Phenylacetic Acid and Arterial Vascular Properties in Patients with Chronic Kidney Disease Stage 5 on Hemodialysis Therapy

Abstract

Background: Phenylacetic acid (PAA) is a recently described uremic toxin that inhibits inducible nitric oxide synthase expression and plasma membrane calcium ATPase and may therefore also be involved in remodeling of arteries. Such vascular effects have not been evaluated yet in patients with chronic kidney disease stage 5. Method: We prospectively measured the plasma concentrations of PAA using nuclear magnetic resonance spectroscopy in 50 patients with chronic kidney disease stage 5 (37 men, 13 women) on maintenance hemodialysis. Arterial vascular properties were quantified by the reflective index obtained from digital photoplethysmography. Results: During the hemodialysis session the plasma PAA concentration was reduced from 3.38 ± 0.24 mmol/l (mean ± SEM; median, 2.85 mmol/l; interquartile range, 2.02–4.52 mmol/l) to 2.25 ± 0.11 mmol/l (median, 2.06 mmol/l; interquartile range, 1.62–2.86 mmol/l; n = 50; p < 0.001). There was a significant correlation between the PAA concentration and the reflective index before the start of the hemodialysis session. Conclusion: The study demonstrates an association of PAA and arterial vascular properties in patients with chronic kidney disease stage 5.

Cardiovascular Burden Associated with Uremic Toxins in Patients with Chronic Kidney Disease

“…cardiac failure, hypertension, fluid overload) [2]. Multiple studies have implicated elevated concentrations of a variety of uremic toxins, including indoxyl sulfate, p -cresol, p -cresyl sulfate, PAA, blood urea nitrogen, and uric acid in the CVD seen in CKD patients [18,19,20,21,22,23,24,25,26,27,28,29,30,31]. The association of elevated uric acid concentrations with CVD in these epidemiologic studies has been corroborated by results of prospective clinical trials involving allopurinol, which decreases serum uric acid levels by inhibiting xanthine oxidase [32,33].…”

Gases as Uremic Toxins: Is There Something in the Air?

“…Interestingly, an association of PAA and arterial vascular properties in patients with chronic kidney disease (CKD) stage 5 has been documented recently. 10 Furthermore, PAA interacts with the innate immune response: PAA has inhibitory effects on the macrophage-killing function, which are mediated by inhibitory effects on transcriptional iNOS regulation.…”

“…More than 500 different VOCs have been identified. 10 These volatile substances may be of endogenous origin or may be absorbed from the environment. Physicians have tried to make diagnostic use of specific odors in the exhaled air of their patients for centuries.…”

“…10 Ammonia (NH 3 ) has been detected as one of the compounds underlying this specific odor and assessment of ammonia concentrations in the breath has been postulated to be a possible tool to monitor the efficacy of hemodialysis. [12][13][14] Moreover, it has been shown that breath ammonia is correlated with blood urea nitrogen and creatinine levels and it was concluded that breath ammonia measurements could be used as a surrogate measure of the retention status of patients with renal failure.…”

“…17 Breath ammonia concentrations have been found to be correlated positively to blood urea levels in cyclic automated peritoneal dialysis and hemodialysis patients. 10,14 A recent study showed that ammonia concentrations in the breath also are increased in chronic renal failure not requiring dialysis. 18 In 1977, Simenhoff et al 17 already found that, apart from ammonia, trimethylamine (TMA) and dimethylamine (DMA) underlie the fishy odor in uremia.…”