Osmolar Clearance Research Articles

Diuretic Effect of the Aqueous Extract of Cymbopogon nardus (L.) Rendle Compared with Furosemide in Wistar Rats

Cymbopogon nardus (L.) Rendle is one of the medicinal plants widely used in folk medicine to cure certain diseases. The current work aims to assess the diuretic potential of C. nardus using animal models. Urine electrolytes (sodium and potassium), serum electrolytes (sodium, potassium, and chloride), blood urea, creatinine, creatinine clearance, osmolar clearance, urinary osmolarity, and urine flow were determined. To assess the diuretic effect of the studied plant, four groups of rats were used (n = 6). The control group received 10 mL of water, the second and third groups received two doses of the plant (100 and 150 mg/kg bw), and the last group received furosemide (10 mg/kg bw), the experiment sustained for seven days. Urine flow and electrolytes levels were studied. The single dose of C. nardus extract significantly increased urine flow after oral administration. In addition, daily administration of both doses of C. nardus significantly elevated urine excretion, opposite to the first group. C. nardus enhanced the urine elimination of sodium and potassium. Importantly, both doses have no effect on serum potassium level. Creatinine clearance was significantly elevated in a dose-dependent manner. This information will be considered as a keystone for further studies forward in applying new process to isolate active compounds of C. nardus responsible for its biological properties.

Renal and Endocrine Responses to Arm Exercise in Persons with Cervical Spinal Cord Injury

The aim of this study was to assess renal functions and endocrine responses to arm exercise in persons with cervical spinal cord injury (CSCI) under euhydrated conditions (free drinking of water), and to determine the physiological effects of exercise on renal function in these subjects. Eleven CSCI individuals (spinal lesions between C6 and C8, American Spinal Injury Association impairment scale A) and nine able-bodied (AB) persons rested for 30 min before performing 30 min arm-crank ergometer exercises at 50% of their maximum oxygen consumption, followed by 60-min of rest/recovery. Urine and blood samples were collected before and immediately after the exercise and recovery period. The CSCI patients showed no increase in plasma adrenaline and plasma renin activity compared with the AB controls, but showed similar changes in plasma aldosterone and the plasma antidiuretic hormone in response to the exercise. Creatinine clearance, osmolal clearance, free water clearance, and the fractional excretion of Na+ did not change during exercise in both groups of subjects, however free water clearance in the CSCI group was higher than in the AB group throughout the study. These findings suggested that activated plasma aldosterone without an increase in adrenaline or renin activity during exercise in CSCI individuals may reflect an adaptation to the disturbance of the sympathetic nervous system to compensate for renal function. As a result, no adverse effects of exercise on renal function in CSCI patients were observed.

Kidney Dysfunction After Traumatic Brain Injury: Pathophysiology and General Management.

Traumatic brain injury (TBI) remains a major cause of mortality and morbidity, and almost half of these patients are admitted to the intensive care unit. Of those, 10% develop acute kidney injury (AKI) and 2% even need kidney replacement therapy (KRT). Although clinical trials in patients with TBI who have AKI are lacking, some general principles in this population may apply. The present review is an overview on the epidemiology and pathophysiology of AKI in patients with TBI admitted to the intensive care unit who are at risk for or who have developed AKI. A cornerstone in severe TBI management is preventing secondary brain damage, in which reducing the intracranial pressure (ICP) and optimizing the cerebral perfusion pressure (CPP) remain important therapeutic targets. To treat episodes of elevated ICP, osmolar agents such as mannitol and hypertonic saline are frequently administered. Although we are currently awaiting the results of a prospective randomized controlled trial that compares both agents, it is important to realize that both agents have been associated with an increased risk of developing AKI which is probably higher for mannitol compared with hypertonic saline. For the brain, as well as for the kidney, targeting an adequate perfusion pressure is important. Hemodynamic management based on the combined use of intravascular fluids and vasopressors is ideally guided by hemodynamic monitoring. Hypotonic albumin or crystalloid resuscitation solutions may increase the risk of brain edema, and saline-based solutions are frequently used but have a risk of hyperchloremia, which might jeopardize kidney function. In patients at risk, frequent assessment of serum chloride might be advised. Maintenance of an adequate CPP involves the optimization of circulating blood volume, often combined with vasopressor agents. Whether individualized CPP targets based on cerebrovascular autoregulation monitoring are beneficial needto be further investigated. Interestingly, such individualized perfusion targets are also under investigation in patients as a strategy to mitigate the risk for AKI in patients with chronic hypertension. In the small proportion of patients with TBI who need KRT, continuous techniques are advised based on pathophysiology and expert opinion. The need for KRT is associated with a higher risk of intracranial hypertension, especially if osmolar clearance occurs fast, which can even occur in continuous techniques. Precise ICP and CPP monitoring is mandatory, especially at the initiation of KRT.

