De Novo Thrombotic Microangiopathy After Kidney Transplantation: Clinical Features, Treatment, and Long-Term Patient and Graft Survival

Caires, Renato Antunes; Marques, Inara; Repizo, Liliany Pinhel; Sato, Victor Augusto Hamamoto; Carmo, Lilian P. F.; Machado, David; Paula, Flávio Jota de; Nahas, William Carlos; David‐Neto, Elias

doi:10.1016/j.transproceed.2012.07.039

Cited by 48 publications

(44 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…6,7,10,[17][18][19] The reported rates of de novo TMA vary from 1.1% to 14%. [4][5][6][7][8][9][10][11][12][13][14][15] As we observed, the incidence of Escherichia coliassociated typical hemolytic uremic syndrome is significantly low in renal transplant patients. 3,7 Renal transplant patients with TMA usually do not have systemic signs of hemolytic uremic syndrome.…”

Section: Discussionmentioning

confidence: 97%

“…2,7,10 De novo TMA often occurs in the early posttransplant period (first 6 months), but it may also develop later. 8,10,17 It has been well documented that chronic administration of cyclosporine or tacrolimus is associated with microvascular disease, with calcineurin inhibitor toxicity reported to be the most common cause of posttransplant de novo TMA. 5,7,10,12 A recent experimental study showed that cyclosporine induces increased endothelial release of complement-activating microparticles, suggesting that blocking complement activation may help to alleviate the condition.…”

Section: Discussionmentioning

confidence: 99%

“…1,2,7 The histopathologic features of TMA in the transplanted kidney include occlusion or narrowing of the capillaries, subendothelial amorphous material accumulation in glomeruli, and fibrinoid changes in the intima of small arteries. 2,4,8 The risk for development of TMA is highest in the first 3 months after transplant, and presence of de novo TMA is much less common than recurrent hemolytic uremic syndrome. [1][2][3]7,9,10 Because of its distinct characteristics and clinical courses, it has been suggested to classify posttransplant TMA into localized and systemic forms.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3][4][5][6]7,10,15 Glomerular and arteriolar thrombi in renal transplant biopsies with the diagnosis of AMR and chronic antibodymediated rejection are frequently reported, whereas reports of presence of peritubular capillary (PTC) thrombi are scarce. 2,6,8,15,16 This study examined the incidence of renal TMA in patients with acute humoral rejection (AHR), chronic active humoral rejection (CAHR), polyomavirus nephropathy (PVN), acute cellular rejection (ACR), and immunoglobulin A (IgA) recurrence.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Untitled

Özdemir

Atılgan²,

Akçay³

et al. 2018

Exp Clin Transplant

View full text Add to dashboard Cite

Objectives: Thrombotic microangiopathy is a form of renal capillary injury possibly associated with calcineurin inhibitor toxicity, acute humoral rejection, infections, and recurrent diseases. Here, we examined its incidence in patients diagnosed with acute and chronic active humoral rejection, polyomavirus nephropathy, acute cellular rejection, and immunoglobulin A recurrence. Materials and Methods: In total, 272 renal allograft recipients who met the inclusion criteria were reevaluated for presence of renal thrombotic microangiopathy. Thrombotic microangiopathy diagnosis was established by clinical, laboratory, and histologic features. C4d expression in peritubular capillaries was determined. Clinical data were collected from medical records. Results: Of 272 patients (mean age of 42.8 ± 12.7 years), only 74 patients (27.2%) had de novo thrombotic microangiopathy, which was found in 30/90 patients (33.3%) with acute humoral rejection, 9/51 (17.6%) with acute cellular rejection, 22/53 (41.5%) with chronic active humoral rejection, 10/55 (18.2%) with polyomavirus nephropathy, and 3/23 (13%) with immunoglobulin A nephropathy. Significant differences were shown between therapy type and thrombotic microangiopathy development (P = .02). Patients who received cyclosporine (38.5%) tended to show higher incidence of thrombotic microangiopathy than patients who received tacrolimus (20.7%) or sirolimus (7.7%). Patients with C4d-positive acute humoral (97.6% vs 2.4%) and chronic active humoral rejection (68.2% vs 31.8%) had greater incidence of thrombotic microangiopathy versus those who were C4d-negative. Graft loss was significantly higher in C4d-positive than in C4d-negative thrombotic microangiopathy groups (P < .001). Overall 1-, 3-, and 5-year graft survival was 94%, 85%, and 85% versus 83%, 51%, and 51% in thrombotic microangiopathy-negative versus thrombotic microangiopathy-positive patients (P < .001). Conclusions: Acute humoral rejection and chronic active humoral rejection were the most common and therefore most important causes of de novo thrombotic microangiopathy in renal transplant patients. Its presence in the renal allograft biopsy should arouse suspicion for underlying acute or chronic active humoral rejection. Key words: Acute cellular rejection, Acute humoral rejection, C4d expression, Chronic active humoral rejection, IgA nephropathy, Polyomavirus nephropathy, Renal allograft biopsy IntroductionThrombotic microangiopathy (TMA) describes a pathologic lesion in which abnormalities in the vessel wall of arterioles and capillaries lead to microvascular thrombosis. The clinical features of TMA result from the obstruction of the microcirculation and ultimately depend on the distribution of involved vascular beds. Microangiopathic hemolysis is the hallmark feature of this obstructed microcirculation. Thrombotic microangiopathy is a pathologic diagnosis, but its presence is commonly inferred from observations of thrombocytopenia and microangiopathic hemolysis in the appropriate clinical setting. [1][2]...

