Abstracts

Background: Our clinical understanding of acute kidney injury (AKI) has dramatically increased over the last decades, but an effective intervention for AKI is still missing. An early intervention would be desirable, since preclinical models could show a massive delay or even prevention of AKI when treated early enough, which would improve recovery and decrease mortality. New potent biomarker candidates have been identified recently: Altered plasma concentrations of pro-Enkephalin (pENK) were shown in patients with restricted renal function. Relaxin 2 (RLX2) is known to alter renal hemodynamics in pregnant women and recently the recombinant RLX2 was suggested as therapeutic intervention in several diseases involving renal dysfunction. Methods: 3 new assay systems were developed and termed pENKrat, pENKurine and pro-RLX2. Paraphinated slices of healthy human renal tissue were examined for pENK expression using immunohistochemical procedures. pENKplasma concentrations were determined with the pENKrat assay in rat models of gentamycin-induced nephrotoxicity and CLP-induced sepsis. pENKplasma and pENKurine concentrations were determined in healthy kidney donors and corresponding recipients with sphingotest penKid and the pENKurine assay. pENKplasma and pro-RLX2 plasma concentrations were determined in healthy individuals using the sphingotest penKid and pro-RLX2. pro-RLX2 plasma concentrations were determined in pregnant women with uncomplicated and preeclamptic pregnancy as well as in non-pregnant individuals with acute and chronic heart failure with pro-RLX2.Results: PENK expression was localized throughout the renal tubules even though results were not reproducible. In different rat studies the association of pENKplasma concentration with renal dysfunction was shown by specific increase of pENKplasma concentration by induction of selective renal injury. pENKurine concentrations were associated with renal injury, too. In pregnancy, pENKplasma was shown to vary with gestational age. Even though measurability of pro-RLX2 in non-pregnant adults was restricted, a weak connection of pro-RLX2 plasma concentration with renal dysfunction could be shown in patients with heart failure. In pregnancy, pro-RLX2 decreased with increasing gestational age, but was shown to be a poor marker of preeclampsia.Conclusion: A combination of pENKplasma and pENKurine measurement could be a promising approach to achieve an earlier recognition of AKI. Nevertheless, the function pENK exhibits within the kidney remains unclear.pro-RLX2 was shown to be less useful as biomarker, despite being directly involved in pathology of cardiorenal injury. Exogenous RLX2 (Serelaxin) is a promising approach for new therapeutic action, but monitoring of endogenous pro-RLX2 is difficult. Hintergrund: Unser klinisches Verstndnis von akutem Nierenversagen (AKI) hat ber die letzten Jahrzehnte dramatisch zugenommen, aber eine effektive Intervention fr AKI fehlt noch. Eine frhe Intervention wre