Incidence, Risk Factors for and Outcomes of Transplant‐Associated Thrombotic Microangiopathy (original) (raw)
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PLOS ONE
Introduction Thrombotic microangiopathy (TMA) in post-transplant setting has heterogeneous clinical manifestations. Methods We retrospectively studied data of 89 patients with post-transplant TMA, which was characterized by thrombi in at least one glomerulus and/or arteriole. Systemic TMA was defined by thrombocytopenia and microangiopathic anemia and early onset TMA, when occurred less than 90 days post transplant. Results The cumulative incidence was 0.93%. The majority of the recipients were young (mean age 39 years), female (52%) and Caucasian (48%) with primary kidney disease of unknown etiology (37%). Early TMA occurred in 51% of the patients and systemic TMA, in 25%. Underlying precipitating factors were: infection (54%), acute rejection (34%), calcineurin inhibitor toxicity (13%) and pregnancy (3%). 18% of the patients had several triggers. Glomerular TMA was observed in 50% of the biopsies and endothelial cell activation, in 61%. The 1year patient survival was 97% and corresponding graft survival, 66%. Allograft survival was inferior when acute antibody mediated rejection (ABMR) occurred (with 41%; without 70%, p = 0.01), however no differences were determined by hemolysis, time of onset, thrombi location or endothelial cell activation. Conclusions Our results suggest that post-transplant TMA is a rare but severe condition, regardless of its clinical and histological presentation, mainly when associated to ABMR.
Blood Advances
This study aimed to identify a risk profile for development of transplant-associated thrombotic microangiopathy (TA-TMA) in children undergoing hematopoietic stem cell transplantation (HSCT). Between 2013 and 2016, 439 children underwent 474 HSCTs at 2 supraregional United Kingdom centers. At a median of 153 days post-HSCT, TA-TMA occurred among 25 of 441 evaluable cases (5.6%) with no evidence of center variation. Sex, underlying disease, intensity of the conditioning, total body irradiation–based conditioning, the use of calcineurin inhibitors, venoocclusive disease, and viral reactivation did not influence the development of TA-TMA. Donor type: matched sibling donor/matched family donor vs matched unrelated donor vs mismatched unrelated donor/haplo-HSCT, showed a trend toward the development of TA-TMA in 1.8% vs 6.1% vs 8.3%, respectively. Presence of active comorbidity was associated with an increased risk for TA-TMA; 13% vs 3.7% in the absence of comorbidity. The risk of TA-TMA...
Dialysis modality and the risk of allograft thrombosis in adult renal transplant recipients
Kidney International, 1999
Allograft vascular thrombosis is a catastrophic complirenal transplant recipients. cation of kidney transplantation. Graft thrombosis is the Background. Renal vascular thrombosis (RVT) is a rare but most common in the early postoperative period, often catastrophic complication of renal transplantation. Although presenting as primary nonfunction or oligoanuric graft a plethora of risk factors has been identified, a large proportion dysfunction. Renal angiography or surgical exploration of cases of RVT is unexplained. Uremic coagulopathy and dialysis modality may predispose to RVT. We investigated the of the allograft bed [1, 2] establishes a definite diagnosis. impact of the pretransplant dialysis modality on the risk of There is no effective treatment, and in most cases, trans-RVT in adult renal transplant recipients. plant nephrectomy is required [2-5]. Graft loss caused Methods. Renal transplant recipients (age 18 years or more) by primary renal vascular thrombosis (RVT) affects 0.4 who were enrolled in the national registry between 1990 and to 7.0% of renal transplants, accounting for a significant 1996 (N ϭ 84,513) were evaluated for RVT occurring within proportion of early graft losses [2, 6-11]. 