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Background: This study aimed to investigate variations of the oxidative status in cats affected by urethral obstruction (UO) under Feline Idiopathic Cystitis (FIC) and Bacterial Cystitis (BC), in comparison with a group of healthy subjects. In both groups, the levels of several markers (either direct or indirect) indicative of the oxidative attack and of the antioxidant response were analyzed on plasma and urine samples. In particular, the plasma samples were evaluated for nitric oxide (NO), hydroperoxides derived by reactive oxygen activity (d-ROMs test), superoxide anion (O 2 - ), glutathione peroxidase activity (GPx), superoxide dismutase activity (SOD), and ferric reducing antioxidant power (FRAP test); while on urine the levels of NO, d-ROMs, FRAP, SOD, malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) were measured. Urine of UO patients was also subjected to urine-culture test., Results: The analytical data on plasma showed that UO, independently of the FIC or BC etiology, induced the insurgence of oxidative stress conditions at the systemic level. In the urine of the UO patients, except for SOD that increased, the markers of redox status were markedly decreased due probably their compromised filtration, thus suggesting involvement of renal function (assessed also by the high levels of plasma creatinine and proteinuria) with no oxidative damage of the lower urinary tract. Moreover, the adoption of a novel oxidative stress index' (OSI) allowed to establish, by means of a numerical value, the different degrees of oxidative stress conditions for single UO patients, both in terms of oxidative attack and antioxidant response., Conclusions: Feline urethral obstruction, induced by Idiopathic Cystitis and Bacterial Cystitis, causes oxidative stress conditions at the systemic level that do not interest the lower urinary tract. Despite to the high variability of the profiles of oxidative stress indexes both in healthy and UO patients, the determination of OSI made possible the evaluation of their single degrees of oxidative stress. Possibly the results of this investigation can be compared with those of correspondent pathologies both in humans and in other animal species., (© 2024. The Author(s).)

Objective: To analyze renal glomerular and tubular function and their association in patients operated for posterior urethral valves and to prognosticate the risk for end-stage kidney disease (ESKD) METHODS: Sixty-three previously treated patients were evaluated for renal function during 1987-1991. The patients' age at evaluation was 11 years (range 2-24). Glomerular function was assessed by measuring glomerular filtration rate (GFR) and urine albumin excretion. Tubular function was determined by measuring urine concentration capacity and excretion of electrolytes (Na, K, Cl, Ca, P, Mg) and β-2-microglobulin. Additionally, the prevalence of hypertension and serum parathyroid hormone and aldosterone values were registered. Tubular function was compared with GFR and the risk of developing ESKD before November 2018., Results: Twenty of the study patients (32%) had decreased GFR. In addition, 19% had proteinuria and 56% were hypertensive. Those without proteinuria or hypertension had better GFR values (P < .01 for both). There was a significant correlation between GFR and all the tubular function (P < .05) variables (except excretion of chloride) measured. Compared to the patients with favorable renal outcome, the patients (n = 10) who later developed ESKD had significantly (P < .01) lower GFR and reduced urinary excretion of all measured electrolytes except calcium. Consistently, urine β-2 microglobulin and serum parathyroid hormone and aldosterone values were significantly higher in the patients who developed ESKD (P ≤ .01)., Conclusion: Both glomerular and tubular function decline was common and several parameters were likely to predict ESKD in posterior urethral valves patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Urgency, frequency and incomplete emptying are the troublesome symptoms often shared between benign prostatic obstruction-induced (BLUTD) and neurogenic (NLUTD) lower urinary tract dysfunction. Previously, using bladder biopsies, we suggested a panel of miRNA biomarkers for different functional phenotypes of the bladder. Urine is a good source of circulating miRNAs, but sex- and age-matched controls are important for urinary metabolite comparison. In two groups of healthy subjects (average age 32 and 57 years old, respectively) the total protein and RNA content was very similar between age groups, but the number of secreted extracellular vesicles (uEVs) and expression of several miRNAs were higher in the young healthy male volunteers. Timing of urine collection was not important for these parameters. We also evaluated the suitability of urinary miRNAs for non-invasive diagnosis of bladder outlet obstruction (BOO). A three urinary miRNA signature (miR-10a-5p, miR-301b-3p and miR-363-3p) could discriminate between controls and patients with LUTD (BLUTD and NLUTD). This panel of representative miRNAs can be further explored to develop a non-invasive diagnostic test for BOO. The age-related discrepancy in the urinary miRNA content observed in this study points to the importance of selecting appropriate, age-matched controls.

