Daily Urine Volume Research Articles

Relationship between nitrogen loss and blood urea nitrogen concentrations in patients requiring continuous renal replacement therapy.

AimIt is well known that continuous renal replacement therapy (CRRT) produces some amount of nitrogen loss, but there are few tools that are easily applied to measure it. This study aimed to evaluate nitrogen loss using blood urea nitrogen (BUN) measurement in patients receiving CRRT.MethodsThe subjects were 28 patients who received CRRT (except for liver failure) between 2010 and 2012. Nutrition data and nitrogen excretion in dialysate and urine were measured.ResultsThe median age of the patients was 61 years, with an Acute Physiology and Chronic Health Evaluation score of 27 points and a Sequential Organ Failure Assessment score of 12 points. All‐cause hospital mortality was 50%. Median protein intake was 40 g/day. The daily urinary volume was 245 mL and volume of dialysate was 26,000 mL/day. The median amount of nitrogen loss was 10.58 g/day, with BUN showing a strong correlation (r = 0.804, P < 0.0001). There was a poor relation between protein intake (g/kg body weight) and nitrogen balance (r = 0.322, P = 0.002).ConclusionsIn patients receiving CRRT, the nitrogen loss showed a positive correlation with BUN but not with protein intake. According to the guidelines, recommended protein intake was 1.5–2.0 g/kg/day, but we should be careful to avoid elevating BUN at the same time. The results showed that BUN might be a useful marker to check nitrogen balance in the nutritional management of patients receiving CRRT.

Identification of five novel arginine vasopressin gene mutations in patients with familial neurohypophyseal diabetes insipidus.

Familial neurohypophyseal diabetes insipidus(FNDI) is a genetic disorder presenting with polyuria and polydipsia and is caused by mutations in the arginine vasopressin-neurophysinII(AVP-NPII) gene. The clinical manifestations of this disorder vary greatly depending on different mutations. The present study reports the genetic, clinical and biochemical characteristics of patients with FNDI caused by five novel mutations. Ten patients encompassing two pedigrees and four individual cases diagnosed with FNDI were included. Biochemical markers and magnetic resonance imaging(MRI) were evaluated and genomic DNA was sequenced. The results revealed that age at onset ranged from 1.0to 11.0years. Daily urine volumes ranged from 2.0to 12.0liters. One patient had mental retardation and three patients had puberty retardation; one patient had nausea, vomiting and mental retardation; and two patients had fever. Treatments, if given, included desmopressin and vasopressin tannate. Posterior pituitary T1-weighted MRI high-intensity signals were absent in two cases and present in four cases. Sequencing revealed five novel mutations in the AVP-NPII gene. On the whole, the findings of the present study indicate that FNDI exhibits different clinical manifestations and a diverse age at onset. Posterior pituitary MRI does not provide a definite diagnosis of FNDI. We also identified five novel AVP-NPII mutations. Thus, an enhanced understanding of FNDI pathogenesis may provide a basis for the development of presymptomatic FNDI diagnotic tools.

Influence of Physical Activity and Ambient Temperature on Hydration: The European Hydration Research Study (EHRS).

This study explored the effects of physical activity (PA) and ambient temperature on water turnover and hydration status. Five-hundred seventy three healthy men and women (aged 20–60 years) from Spain, Greece and Germany self-reported PA, registered all food and beverage intake, and collected 24-h urine during seven consecutive days. Fasting blood samples were collected at the onset and end of the study. Food moisture was assessed using nutritional software to account for all water intake which was subtracted from daily urine volume to allow calculation of non-renal water loss (i.e., mostly sweating). Hydration status was assessed by urine and blood osmolality. A negative association was seen between ambient temperature and PA (r = −0.277; p < 0.001). Lower PA with high temperatures did not prevent increased non-renal water losses (i.e., sweating) and elevated urine and blood osmolality (r = 0.218 to 0.163 all p < 0.001). When summer and winter data were combined PA was negatively associated with urine osmolality (r = −0.153; p = 0.001). Our data suggest that environmental heat acts to reduce voluntary PA but this is not sufficient to prevent moderate dehydration (increased osmolality). On the other hand, increased PA is associated with improved hydration status (i.e., lower urine and blood osmolality).

