Metabolomic Profile and Its Correlation with the Plasmatic Levels of Losartan, EXP3174 and Blood Pressure Control in Hypertensive and Chronic Kidney Disease Patients

Int J Mol Sci. 2023 Jun 7;24(12):9832. doi: 10.3390/ijms24129832.

Abstract

Systemic arterial hypertension (SAH) is one of the most prevalent chronic diseases worldwide and, when dysregulated, may cause serious complications. Losartan (LOS) blocks relevant physiological aspects of hypertension, acting mainly on the reduction of peripheral vascular resistance. Complications of hypertension include nephropathy, in which diagnosis is based on the observation of functional or structural renal dysfunction. Therefore, blood pressure control is essential to attenuate the progression of chronic kidney disease (CKD). In this study, 1H NMR metabolomics were used to differentiate hypertensive and chronic renal patients. Plasmatic levels of LOS and EXP3174, obtained by liquid chromatography coupled with mass-mass spectroscopy, were correlated with blood pressure control, biochemical markers and the metabolomic fingerprint of the groups. Some biomarkers have been correlated with key aspects of hypertension and CKD progression. For instance, higher levels of trigonelline, urea and fumaric acid were found as characteristic markers of kidney failure. In the hypertensive group, the urea levels found could indicate the onset of kidney damage when associated with uncontrolled blood pressure. In this sense, the results point to a new approach to identify CKD in early stages and may contribute to improving pharmacotherapy and reducing morbidity and mortality associated with hypertension and CKD.

Keywords: EXP3174; chronic kidney disease; hypertension; losartan; metabolomics; plasmatic.

MeSH terms

  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure
  • Humans
  • Hypertension*
  • Losartan / pharmacology
  • Losartan / therapeutic use
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / drug therapy
  • Urea / pharmacology

Substances

  • losartan carboxylic acid
  • Losartan
  • Antihypertensive Agents
  • Urea