Correlations between Plasma Levels of Anionic Uremic Toxins and Clinical Parameters in Hemodialysis Patients

Abstract

When the kidney is seriously impaired, various uremic toxins (UTs) accumulate in the body, often exerting unfavorable eŠects on physiological functions and drug pharmacokinetics. To prevent this, it is important to determine plasma UT levels accurately in chronic kidney disease patients. Although attempts to predict plasma UT levels using biomarkers have been made, the correlation between UT levels and the markers is not yet fully understood. In this study, we assessed the correlations among plasma levels of indoxyl sulfate (IS), indoleacetic acid (IA), and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) in 20 hemodialysis patients and evaluated the relationship between the plasma levels of UTs and clinical parameters, such as serum creatinine (Scr), blood urea nitrogen, and estimated glomerularˆltration rate (eGFR), with special focus on IS. There were no correlations among the plasma levels of the three UTs before and immediately after hemodialysis. However, a signiˆcant correlation was observed between plasma IS levels and Scr before hemodialysis (r＝0.643, p＝0.002), with the correlation becoming much stronger when using the data obtained immediately after hemodialysis (r＝0.744, p＜0.001). Further, plasma IS levels showed a signiˆcant negative correlation with eGFR (r＝-0.558, p＝0.011). However, no correlations were observed for IA or CMPF. The results obtained from this study suggest that plasma IS levels can be predicted from Scr values, although the precise mechanism behind the correlation remains to be clariˆed.

Different Correlation between Serum Levels of Indoxyl Sulfate and Estimated GFR in the Elderly with or without Dementia

“…In order to access this, we first compared the correlation between serum IS levels and eGFR between the elderly with or without dementia. Consistent with previous studies, 21,22) there was a significant correlation between serum IS levels of 37 residents and their eGFR (Fig.1A). However, the r value was at most -0.420, indicating that the correlation between them was not so relevant.…”

“…20) Accordingly, many interests have been placed on the blood IS levels in CKD patients and it has been suggested that eGFR is a useful parameter to roughly know blood IS levels. 21,22) However, little information is available about how the relationship between eGFR and serum IS levels changes in CKD patients when they suffer from various complications. It is well known that CD including dementia is frequent in CKD patients.…”

Uremic Toxins and Their Relation with Oxidative Stress Induced in Patients with CKD

“…Indeed, they believe that it is an indicator associated with better nutritional status and may be a marker of a healthy diet and omega 3 consumption. Its elevated serum levels in CKD patients were not associated with mortality and cardiovascular disease [102].…”

“…The level of CMPF in serum was significantly higher after hemodialysis (27.3 ±1.8 mg/L) compared to pre-hemodialysis [32]. In contrast, it is known that the concentration of CMPF in plasma does not change before and after hemodialysis [101,102]. The ratio of CMPF binding to proteins is nearly 100% and this bond is stronger than for IS or PCS [99].…”

Relationship of plasma 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid concentration with OATP1B activity in patients with chronic kidney disease

“…On the other hand, there was no significant correlation between CP-1 and eGFR at all the cutoff CMPF concentrations. Ichimura et al 26 reported that plasma indoxyl sulfate concentration correlated negatively with eGFR in 20 patients on hemodialysis, whereas plasma CMPF concentration did not. Given the above results and evidence, plasma CMPF concentration may be a more prominent factor influencing OATP1B activity than eGFR.…”