Surgical validation of functional magnetic resonance urography in the study of ureteropelvic junction obstruction in a pediatric cohort.

INTRODUCTION: Ureteropelvic junction obstruction (UPJO) is one of the most common urological diseases in children. The etiology can be intrinsic, extrinsic (crossing vessel [CV] or adhesions), or mixed. To date, ultrasonography and scintigraphy are considered gold-standard imaging techniques for the study of UPJO. Functional magnetic resonance urography (fMRU) combines anatomical and functional information and has been recently evaluated for the detection of CVs in UPJO. OBJECTIVE: The objective of the study was to evaluate the concordance between fMRU and surgery in determining the etiology of UPJO and the presence of obstructing/non-obstructing CVs. STUDY DESIGN: Patients with unilateral hydronephrosis who underwent surgery after an fMRU were included in the sample. Surgical data regarding the etiology of UPJO were compared with radiological results. The etiology was divided into intrinsic, extrinsic due to CV, extrinsic due to adhesions, and mixed or cicatricial (postoperative). The concordance was calculated by means of the Cohen's kappa coefficient. RESULTS: The observed agreement between fMRU and surgical findings regarding the etiology and the presence of CV were 83.2% and 89.4%, respectively (with substantial Cohen's kappa coefficient). The sensitivity and specificity of fMRU were 0.84 and 0.93, respectively; the positive predictive value (PPV) and negative predictive value (NPV) were 0.889 and 0.897, respectively. The observed agreement regarding the type of vessel was 88.3% with a Cohen's kappa coefficient of 0.787 (substantial). DISCUSSION: In children with hydronephrosis, it is very important for the surgeon to quantify the extent of dilation, define the etiology of the obstruction, and the presence or absence of CVs. fMRU is a 'one-stop-shop' technique which provides both anatomical and functional information showing a high concordance with surgical findings, avoiding radiation exposure. CONCLUSIONS: fMRU should be considered a valid imaging technique in the study of pediatric UPJO, as it provides the surgeon with important information regarding the etiology of the obstruction for the preoperative planning.

Regulation of innate immunity by the nucleotide pathway in children with idiopathic nephrotic syndrome.

Activation of the oxidative burst and failure of CD4(+) CD25(+) cell regulation have been implicated in idiopathic nephrotic syndrome (iNS). The intimate mechanism is, however, unknown and requires specifically focused studies. We investigated reactive oxygen species (ROS) generation [di-chlorofluorescein-diacetate (DCFDA)] fluorescence assay and the regulatory adenosine 5'-triphosphate (ATP) pathways in the blood of 41 children with iNS, utilizing several agonists and antagonists of nucleotide/nucleoside receptors, including the addition of soluble apyrase. The CD4(+) CD25(+) CD39(+) /CD73(+) expression was determined in vivo in parallel during disease activity. Overall, we found that the percentage of CD39(+) CD4(+) CD25(+) was reduced markedly in iNS by 80% (3·43±0·04% versus 13·14±0·07% of total lymphocytes, P<0·001). In these patients, reactive oxygen species (ROS) generation by polymorphonuclear neutrophils (PMN) at rest was a function of apyrase (CD39) expressed by CD4(+) CD25(+) , with higher rates in patients with very low CD39(+) CD4(+) CD25(+) levels (<7·5%). Addition of apyrase reduced ROS generation by 40% in both iNS and controls and was mainly effective in patients. The quota of ROS surviving ATP elimination was higher still in iNS. In vitro studies to limit ROS generation with adenosine analogues (2'-chloroadenosine and 5'-N-ethylcarboxamidoadenosine) produced minor effects. At variance, antagonizing ATP efflux with carbenoxolone or by antagonizing ATP effects (Brilliant Blue G, KN62 and A437089) reduced ROS generation comparable to apyrase. These results confirm a key role of ATP in the regulation of innate immunity and minimize the effect of adenosine. Decreased CD39(+) CD4(+) CD25(+) expression in iNS highlights an impairment of ATP degradation in this pathology. However, high ROS surviving ATP consumption implies a major role of other regulatory pathways.

Failure of regulation results in an amplified oxidation burst by neutrophils in children with primary nephrotic syndrome.

The mechanism responsible for proteinuria in non-genetic idiopathic nephrotic syndrome (iNS) is unknown. Animal models suggest an effect of free radicals on podocytes, and indirect evidence in humans confirm this implication. We determined the oxidative burst by blood CD15+ polymorphonucleates (PMN) utilizing the 5-(and-6)-carboxy-2',7'-dichlorofluorescin diacetate (DCF-DA) fluorescence assay in 38 children with iNS. Results were compared with PMN from normal subjects and patients with renal pathologies considered traditionally to be models of oxidative stress [six anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis, seven post-infectious glomerulonephritis]. Radicals of oxygen (ROS) production was finally determined in a patient with immunodeficiency, polyendocrinopathy, enteropathy X-linked (IPEX) and in seven iNS children after treatment with Rituximab. Results demonstrated a 10-fold increase of ROS production by resting PMN in iNS compared to normal PMN. When PMN were separated from other cells, ROS increased significantly in all conditions while a near-normal production was restored by adding autologous cells and/or supernatants in controls, vasculitis and post-infectious glomerulonephritis but not in iNS. Results indicated that the oxidative burst was regulated by soluble factors and that this regulatory circuit was altered in iNS. PMN obtained from a child with IPEX produced 100 times more ROS during exacerbation of clinical symptoms and restored to a near normal-level in remission. Rituximab decreased ROS production by 60%. In conclusion, our study shows that oxidant production is increased in iNS for an imbalance between PMN and other blood cells. Regulatory T cells (Tregs) and CD20 are probably involved in this regulation. Overall, our observations reinforce the concept that oxidants deriving from PMN are implicated in iNS.