Quantification of Fetal Renal Function Using Fetal Urine Production Rate and Its Reflection on the Amniotic and Fetal Creatinine Levels During Pregnancy.

Adequate prediction of fetal exposure of drugs excreted by the kidney requires the incorporation of time-varying renal function parameters into a pharmacokinetic model. Published data on measurements of fetal urinary production rate (FUPR) and creatinine at various gestational ages were collected and integrated for prediction of the fetal glomerular filtration rate (GFR). The predicted GFR values were then compared to neonatal values recorded at birth. Collected data for FUPR across different gestational ages using both 3D (N = 517) and 2D (N = 845) ultrasound methods showed that 2D techniques yield significantly lower estimates of FUPR than 3D (p < 0.0001). A power law function was shown to best capture the change in FUPR with fetal age (FA) for both 2D ( F U P R 2 D ( m L min ) = 0 . 000169     FA 2 . 19 ); and 3D ( F U P R 3 D   ( m L min ) =   3 . 21 × 1 0 - 7   FA 4 . 21 ) data. The predicted FUPR based on the observed 3D data was shown to be strongly linearly related (R 2 = 0.95) to measured values of amniotic creatinine concentration (N = 664). The FUPR3D data together with creatinine levels in the fetal urine and serum resulted in median predicted fetal GFR values of 0.47, 1.2, 2.5, and 4.9 ml/min at 23, 28, 33, and 38 weeks of fetal age (50% CV), respectively. These values are in good agreement with neonatal values observed immediately at birth. The derived FUPR and creatinine functions can be utilized to assess fetal renal maturation and predict fetal renal clearance.

Reduced fetal urine production rate-An early marker of fetal inflammatory response syndrome in preterm premature rupture of membranes: Prospective cohort study.

OBJECTIVE: To find association between fetal urine production rate (FUPR) and fetal inflammatory response syndrome (FIRS) in preterm premature rupture of membranes (PPROM). METHODS: A prospective cohort study of 70 pregnant women with PPROM at 28-34 weeks of pregnancy was conducted. FUPR was calculated by performing serial fetal bladder volume measurements ultrasonographically and was repeated weekly until delivery. After delivery, cord blood interleukin-6 (IL-6) levels were measured. Placental tissue histopathology was performed and neonatal outcomes were noted. RESULTS: Out of 70 recruited patients with PPROM, 44 had evidence of FIRS (62.86%). Mean FUPR at the time of delivery was significantly reduced in neonates with evidence of FIRS compared with the Non-FIRS group (13.89 ± 8.06 ml/h vs. 25.89 ± 4.94 ml/h). Out of 41 patients with reduced FUPR, 39 neonates had FIRS whereas only five out of 29 neonates with normal FUPR had FIRS (P < 0.001). Severe neonatal morbidity was found in 24 out of 41 (58.54%) neonates with reduced FUPR prenatally. The occurrence of respiratory distress syndrome, necrotizing enterocolitis, and sepsis was significantly high in neonates with reduced FUPR. CONCLUSION: Reduced FUPR is strongly associated with FIRS in cases of PPROM and hence can be used as an early predictor of adverse neonatal outcomes.

Physiological rhythms are influenced by photophase wavelength in a nocturnal and a diurnal rodent species from South Africa.

The quality and quantity of light changes significantly over the course of the day. The effect of light intensity on physiological and behavioural responses of animals has been well documented, particularly during the scotophase, but the effect of the wavelength of light, particularly during the photophase, less so. We assessed the daily responses in urine production, urinary 6-sulfatoxymelatonin (6-SMT) and glucocorticoid metabolite (uGCM) concentrations in the nocturnal Namaqua rock mouse (Micaelamys namaquensis) and diurnal four striped field mouse (Rhabdomys pumilio) under varying wavelengths of near monochromatic photophase (daytime) lighting. Animals were exposed to a short-wavelength light cycle (SWLC; ∼465-470 nm), a medium-wavelength light cycle (MWLC; ∼515-520 nm) and a long-wavelength light cycle (LWLC; ∼625-630 nm). The SWLC significantly attenuated mean daily urine production rates and the mean daily levels of urinary 6-SMT and of uGCM were inversely correlated with wavelength in both species. The presence of the SWLC greatly augmented overall daily 6-SMT levels, and simultaneously led to the highest uGCM concentrations in both species. In M. namaquensis, the urine production rate and urinary 6-SMT concentrations were significantly higher during the scotophase compared to the photophase under the SWLC and MWLC, whereas the uGCM concentrations were significantly higher during the scotophase under all WLCs. In R. pumilio, the urine production rate and uGCM were significantly higher during the scotophase of the SWLC, not the MWLC and LWLC. Our results illustrate that wavelength in the photophase plays a central role in the entrainment of rhythms in diurnal and nocturnal African rodent species.