Analysis of the effect of tubular dysfunction on the likelihood of developing cardiovascular complications in patientswith hypertension in the late period after acute coronarysyndrome

BACKGROUND. The study of the prognostic significance of markers of tubular dysfunction in patients with the acute coronary syndrome (ACS) and arterial hypertension (AH) is highly relevant, due to the unity of pathogenetic mechanisms and their consequences that develop during an acute coronary event. PURPOSE. Analysis of the influence of tubular dysfunction indi­cators on the risk of cardiovascular complications in patients with hypertension in the late period after ACS. PATIENTS ANDMETHODS. The study included 103 patients with hypertension and ACS. All patients included in the study underwent coronary angiography (CAG) with stenting of the coronary arteries. Before CAG, clinical and anamnestic data were collected, labora­tory (including creatinine and urea, potassium and sodium, plasma osmolarity), and instrumental diagnostic methods were used. The concentration of potassium and sodium in the daily urine, potassium and natriuresis, osmolarity of urine, and the calculated osmolar clearance index (ОС) were determined. Impedance spectrometry was performed to determine the water balance of the body's liquid media. After 17.0±0.51 months, the endpoints of the study were registered: AMI, NS, stable stress angina, repeated myocardial revascularization (RM), and death. RESULTS. It was found that an increase in ОС is associated with the risk of developing repeated RM in the late period after ACS (x2-criterion = 3.89, p = 0.04). Among the indicators of the electrolyte balance of urine, a statistically significant effect on the risk of repeated RM was found with an increase in the con­centration of potassium in the urine (x2-criterion = 4.63, p = 0.03) and daily potassium urea (x2-criterion = 4.85, p = 0.03). The ОС index and an increase in the electrolyte balance of urine were considered and justified as markers of tubular dysfunction. The complex effect of increasing the ОС and reducing the volume of intracellular fluid from the proper values (x2-criterion = 6.16, p = 0.4) on the risk of repeated RM was established. It was found that when the balance of the volume of total fluid and CA is changed, the risk of developing repeated RM is potentiated. It is shown that with the excessive introduction of fluid volume into the body, mainly intravenously and an increase in ОС, the risk of developing repeated RM increases significantly. CONCLU­SION. The study revealed that the presence of tubular dysfunction can be considered as a predictor of adverse cardiovascular prognosis in patients with ACS and hypertension. For a comprehensive analysis of the risk value, it is necessary to control homeostasis and individual selection of the volume of intravenous infusions.

The pathophysiological effects of Russell's viper (Daboia siamensis) venom and its fractions in the isolated perfused rabbit kidney model: A potential role for platelet activating factor.

The pathophysiological effects of Russell's viper venom (RVV) and its fractions, including phospholipase A2 (RvPLA2), metalloprotease (RvMP), L-amino acid oxidase (RvLAAO), and phosphodiesterase (RvPDE) on renal functions were investigated using the isolated perfused rabbit kidney (IPK) model. Moreover, whether their effects on renal alterations were promoted by platelet activating factor (PAF) was tested using the PAF receptor antagonist, WEB 2086. There was a marked reduction in the perfusion pressure (PP) and renal vascular resistance (RVR) 10 min after RVV administration (1.0 mg/100 ml of perfusate), thereafter both PP and RVR gradually increased and approached the control level within 90 min. These effects were abolished by pretreatment with WEB2086 (2 μg/μl). Administration with RvPLA2 (280 μg/ml), RvMP (280 μg/ml), or RvLAAO (135 μg/ml) alone increased both the PP and RVR, whereas RvPDE (100 μg/ml) reduced both the PP and RVR. Pretreatment with WEB 2086 completely abolished the effects induced by RvMP, but not the other fractions. The RVV also caused a marked decrease in the glomerular filtration rate (GFR), urinary flow rate (UF), and osmolar clearance (Cosm), and these effects were not inhibited by pretreatment with WEB2086. Each RVV fraction also increased, to varying extents, the GFR, UF, and Cosm, and these effects induced by RvPLA2 or RvMP, but not the other fractions, were completely blocked by WEB 2086. Changes in percent filtered Na+ and K+ excreted in the IPK by RVV, RvPDE, and RvMP were abolished by pretreatment with WEB 2086. Histological evaluation profiled mainly tubulonephrosis in the treated kidney. These results reveal that the alterations in renal functions induced by RVV and its fractions are due to the synergistic action of the different components of snake venom, instead of the action of a single component. The effects of RVV and its fractions in rabbit IPK are mediated at least in part by PAF.

