Serum Levels of Pigmentation Markers Are Elevated in Patients Undergoing Hemodialysis

Abstract

Background: Diffuse hyperpigmentation is common among patients with chronic renal failure undergoing hemodialysis (HD). We have examined serum levels of 5-S-cysteinyldopa (5SCD, a pheomelanin precursor), pheomelanin, eumelanin, and protein-bound (PB-) 3,4-dihydroxyphenylalanine (DOPA) and PB-5SCD in HD patients. Methods: Pheomelanin and eumelanin were assayed by chemical degradation methods. Results: Serum levels of free 5SCD in HD patients (n = 16) were 9-fold higher than in healthy controls (n = 16). Levels of pheomelanin in HD patients were 2.6-fold higher than in controls, while levels of eumelanin did not differ between HD patients and controls. Levels of PB-DOPA and PB-5SCD in HD patients were approximately 1.5-fold higher than in controls. Serum levels of free 5SCD were positively correlated to the duration of HD therapy. Conclusions: The high constitutive levels of free 5SCD, pheomelanin, and PB-DOPA in the blood may be deteriorating in HD patients through the production of reactive oxygen species.

Pigmentation Markers: More Color in the Picture of Uremic Toxicity?

“…The results reported by Murakami et al [4] should be considered with care as they are based on only 16 hemodialysis patients and, therefore, need confirmation; of note, 6 of these patients were diabetics, who are known to suffer from an exponential degree of oxidative stress as compared to non-diabetic chronic kidney failure patients. This is a matter of concern since most of the solutes depicted in their article are the result of oxidative modifications.…”

“…Apart from their link to melanoma [7] and skin and hair pigmentation [8,9] , there is only scant information about the clinical and biochemical significance of these pigmentation markers, but a number of features referred to in the article by Murakami et al [4] are nevertheless striking, especially for those interested in uremic toxicity and the therapeutic options for fighting this condition. Basically, four reflections come to mind.…”

“…In this issue of Blood Purification, pigmentation markers or melanins, previously unknown as retention solutes, are added as a new set of uremic compounds to the existing list of known uremic toxins [1] by Murakami et al [4] . At the same time the authors offer information related to one of the most intriguing but insufficiently explained epiphenomena of the uremic syndrome: hyperpigmentation from which many patients with chronic kidney disease suffer [5,6] .…”

“…Hence, if the held hypothesis is correct, hyperpigmentation could be avoided by eradicating or discouraging any inflammation-generating condition, such as chronic sources of infection like periodontitis, the use of central vein catheters, the application of bio-incompatible dialysis membranes, and/or contact with bacteriologically contaminated dialysis water. With the link to inflammation in mind, it is a bit unfortunate that Murakami et al [4] did not assess any correlation with inflammatory parameters such as C-reactive protein or cytokine levels.…”

“…One should, however, be conscious of the fact that the concentration of these compounds not only depends on oxidation, but also on (lack of) clearance by kidneys and/or dialysis and on the impact of ultraviolet light on the skin [8] , hence creating a potential bias for the use of these compounds as an oxidative marker. In addition, the solutes studied by Murakami et al [4] cannot be considered as stable chemical structures. Conceivably they are further metabolized to other compounds at unpredictable but often short intervals, partly again by oxidation [16] .…”