histological entity. Indian J Transplant [serial online] 2019 [cited 2020 Jul 5];13:225-7. Available from: http://www.ijtonline.in/text.asp?2019/13/3/225/266956

  Introduction Top

Banff Revised Classification has added certain salient features to make a diagnosis of renal allograft pathology much easier. Despite better understanding in pathogenesis, a better evaluation and correlation of histopathology findings, and thereby, an appropriate management strategy may be done. With the increasing number of renal transplantations worldwide and increasing renal transplant histopathology centers, there is a continuous addition of certain findings toward better understanding of graft dysfunction and thus the development of newer treatment modalities.

Isolated endarteritis is an inflammation of endothelium without evidence of inflammation in other histology compartments of renal graft. Although case reports of isolated arteritis exist since 2007, Banff guidelines-2011 redefined isolated V1 lesions as mild–moderate arteritis with mild interstitial inflammation and mild tubulitis.

Isolated endarteritis can coexist with minimal tubulitis and parenchymal inflammation. Whether to treat these isolated V1 lesions has been controversial. It remains unanswered whether this entity should be treated as antibody-mediated acute vascular rejection or a T-cell-mediated rejection. Herein, we report C4d-negative isolated arteritis in two patients treated with plasmapheresis, intravenous immunoglobulins with a good 1-year graft survival.

  Case Report Top

Isolated endarteritis is an entity which if identified early and managed appropriately would lead to successful outcomes. Herein, we report two patients who underwent deceased donor transplantation, had delayed graft function and had isolated endarteritis on graftbiospy. This was treated with Plasmapheresis, high dose IV immunoglobulins [Table 1].
Table 1: Case details

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  Discussion Top

Isolated endarteritis without significant interstitial inflammation is an entity which needs to be yet understood. Various factors were described to be associated with isolated endarterites such as preexisting donor-specific antibodies, glomerulitis, transplant glomerulopathy, and C4d positivity, thus linking the pathogenesis similar to acute antibody-mediated rejection.[1],[2] Few studies have shown that isolated endarteritis is not T-cell mediated based on minimal T-cell activity markers in renal allograft.[3],[4],[5],[6] Studies reported variable outcomes of this lesion that the lesion may be benign or may be associated with severe tubulointerstitial inflammation. Because of lack of understanding in the pathogenesis, there are no definitive treatment strategies described for successful management of these patients. Whether plasmapheresis, intravenous immunoglobulins, and anti-T-cell therapies are beneficial is not known.

Natural history or the course of isolated endarteritis is not completely studied. Variable outcomes have been reported in different studies with favourable prognosis in the study done by Wu et al[7] and outcomes similar to vascular rejection in the study done by Shimizu et al.[8]

In a multicenter collaborative study by Sis et al.[1] in 307 kidney transplant patients with C4d-negative isolated endarteritis, three groups of isolated endarteritis, positive control with T-cell-mediated rejection, negative control of normal graft biopsy with outcomes were studied. In this study, treatment with corticosteroids with or without T-cell depletion therapies showed a significant benefit on short-term and long-term graft outcome. A comparable outcome was noted in both the groups with functional improvement in 80% of isolated endarteritis and 81% in T-cell rejection group. It was also observed that treatment in cases of isolated endarteritis with T-cell depletion therapies was more frequent than in those with T-cell-mediated rejection. Hence, in this study, it was concluded that isolated endarteritis represents a form of T-cell-mediated rejection. Response to treatment was not seen in 20% of the population who progressed to graft loss. This may suggest that isolated endarteritis may be treated in similar lines as T-cell rejection though molecular pathogenesis of presence of minimal T-cell inflammatory cytokines and signatures did not support the T-cell mediation of rejection process.
Figure 1: Biopsy of first patient - third graft biopsy showing features of arteritis

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Figure 2: Biopsy image of second patient showing arteritis

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In our patients, both of whom were hepatitis C positive, were treated, and were in remission by the time of transplantation had delayed graft function. In patient 1, though the initial biopsies favored acute tubular necrosis and mild interstitial inflammation, the presence of vascular inflammation was found only in the third biopsy. Till the time of the third biopsy, the patient was given corticosteroids and a single dose of T-cell depletion therapies. Subsequent dose of T-cell depletion therapy was not given in view of side effects. With the presence of vascular inflammation, although C4d was negative, plasmapheresis along with high-dose intravenous immunoglobulins was given. Urine output improved after the fourth session of plasmapheresis.

