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

OBJECTIVE: Because the literature on the predictive value of fetal urinalysis is controversial in fetuses with lower urinary tract obstruction, we determined the best model of fetal urine biochemical markers correlated with long-term postnatal renal function based on glomerular filtration rate (GFR). METHOD: This retrospective study concerned 89 fetuses with lower urinary tract obstruction and their renal function after 10 years of age. We correlated fetal urine biochemical markers (total protein, ß2-microglobulin, sodium, chloride, glucose, calcium, and phosphorus) with GFR at 10 to 30 years of age in 89 patients with posterior urethral valves. We defined five stages of chronic kidney disease (CKD). RESULTS: Of the 89 patients, 18 (20%) are 20 years old or over. Postnatal renal function was good in 67.4% (GFR > 60 mL/min/1.73 m2 ) and poor in 17% (GFR < 30 mL/min/1.73 m2 ). All fetal urine markers differed between CKD stage 1 + 2 and CKD stage 4 + 5 (P < 0.001). ß2-microblobulin showed an 87% sensitivity for a 72% specificity. A combination of ß2-microglobulin and chloride gave the best results (93% sensitivity and 71% specificity) versus amniotic fluid volume (80% sensitivity and 73% specificity). CONCLUSION: Fetal urine biochemistry predicts long-term (10-30 years) postnatal renal function.

Downregulation of the Cl-/HCO3-Exchanger Pendrin in Kidneys of Mice with Cystic Fibrosis: Role in the Pathogenesis of Metabolic Alkalosis.

BACKGROUND/AIMS: Patients with cystic fibrosis (CF) are prone to the development of metabolic alkalosis; however, the pathogenesis of this life threatening derangement remains unknown. We hypothesized that altered acid base transport machinery in the kidney collecting duct underlies the mechanism of impaired bicarbonate elimination in the CF kidney. METHODS: Balance studies in metabolic cages were performed in WT and CFTR knockout (CF) mice with the intestinal rescue in response to bicarbonate loading or salt restriction, and the expression levels and cellular distribution of acid base and electrolyte transporters in the proximal tubule, collecting duct and small intestine were examined by western blots, northern blots and/or immunofluorescence labeling. RESULTS: Baseline parameters, including acid-base and systemic vascular volume status were comparable in WT and CF mice, as determined by blood gas, kidney renin expression and urine chloride excretion. Compared with WT animals, CF mice demonstrated a significantly higher serum HCO3- concentration (22.63 in WT vs. 26.83 mEq/l in CF mice; n=4, p=0.013) and serum pH (7.33 in WT vs. 7.42 in CF mice; n=4, p=0.00792) and exhibited impaired kidney HCO3- excretion (urine pH 8.10 in WT vs. 7.35 in CF mice; n=7, p=0.00990) following a 3-day oral bicarbonate load. When subjected to salt restriction, CF mice developed a significantly higher serum HCO3- concentration vs. WT animals (29.26 mEq/L in CF mice vs. 26.72 in WT; n=5, p=0.0291). Immunofluorescence labeling demonstrated a profound reduction in the apical expression of the Cl-/HCO3- exchanger pendrin in cortical collecting duct cells and western and northern blots indicated diminished plasma membrane abundance and mRNA expression of pendrin in CF kidneys. CONCLUSIONS: We propose that patients with cystic fibrosis are prone to the development of metabolic alkalosis secondary to the inactivation of the bicarbonate secreting transporter pendrin, specifically during volume depletion, which is a common occurrence in CF patients.

Involvement of Glucagon-Like Peptide-1 in the Regulation of Selective Excretion of Sodium or Chloride Ions by the Kidneys.

An increase of total glucagon-like peptide-1 (GLP-1) concentration in the plasma in rats was revealed 5 min after oral, but not intraperitoneal administration of NaCl or Trizma HCl solutions. The increase in GLP-1 level was similar to that after oral glucose administration. After intraperitoneal administration of 2.5% NaCl, GLP-1 mimetic exenatide accelerated natriuresis and urinary chloride excretion. Under conditions of normonatriemia and hyperchloremia induced by injection of 6.7% Trizma HCl, exenatide stimulated chloride excretion and reabsorption of sodium ions in the kidneys. These findings suggest that GLP-1 participates in selective regulation of the balance of sodium and chloride ions.