Effect of Icodextrin Solution on the Preservation of Residual Renal Function in Peritoneal Dialysis Patients: A Randomized Controlled Study.

Although icodextrin solution has been highlighted in the fluid management compared to glucose-based solutions, proof of a beneficial effect of icodextrin solution on residual renal function (RRF) is lacking. We conducted a multicenter prospective randomized controlled open-label trial to investigate whether icodextrin solution can preserve RRF.One hundred patients with urine volume ≥750 mL/day from 8 centers in Korea were randomly assigned to receive 1 exchange of icodextrin solution for a ≥8 hour-dwell time and 2 exchanges of 1.5% glucose-based biocompatible neutral pH solution or 1 exchange of ≥2.5% and 2 exchanges of 1.5% glucose-based biocompatible solutions. Using mixed-effects general linear models, we analyzed changes in residual glomerular filtration rate (GFR) and daily urine volume at 1 year.Forty-nine patients were assigned to the icodextrin group and 51 to the glucose solution group. During follow-up, the slope of the decline in residual GFR was −0.170 mL/min/month/1.73 m2 in the icodextrin group, while it was −0.155 mL/min/month/1.73 m2 in the glucose solution group (95% confidence interval [CI], −0.06 to 0.10; P = 0.701). Daily urine volume decreased faster in the glucose solution group than in the icodextrin group (−31.02 vs −11.88 mL per month; 95% CI, −35.85 to −2.44; P = 0.025). Results were consistent when we analyzed using intention-to-treat and per protocol principles. There were no differences in fluid status, peritoneal ultrafiltration, and peritoneal transport between groups during follow-up.This study clearly showed that icodextrin solution preserves residual urine volume better than glucose solution.

Effects of a supplementation on sodium chloride or ammonium chloride on urolithic potential in the rabbit

Reduction of urolithic potential by means of increased water intake and urine dilution through supplementation of sodium chloride (NaCl) or decrease of urine pH by supplementation of ammonium chloride (NH4Cl) in rabbits. Sixteen female, 6-month-old dwarf rabbits received the following three feeding regimens in a random order: complete feed without supplements = control; complete feed + 10g NaCl/kg feed = NaCl; complete feed + 2.5g NH4Cl/kg feed = NH4Cl. The diets were fed ad libitum over a period of 27 days without roughage. Water was provided ad libitum by a drinker. A 14-day wash-out-period (hay feeding) was performed between the different diets. Blood, faeces, and urine were collected at the beginning of each feeding period, after 21-day adaptation to the respective diet, and after the 3-day collection period. The following parameters were analysed: water and food intake as well as acid-base balance and mineral content in blood, urine, and faeces. NaCl supplementation numerically increased the daily water intake from 40.5±14.4ml/kg body weight (BW) (control) up to 49.5± 14.3ml/kg BW and significantly increased the daily urine volume from 16.9± 7.8ml/kg BW (control group) to 21.1±7.4ml/kg BW. The specific gravity of urine samples from NaCl supplementation decreased from 1.060±0.008 to 1.044±0.008. NH4Cl supplementation did not induce significant changes in urine pH, blood acid-base parameters, or calcium retention. Relative supersaturations (RSS) for calcium oxalate and calcium phosphate showed no significant changes after treatment. RSS for struvite increased from 360±735 (after hay feeding) to 3312±6188 on control feeding, 2910±4913 with NaCl supplementation, and 3022±6635 with NH4Cl supplementation (p<0.05). NaCl supplementation significantly increased the urine volume and decreased its specific gravity. Therefore, NaCl supplementation might be an additional dietary treatment to increase the elimination of urine crystals in rabbits. NH4Cl supplementation did not induce acidification of the urine.

Pro-inflammatory cytokines: a possible relationship with dialytic adequacy and serum albumin in peritoneal dialysis patients.

