Homoarginine and progression of chronic kidney disease: results from the Mild to Moderate Kidney Disease Study

PLoS One. 2013 May 15;8(5):e63560. doi: 10.1371/journal.pone.0063560. Print 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Disease Progression
  • Female
  • Glomerular Filtration Rate
  • Homoarginine / blood*
  • Humans
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / physiopathology
  • Male
  • Middle Aged
  • Prospective Studies
  • Severity of Illness Index

Substances

  • Homoarginine

Grants and funding

Parts of this work were supported by the "Genomics of Lipid-associated Disorders – GOLD" of the "Austrian Genome Research Programme GEN-AU" to F. Kronenberg. The work was furthermore supported by a fellowship grant from the Medical Faculty of the University of Würzburg (Habilitationsstipendium) to C. Drechsler. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.