Are ultrasound renal aspects associated with urinary biochemistry in fetuses with lower urinary tract obstruction?

OBJECTIVE: To evaluate the association between ultrasonographic renal parameters and urine biochemistry in fetuses with lower urinary tract obstruction (LUTO). METHODS: Data were collected prospectively from 31 consecutive fetuses with LUTO that underwent vesicocentesis for fetal urinary biochemistry between April 2013 and September 2015. The following renal ultrasound markers were assessed immediately before the vesicocentesis: renal echogenicity, presence of cortical cysts, presence of findings suggestive of 'renal dysplasia' (hyperechogenic cystic kidneys with no cortical-medullary differentiation) and severe oligohydramnios (amniotic fluid < 5th percentile). The association of these parameters to the fetal urinary concentration of sodium, chloride, calcium, osmolality and beta2-microglobulin was investigated by logistic regression analysis. RESULTS: There was no relationship between any of the ultrasonographic fetal renal characteristics and fetal urinary biochemistry. CONCLUSIONS: In LUTO, the ultrasound appearance of the fetal kidneys and urinary biochemistry are not correlated. It may be better to take both ultrasound and biochemistry into account when evaluating fetuses with fetal LUTO. © 2016 John Wiley & Sons, Ltd.

Estrogen directly and specifically downregulates NaPi-IIa through the activation of both estrogen receptor isoforms (ERα and ERß) in rat kidney proximal tubule.

We have previously demonstrated that estrogen (E2) downregulates phosphate transporter NaPi-IIa and causes phosphaturia and hypophosphatemia in ovariectomized rats. In the present study, we examined whether E2 directly targets NaPi-IIa in the proximal tubule (PT) and studied the respective roles of estrogen receptor isoforms (ERα and ERß) in the downregulation of NaPi-IIa using both in vivo and an in vitro expression systems. We found that estrogen specifically downregulates NaPi-IIa but not NaPi-IIc or Pit2 in the kidney cortex. Proximal tubules incubated in a "shake" suspension with E2 for 24 h exhibited a dose-dependent decrease in NaPi-IIa protein abundance. Results from OVX rats treated with specific agonists for either ERα [4,4',4″;-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol, PPT] or ERß [4,4',4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol, DPN] or both (PPT + DPN), indicated that only the latter caused a sharp downregulation of NaPi-IIa, along with significant phosphaturia and hypophosphatemia. Lastly, heterologous expression studies demonstrated that estrogen downregulated NaPi-IIa only in U20S cells expressing both ERα and ERß, but not in cells expressing either receptor alone. In conclusion, these studies demonstrate that rat PT cells express both ERα and ERß and that E2 induces phosphaturia by directly and specifically targeting NaPi-IIa in the PT cells. This effect is mediated via a mechanism involving coactivation of both ERα and ERß, which likely form a functional heterodimer complex in the rat kidney proximal tubule.

Efecto diurético agudo de los extractos etanólico y acuoso de Ceratopteris pteridoides (Hook) en ratas normales / Acute diuretic effect of ethanolic and aqueous extracts of Ceratopteris pteridoides (Hook) in normal rats

Introducción. Ceratopteris pteridoides es un helecho semiacuático de la familia Parkeriacea, ampliamente utilizado en la medicina popular colombiana como diurético y colelitiásico, sobre el cual no existen reportes científicos que avalen su uso popular como diurético. Objetivo. Evaluar el efecto diurético agudo en dosis única y dosis repetidas a corto plazo, de los extractos etanólico y acuoso de C. pteridoides en un modelo in vivo . Materiales y métodos. El extracto etanólico total fue obtenido por maceración de la planta entera de C. pteridoides con etanol y el extracto acuoso fue obtenido por decocción a 60 °C por 15 minutos. Ambos extractos se sometieron a análisis fitoquímico preliminar y estudio histológico posterior a la administración de los extractos durante ocho días consecutivos (1.000 mg/kg). El efecto diurético se evaluó en ratas Wistar, tratadas con los extractos (500 mg/kg), en forma aguda y en dosis repetidas a corto plazo, cuantificando la eliminación de agua y la excreción renal de sodio y potasio por espectrofotometría de absorción atómica y, de cloruros, por titulación mercurimétrica. Resultados. En el modelo agudo, ambos extractos mostraron un significativo efecto diurético y de excreción renal de sodio y potasio en comparación con el control, mientras que con la administración en dosis repetidas a corto plazo mostraron efecto diurético sin eliminación de electrolitos. El estudio histopatológico no sugirió efectos tóxicos hepáticos o renales. Conclusión. Los resultados demuestran la actividad diurética de C. pteridoides y sustentan el uso popular dado a esta planta como diurético en la costa norte colombiana. Se requieren estudios posteriores que permitan aislar e identificar los compuestos responsables de la actividad y los mecanismos de acción involucrados.