BackgroundInflammation and serum albumin concentration are both important predictors of survival in patients treated with peritoneal dialysis (PD). Furthermore, systemic and local inflammatory mediators may induce structural and functional alterations in the peritoneal membrane, thus interfering with dialysis adequacy. PD adequacy is monitored primarily by indices of small solute clearance, such as Kt/V urea and weekly creatinine clearance (wCc). The aim of this study was to investigate the possible relationship between pro-inflammatory cytokines, such as interleukin-6 (IL-6) and interleukin-1β (IL-1β), and serum albumin and C-reactive protein (CRP). Moreover, the relationship between IL-6 and IL-1β and PD adequacy has been analysed.MethodsWe enrolled 46 stable PD patients undergoing maintenance PD for a minimum of 3 months. Plasma levels of serum albumin, high-sensitivity (hs)-CRP, IL-6 and IL-1β were measured in all patients. We used weekly Kt/V urea and wCc to monitor PD adequacy. Daily urine volume was measured in all patients.ResultsThe median values of serum albumin, hs-CRP, IL-6 and IL-1β showed no significant differences between continuous ambulatory PD and automated PD patients. IL-6 levels showed a positive correlation with hs-CRP levels (P < 0.001) and a negative correlation with serum albumin concentration (P = 0.01). There was no statistically significant relationship between IL-1β and hs-CRP or serum albumin concentrations. Subsequently, PD patients were divided into two groups based on Kt/V urea value. PD patients with Kt/V ≤1.7 had significantly higher IL-6 levels compared with PD patients with Kt/V >1.7 (P = 0.015). No statistically significant relationship between IL-6 and wCc was observed. There was no significant difference in IL-1β levels between PD patients with Kt/V ≤1.7 and with Kt/V >1.7 [median (interquartile range) 0.82 (0.88–5.2) versus 1.82 (0.95–2.7)]. There was no significant difference in IL-6 and IL-1β levels in PD patients with and without residual diuresis (P = 0.32 and P = 0.77, respectively).ConclusionOur data suggest a possible relationship between serum IL-6 levels and serum albumin and hs-CRP in PD patients. Furthermore, IL-6 seems to be higher in patients with lower Kt/V, thus suggesting a possible use of this inflammatory biomarker in PD adequacy monitoring.

Effect of Initial PET Status on Clinical Course in Peritoneal Dialysis Patients

Abstract Introduction. To investigate the effect on mortality of initial peritoneal equilibration test (PET) in PD patients (pts). Methods. We included patients who initiated therapy between 2001-2014. Patients underwent initial PET in the first three months. They were divided into four groups according to the initial PET (high, high-average, lowaverage, low transport). Sociodemographic data, clinical courses and infectious complications between groups were compared, and the reasons for PD withdrawal were obtained. Technique survival analyses of patients were done. Results. In a total of 367 pts were PD was started, 104 pts were excluded. Data of the remaining 263 patients were evaluated. Thirty-seven pts (23F, mean age 44.6±16.5 years, mean follow-up 30.5±20.8 months) had high transport, 90 pts (49F, mean age 41.5±16 years, mean followup 42.6±27.7 months) had high-average transport, 91 pts (55F, mean age 44.5±14.9 years, mean follow-up 50±29.2 months) had low-average transport and 45 pts (17F, mean age 43.5±14 years, mean follow-up (63.4±34.5 months) had low transport. There was no difference between groups in terms of age, gender, body mass index, initial daily urine and ultrafiltration volume, initial albumin levels, presence of diabetes mellitus (p&gt;0.05). Peritonitis and catheter exit-site/tunnel infection attacks were higher in patients with high transport (p=0.01 and 0.008, respectively). There was a difference between groups with respect to the last status of patients (p&lt; 0.009). The major causes of deaths were peritonitis and/or sepsis and cardiovascular causes in all patients. The mortality and technique survival rate was found higher in patients with high transport (log rank: 0.004 and 0.027, respectively). Age (OR:1.045, p&lt;0.001), initial albumin (OR: 0.482, p= 0.007), daily urine volume (OR: 1.045, p&lt;0.001) and presence of catheter exit-site/tunnel infection (OR: 0.249, p&lt;0.001) were found to predict patient survival. Only presence of catheter exit-site/tunnel infection (OR: 0.452, p=0.013) were found to predict patient survival. Conclusions. Initial PET has effects on PD patient survival; patients with high transport have the worst survival and frequent infectious complications.

