Homocysteine, cysteine, and B vitamins as predictors of kidney disease progression.
BACKGROUND
Pathological similarities between atherosclerosis and glomerulosclerosis suggest that risk factors for the two processes may be similar. Elevated total homocysteine (tHcy) levels and low B vitamin levels are risk factors for atherosclerosis, but have not been evaluated sufficiently as risk factors for the progression of kidney disease.


METHODS
Frozen samples from the Modification of Diet in Renal Disease Study were assayed for serum tHcy, cysteine, pyridoxal 5-phosphate (PLP), folate, and vitamin B12 levels in 804 participants. These factors were evaluated in both continuous and categorical analyses as risk factors for glomerular filtration rate (GFR) decline by using univariate and multivariable analyses.


RESULTS
At baseline, mean tHcy levels in study A (GFR, 25 to 55 mL/min/1.73 m2) and study B (GFR, 13 to 24 mL/min/1.73 m2) were 16.9 micromol/L (median, 15.6 micromol/L) and 23.0 micromol/L (median, 20.5 micromol/L), respectively. Mean follow-up was 2.2 years. Mean GFR declines were -4.35 and -3.65 mL/min/y in studies A and B, respectively. There was no significant association between change in GFR with baseline level of tHcy in univariate (-0.26 mL/min/y per 1-SD unit increase in tHcy level; 95% confidence interval [CI], -0.67 to 0.15) or multivariable (-0.18 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.53 to 0.17) analysis in study A or univariate (0.07 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.36 to 0.51) or multivariable (0.24 mL/min/y per 1-SD unit increase in tHcy level; 95% CI, -0.16 to 0.64) analysis in study B. Similarly, higher cysteine levels and lower B vitamin levels were not associated with faster rates of GFR decline in multivariable analysis in either study.


CONCLUSIONS
Higher tHcy or cysteine levels and lower folate, PLP, and vitamin B12 levels are not independent risk factors for progression of nondiabetic kidney disease.
Sarnak
Mark J
MJ
New England Medical Center, Boston, MA 02111, USA. msarnak@lifespan.org
Wang
Shin-Ru
SR
Beck
Gerald J
GJ
Kusek
John W
JW
Selhub
Jacob
J
Greene
Tom
T
Levey
Andrew S
AS
D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D015415:Biomarkers / Q000097:blood*; D018660:Blood Pressure Monitoring, Ambulatory / Q000379:methods; D003545:Cysteine / Q000097:blood*; D018753:Diet, Protein-Restricted; D018450:Disease Progression; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000097:blood*; D006801:Humans; D007674:Kidney Diseases / Q000097:blood* / Q000175:diagnosis / Q000178:diet therapy; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011732:Pyridoxal Phosphate / Q000097:blood; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood*
D015415:Biomarkers; D006710:Homocysteine; D011732:Pyridoxal Phosphate; D005492:Folic Acid; D003545:Cysteine; D014805:Vitamin B 12