Post-void residual urine ratio: A novel clinical approach to the post-void residual urine in the assessment of males with lower urinary tract symptoms.

PURPOSE: To assess the correlation between post-void residual urine ratio (PVR-R) and pathological bladder emptying diagnosed by pressure-flow studies (PFS) in males with lower urinary tract symptoms (LUTS). MATERIALS AND METHODS: PVR-R and PVR urine were evaluated in 410 males underwent PFS for LUTS. PVR-R was the percentage of PVR to bladder volume (voided volume+PVR). Schafer and International Continence Society (ICS) nomograms, Bladder Contractility Index (BCI) were used to diagnose bladder outlet obstruction (BOO) and detrusor underactivity (DUA). We subdivided the cohort in 4 groups: Group I, BOO+/DUA+; Group II, BOO-/DUA+; Group III, BOO+/DUA-; Group IV, BOO-/DUA- (control group). We subdivided the 4 groups according to PVR-R strata: (1) 0%-20%; (2) 21%-40%; (3) 41%-60%; (4) 61%-80%; (5) 81%-100%. RESULTS: Group I had a greater median PVR-R (50%) with a >40% in 61.4% of the cohort. Median PVR-R was 16.6% in Group II, 24% in Group III, and 0% in the control Group. According to ICS nomograms and BCI, median PVR-R and PVR were significantly higher (p<0.001) in obstructed and underactive males. PVR-R threshold of 20% allowed to recognize males with voiding disorders with high sensibility, specificity, PPV, and NPV. A PVR-R cut-off of 40% identified males with associated BOO and DUA and more severe voiding dysfunction. CONCLUSIONS: A higher PVR-R is related to a more severe pathological bladder emptying, and to the association of BOO and DUA. PVR-R may have a clinical role in first assessment of males with LUTS and severe voiding dysfunction.

MicroRNAs as potential biomarkers to predict the risk of urinary retention following intradetrusor onabotulinumtoxin-A injection.

AIMS: MicroRNAs (miRs) control post-transcriptional gene expression, and this is relevant in understanding better chronic diseases and treatment outcomes. The role of miRs in the pathology and treatment outcomes of overactive bladder (OAB) is unknown. In this study, we assessed the differential expression of miRs in OAB patients responding with either normal or elevated post-void residual volumes (PVRs) ≥200 mL following intradetrusor injection of onabotulinumtoxin-A (onaBoNT-A). METHODS: Female OAB patients refractory to OAB drugs were consented for this study. Cystoscopic-guided punch bladder biopsy was obtained at the time of injection of onaBoNT-A 100 units. The expression of 13 miR species, selected for their known effect on neurotrophin expression and smooth muscle function, was measured. PVRs and urine nerve growth factor (NGF) levels were measured at baseline and at the follow-up visit. RESULTS: Fourteen patients with mean age of 66 years were consented. Of these patients, nine maintained PVRs <200 mL after onaBoNT-A injection to comprise the low PVR group. The other five patients with PVRs ≥200 mL comprised the high PVR group. The expression of miR221 and miR125b was upregulated by 11- and 2-fold, respectively, in patients who responded with low PVRs after onaBoNT-A (P < 0.05). Urine NGF levels at baseline were not different between the two groups. CONCLUSIONS: This study suggests that deficiency in the pretreatment expression of miR221 and miR125b may predispose OAB patients to high PVRs following intradetrusor onaBoNT-A. Additional studies are needed to better understand the role of miRs in OAB.

Urinary biomarkers in patients with detrusor underactivity with and without bladder function recovery.