Risk factors for loss of residual renal function in children treated with chronic peritoneal dialysis

In dialyzed patients, preservation of residual renal function is associated with better survival, lower morbidity, and greater quality of life. To analyze the evolution of residual diuresis over time, we prospectively monitored urine output in 401 pediatric patients in the global IPPN registry who commenced peritoneal dialysis (PD) with significant residual renal function. Associations of patient characteristics and time-variant covariates with daily urine output and the risk of developing oligoanuria (under 100 ml/m2/day) were analyzed by mixed linear modeling and Cox regression analysis including time-varying covariates. With an average loss of daily urine volume of 130 ml/m2 per year, median time to oligoanuria was 48 months. Residual diuresis significantly subsided more rapidly in children with glomerulopathies, lower diuresis at start of PD, high ultrafiltration volume, and icodextrin use. Administration of diuretics significantly reduced oligoanuria risk, whereas the prescription of renin–angiotensin system antagonists significantly increased the risk oligoanuria. Urine output on PD was significantly associated in a negative manner with glomerulopathies (−584 ml/m2) and marginally with the use of icodextrin (−179 ml/m2) but positively associated with the use of biocompatible PD fluid (+111 ml/m2). Children in both Asia and North America had consistently lower urine output compared with those in Europe perhaps due to regional variances in therapy. Thus, in children undergoing PD, residual renal function depends strongly on the cause of underlying kidney disease and may be modifiable by diuretic therapy, peritoneal ultrafiltration, and choice of PD fluid.

PP.11.18

Objective: Evidences indicate that in addition to long term regulation of blood pressure, in the kidney resides the initial trigger for the development of hypertension. Altered capacity of the kidney to excrete sodium and water in relation to intake has been proposed as a basic mechanism of initiating hypertension. Betaine is one of the major organic osmolytes and the upregulation of its betaine/gamma-aminobutyric acid transporter (BGT1) in the renal medulla is related to high extracellular tonicity and urinary osmolality. Design and method: The present study investigated the abnormalities in water and sodium balance and osmoregulation in a model of polygenic multifactorial arterial hypertension, the spontaneously hypertensive rats (SHR, n = 58) and compared with their normotensive controls Wistar Kyoto (WKY, n = 46 from their prehypertensive phase (4 weeks of age) until the development hypertension and of organ damage (28–30 weeks of age). Rats were housed in metabolic cages to monitor water and salt balance parameters at the age of 4–5, 14–16 and 28–30 weeks of age. Results: No difference of blood pressure (both indirectly tail cuff method and invasively, as well heart rate, body weight, serum sodium, potassium and creatinine levels) was measured at the age of 5 weeks of age between SHR and WKY. Daily urinary volume was reduced in prehypertensive SHR as compared to WKY (-36 %, p Conclusions: All these results suggest in prehypertensive SHR an early positive balance of water before sodium balance alteration.

PWE-233 An organic marine hydrocolloid acts as a stool thickener in patients with diarrhoea and enteric hyperoxaluria due to short bowel syndrome

