title: Homocysteine, cysteine, and B vitamins as predictors of kidney disease progression.
abstract: 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.
authors.affiliation: New England Medical Center, Boston, MA 02111, USA. msarnak@lifespan.org
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Sarnak
authors.forename: Shin-Ru
authors.initials: SR
authors.lastname: Wang
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Beck
authors.forename: John W
authors.initials: JW
authors.lastname: Kusek
authors.forename: Jacob
authors.initials: J
authors.lastname: Selhub
authors.forename: Tom
authors.initials: T
authors.lastname: Greene
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Levey
mesh_terms: 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*
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D011732:Pyridoxal Phosphate; D005492:Folic Acid; D003545:Cysteine; D014805:Vitamin B 12