Background: Congenital obstructive uropathy (OU) is a leading cause of pediatric kidney failure, representing a unique mechanism of injury, in part from renal tubular stretch and ischemia. Tubular injury biomarkers have potential to improve OU-specific risk stratification., Methods: Patients with OU were identified in the Chronic Kidney Disease in Children (CKiD) study. "Cases" were defined as individuals receiving any kidney replacement therapy (KRT), while "controls" were age- and time-on-study matched and KRT free at last study visit. Urine and plasma neutrophil gelatinase-associated lipocalin (NGAL), interleukin 18 (IL-18), and liver-type fatty acid-binding protein (L-FABP) levels were measured at enrollment and annually and compared between cases and controls. Urine values were normalized to urine creatinine., Results: In total, 22 cases and 22 controls were identified, with median (interquartile range) ages of 10.5 (9.0-13.0) and 15.9 (13.9-16.9) years at baseline and outcome, respectively. At enrollment there were no differences noted between cases and controls for any urine (u) or plasma (p) biomarker measured. However, the mean pNGAL and uL-FABP/creatinine increased throughout the study period in cases (15.38 ng/ml per year and 0.20 ng/ml per mg/dl per year, respectively, p = 0.01 for both) but remained stable in controls. This remained constant after controlling for baseline glomerular filtration rate (GFR)., Conclusions: In children with OU, pNGAL and uL-FABP levels increased over the 5 years preceding KRT; independent of baseline GFR. Future studies are necessary to identify optimal cutoff values and to determine if these markers outperform current clinical predictors.

Fetal lower urinary tract obstruction (LUTO), which often results in marked perinatal morbidity and mortality, is caused by a heterogeneous group of anatomical defects that lead to blockage of the urethra. The classic prenatal presentation of LUTO includes megacystis with hydronephrosis. While mild forms of the disease can be associated with favorable outcomes, more severe disease commonly leads to dysplastic changes in the fetal kidneys, and ultimately oligohydramnios, which can result in secondary pulmonary hypoplasia and renal failure at birth. The aim of this review is to provide practitioners with a general overview of the diagnosis and treatment of LUTO based on disease severity, along with some points to consider when counseling prospective parents of fetuses with this condition., (© 2020 John Wiley & Sons, Ltd.)

Background: Posterior urethral valves (PUVs) account for 17% of pediatric renal failure. The management of pregnancies involving fetuses with PUV is hampered by the fact that current clinical parameters obtained from fetal ultrasound and/or fetal urine biochemistry are insufficient to predict postnatal renal function. We previously have developed a fetal urine peptide signature (12PUV) that predicted with high precision postnatal renal failure at 2 years of age in fetuses with PUV. Here, we evaluated the accuracy of this signature to predict postnatal renal outcome in fetuses with PUV in an independent single-center study., Methods: Thirty-three women carrying fetuses with suspected PUV were included. Twenty-five fetuses received vesicoamniotic shunts during pregnancy. PUV was confirmed postnatally in 23 patients. Of those 23 fetuses, 2 were lost in follow-up. Four and 3 patients died in the pre- and perinatal periods, respectively. Follow-up renal function at 6 months of age was obtained for the remaining 14 patients. The primary outcome was early renal failure, defined by an eGFR < 60 mL/min/1.73 m 2 before 6 months of age or pre- or perinatal death., Results: The peptide signature predicted postnatal renal outcome in postnatally confirmed PUV fetuses with an AUC of 0.94 (95%CI 0.74-1.0) and an accuracy of 90% (95%CI 78-100). The signature predicted postnatal renal outcome for the suspected PUV cases with an AUC of 0.89 (95%CI 0.72-0.97) and an accuracy of 84% (95%CI 71-97)., Conclusions: This single-center study confirms the predictive power of the previously identified 12PUV fetal urinary peptide signature.

Objectives: Cardiac remodeling due to renal dysfunction may have an impact on myocardial function (MF) of fetuses with lower urinary tract obstruction (LUTO). The aim was to identify possible differences in MF in LUTO fetuses compared with healthy controls and to look for interactions between urine biochemistry and MF indices., Methods: This is a cohort study consisting of 31 LUTO fetuses and 45 healthy controls. Subgroups were generated according to intrauterine therapy (group 1: LUTO after therapy, group 2: LUTO without therapy at the time of examination, and group 3: controls). MF indices were measured using pulsed wave tissue Doppler imaging and M-mode. Furthermore, results of fetal urine biochemistry were gathered retrospectively., Results: Among other findings, right ventricular (RV) e'/a' ratio was lower in group 1 compared with group 3 (p = .050). According to gestational age (GA) level-dependent analysis, RV isovolumetric relaxation time was significantly longer in group 2 compared with group 1 and group 3 at GA level 1 (19 wk of gestation). A significant positive correlation between RV e'/a' ratio and β-2-microglobulin as well as α-1-microglobulin and potassium could be observed., Conclusion: We observed differences in MF and an association between ventricular filling pattern and renal protein secretion in LUTO fetuses. This can be interpreted as a sign of intrauterine cardiac remodeling., (© 2019 John Wiley & Sons, Ltd.)

Obstructive nephropathy is characterized by alterations in renal function that depends on the degree and type of obstruction. To increase the knowledge about the physiopathological mechanisms involved in the renal damage associated with bilateral ureteral obstruction (BUO), we studied the renal expression and function (as urinary citrate excretion) of sodium-dependent dicarboxylate cotransporter (NaDC1) in rats. In addition, we evaluated the urinary excretion of NaDC1 as a candidate biomarker for this pathology. Male Wistar rats underwent bilateral ureteral obstruction for 1 (BUO1), 2 (BUO2), 5 (BUO5), and 24 (BUO24) h or sham operation. After 24 h of ureteral releasing, traditional parameters of renal function and citrate levels were determined, and NaDC1 levels were evaluated in total renal homogenates, apical plasma membranes, and urine by electrophoresis and Western blotting. Traditional parameters of renal function were only modified in BUO5 and BUO24. The renal expression of NaDC1 was decreased in BUO5 and BUO24, with a concomitant increase in urinary excretion of citrate. Moreover, the urinary excretion of NaDC1 increased after short times of ureteral obstruction (BUO1 and BUO2) and was positively correlated with the time elapsed after obstruction. The results obtained from the renal expression of NaDC1 could explain an adaptive mechanism to prevent the formation of kidney stones by increasing the levels of citrate, a calcium chelator. The urinary excretion of NaDC1 could be postulated as an early biomarker of obstructive nephropathy that also gives information about the duration of the obstruction.

