Abstract
Background and AimsHomoarginine, 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 measurementsWe enrolled 168 consecutive predialysis CKD patients (Age: 70±11 yrs; 26% Diabetics; eGFR 34±18 ml/min/1.73 m2) 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.ResultsOn 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).ConclusionsHomoarginine 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.
Highlights
Reduced nitric oxide (NO) bioavailability is a major risk factor for cardiovascular disease and progression to kidney failure in patients with chronic kidney disease (CKD) [1,2,3]
In this study we investigated the relationship between circulating homoarginine with traditional and non-traditional cardiovascular risk factors in an incident cohort of CKD patients and tested the relationship between this aminoacid and all-cause and cardiovascular death, and renal outcomes
Correlates of Homo-Arginine On crude (Figure 1) and adjusted (Table 2) analyses homoarginine was directly related to L-arginine, serum albumin and body mass index, and inversely related to proteinuria, Creactive protein and age
Summary
Reduced nitric oxide (NO) bioavailability is a major risk factor for cardiovascular disease and progression to kidney failure in patients with chronic kidney disease (CKD) [1,2,3]. Accumulation of endogenous inhibitors of NO synthase apart, low homoarginine levels associated with decreased renal function [5] may contribute to reduce NO synthesis in CKD This lysine-derived cationic amino acid may increase NO bioavailability by multiple mechanisms [6]. The same authors documented an inverse association between plasma homoarginine, left ventricular systolic dysfunction, and all-cause and cardiovascular mortality in the same cohort, and confirmed this association in a second cohort of hemodialysis patients with type-2 diabetes [8] These findings implicate progressive homoarginine deficiency brought about by declining renal function in the high cardiovascular risk engendered by progressive CKD. 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
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