Introduction. Ceratopteris pteridoides is a semiaquatic fern of the Parkeriacea family, widely used in the Colombian folk medicine as a diuretic and cholelithiasic, of which there are no scientific reports that validate its popular use. Objective. To evaluate the acute and short-term repeated-dose diuretic effect of the ethanolic and aqueous extracts of C. pteridoides in an in vivo model. Materials and methods. The total ethanolic extract was obtained by maceration of the whole plant of C. pteridoides with ethanol and the aqueous extract by decoction at 60°C for 15 minutes. Both extracts were evaluated in preliminary phytochemical analysis and histological studies after the administration of the extracts for 8 consecutive days (1000 mg/Kg). The diuretic effect was evaluated using Wistar rats treated with the extracts (500 mg/Kg), using an acute and a short-term repeated-dose model, and quantifying water elimination, sodium and potassium excretion by atomic absorption spectrophotometry, and chloride excretion by mercurimetric titration. Results. In the acute model both extracts showed significant diuretic, natriuretic, and kaliuretic effect compared to the control group. Whereas, a short-term repeated-dose administration showed a diuretic effect without elimination of electrolytes. The histopathologic study did not suggest a toxic effect in liver or kidney. Conclusion. The results represent evidence of the diuretic activity of C. pteridoides and give support the popular use given to this plant in the north coast of Colombia. Further studies are required to isolate and identify the compounds responsible for the activity and the mechanism of action involved.

Influence of gender and estrous cycle on plasma and renal catecholamine levels in rats.

Several studies have demonstrated that gonadal hormones show significant effects on the brain and signaling pathways of effector organs/cells that respond to neurotransmitters. Since little information is available concerning the impact of male and female gonadal hormones on the renal and peripheral sympathetic system, the objective of this study was to further assess whether and how the renal content and plasma concentration of catecholamines are influenced by gender and the estrous cycle in rats. To achieve this, males Wistar rats were divided into 4 groups: (i) sham (i.e., control), (ii) gonadectomized, (iii) gonadectomized and nandrolone decanoate replacement at physiological levels or (iv) gonadectomized and nandrolone decanoate replacement at high levels. Female Wistar rats were divided into 6 groups: (i) ovariectomized (OVX), (ii) estrogen replacement at physiological levels and (iii) estrogen replacement at at high levels, (iv) progesterone replacement at physiological levels and (v) progesterone replacement at at high levels, and (vi) sham. The sham group was subdivided into four subgroups: (i) proestrus, (ii) estrus, (iii) metaestrus, and (iv) diestrus. Ten days after surgery, the animals were sacrificed and their plasma and renal catecholamine levels measured for intergroup comparisons. Gonadectomy led to an increase in the plasma catecholamine concentration in females, as well as in the renal catecholamine content of both male and female rats. Gonadectomized males also showed a lower level of plasma catecholamine than the controls. The urinary flow, and the fractional excretion of sodium and chloride were significantly increased in gonadectomized males and in the OVX group when compared with their respective sham groups.

Cisplatin increases urinary sodium excretion in rats: gender-related differences.