Introduction Calcium oxalate is the predominant component of most renal stones; they occur in 10% of patients with bile salt and/or fatty acid malabsorption due to enteric hyperoxaluria1. Patients who have undergone extensive ileal resection, jejuno-ileal bypass surgery or a Roux-en-Y gastric bypass, whose colon remains in continuity, are at a greater risk of developing enteric hyperoxaluria. It is managed by dietary restriction of oxalate and fat, a high calcium intake, and increasing water intake to ensure a daily urine volume of more than 3 litres. The latter is difficult to achieve in patients with short bowel syndrome. Ox-Absorb® is an organic marine hydrocolloid derived from plants and seaweed and was first described in the 1980’s as a promising new treatment for enteric hyperoxaluria. It was also noted that it thickened stools and reduced stool frequency. Ox-Absorb®is unlicensed in the UK and imported on a named patient basis from the USA. When it was used by the renal physicians at North Bristol NHS Trust to reduce oxalate stone formation, patients reported beneficial effect on stool frequency and consistency. Method We conducted a retrospective case note review of all patients prescribed Ox-Absorb® in North Bristol NHS Trust. Drug history, weight, change in stool consistency and urinary oxalate levels were documented. Net reduction in tablet burden and a cost analysis of the use of Ox-Absorb®were calculated. Results 8 patients were prescribed Ox-Absorb®. 7/8 patients reported thicker stools and reduced stool frequency and there was a reduction in tablet burden (mean 8.6 tablets; range 2 to 22; median 7). Mean net reduction of tablets was 22% (median 29%). There was a cost reduction in 3/8 patients, all of whom were taking higher doses of loperamide, codeine phosphate and Creon®(£1.09, £0.57 and £0.15 per day). 3/8 patients had to stop the drug due to supply problems and all noted worsening in diarrhoea symptoms which improved on restarting the drug. Urinary oxalate was reduced in only 2/8 patients. Conclusion In this small cohort, patients who were prescribed Ox-Absorb® reported thicker stools and were able to reduce their net anti-diarrhoeal tablet burden. This was cost effective in patients taking higher doses of loperamide, codeine and Creon®. We believe a larger study of this drug relative to standard treatments is justified. Disclosure of interest None Declared.

Vasopressin V2 receptor antagonist tolvaptan is effective in heart failure patients with reduced left ventricular systolic function and low blood pressure.

Diuresis is a major therapy for the reduction of congestive symptoms in acute decompensated heart failure (ADHF) patients. Carperitide has natriuretic and vasodilatory effects, and tolvaptan produces water excretion without electrolyte excretion. We previously reported the usefulness of tolvaptan compared to carperitide in ADHF patients with fluid volume retention. The purpose of this study was to examine whether the efficacy of tolvaptan was altered in ADHF patients with reduced left ventricular systolic function and in those with hypotension. A total of 109 hospitalized ADHF patients were randomly assigned to either a tolvaptan or a carperitide treatment group. Baseline clinical characteristics were not different between the two groups. We divided these patients based on the left ventricular ejection fraction (EF) by echocardiography, and blood pressure (BP) at the time of admission. Daily urine volume between the tolvaptan and carperitide groups in patients with preserved EF (≥ 50%) was not different, however, in those with reduced EF (< 50%), the urine volume was significantly higher in the tolvaptan group than in the carperitide group (day 2, 3, 4, P < 0.05 for all). Daily urine volume did not differ between these two groups in the high blood pressure group (BP ≥ 140 mmHg), but was significantly higher in the tolvaptan group than in the carperitide group (day 1, P = 0.021; day 3, P = 0.017) in the low blood pressure group (BP < 140 mmHg). The present study reveals that tolvaptan is more effective than carperitide, especially in ADHF patients with reduced left ventricular systolic function and without hypertension.

Prevalence of erectile dysfunction and its association with residual renal function in Chinese peritoneal dialysis patients.

The study was to investigate the prevalence and associated factors of erectile dysfunction (ED) in peritoneal dialysis (PD) patients. This was a cross-sectional survey. Eligible patients were interviewed by questionnaire: the five-item version of International Index of Erectile Function. Residual renal function (RRF) was assessed by daily urine volume and residual glomerular filtration rate. Totally, 176 male prevalent PD patients were interviewed, six of them were not included in analysis for sexually inactive unrelated to ED. The prevalence of ED was 80.6 %. After adjusting for confounding factors, advance age (P = 0.014), less daily urine volume (P = 0.032) and higher high-sensitivity C-reactive protein (hs-CRP) (P = 0.043) were independent risk factors for the development of ED. The prevalence of ED was high in Chinese PD patients. Advanced age, poor RRF and higher hs-CRP were independently associated with the prevalence of ED.