PURPOSE: Detrusor underactivity (DU) is frequently encountered in elderly patients. Part of patients with DU might have bladder function recovery after treatment. This study investigated urinary proteins in these DU patients with and without bladder function recovery. METHODS: A total of 37 patients with chronic urinary retention and urodynamically proven DU were enrolled. After treatment, 24 DU patients had bladder function recovery whereas 13 had not, after 1-year follow-up. Urine collection at baseline was performed, and the urinary protein including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and prostaglandin E2 (PGE2) were measured by ELISA. Twenty urodynamically normal, 34 detrusor overactivity (DO) and 15 detrusor hyperactivity and inadequate contractility (DHIC) patients served as comparative groups. RESULTS: Urinary NGF levels were significantly higher than normal in patients with DU (9.2 ± 20.3 vs 1.85 ± 2.9 pg/ml, p = 0.037). Urinary BDNF level was only significantly higher in patients with DU than that of the control group (153 ± 199 vs 77.4 ± 47.7 pg/ml, p = 0.033) but not in patients with DHIC or DO. Compared with the control group, the urinary BDNF level was significantly higher in DU patients with bladder function recovery (190 ± 239 pg/ml, p = 0.033) but not in patients without recovery (85.8 ± 43.7 pg/ml, p = 0.612). The PGE2 level was significantly higher than the control group in DU patients with bladder function recovery (1290 ± 836 pg/ml, p < 0.0001) but not in patients without recovery (383 ± 237 pg/ml, p = 0.130). CONCLUSION: Patients with DU and higher urinary PGE2 and BDNF levels might have a chance to recover bladder function than those with a lower protein level.

Ranolazine-induced severe bladder hypotonia.

OBJECTIVE: To describe a case of acute urinary retention due to bladder hypotonia during ranolazine treatment. CASE SUMMARY: An 81-year-old male with multiple cardiovascular diseases was hospitalized for worsening angina and heart failure symptoms. Ranolazine 375 mg twice daily was started, in addition to ongoing therapy (clopidogrel 75 mg once daily, diltiazem 60 mg 3 times daily, isosorbide mononitrate 40 mg 3 times daily, carvedilol 6.25 mg twice daily, rosuvastatin 20 mg once daily, enoxaparin 5000 IU once daily, pentoxifylline 600 mg twice daily, pantoprazole 40 mg twice daily, enalapril 20 mg twice daily, furosemide 150 mg once daily, and spironolactone 37 mg once daily). Two months later, the ranolazine dose was increased to 500 mg twice daily; shortly thereafter, acute urinary retention occurred and persisted despite institution of α-lytic (alfuzosin) and antiandrogenic (dutasteride) therapy. A urodynamic study revealed that urinary retention was caused by severe hypocontractility of the detrusor muscle. Ranolazine was withdrawn and, within 2 days, the patient recovered his ability to void spontaneously; a second urodynamic study confirmed that detrusor contractility was substantially improved. Drug rechallenge was not performed due to the patient's clinical condition. Nevertheless, a phenotyping test to assess the activity of the cytochrome isoenzymes CYP3A4 and CYP2D6 (responsible for ranolazine metabolism) was performed, with dextromethorphan used as the probe drug. The urinary metabolic ratios indicated relatively low activity for CYP3A4 and intermediate activity for CYP2D6. DISCUSSION: The causal role of ranolazine in our case of bladder hypotonia is probable according to the Naranjo criteria. The mechanism of bladder dysfunction is tentatively ascribed to blockage of late sodium current in smooth muscle cells. Although drug plasma concentrations were not measured, they were probably elevated, since the metabolic activity of CYP3A4 was at the lower end of the reference range. Enzyme inhibition produced by diltiazem may have contributed to decreasing CYP3A4 activity. CONCLUSIONS: Acute urinary retention in elderly men taking ranolazine may be due to drug-induced bladder hypotonia.

Measurement of postvoid residual urine in conscious mice using high-frequency transrectal ultrasound.

