Elevated Levels of Alkanals, Alkenals and 4-HO-Alkenals in Plasma of Hemodialysis Patients

Abstract

Background/Aims: Several studies have implicated reactive carbonyl compounds (RCOs), especially those derived from lipid peroxidation, in the development of complications frequently associated with hemodialysis (HD) treatment. However, there is still much unknown regarding the nature and concentration of RCOs in HD patients. This study was designed to evaluate the level of toxic aldehydes in the plasma of HD patients and to determine the extent to which these aldehydes contribute to RCO toxicity among these patients. Methods: 15 aldehydes of the alkanal, alkenal and 4-HO-alkenal type were measured in the plasma of 17 HD patients and 20 healthy controls. In addition, protein modification markers such as carbonyl content (CO), free thiol (SH) and residual free amino groups, as well as amyloid fibrils were also determined. Results: 11 of the 15 aldehydes were significantly elevated in the HD group when compared with the controls. Correlation studies in the HD group revealed high relationships between total alkenals plus total 4-HO-alkenals versus CO, total alkanals versus NH₂, total aldehydes versus SH, and total 4-HO-alkenals versus fibril. Conclusion: The increased levels of alkanals, alkenals and 4-HO-alkenals of lipid peroxidation in the plasma of HD patients may greatly contribute to the toxicity of RCOs. The pattern of modification of plasma protein by each group of aldehydes may provide new evidence on the in vivo mechanisms of toxicity triggered by these aldehydes on their target molecules.

Two Toxic Lipid Aldehydes, 4-hydroxy-2-hexenal (4-HHE) and 4-hydroxy-2-nonenal (4-HNE), Accumulate in Patients with Chronic Kidney Disease

“…Plasma levels of 4-HHE (4.5-fold) and 4-HNE (six-fold) were higher in CKD 4-5 patients than in controls unambiguously evidencing the presence of oxidative stress before the initiation of dialysis. These results are in line with the report of Alhamdani et al [29] who observed an increase in both 4-HHE (2.5-fold) and 4-HNE (seven-fold) in hemodialysis patients. These data suggest that oxidative stress could rather result from the uremic/inflammatory environment than from the renal replacement therapy (such as HD).…”

“…Few studies previously reported that plasma lipid aldehydes (among which 4-HNE and 4-HHE) concentrations were increased in chronic hemodialysis patients [29]. However, no data is available in the literature regarding the actual concentration of 4-HNE and 4-HHE in CKD patients before initiation of renal replacement therapy, a process that exacerbates oxidative stress [31,34].…”

Modified Lipids and Lipoproteins in Chronic Kidney Disease: A New Class of Uremic Toxins

“…In a study by Sommerburg et al, mean level of 4-HNE was 3 fold higher in HD patients compared to healthy controls [257]. Alhamdani et al showed that alkanals, alkenals and 4-hydroxy-alkenals concentrations are increased in HD patients compared to controls [258] (Table 1). Interestingly, HD procedure tends to reduce the 4-HNE concentration in several reports [116,119,120].…”

Chromatographic determination of low-molecular mass unsaturated aliphatic aldehydes with peroxyoxalate chemiluminescence detection after fluorescence labeling with 4-(N,N-dimethylaminosulfonyl)-7-hydrazino-2,1,3-benzoxadiazole

“…From these end products, the low-molecular mass unsaturated aliphatic aldehydes (LMMUAA) are the most cytotoxic one due to the presence of both alkene and aldehydic group. These reactive groups can react rapidly with DNA and protein leading to many pathological diseases such as atherosclerosis, diabetes mellitus (DM), rheumatic arthritis (RA), chronic renal failure, cancer and neurodegenerative diseases [1,[3][4][5][6][7][8].…”