Clinical Nephrology – Epidemiology – Clinical Trials
Kidney International (2003) 63, 1104–1115; doi:10.1046/j.1523-1755.2003.00833.x
Role of endogenous nitric oxide in unilateral ureteropelvic junction obstruction in children
Patricia G Vallés, Luis Pascual, Walter Manucha, Liliana Carrizo and Maria Rüttler
Cátedra de Fisiopatología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo and Hospital H. Notti, Mendoza, Argentina
Correspondence: Patricia G. Vallés, M.D., Cátedra de Fisiopatología, Facultad de Ciencias Médicas, Universidad Nacional de Cuyo, Centro Universitario CP 5500, Mendoza, Argentina. E-mail: pvalles@fmed2.uncu.edu.ar
Received 15 October 2001; Revised 24 October 2002; Accepted 28 October 2002.
Abstract
Role of endogenous nitric oxide in unilateral ureteropelvic junction obstruction in children.
Background
Obstructive nephropathy leads to tubulointerstitial fibrosis and loss of renal function. Nitric oxide has been shown to have antifibrotic properties. We examined nitric oxide synthase (NOS) activity and expression in kidneys from children who underwent surgery release of unilateral ureteropelvic junction (UPJ) obstruction in relation to clinical and histologic parameters.
Methods
NOS activity and the expression of NOS isoforms measured at the mRNA level by reverse transcription-polymerase chain reaction (RT-PCR) assay were determined in tissue obtained by biopsy from obstructed kidneys of 18 children at the time of pyeloplasty. Tissue from kidneys removed because of various malignancies were issued as control.
Results
A significant increase in calcium/calmodulin-independent NOS activity (iNOS) and iNOS mRNA expression was found in the medulla of obstructed kidneys. Calcium/calmodulin-dependent NOS activity (cNOS) and endothelial (eNOS) mRNA, by contrast, were increased in the cortex from obstructed kidneys. A role of tumor necrosis factor-
(TNF-) on enhanced iNOS was suggested by the finding of increased urine levels in obstructed pelvis. Increased interstitium macrophage number, by immunolabeling of CD68, was related to the delay in obstruction release and to decreased glomerular filtration rate (GFR) at surgery. A positive linear relationship was found between cNOS activity in cortex and creatinine clearance. The degree of interstitial fibrosis correlated negatively with cNOS activity in cortex.
Conclusion
In kidneys from children with UPJ obstruction an increased activity and expression of iNOS in medulla and cNOS-dependent eNOS in cortex were demonstrated. A role of cNOS in modulating GFR and interstitial fibrosis can be suggested. Prolonged UPJ obstruction would lead to a worsened prognosis on renal injury .
Keywords:
unilateral ureteropelvic junction obstruction, nitric oxide synthase activity, inducible nitric oxide synthase mRNA, tumor necrosis factor-, macrophage, endothelial nitric oxide synthase mRNA
