Indicators of Acute and Persistent Renal Damage in Adult Thrombotic Microangiopathy

Dierkes, Firuseh; Andriopoulos, Nikolaos; Sucker, Christoph; Kuhr, Kathrin; Hollenbeck, Markus; Hetzel, Gerd R.; Burst, Volker; Teschner, Sven; Rump, Lars Christian; Benzing, Thomas; Grabensee, B; Kurschat, Christine

doi:10.1371/journal.pone.0030886

Cited by 15 publications

(12 citation statements)

References 32 publications

(47 reference statements)

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“…“secondary TTP”) has a worse prognosis than idiopathic acquired TTP, and that TTP associated with hematopoietic stem cell transplant responds poorly to plasma exchange . Some studies have associated male sex , age, serum creatinine > 2 , coma , and platelet recovery rate to poor outcomes while others have failed to confirm these associations . Thus, given the emergence of new options for treatment of acute TTP, additional information concerning clinical factors that identify patients at high risk for poor outcomes is needed.…”

Section: Introductionmentioning

confidence: 99%

Management and outcomes for patients with TTP: analysis of 100 cases at a single institution

et al. 2013

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The advent of plasma exchange has led to a dramatic improvement in the survival of patients with thrombotic thrombocytopenic purpura (TTP), though approximately 10% of patients still die and a third suffer relapses. Clinical features that identify poor risk patients have not been clearly identified. We reviewed 100 patients who were treated for a first episode of TTP at the Cleveland Clinic between 2000 and 2012 to identify factors predictive of poor outcomes. On multivariate analysis, increasing age, especially age > 60 (RR: 7.08, 95% CI: 2.15-23.39, P = 0.002), severe neurological symptoms at presentation (RR: 18.37, 95% CI: I4.19-80.13, P < 0.001) and a persistently elevated LDH level after two plasma exchanges were predictive of mortality. Patients with ADAMTS13 activity above or below 5% did not differ in terms of clinical presentation or mortality and relapse rates, although ADAMTS13 activity > 5% was an independent predictor of adverse renal outcomes (need for dialysis and progression to chronic kidney disease). These variables may be useful for risk stratification and identification of patients who could potentially benefit from early institution of adjunctive therapy.

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Section: Introductionmentioning

confidence: 99%

Management and outcomes for patients with TTP: analysis of 100 cases at a single institution

et al. 2013

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“…Thirty studies reported the incidence of relapse among patients with TMA treated with plasma exchange and all studies reported mortality (Table ) . Among patients followed for at least 6 months, the median (range) incidence of relapse was 18% (3–84%).…”

Section: Resultsmentioning

confidence: 99%

“…While the focus over the last two decades has appropriately been on short‐term outcomes of TMA with use of plasma exchange, longer‐term outcomes among survivors now have greater relevance. In addition to acute ischemic events such as stroke, myocardial infarction, and acute kidney injury , clinical experience and small cohort studies suggest an association between TMA and long‐term morbidities, such as cardiovascular disease, cerebrovascular disease, and chronic kidney disease . In a condition that typically affects young and otherwise healthy adults, the impact of these adverse outcomes may be large.…”

Section: Introductionmentioning

confidence: 99%

Long‐term outcomes of thrombotic microangiopathy treated with plasma exchange: A systematic review

et al. 2016

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With the adoption of plasma exchange as standard treatment for thrombotic microangiopathy (TMA), more patients are surviving and long-term outcomes have greater relevance. We conducted a systematic review to synthesize and evaluate the quality of evidence on long-term outcomes of TMA among adults treated with plasma exchange and to identify factors that may be associated with a worse long-term prognosis. We searched databases from 1980 to 2013 for eligible articles published in any language. We included studies that reported outcomes in at least ten adults with a history of TMA treated with plasma exchange and at least 6 months of follow-up. We abstracted data in duplicate and assessed the methodological quality of each study using an assessment tool developed based on recommended validity criteria. We screened 6672 articles, reviewed 213, and included 34 studies totaling 1182 patients (study median [range], 24 ). The mean (or median) follow-up ranged from 6 months to 13 years. The cumulative incidence of relapse and mortality was highly variable and ranged from 3 to 84 and 0 to 61%, respectively. The incidence of other outcomes across 10 studies also varied (outcomes included hypertension, kidney disease, preeclampsia, stroke, seizure, severe cognitive impairment, and depression); in three other studies, long-term neurocognitive function and health-related quality of life were significantly lower than in the general population. Patients who survive an episode of TMA may be susceptible to long-term vascular complications, but the magnitude of this risk and how to mitigate it remains unclear.

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“…Although mortality associated with TMA has decreased since the introduction of plasma exchange therapy, it can still be a life-threatening condition [13]. In patients who have undergone renal transplantation, the incidence of TMA is higher than in the general population and can lead to graft loss [14], reaching as high as 50% [6].…”

Section: Discussionmentioning

confidence: 99%

Use of Belatacept as Alternative Immunosuppression in Three Renal Transplant Patients withDe NovoDrug-Induced Thrombotic Microangiopathy

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et al. 2013

Case Reports in Medicine

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Thrombotic microangiopathy (TMA), a severe complication of renal transplantation, is a pathological process involving microvascular occlusion, thrombocytopenia, and microangiopathic hemolytic anemia. It generally appears within the first weeks after transplantation, when immunosuppressive drugs are used at high doses. De novo TMA may also be drug-induced when calcineurin inhibitors or proliferation signal inhibitors are used. We report three cases of de novo drug-induced TMA in renal transplant patients who were managed by replacing calcineurin inhibitors or proliferation signal inhibitors with belatacept, a primary maintenance immunosuppressive drug, which blocks the CD28 costimulation pathway, preventing the activation of T lymphocytes. To identify the cause of TMA, we ruled out HUS, hepatitis C serology, HIV serology, parvovirus B19, cytomegalovirus, anti-HLA antibodies, and prolonged activated partial thromboplastin time. We suspect that the TMA was caused by the calcineurin inhibitors or proliferation signal inhibitors. Belatacept treatment was initiated at a dose of 10 mg/kg on days 1, 5, 14, 28, 60, and 90; maintenance treatment was 5 mg/kg once a month for 1 year. Belatacept, in combination with other agents, prevented graft rejection in three patients.

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Indicators of Acute and Persistent Renal Damage in Adult Thrombotic Microangiopathy

Cited by 15 publications

References 32 publications

Management and outcomes for patients with TTP: analysis of 100 cases at a single institution

Management and outcomes for patients with TTP: analysis of 100 cases at a single institution

Long‐term outcomes of thrombotic microangiopathy treated with plasma exchange: A systematic review

Use of Belatacept as Alternative Immunosuppression in Three Renal Transplant Patients withDe NovoDrug-Induced Thrombotic Microangiopathy

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