Einfluss der Haptoglobinkonzentration auf die Inzidenz akuter Nierenschädigung und Validierung eines Frühmarkers der akuten Nierenschädigung nach kardiochirurgischen Operationen

Influence of haptoglobin levels on the incidence of acute kidney injury and validation of an early biomarker for acute kidney injury after cardiac surgery

by Eva Magdalena Richardt
Doctoral thesis
Date of Examination:2022-03-29
Date of issue:2022-03-22
Advisor:Dr. Anna Lux geb. Wetz
Referee:Prof. Dr. Anselm Bräuer
Referee:Prof. Dr. Oliver Gross
Referee:Prof. Dr. Ralf Dressel
Persistent Address: http://dx.doi.org/10.53846/goediss-9134

 

 

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Abstract

English

Acute Kidney Injury (AKI) is a complex and multifactorial induced syndrome leading to increased morbidity and mortality. It is frequently seen after cardiac surgery with cardiopulmonary bypass. One major risk factor for AKI is intravascular hemolysis occurring due to cardiopulmonary bypass. The release of free hemoglobin causes tubular cell injury after exceeding the binding capacity of haptoglobin. The objective of this prospective study was to investigate the perioperative changes of free hemoglobin and haptoglobin levels and to examine their influence on the incidence of AKI after cardiac surgery. 154 patients undergoing cardiopulmonary-bypass-surgery were included in the study. Postoperative AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) classification. AKI was detected in 45.5 % of the patients. During surgery there was an increase in the levels of free hemoglobin and a fast decrease after surgery. This indicates that processes have taken place to eliminate free hemoglobin, such as glomerular filtration, endozytosis and binding to haptoglobin. There was at no time a significant difference in the levels of free hemoglobin between patients with and without postoperative Acute Kidney Injury. The hypothesis that patients with higher free hemoglobin levels have a higher incidence of Acute Kidney Injury could not be confirmed. As expected, the highest level of haptoglobin was preoperatively. Due to complex-building there was a perioperative decrease in the haptoglobin levels, with the lowest level on the evening of the day of surgery and it stayed at a low level until the following morning. A negative correlation could be detected between free hemoglobin and haptoglobin during surgery indicating that the binding-capacity of haptoglobin was reached at this point. The level of haptoglobin was at a low level postoperatively while free hemoglobin level already was within normal levels indicating the ongoing consumption of haptoglobin. There was at no time a significant difference in the haptoglobin levels between patients with and without postoperative Acute Kidney Injury, refuting the hypothesis that higher haptoglobin levels have a preventive effect on Acute Kidney Injury. Novel biomarkers aim to detect AKI at the time of damage to the kidneys so that preventive and therapeutic treatments can be prescribed early enough to protect from or lessen AKI. In this study it was investigated whether the novel urine biomarkers Tissue-Inhhibitor-Metalloproteinase 2 (TIMP-2) and Insulin-Like-Growth-Factor-Binding-Protein 7 (IGFBP-7) discriminate AKI early and precisely after cardiopulmonary bypass-surgery. It was shown that [TIMP-2]*[IGFBP-7] was able to discriminate AKI on the first postoperative day. Measurements made on the day of surgery were too early to be able to discriminate. Applying known Cut-off-levels 0.3 for the risk of AKI and 2.0 for a higher level AKI could not be confirmed. The optimal Cut-off-level in this study at the first postoperative day was 1.065.
Keywords: Biomarker; Acute Kidney Injury; Haptoglobin; Hemoglobin
 
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