Daily haemodialysis improves indices of protein glycation.
BACKGROUND
Advanced glycation end-products (AGEs) accumulate in uraemia, regardless of hyperglycaemic conditions, and may contribute to the onset of some long-term complications, such as atherosclerosis, amyloidosis, and neurodegenerative processes. In this study, we compare a daily with a standard 3 times/week dialysis rhythm (DHD and SHD, respectively) in correcting some protein glycation indices in end-stage renal disease (ESRD) patients.


METHODS
Twenty-one normoglycaemic and 11 diabetic patients on chronic haemodialysis (HD) with low-flux dialysers were studied in a prospective protocol to compare two different dialysis schedules, namely: 4 h, 3 times/week (SHD) and 2 h, 6 times/week (DHD). The patients were studied before and after 6 months of DHD. To further check the effect of DHD on glycation parameters, 4 normoglycaemic HD patients were studied in a third step in which they returned for 3 months to the SHD rhythm. Also, 11 chronic renal failure (CRF) patients not yet on HD and 11 age- and sex-matched healthy controls were studied. A new HPLC method was used to measure the following glycation indexes on plasma: the early product furosine and the advanced products protein-bound and free pentosidine, and two heterogeneous classes of low molecular mass (LMM) AGE peptides.


RESULTS
All the parameters studied showed an accumulation that worsened with the progression of renal failure (controls <CRF <HD). Diabetic patients on SHD showed similar levels of glycation indexes as non-diabetic patients, except for the early product furosine that was notably higher. The shift from SHD to DHD was effective in lowering the concentration of all the glycation parameters measured, both in non-diabetic and diabetic patients. In the total HD population, LMM-AGEs (MM range of approx. 1.5-6.0 kDa) detected at 385 nm emission was lowered by 56% (P<0.001) and LMM-AGEs detected at 440 nm emission and furosine decreased by 23 and 19%, (P< or =0.001 and <0.01, respectively). All these three classes of compounds reached concentrations comparable with those observed in the CRF patients, even if remaining above the control range. The levels of both free and protein-bound pentosidine after DHD decreased by 34% (P<0.001) and 22% (P< or =0.05), respectively. The return for 3 months to SHD in four non-diabetic DHD patients led to a trend toward an increase in all five glycation parameters.


CONCLUSIONS
This study demonstrates for the first time that a DHD regimen can effectively lower the mean levels of glycation-related substances observed in SHD. Therefore, DHD can provide a better control of AGE produced in ESRD. This could result in a lower incidence of long-term effects of AGE accumulation in HD.
Floridi
Ardesio
A
Department of Internal Medicine, Section of Applied and Clinical Biochemistry, University of Perugia, Italy.
Antolini
Francesco
F
Galli
Francesco
F
Fagugli
Riccardo Maria
RM
Floridi
Emanuela
E
Buoncristiani
Umberto
U
D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000097:blood; D002940:Circadian Rhythm; D003928:Diabetic Nephropathies / Q000097:blood / Q000503:physiopathology / Q000628:therapy; D005260:Female; D017127:Glycation End Products, Advanced / Q000037:antagonists & inhibitors* / Q000097:blood* / Q000737:chemistry; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood / Q000503:physiopathology / Q000628:therapy; D008137:Longitudinal Studies; D008239:Lysine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000097:blood; D008297:Male; D008875:Middle Aged; D008970:Molecular Weight; D011446:Prospective Studies; D006435:Renal Dialysis / Q000009:adverse effects
D017127:Glycation End Products, Advanced; C018948:furosine; D001120:Arginine; C062187:pentosidine; D008239:Lysine