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Long-term Kidney Outcomes in Patients With Acquired Thrombotic Thrombocytopenic Purpura.

ABSTRACT: Introduction:Severe acute kidney injury (AKI) and chronic kidney disease (CKD) are considered to be uncommon in patients with acquired thrombotic thrombocytopenic purpura. However, a recent case series from a tertiary care hospital indicated that 54 (59%) of 92 patients with thrombotic thrombocytopenic purpura presented with AKI; 14 (15%) required dialysis; and 12 (22%) of the 54 patients had CKD at follow-up. Methods:In this prospective analysis of 78 patients diagnosed with their first episode of thrombotic thrombocytopenic purpura and enrolled in the Oklahoma Thrombotic Thrombocytopenic Purpura Registry from 1995 to 2015, we assessed AKI at diagnosis using Kidney Disease: Improving Global Outcomes criteria, and CKD at follow-up as defined by estimated glomerular filtration rate <60 ml/min per 1.73 m2 determined by the Chronic Kidney Disease-Epidemiology Collaboration equation. Results:Forty-five (58%) patients had AKI; 8 (10%) had stage 3 AKI, and 3 (4%) required dialysis. AKI was not associated with the patients' demographic or presenting clinical features. Three of the 8 patients with stage 3 AKI died; among the 5 survivors, estimated glomerular filtration rate was 77 to 107 ml/min per 1.73 m2 (median, 92) with median follow-up of 8.1 years. Among all 62 surviving patients who have had follow-up serum creatinine measurements, 4 (6%) had CKD with median follow-up of 6.4 years. AKI was not associated with the occurrence of CKD (P = 0.74). No patients have required continuing renal replacement therapy. Discussion:In this population-based prospective cohort of consecutive patients with thrombotic thrombocytopenic purpura, without selection or referral bias, severe AKI and CKD are uncommon.

SUBMITTER: Little DJ

PROVIDER: S-EPMC5733749 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Long-term Kidney Outcomes in Patients With Acquired Thrombotic Thrombocytopenic Purpura.

Little Dustin J DJ Mathias Lauren M LM Page Evaren E EE Kremer Hovinga Johanna A JA Vesely Sara K SK George James N JN

Kidney international reports 20170621 6

<h4>Introduction</h4>Severe acute kidney injury (AKI) and chronic kidney disease (CKD) are considered to be uncommon in patients with acquired thrombotic thrombocytopenic purpura. However, a recent case series from a tertiary care hospital indicated that 54 (59%) of 92 patients with thrombotic thrombocytopenic purpura presented with AKI; 14 (15%) required dialysis; and 12 (22%) of the 54 patients had CKD at follow-up.<h4>Methods</h4>In this prospective analysis of 78 patients diagnosed with thei ...[more]

PMID: 29270517

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Project description:BackgroundAcquired thrombotic thrombocytopenic purpura (TTP) is an autoimmune disease in which anti-ADAMTS13 autoantibodies cause severe enzyme deficiency. ADAMTS13 deficiency causes the loss of regulation of von Willebrand factor multimeric size and platelet-tethering function, which results in the formation of disseminated microvascular platelet microthrombi. Precisely how anti-ADAMTS13 autoantibodies, or antibody subsets, cause ADAMTS13 deficiency (ADAMTS13 activity generally < 10%) has not been formally investigated.MethodsWe analysed 92 acquired TTP episodes at presentation, through treatment and remission/relapse using epitope mapping and functional analyses to understand the pathogenic mechanisms of anti-ADAMTS13 IgG.Results89/92 of TTP episodes had IgG recognising the ADAMTS13 N-terminal domains. The central spacer domain was the only N-terminal antigenic target detected. 38/92 TTP episodes had autoantibodies recognising the N-terminal domains alone; 54/92 TTP episodes also had antibodies against the ADAMTS13 C-terminal domains (TSP2-8 and/or CUB domains). Changes in autoantibody specificity were detected in 9/16 patients at relapse, suggesting a continued development of the disease. Functional analyses on IgG from 43 patients revealed inhibitory IgG were limited to anti-spacer domain antibodies. However, 15/43 patients had autoantibodies with no detectable inhibitory action and as many as 32/43 patients had autoantibodies with inhibitory function that was insufficient to account for the severe deficiency state, suggesting that in many patients there is an alternative pathogenic mechanism. We therefore analysed plasma ADAMTS13 antigen levels in 91 acquired TTP presentation samples. We demonstrated markedly reduced ADAMTS13 antigen levels in all presentation samples, median 6% normal (range 0-47%), with 84/91 patients having < 25% ADAMTS13 antigen. ADAMTS13 antigen in the lowest quartile at first presentation was associated with increased mortality (odds ratio 5.7).ConclusionsAnti-spacer domain autoantibodies are the major inhibitory antibodies in acquired TTP. However, depletion of ADAMTS13 antigen (rather than enzyme inhibition) is a dominant pathogenic mechanism. ADAMTS13 antigen levels at presentation have prognostic significance. Taken together, our results provide new insights into the pathophysiology of acquired TTP.

Dataset Information

Long-term Kidney Outcomes in Patients With Acquired Thrombotic Thrombocytopenic Purpura.

Publications

Long-term Kidney Outcomes in Patients With Acquired Thrombotic Thrombocytopenic Purpura.

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