30 days of transplantation. Each case was matched with two controls from the same transplant center and with the year of In addition to the well-established systemic hypercoatransplantation. The association between RVT and 18 factors gulable states, other risk factors for RVT include techniwas studied with multivariate conditional logistic regression. cal problems during organ procurement and vascular Results. Forty-nine percent of all cases of RVT (365 out of anastomosis, acute rejection, extremes of donor age, 743) occurred in repeat transplant recipients with an adjusted perioperative hemodynamics, multiple donor renal arodds ratio (OR) of 5.72 compared with first transplants (P Ͻ 0.001). There were a significantly higher odds of RVT in perito-teries, primary cause of end-stage renal disease (ESRD), neal dialysis (PD)-compared with hemodialysis (HD)-treated pretransplant thrombocytosis, high hematocrit and use patients (OR ϭ 1.87, P ϭ 0.001). Change in dialysis modality of erythropoietin, and a history of prior renal transwas an independent predictor of RVT: switching from HD to plantation [2, 8, 11-18]. Several investigators have re-PD (OR ϭ 3.59, P Ͻ 0.001) and from PD to HD (OR ϭ 1.62, ported a threefold to fourfold increase in the incidence P ϭ 0.047). Compared with primary transplant recipients on of RVT in renal transplant recipients treated with HD (OR ϭ 1.00), the highest odds of RVT were in repeat transplant recipients treated with PD (OR ϭ 12.95, P Ͻ 0.001) cyclosporine (CsA) when compared with recipients who and HD (OR ϭ 4.50, P Ͻ 0.001). Other independent predictors received only azathioprine and prednisone [2, 9, 12, 19]. of RVT were preemptive transplantation, relatively young and More recently, attention has been drawn to antiphosphoold donor age, diabetes mellitus and systemic lupus erythemalipid antibody syndromes, factor V Leiden mutation, and tosus as causes of end-stage renal disease, recipient gender, hyperhomocysteinemia as possible causes of RVT [4, 6, and lower panel reactive antibody levels (PRAs). Conclusions. The strongest risk factors for RVT were re-20-24]. transplantation and prior PD treatment. Prevention of RVT Despite the plethora of risk factors, a significant prowith perioperative anticoagulation should be studied in paportion of RVT occurs in the absence of any established tients who have a constellation of the identified risk factors.
Amer J Kidney Dis, 2004
Background: Pulmonary embolism (PE) is the most common preventable cause of death in hospitalized patients. Patients with severe chronic kidney disease (CKD) may be at increased risk for PE in comparison to the general population. Whether severe CKD is associated with increased risk for late venous thromboembolism (VTE) in a population of renal transplant recipients has not been determined. Methods: Using the US Renal Data System database, we studied 28,924 patients receiving a kidney transplant from January 1, 1996, to July 31, 2000, with Medicare as primary payer, followed up until December 31, 2000. Cox proportional hazards regression models were used to calculate the association of transplant recipient estimated glomerular filtration rate (eGFR; by the Modification of Diet in Renal Disease formula) less than 30 mL/min/1.73 m 2 (versus >30 mL/min/1.73 m 2) 1 year after renal transplantation with Medicare claims for VTE (either deep-venous thrombosis or PE/infarction) 1.5 to 3 years after renal transplantation. Results: The rate of VTE occurring 1.5 to 3 years after transplantation was 2.9 episodes/1,000 person-years. eGFR less than 30 mL/min/1.73 m 2 versus higher at the end of the first year after renal transplantation was associated with significantly increased risk for later VTE (adjusted hazard ratio, 2.05; 95% confidence interval, 1.08 to 3.89). Conclusion: Patients with severe CKD after renal transplantation should be regarded as high risk for late VTE, which is a potentially preventable cause of death in this population. Am J Kidney Dis 43:120-130. This is a US government work. There are no restrictions on its use.
2014
Background: Transplant-associated thrombotic microangiopathy (TA-TMA) is considered one of the most severe complications after hematopoietic stem cell transplantation. Unfortunately, controversial approaches on TA-TMA diagnostic criteria contribute to a delay in both diagnosis and treatment. Recommendations for TA-TMA based in the past on case reports or retrospective studies lack a reasonable level of evidence. One of the most promising drugs for TA-TMA likely induced by endothelium damage is Defibrotide, a polydisperse oligonucleotide. Auto-antibody depleting or complement blocking therapy has also emerged as new strategy to decrease TA-TMA-associated morbidity and mortality. Methods: A joint study group of experts on TA-TMA met during the 2013 ASH Meeting (New Orleans, USA) and the 2014 EBMT Meeting (Milan, Italy) with the aim of proposing a reliable treatment for this complication. Common diagnostic criteria for TA-TMA have been discussed and are described in the review. Factors...