Osmotic diuresis by SGLT2 inhibition stimulates vasopressin-induced water reabsorption to maintain body fluid volume.

Most of the filtered glucose is reabsorbed in the early proximal tubule by the sodium‐glucose cotransporter SGLT2. The glycosuric effect of the SGLT2 inhibitor ipragliflozin is linked to a diuretic and natriuretic effect that activates compensatory increases in fluid and food intake to stabilize body fluid volume (BFV). However, the compensatory mechanisms that are activated on the level of renal tubules remain unclear. Type 2 diabetic Goto‐Kakizaki (GK) rats were treated with vehicle or 0.01% (in diet) ipragliflozin with free access to fluid and food. After 8 weeks, GK rats were placed in metabolic cages for 24‐hr. Ipragliflozin decreased body weight, serum glucose and systolic blood pressure, and increased fluid and food intake, urinary glucose and Na+ excretion, urine volume, and renal osmolar clearance, as well as urine vasopressin and solute‐free water reabsorption (TcH2O). BFV, measured by bioimpedance spectroscopy, and fluid balance were similar among the two groups. Urine vasopressin in ipragliflozin‐treated rats was negatively and positively associated with fluid balance and TcH2O, respectively. Ipragliflozin increased the renal membrane protein expression of SGLT2, aquaporin (AQP) 2 phosphorylated at Ser269 and vasopressin V2 receptor. The expression of SGLT1, GLUT2, AQP1, and AQP2 was similar between the groups. In conclusion, the SGLT2 inhibitor ipragliflozin induced a sustained glucosuria, diuresis, and natriuresis, with compensatory increases in fluid intake and vasopressin‐induced TcH2O in proportion to the reduced fluid balance to maintain BFV. These results indicate that the osmotic diuresis induced by SGLT2 inhibition stimulates compensatory fluid intake and renal water reabsorption to maintain BFV.

Investigation of Acanthocephalan parasites in some marine fishes as a bio-indicator for heavy metals pollution

The effect of deliberate hypotension induced by labetalol on renal function, was studied in 25 patients undergoing middle-ear surgery. The patients were randomized into three groups, one enflurane (E) group and two isoflurane (I and F) groups. Group F received frusemide 0.5 mg kg-1 at the onset of hypotension. The mean arterial pressure was 50 mmHg (6.7 kPa) in Groups E and I, and 49 mmHg (6.5 kPa) in Group F during hypotension. During hypotension, urine flow rate, effective renal blood flow, endogenous creatinine clearance, and osmolar clearance decreased. Free-water clearance and fractional electrolyte excretions also indicated deterioration of renal function during hypotension, but it returned to normal after anaesthesia. The effects of frusemide appeared mainly after anaesthesia. Frusemide reduced the amount of labetalol and isoflurane needed to maintain hypotension. Serum fluoride concentration did not increase to a potentially nephrotoxic level.

Pathogenetic justification of possibility of antidiuretic hormone use in incontinent women

