Urinary creatinine and serum cystatin C in asthmatic children treated with inhaled corticosteroid and beta 2 agonist

ABSTRACT

L-arginine, an amino acid involved in the production of urea, creatinine and nitric oxide [NO] that is known to play an important role as an inflammatory mediator in the airways. Inhaled corticosteroids and beta [2] agonists are the most frequently prescribed medications in the management of chronic asthma. Current guidelines emphasis their complementary role. Although many patients use both drugs, there is little information on the effectiveness of their combination. In the present study we investigated the effect of a combination of glucocorticoids and beta [2] -agonists inhaled by asthmatics on the metabolism of L-arginine. Sixty-six children with mild-to moderate asthma were enrolled in this study and treated with different regimens of inhaled drugs but fifty three children only completed the study [Twenty one with inhaled beta [2] agonist [salmeterol], 15 with inhaled corticosteroid [fluticasone propionate], and 17 with a combination of inhaled salmeterol and fluticasone propionate]. Fifteen healthy-matched children served as a control group. Pulmonary function tests [forced expiratory volume in one second [FEV[1]], peak expiratory flow rate [PEFR]], methacholine challenge tests, serum cystatin C, 24 hours urinary measurement of urea, creatinine, nitrates, and urinary osmolality were performed before and after three months of the inhaled drug therapy. The results of this study demonstrated [1] Non significant differences in serum cystatin C and urinary urea, creatinine, nitrates, osmolality were noted in asthmatic children vs control group. [2] non significant differences in serum cystatin C level and urine osmolality were observed in different groups before and after therapy. [3] compared to that before therapy, children treated by the combination of corticosteroid and beta [2] agonist had a significant higher level of urinary creatinine [p=0.0001] and a higher creatinine/urea ratio [c/u ratio] [p=0.0001] with significantly lower levels of urinary urea [p=0.002], and urinary nitrates [p=0.0001]. [4] in children treated by the combination of corticosteroid and beta [2] -agonist, there were a significant positive correlations between urinary creatinine and both FEV[1] [r= +0.699, p<0.01] and methacholine provocative dose causing a 20% fall in FEV[1] [R= +0.695, P< 0.01]. Also there were significant positive correlations between c/u ratio and both FEV[1] [r= +0.821, p = <0.01] and methacholine provocative dose causing a 20% fall in FEV[1] [r= +0.850, p< 0.01]. [5] in children treated with corticosteroid alone, only urinary nitrates was significantly lower after treatment as compared to that before treatment. [6] in children treated with beta [2] agonist alone, no significant differences in urinary urea, creatinine, nitrates and c/u ratio as compared to that before therapy. In asthmatic children, treatment with a combination of inhaled corticosteroid and beta [2] -agonist had a beneficial augmenting influence on the metabolism of L-arginine with better improvement of lung functions and bronchial hyperreactivity than treatment with either corticosteroid or beta [2] -agonist alone. Also creatininuria and urinary c/u ratio can be used as a simple and noninvasive parameters for assessment of response to treatment in these children. Also our results demonstrated normal serum cystatin C concentrations in asthmatic children in between attacks and remained unaffected by a therapy with inhaled corticosteroid, beta [2] agonist or a combination of both