Etiology and Outcomes of Kidney-Limited and Systemic Thrombotic Microangiopathy

The syndromes of thrombotic microangiopathy (TMA) are associated with acute kidney injury and end-stage kidney disease. TMAs typically present with thrombocytopenia and microangiopathic hemolytic anemia (ie, systemic TMA). Kidney-limited TMA can occur, although often overlooked and undertreated. In this study, we studied the etiology and outcome of kidney-limited TMA. Patients with TMA on kidney biopsy, either systemic or kidney-limited, were recruited and classified as definite complement-mediated (C-)TMA (ie, ≥1 pathogenic complement gene variant), probable C-TMA (ie, massive ex vivo C5b9 formation without a pathogenic complement gene variant), and non (n)C-TMA (ie, normal ex vivo C5b9 formation). Morphologic features of TMA on kidney biopsy and their clinical correlates were studied. Patients were classified as definite C-TMA (N = 14; 18%), probable C-TMA (N = 21; 27%), or nC-TMA (N = 42; 55%), including 51 (66%) out of 77 patients with kidney-limited TMA. Patients with definite and probable C-TMA often presented with hemolysis (79% and 62% vs 34%; P = .007), glomerular thrombosis (79% and 76% vs 43%), a higher creatinine level (974 and 502 vs 280 μmol/L; P = .001), and a younger age (33 and 33 vs 40 years; P = .029) as compared with nC-TMA. Morphologic features neither defined etiology nor differed between systemic and kidney-limited TMA. Eculizumab improved kidney outcomes in patients with kidney-limited C-TMA but not in those with nC-TMA akin to patients with systemic C-TMA. Kidney outcomes were not affected by chronicity grading on kidney biopsy. Kidney-limited TMA is common in diverse TMAs, including C-TMA. A kidney biopsy is needed to detect TMA at the earliest possible stage of the disease. Morphology does not allow for the identification of etiology, and patients with kidney-limited TMA should therefore be screened for complement dysregulation, having a major impact on treatment and prognosis.