Hypothesis/aims of study. Urine incontinence seems to include several pathogenetic forms, as efficient therapy is provided by different medications. Commonly used in the treatment of female patients with overactive bladder and nocturnal polyuria is desmopressin which normalizes the water excretion of the kidney, which is disturbed by a presumed inverted rhythm of vasopressin secretion in these patients. The current analysis was undertaken to evaluate the clinical efficiency of desmopressine in incontinent patients with nocturnal polyuria and polyuria.
 Study design, materials and methods. A total of 84 patients with complaints of urinary incontinence, polyuria (24-urine volume of 40 mL/kg bodyweight or above) or nocturnal polyuria (nocturnal volume/24-h urine volume of 0.33 or above) and 14 control subjects were included. Mean patient age was 43.6 ± 4.6 years, in control subjects 38.5 ± 6.4 (p > 0.05). All participants performed 24h-urinecollection to determine the voided volumes and the levels of creatinine, osmolality, sodium, magnesium and potassium for each sample. A blood sample was taken during the 24-urinecollection to determine the levels of creatinine, osmolality, sodium, magnesium and potassium. The examination of patients with polyuria and nocturnal polyuria was performed twice: in the initial state and one month after the start of treatment with optimal dose of desmopressin. Optimal dose was established through an open-label dose-titration using 0.1 mg, 0.2 mg and 0.4 mg of desmopressin (Minirin). Safety parameters assessed included incidence of adverse events, vital signs and serum sodium levels.
 Results. In patients with polyuria and nocturnal polyuria the glomerular filtration rate was normal, whereas diuresis and solute (sodium, magnesium, potassium) excretion in night samples in nocturnal polyuria and both in night and day samples in polyuria were increased. The higher diuresis and the higher solute excretion observed in nocturnal polyuria and polyuria are accompanied by an increase of free water reabsorption. In nocturnal polyuria and polyuria a high correlation was found between the free water reabsorption and solute excretion. This occurs against the background of the high night and day osmotic concentration. The statistically significant recovery of renal function occurred in 12 incontinent women with polyuria and 18 with nocturnal polyuria. In these papients there was a statistically significant decrease in diuresis, osmolar clearance and excretion of sodium, potassium and magnesium.
 Concluding message. As desmopressin affects cells of the thick ascending limb of Henle’s loop, it is likely that nocturnal polyuria and polyuria result from a disturbed regulation of the function of these cells. Normalization can be achieved by desmopressin administration to stimulate V2-receptors, which increase water permeability and water reabsoption in collecting ducts as well as ion reabsorption by cells of the thick ascending limb of Henle’s loop.

Acute renal effects of the GLP-1 receptor agonist exenatide in overweight type 2 diabetes patients: a randomised, double-blind, placebo-controlled trial.

Aims/hypothesisThis study aimed to investigate the acute renal effects of the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide in type 2 diabetes patients.MethodsWe included overweight (BMI 25–40 kg/m2) men and postmenopausal women, aged 35–75 years with type 2 diabetes (HbA1c 48–75 mmol/mol; 6.5–9.0%) and estimated GFR ≥ 60 ml min−1 1.73 m−2. Exenatide or placebo (NaCl solution, 154 mmol/l) was administrated intravenously in an acute, randomised, double-blind, placebo-controlled trial conducted at the Diabetes Center VU University Medical Center (VUMC). GFR (primary endpoint) and effective renal plasma flow (ERPF) were determined by inulin and para-aminohippurate clearance, respectively, based on timed urine sampling. Filtration fraction (FF) and effective renal vascular resistance (ERVR) were calculated, and glomerular hydrostatic pressure (PGLO) and vascular resistance of the afferent (RA) and efferent (RE) renal arteriole were estimated. Tubular function was assessed by absolute and fractional excretion of sodium (FENa), potassium (FEK) and urea (FEU), in addition to urine osmolality, pH and free water clearance. Renal damage markers, BP and plasma glucose were also determined.ResultsOf the 57 patients randomised by computer, 52 were included in the final analyses. Exenatide (n = 24) did not affect GFR (mean difference +2 ± 3 ml min−1 1.73 m−2, p = 0.489), ERPF, FF, ERVR or PGLO, compared with placebo (n = 28). Exenatide increased RA (p < 0.05), but did not change RE. Exenatide increased FENa, FEK, urine osmolality and pH, while FEU, urinary flow and free water clearance were decreased (all p < 0.05). Osmolar clearance and renal damage makers were not affected. Diastolic BP and mean arterial pressure increased by 3 ± 1 and 6 ± 2 mmHg, respectively, whereas plasma glucose decreased by 1.4 ± 0.1 mmol/l (all p < 0.05).Conclusions/interpretationExenatide infusion does not acutely affect renal haemodynamics in overweight type 2 diabetes patients at normal filtration levels. Furthermore, acute GLP-1RA administration increases proximal sodium excretion in these patients.Trial registrationClincialTrials.gov NCT01744236FundingThe research leading to these results has been funded from: (1) the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 282521 – the SAFEGUARD project; and (2) the Dutch Kidney Foundation, under grant agreement IP12.87.Electronic supplementary materialThe online version of this article (doi:10.1007/s00125-016-3938-z) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

Low Na, high K diet and the role of aldosterone in BK-mediated K excretion.

