Abstract
BackgroundHomoarginine 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).MethodsWe 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.ResultsStudy 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).ConclusionsHomoarginine 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.
Highlights
Chronic kidney disease (CKD) represents a major public health problem with an increasing prevalence as well as an increase in the incidence rate of end-stage renal disease [1,2]
Homoarginine concentrations were incrementally lower at lower levels of GFR with mean concentrations of 2.9061.02 mmol/L, 2.6461.06 mmol/L, 2.5261.24 mmol/L and 2.0560.78, respectively
Homoarginine concentrations were significantly related to GFR (r = 0.25, p = 0.001), proteinuria (r = 20.21, p = 0.005) and creatinine (r = 20.31, p,0.001)
Summary
Chronic kidney disease (CKD) represents a major public health problem with an increasing prevalence as well as an increase in the incidence rate of end-stage renal disease [1,2]. The costs of treatment put an enormous burden on health care resources since renal replacement therapy represents one of the most expensive chronic therapies. Patients with a moderately impaired kidney function already have a high risk to develop cardiovascular complications [4]. Cardiovascular risk further increases with the decline in kidney function, and the majority of CKD patients die from cardiac and vascular events before reaching end-stage renal disease. Prevention of disease progression and associated complications is highly important including the treatment of renal risk factors. We aimed to investigate the relation between homoarginine, kidney function and progression of chronic kidney disease (CKD)
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