Update on the long-term complications of renal transplantation
British Medical Bulletin, 2013
Introduction: Powerful immunosuppressive regimens have reduced rejection risk, leading to an expanding cohort of long-term kidney transplant recipients who are likely to encounter practitioners in other specialties. Sources of data: Key review papers and primary literature identified through searches of PubMed, Google Scholar and Medline. Areas of agreement: Death from cardiovascular disease and malignancy remain the chief causes of transplant loss. Risk factors and phenotypes for these differ from the general population. Areas of controversy: Many guidelines for renal transplant recipients are based on extrapolation from studies on non-transplant cohorts and may not be appropriate. Emerging studies demonstrate that established interventions in the general population are less efficacious in transplant recipients. Growing points: The influence of immunosuppression on the development of complications. Areas timely for developing research: Markers to guide individualized optimal immunosuppression and predict the development of complications would allow for targeted early intervention.
Risk Factors Associated With Graft Loss and Patient Survival After Kidney Transplantation
Transplantation Proceedings, 2009
Objective. To evaluate the influence of traditional risk factors on major kidney transplantation outcome. Patients and Methods. Data from kidney transplantation procedures performed between 2003 and 2006 were retrospectively analyzed for the influence of traditional risk factors on transplantation outcome. Of 2364 transplants, 67% were from living donors, 27% were from donors who met standard criteria, and 6% were from donor who met expanded criteria. Two hundred thirty-nine procedures (10%) were performed in pediatric patients. Immunosuppression was selected on the basis of subgroup population. Results. At 1 year posttransplantation, cumulative freedom from a treated acute rejection episode (ARE) was 76.7%, with no difference between black vs nonblack recipients (75.0% vs 73.4%; P ϭ .79). At 2 years, survival for patients (95.3% vs 88.3% vs 82.1%; P Ͻ .001) and grafts 92.3% vs 80.3% vs 70.9%; P Ͻ .001) was better in recipients of living donor grafts compared with donors who met standard or expanded criteria, respectively. Moreover, graft survival was poorer in black vs nonblack patients (83.6% vs 88.7%; P Ͻ .05) because of high mortality (13% vs 7%; PϽ.001). Risk factors associated with death included cadaveric donor organ (odds ratio [OR], 2.4) and black race (OR, 1.8), and risk factors associated with graft loss included cadaveric donor organ (OR, 2.
American Journal of Kidney Diseases, 2004
Background: Pulmonary embolism (PE) is the most common preventable cause of death in hospitalized patients. Patients with severe chronic kidney disease (CKD) may be at increased risk for PE in comparison to the general population. Whether severe CKD is associated with increased risk for late venous thromboembolism (VTE) in a population of renal transplant recipients has not been determined. Methods: Using the US Renal Data System database, we studied 28,924 patients receiving a kidney transplant from January 1, 1996, to July 31, 2000, with Medicare as primary payer, followed up until December 31, 2000. Cox proportional hazards regression models were used to calculate the association of transplant recipient estimated glomerular filtration rate (eGFR; by the Modification of Diet in Renal Disease formula) less than 30 mL/min/1.73 m 2 (versus >30 mL/min/1.73 m 2) 1 year after renal transplantation with Medicare claims for VTE (either deep-venous thrombosis or PE/infarction) 1.5 to 3 years after renal transplantation. Results: The rate of VTE occurring 1.5 to 3 years after transplantation was 2.9 episodes/1,000 person-years. eGFR less than 30 mL/min/1.73 m 2 versus higher at the end of the first year after renal transplantation was associated with significantly increased risk for later VTE (adjusted hazard ratio, 2.05; 95% confidence interval, 1.08 to 3.89). Conclusion: Patients with severe CKD after renal transplantation should be regarded as high risk for late VTE, which is a potentially preventable cause of death in this population. Am J Kidney Dis 43:120-130. This is a US government work. There are no restrictions on its use.