The aim of this study was to develop a novel technique for a minimally invasive ultrasound measurement of postvoid residual urine (PVR) in conscious mice using a miniature ultrasound probe and a transrectal approach. The PVR was determined by the ellipsoid formula in the maximum sectional image of the bladder visualized with a 20-MHz ultrasound probe (2 mm in diameter) inserted into the rectum. The accuracy, including the intra- and interobserver reproducibilities, of the ultrasonic PVR measurements (in 10 5- to 50-week-old mice) was evaluated, which revealed excellent internal consistency. In M(3) muscarinic acetylcholine receptor knockout male mice, a chronological evaluation of the PVR identified abnormal urinary retention present at infancy and exacerbated with aging, suggesting significant voiding dysfunction. Our technique for the measurement of PVR in conscious mice was accurate and useful for identifying the voiding dysfunction in mice.

Clinical observation on the acupuncture treatment in patients with urinary retention after radical hysterectomy.

OBJECTIVE: To observe the acupuncture therapy effect on the urinary retention after radical: hysterectomy. METHODS METHODS: Eighty cases of urinary retention after radical hysterectomy were randomly assigned to: the treatment group and control group according to the random number table method, 40 cases in each group. From the 15th day post operation, the patients in the two groups started to be treated and 7 days as a course with 5 days treatment and 2 days interval. The treatment group applied acupuncture with modalities of common needling on Zusanli (ST36) bilaterally, electroacupuncture on Sanyinjiao (SP6), Shuidao (ST28), and Scalp Reproduction Area bilaterally, moxibustion on Shenque (CV8). The control group applied acupoint injection with vitamin B B12 12, and Sanyinjiao and Zusanli were selected. Take turns on both sides. The courses for the recovery, of bladder function and residual urine volume for those who had voluntary micturition more than 200 mL after the first and second course of treatment were compared between the two groups. RESULTS: Within 1 course and 2: courses of treatment, the patients with bladder function recovery in the treatment group were 21 (21/40) and 36 (36/40), and those in the control group were 12 (12/40) and 29 (29/40), both with a significant difference (P<0.05). After the first course and second course, residual urine volume for those who had voluntary micturition more than 200 mL in the treatment group was 91.7 ± 17.5 mL and 93.5 ± 15.5 mL, in the control group 102.4 ± 13.7 mL and 102.5 ± 15.7 mL, both with a significant difference (P<0.05). CONCLUSIONS: Combination of acupuncture: modalities was better than acupoint injection for the recovery of bladder function in urinary retention after radical hysterectomy. It would shorten the course of treatment and get a better recovery, decrease urinary retention cases of refractoriness, and extending the treatment could raise the healing rate of urinary retention.

[Association between residual urinary volume and urinary tract infection: prospective trial in 225 male patients]. / Assoziation zwischen Restharnvolumen und Harnwegsinfektion : Prospektive Studie an 225 Männern.

PURPOSE: Urinary tract infections can result from bladder outlet obstruction and consecutive post-void residual urine. In a recent publication, a cutoff for post-void residual urine of 180 ml was calculated, revealing sensitivity and specificity of 87 and 98.5%, respectively, regarding occurrence of significant bacteriuria in asymptomatic men. In the present study the association between post-void residual urine volume and urinary tract infection was evaluated, and different cutoff values were validated. MATERIALS AND METHODS: A total of 225 asymptomatic patients (median age 66 years) were prospectively evaluated regarding the following criteria: prostate-specific antigen, prostate volume, International Prostate Symptom Score, peak urinary flow rate, urine culture results, urinary test strip, and post-void residual urine volume. By ROC analysis a cutoff predicting significant bacteriuria was calculated, and different cutoff values were validated. The independent influence of several parameters on the incidence of urinary tract infection was measured using multivariate regression analyses. RESULTS: Of the patients, 60% were able to completely empty the bladder (post-void residual urine volume

Influence of delayed isotopic equilibration in urine on the accuracy of the (2)H(2)(18)O method in the elderly.