A low Na, high K diet (LNaHK) is associated with a low rate of cardiovascular (CV) disease in many societies. Part of the benefit of LNaHK relies on its diuretic effects; however, the role of aldosterone (aldo) in the diuresis is not understood. LNaHK mice exhibit an increase in renal K secretion that is dependent on the large, Ca-activated K channel, (BK-α with accessory BK-β4; BK-α/β4). We hypothesized that aldo causes an osmotic diuresis by increasing BK-α/β4-mediated K secretion in LNaHK mice. We found that the plasma aldo concentration (P[aldo]) was elevated by 10-fold in LNaHK mice compared with control diet (Con) mice. We subjected LNaHK mice to either sham surgery (sham), adrenalectomy (ADX) with low aldo replacement (ADX-LA), or ADX with high aldo replacement (ADX-HA). Compared to sham, the urinary flow, K excretion rate, transtubular K gradient (TTKG), and BK-α and BK-β4 expressions, were decreased in ADX-LA, but not different in ADX-HA. BK-β4 knockout (β4KO) and WT mice exhibited similar K clearance and TTKG in the ADX-LA groups; however, in sham and ADX-HA, the K clearance and TTKG of β4KO were less than WT. In response to amiloride treatment, the osmolar clearance was increased in WT Con, decreased in WT LNaHK, and unchanged in β4KO LNaHK. These data show that the high P[aldo] of LNaHK mice is necessary to generate a high rate of BK-α/β4-mediated K secretion, which creates an osmotic diuresis that may contribute to a reduction in CV disease.

Acute effect of Russell’s viper (Daboia siamensis) venom on renal tubular handling of sodium in isolated rabbit kidney

Abstract Background: The common complication in cases of poisoning by Russell’s viper (Daboia siamensis) venom (RVV) is acute renal failure, but the pathogenesis involved in the alteration of kidney function is still not well understood. Objective: To clarify the role of RVV in the pathogenesis of renal damage, the present study examines the functional short-term alterations acutely induced by RVV in isolated perfused rabbit kidney. Methods: Effects of RVV on renal tubular handling of sodium including mean perfusion pressure (PP), the renalvascular resistance (RVR), the glomerular filtration rate (GFR), the urinary flow (V) and osmolar clearance (Cosm) were studied in two groups of isolated perfused rabbit kidneys; each group had four isolated rabbit kidneys. RVV was added to the perfusion system to obtain the final concentration of 10 ⃞g/ml. Results: Immediate decreases in PP and RVR caused by the venom were significantly apparent (p &lt; 0.05) in the first 15 min after RVV administration. A gradual rise in both PP and RVR occurred 15 min after the initial reduction of the first phase, but its remained below pretreatment values. The GFR, V, and Cosm decreased significantly throughout experiments after venom perfusion (p &lt; 0.05). The total fractional sodium excretion increased significantly after venom perfusion throughout experiments, while significant reductions (p &lt; 0.05) of renal tubular handling of sodium were apparent for proximal absolute reabsorption of sodium and proximal fractional reabsorption of sodium including marked reductions of distal absolute reabsorption of sodium and distal fractional reabsorption of sodium of the venom treated kidney. Optical microscopy of treated kidney tissue showed acute tubular necrosis at the end of experiment. Conclusion: The present study suggests that an administration of RVV in the isolated rabbit kidney causes direct acute nephrotoxicity and acute alterations of main functional parameters that are probably mediated by either the direct action of venom components or an indirect effect from vasoactive mediators released from renal cells of the RVV-treated kidney.