Effect of spironolactone and benazepril on furosemide-induced diuresis and renin-angiotensin-aldosterone system activation in normal dogs.

BACKGROUND: Diuretic braking during furosemide continuous rate infusion (FCRI) curtails urine production. HYPOTHESIS: Renin-angiotensin-aldosterone system (RAAS) activation mediates braking, and RAAS inhibition will increase urine production. ANIMALS: Ten healthy purpose-bred male dogs. METHODS: Dogs received placebo, benazepril, or benazepril and spironolactone PO for 3 days before a 5-hour FCRI (0.66 mg/kg/h) in a 3-way, randomized, blinded, cross-over design. Body weight (BW), serum creatinine concentration (sCr), serum electrolyte concentrations, PCV, and total protein concentration were measured before PO medications, at hours 0 and 5 of FCRI, and at hour 24. During the FCRI, water intake, urine output, urine creatinine concentration, and urine electrolyte concentrations were measured hourly. Selected RAAS components were measured before and after FCRI. Variables were compared among time points and treatments. RESULTS: Diuretic braking and urine production were not different among treatments. Loss of BW, hemoconcentration, and decreased serum chloride concentration occurred during FCRI with incomplete recovery at hour 24 for all treatments. Although unchanged during FCRI, sCr increased and serum sodium concentration decreased at hour 24 for all treatments. Plasma aldosterone and angiotensin-II concentrations increased significantly at hour 5 for all treatments, despite suppressed angiotensin-converting enzyme activity during benazepril background treatment. CONCLUSIONS: The neurohormonal profile during FCRI supports RAAS mediation of diuretic braking in this model. Background treatment with benazepril with or without spironolactone did not mitigate braking, but was well tolerated. Delayed changes in sCr and serum sodium concentration and incomplete recovery of hydration indicators caused by furosemide hold implications for clinical patients.

Acardiac twin pregnancies part V: Why does an acardiac twin with renal tissue produce polyhydramnios?

BACKGROUND: Acardiac twinning is a complication of monochorionic twin pregnancies. From literature reports, 30 of 41 relatively large acardiac twins with renal tissue produced polyhydramnios within their amniotic compartment. We aim to investigate the underlying mechanisms that cause excess amniotic fluid using an established model of fetal fluid dynamics. METHODS: We assumed that acardiac onset is before 13 weeks, acardiacs with renal tissue have normal kidney function and produce urine flow from 11 weeks on, and acardiac urine production requires a pressure of half the pump twin's mean arterial pressure. We apply a resistance network with the pump twin's arterio-venous pressure as source, pump umbilical arteries, placenta, placental arterio-arterial (AA) anastomoses and acardiac resistances. Acardiac amniotic fluid dynamics excluded acardiac lung fluid secretion, swallowing and the relatively small intramembranous flow. RESULTS: In small acardiacs with sufficient urine production, polyhydramnios will occur due to the lack of amniotic fluid resorption. Urine production is dependent upon having sufficient mean arterial pressure, which requires nearly a two-fold larger resistance within the acardiac as compared to the placental AA resistance. Subphysiologic arterial pressure may result in renal dysgenesis. CONCLUSION: Our findings suggest the potential for prediction of which clinical acardiac cases may or may not develop polyhydramnios based upon noninvasive assessments of renal tissue, blood flow and urine production. This information would be of great value in determining early obstetric interventions as opposed to conservative management. These findings may also contribute to an improved knowledge of the fascinating pathophysiology that surrounds acardiac twinning.