Objective: Because the literature on the predictive value of fetal urinalysis is controversial in fetuses with lower urinary tract obstruction, we determined the best model of fetal urine biochemical markers correlated with long-term postnatal renal function based on glomerular filtration rate (GFR)., Method: This retrospective study concerned 89 fetuses with lower urinary tract obstruction and their renal function after 10 years of age. We correlated fetal urine biochemical markers (total protein, β2-microglobulin, sodium, chloride, glucose, calcium, and phosphorus) with GFR at 10 to 30 years of age in 89 patients with posterior urethral valves. We defined five stages of chronic kidney disease (CKD)., Results: Of the 89 patients, 18 (20%) are 20 years old or over. Postnatal renal function was good in 67.4% (GFR > 60 mL/min/1.73 m 2 ) and poor in 17% (GFR < 30 mL/min/1.73 m 2 ). All fetal urine markers differed between CKD stage 1 + 2 and CKD stage 4 + 5 (P < 0.001). β2-microblobulin showed an 87% sensitivity for a 72% specificity. A combination of β2-microglobulin and chloride gave the best results (93% sensitivity and 71% specificity) versus amniotic fluid volume (80% sensitivity and 73% specificity)., Conclusion: Fetal urine biochemistry predicts long-term (10-30 years) postnatal renal function., (© 2018 John Wiley & Sons, Ltd.)

The authors present an overview of lower urinary tract obstruction (LUTO) in the fetus with a particular focus on the insult to the developing renal system. Diagnostic criteria along with the challenges in estimating long-term prognosis are reviewed. A proposed prenatal LUTO disease severity classification to guide management decisions with fetal intervention to maintain or salvage in utero and neonatal pulmonary and renal function is also discussed. Stage I LUTO (mild form) is characterized by normal amniotic fluid index after 18 weeks, normal kidney echogenicity, no renal cortical cysts, no evidence of renal dysplasia, and favorable urinary biochemistries when sampled between 18 and 30 weeks; prenatal surveillance is recommended. Stage II LUTO is characterized by oligohydramnios/anhydramnios, hyperechogenic kidneys but absent renal cortical cysts or apparent signs of renal dysplasia and favorable fetal urinary biochemistry; fetal vesicoamniotic shunting (VAS) or fetal cystoscopy is indicated to prevent pulmonary hypoplasia and renal failure. Stage III LUTO is oligohydramnios/anhydramnios, hyperechogenic kidneys with cortical cysts and renal dysplasia and unfavorable fetal urinary biochemistry after serial evaluation; fetal vesicoamniotic shunt may prevent severe pulmonary hypoplasia but not renal failure. Stage IV is characterized by intrauterine fetal renal failure, defined by anhydramnios and ultrasound (US) findings suggestive of severe renal dysplasia, and is associated with death in 24 h of life or end-stage renal disease (ESRD) within the first week of life; fetal vesicoamniotic shunt and fetal cystoscopy are not indicated.

Objectives: To assess the value of fetal urine biochemistry before 23 weeks of gestation in cases of lower urinary tract obstruction (LUTO) to refine prognosis and to select potential candidates for in-utero intervention., Methods: This was a retrospective study including 72 cases of LUTO with fetal urine sampled before 23 weeks and assayed for total protein, β-2-microglobulin, sodium, chloride, calcium, phosphorus, glucose and gamma-glutamyl transpeptidase (GGTP). Two groups were defined according to renal outcome: 1) bilateral renal dysplasia on histological examination or renal failure at birth; 2) normal postnatal renal function or histologically normal appearance of the kidneys. Correlations between fetal urinary biochemical markers and postnatal renal function were studied., Results: LUTO was isolated in 56/72 (77.8%) cases and was associated with other malformations in 16/72 (22.2%) cases. High GGTP levels (236 IU/L vs 5 IU/L; P < 0.0001) were observed in fetal urine in the five cases of urodigestive fistula. A significant difference between outcome groups was observed for β-2-microglobulin (P = 0.0017), sodium (P = 0.0008), chloride (P = 0.0028) and calcium (P = 0.0092) but not for protein, glucose or phosphorus. Sensitivity and specificity in defining a poor renal prognosis were 80.6% and 89% for β-2-microglobulin, 61.3% and 100% for sodium and 64.5% and 100% for calcium, respectively., Conclusions: Fetal urinalysis before 23 weeks of gestation allowed distinction between three groups: 1) fetuses with normal urine biochemistry for which fetal therapy should be discussed; 2) fetuses with abnormal urine biochemistry for which prognosis for renal outcome is poor and for which the benefit of fetal therapy is likely to be compromised; 3) fetuses with urodigestive fistula., (Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.)