OBJECTIVE. There are well-documented reports of cisplatin-associated hyponatremia in the literature, but there are no data on gender-dependent differences. The aim of the present study was to define characteristics of 24-hour urinary sodium excretion in young adult Wistar rats of both genders and to evaluate the gender-related effect of cisplatin. MATERIALS AND METHODS. Twelve control Wistar rats (6 males and 6 females) and 12 cisplatin-treated Wistar rats (6 males and 6 females) after a single and repeated injection of cisplatin (once a day for 3 days) at a dose of 2.5 mg/kg body weight into the caudal vein were examined. The experiment was carried out by measuring 24-h urinary sodium, potassium, chloride, magnesium, creatinine excretion and pH in the urine of age-matched male and female rats. RESULTS. The 24-h urinary sodium excretion, sodium/chloride ratio, and diuresis showed no gender-related differences in control rats. After a single administration of 2.5 mg/kg cisplatin, 24-h urinary sodium excretion was not significantly higher in cisplatin-treated rats than in gender-matched controls. After repeated cisplatin administration, 24-h urinary sodium excretion was significantly higher in cisplatin-treated male rats as compared to matched controls (P<0.05). No such effect was found in cisplatin-treated female rats. CONCLUSION. The study data show that cisplatin enhances urinary sodium excretion in male but not in female rats. The mechanism of such a gender-related effect is not yet clear. Further investigations are necessary to elucidate the mechanism of this pharmacological effect of cisplatin.

Hepatoprotective and anti-hepatocarcinogenic effects of glycyrrhizin and matrine.

Matrine (Mat), a component extracted from Sophora flavescens Ait, has a wide spectrum of pharmacological effects. Glycyrrhizin (Gly), a major active constituent of licorice (Glycyrrhiza glabra) root, has various pharmacological effects. Gly and Mat are ancillary drugs used clinically in China for protection of liver function and treatment of tumors. However, habitual administration of Gly may cause adverse effects marked by the development of pseudohypercorticosteroidism. This work was designed to see whether combination use of Gly and Mat could offer better liver protective and anti-hepatocarcinogenic effects than Gly or Mat alone, and whether it could reduce the adverse effects of Gly alone by acetaminophen-induced hepatotoxicity, diethylnitrosamine-induced hepatocarcinogenesis, induction of immunosuppression, albumen-induced swelling of rat hind paws. The results showed that compared with Gly or Mat alone, Gly+Mat reduced the mortality of acetaminophen overdosed mice more effectively, attenuate acetaminophen-induced hepatotoxicity, and reduced the number and area of gamma-GT positive foci, thus protecting liver function and preventing HCC from occurring. In addition, Gly+Mat had a protective effect on immunosuppression, a strong non-specific anti-inflammatory effect, and an effect of reducing the incidence of sodium and water retention.

Central cholinergic mechanisms mediate swallowing, renal excretion, and c-fos expression in the ovine fetus near term.

Fetal swallowing and renal metabolism contribute importantly to amniotic and body fluid homeostasis. To determine central cholinergic modulation of swallowing activity and renal excretion associated with neural activity, we examined the effects of intracerebroventricular injection of carbachol, a cholinergic agonist, in ovine fetuses at 0.9 gestation. Fetuses were chronically prepared with thyrohyoid, nuchal and thoracic esophagus, and diaphragm electromyogram electrodes, as well as lateral ventricle and vascular catheters. Electrodes were also implanted on the parietal dura for determination of fetal electrocorticogram (ECoG). After 5 days of recovery, fetal swallowing, ECoG, and urine output were monitored during basal period and the experimental period following intracerebroventricular injection of 0.9% NaCl as the control (n = 5) or carbachol (3 microg/kg, n = 5). Central carbachol did not significantly change fetal low voltage (LV) and high voltage (HV) ECoG temporal distributions. However, swallowing activity during LV ECoG was elevated significantly after intracerebroventricular carbachol. Associated with the swallowing activation, c-fos immunoreactivity in the putative dipsogenic center, subfornical organ, was enhanced significantly. The fetal urine flow rate and renal Na+, K+, and Cl(-) excretion were markedly increased following intracerebroventricular carbachol and sustained at the high level for at least 2 h. The results indicate that the central cholinergic mechanism is established and functional in regulation of fetal behavior and renal excretion at least at 0.9 gestation, which plays an important role in maintenance of fetal body fluid homeostasis.

Estimation of renal function -- what is appropriate in cancer patients?

AIMS: To compare the accuracy of renal assessment in patients with cancer using radioisotope glomerular filtration rate (GFR), urine collection for creatinine clearance, Cockroft-Gault, Modification of Diet in Renal Disease (MDRD) and Wright formulae. MATERIALS AND METHODS: Measurements of isotope GFR from 367 patients were compared with estimates from the described methods (Cockroft-Gault, MDRD, Wright). An analysis including a further 252 patients with an isotope GFR < or = 50 ml/min was also carried out. RESULTS: The Wright formula was the most accurate form of estimating renal function for the first study group. The formulae were similar in accuracy in the second study group. CONCLUSIONS: The Wright formula is the most accurate form of estimation of renal function in comparison with the isotope GFR for cancer patients. When there is a large proportion of patients with a low isotope GFR (< or = 50 ml/min), the formulae have similar accuracy.