Hyperthermia and dehydration: their independent and combined influences on physiological function during rest and exercise.

PURPOSE: This experiment was designed to quantify the independent and combined influences of hyperthermia and dehydration on effector control during rest and exercise. METHODS: To achieve that, whole-body hydration of healthy adults (N = 8) was manipulated into each of three states (euhydrated, 3% and 5% dehydrated), and then clamped within each of two thermal states (normothermia [mean body temperature: 36.1 °C] and moderate hyperthermia [mean body temperature: 38.2 °C]). Those treatment combinations provided six levels of physiological strain, with resting physiological data collected at each level. The effects of isothermal, thermally unclamped and incremental exercise were then investigated in normothermic individuals during each level of hydration. RESULTS: At rest, dehydration alone reduced urine flows by 83% (3% dehydrated) and 93% (5% dehydrated), while the reduction accompanying euhydrated hyperthermia was 86%. The sensitivities of renal water conservation to 3% dehydration (-21% mOsm-1 kg H2O-1) and moderate hyperthermia (-40% °C-1) were independent and powerful. Evidence was found for different renal mechanisms governing water conservation between those treatments. Cutaneous vasomotor and central cardiac responses were unresponsive to dehydration, but highly sensitive to passive thermal stress. Dehydration did not impair either whole-body or regional sweating during rest or exercise, and not even during incremental cycling to volitional exhaustion. CONCLUSION: In all instances, the physiological impact of these thermal- and hydration-state stresses was independently expressed, with no evidence of interactive influences. Renal water-conservation was independently and powerfully modified, exposing possible between-treatment differences in sodium reabsorption.

Lack of Change in the Adaptation Ability of the Bladder for the Urine Production Rate in Aged Men with Nocturia.

INTRODUCTION: To investigate the association between bladder capacity and the urine production rate in aged men with or without nocturia using a frequency volume chart (FVC). MATERIALS AND METHODS: One-hundred and thirty-eight men aged 65-80 years were enrolled. After the International Prostate Symptom Score (IPSS) and 3 consecutive days FVC were evaluated, men were divided into 2 groups: Nocturia group, with any total IPSS, and ≥1.5 micturition on average at night; and Control group, with total IPSS < 8 and < 1.5 micturition on average at night. Each parameter was compared between the 2 groups using unpaired t tests. Linear and multiple regression analyses were performed between the urine production rate and volume/voids. RESULTS: Men numbering 45 and 21 were assigned to the Nocturia and Control groups respectively. There were no differences in background factors between the 2 groups. Volume/voids positively correlated with the urine production rate in both groups for day and night. A multivariate regression model also showed the same results. In the Control group, the degree of slope at night was higher than that during the day. However, in the Nocturia group, there were no differences in the degree of slope between day and night. CONCLUSIONS: This novel finding has led to a possibility for resolving nocturia.

The effect of changing the moisture levels of dry extruded and wet canned diets on physical activity in cats.

Obesity levels in cats are increasing and the main causative factor is higher energy intake v. energy expenditure over time. Therefore, altering energy expenditure by enhancing physical activity of the cat could be a strategy to reduce obesity. Hydrating commercial dry diets with water increased activity in cats; however, no study has compared this approach with feeding high-moisture canned diets. Eight healthy male neutered domestic shorthair cats were fed four different dietary treatments in a Latin square design. Treatments were a canned diet 'as is' (82 % moisture) and freeze-dried (4 %), a dry diet 'as is' (3 %) and with added water (70 %). Cat activity was measured continuously using Actical® accelerometers. Cats were group housed during the first 14 d of each period and then moved to individual cages for 7 d with faecal and urine production measured over the final 4 d. Intake was similar for each diet. The average activity over 24 h was not different between treatments (P > 0·05). However, the ratio between average activity during the day v. at night was higher when cats were fed the dry diet (P = 0·030). Total water intake and urine volume increased when the canned diet was fed (P < 0·001). The similarity in total activity of the cats on the treatments indicates that dietary moisture or diet type did not have a major effect on these cats. However, the stronger diurnal activity patterns observed in the cats when they were fed the dry diet are intriguing and require further study.