However, in the second patient, only one graft biopsy was done, which revealed isolated vascular endarteritis. This patient was given plasmapheresis along with high-dose immunoglobulins. No T-cell therapies were given in this patient. Both the patients received 3–5 sessions of plasmapheresis and 5–7 doses of high-dose immunoglobulin (1 g/kg). This patient showed a good graft function and was discharged with normal serum creatinine. One-year follow-up of these patients shows a good graft survival.

  Conclusion Top

Isolated endarteritis is a distinct entity to be recognized. This entity is yet to be understood. Although the retrospective study showed a significant benefit with T-cell depletion therapies, in both our patients, minimal or no T-cell depletion therapies were given. An improvement in graft recovery with plasmapheresis and intravenous immunoglobulins was observed. Hence, instead of managing isolated endarteritis with anti-T-cell depletion therapies alone, corticosteroids, plasmapheresis, and intravenous immunoglobulins should be given to salvage the graft. This observation needs to be confirmed in larger studies.

Points of interest

  1. Isolated endarteritis needs to be recognized as a distinct entity causing graft dysfunction
  2. Early identification and apt treatment with corticosteroids, plasmapheresis, and immunoglobulins may give successful outcomes instead of relying on T-cell depletion therapies.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Sis B, Bagnasco SM, Cornell LD, Randhawa P, Haas M, Lategan B, et al. Isolated endarteritis and kidney transplant survival: A multicenter collaborative study. J Am Soc Nephrol 2015;26:1216-27.  Back to cited text no. 1
Haas M, Sis B, Racusen LC, Solez K, Glotz D, Colvin RB, et al. Banff 2013 meeting report: Inclusion of C4d-negative antibody-mediated rejection and antibody-associated arterial lesions. Am J Transplant 2014;14:272-83.  Back to cited text no. 2
Mueller TF, Einecke G, Reeve J, Sis B, Mengel M, Jhangri GS, et al. Microarray analysis of rejection in human kidney transplants using pathogenesis-based transcript sets. Am J Transplant 2007;7:2712-22.  Back to cited text no. 3
Reeve J, Sellarés J, Mengel M, Sis B, Skene A, Hidalgo L, et al. Molecular diagnosis of T cell-mediated rejection in human kidney transplant biopsies. Am J Transplant 2013;13:645-55.  Back to cited text no. 4
Halloran PF, Pereira AB, Chang J, Matas A, Picton M, De Freitas D, et al. Potential impact of microarray diagnosis of T cell-mediated rejection in kidney transplants: The INTERCOM study. Am J Transplant 2013;13:2352-63.  Back to cited text no. 5
Salazar ID, Merino López M, Chang J, Halloran PF. Reassessing the significance of intimal arteritis in kidney transplant biopsy specimens. J Am Soc Nephrol 2015;26:3190-8.  Back to cited text no. 6
Wu KY, Budde K, Schmidt D, Neumayer HH, Rudolph B. Acute cellular rejection with isolated v-lesions is not associated with more favorable outcomes than vascular rejection with more tubulointerstitial inflammations. Clin Transplant 2014;28:410-8.  Back to cited text no. 7
Shimizu T, Tanabe T, Shirakawa H, Omoto K, Ishida H, Tanabe K, et al. Acute vascular rejection after renal transplantation and isolated v-lesion. Clin Transplant 2012;26 Suppl 24:2-8.  Back to cited text no. 8


  [Figure 1], [Figure 2]

  [Table 1]


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