Trial design: blood pressure control and weight gain prevention in prehypertensive and hypertensive smokers: the treatment and prevention study.

BACKGROUND: Cigarette smokers with elevated blood pressure (BP) are at substantially higher risk for cardiovascular events compared to normotensive smokers. Although smoking cessation should be a primary treatment goal for these patients, increases in body weight accompanying smoking abstinence may further increase BP. Intervention strategies that facilitate smoking cessation and modify adverse changes in body weight and BP are needed. METHODS: We describe an ongoing multi-site, two-phase, five-year randomized clinical trial. Participants are cigarette smokers with Prehypertension or Stage I Hypertension. In the first phase, participants receive a smoking cessation intervention combining behavioral counseling and nicotine replacement in an open-label fashion. In the second phase, participants who successfully quit smoking are randomly assigned to one of three lifestyle interventions: 1) weight gain prevention, 2) blood pressure control, or 3) usual lifestyle. Participants are followed for one year to assess changes in blood pressure, body weight, dietary intake, and physical activity. CONCLUSIONS: Results from the proposed study will provide important insights into the efficacy of various approaches to lifestyle modification in smokers at increased risk for cardiovascular events.

Endothelin ETA receptor blockade with darusentan increases sodium and potassium excretion in aging rats.

This study investigated whether intrarenal endothelin-1(ET-1) contributes to sodium excretion in aged rats. Metabolic function studies were performed in male Wistar rats (3 and 24 months) treated with placebo or the orally active ET(A) receptor antagonist darusentan (20 mg/kg/d) for 4 weeks. Mean arterial pressure was measured using an intra-arterial catheter. Electrolytes, aldosterone levels, renin activity, and angiotensin converting enzyme activity were determined in plasma, and mRNA expression of epithelial sodium channel (ENaC) and Na(+), K(+)-ATPase subunits was measured in the renal cortex and medulla. Aging was associated with a marked decrease in urinary excretion of sodium, chloride, and potassium (all P < 0.001) as well as renin activity (P < 0.05), but had no significant effect on gene expression of ENaC or Na(+), K(+)-ATPase subunits. In aged rats, darusentan treatment increased ion excretion (P < 0.05), reduced cortical gene expression of alphaENaC and alpha(1)-Na(+), K(+)-ATPase (both P < 0.05), and increased plasma aldosterone levels (P < 0.01). These data demonstrate a decrease of sodium and potassium excretion in aged rats, changes that are partly sensitive to ETA receptor blockade. Treatment with darusentan also reduced cortical expression of alphaENaC and alpha(1)-Na(+), K(+)-ATPase and increased plasma aldosterone levels independently of blood pressure, electrolytes, renin activity, or angiotensin converting enzyme activity. These findings may provide new pathogenetic links between aging and sodium sensitivity.

Butein ameliorates renal concentrating ability in cisplatin-induced acute renal failure in rats.

The present study examined whether the cisplatin-induced nephropathy could be ameliorated by administration of butein isolated from the stems of Rhus verniciflua STOCKS. The present study showed that polyuric profile was revealed in cisplatin-induced acute renal failure (ARF) rats associated with decreases in urinary sodium, potassium, chloride, and creatinine excretion, and osmolality. Among these renal functional parameters, urinary volume and osmolality were partially restored by administration of butein (10 mg/kg, i.p.), but electrolytes and creatinine excretion were not restored. Both solute-free water reabsorption and creatinine clearance were also significantly decreased in rats subjected to cisplatin. When butein was administered in rats with cisplatin-induced ARF for 4 d, solute-free water reabsorption was improved by 91% compared with that of cisplatin-induced ARF rats, but creatinine clearance was not restored. The expression levels of aquaporin 2 (AQP 2) in the inner, outer medulla, and cortex were significantly decreased in the kidney of ARF, which were partially reverted by administration of butein. In histological examination of the kidney, butein treatment partially prevented the lesions at tubules of renal cortex in cisplatin-induced ARF rats, while the lesions at glomeruli were not ameliorated. Taken together, butein ameliorates renal concentrating ability via up-regulation of renal AQP 2 water channel in rats with cisplatin-induced ARF without ameliorating effect on renal filtration defect.

