Pilot Study on the Molecular Pathogenesis of Pyeloureteral Junction Obstruction: Underdevelopment or Fibrosis?

Background and Objectives: Congenital ureteral stenosis is one of the leading causes of impaired urinary drainage and subsequent dilatation of the urinary collecting system, known as hydronephrosis or ureterohydronephrosis. The mechanism that leads to obstruction is not clearly known. Multiple studies in rat models have shown increased angiotensin II and TGFß levels in obstructed ureteral tissue. The aim of the study is to investigate the expression of fibrosis-related genes in obstructive and normal ureteral tissue. Material and Methods: It is a monocentric pilot study in which nineteen patients were selected prospectively. 17 patients underwent Hynes-Anderson pyeloplasty due to the PUJO; two patients underwent ureteroneocystostomy due to ureterovesical junction obstruction (UVJO); and six patients were chosen for the control group: five underwent nephrectomies due to the kidney tumor and one underwent upper pole heminephrectomy due to the duplex kidney with normal pyeloureteric junctions in all. Tissue RNA was chemically extracted after freezing the biopsy samples in liquid nitrogen, with cDNA synthesis performed immediately after nucleic acid isolation. qPCR was performed to evaluate the relative expression of Tgfb1, Mmp1, Timp1, Pai1, Ctgf, and Vegfa. Expression levels of the Gapdh and Gpi genes (geometric average) were used to calculate the relative expression of the investigated genes. Outliers were removed prior to calculating confidence intervals for the experimental groups, and a Wilcoxon rank-sum test was performed to determine the statistical significance of the differences. Results: Significant differences between healthy and stenotic tissue samples in Ctgf gene expression levels were observed, with the samples from afflicted tissue showing lower expression. No statistical difference in expression levels of Tgfb1, Timp1, Vegfa, Mmp1, and Pai1 was found. Conclusions: These findings suggest that tissue fibrosis, similar to other tissues and organs, is not the leading cause of stenosis, at least at the moment of surgery. Decreased CTGF expression is indicative of the developmental origin of obstruction.

Definition, diagnosis and management of fetal lower urinary tract obstruction: consensus of the ERKNet CAKUT-Obstructive Uropathy Work Group.

Fetal lower urinary tract obstruction (LUTO) is associated with high mortality and postnatal morbidity caused by lung hypoplasia and impaired kidney function. Specific diagnostic features that can guide clinical approach and decisions are lacking; thus, the European Reference Network for Rare Kidney Diseases established a work group to develop recommendations regarding the clinical definition, diagnosis and management of prenatally detected LUTO. The work group recommends the use of antero-posterior diameter of renal pelvis as the most reliable parameter for suspecting obstructive uropathies and for suspecting prenatal LUTO in the presence of fetal megacystis. Regarding prenatal and postnatal prognosis of fetuses with LUTO, the risk of fetal and neonatal death depends on the presence of oligohydramnios or anhydramnios before 20 weeks' gestation, whereas the risk of kidney replacement therapy cannot be reliably foreseen before birth. Parents of fetuses with LUTO must be referred to a tertiary obstetric centre with multidisciplinary expertise in prenatal and postnatal management of obstructive uropathies, and vesico-amniotic shunt placement should be offered in selected instances, as it increases perinatal survival of fetuses with LUTO.

Urine Biomarkers Combined With Ultrasound for the Diagnosis of Obstruction in Pediatric Hydronephrosis.

Introduction: To establish the efficacy of ultrasound (US) combined with urine biomarkers in differentiating patients who require surgical management from those who do not, avoiding invasive investigations. Materials and Methods: From February 2019 to February 2021, all pediatric patients who presented with hydronephrosis were selected for the study. All renal units (RU) were evaluated by US, and fresh frozen voided urine samples were collected at the time of inclusion. Hydronephrosis grade was evaluated by the Society for Fetal Urology (SFU) and an alternative grading system (AGS). Patients who had high-grade hydronephrosis on US were referred to renal scan (RS) or intervention, when there was an increase of dilatation in subsequent follow-up images. Fresh frozen urine from the control group with no history of renal diseases and no renal anomalies on US was collected. We compared differences of US parameters combined with urine biomarkers between surgically and non-surgically managed patients and between the groups of patients when they were stratified by different RS findings and analyzed whether urinary biomarkers give any additional value to US. Instead of the anterior-posterior diameter (APD), we used its ratio with mid-parenchymal thickness. The additional efficacy of biomarkers to US was calculated when the US component was derived to a cumulative APD/mid-parenchymal ratio. Results: Sixty-four patients with hydronephrosis were prospectively included in the study accounting for a total of 81 patient visits and 162 RUs evaluated. A control group of 26 patients was collected. The mean age at inclusion in the hydronephrosis group was 43.7(±45.5) months, and a mean age in a control group was 61.2(±41.3) months. The cumulative APD/mid-parenchymal ratio combined with urinary albumin, ß2 microglobulin (ß2-M), and urinary neutrophil gelatinase-associated lipocalcin may have a better performance in the prediction of surgical intervention than the cumulative APD/mid-parenchymal ratio alone (p = 0.1). The best performance to detect the increased tissue transit time and obstructive curve on RS was demonstrated by the ß2-M creatinine ratio. An increased cumulative APD/mid-parenchymal ratio with biomarkers together had a fairly good sensitivity and specificity for detection of DRF < 40%. Conclusions: According to our data, the APD/mid-parenchymal ratio alone has good efficacy in prediction of surgery and abnormal RS findings especially when combined with urine biomarkers.