Incomplete varying obstruction of the urinary tract was reproduced by injecting artificial stomatological material into the rat bladder. Inflammatory changes and nephrosclerosis were detected in the renal tissue on days 14 and 21 of the experiment. Urinary concentration of total protein and activity of γ-glutamylaminotransferase increased. A direct positive correlation between the volume percentage of connective tissue and activities of the renal enzymes in the urine was detected.

Background: Microalbuminuria (MA) has been shown to be an early biomarker of renal damage. It is postulated that MA is the early result of hyperfiltration, which could evolve into glomerular sclerosis and renal failure if hyperfiltration is left untreated. We hypothesized that MA is a good indicator of hyperfiltration in children with kidney disorders, obviating the need to calculate the filtration fraction (FF)., Methods: A total of 155 children or young adults were prospectively included [42 single kidney (SK), 61 vesico-ureteral reflux, 23 obstructive uropathies, 29 other kidney diseases]. We measured inulin, para-aminohippuric acid clearances, FF and MA. Prediction of hyperfiltration was explored by studying the association between the FF and other variables such as urinary albumin (Alb), urinary albumin-creatinine ratio (ACR) and creatinine clearance., Results: A significant but weak association between urinary Alb or ACR and FF was found in subjects with an SK (Spearman correlation coefficients 0.32 and 0.19, respectively). Multivariate analysis also showed that urinary Alb and ACR significantly predict FF only in subjects with an SK (r(2) = 0.17, P = 0.01 and r(2) = 0.13, P = 0.02, respectively). This holds true only in subjects with an SK and inulin clearance >90 mL/min/1.73 m(2) (r(2) = 0.41, P < 0.001). There was no association between creatinine clearance and FF., Conclusions: MA is not associated with FF in our subjects with nephro-urological disorders, except in those with an SK, where the association is weak, indicating that MA is due to other mechanisms than high FF and cannot predict hyperfiltration in such groups.

Background and Objectives: Obstructive nephropathy is a leading cause of CKD in children. The assessment of severity of renal impairment and the prediction of which children will progress to renal failure are, however, challenging., Design, Setting, Participants, & Measurements: This case-control study measured the urinary excretion of candidate biomarkers in 27 prevalent case-patients with posterior urethral valves (PUVs) and 20 age-matched controls, correlated their urinary concentration with GFR, and analyzed receiver-operating characteristic (ROC) curve and regression analyses to assess their performance as tests for low GFR., Results: The median urinary protein-to-creatinine ratio was higher in children with PUV (45 g/mol; range, 5-361 g/mol) than in controls (7 g/mol; range, 3-43 g/mol) (P<0.01) and correlated inversely with renal function (r = -0.44; P<0.05). In whole urine, excretion of aquaporin-2 was significantly decreased, whereas that of TGFβ and L1 cell adhesion molecule (L1CAM) was significantly increased. Whole-urine TGFβ excretion correlated inversely with GFR (r = -0.53; P<0.05). As tests for low GFR, whole-urine TGFβ, L1CAM, and urinary protein-to-creatinine ratio performed best, with areas under the ROC curves of 0.788, 0.795, and 0.814, respectively. By linear regression analysis, whole-urine TGFβ, L1CAM, and urinary protein-to-creatinine ratio were associated with low GFR in the case-patients., Conclusions: Candidate biomarkers of obstructive nephropathy can be readily measured in whole urine and in urine exosomes. In boys with PUV, these biomarkers correlate with GFR.

Background: Urinary tract obstruction (UTO) is a common problem that can lead to permanent loss of kidney function. Unilateral UTO may be difficult to diagnose. Urinary neutrophil gelatinase-associated Lipocalin (uNGAL) may identify unilateral and bilateral UTO., Methods: Retrospective case-control study of patients undergoing hospital admission at three sites. UTO was determined by review of medical records and cases were matched to control patients. uNGAL was measured by immunoblot., Results: Twenty-four unilateral UTO and 15 bilateral UTO cases were identified. Admission serum creatinine (sCr) (milligram per decilitre) was significantly higher in bilateral UTO, 2.0 (1.1-5.3), but not unilateral UTO, 1.1 (0.8-1.5), compared to controls, 0.9 (0.8-1.2). uNGAL (nanogram per millilitre) was significantly higher both in patients with bilateral UTO, 140 (40-450), and unilateral UTO, 50 (20-100), compared to controls, 20 (10-45)., Discussion: uNGAL identifies kidney injury in unilateral and bilateral UTO even in the absence of an elevated sCr.