show abstract

Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Untitled

Özdemir

Atılgan²,

Akçay³

et al. 2018

Exp Clin Transplant

View full text Add to dashboard Cite

show abstract

“…24 These infections are considered as causes of HUS not just triggers for the disease, although the distinction between cause and trigger is not evident. In addition to infections, secondary HUS may be associated with transplantation (solid organ or bone marrow), [25][26][27][28] autoimmune disease, 29,30 cancer, 31,32 pregnancy, 33 and the use of certain cytotoxic drugs. 34,35 The common feature for these coexisting diseases or conditions is that they may cause direct cell damage, promote activation of the complement system in general, or enhance activation of complement on self cells (Figure 1).…”

Section: Secondary Husmentioning

confidence: 99%

HUS and atypical HUS

Jokiranta

2017

Blood

232

260

View full text Add to dashboard Cite

Hemolytic uremic syndrome (HUS) is a thrombotic microangiopathy characterized by intravascular hemolysis, thrombocytopenia, and acute kidney failure. HUS is usually categorized as typical, caused by Shiga toxin–producing Escherichia coli (STEC) infection, as atypical HUS (aHUS), usually caused by uncontrolled complement activation, or as secondary HUS with a coexisting disease. In recent years, a general understanding of the pathogenetic mechanisms driving HUS has increased. Typical HUS (ie, STEC-HUS) follows a gastrointestinal infection with STEC, whereas aHUS is associated primarily with mutations or autoantibodies leading to dysregulated complement activation. Among the 30% to 50% of patients with HUS who have no detectable complement defect, some have either impaired diacylglycerol kinase ε (DGKε) activity, cobalamin C deficiency, or plasminogen deficiency. Some have secondary HUS with a coexisting disease or trigger such as autoimmunity, transplantation, cancer, infection, certain cytotoxic drugs, or pregnancy. The common pathogenetic features in STEC-HUS, aHUS, and secondary HUS are simultaneous damage to endothelial cells, intravascular hemolysis, and activation of platelets leading to a procoagulative state, formation of microthrombi, and tissue damage. In this review, the differences and similarities in the pathogenesis of STEC-HUS, aHUS, and secondary HUS are discussed. Common for the pathogenesis seems to be the vicious cycle of complement activation, endothelial cell damage, platelet activation, and thrombosis. This process can be stopped by therapeutic complement inhibition in most patients with aHUS, but usually not those with a DGKε mutation, and some patients with STEC-HUS or secondary HUS. Therefore, understanding the pathogenesis of the different forms of HUS may prove helpful in clinical practice.

show abstract

Cytopenias in Transplant Patients

Chandra

Hymes

2019

Principles and Practice of Transplant Infectious Diseases

View full text Add to dashboard Cite

Anemia is commonly seen after solid organ transplant (SOT). It can result from a number of different etiologies including bleeding or hemorrhage, iron deficiency, hemolysis, drug related, lack of erythropoietin, marrow suppression, and congenital etiologies. The frequency and severity of anemia is dependent on the type of solid organ transplant and the duration of time that has passed since the transplant. Much of the data for the causes of anemia following SOT is from renal transplant and cardiac transplant populations. In these renal transplant patients, the prevalence of anemia is about 40% 1-year posttransplant. Severe anemia, defined as Hb <11 g/dL in males and 10 g/dL in females, is seen in 8.5% of patients 6-60 months post-kidney transplant [1]. Anemia to a hematocrit of less than 33% can persist for greater than 5 years in 25% patients and can result in worsened renal graft function and graft loss [2, 3]. Pre-transplant anemia often seen in dialysis can often improve posttransplant, but then may recur if there is graft failure. About 40% of cardiac transplant patients also experience posttransplant anemia [4]. Pre-transplant anemia that is seen in 25% of this population negatively affects 1-year survival posttransplant [5].

show abstract

De Novo Thrombotic Microangiopathy After Kidney Transplantation: Clinical Features, Treatment, and Long-Term Patient and Graft Survival

Cited by 48 publications

References 7 publications

Untitled

Untitled

HUS and atypical HUS

Cytopenias in Transplant Patients

Contact Info

Product

Resources

About