Haemolysis in haemodialysis patients: evidence for impaired defence mechanisms against oxidative stress.
BACKGROUND
Uraemic patients have a decreased ability to withstand oxidative stress. It is postulated that their antioxidant capacity is reduced, yet the mechanism remains unclear. Recently 33 haemodialysis (HD) patients were exposed to chloramine contamination in the water supply. This led to haemolysis in 24 patients, while nine were unaffected. In the former group haemoglobin decreased from 11.7+/-1.1 to 8.5+/- 1.4 g/dl (P<0.0001) and returned to 11.4+/-0.9 g/dl (P<0.0001) following recovery. During haemolysis, haptoglobin was 38.4+/-10.6 vs 138.1+/-8.3 ng/dl (P<0.0001) following recovery.


METHODS
To explore the factors affecting the severity of haemolysis we studied extracellular and intracellular anti-oxidant defence mechanisms 3 months after recovery. In 29 patients and 20 controls we determined plasma glutathione (GSH), and the erythrocyte enzymes glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rx), and superoxide dismutase (SOD). Serum malondialdehyde (MDA) was measured as a marker of oxidative stress.


RESULTS
Plasma GSH was lower in patients as compared to controls (5.49+/-0.26 vs 7.4+/-0.5 micromol/l, P<0.005). There was an inverse correlation between GSH and the degree of haemolysis (r=-0.42, P<0.02). Patients had higher GSH-Rx (4.64+/-0.15 vs 3.97+/-0.12 U/gHb, P<0.02), lower GSH-Px (29. 7+/-1.85 vs 35.5+/-1.62 U/gHb, P<0.001), and similar SOD (0.63+/-0. 02 vs 0.51+/-0.02 U/mgHb) as compared to controls. There was no correlation between the enzyme levels and the degree of haemolysis. MDA was higher in patients (2.37+/-0.07 vs 0.97+/-0.1 nmol/ml, P<0. 0001). There was a correlation between MDA and the years patients were on HD (r=0.43, P<0.02).


CONCLUSIONS
These data indicate that HD patients have an impaired anti-oxidant response, which may be attributed in part, to plasma GSH deficiency. Patients with the lowest plasma GSH levels are more susceptible to oxidative stress and consequent haemolysis.
Weinstein
T
T
Department of Nephrology, Rabin Medical Centre-Golda Campus, Petah-Tikva, Sackler Medical School, Tel-Aviv University, Israel.
Chagnac
A
A
Korzets
A
A
Boaz
M
M
Ori
Y
Y
Herman
M
M
Malachi
T
T
Gafter
U
U
D000328:Adult; D000368:Aged; D004912:Erythrocytes / Q000201:enzymology; D005260:Female; D005978:Glutathione / Q000097:blood; D005979:Glutathione Peroxidase / Q000097:blood; D005980:Glutathione Reductase / Q000097:blood; D006242:Haptoglobins / Q000032:analysis; D006454:Hemoglobins / Q000032:analysis; D006461:Hemolysis; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D018384:Oxidative Stress; D012016:Reference Values; D012044:Regression Analysis; D006435:Renal Dialysis; D013482:Superoxide Dismutase / Q000097:blood; D014511:Uremia / Q000097:blood / Q000503:physiopathology* / Q000628:therapy*
D006242:Haptoglobins; D006454:Hemoglobins; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D005978:Glutathione