UPLC-QTOF MS-Based Serum Metabolomic Profiling Analysis Reveals the Molecular Perturbations Underlying Uremic Pruritus

Abstract

As one of the most troublesome complications in patients with chronic renal disease, the etiology of uremic pruritus remains unknown, and the current therapeutic approaches are limited and unsatisfactory. To identify potential biomarkers for improving diagnosis and treatment and obtain a better understanding of the pathogenesis of uremic pruritus, we compared serum metabolome profiles of severe uremic pruritus (HUP) patients with mild uremic pruritus (LUP) patients using ultraperformance liquid chromatography-quadruple time-of-flight mass spectrometry (UPLC-QTOF MS). Partial least squares discriminant analysis (PLS-DA) showed that the metabolic profiles of HUP patients are distinguishable from those of LUP patients. Combining multivariate with univariate analysis, 22 significantly different metabolites between HUP and LUP patients were identified. Nine of the 22 metabolites in combination were characterized by a maximum area-under-receiver operating characteristic curve (AUC = 0.899) with a sensitivity of 85.1% and a specificity of 83.0% distinguishing HUP and LUP. Our results indicate that serum metabolome profiling might serve as a promising approach for the diagnosis of uremic pruritus and that the identified biomarkers may improve the understanding of pathophysiology of this disorder. Because the 9 metabolites were phospholipids, uremic toxins, and steroids, further studies may reveal their possible role in the pathogenesis of uremic pruritus.

Metabolomic analysis of uremic pruritus in patients on hemodialysis

“…A more sophisticated analysis of plasma from a larger number of patients might however identify related chemical structures which can trigger pruritus. In this regard, a previous metabolomic analysis did show separation in the solute profiles of patients with more and less pruritus but did not identify individual solutes or common chemical structures with which pruritus was associated [17]. Finally, the measurement of pruritus is subjective.…”

Chronic Kidney Disease-Associated Pruritus

“…Another study used ultraperformance liquid chromatography coupled with time-of-flight mass spectrometry (UPLCMS) for metabolic profiling of serum from CKD-aP patients to find diagnostic biomarkers for uremic pruritus, if any. They divided the patients into two groups according to the severity of pruritus and found nine metabolites (LysoPE (20:3(5Z,8Z,11Z)/0:0), p-cresol glucuronide, LysoPC(20:2(11Z,14Z)), hypotaurine, 4-aminohippuric acid, LysoPC(16:0), phenylacetic acid, kynurenic acid, and androstenedione) to be responsible for severe CKD-aP [ 28 ].…”

Emerging Role of Transient Receptor Potential Vanilloid 4 (TRPV4) Ion Channel in Acute and Chronic Itch

“…Mass spectrometry of lesional skin from atopic dermatitis patients revealed an increase in short-chain LPC species [ 43 ]. Moreover, a recent study found that LPC concentrations are significantly elevated systemically in uremic patients with pruritus [ 44 ]. In our recent study [ 16 ], we demonstrated that LPC, as a novel pruritogen, is robustly pruritic in mice, and that TRPV4 in skin keratinocytes is essential for LPC-induced itch and itch in mice with cholestasis in a model of α-naphthyl-isothiocyanate (ANIT).…”