De novo Thrombotic Microangiopathy in Renal Allograft Biopsies-Role of Antibody-Mediated Rejection

Thrombotic microangiopathy (TMA) is an uncommon, life-threatening complication that adversely affects kidney transplant recipient and allograft survival. Post-transplantation TMA can occur as recurrence of the primary TMA or as a de novo condition. The latter can be triggered by numerous factors post-transplantation including calcineurin inhibitors, certain infections and antibody-mediated rejection. Rejection-associated TMAs carry a significantly lower graft survival rate compared with post-transplant TMAs that are not associated with rejection. In this case report, we present a rare case of rejection-associated TMA in a recently transplanted renal allograft that was managed in Al-Hada Armed Forces Hospital. Despite the poor expected outcome of this condition; the patient was successfully treated after early initiation of medical interventions. Transplantation teams may face many challenges managing such a combination of medical conditions, which may halt pursuing appropriate diagnostic and therapeutic measures in a timely fashion. This article highlights some of these challenges for better understanding of such a complex condition.

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P1654INCIDENCE AND RISK FACTORS OF THROMBOTIC MICROANGIOPATHY AFTER KIDNEY TRANSPLANTATION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1654 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Kenta Futamura ◽

Goto Norihiko ◽

Hiroki Fukuhara ◽

Takaaki Nawano ◽

Akiko Kanda ◽

...

Keyword(s):

Risk Factors ◽

Kidney Transplantation ◽

Graft Survival ◽

Thrombotic Microangiopathy ◽

De Novo ◽

Pathological Findings ◽

Post Transplant ◽

Antibody Mediated Rejection ◽

Abo Incompatibility ◽

Biopsy Specimens

Abstract Background and Aims Thrombotic microangiopathy (TMA) is characterized by mechanical hemolytic anemia, thrombocytopenia, and renal impairment. TMA that occurs in kidney transplant recipients has multiple etiologies and may be de novo or recurrent. Main causes of TMA among recipients are atypical hemolytic uremic syndrome (aHUS), immunosuppressive drugs, ischemia-reperfusion injury (IRI), viral infections, and antibody-mediated rejection (ABMR). Pathological findings of TMA with thrombosis in glomeruli and arterioles are not rare in graft biopsies, but the clinical signs vary widely by etiologies, and incidence and risk factors for each are uncertain. The purpose of this study is to clarify the current status of TMA after kidney transplantation. Method The subjects were 1,336 patients (5,425 biopsy specimens) who underwent kidney transplantation (851 ABO-compatible and 485 ABO-incompatible) at Japanese Red Cross Nagoya Daini Hospital and Masuko Memorial Hospital from January 1, 2000 to June 30, 2018. We investigated patient characteristics and graft survival in 69 patients with pathological findings of TMA (12 with symptomatic TMA and 57 with asymptomatic TMA) and 1,207 patients without findings of TMA. Sixty patients were excluded because of incomplete data or biopsy specimens. TMA patients with acute kidney injury (AKI) were defined as symptomatic TMA in this study. Results The incidence of post-transplant TMA was 5.2% (symptomatic TMA : 0.9%, asymptomatic TMA : 4.3%) in our cohort. Multivariate analysis revealed significant risk factors for TMA were presence of donor specific antibodies (DSA) and use of cyclosporine (odds ratio [OR] 3.52; 95% confidence interval [CI] 1.58-7.88; p=0.002 and OR 3.70; 95% CI 1.68-8.11; p=0.001, respectively). Causes of symptomatic TMA were ABMR : 66.7% (5 patients with ABO-incompatibility, 3 with preformed DSA), aHUS : 16.7%, cytomegalovirus and adenovirus infection : 8.3%, and causes of asymptomatic TMA were drug-induced: 40.4% (21 patients with calcineurin inhibitor, 2 with everolimus), ABMR: 31.6% (10 with ABO-incompatibility, 8 with de novo DSA), IRI : 14.0 %. Onset of post-transplant TMA was significantly associated with lower graft survival (Figure A), with a stronger correlation in symptomatic TMA than in asymptomatic TMA (Figure B and C). Conclusion TMA with AKI that occurred after kidney transplantation had a poor graft prognosis. Therefore, avoiding transplantation, changing donors or using tacrolimus instead of cyclosporine should be considered for patients with DSA or ABO-incompatibility.

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The Role of Donor-Derived Cell-Free DNA in the Identification of Injury in Kidney Allografts with Antibody-Mediated Rejection or De Novo DSA

Transplantation Journal ◽

10.1097/01.tp.0000542540.14037.ad ◽

2018 ◽

Vol 102 ◽

pp. S5-S6

Author(s):

Huanxi Zhang ◽

Longshan Liu ◽

Chunting Zheng ◽

Xirui Li ◽

Qian Fu ◽

...

Keyword(s):

De Novo ◽

Cell Free Dna ◽

Antibody Mediated Rejection ◽

Free Dna

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From Humoral Rejection to Generalized Thrombotic Microangiopathy?Role of Acquired ADAMTS13 Deficiency in a Renal Allograft Recipient

American Journal of Transplantation ◽

10.1111/j.1600-6143.2006.01574.x ◽

2006 ◽

Vol 6 (12) ◽

pp. 3030-3036 ◽

Cited By ~ 12

Author(s):

T. Ulinski ◽

A. Charpentier ◽

M. Colombat ◽

C. Desconclois ◽

G. Deschênes ◽

...

