Evaluation of nitric oxide (indirect method) in dogs and cats affected with chronic kidney diseases

Human patients affected with chronic kidney disease (CKD) show a decrease in endogenous production of nitric oxide (NO). Similar observations were detected in experimental models in laboratory animals. The aim of this study is to evaluate the metabolism of endogenous NO in dogs and cats affected with CKD by an indirect method: the determination of its stable oxidation products nitrite and nitrate (NOx). Serum and urine samples were analysed from privately owned 12 dogs and 15 cats affected by CKD during the monitoring of the diseases and from 5 healthy dogs and 5 healthy cats during their routine sanitary check-up. Serum urea and creatinine, proteinuria, creatininuria and serum and urinary NOx were assessed. All the parameters were determined by an automated spectrophotometr (Cobas Mira®, Roche). Statistic analysis (analysis of variance and linear regression) was performed by JMP7 (SAS Inc). Analysis of data revealed a significant difference between serum NOx levels determined in CKD and healthy groups (p=0.0465) in both species, with a tendency to lower values in the pathological animals. Furthermore serum NOx wasn’t significantly related with the other parameters evaluated. In cats, a significant variance was shown between urinary NOx levels in healthy and CKD groups (p=0.049), with a tendency to higher values in healthy cats. Because only one cat was proteinuric, the relation of urinary NOx vs proteinuria, creatininuria and urine protein to creatinine ratio (UPC) was not evaluated. In dogs, a statistically significant variance between urinary NOx levels in healthy and pathological groups was not detected. The linear regression showed that urinary NOx tends to increase with increasing of proteinuria (p=0.0019) and UPC (p=0.0009). This preliminary study supports the hypothesis that the decrease in serum NO in animals affected by CKD may be due to its lower production or to a greater degradation in the course of this disease, as it has been demonstrated in human medicine. Moreover, this study indicates the need to assess the urinary NOx levels in relation to the degree of proteinuria. In fact, the increase of urinary NOx, in the proteinuric subjects, could arise from its increased local synthesis in course of inflammatory or degenerative glomerular diseases. It has been already demonstrated that in these pathological conditions the inflammatory cytokines stimulate a higher production of NO through the activity of NO sintetase - inducible form.