An orally active adenosine A1 receptor antagonist, FK838, increases renal excretion and maintains glomerular filtration rate in furosemide-resistant rats.

1. Loop and thiazide diuretics are common therapeutic agents for the treatment of sodium retention and oedema. However, resistance to diuretics and decreases in renal function can develop during diuretic therapy. Adenosine causes renal vasoconstriction, sodium reabsorption, and participates in the tubuloglomerular feedback mechanism for the regulation of glomerular filtration rate. 2. We tested the hypothesis that the selective adenosine A(1) receptor antagonist FK838 is orally active and causes diuresis and natriuresis, but maintains glomerular filtration rate in normal rats or in rats with furosemide resistance. 3. In normal male Sprague - Dawley rats, FK838 dose-dependently increased urine flow and sodium and chloride excretion while sparing potassium. In combination with furosemide, FK838 enhanced the diuretic and natriuretic actions of furosemide to the same extent as hydrochlorothiazide and did not increase the potassium loss in normal rats. In furosemide-resistant rats, FK838 increased urine flow and electrolyte excretion to a greater extent than hydrochlorothiazide. In addition, hydrochlorothiazide significantly decreased glomerular filtration rate, whereas FK838 maintained glomerular filtration rate in furosemide-resistant rats. 4. This study shows that the adenosine A(1) receptor antagonist FK838 is orally active and causes potent diuresis and natriuresis and maintains glomerular filtration rate in normal or furosemide-resistant rats. Adenosine A(1) receptor antagonists may be novel therapeutics for the treatment of oedema in normal or otherwise diuretic-resistant patients.

Renal and cardiovascular effects of renal denervation in conscious rats after adenosine administration and nitric oxide synthase inhibition.

The role of renal nerves on renal and cardiovascular responses to adenosine administration and/or acute NO synthase inhibition was investigated. Conscious male Wistar rats with implanted catheters in femoral artery for blood pressure registration, femoral vein for drug infusion and bladder for urine collection were used. Adenosine was applied i.v. (1.0 mg/kg BW bolus) followed by infusion of 0.1 mg/kg.min, and/or nitric oxide synthase inhibition (NOSI) was performed by i.v. administration of 10 mg/kg BW N-Omega-nitro-L-arginine methyl ester (L-NAME) before and 1 week after bilateral renal denervation (BRD). NOSI decreased HR and increased SAP, MAP and DAP both in intact and BRD rats. Baroreflex sensitivity increased in intact and BRD rats. Adenosine did not change HR, blood pressure or baroreflex sensitivity in intact as well as BRD rats. NOSI increased V, VU(Na) and VU(CI) in intact rats but decreased V and did not alter VU(Na) and VU(CI) in BRD rats. Adenosine increased V, VU(CI) and C(cr) in intact rats but did not change renal excretory function in BRD rats. Combined application of adenosine and L-NAME led to a dramatic increase of V, VU(Na), VU(Cl) and C(cr) in intact rats. However, VU(Na) and VU(CI) in BRD rats were lower as compared to intact rats. Therefore, changes in renal excretory function seen after NOSI are not exclusively the result of pressure diuresis and natriuresis but in some way are dependent on renal nerves. Renal denervation attenuates the renal excretory response to adenosine. Sympathetic nervous system is important in mediating the effects of adenosine and/or NO on renal excretory function. Renal denervation did not change the pattern of baroreflex sensitivity after adenosine and/or L-NAME administration.

Osmoregulation in the terrestrial Christmas Island red crab Gecarcoidea natalis (Brachyura: Gecarcinidae): modulation of branchial chloride uptake from the urine.

