Complement Prospective Evaluation of Thrombotic Microangiopathy on Endothelium

Inclusion criteria

• Males or females at least 18 years of age;
• Have acute kidney injury, defined as estimated GFR <45 mL/min/1.73m2;
• Have documented TMA either on peripheral blood, defined as Coombs negative microangiopathic hemolytic anemia (hematocrit <30%, hemoglobin <6.5 mmol/L [<10 g/dL], lactate dehydrogenase >500 U/L, and either schistocytes on peripheral blood smear or undetectable haptoglobin), and platelets <150,000 per µL, or kidney biopsy;
• Have primary atypical HUS or a coexisting condition linked to complement dysregulation:

• Hypertensive emergency, defined as SBP/DBP of >180/120 mmHg and impending organ damage secondary to hypertension (at least one of the following: neurologic disease, hypertensive retinopathy grade III and/or IV, left ventricular hypertrophy); OR
• Pregnancy, including 12 weeks postpartum; OR
• Kidney donor recipient; OR
• Systemic auto-immune disease associated with TMA, including systemic sclerosis, systemic lupus erythematosus, anti-phospholipid syndrome;
• Have the ability to understand the requirements of the study, provide written informed consent, and comply with the study protocol procedures.

Exclusion criteria

• Have secondary causes of hypertensive emergency, including renovascular hypertension, Cushing syndrome, aldosteronism, pheochromocytoma, thyroid disease;
• Have a nephropathy not related to thrombosis on kidney biopsy;
• Have ADAMTS13 deficiency, defined as ADAMTS13 activity <10%;
• Have a positive stool culture for Shiga toxin producing bacteria;
• Have positive serologic test for viral infections, including HIV and CMV;
• Have a history of malignant disease, excluding non-melanoma skin cancer;
• Have a history of bone marrow or solid organ transplantation, excluding kidney transplantation;
• Received at least one of the following agents: chemotherapeutics, sirolimus, anti-VEGF agents;
• Have a history of recent past exposure to illicit drug(s).