Preliminary Study on J-Resolved NMR Method Usability for Toxic Kidney's Injury Assessment

Abstract

Background. Nowadays, the Nuclear Magnetic Resonance (NMR) techniques are tested for metabolomic urine profile in order to detect early damage of kidney. Objectives. The purpose of this investigation was the initial assessment of two-dimensional J-resolved NMR urine spectra analysis usability for early kidney injuries detection. The amino acids (AA) and acids profile change after the exposure to nephrotoxic agent (the cisplatin infusion) was examined. Material and Methods. The material was the urine of patients with non-small-cell lung cancer, treated with cisplatin in Pulmonology and Lung Cancers Clinic in Wrocław. The urine of healthy volunteers was also examined. The identification of metabolites in urine was based on two-dimensional JRES signals in spectra, described in Human Metabolites Database (HMD). The molar concentration of metabolites was calculated from the volume under the signals. The analysis was focused on amino acids and organic acids (lactid acid and pyruvic acid) profiles. Results. Any specific amino acids were identified after cisplatin infusion in comparison to the state before infusion. However, the differences in concentration were observed over 2-fold increase in valine, isoleucine and leucine, over 3-fold in alanine. Also, the concentration of pyruvic and lactic acids increased significantly (p ≤ 0.05, p ≤ 0.01). Conclusions. There were no specific amino acids identified in response to the infusion of cisplatin; however, some changes in the concentrations of amino acids and other small molecules were found. The analysis of two-dimensional JRES spectra showed an increase of alanine, leucine, isoleucine and valine concentration after the application of cisplatin. It seems that it is worth developing the JRES method based on special computer program (Adv Clin Exp Med 2015, 24, 4, 629-635).

Defining the optimal duration for normothermic regional perfusion in the kidney donor: A porcine preclinical study

“…38 Lactate/pyruvate ratio and LDH levels increased from No-NRP to 2 hours NRP, likely due to the metabolism disturbances of WI, 39,40 suggesting ischemic impairment. 41,42 These markers returned to basal values between 4 and 6 hours NRP, suggesting a better balance in supply and demand in organ perfusion and an efficient adjustment of tissue oxygenation and adequate perfusion. Collectively, these markers are related to tissue hypoperfusion, but the observed return to normal values highlights the potential benefits of NRP in re-establishing sustained aerobic metabolism, supporting the reconditioning role of NRP through maintenance of oxygenated blood circulation and normothermia.…”

“…HO-1 expression attenuates IRI and improves survival in rat renal allografts 37. Lactate/pyruvate ratio and LDH levels increased from No-NRP to 2 hours NRP, likely due to the metabolism disturbances of WI,39,40 suggesting ischemic impairment 41,42. Lactate/pyruvate ratio and LDH levels increased from No-NRP to 2 hours NRP, likely due to the metabolism disturbances of WI,39,40 suggesting ischemic impairment 41,42.…”

Multi-Organ NMR Metabolomics to Assess In Vivo Overall Metabolic Impact of Cisplatin in Mice

“…In cancer treatment with cDDP, metabolomics has been applied to several human cancer cell lines in search of biomarkers of chemotherapy efficacy (lung [10,11], breast [12,13], bone [14,15], brain [16], and ovarian [17,18]) or resistance (ovarian [17,18,19], ovarian and lung [20], breast [21]). CDDP treatment efficacy and nephrotoxicity have also been assessed through kidney tissue metabolomics in a mouse model of metastatic melanoma [22], and biofluids, namely serum/plasma [23,24,25] and urine [26], in a model of lung cancer, both for cDDP sole [24,25] and combined administration [23,24].…”

Urinary NMR Profiling in Pediatric Acute Kidney Injury—A Pilot Study

“…Previous human AKI studies resulted in the identification of a variety of potential metabolite biomarkers [14,24]. Interestingly, almost no overlap exists between the respective metabolites [28][29][30][31][32][33][34] and the metabolites identified in our study. For example, Beger et al identified homovanillinic acid sulfate, a dopamine metabolite as the most important marker in the urine of children who developed AKI after cardiac surgery [21].…”