Effects of photophase illuminance on locomotor activity, urine production and urinary 6-sulfatoxymelatonin in nocturnal and diurnal South African rodents.

Effects of photophase illuminance (1, 10, 100 and 330 lx of white incandescent lighting) on daily rhythms of locomotor activity, urine production and 6-sulfatoxymelatonin (6-SMT; 10 versus 330 lx) were studied in nocturnal Namaqua rock mice (Micaelamys namaquensis) and diurnal four-striped field mice (Rhabdomys pumilio). Micaelamys namaquensis was consistently nocturnal (∼90-94% nocturnal activity), whereas considerable individual variation marked activity profiles in R. pumilio, but with activity mostly pronounced around twilight (∼55-66% diurnal activity). The amplitude of daily activity was distinctly affected by light intensity and this effect was greater in M. namaquensis than in R. pumilio Only M. namaquensis displayed a distinctive daily rhythm of urine production, which correlated with its activity rhythm. Mean daily urine production appeared to be attenuated under dim photophase conditions, particularly in R. pumilio The results suggest that the circadian regulation of locomotor activity and urine production possesses separate sensitivity thresholds to photophase illuminance. Micaelamys namaquensis expressed a significant daily 6-SMT rhythm that peaked during the late night, but the rhythm was attenuated by the brighter photophase cycle (330 lx). Rhabdomys pumilio appeared to express an ultradian 6-SMT rhythm under both lighting regimes with comparable mean daily 6-SMT values, but with different temporal patterns. It is widely known that a natural dark phase which is undisturbed by artificial light is essential for optimal circadian function. Here, we show that light intensity during the photophase also plays a key role in maintaining circadian rhythms in rodents, irrespective of their temporal activity rhythm.

Thermodynamic considerations in renal separation processes.

BACKGROUND: Urine production in the kidney is generally thought to be an energy-intensive process requiring large amounts of metabolic activity to power active transport mechanisms. This study uses a thermodynamic analysis to evaluate the minimum work requirements for urine production in the human kidney and provide a new perspective on the energy costs of urine production. In this study, black-box models are used to compare the Gibbs energy inflow and outflow of the overall kidney and physiologically-based subsections in the kidney, to calculate the work of separation for urine production. RESULTS: The results describe the work done during urine production broadly and for specific scenarios. Firstly, it shows glomerular filtration in both kidneys requires work to be done at a rate of 5 mW under typical conditions in the kidney. Thereafter, less than 54 mW is sufficient to concentrate the filtrate into urine, even in the extreme cases considered. We have also related separation work in the kidney with the excretion rates of individual substances, including sodium, potassium, urea and water. Lastly, the thermodynamic calculations indicate that plasma dilution significantly reduces the energy cost of separating urine from blood. CONCLUSIONS: A comparison of these thermodynamic results with physiological reference points, elucidates how various factors affect the energy cost of the process. Surprisingly little energy is required to produce human urine, seeing that double the amount of work can theoretically be done with all the energy provided through pressure drop of blood flow through the kidneys, while the metabolic energy consumption of the kidneys could possibly drive almost one hundred times more separation work. Nonetheless, the model's outputs, which are summarised graphically, show the separation work's nuances, which can be further analysed in the context of more empirical evidence.

Indoor cold exposure and nocturia: a cross-sectional analysis of the HEIJO-KYO study.