Association between bioimpedance analysis parameters and left ventricular hypertrophy in peritoneal dialysis patients

Chronic volume overload, hypertension and left ventricular hypertrophy are major risk factors contributing to the high mortality rate in peritoneal dialysis (PD) patients. In this study, we aimed to determine the impact of blood pressure measurements and volume status determined by bioelectrical impedance analysis (BIA) measurements over left ventricular hypertrophy (LVH) in PD patients. Thirty-one prevalent PD patients were enrolled. Patients with a documented cardiovascular disease and uncontrolled hypertension were excluded. BIA and transthoracic echocardiography were performed in all patients All measurements were taken with the empty abdominal cavity. Routine laboratory parameters were also assessed in all patients. Extracellular water (ECW) in liters and ECW/total body water (TBW) ratio were used for determining volume status. Mean age of the patients was 43.9 ± 15.4 years, and mean PD duration was 39.5 ± 29.6 months. Mean ECW/TBW ratio was 44.3 %. Left ventricular mass index (LVMI) was 134.3 ± 34.9 g/m(2). Fifty-eight percent of patients had LVH. Mean LVMI was negatively correlated with daily urine volume (r -0.568, p 0.001) and weekly Kt/V (r -0.393, p 0.029); positively correlated with daily ultrafiltration (r +0.585, p 0.001) and office systolic (r +0.500, p 0.004) and diastolic (r +0.459, p 0.009) blood pressures. In linear regression analysis, daily urine volume (B -0.426, p 0.002) mean diastolic blood pressure (B 0.550, p <0.001), ECW/TBW ratio (B 0.313, p 0.02) and waist circumference (B 0.304, p 0.016) were independent risk factors for LVH. We want to underline that, besides maintaining residual renal function, strict blood pressure control, particularly diastolic blood pressure, and avoiding hypervolemia and abdominal obesity should be main clinical goals in follow-up of PD patients in order to prevent LVH progression.

Sonographic measurement of renal size in patients undergoing chronic hemodialysis: Correlation with residual renal function.

Previous studies have reported that renal size may change when the function is compromised. However, it is not known whether sonographically measured renal size reflects the residual renal function (RRF) in patients undergoing chronic hemodialysis. A total of 140 patients undergoing chronic hemodialysis (≥3 months) were investigated in the present study. The patients were divided into two groups according to the daily urine volume: Individuals with RRF (RRF+ group; ≥200 ml; n=65) and without RRF (RRF− group; <200 ml; n=75). Renal sizes were measured using sonography and renal volumes were calculated with the ellipsoid formula. Univariable and multivariable stepwise forward logistic regression analyses were performed to examine the correlation between the presence of RRF and various variables. The results indicated that there were statistically significant differences (P<0.001) between the RRF+ and RRF− groups with regard to renal length, width, thickness and volume of the left (length, 7.9±1.2 vs. 6.8±1.2 cm; volume, 60.0±26.7 vs. 40.2±18.1 ml, respectively) and right (length, 7.6±1.2 vs. 6.7±1.2 cm; volume, 50.2±26.5 vs. 33.9±15.3 ml, respectively) sides of the kidney. Multivariable stepwise forward logistic regression analyses showed that the mean renal length or volume and hemodialysis duration were independent predictors of the presence of RRF. Therefore, renal size assessment by ultrasonography may be useful for RRF evaluation in patients undergoing chronic hemodialysis.

Preservation of residual renal function by not removing water in new hemodialysis patients: a randomized, controlled study