Isotopic determination of total energy expenditure (TEE) by the doubly labeled water (DLW) method may be affected by urine retention in the elderly. The isotopic enrichments in urine and plasma sampled simultaneously 4 h post-DLW dose were compared in a subset of 281 subjects [139 women, 142 men, 75 +/- 3 (SD) yr] of the 3,075 participants in the Health, Aging, and Body Composition study. Based on analytic precisions, a +/- 2% urine-plasma difference was set as the cut-off value. Ten percent of the population presented a difference lower than -2%, suggesting a delay in urine isotopic equilibration. This -13 +/- 10% urine-plasma difference was not linked to analytic errors, illnesses, the sampling time, or the time and quantity of water intake, suggesting that urine retention may be the main factor. The consequences are an 18 +/- 13 and 21 +/- 16% overestimation of the total body water and the TEE, respectively. Unexpectedly, 21% of the population presented a urine-plasma difference higher than +/- 2% that resulted, however, in a nonsignificant TEE underestimation of -3 +/- 5%. In conclusion, the delayed isotopic equilibration observed in urine reduces the accuracy of the DLW method in the elderly. It is recommended, when blood sampling is impossible, to adopt the intercept method with urine sampling 24 h postdose.

Characteristics of protein excretion in patients with acute urinary retention.

OBJECTIVE: To evaluate changes in protein leakage in the glomerular filtration barrier, and in the ability of the tubule to reabsorb proteins during and after acute urinary retention (AUR). PATIENTS AND METHODS: Glomerular and tubular function was investigated in 24 men during AUR (mean age 68 years, mean retention time 31 h and mean retention volume 1140 mL) who were then followed for 6 months by measuring the urinary excretion of glomerular and tubular proteins, and the glomerular filtration rate (GFR). Retention was relieved by inserting a suprapubic catheter and the cause of retention treated one month later. No patient had a previous renal disease or diabetes. RESULTS: During AUR, and after 1 and 6 months, albuminuria was detected in 100%, 92% and 54% of patients, and increased excretion of alpha1-microglobulin in 52%, 36% and 58%, of IgG in 79%, 58% and 40%, and of IgG4 in 67%, 42% and 20%, respectively. The mean GFR was normal during retention and during the follow-up. CONCLUSION: AUR causes disturbances in both the glomerular filtration and tubular reabsorption of proteins. Albuminuria and increased excretion of IgG, IgG4 and alpha1-microglobulin occurred in most patients during AUR. After relieving retention, the albuminuria and elevated alpha1-microglobulin excretion persisted, indicating slight glomerular dysfunction and a permanent defect in the proximal tubule to reabsorb proteins. This could be caused partly by previous chronic obstruction. AUR should be relieved immediately and the basic cause treated effectively to prevent further deterioration of renal function.

[Recurrent nonparasitic chyluria]. / Quiluria redicivante no parasitaria.

OBJECTIVE: To describe a case of recurrent chyluria and review the diagnostic and therapeutic methods. METHODS/RESULTS: A case of non parasitic recurrent chyluria is presented. Retrograde pyelography demonstrated pyelolymphatic reflux. The patient presented chemical pyelitis secondary to the contrast medium which caused remission of the condition. CONCLUSIONS: Chyluria is uncommon in our setting. Postprandial cystoscopy permits identification of the compromised renoureteral unit and perform pyelic instillation of sclerosing agents. Surgery should be reserved for those cases in whom conservative management has failed.

Measurement of residual urine volume using a portable ultrasound instrument.

A portable ultrasound unit (BladderScan BVI 2000) has been developed which offers a non-invasive procedure to determine urine volume. This study was undertaken to evaluate the accuracy of measurements by this method. A high correlation was demonstrated between the catheterized volume and ultrasound estimation (r = 0.98, p < 0.0001). In patients with residual urine of > 50 ml, the unit could correctly identify 93%. This instrument is useful in estimating the residual urine volume, and its application is recommended as an alternative to catheterization for the determination of residual urine.

The effect of ranitidine on urine mucus concentration in patients with enterocystoplasty.

