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ORIGINAL RESEARCH ARTICLE

Accumulation of Symmetric Dimethylarginine in Hepatorenal Syndrome

Paloma Lluch^*, Maria D. Mauricio, José M. Vila^,1, Gloria Segarra, Pascual Medina, Juan A. del Olmo^*, José M. Rodrigo^* and Miguel A. Serra^*

^* Servicio de Hepatología, Hospital Clínico Universitario, Departamento de Medicina, Universidad de Valencia, Valencia, Spain; Departamento de Fisiología, Universidad de Valencia, Valencia, Spain; and Unidad Mixta de Investigación, Hospital Clínico Universitario de Valencia, Valencia, Spain

To whom requests for reprints should be addressed at ¹ Departamento de Fisiología, Facultad de Medicina, Universidad de Valencia, Blasco Ibáñez, 17, 46010 Valencia, Spain. E-mail: jose.m.salinas{at}uv.es.

In patients with cirrhosis, nitric oxide (NO), asymmetric dimethylarginine (ADMA), and possibly symmetric dimethylarginine (SDMA) have been linked to the severity of the disease. We investigated whether plasma levels of dimethylarginines and NO are elevated in patients with hepatorenal syndrome (HRS), compared with patients with cirrhosis without renal failure (no-HRS). Plasma levels of NO, ADMA, SDMA, and L-arginine were measured in 11 patients with HRS, seven patients with no-HRS, and six healthy volunteers. SDMA concentration in HRS was higher than in no-HRS and healthy subjects (1.47 ± 0.25 vs. 0.38 ± 0.06 and 0.29 ± 0.04 µM, respectively; P < 0.05). ADMA and NO_x concentrations were higher in HRS and no-HRS patients than in healthy subjects (ADMA, 1.20 ± 0.26, 1.11 ± 0.1, and 0.53 ± 0.06 µM, respectively; P < 0.05; NO_x, 94 ± 9.1, 95.5 ± 9.54, and 37.67 ± 4.62 µM, respectively; P < 0.05). In patients with HRS there was a positive correlation between serum creatinine and plasma SDMA (r² =0.765, P < 0.001) but not between serum creatinine and ADMA or NO_x. The results suggest that renal dysfunction is a main determinant of elevated SDMA concentration in HRS. Accumulation of ADMA as a result of impaired hepatic removal may be the causative factor initiating renal vasoconstriction and SDMA retention in the kidney.

Key Words: nitric oxide • methylarginines • cirrhosis • renal failure

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