Abstract
Carbamoylation is an important risk factor for accelerated atherogenesis and mortality in patients undergoing hemodialysis (HD). We intended to explore whether carbamoylation as assessed by near-infrared (NIR) analysis of nail proteins is associated with (a) plasma concentrations of representative uremic toxins and (b) mortality in HD patients. A total of 53 healthy volunteers and 84 consecutive HD patients were enrolled in this cross-sectional cohort study. Standard laboratory methods were used to measure routine parameters, whereas levels of uremic toxins were determined using reversed-phase high-performance liquid chromatography (RP-HPLC). Spectra of distal fingernail clippings were obtained using an Avantes NIR spectrometer and processed using chemometric data analysis. The second derivative of the peak intensity at 1494 nm attributed to N-H amide bands from NH2 of carbamoyl (-CONH2) groups was higher in HD patients than in control subjects (p < 0.0001). Peak intensity levels were associated with age and plasma levels of representative uremic toxins. Cox-regression analysis revealed a significant association with all-cause mortality, even after adjustment for age. In conclusion, our data revealed that carbamoylation as assessed by NIR analysis of nail proteins is associated with plasma concentrations of uremic toxins and also with mortality in HD patients. Further research to explore whether it is a surrogate marker or a hard indicator of mortality risk is warranted.
Highlights
Chronic kidney disease (CKD) is a global public health problem with a varying prevalence ranging from 3–18%, depending on the region and population studied [1]
Univariate Cox regression analysis revealed that age (hazard ratio (HR) = 1.065, 95% confidence interval (CI) = 1.028–1.10, p = 0.0005), history of cardiovascular disease (CVD) (HR = 2.81, 95% CI = 1.22–6.50, p = 0.016), free PCG
We identified for the first time several spectral features related to carbamoylation in distal fingernail clippings of HD patients
Summary
Chronic kidney disease (CKD) is a global public health problem with a varying prevalence ranging from 3–18%, depending on the region and population studied [1]. Several biomarkers have been proposed to assess the extent of protein carbamoylation in biological samples. Characteristic compounds such as homocitrulline often require specialized analytical techniques such as liquid chromatography–tandem mass spectrometry (LC-MS/MS) [6]. Nail keratins have the potential to accumulate PTMs such as carbamoylation due to their high protein content (80% of total mass) and long half-life (Figure 1) [2], which may eventually lead to changes in the near-infrared (NIR) spectrum of the nail [7]. We intended to explore whether carbamoylation as assessed by NIR analysis of nail proteins is associated with (a) plasma concentrations of uremic toxins and (b) mortality in HD patients
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