Kardiyopulmoner Baypas Sonrası Gelişen Akut Böbrek Yetmezliğinin Erken Tanısı İçin Omiks Yaklaşımlar ve Elektroanalitik Çalışmalar

Abstract

Patients exposed to cardiopulmonary bypass may develop acute renal failure (ARF) as a result of blood coming into contact with the heart-lung machine circuits. The serum creatinine level is checked for the diagnosis of ARF, but it may vary according to the age, weight, muscle mass and hydration status of the patient. In addition, the serum creatinine level may not be detected without a 50% reduction in renal function. This situation causes delay in the diagnosis of ARF and delays in the initiation of the necessary treatment. New biomarkers that can replace creatinine may facilitate early diagnosis of the disease. For this purpose, non-targeted metabolomic analyzes were performed with gas chromatography-mass spectrometry in the thesis study. Plasma metabolomic profiles of subjects who developed ARF(patient) (n=9) and those who did not (control) (n=96) were compared before and at 0.5, 4, 12 and 24 hours after bypass. As a result of the analysis, 222 known and 1076 unknown metabolites were identified. It was observed that the amounts of cysteine, fumaric acid, galacturonic acid, gluconic acid, hippuric acid, hypoxanthine (HXA), malonic acid, methionine, phenylacetaldehyde, threonine and uric acid (UA) changed significantly in the patient group. It is important to conduct targeted studies for metabolites found as biomarker candidates. In the second phase of the thesis, an electroanalytical method was developed for the analysis of significantly altered UA and HXA and xanthine (XA) in the same pathway from plasma samples, which can be used in the early diagnosis of ARF. Glassy carbon electrode modified with reduced graphene oxide was used as the sensor.After the developed method was optimized, validation study was carried out. The LLOQ values for UA, XA and HXA are 0.12 µM, 0.13 µM and 0.43 µM, respectively. As a result of the analyzes, it was observed that UA and HXA differed significantly in the patient and control groups.