Treatment of hyperhomocysteinemia with folic acid reduces oxidative stress in renal transplant recipients

New-onset diabetes after transplantation (NODAT) is a frequent complication in renal transplant recipients (RTR). Although oxidative stress has been associated with diabetes mellitus, data regarding NODAT are limited. We aimed to prospectively investigate the long-term association between the oxidative stress biomarker malondialdehyde (measured by high-performance liquid chromatography) and NODAT in an extensively phenotyped cohort of non-diabetic RTR with a functioning graft ≥1 year. We included 516 RTR (51 ± 13 years-old, 57% male). Median plasma malondialdehyde (MDA) was 2.55 (IQR, 1.92–3.66) µmol/L. During a median follow-up of 5.3 (IQR, 4.6–6.0) years, 56 (11%) RTR developed NODAT. In Cox proportional-hazards regression analyses, MDA was inversely associated with NODAT, independent of immunosuppressive therapy, transplant-specific covariates, lifestyle, inflammation, and metabolism parameters (HR, 0.55; 95% CI, 0.36–0.83 per 1-SD increase; p < 0.01). Dietary antioxidants intake (e.g., vitamin E, α-lipoic acid, and linoleic acid) were effect-modifiers of the association between MDA and NODAT, with particularly strong inverse associations within the subgroup of RTR with relatively higher dietary antioxidants intake. In conclusion, plasma MDA concentration is inversely and independently associated with long-term risk of NODAT in RTR. Our findings support a potential underrecognized role of oxidative stress in post-transplantation glucose homeostasis.

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Folic acid supplementation and homocyst(e)ine level in renal transplant recipients

Transplantation Proceedings ◽

10.1016/s0041-1345(00)02785-8 ◽

2001 ◽

Vol 33 (1-2) ◽

pp. 2049-2050 ◽

Cited By ~ 3

Author(s):

B Grandtnerová ◽

L Laca ◽

D Gábor ◽

E Gregová ◽

S Korónyi

Keyword(s):

Folic Acid ◽

Renal Transplant ◽

Folic Acid Supplementation ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Acid Supplementation

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The Relationship Between Antioxidant Supplements and Oxidative Stress in Renal Transplant Recipients: A Review

ASAIO Journal ◽

10.1097/01.mat.0000138077.90404.c8 ◽

2004 ◽

Vol 50 (5) ◽

pp. 451-457 ◽

Cited By ~ 8

Author(s):

Melanie L. Blackhall ◽

Jeff S. Coombes ◽

Rob Fassett

Keyword(s):

Oxidative Stress ◽

Renal Transplant ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Antioxidant Supplements ◽

The Relationship ◽

And Oxidative Stress

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Homocysteine in the Plasma of Renal Transplant Recipients: Effects of Cofactors for Methionine Metabolism

Clinical Science ◽

10.1042/cs0610743 ◽

1981 ◽

Vol 61 (6) ◽

pp. 743-749 ◽

Cited By ~ 97

Author(s):

D. E. L. Wilcken ◽

Vatsala J. Gupta ◽

A. K. Betts

Keyword(s):

Folic Acid ◽

Amino Acid ◽

Renal Transplant ◽

Serum Creatinine ◽

Vitamin B12 ◽

Normal Subjects ◽

Serum Folate ◽

Renal Transplant Recipients ◽

Transplant Recipients ◽

Erythrocyte Folate

1. Homocysteine which is formed during the metabolism of methionine is readily oxidized and is measured by the amino acid analyser as cysteine—homocysteine mixed disulphide and homocystine. We measured plasma amino acid concentrations after an overnight fast in 27 stable long-term renal transplant recipients and 25 age-and sex-matched normal subjects with particular emphasis on sulphur-containing amino acids. 2. Plasma cysteine—homocysteine mixed disulphide was increased in the patients (mean 6.0 ± sd 3.2 μmol/l; normal 3.1 ± 0.9 μmol/l, P < 0.001) and homocystine was detectable in low concentration (< 1.0 μmol/l) in 24; the elevation in cysteine—homocysteine was related to serum creatinine (r = 0.60, P < 0.002). Cystine was also increased (91.6 ± 29.3 μmol/l; normal subjects 64.0 ± 16.7 μmol/l, P < 0.001), but methionine concentrations were normal. 3. When pyridoxine, folic acid and vitamin B12, cofactors for homocysteine metabolism, were administered sequentially to 11 arbitrarily selected transplant recipients cysteine—homocysteine decreased from 7.3 ± 2.1 to 4.3 ± 0.8 μmol/l (P < 0.001) and homocystine became undetectable. the response coincided with the giving of folic acid and occurred without alteration in serum creatinine and with normal serum folate and vitamin B12 concentrations. 4. in eight patients in whom pretreatment erythrocyte folate was measured, folic acid therapy reduced cysteine—homocysteine from 9.0 ± 3.1 to 5.4 ± 1.6 μmol/l over a 4 week period (P < 0.001), the largest response being in the one patient with subnormal erythrocyte folate; values were in the low-normal or normal range in the other seven. 5. We conclude that plasma homocysteine is increased in renal transplant recipients when serum creatinine is only moderately elevated and that the homocysteine concentrations are decreased by treatment with folic acid, suggesting that both reduced homocysteine excretion and relative shortages of folic acid are responsible.

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