Aim: Obstructive uropathies (OU) in childhood constitute one of the major causes of chronic renal insufficiency. Transforming growth factor-β1 (TGF-β1) is considered to be the major fibrogenic growth factor. The aim of the present study was to investigate urinary TGF-β1 levels in children with obstructive and non-obstructive uropathies (NOU)., Methods: This study involved 19 children with OU, 11 children with non-obstructive hydronephrosis and 21 healthy children. Urinary TGF-β1, proteinuria, microalbuminuria and urinary α1-microglobulin were measured, and renal function was assessed. The results were statistically analyzed., Results: Mean urinary TGF-β1 concentrations in patients with OU were significantly higher than those with NOU (4.14 ± 0.67 creatinine vs 1.80 ± 0.24 pg/mmol creatinine, P < 0.05) and healthy controls (1.66 ± 0.28 pg/mmol creatinine, P < 0.05). Positive correlations of urinary TGF-β1 concentrations with proteinuria (r = 0.87, P < 0.0001) and urinary α1-microglobulin (r = 0.82, P = 0.0002) were found in patients with OU., Conclusion: Children with OU have higher urinary TGF-β1 than children with NOU. Urinary TGF-β1 may be a useful non-invasive tool for the differential diagnosis between OU and NOU in children. A positive correlation of TGF-β1 with markers of renal tissue damage in patients with OU was found., (© 2011 The Authors. Nephrology © 2011 Asian Pacific Society of Nephrology.)

Feline lower urinary tract diseases in general, and urethral obstruction (UO) in particular, are common clinical conditions in cats. The aims of this study were to identify risk factors for UO, to characterise clinical and clinicopathological signs, outcome and recurrence, as well as risk factors for mortality and recurrence. Eighty-two cats with UO were compared to 82 sex and time matched controls. The mean age of cats with UO was significantly lower compared to controls, while the mean body weight was higher. The proportion of indoors-outdoors cats was significantly lower in the study group compared to the control group, and the proportion of cats consuming only dry food was higher. Overall mortality was 8.5%. Ionised calcium was significantly higher in survivors compared to non-survivors, and the prevalence of hypocalcaemia was lower. Recurrence in 6 months and 2 years were 22% and 24%, respectively. Cats with recurrence had significantly lower urine pH at presentation., (Copyright © 2010 ISFM and AAFP. Published by Elsevier Ltd. All rights reserved.)

Objective: To evaluate the clinical usefulness of analysis of fetal urine in the prediction of poor postnatal renal function in cases of congenital urinary tract obstruction., Methods: A systematic review was performed. We conducted extensive electronic searches (database inception-2006). The reference lists of articles obtained were searched for any further articles. Two reviewers independently selected the articles in which the accuracy of fetal urinalysis was evaluated to predict poor postnatal renal function. There were no language restrictions. Data were extracted on study characteristics, quality and results, to construct 2 x 2 tables. Likelihood ratios for positive (LR+) and negative (LR-) test results were generated for the different fetal urinary analytes at various thresholds., Results: There were 23 articles that met the selection criteria, including a total of 572 women and 63 2 x 2 tables. The two most accurate tests were calcium > 95th centile for gestation (LR + 6.65, 0.23-190.96; LR - 0.19, 0.05-0.74) and sodium > 95th centile for gestation (LR + 4.46, 1.71-11.6; LR - 0.39, 0.17-0.88). beta(2)-microglobulin was found to be less accurate (LR + 2.92, 1.28-6.69; LR - 0.53, 0.24-1.17)., Conclusion: The current evidence demonstrates that none of the analytes of fetal urine investigated so far can be shown to yield clinically significant accuracy to predict poor postnatal renal function.

The goal of this study was to improve the understanding of the potential significance of dietary soy for human health by investigating its effects in the animal models of nonbacterial prostatitis and urethral obstruction. Nonbacterial prostatitis was induced in adult Noble rats with the combined treatment of testosterone and 17beta-estradiol. The inflammatory foci categorized into three forms were counted and correlated with expression of an estrogen-responsive gene, progesterone receptor (PR), in the dorsolateral lobes of the rats on soy (+) and soy (-) diets. Development of obstructive voiding after neonatal estrogenization of Noble rats (NeoDES rats) was followed with urodynamic measurements in rats on soy (+) and soy (-) diets. The amounts of genistein and daidzein, two major soy-derived isoflavones, were measured in the urine of Noble rats by the high-performance liquid chromatography-photodiodearray method. Dietary soy decreased the total number of inflammatory foci while no demonstrable effects were seen on the cellular composition of the infiltrates. Soy did not increase the weights of the pituitary gland, testes, or sex accessory glands, but it did increase the number of PR-positive epithelial cells in the dorsolateral prostate. It also decreased the bladder pressures in NeoDES rats but did not increase the flow rates. The soy effects may be mediated by the strong estrogen influence involved in the animal models. Dietary soy had anti-inflammatory effects in the prostate but only marginal effects on the development of obstructive voiding in Noble rats. The anti-inflammatory effects of soy may contribute to the lower prevalence of prostatitis-like symptoms and the historically lower risk of benign prostatic hyperplasia in Japan; however, no evidence was found that regular consumption of soy influences the age-related development of lower urinary tract symptoms or decline of flow rate.

