Clinical Associations, Treatment, and Outcomes of Renal-Limited Thrombotic Microangiopathy
Authors: Saba Elias Simon , Cambron Julia Claire , Go Ronald S. , Leung Nelson , Sridharan Meera 
Published: October 2019

Background

Thrombotic microangiopathy (TMA) is a clinicopathologic diagnosis that can be characterized by microangiopathic hemolytic anemia (MAHA), thrombocytopenia and end-organ damage. Though most patients will present with the hematologic abnormalities of MAHA and thrombocytopenia, there are some that never demonstrate those features and only present with acute renal injury. Here we describe the clinical presentation, laboratory assessment, management, and outcomes of patients with renal-limited TMA (rTMA).

Methods

After IRB approval, the electronic medical record was searched from 2008-March 2017 for patients managed at our institution with a clinical diagnosis of rTMA supported by renal biopsy. Inclusion criteria were as follows: 1) Presence of TMA on renal biopsy, 2) Absence of MAHA 3) No history of renal transplant prior to diagnosis of TMA. Clinical notes were reviewed to document the physician-determined cause of TMA. If no cause was listed, cause of TMA was based off of labs and clinical observation.

Results

Thirty-five patients (18 female) met clinical criteria for a diagnosis of rTMA. Median age at time of biopsy was 59 years (range 9 to 87). Creatinine at time of biopsy was 2.4 mg/dL (range 0.55 to 6.4). Evidence of chronic TMA was noted on 17 specimens and an additional 3 had findings of chronic and acute TMA.

Ten patients had ADAMTS13 activity performed and all were >10% with negative inhibitor screen (median 66%(26-100)). 24 patients (68.6%) had complement serology assessed. Three patients (12.5%) had low C3 while C4 was normal in 19 patients (79%). One patient in our cohort had complement mutational testing performed with no evidence of a pathogenic variant.

Most common etiology of rTMA was medications (28.5%) and underlying rheumatologic disorder (20%)(Table 1). In 6 patients (17%), an identifiable cause was not elucidated.

Management of TMA was dependent on underlying etiology of rTMA. Discontinuation or dose adjustment of TMA-causative medications was recommended in 4 patients and 25% of patients had normalization of Cr. Four patients received therapeutic plasma exchange (TPE) for median 5 (2-5) days. Causes of rTMA for those receiving TPE were gemcitabine, bevacizumab, unspecified connective tissue disease, and rTMA due to an unknown cause. 50% of patients were noted to have improvement in Cr with TPE. Antihypertensive medications were used for rTMA secondary to uncontrolled hypertension (n=4) and scleroderma (n=4). 11 patients (31%) were observed or treatment for causative underlying etiology was pursued, while 7 patients were treated with glucocorticoids. Of 6 patients, with no identifiable underlying cause, 4 were treated with observation, 1 was treated with GC, and one was treated with TPE

Fourteen patients (38.9%) required dialysis; 6 of these patients were able to discontinue dialysis less than two months after initiation. Three patients (8.3%) with rTMA, respectively due to tacrolimus toxicity, longstanding hypertension, and systemic lupus erythematosus, received a renal transplant, and one additional pt (2.8%) with rTMA due to scleroderma remained on the renal transplant waiting list at time of death.

In a median follow-up time of 8.73 months (range 0 to 47.9), 16 patients (44.4%) died. Median time from diagnosis of TMA to death was 12.1 months (range 1.47 to 58.2). No deaths were directly attributable to underlying TMA.

Conclusion

Renal-limited TMA is a pathologic diagnosis that in our cohort was most likely to medications or underlying rheumatologic conditions. rTMA was managed by treating the underlying disorder or removing the causative medication. Though cause of rTMA was evident in the majority of patients, 17% had no identifiable precipitating factor predisposing to rTMA. Larger studies are required to delineate optimal management and surveillance strategies for these patients.

Disclosures

No relevant conflicts of interest to declare.