We describe the effect of ranitidine in reducing mucus in urine in 8 patients with enterocystoplasty and present a simple technique for measuring the concentration of mucus in urine. After a 10-day course of ranitidine (300 mg daily in divided doses) the concentration of mucus had fallen significantly from an initial level of 1.38 +/- 0.18 to 0.39 +/- 0.04 mg/ml.

Alfuzosin for treatment of benign prostatic hypertrophy. The BPH-ALF Group.

To assess the long-term efficacy and safety of alfuzosin, a selective alpha 1-adrenergic antagonist, 518 symptomatic patients with benign prostatic hypertrophy (BPH) were randomised to received either alfuzosin (daily dose 7.5-10 mg) or placebo for 6 months. Obstructive and irritative symptoms, assessed according to the Boyarsky scale, significantly improved in the alfuzosin group compared with the placebo group (p = 0.0004). Fewer patients in the alfuzosin group than in the placebo group dropped out due to lack of efficacy (6.8% vs 14.6%, p = 0.004) and the prevalence of spontaneous acute urine retention was lower in the alfuzosin group (0.4% vs 2.6%, p = 0.04). By 6 months, mean urinary flow rates had increased (p less than 0.05) and residual volume had decreased (p = 0.017) in the alfuzosin group, although the two groups were broadly similar with respect to increase in peak flow rate. The overall incidence of adverse events was similar in the two groups, which led to the withdrawal of 10.8% and 9.0% of patients, respectively. The findings emphasise the magnitude of the placebo response in symptomatic patients with BPH and show that treatment with alpha 1 adrenergic antagonist drugs provides long-lasting improvement in such patients.

Evidence that high dose cortisol-induced Na+ retention in man is not mediated by the mineralocorticoid receptor.

We have previously shown that high dose cortisol (F; 240 mg/day)-induced Na+ retention and systolic blood pressure (BP) increases are not inhibited by the glucocorticoid (type II) receptor antagonist RU486. Adequacy of type II receptor blockade with RU486 was clearly demonstrated, indicating that the Na+ retention was not mediated through the glucocorticoid receptor. Spironolactone (Sp: 400 mg/day), in a preliminary assessment, also did not inhibit F-induced Na+ retention. The purpose of this study was to determine whether the Na+ retention produced by F administration is mediated by the type I receptor by comparing the effects of F to a potent type I agonist [9 alpha-fludrohydrocortisone (9 alpha FF)] with and without Sp administration. The effects of the two agonists and Sp on urinary K excretion and BP were also compared. Normal male volunteers, on a constant daily diet for 10 days, received either F (240 mg/day) or 9 alpha FF (3.0 mg/day) with or without Sp (400 mg/day) for the last 5 days. The mean cumulative reductions in Na+ excretion during the 5 days compared to baseline values before hormone administration were 255 +/- 38 and 494 +/- 81 mmol/5 days for F (n = 9) and 9 alpha FF (n = 5), respectively (P = 0.01). Sp (n = 5) completely inhibited 9 alpha FF-induced Na+ retention (494 +/- 81 vs. -37 +/- 130 mmol/5 days; P less than 0.01), but had no effect (n = 5) on F-induced Na+ retention (255 +/- 38 vs. 193 +/- 50 mmol/5 days; P = NS). After the expected first day kaliuresis, the effects of both steroids on net cumulative urinary K+ excretion were minimal. Systolic BP was increased by F, but not 9 alpha FF, and Sp did not inhibit this increase. A 2-fold greater Sp-inhibitable Na(+)-retaining effect of the mineralocorticoid demonstrates that the failure of Sp to block F-induced Na+ retention is not due to inadequate type I receptor blockade. Based on these findings and earlier studies, we conclude that high dose (stress level) F-induced Na+ retention and systolic BP increase are not mediated by either the mineralo- or glucocorticoid receptor in normal man.