L-FABP und H-FABP als neue prognostische Biomarker für den Beginn einer Nierenersatztherapie im Falle eines akuten Nierenversagens

Acute kidney injury (AKI) has an important meaning in modern medicine. A lot of surveys could demonstrate that acute kidney injury is an independent risk factor for mortality. Despite the importance of acute kidney injury, clear consensus about the diagnostic criteria or clinical definition has been long been absent with almost 35 different definitions of the condition found in medical literature, further complicating investigation of the disease. Although the management of AKI changed with the development of modern methods of renal replacement therapy (RRT), these changes did not improve the patients´ outcome. This may be due to the fact that in spite of established indications, the optimal timing for initiating renal RRT is still not known, with serum creatinine serving as a relatively inconsistent marker for early diagnosis of AKI. The intention of this prospective clinical experimental study was to discover new possibilities in order to optimize the timing of RRT in AKI. Therefore, patients with AKI were divided into two different groups (dialysis (D) vs. non-dialysis (ND)) depending on the necessity of RRT. In this study two strategies were pursued. On the one hand it was tried to calculate an algorithm with established blood and urine parameters, which should help to predict the necessity of RRT in AKI. On the other hand, proteomic urine analytic on the basis of 2-D gel-electrophoresis and mass spectrometry was performed to find a biomarker which allows early diagnosis of AKI requiring RRT. As a result of this study an algorithm was found which classifies patients into the correct group with an AUC of 88 %, sensitivity of 82 % and an optimal cut-off to distinguish between the necessity of RRT of 0,48. In addition, excretion differences of two types of fatty acid binding proteins were found. These are liver-fatty acid binding protein (L-FABP; FABP1), which shows a regulation difference of 6,490 (p = 0,001) from the ND- to the D-group, and heart-fatty acid binding protein (H-FABP; FABP3), which has a significant upwards regulation from the ND- to the D- group of 5,076 (p = 0,05). In independent experiments, the excretion difference for these two lipid binding proteins was confirmed via Dot Blot. Up to now, nine different types of FAPBs have been identified, named by the tissue they were found in for the first time. It is already known that the transport of fatty acids is a key role of L-FABBs and that they are also involved in the regulation of gene expression and cellular differentiation. H-FABP is a cytoplasmic protein, which is basically found in cardiac myocytes and here also involved in absorption, transport and metabolism of fatty acid. L- and H-FABP as well as the algorithm, which was described in this study, may help to create criteria for RRT initiation in patient with acute AKI. Further studies are necessary to better verify the results.