Hydronephrosis and crossing vessels in children: Optimization of diagnostic-therapeutic pathway and analysis of color Doppler ultrasound and magnetic resonance urography diagnostic accuracy.

INTRODUCTION: Ureteropelvic junction obstruction (UPJO) is one of the most frequent urological diseases affecting the pediatric population. It can be due to both intrinsic stenosis of the junction and extrinsic causes such as the presence of crossing vessels (CVs), which can be detected by color Doppler ultrasound (CD-US). Magnetic resonance urography (MRU) is a good alternative, but sedation and infusion of a contrast agent are required. OBJECTIVE: The aim of this study was to analyze the diagnostic accuracy of CD-US and MRU in visualizing CVs in pediatric hydronephrosis, in order to decide the correct diagnostic pathway in the pre-operative phase. MATERIAL AND METHODS: A retrospective review was performed of medical records for all patients who underwent surgical treatment for hydronephrosis from August 2006 to February 2016. Ultrasound and scintigraphy had been performed on all patients. Data about CD-US and MRU were collected. A high-level technology ultrasound scanner and a 1.5 T MR scanner were used. The presence of CVs at surgery was considered the gold standard. Sensitivity, specificity, positive and negative predictive values (NPV) were calculated and reported for both of the imaging techniques. RESULTS: A total of 220 clinical charts were reviewed. Seventy-three CVs were identified at surgery (33.2% of UPJO). The median age was statistically higher in the group with CVs compared to the group without CVs (P < 0.001). The sensitivity and NPV of CD-US in detecting CVs were higher than MRU (sensitivity 93.3% vs. 71.7%, NPV 95.7% vs. 77.6%, respectively). DISCUSSION: According to the data, CD-US had higher sensitivity and NPV than MRU, resulting in superior detection of CVs. It is important for a surgeon to know that a child has a CV, especially in older children in which the incidence of extrinsic UPJO is higher. The main limitation of this study was the presence of incomplete data, due to the retrospectivity. CONCLUSIONS: In the pre-operative phase, the CD-US should be considered as the investigation of choice to detect CVs in children with hydronephrosis (Summary Fig). Moreover, CD-US has lower costs than MRU, and sedation with infusion of contrast agent is unnecessary. For the future, it could be useful to lead a prospective comparison between the two imaging techniques.

SOD1 deficiency causes salt sensitivity and aggravates hypertension in hydronephrosis.

Hydronephrosis causes renal dysfunction and salt-sensitive hypertension, which is associated with nitric oxide deficiency and abnormal tubuloglomerular feedback (TGF) response. We investigated the role of oxidative stress for salt sensitivity and for hypertension in hydronephrosis. Hydronephrosis was induced in superoxide dismutase 1-transgenic (SOD1-tg), SOD1-deficient (SOD1-ko), and wild-type mice and in rats. In mice, telemetric measurements were performed during normal (0.7% NaCl) and high-sodium (4% NaCl) diets and with chronic tempol supplementation. The 8-iso-prostaglandin-F(2alpha) (F2-IsoPs) and protein excretion profiles and renal histology were investigated. The acute effects of tempol on blood pressure and TGF were studied in rats. In hydronephrosis, wild-type mice developed salt-sensitive hypertension (114 +/- 1 to 120 +/- 2 mmHg), which was augmented in SOD1-ko (125 +/- 3 to 135 +/- 4 mmHg) but abolished in SOD1-tg (109 +/- 3 to 108 +/- 3 mmHg). SOD1-ko controls displayed salt-sensitive blood pressure (108 +/- 1 to 115 +/- 2 mmHg), which was not found in wild types or SOD1-tg. Chronic tempol treatment reduced blood pressure in SOD1-ko controls (-7 mmHg) and in hydronephrotic wild-type (-8 mmHg) and SOD1-ko mice (-16 mmHg), but had no effect on blood pressure in wild-type or SOD1-tg controls. SOD1-ko controls and hydronephrotic wild-type and SOD1-ko mice exhibited increased fluid excretion associated with increased F2-IsoPs and protein excretion. The renal histopathological changes found in hydronephrotic wild-type were augmented in SOD1-ko and diminished in SOD-tg mice. Tempol attenuated blood pressure and normalized TGF response in hydronephrosis [DeltaP(SF): 15.2 +/- 1.2 to 9.1 +/- 0.6 mmHg, turning point: 14.3 +/- 0.8 to 19.7 +/- 1.4 nl/min]. Oxidative stress due to SOD1 deficiency causes salt sensitivity and plays a pivotal role for the development of hypertension in hydronephrosis. Increased superoxide formation may enhance TGF response and thereby contribute to hypertension.

Role of nitric oxide deficiency in the development of hypertension in hydronephrotic animals.

