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.

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.

Sequential fetal serum ß2-microglobulin to predict postnatal renal function in bilateral or low urinary tract obstruction.

OBJECTIVE: Fetal serum ß2-microglobulin has been shown to predict postnatal renal outcome in cases of fetal obstructive uropathy. We assessed the value of serial measurements of fetal serum ß2-microglobulin in the prediction of postnatal renal outcome. METHODS: We retrospectively studied renal outcome in 42 fetuses with bilateral or low urinary tract obstruction that had fetal blood sampling on at least two occasions to assay serum levels of ß2-microglobulin. Amniotic fluid volume at the time of each sampling was recorded. We classified renal outcome as either favorable (when postnatal renal function was normal) or adverse (when postnatal chronic renal failure occurred or when renal dysplasia at autopsy was noted). A ß2-microglobulin cut-off of 5 mg/L and amniotic fluid index of 5 cm were used to predict postnatal renal outcome. RESULTS: Renal outcome was adverse in 28 cases and favorable in 14. In 12 (28.6%) cases, fetal serum ß2-microglobulin concentration differed between the first and last measurement. Prediction of postnatal renal outcome was correct in 11 of these cases based on the last ß2-microglobulin measurement. The sensitivity of ß2-microglobulin in predicting renal outcome was significantly higher (P = 0.005) when using the last rather than the first measurement (96.4% vs 64.3%), with similar specificity for both measurements (85.7% vs 78.6%, non-significant). The sensitivity of amniotic fluid volume was also significantly higher (P = 0.005) when using the last rather than the first measurement (75.0% vs 35.7%), with similar specificity for both measurements (64.3% vs 71.4%, non-significant). CONCLUSION: Sequential measurement of serum ß2-microglobulin, performed for adverse ultrasound findings, such as renal parenchymal abnormality or decreasing amniotic fluid volume, predicts postnatal renal outcome more accurately than does a single assay. This may be due to possible worsening of renal injury with increasing duration of urinary tract obstruction. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

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.

Prostatic inflammation and obstructive voiding in the adult Noble rat: impact of the testosterone to estradiol ratio in serum.

BACKGROUND: The age-related decline of the testosterone to estradiol (T-to-E(2)) ratio in serum is associated with the increased prevalence of prostatic inflammation and lower urinary tract symptoms suggesting obstructive voiding. The impact of the T-to-E(2) ratio on the development and reversal of non-bacterial prostatic inflammation and obstructive voiding was tested in adult Noble rats. METHODS: Adult male Noble rats (n = 16) were treated with estradiol (83 microg/day) and two different doses (280 and 830 microg/day) of testosterone to cause hypoandrogenic and hyperandrogenic states with elevated estrogen. After the 13-week hormonal treatment, urodynamical measurements and electrical activity recording of the rhabdosphincter muscle were performed under anesthesia. Testosterone, estradiol, and prolactin concentrations in serum were measured and inflammatory changes in the dorsolateral prostate were classified and counted. RESULTS: Histopathological and urodynamical analyses indicated that the hypoandrogenic animals with a decreased T-to-E(2) ratio (10 versus > 300 in control) developed prostatic inflammation and non-obstructive voiding. The hyperandrogenic state with decreased T-to-E(2) ratio of 50 decreased the aggressiveness of the inflammation and the number of inflamed acini in the prostate and caused urethral obstruction associated with rhabdosphincter dysfunction. CONCLUSIONS: Different responses of the prostatic inflammation and voiding function to the change in T-to-E(2) ratio imply that non-bacterial prostatic inflammation is not a sufficient condition for the development of obstructive voiding. The present study finds no support for the idea that age- and/or obesity-related hypoandrogenic state with a decreased ratio of T-to-E(2) would cause urethral obstruction.

Fetal surgery for posterior urethral valves: long-term postnatal outcomes.

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.

The Whitaker hook in the treatment of posterior urethral valves.

OBJECTIVE: To assess the efficacy of the Whitaker diathermy hook in the treatment of posterior urethral valves (PUV). PATIENTS AND METHODS: Seventeen patients with PUV underwent primary treatment under general anaesthesia using a diathermy hook. The results were assessed by the clinical course of the patient, serial measurements of serum creatinine level and repeat cystography 6 weeks and 6 months after treatment. RESULTS: There were no complications in 12 patients and they required no further treatment of the valves. Three patients required a repeat procedure which resolved the urethral obstruction. Two patients continued to show incomplete disruption of the valves and required endoscopic treatment. Two patients developed ureteric obstruction after disruption of the valves, which was treated by supravesical diversion and later reversed with no further treatment of the valves. CONCLUSIONS: The Whitaker diathermy hook is a safe and effective instrument which has not gained its rightful place in the treatment of patients with PUV.

[Posterior urethral valves. Prognostic factors in the clinical course]. / Válvulas de uretra posterior. Factores pronóstico en la evolución.

A retrospective study was conducted in 27 patients with posterior urethral valves that had been treated between 1978 and 1991 in order to determine the prognostic factors of renal function. Patient age ranged from 12 days to 12 years. The mean follow-up was 5 years. Urinary infection was the most common symptom. We used micturating cystography, intravenous urography, US, urodynamics and cystoscopy for the diagnosis. Renal function was evaluated by serum creatinine. All the valves were treated endoscopically by transurethral fulguration. Nineteen patients also underwent ureteral reimplantations. There were 5 nephrectomies and 12 upper tract diversions. There was a strong correlation between serum creatinine at the beginning and after a year and the final renal function (p > 0.001 and p = 0.030, respectively). The correlation between the age and initial serum creatinine was almost significant (p = 0.065). There was no significant correlation between the age at diagnosis, the reflux and the final renal function.

Routine estimation of prostate specific antigen prior to clinic attendance in patients with symptoms of bladder outlet obstruction.

We report the use of serum prostate specific antigen (PSA) estimations prior to clinic attendance in 234 patients referred with symptoms of bladder outlet obstruction to a general urology clinic. Ninety-three patients with PSA levels > 10 ng/ml were seen earlier than planned and offered transurethral resection or transrectal biopsy of the prostate gland. Forty-six patients (49%) proved to have carcinoma of the prostate, compared with 10 of 141 (7%) patients who had PSA values < 10 ng/ml. With a decision value of 10 ng/ml, the sensitivity for detecting carcinoma was 82% and specificity 73.5%. Using a decision value of 7 ng/ml improved the sensitivity to 95% without significantly affecting the specificity (70%). Twenty-four patients with prostatic cancer had bone metastases; the sensitivity of PSA for predicting a positive bone scan using a decision value of 25 ng/ml was 92%, but the specificity was only 31%.

Acute retention of urine and hypogonadism in a man.

We report on a man with castrate levels of testosterone who had acute retention of urine secondary to prostatic obstruction.