OBJECTIVES: To investigate the association between indoor cold exposure and the prevalence of nocturia in an elderly population. SUBJECTS AND METHODS: The temperature in the living rooms and bedrooms of 1 065 home-dwelling elderly volunteers (aged ≥60 years) was measured for 48 h. Nocturia (≥2 voids per night) and nocturnal urine production were determined using a urination diary and nocturnal urine collection, respectively. RESULTS: The mean ± sd age of participants was 71.9 ± 7.1 years, and the prevalence of nocturia was 30.8%. A 1 °C decrease in daytime indoor temperature was associated with a higher odds ratio (OR) for nocturia (1.075, 95% confidence interval [CI] 1.026-1.126; P = 0.002), independently of outdoor temperature and other potential confounders such as basic characteristics (age, gender, body mass index, alcohol intake, smoking), comorbidities (diabetes, renal dysfunction), medications (calcium channel blocker, diuretics, sleeping pills), socio-economic status (education, household income), night-time dipping of ambulatory blood pressure, daytime physical activity, objectively measured sleep efficiency, and urinary 6-sulphatoxymelatonin excretion. The association remained significant after adjustment for nocturnal urine production rate (OR 1.095 [95% CI 1.042-1.150]; P < 0.001). CONCLUSIONS: Indoor cold exposure during the daytime was independently associated with nocturia among elderly participants. The explanation for this association may be cold-induced detrusor overactivity. The prevalence of nocturia could be reduced by modification of the indoor thermal environment.

Usefulness of fetal urine production measurement for prediction of perinatal outcomes in uteroplacental insufficiency.

OBJECTIVES: To evaluate whether fetal urine production measurement is useful for predicting adverse outcomes in patients with uteroplacental insufficiency. METHODS: We enrolled patients with uteroplacental insufficiency at 24 to 40 weeks' gestation and normal pregnancies matched for gestational age and divided them into 3 groups according to perinatal outcomes: group 1 (n = 141), a control group of normal pregnancies; group 2 (n = 29), uteroplacental insufficiency without adverse outcomes; and group 3 (n = 18), uteroplacental insufficiency with adverse outcomes. An adverse outcome was defined as 1 or more of the following: (1) cesarean delivery because of fetal distress; (2) admission to the neonatal intensive care unit; (3) cord arterial pH less than 7.15 at birth; and (4) low 5-minute Apgar score (<7). The fetal urine production rate was obtained by serial bladder volume measurement using virtual organ computer-aided analysis. For bladder volume determination, we scanned the bladder in the 3-dimensional mode and defined the bladder surface contour in the reference plane, repeating the rotation of the reference plane with an angle of 30° and determining the surface contour on each plane. Statistical methods, including the Mann-Whitney U test, Fisher exact test, χ(2) test, and Kruskal-Wallis analysis of variance, were used. RESULTS: Group 3 had a lower mean fetal urine production rate than groups 1 and 2, whereas the urine production rate was not different between groups 1 and 2 (group 1, 49.0 mL/h; group 2, 59.4 mL/h; group 3, 20.7 mL/h; P < .001 between groups 1 and 3 and between groups 2 and 3). This difference between groups 2 and 3 remained significant after adjusting for the amniotic fluid index, umbilical artery Doppler pulsatility index, and presence of fetal growth restriction. CONCLUSIONS: Uteroplacental insufficiency cases with adverse perinatal outcomes had a lower fetal urine production rate than those without adverse outcomes. This difference might be used to predict adverse perinatal outcomes in uteroplacental insufficiency.

Measuring the rate of fetal urine production using three-dimensional ultrasound during normal pregnancy and pregnancy-associated diabetes.

OBJECTIVE: To establish a nomogram of fetal urine production according to gestational age as a predictor for fetal well-being in normal and diabetic women. STUDY DESIGN: Prospective observational study included 180 pregnant women classified into two groups: Group I (120 women) without any medical complications and Group II (60 women) with gestational diabetes mellitus (GDM). The fetal bladder is measured by the virtual organ computer-aided analysis VOCAL 3D ultrasound scanner. RESULTS: There was a significant positive correlation between gestational age and fetal urine production rate (UPR) (the mean UPR rate in normal pregnancy at 25, 30, 35, 40 weeks were 12.3, 14.38, 56.13 and 90.73 ml/h, respectively). There was no significant difference regarding UPR ml/h between women with normal pregnancy and those with controlled GDM (p = 0.9). There was a statistically significant difference regarding UPR ml/h between women with normal pregnancy and those with uncontrolled GDM (p = 0.012) and a statistically significant difference between women with controlled GDM and those with uncontrolled GDM (p = 0.03). CONCLUSION: Fetal UPR is considered to be more reliable as an assessment method for fetal well-being and shows significant increase in patients with uncontrolled gestational DM.