To investigate the effect of no water removal (NWR) on preservation of residual renal function (RRF) in new hemodialysis (HD) patients. Fifty-six patients with a daily urine volume ≥ 1,000 mL were included. Patients were randomized to different fluid management groups of NWR or water removal (WR) for 6 months. If predialysis BP was >150/90 mmHg, patients could take antihypertensive drugs. The primary endpoints included death, cardio-cerebral vascular disease, refractory hypertension, and edema or an auxiliary examination indicating obvious fluid retention. The secondary endpoint was oliguria. A daily urine volume, 24-h urine creatinine clearance, the defined daily dose (DDD) index of antihypertensive drugs, erythropoietin resistance index, cardiothoracic ratio, and left ventricular mass index (LVMI) were recorded. Eight patients in the NWR group reached the primary endpoints. Nine patients in the WR group reached the secondary endpoint. At the end of the study, patients in the NWR group had more increased systemic blood pressure (9.0 ± 8.3 vs. -2.4 ± 2.0 mmHg, p < 0.001), DDD index (1.2 ± 1.02 vs. -0.9 ± 0.51, p < 0.001), daily urine volume (164 ± 351 vs. -726 ± 342 mL, p < 0.001), cardiothoracic ratio (0.02 ± 0.04 vs. -0.03 ± 0.03, p < 0.001), LVMI (9.6 ± 17.0 vs. -12.0 ± 21.4 g/m(2), p < 0.001), and less decreased urine creatinine clearance (-1.0 ± 0.4 vs. -2.0 ± 1.0, p < 0.001), compared with those patients in the WR group. Preservation of RRF by NWR is warranted in new HD patients, but is not appropriate for all patients.

Development of Diurnal Micturition Pattern in Mice After Weaning

The development of micturition in mice has been poorly studied because of the minute urine volume voided per micturition. We characterized development of the micturition pattern in young mice. Micturition in young and adult C57BL/6 strain mice, including 5 males and 4 females at age 3 weeks immediately after weaning, and 5 of each gender at ages 9 to 10 weeks, respectively, was recorded by the automated voided stain on paper method. Micturition data were obtained under 12-hour light/dark cycles in young mice for 16 days and in adult mice for 4 days. Diurnal variations were assessed during 8 hours until the first void after lights off and those until lights on. The 24-hour rhythmicity of urinary frequency was calculated for 4-day data at the beginning and at the end on young mice, and for 4-day data on adult mice using a chi-square periodogram and relative power spectral density. Mean frequency was 20 to 30 times per day. Total daily urine volume and mean daily urine volume voided per micturition increased with age. The diurnal rhythm of frequency matured to adult levels with development, which was primarily achieved by maturation of the diurnal variation of urine volume in male mice, followed by female mice. Diurnal variation of urine volume voided per micturition was indistinct at the initial stage and gradually matured toward adult levels. The automated voided stain on paper method was used to record micturition development in young mice. This generated data corresponding to frequency-volume charts in humans. Our findings could lead to the establishment of a mouse model of developmental micturition disorders, such as nocturnal enuresis.

1415 The Diuretic Effect of Urea Analog Dimethylthiourea in Rats

Background and AimsUrea plays important roles in urinary concentrating mechanisms in the kidney by contributing greatly in generation of hyperosmolar medulla, due to presence of urea transporters which mediate facilitated...

The diuretic effect of urea analog dimethylthiourea in female Wistar rats

Urea plays an important role in the urinary concentrating mechanism in the kidney by contributing greatly in the generation of hyperosmolar medulla due to the presence of urea transporters, which mediate facilitated transport of urea. In this study, we investigated the possible diuretic effect of urea analog and urea transporter inhibitor, dimethylthiourea (DMTU), in rats. Female Wistar rats were divided into two groups, group 1 (control group, n = 7) rats were injected with saline intraperitoneally (i.p.), while group 2 (DMTU group, n = 7) rats were injected with 500 mg/kg DMTU (i.p.) and an additional dose of 125 mg/kg DMTU after 8 h. DMTU administration induced an approximately three times increase in daily urine volume (p < 0.001) and decreased urine osmolality to approximately 35% of controls (p < 0.0001). DMTU also increased free water clearance (p < 0.0001) without a significant change in osmolar clearance. DMTU treatment caused an increase in urea clearance (p < 0.05) and fractional excretion of urea (p < 0.05) with a decrease in serum urea concentration (p < 0.001). DMTU had no effect on creatinine clearance or serum electrolytes, creatinine levels and osmolality. With these findings, we report for the first time that DMTU has a prominent diuretic effect with increased urea excretion, which may be explained by the inhibitory effect of the drug on urea transporters. Our findings suggest that DMTU may be used as a diuretic agent and also could be used as a lead compound for the development of novel diuretics.