Crabs generally produce urine iso-osmotic to their haemolymph, but terrestrial crabs are able to vary the composition of their final excretory fluid (termed P) postrenally, in the branchial chambers. Regulatory aspects of branchial urine processing were investigated in the Christmas Island red crab Gecarcoidea natalis acclimated to drinking either freshwater (FW crabs) or 70% seawater (SW crabs). FW crabs released dilute P (mean [Cl(-)] 8.8 mmol l(-1)). Drinking 70% seawater caused the mean [Cl(-)] of the P to rise to 376 mmol l(-1) over 5 days, approaching the haemolymph [Cl(-)]. FW crabs with saline-perfused branchial chambers absorbed chloride at a high rate (10 mmol kg(-1) h(-1)), and haemolymph [Cl(-)] increased at approximately 20 mmol l(-1) h(-1). SW crabs exhibited elevated haemolymph osmolalities and ion concentrations and zero branchial chloride uptake. FW crabs that were salt-loaded by branchial chamber perfusion over several hours downregulated, and eventually ceased, chloride uptake. The rate of downregulation, but not the initial chloride flux, was dependent on initial haemolymph [Cl(-)]. Intravascular infusion of NaCl caused immediate reduction in branchial [Cl(-)] of 80%. Crabs ingested and regurgitated the perfusion saline, supporting suggestions that reingestion of urine could conserve water and ions. Dopamine upregulated branchial chloride transport in G. natalis. This is consistent with the ion-regulatory effects of dopamine in euryhaline marine brachyurans but contrasts with its inhibitory effects in the terrestrial anomuran Birgus latro. Dopamine increased the rate of urine release in FW crabs. Urine composition appears to be unimportant in ionic regulation, except in the case of magnesium, levels of which were elevated in the urine of SW crabs.

Effect of octreotide acetate on the plasma concentration and urinary excretion of uridine and purine bases.

To determine the effect of octreotide acetate on urinary excretion of uric acid and plasma concentration of uridine, we subcutaneously administered octreotide acetate (1 microg/kg of body weight) to 5 healthy subjects. Ninety minutes after administration, octreotide acetate increased the plasma concentration of uridine by 15% and decreased the plasma concentration of glucagon by 24% and that of insulin to below the detection limits. In addition, octreotide acetate decreased the urinary excretion of uric acid, sodium, and chloride by 60%, 40%, and 38%, respectively, at 1 hour after administration. However, octreotide acetate did not affect the concentrations of hypoxanthine, xanthine, uric acid, cyclic AMP in plasma, lactic acid and pyruvic acid in blood, urinary excretion of hypoxanthine and xanthine, or creatinine clearance. From these results, we speculated that octreotide acetate decreases the urinary excretion of uric acid by decreasing the concentration of glucagon and/or urinary excretion of sodium, and increases the plasma concentration of uridine via decreased concentrations of glucagon and insulin.

Potentiation of urinary atrial natriuretic peptide interferes with macula densa function.

OBJECTIVES: Neutral endopeptidase (NEP) inhibition potentiated the renal action of Atrial Natriuretic Peptide (ANP) and was associated with appearance of the peptide in the urine, providing evidence of protection of the filtrated peptide along the course of the nephron. The macula densa, composed of epithelial cells, receives ionic information from the urinary compartment via Na-K-2Cl cotransport and influences renin secretion by the myoepithelioïd cells in the afferent arteriole. bNOS constitutively expressed in the epithelial cells of the macula densa is involved in this feed-back. NEP inhibition was associated with the absence of any increase in renin secretion. The hypothesis is that potentiation of urinary ANP by NEP inhibition could limit renin secretion by directly or indirectly targeting the macula densa in vivo. METHODS AND RESULTS: We tested the interaction between NEP inhibition (candoxatril) and Na-K-2Cl inhibition (bumetanide) on electrolyte and ANP urinary excretion, renin secretion, macula densa activity (NADPH diaphorase activity and bNOS mRNA) and TSC-1 mRNA expression in the renal cortex and BSC-1 in the renal medulla of rats treated for 5 days. Bumetanide increased urinary electrolyte excretion whereas candoxatril did not. Candoxatril increased urinary ANP and cyclic GMP excretion. Bumetanide increased renin and aldosterone secretion whereas candoxatril decreased renin secretion. This effect on renin release was associated with an increase in macula densa NADPH diaphorase activity in the bumetanide-treated group which was blunted by candoxatril. Lastly, bumetanide increased TSC-1 mRNA expression in the cortex and this effect was blunted by candoxatril. CONCLUSION: These results suggest that potentiation of ANP by NEP inhibition could interfere with tubular function at different levels and limit renin secretion by a urinary pathway involving macula densa activity.

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.