- Severe coexisting conditions, such as severe renal insufficiency (GFR < 60 ml/min•1.73m2), severe hepatic dysfunction [elevated ALT (glutamic-pyruvic transaminase) or AST (glutamic-oxal acetic transaminase) level by more than three-fold of the normal limitation], acute or chronic heart failure (NYHA III-IV), acute infectious diseases, immune disorders, malignancy, etc.