As a result of these dosing difficu

As a result of these dosing difficulties in the first days after heart and lung transplantation, tacrolimus nephrotoxicity, which originates from vasoconstriction of afferent and efferent glomerular arterioles, often ensues 55. When whole blood and especially unbound tacrolimus plasma concentrations are increased, a stronger vaso‐constrictive effect is suspected leading to acute kidney injury. The acute kidney injury is further aggravated by cardiac dysfunction, hypoxia, hypovolemia, large volume shifts and use of vasopressors (Table 1) 56. Pretransplant risk factors such as impaired renal function, hypertension, diabetes, renal hypoperfusion, poor nutritional status, low muscle mass, weight loss and edema increase the risk for postoperative kidney injury 57-59. Importantly, renal injury observed early after transplantation indicates an increased risk of developing chronic renal failure, which has been found in up to 50% after one year and 70% after five years 3, 60. This underscores the need to address the unresolved clinical problem of maintaining whole blood tacrolimus trough concentrations within the therapeutic range to prevent nephrotoxicity.