Hydronephrotic animals develop renal injury and hypertension, which is associated with an abnormal tubuloglomerular feedback (TGF). The TGF sensitivity is coupled to nitric oxide (NO) in the macula densa. The involvement of reduced NO availability in the development of hypertension in hydronephrosis was investigated. Hydronephrosis was induced by ureteral obstruction in young rats. Blood pressure and renal excretion were measured in adulthood, under different sodium conditions, and before and after chronic administration of either N(G)-nitro-l-arginine methyl ester (l-NAME) or l-arginine. Blood samples for ADMA, SDMA, and l-arginine analysis were taken and the renal tissue was used for histology and determination of NO synthase (NOS) proteins. TGF characteristics were determined by stop-flow pressure technique before and after administration of 7-nitroindazole (7-NI) or l-arginine. Hydronephrotic animals developed salt-sensitive hypertension, which was associated with pressure natriuresis and diuresis. The blood pressure response to l-NAME was attenuated and l-arginine supplementation decreased blood pressure in hydronephrotic animals, but not in the controls. Under control conditions, reactivity and sensitivity of the TGF response were greater in the hydronephrotic group. 7-NI administration increased TGF reactivity and sensitivity in control animals, whereas, in hydronephrotic animals, neuronal NOS (nNOS) inhibition had no effect. l-Arginine attenuated TGF response more in hydronephrotic kidneys than in controls. The hydronephrotic animals displayed various degrees of histopathological changes. ADMA and SDMA levels were higher and the renal expressions of nNOS and endothelial NOS proteins were lower in animals with hydronephrosis. Reduced NO availability in the diseased kidney in hydronephrosis, and subsequent resetting of the TGF mechanism, plays an important role in the development of hypertension.

Diabetes-induced microvascular dysfunction in the hydronephrotic kidney: role of nitric oxide.

BACKGROUND: Renal hemodynamics in early diabetes are characterized by preglomerular and postglomerular vasodilation and increased glomerular capillary pressure, leading to hyperfiltration. Despite intensive research, the etiology of the renal vasodilation in diabetes remains a matter of debate. The present study investigated the controversial role of nitric oxide (NO) in the renal vasodilation in streptozotocin-induced diabetic rats. METHODS: In the renal microcirculation, basal tone and response to NO synthase blockade were studied using the in vivo hydronephrotic kidney technique. L-arginine analog N-nitro-L-arginine methyl ester (L-NAME) was administered locally to avoid confounding by systemic blood pressure effects. The expression of endothelial NO synthase (eNOS) was investigated in total kidney by immunocytochemistry and in isolated renal vascular trees by Western blotting. Urinary excretion of nitrites/nitrates was measured. RESULTS: Diabetic rats demonstrated a significant basal vasodilation of all preglomerular and postglomerular vessels versus control rats. Vasoconstriction to L-NAME was significantly increased in diabetic vessels. After high-dose L-NAME, there was no difference in diameter between diabetic and control vessels, suggesting that the basal vasodilation is mediated by NO. Immunocytochemically, the expression of eNOS was mainly localized in the endothelium of preglomerular and postglomerular vessels and glomerular capillaries, and was increased in the diabetic kidneys. Immunoblots on isolated renal vascular trees revealed an up-regulation of eNOS protein expression in diabetic animals. The urinary excretion of nitrites/nitrates was elevated in diabetic rats. CONCLUSION: The present study suggests that an up-regulation of eNOS in the renal microvasculature, resulting in an increased basal generation of NO, is responsible for the intrarenal vasodilation characteristic of early diabetes.

[The effect of captopril on the arterial pressure, structural resistance and vascular reactivity of the kidney in rats with nephrogenic hypertension]. / Vliianie kaptoprila na arterial'noe davlenie, strukturnoe soprotivlenie i reaktivnost' sosudov pochi u krys s nefrogennoi gipertenziei.

The angiotensin-converting enzyme inhibiting agent captopryl suppressed a moderate hypertension in rats with pyelonephritis and with ureteral obstruction, but not in rats with ureteral obstruction combined with the renal artery constriction. The suppression of the hypertension was accompanied by a reversion of structural alterations in the blood vessels.

Renal function in idiopathic hydronephrosis in children. Follow-up after conservative and surgical treatment.

In 64 children (age 1-15, mean 7.3 years) with unilateral idiopathic hydronephrosis, measurements were made of glomerular filtration rate (GFR), separate glomerular filtration rate (SGFR, measured as 51Cr-EDTA clearance combined with renography) and renal concentrating capacity. Onset symptoms were urinary tract infection in 34 children and abdominal pain in 25, while 5 were asymptomatic. Surgery was performed soon after the first investigation in 34 children and during the follow-up period in 14, and 16 children received only conservative treatment. The mean follow-up time was 4.4 years. At the time of diagnosis the total GFR and the SGFR of the affected kidney were normal or almost normal in all the children (respective means 108 +/- 16 and 50 +/- 12 ml min-1 X 1.73 m2(-1)). The total GFR remained normal at follow-up, but SGFR became subnormal in two conservatively and two surgically treated children. The concentrating capacity was initially lower in the children with, than in those without urinary tract infection. The former values had increased significantly at follow-up examination. The study indicates that the parenchymal function in unilateral idiopathic hydronephrosis in children more than 1 year old usually is normal, but may deteriorate due to urinary tract infection. Such infection should be carefully searched for and treated. Since very few of these children seem to have pelvic obstruction, surgery seldom is primarily necessary.

Normo-osmolar, nonketotic, hyponatremic diabetic syndrome associated with impaired renal function.

A case is reported of a nonketotic woman with diabetes who presented with a blood glucose of 72.8 mmol/L (1310 mg/dl), plasma sodium of 92 mmol/L, normal osmolality, impaired renal function, and alert clinical state. Before the implication of the unusual nature of the metabolic disturbance was fully considered, the initial treatment was with a rapid infusion of saline. On consideration, however, it was postulated that as her hyperglycemia had developed, the expected osmotic diuresis was prevented by the impairment of her renal function. This had allowed compensatory hyponatremia to develop to maintain normal osmolality and protect the patient from coma. The high-dose saline infusion was stopped, and she was successfully treated with insulin and potassium but only minimal saline. The use of large quantities of saline in normo-osmolar, nonketotic, hyponatremic diabetic syndrome associated with impaired renal function and alert mental state is unnecessary and potentially dangerous.