Homoarginine and Mortality in Pre-Dialysis Chronic Kidney Disease (CKD) Patients

BACKGROUND AND AIMS Homoarginine, a precursor of nitric oxide, is an inverse predictor of death in dialysis patients and in subjects with cardiovascular disease and normal kidney function but its relationship with clinical outcomes in chronic kidney disease (CKD) patients not yet on dialysis is unknown. DESIGN SETTING PARTICIPANTS AND MEASUREMENTS We enrolled 168 consecutive predialysis CKD patients (Age: 70 ± 11 yrs; 26% Diabetics; eGFR 34 ± 18 ml/min/1.73 m(2)) referred to a tertiary care centre and measured laboratory data on kidney function and cardiovascular risk factors. We modeled progression to dialysis or death as a function of homoarginine, using Cox's regression, accounting for clinical characteristics, baseline levels of kidney function, and markers of inflammation. RESULTS On crude and adjusted analyses homoarginine was directly associated with the eGFR and patients with more compromised renal function exhibited lower homoarginine levels. Furthermore homoarginine was also independently related to L-arginine, serum albumin and body mass index, and inversely related to proteinuria, C-reactive protein and age. During the study (follow up median time 4 years, inter-quartile range 1.7 to 7.0 years) 56 patients started dialysis and 103 died and homoarginine was a strong inverse predictor of the incidence rate of both outcomes (P=0.002 and P=0.017). CONCLUSIONS Homoarginine declines with advancing renal disease and is inversely related to progression to dialysis and mortality. The nature of the link between homoarginine and clinical outcomes is amenable to testing in clinical trials.