Urinary proteomics reveals biological processes related to acute kidney injury in Bothrops atrox envenomings.

Acute kidney injury (AKI) is a critical systemic complication caused by Bothrops envenoming, a neglected health problem in the Brazilian Amazon. Understanding the underlying mechanisms leading to AKI is crucial for effectively mitigating the burden of this complication. This study aimed to characterize the urinary protein profile of Bothrops atrox snakebite victims who developed AKI. We analyzed three groups of samples collected on admission: healthy subjects (controls, n = 10), snakebite victims who developed AKI (AKI, n = 10), and those who did not evolve to AKI (No-AKI, n = 10). Using liquid-chromatography tandem mass spectrometry, we identified and quantified (label-free) 1190 proteins. A panel of 65 proteins was identified exclusively in the urine of snakebite victims, with 32 exclusives to the AKI condition. Proteins more abundant or exclusive in AKI's urine were associated with acute phase response, endopeptidase inhibition, complement cascade, and inflammation. Notable proteins include serotransferrin, SERPINA-1, alpha-1B-glycoprotein, and NHL repeat-containing protein 3. Furthermore, evaluating previously reported biomarkers candidates for AKI and renal injury, we found retinol-binding protein, beta-2-microglobulin, cystatin-C, and hepcidin to be significant in cases of AKI induced by Bothrops envenoming. This work sheds light on physiological disturbances caused by Bothrops envenoming, highlighting potential biological processes contributing to AKI. Such insights may aid in better understanding and managing this life-threatening complication. Author summary: Envenomings caused by Bothrops species are a public health problem in the Brazilian Amazon. These envenomings can lead to a renal clinical complication called acute kidney injury. A better understanding of the causes leading to this complication is crucial for patient care. We aimed to describe the protein profile in the urine of patients who suffered envenoming and developed acute kidney injury. For this, we used large-scale analysis methods to compare the urine protein content of three groups of samples: healthy individuals, and snakebite patients with and without acute kidney injury. We identified a total of 1190 proteins, 65 of which were exclusive to patients suffering from snake bite envenoming. For patients with a kidney injury outcome, 32 unique proteins were found, of which the most abundant were associated with the body's inflammatory response. We highlight 4 proteins, including serotransferrin and SERPINA-1. Furthermore, we also evaluated candidate biomarkers of kidney injury already reported in the literature, such as retinol-binding protein, cystatin-C, and hepcidin, concluding that they are significant in cases of kidney injury caused by a jararaca snakebite. This work can help to better understand this serious complication that threatens the lives of the population living in the Amazon. [ABSTRACT FROM AUTHOR]