Purpose: Pressure-flow studies are currently recognized as the criterion standard to quantify urethral obstruction and its consequence on detrusor contractility. These tests have some disadvantages: they are invasive, time-consuming and expensive and entail risk of disease for the patient. Less invasive methods have been proposed to give the same results without the disadvantages. In this study, we conducted a critical analysis of the devices and techniques and their results., Method: After a brief reminder of the general behavior of the flow in an obstructed urethra, we describe the main non-invasive techniques: penile urethral compression-release (PCR), cuffs, and condoms. Using the VBN method, we tried to quantify data from these techniques to specify the relation with the usual parameters of bladder outlet obstruction., Results: In the absence of brisk change of the flow rate, the voiding phases are easily analyzed. With minor corrections, recorded external or cuff pressures could be used in the ICS nomogram; unfortunately, these pressures are greatly modified by perturbations of the nervous control. The spike of flow (due to urine storage in the urethra) observed at resumption of flow after each interruption presents mathematical difficulties for quantitative and reliable modeling but could give a consistent empirical interpretation., Conclusion: Of the reported non-invasive tests, all except PCR have an important instrumental heaviness and induce strong perturbations of the nervous control. If they cannot allow an accurate quantification of urethral obstruction and detrusor contractility, they could allow for classification of benign prostatic hypertrophy (BPH) patients. Despite the mathematical problems set by the theory of spikes, the empirical use of the spikes amplitude could perhaps be clinically useful.

Objective: We reviewed the prenatal and postnatal management of fetal lower urinary tract obstruction (LUTO) in a large geographically defined population., Methods: The records of 113 cases of LUTO seen over a 14-year period were examined. The predictive accuracy of prenatal findings for chronic renal failure (CRF) and a comparison of prenatal-suspected and non-suspected cases were made., Results: The incidence of LUTO was 2.2 in 10 000 births. During the study period, prenatal detection improved from 33 to 62%. Sensitivity of prenatal ultrasound detection of renal dysplasia and fetal urinary sodium, calcium, and beta2-microglobulin for CRF or renal dysplasia on autopsy were 59, 33, 66, and 63% respectively. Compared to undetected cases, those detected prenatally had higher mortality and a higher rate of CRF at 24 months (17% vs 57%, p < 0.01)., Conclusion: Our observations confirm the poor prognosis associated with fetal LUTO. The value of serial fetal urine biochemistry, other prenatal predictors of postnatal renal function, and the benefits of vesicoamniotic shunting require larger series and longer follow-up., (Copyright (c) 2005 John Wiley & Sons, Ltd.)

The aim of this study is to implement the use of biochemical parameters in the analysis of fetal urine to assist with decision making for surgical intervention for fetal obstructive uropathy. Three patients were selected over a 6 month period following ultrasound diagnosis of megabladder and oligohydramnios. Amniocentesis and cystocentesis were performed for karyotyping and biochemical urinary electrolyte evaluation, respectively. Fetal urine biochemistry assisted in decision making with regard to patient and fetal well being. In each of the cases the parameter cutoffs were diagnostic of fetal condition. While the long term benefits of fetal intervention for obstructive uropathy are still debated, we feel that the use of urine biochemical criterIa provide the best current method to select the subjects to be submitted to vesicoamniotic shunt centres.

Objective: Fetal intervention for obstructive uropathy was first performed at the University of California, San Francisco in 1981. Indications for treatment were bilateral hydronephrosis with oligohydramnios. Preintervention criteria included fetal urinary electrolytes with beta-microglobulin levels, karyotyping, and detailed sonography specifically looking for renal cortical cysts. We reviewed the outcomes of children who underwent fetal intervention with specific long-term follow-up in patients who were found postnatally to have posterior urethral valves., Methods: A retrospective review of the University of California, San Francisco fetal surgery database was performed for patients with a prenatal diagnosis of obstructive uropathy. Medical records from 1981 to 1999 were reviewed. Long-term follow-up was documented if the cause of the urinary tract obstruction was posterior urethral valves. We collected data points, focusing on time and type of intervention, fetal urinary electrolytes, appearance of fetal kidneys, present renal function, length of follow-up, and present status of the urinary tract., Results: Forty patients were evaluated for fetal intervention; 36 fetuses underwent surgery during this time period. Postnatal confirmation of posterior urethral valves was demonstrated in 14 patients. All patients had favorable fetal urinary electrolytes. Mean gestational age at intervention was 22.5 weeks. The procedures performed included creation of cutaneous ureterostomies in 1, fetal bladder marsupialization in 2, in utero ablation of valves in 2, and placement of vesicoamniotic catheter in 9. Six deaths occurred before term delivery with premature labor and the newborns succumbing to respiratory failure. One pregnancy was terminated electively because of shunt failure and declining appearance of fetal lungs and kidney. The remaining 8 living patients had a mean follow-up of 11.6 years. Chronic renal disease with abnormal serum creatinine was present in 5 patients. Two patients have undergone renal transplantation, and 1 is awaiting organ donation. Five of the 8 living patients have had urinary diversion with vesicostomy, cutaneous ureterostomy, or augmentation cystoplasty with later reconstruction., Conclusions: Fetal intervention for posterior urethral valves carries a considerable risk to the fetus with fetal mortality rate of 43%. The long-term outcomes indicate that intervention may not change the prognosis of renal function or be a predictor for possible urinary diversion. Despite all of these patients' having favorable urinary electrolytes, this did not seem to have any implication postnatally. When counseling families about fetal intervention, efforts should be focused on that intervention may assist in delivering the fetus to term and that the sequelae of posterior urethral valves may not be preventable. Fetal surgery for obstructive uropathy should be performed only for the carefully selected patient who has severe oligohydramnios and "normal"-appearing kidneys.

