title: Homoarginine and progression of chronic kidney disease: results from the Mild to Moderate Kidney Disease Study.
abstract: BACKGROUND
  Homoarginine is an amino acid derivative mainly synthesized in the kidney. It is suggested to increase nitric oxide availability, enhance endothelial function and to protect against cardiovascular diseases. We aimed to investigate the relation between homoarginine, kidney function and progression of chronic kidney disease (CKD).
  
  
  METHODS
  We measured plasma homoarginine concentrations in baseline samples of the Mild to Moderate Kidney Disease (MMKD) Study, a prospective cohort study of 227 patients with CKD in Europe. Homoarginine concentrations were available in 182 of the baseline samples and in 139 of the prospectively-followed patients. We correlated homoarginine concentrations to parameters of kidney function. The association between homoarginine and progression of CKD was assessed during a follow-up of up to seven years (median 4.45 years, interquartile range 2.54-5.19) using Cox regression analysis. Progression of CKD was defined as doubling of baseline serum creatinine and/or end-stage renal disease.
  
  
  RESULTS
  Study participants were at baseline on average 47±13 years old and 65% were male. Mean±standard deviation of homoarginine concentrations were 2.5±1.1 µmol/L and concentrations were incrementally lower at lower levels of GFR with mean concentrations of 2.90±1.02 µmol/L (GFR>90 ml/min), 2.64±1.06 µmol/L (GFR 60-90 ml/min), 2.52±1.24 µmol/L (GFR 30-60 ml/min) and 2.05±0.78 µmol/L (GFR<30 ml/min), respectively (p = 0.002). The age- and sex-adjusted risk to reach the renal endpoint was significantly higher by 62% with each decrease by one standard deviation (1.1 µmol/L) of homoarginine (HR 1.62, 95% CI 1.16-2.27, p = 0.005). This association was independent of proteinuria (HR 1.56, 95% CI 1.11-2.20, p = 0.01), and was slightly attenuated when adjusting for GFR (HR 1.40 (95% CI 0.98-1.98, p = 0.06).
  
  
  CONCLUSIONS
  Homoarginine concentrations are directly correlated with kidney function and are significantly associated with the progression of CKD. Low homoarginine concentrations might be an early indicator of kidney failure and a potential target for the prevention of disease progression which needs further investigations.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Würzburg, Würzburg, Germany.
authors.forename: Christiane
authors.initials: C
authors.lastname: Drechsler
authors.forename: Barbara
authors.initials: B
authors.lastname: Kollerits
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinitzer
authors.forename: Winfried
authors.initials: W
authors.lastname: März
authors.forename: Eberhard
authors.initials: E
authors.lastname: Ritz
authors.forename: Paul
authors.initials: P
authors.lastname: König
authors.forename: Ulrich
authors.initials: U
authors.lastname: Neyer
authors.forename: Stefan
authors.initials: S
authors.lastname: Pilz
authors.forename: Christoph
authors.initials: C
authors.lastname: Wanner
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
mesh_terms: D000328:Adult; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D006709:Homoarginine / Q000097:blood*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012720:Severity of Illness Index
chemical_list: D006709:Homoarginine