Keyword(s):

Thrombotic Microangiopathy ◽

Renal Allograft ◽

Renal Allograft Recipient ◽

Humoral Rejection ◽

Adamts13 Deficiency

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Thrombotic Microangiopathy After Kidney Transplantation: An Underdiagnosed and Potentially Reversible Entity

Frontiers in Medicine ◽

10.3389/fmed.2021.642864 ◽

2021 ◽

Vol 8 ◽

Author(s):

Ana Ávila ◽

Eva Gavela ◽

Asunción Sancho

Keyword(s):

Renal Failure ◽

Thrombotic Microangiopathy ◽

De Novo ◽

Organ Procurement ◽

Ischemia Reperfusion ◽

Atypical Hemolytic Uremic Syndrome ◽

Antiphospholipid Antibody ◽

Antiphospholipid Antibody Syndrome ◽

Post Transplant ◽

Antibody Mediated Rejection

Thrombotic microangiopathy is a rare but serious complication that affects kidney transplant recipients. It appears in 0.8–14% of transplanted patients and negatively affects graft and patient survival. It can appear in a systemic form, with hemolytic microangiopathic anemia, thrombocytopenia, and renal failure, or in a localized form, with progressive renal failure, proteinuria, or arterial hypertension. Post-transplant thrombotic microangiopathy is classified as recurrent atypical hemolytic uremic syndrome or de novo thrombotic microangiopathy. De novo thrombotic microangiopathy accounts for the majority of cases. Distinguishing between the 2 conditions can be difficult, given there is an overlap between them. Complement overactivation is the cornerstone of all post-transplant thrombotic microangiopathies, and has been demonstrated in the context of organ procurement, ischemia-reperfusion phenomena, immunosuppressive drugs, antibody-mediated rejection, viral infections, and post-transplant relapse of antiphospholipid antibody syndrome. Although treatment of the causative agents is usually the first line of treatment, this approach might not be sufficient. Plasma exchange typically resolves hematologic abnormalities but does not improve renal function. Complement blockade with eculizumab has been shown to be an effective therapy in post-transplant thrombotic microangiopathy, but it is necessary to define which patients can benefit from this therapy and when and how eculizumab should be used.

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Role of de novo DQ donor-specific antibody in antibody-mediated rejection in renal transplant recipient: A case study

Asian Journal of Transfusion Science ◽

10.4103/ajts.ajts_1_18 ◽

2019 ◽

Vol 13 (2) ◽

pp. 136

Author(s):

Mohit Chowdhry ◽

Manthan Patel ◽

Yogita Thakur ◽

Vandana Sharma

Keyword(s):

Renal Transplant ◽

Transplant Recipient ◽

Renal Transplant Recipient ◽

Specific Antibody ◽

De Novo ◽

Antibody Mediated Rejection

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Renal Thrombotic Microangiopathy Associated with Anticardiolipin Antibodies in Hepatitis C-Positive Renal Allograft Recipients

Journal of the American Society of Nephrology ◽

10.1681/asn.v101146 ◽

1999 ◽

Vol 10 (1) ◽

pp. 146-153

Author(s):

SEEMA BAID ◽

MANUEL PASCUAL ◽

WINFRED W. WILLIAMS ◽

NINA TOLKOFF-RUBIN ◽

STEPHEN M. JOHNSON ◽

...

Keyword(s):

Hepatitis C ◽

Thrombotic Microangiopathy ◽

Renal Allograft ◽

De Novo ◽

Anticardiolipin Antibodies ◽

Hcv Infection ◽

Enzyme Linked Immunosorbent Assay ◽

Control Group ◽

Positive Serology ◽

Pathologic Features

Abstract. Hepatitis C virus (HCV) infection has been associated with de novo or recurrent membranoproliferative glomerulonephritis and acute transplant glomerulopathy in transplanted kidneys. Recently, anticardiolipin antibodies (ACA) have been linked with chronic HCV infection. A few reports have suggested an association between ACA and renal allograft thrombosis. This study examines the clinical and pathologic features of HCV-positive renal allograft recipients at our institution. From 1990 to 1996, 379 kidney transplants were performed. We identified 18 recipients (4.8%) with HCV-positive serology pretransplant. Determination of IgG and IgM ACA was performed by enzyme-linked immunosorbent assay, using pretransplant sera. Among the 18 patients, five patients presented with biopsy-proven de novo renal thrombotic microangiopathy (RTMA), occurring 5 to 120 d (median, 14 d) after transplant. No differences in pretransplant characteristics were observed between patients with (n = 5) or without (n = 13) RTMA. All five patients had a positive ACA test (either IgG or IgM titer > 2 SD above normal), compared with only one of 13 patients without RTMA. The mean value for IgG ACA was significantly higher in the RTMA patients than in patients without RTMA (22.9 ± 14.1 versus 6.9 ± 4.9 IgG phospholipid units, P = 0.02); however, there were no significant differences in IgM ACA titers. Rheumatoid factor and complement C4 levels were normal in pretransplant sera of patients with RTMA. Patients with RTMA had their cyclosporine withdrawn (four of five) or the dose was decreased (one of five), and one of five underwent plasmapheresis. Four of five patients died within 5 yr after transplant, compared with no deaths in the other 13 patients. Finally, as a control group, seven HCV-negative renal allograft recipients who presented with RTMA/hemolytic uremic syndrome during the same time period were found to have normal ACA values (IgG or IgM). RTMA associated with ACA in HCV-positive renal allograft recipients may represent a new clinical entity. The occurrence of this syndrome may have deleterious consequences for patient and graft survival.

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