Inhibitor of intramembranous absorption in ovine amniotic fluid.

Intramembranous absorption increases during intra-amniotic infusion of physiological saline solutions. The increase may be due partly to the concomitant elevation in fetal urine production as fetal urine contains a stimulator of intramembranous absorption. In this study, we hypothesized that the increase in intramembranous absorption during intra-amniotic infusion is due, in part, to dilution of a nonrenal inhibitor of intramembranous absorption that is present in amniotic fluid. In late-gestation fetal sheep, amniotic fluid volume and the four primary amniotic inflows and outflows were determined over 2-day intervals under three conditions: 1) control conditions when fetal urine entered the amniotic sac, 2) during intra-amniotic infusion of 2 l/day of lactated Ringer solution when urine entered the amniotic sac, and 3) during the same intra-amniotic infusion when fetal urine was continuously replaced with lactated Ringer solution. Amniotic fluid volume, fetal urine production, swallowed volume, and intramembranous absorption rate increased during the infusions independent of fetal urine entry into the amniotic sac or its replacement. Lung liquid secretion rate was unchanged during infusion. Because fetal membrane stretch has been shown not to be involved and because urine replacement did not alter the response, we conclude that the increase in intramembranous absorption that occurs during intra-amniotic infusions is due primarily to dilution of a nonrenal inhibitor of intramembranous absorption that is normally present in amniotic fluid. This result combined with our previous study suggests that a nonrenal inhibitor(s) together with a renal stimulator(s) interact to regulate intramembranous absorption rate and, hence, amniotic fluid volume.

Guidance on water intake effectively improves urinary frequency in patients with nocturia.

OBJECTIVES: To evaluate how guidance on water-intake impacts the degree of nocturia. METHODS: A total of 67 male patients were enrolled in the present study. Patients were asked to adjust their water and food intakes so that their 24-h urine production/bodyweight would be equal or lower than 30 mL/kg. One month after the treatment, the therapeutic gain from and adverse effects of fluid restriction were examined by comparing the pretreatment and post-treatment value of various parameters. RESULTS: Overall, 65 eligible patients were evaluated. In 44 patients (67%), the frequency of nocturia was improved to one or more times. The change in frequency of nocturia showed a positive correlation with the change in nocturnal urine volume. The change in nocturnal urine volume showed a positive correlation with the changes in 24-h urine production/bodyweight, 24-h drinking volume and daytime drinking volume. The changes in 24-h urine production/bodyweight and daytime drinking volume were independent factors influencing therapeutic effect. None of the participants reported any adverse event. CONCLUSIONS: In patients with a 24-h urine production/bodyweight equal or higher than 30 mL/kg, guidance on water intake might be considered effective and safe as a lifestyle therapy. Water restriction should be carried out not only in the evening, but also during daytime.

Assessment of the rate of fetal urine production rate in twin-to-twin transfusion syndrome with three-dimensional ultrasonography / 中华超声影像学杂志

ObjectiveTo evaluate the clinical value of the rate of fetal urine production rate (UPR) in fetus with twin-to-twin transfusion syndrome(TTTS).Methods 22 continuative normal monochorionic diamniotic(MCDA) twin fetuses were selected as controll group.Eight fetuses with TTTS were selected as disease group,and UPR was measured by three-dimensional ultrasound virtual organ computer-aided analysis (VOCAL) and the rate of UPR in twin was calculated.Results1)The rate of UPR of twin fetuses in MCDA did not vary significantly throughout pregnancy (0.97 ± 0.28).The correlation coefficient between the rate of UPR and gestational age was 0.13,without obvious correlation.2)The rate of UPR-recipient/UPR-donor in TTTS fetuses increased significantly compared with MCDA twin fetus (7.83 ± 2.61,t =6.19,P ＜0.05).ConclusionsThe rate of UPR may be an important index in the assessment of TTTS.