A Combination of Biocompatible Peritoneal Dialysis Solutions and Residual Renal Function, Peritoneal Transport, and Inflammation Markers: A Randomized Clinical Trial

The benefits of biocompatible peritoneal dialysis (PD) fluids, particularly for residual renal function (RRF), are controversial. Moreover, the clinical effects of a PD regimen consisting of different biocompatible PD fluids have not been fully established. Prospective, randomized, controlled, open-label study. Patients with end-stage kidney disease newly started on continuous ambulatory PD therapy (N = 150). A 12-month intervention with 3 biocompatible PD fluids (a neutral-pH, low glucose degradation product, 1.5% glucose solution; a solution with 1.1% amino acid; and a fluid with 7.5% icodextrin) or conventional PD fluid. The primary outcome was change in RRF and daily urine volume. Secondary outcomes were peritoneal transport and inflammation markers. RRF, daily urine volume, serum and dialysate cytokine levels. RRF(3.24 ± 1.98 vs 2.88 ± 2.43 mL/min/1.73 m(2); P = 0.9) and rate of decline in RRF (-0.76 ± 1.77 vs -0.91 ± 1.92 mL/min/1.73 m(2) per year; P = 0.6) did not differ between the biocompatible- and conventional-PD-fluid groups. However, patients using the biocompatible PD fluids had better preservation of daily urine volume (959 ± 515 vs 798 ± 615 mL/d in the conventional group, P = 0.02 by comparison of difference in overall change by repeated-measures analysis of variance). Their dialysate-plasma creatinine ratio at 4 hours was higher at 12 months (0.78 ± 0.13 vs 0.68 ± 0.12; P = 0.01 for comparison of the difference in overall change by repeated-measures analysis of variance). They also had significantly higher serum levels of adiponectin and overnight spent dialysate levels of cancer antigen 125, adiponectin, and interleukin 6 (IL-6). No differences between the 2 groups were observed for serum C-reactive protein and IL-6 levels. Unblinded, relatively short follow-up; no formal sample-size calculations. Use of a combination of 3 biocompatible PD fluids for 12 months compared with conventional PD fluid did not affect RRF, but was associated with better preservation of daily urine volume. The biocompatible PD fluids also lead to changes in small-solute transport and an increase in dialysate cancer antigen 125, IL-6, adiponectin, and systemic adiponectin levels, but have no effect on systemic inflammatory response. The clinical significance of these changes, while of great interest, remains to be determined by further studies.

Effluent Free Radicals Are Associated with Residual Renal Function and Predict Technique Failure in Peritoneal Dialysis Patients

Residual renal function (RRF) is associated with low oxidative stress in peritoneal dialysis (PD). In the present study, we investigated the relationship between the impact of oxidative stress on RRF and patient outcomes during PD. Levels of free radicals (FRs) in effluent from the overnight dwell in 45 outpatients were determined by electron spin resonance spectrometry. The FR levels, clinical parameters, and the level of 8-hydroxy-2'-deoxyguanosine were evaluated at study start. The effects of effluent FR level on technique and patient survival were analyzed in a prospective cohort followed for 24 months. Levels of effluent FRs showed significant negative correlations with daily urine volume and residual renal Kt/V, and positive correlations with plasma β(2)-microglobulin and effluent 8-hydroxy-2'-deoxyguanosine. A highly significant difference in technique survival (p < 0.05), but not patient survival, was observed for patients grouped by effluent FR quartile. The effluent FR level was independently associated with technique failure after adjusting for patient age, history of cardiovascular disease, and presence of diabetes mellitus (p < 0.001). The level of effluent FRs was associated with death-censored technique failure in both univariate (p < 0.001) and multivariate (p < 0.01) hazard models. Compared with patients remaining on PD, those withdrawn from the modality had significantly higher levels of effluent FRs (p < 0.005). Elevated effluent FRs are associated with RRF and technique failure in stable PD patients. These findings highlight the importance of oxidative stress as an unfavorable prognostic factor in PD and emphasize that steps should be taken to minimize oxidative stress in these patients.