Objectives: Patients with posterior urethral valves (PUV) are at significant risk for progression to end-stage renal disease, despite early correction of the obstruction. Experimental models of urinary obstruction demonstrate increased renal expression of the profibrotic inflammatory mediator, transforming growth factor-beta(1) (TGF-beta(1)). Urinary TGF-beta(1) excretion is elevated in certain glomerular diseases, but has not been well studied in patients with obstructive lesions. The objective of this study was to examine urinary TGF-beta(1) excretion in children with PUV., Methods: Fourteen patients with PUV, aged 3.2 to 14.5 years, with estimated glomerular filtration rates (GFRs) of 12.8 to 139 mL/min/1.73 m(2) were enrolled. Sixteen normal subjects (9 male, 7 female), aged 4.3 to 20.5 years, served as controls. Total urinary TGF-beta(1) concentration was assayed by enzyme-linked immunoabsorbent assay, and expressed as a ratio to urinary creatinine concentration., Results: Urinary TGF-beta(1) excretion was significantly greater in patients with PUV (range 0 to 0.063, median 0.019 ng/mg urine creatinine) compared with that of healthy controls (range 0 to 0.022, median 0.005 ng/mg urine creatinine) (P <0.01). There was no correlation between urinary TGF-beta(1) excretion and estimated GFR, past urinary diversion surgery, or bladder wall thickening. Among healthy controls, urinary TGF-beta(1) was not correlated with age or gender., Conclusions: Results from this study suggest that TGF-beta(1) may contribute to progressive renal insufficiency in patients with PUV. Further studies are indicated to determine if agents that affect TGF-beta(1) expression, such as angiotensin-converting enzyme inhibitors, can slow the progression of renal disease in PUV.

Xanthine calculi were found in a 7-month-old male Cavalier King Charles spaniel with urethral obstruction and renal insufficiency. Because the only two other reported cases of naturally occurring xanthine urolithiasis concerned a Cavalier King Charles and a King Charles spaniel the urine of the littermates and parents of the patient were also examined for xanthinuria. Semi-quantitative analysis revealed high urine concentrations of hypoxanthine and xanthine in the patient and his female littermate. Quantitative analysis by high-pressure liquid chromatography (HPLC) of the urine samples from the family of this Cavalier King Charles spaniel and nine control dogs revealed that hypoxanthine and xanthine excretion was 30 and 60 times higher in the affected patient and the female littermate than in the others dogs. The pattern of xanthinuria, which is caused by a deficiency of the enzyme xanthine oxidase, in the relation diagram of this family of Cavalier King Charles Spaniels was consistent with an autosomal recessive mode of inheritance.

Objective: Our goal was to assess fetal kidney function in fetuses with megavesica diagnosed during the first half of pregnancy before treatment., Study Design: In a prospective interventional study 9 fetuses with megavesica diagnosed during the first half of pregnancy underwent vesicocentesis. Fetal urine biochemical markers (urine electrolytes, osmolarity, and beta 2-microglobulins) were determined after diagnostic vesicocentesis of the fetal megavesica., Results: Surprisingly, in four fetuses who underwent sampling at 13 to 18 postmenstrual weeks, vesicocentesis proved both diagnostic and therapeutic. Pregnancy proceeded with normal amniotic fluid volume, a normal-sized urinary bladder with normal dynamics, and normal postnatal renal function. A fifth fetus had trisomy 18. In three of the remaining four fetuses in whom sampling was performed at 16 to 20 postmenstrual weeks, biochemical markers indicated a poor prognosis. In the remaining fetus marginal results of biochemical studies prompted intrauterine treatment, but death from respiratory problems ensued after premature delivery at 31 weeks., Conclusions: Fetal megavesica in the first half of pregnancy is an indication for an immediate diagnostic vesicocentesis. This is the first report emphasizing early diagnosis of fetal megavesica with subsequent fetal vesicocentesis and demonstrating that this minimally invasive procedure can be life-saving if performed in early pregnancy.

We evaluated 8 second-trimester fetuses who had undergone termination because of obstructive uropathies and correlated the renal histopathology with fetal urine biochemical prognostic parameters. Prenatal evaluation included serial vesicocentesis, karyotyping, and sonography. According to the urinary biochemical parameters, 3 fetuses were classified to be in the good prognostic category, 2 in the borderline prognostic category, and 3 in the poor prognostic category. The kidneys were evaluated both grossly and microscopically for hydronephrosis, pelvicaliceal dilatation, cystic changes and fibrosis. Fetuses in the poor prognostic category had severely damaged renal architecture, microcysts, macrocysts, and extensive fibrosis. Fetuses in the good prognostic category had minimal histopathologic changes with preservation of the architecture. Fetuses in the borderline category showed a moderate degree of renal damage but with focally preserved architecture. We conclude (1) that there is a direct correlation between elevation in urinary electrolytes and proteins and extent of underlying renal histopathological damage and (2) that appropriate detailed prenatal evaluation of the renal function can identify fetuses who could potentially benefit from in utero therapy.