Diuretic Enhanced Ultrasonography in the Diagnosis of Pyeloureteral Obstruction.

Background and Objectives: To determine the value of diuretic ultrasonography for the diagnosis of obstructive hydronephrosis. Materials and Methods: Diuretic enhanced ultrasonography was used routinely as a part of examination of patients with hydronephrosis in our Department. There were 72 patients (42 males, 30 females; aged 2 months to 17 years; median age 7.07 years) with a sonoscopic diagnosis of hydronephrosis included from January 2006 until October 2011. The anteroposterior diameter (AD) of renal pelvis was measured sonoscopically before and at sixty minutes after furosemide injection. A weight-adjusted dose of 1 mg/kg of furosemide was administered intravenously. Results: Patients were operated on if pyeloureteral obstruction was suspected because of low or deteriorating differential renal function, increasing hydronephrosis or symptoms thereof. Hydronephrosis was unilateral in 61 (84.7%) and bilateral in 11 (15.3%) patients. The median AD of pelvis before furosemide injection was 22 mm in operated and 17 mm in non-operated patients (p = 0.005). Sixty minutes after furosemide injection, the AD of pelvis in operated patients was 35.5 mm and 25.8 mm in non-operated-25.8 mm (p < 0.001). Logistic regression model demonstrated that significant factors for surgery were: AD 60 min after furosemide infection and ultrasonographic parenchymal sclerosis. Conclusion: Ultrasound measurement of the AD of renal pelvis 1 h after the injection of furosemide used as an additional investigation can help in predicting obstructive hydronephrosis.

Infantile hemangioma: Predicting proliferation by infrared thermography.

BACKGROUND AND OBJECTIVE: Infantile hemangiomas (IHs) are benign lesions found in infants. Predicting the cosmetic outcome of these lesions is very difficult. Therefore, in this prospective study, we assessed whether using an infrared thermometer (IRT) to measure the surface temperature of IHs would help to predict their proliferative potential. MATERIALS AND METHODS: Between January 2012 and March 2014, we prospectively investigated 103 children up to 6 months of age with a diagnosis of IH. None of them required immediate treatment. Two projection plain photographs of the IHs were obtained and the temperature of the IH surface was measured with the IRT at each visit. The IHs in these patients were divided into three groups: stable, slightly growing and growing IHs. We analyzed temperature differences between the groups, relative operating characteristic (ROC) curves, and possible application of this method to clinical practice. RESULTS: The median initial temperatures in the groups were 36.7°C for the stable group, 37°C for the slightly growing group, and 37.4°C for the growing group (P<0.01). The area under the ROC curve for the temperature values to predict growth was 0.929. Temperatures at or above 37.4°C showed a specificity of 95%, a sensitivity of 75%, a positive predictive value 81%, and a negative predictive value of 95%. CONCLUSIONS: IRT is a time and cost effective tool, and is easy to learn. The surface temperature of IH reflects its remaining growth potential and could be used in the outpatient setting for the evaluation and follow-up of IH.

Incidence of High Infertility Risk among Unilateral Cryptorchid Boys.

BACKGROUND: Increasing evidence of progressive damage to germ cell development in boys with cryptorchidism suggests recommending surgery until one year of age. However, despite early and successful orchidopexy, cryptorchid boys with impaired mini-puberty will suffer from infertility. We reviewed changes in the timing of surgery during the past decade and the incidence of unilateral cryptorchid boys with defective mini-puberty. METHODS: Medical registries were reviewed for all patients who were operated on for cryptorchidism at the main pediatric urological center of the country. The ages of surgery in cases of unilateral cryptorchidism were compared between the years 2000-2001 and 2012-2013. A high risk of infertility was considered when no Ad spermatogonia were found. Two groups were compared: group I--operated on until the age of 1.5 years and group II--older than 1.5 years. RESULTS: The average age at operation decreased from 5.3 to 4.1 years. Forty-six biopsies in boys with unilateral cryptorchidism were made during orchidopexy on undescended testicles. Overall, 44% in group I and 50 % in group II (p > 0.05) had no Ad spermatogonia. CONCLUSIONS: The average age of operation for cryptorchidism has decreased, but remains far above the recommended age. The high prevalence of histologically proven risk of infertility underscores the necessity of more education regarding the importance of earlier surgery and the research on hormonal prevention of infertility.