Altered Eicosanoid Metabolism Associates with the Salutary Changes of Salt Restriction In Chronic Kidney Disease

Abstract

Chronic Kidney Disease (CKD) is a global health crisis affecting 11 to 13% of people worldwide. It often coincides with the development of hypertension, making hypertension a critical predictor of CKD progression. Hypertension is generally linked to increased salt intake and can be treated with antihypertensive drugs and/or a salt restricted diet (SRD). However, antihypertensive medications don’t work in patients with salt sensitivity, which means their only treatment option is a salt restricted diet. Diagnosis of salt sensitivity takes time, since the current method of identification is inconvenient and tedious. Generally, salt sensitivity is determined when physicians recognize the ineffectiveness of antihypertensive drugs. As more hypertensive patients have become salt sensitive, the necessity of a simpler, more effective identification method has increased. Current studies are focusing on finding potential biomarkers of salt sensitivity, but little is done in patients with CKD. Our study aimed to identify potential eicosanoid metabolites as salt sensitivity biomarkers in CKD patients by studying their concentration changes in response to SRD. Serum and urine samples were collected from 34 patients enrolled in the LoSalt trial. This is a randomized crossover trial of CKD stage 3-4 patients who underwent SRD. Targeted metabolomic analysis of eicosanoid metabolites in pre and post SRD serum and urine were performed with liquid chromatography-mass spectrometry. While we did not find significant evidence of SRD’s effects on eicosanoid concentration, we did see trends that indicate a relationship. Arachidonic acid and resolvin D1 demonstrated a trend of increased concentration, while 14(15)-epoxyeicosatrienoic acid and 5-iso-Prostaglandin F2α-VI demonstrated a trend of decreased concentration. In order to identify these four eicosanoids as salt sensitivity markers, further studies are needed to determine if SRD has a significant effect on them as well as the eicosanoids’ connection to changes in blood pressure.