Blood plasma and urinary biomarkers of oxidative stress in cats with urethral obstruction.

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 (O2-), 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.

Urinary miRNA profiles discriminate between obstruction-induced bladder dysfunction and healthy controls.

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.

Association of Renal Glomerular and Tubular Function With Renal Outcome in Patients With Posterior Urethral Valves.

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 ß-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 ß-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.

Neutrophil gelatinase-associated lipocalin is an early marker of renal damage in lower urinary tract obstruction in rats / NGAL es un marcador precoz de daño renal en la obstrucción del tracto urinario inferior en ratas

OBJECTIVES: To compare the urinary NGAL levels with serum creatinine levels as an early biomarker for renal injury in rats with bladder outlet obstruction (BOO). METHODS: Twenty male Wistar Albino rats divided into 4 groups. In each group basal serum creatinine and urinary NGAL levels were evaluated. In Group 1 (Sham/Control group) only laparotomy was performed. In Group 2 (14th day partial BOO) and Group 3 (28th day partial BOO) partial obstruction and in Group 4 (Complete BOO) complete obstruction was performed. Serum creatinine levels and urinary NGAL levels were evaluated in Group 4 on the third day of the study, in Group 2 on the 14th day and in Group 3 and Group 1 on the 28th day. Urethra, ureters and kidneys were excracted by laparotomy and evaluated for histopathologic examination. RESULTS: The increase in plasma creatinine levels after obstruction was statistically significant in Group 4 (p < 0.05). There was significant difference between the groups in urinary NGAL levels after obstruction (p < 0.05). Post-obstruction urinary NGAL levels was highest in Group 4 and it was statistically significant when compared to beginning levels (p < 0.05). In Group 3, increase in urinary NGAL levels were higher (p < 0.05) with no increase in plasma creatinine levels after obstruction. CONCLUSIONS: It can be concluded that urinary NGAL levels might be an early biomarker for renal dysfunction in partial bladder outlet obstruction which may cause renal impairment through upper urinary tract injury. Therefore, urinary NGAL may play role during the treatment choice and follow-up in BOO patients

OBJETIVOS: Comparar los niveles urinarios de NGAL con la creatinina sérica como marcador precoz de daño renal en ratas con obstrucción del tracto urinario inferior. MÉTODOS: 20 ratas Wistar Albino masculinas fueron divididas en 4 grupos. En cada grupo se midió el nivel basal de creatinina en suero así como los niveles urinarios de NGAL. En el grupo 1 (Sham/Grupo Control) solo se realizó laparotomía. En el grupo 2 (14 días después de una obstrucción tracto urinario inferior parcial) y el grupo 3 (28 días después de una obstrucción tracto urinario inferior parcial) se realizó una obstrucción parcial y en el grupo 4 (obstrucción completa) una obstrucción completa. Los niveles de creatinina sérica y NGAL urinario fueron evaluados en el grupo 4 en el 3er día del estudio; en el grupo 2 en el día 14 del estudio y en el grupo 1 en el día 28. Uretra, uréteres y riñones se quitaron por laparotomía y se hizo un análisis histológico. RESULTADOS: El incremento en la creatinina sérica después de la obstrucción fue estadísticamente significativo en el grupo 4 (p < 0,05). Hubo suficiente diferecia entre los grupos en términos de NGAL urinario después de la obstrucción (p < 0,005). Los niveles de NGA post-obstructivos fueron superiores en el grupo 4 y fue estadísticamente significativo en comparación con los niveles iniciales. En el grupo 3, el incremento en los niveles de NGAL urinario fue superior (p < 0,005) sin incrementeo en los niveles de creatinina en plasma después de la obstrucción. CONCLUSIONES: Se puede concluir que los niveles de NGAL urinarios podrían ser un marcador de lesión renal en caso de obstrucción parcial del tracto urinario inferior. Por tanto, NGAL urinario debe jugar un papel durante la elección de tratamiento y seguimiento de pacientes con obstrucción del tracto urinario inferior

Longitudinal kidney injury biomarker trajectories in children with obstructive uropathy.

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: What should we tell the prospective parents?

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.

A single-center study to evaluate the efficacy of a fetal urine peptide signature predicting postnatal renal outcome in fetuses with posterior urethral valves.

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 m2 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.

Myocardial function in fetuses with lower urinary tract obstruction: Is there a cardiac remodeling effect due to renal damage?

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 ß-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.

Urine biochemistry to predict long-term outcomes in fetuses with posterior urethral valves.

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, ß2-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 m2 ) and poor in 17% (GFR < 30 mL/min/1.73 m2 ). All fetal urine markers differed between CKD stage 1 + 2 and CKD stage 4 + 5 (P < 0.001). ß2-microblobulin showed an 87% sensitivity for a 72% specificity. A combination of ß2-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.

Renal expression and urinary excretion of Na+/dicarboxylate cotransporter 1 (NaDC1) in obstructive nephropathy: a candidate biomarker for this pathology.

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.

Lower urinary tract obstruction: fetal intervention based on prenatal staging.

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.

Fetal urine biochemistry at 13-23 weeks of gestation in lower urinary tract obstruction: criteria for in-utero treatment.

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, ß-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 ß-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 ß-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.

Simulation of incomplete obstructive uropathy in rats by injecting an artificial calculus into the bladder.

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.

Microalbuminuria and hyperfiltration in subjects with nephro-urological disorders.

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.

Urinary biomarkers in obstructive nephropathy.

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 TGFß and L1 cell adhesion molecule (L1CAM) was significantly increased. Whole-urine TGFß excretion correlated inversely with GFR (r = -0.53; P<0.05). As tests for low GFR, whole-urine TGFß, 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 TGFß, 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.

Urine neutrophil gelatinase-associated lipocalin identifies unilateral and bilateral urinary tract obstruction.

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.

Urinary transforming growth factor-ß1 in children with obstructive uropathy.

AIM: Obstructive uropathies (OU) in childhood constitute one of the major causes of chronic renal insufficiency. Transforming growth factor-ß1 (TGF-ß1) is considered to be the major fibrogenic growth factor. The aim of the present study was to investigate urinary TGF-ß1 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-ß1, proteinuria, microalbuminuria and urinary α1-microglobulin were measured, and renal function was assessed. The results were statistically analyzed. RESULTS: Mean urinary TGF-ß1 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-ß1 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-ß1 than children with NOU. Urinary TGF-ß1 may be a useful non-invasive tool for the differential diagnosis between OU and NOU in children. A positive correlation of TGF-ß1 with markers of renal tissue damage in patients with OU was found.

Urethral obstruction in cats: predisposing factors, clinical, clinicopathological characteristics and prognosis.

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.

Systematic review of accuracy of fetal urine analysis to predict poor postnatal renal function in cases of congenital urinary tract obstruction.

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 soy effect in the disease models of nonbacterial prostatitis and obstructive voiding.

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.