Objectives: The assessment of fetal renal function plays a key role in the evaluation of posterior urethral valve obstruction cases. The aim of our study was to determine the value of several urinary compounds, including beta 2-microglobulin, N-acetyl-beta-D-glucosaminidase, and microalbumin in the assessment of prenatal renal function in cases of posterior urethral valve and their potential role in the selection of such cases for in utero shunting., Study Design: A range of urinary compounds was measured, including beta 2-microglobulin, N-acetyl-beta-D-glucosaminidase, and microalbumin in 25 cases of posterior urethral valve obstruction. These cases were divided into four groups based on outcome. The Mann-Whitney test and analysis of covariance were used., Results: Sodium, calcium, and beta 2-microglobulin were the best predictors for fetal survival. beta 2-Microglobulin values > 13 mg/L were almost invariably associated with fatal outcome., Conclusion: The estimation of beta 2-microglobulin may help in counseling parents and in selecting cases for in utero shunting.

Objective: To construct a reference range for fetal urinary sodium, potassium, urea, creatinine, calcium and phosphate with gestation and to assess to what extent these biochemical indices are modified in fetuses with lower urinary tract obstruction., Design: Prospective descriptive study., Setting: Royal Postgraduate Medical School London., Subjects: 24 women between 17 and 35 weeks gestation with an ultrasound diagnosis of fetal lower urinary tract obstruction, with or without renal dysplasia and a control group of 26 women between 16 and 33 weeks gestation with normal amniotic fluid volume and fetal anatomy., Interventions: Fetal urine samples (1-100 ml) were aspirated from the control fetuses either before termination of pregnancy (n = 9) or at the time of intrauterine transfusion for Rh alloimmunization (n = 17). The fetuses with obstructive uropathy had urine samples aspirated on one occasion (n = 14) or serially (n = 10)., Main Outcome Measures: Relation between urine biochemistry and renal damage ascertained clinically or at postmortem., Results: In the control group, urinary sodium and phosphate decreased and creatinine increased significantly with gestational age, consistent with increasing fetal glomerular filtration rate and progressive maturation of tubular function. Urinary sodium and calcium were significantly higher in fetuses with renal dysplasia compared with those with lower urinary tract obstruction but normal renal histology or normal clinical outcome. Serial urinary samples from fetuses with obstructive uropathy showed more pronounced deviation from the normal with increasing gestation in all fetuses with renal dysplasia. The highest sensitivity in the detection of renal dysplasia was shown by urinary calcium (100%) whereas urinary sodium showed the best specificity (80%)., Conclusion: Renal damage is the direct effect of urinary obstruction, rather than an association so that treatment should start as soon as possible. Urinary biochemistry may be helpful in the management of these patients.

Twenty-one patients with chronic obstructive uropathy due to high pressure chronic retention of urine underwent renal functional assessment both during the period of obstruction and repeatedly up to 3 months following its relief. Glomerular filtration rate (GFR) was determined using clearance of 99mTc-DTPA and iohexol. Creatinine, water, urea and electrolyte excretion was assessed from timed urine collections. Excretion of water, urea and electrolyte was normal during obstruction but increased dramatically immediately following relief (e.g. sodium 110 to 234 mmol/24 h). Values returned to normal by 2 weeks (sodium excretion 148 mmol/24 h). No further significant changes occurred up to 3 months. Mean 99mTc-DTPA and iohexol clearances during obstruction were 59.0 and 50.5 ml/min respectively. Following relief of obstruction, no significant improvement occurred at 2 weeks but did at 3 months (mean = 68.4 and 55.7 ml/min). Mean creatinine clearance during obstruction was 32.5 ml/min. This improved 2 days following relief to 46 ml/min. No further improvement was seen until 3 months (mean = 57.3 ml/min). It was concluded that recovery of renal function from obstructive injury occurs in two phases, an early tubular phase lasting up to 2 weeks and a later, predominantly glomerular phase, between 2 weeks and 3 months. There is some disparity between creatinine clearance and more accurate measurements of GFR which may be explained by tubular excretion of creatinine in the early phase of recovery.

Preliminary evidence suggests that the concentration of lactic acid in urine may be a good means of distinguishing lower urinary tract infection (cystitis) from upper urinary tract infection (pyelonephritis) and may be helpful in detecting urinary tract obstruction. To test this hypothesis the lactic acid concentrations in 291 urine samples from 250 children were tested. Sixty-four patients had no bacterial infection and served as the control group. A second group (153 patients) had cystitis, and the third group (24 patients) showed radiologic, clinical, and laboratory evidence of pyelonephritis. A fourth group of nine patients who had prolonged urinary tract retention was also analyzed. Patients in the control group, as well as those with cystitis, showed relatively; low concentrations of urinary lactic acid. All levels were less than 2 mg/dl; (mean, 0.8 mg/dl; range, 0.1-2 mg/dl). Patients who had clinical pyelonephritis had lactic acid concentrations of 3.3 mg/dl (mean, 11.4 mg/dl; range, 3.3 mg/dl-40.5 mg/dl). There was no overlap in lactic acid concentrations between the two groups. Furthermore, lactic acid concentrations in urine from patients who had pyelonephritis gradually declined after the initiation of therapy, attaining a level of less than 1 mg/dl by the end of the treatment. Recurrence of the pyelonephritis was consistently documented by a renewed increase of urinary lactic acid concentration. Lactic acid levels were also elevated in urine samples collected immediately after relief of obstruction in the nine patients who had urethral obstructions, showing a mean concentration of 15.8 mg/dl (range, 4.2-37.2 mg/dl).