Effects of “in vivo” administration of baclofen on rat renal tubular function

The effects of the in vivo administration of baclofen on renal tubular transport and aquaporin-2 (AQP2) expression were evaluated. In conscious animals kept in metabolic cages, baclofen (0.01–1mg/kg, s.c.) induced a dose-dependent increment in the urine flow rate (UFR) and in sodium and potassium excretion, associated with an increased osmolal clearance (Closm), a diminished urine to plasma osmolality ratio (Uosm/Posm) and a decrease in AQP2 expression. The above mentioned baclofen effects on functional parameters were corroborated by using conventional renal clearance techniques. Additionally, this model allowed the detection of a diminution in glucose reabsorption. Some experiments were performed with water-deprived or desmopressin-treated rats kept in metabolic cages. Either water deprivation or desmopressin treatment decreased the UFR and increased the Uosm/Posm. Baclofen did not change the Uosm/Posm or AQP2 expression in desmopressin-treated rats; but it increased the UFR and diminished the Uosm/Posm and AQP2 expression in water-deprived animals. These results indicate that in vivo administration of baclofen promotes alterations in proximal tubular transport, since glucose reabsorption was decreased. The distal tubular function was also affected. The increased Closm indicates an alteration in solute reabsorption at the ascending limb of the Henle's loop. The decreased Uosm/Posm and AQP2 expression in controls and in water-deprived, but not in desmopressin-treated rats, lead us to speculate that some effect of baclofen on endogenous vasopressin availability could be responsible for the impaired urine concentrating ability, more than any disturbance in the responsiveness of the renal cells to the hormone.

The effect of glutamine and alanylglutamine as substrates for the isolated perfused rabbit kidney

Rabbit kidneys were perfused with a high K+ and Mg++ solution as previously described (J S R 21(3);169,1976). Briefly the animals were anesthetized with urethane and pentobarbital and the left kidney perfused at 37ºC with a previously dialyzed solution in an artificial heart‐lung machine custom fabricated. Several functional physiological parameters were evaluated such as perfusate and urine flow, GFR, %TNa, %TK, osmolar clearance, perfusion pressure and vascular resistance. The experiments lasted 2 hours. To measure kidney function creatinine was added to the perfusate and Na,K, and osmolarities were measured every ten minutes. Urinary flow increased 6.5‐fold in AG group when compared to control. Glutamine increased this parameter 16.5 times. The same trend was observed with GFR that was enhanced 5.5 times in the AG group while Glut 1 increased 10.6%. The fractional sodium reabsorption increased 8.87% with AG while Glut increased 11.26%. No changes were observed in the fractional transport of potassium. We conclude that these 2 substrates promote a great improvement in kidney functional preservation in this ex vivo model. These substrates could be important metabolic support when perfusing kidney for transplantation.Financial support: CNPq and FUNCAP Brazil

Comparison of the diuretic effects of medetomidine hydrochloride and xylazine hydrochloride in healthy cats

To investigate dose-related diuretic effects of medetomidine hydrochloride and xylazine hydrochloride in healthy cats. 5 sexually intact cats (4 males and 1 female). The 5 cats received each of 11 treatments. Cats were treated by IM administration of saline (0.9% NaCl) solution (control treatment), medetomidine hydrochloride (20, 40, 80, 160, and 320 μg/kg), and xylazine hydrochloride (0.5, 1, 2, 4, and 8 mg/kg). Urine and blood samples were collected 9 times during a 24-hour period. Variables measured were urine volume, pH, and specific gravity; plasma arginine vasopressin (AVP) concentration; and creatinine and electrolyte concentrations as well as osmolality in both urine and plasma. Both medetomidine and xylazine increased urine production for up to 5 hours after injection. Xylazine had a dose-dependent diuretic effect, but medetomidine did not. Urine specific gravity and osmolality decreased in a dose-dependent manner for both drugs. Free-water clearance increased for up to 5 hours after injection, whereas glomerular filtration rate, osmolar clearance, plasma osmolality, and electrolyte concentrations did not change significantly. Area under the curve for AVP concentrations decreased in a dose-dependent manner for medetomidine but not for xylazine; however, this was not related to diuresis. Both medetomidine and xylazine induced profound diuresis in cats by decreasing reabsorption of water in the kidneys. The diuretic effect of medetomidine, including the change in AVP concentration, differed from that of xylazine. Care must be used when administering these drugs to cats with urinary tract obstruction, hypovolemia, or dehydration.

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.

Effect of Chronic Inhibition of Converting Enzyme on Renal Handling of Salt and Water: A Study on a Pediatric Population

Background/Aims: The effect of angiotensin-converting enzyme inhibition (ACEi) is amply documented in several pathological conditions. However, there are few reports about the effect of chronic ACEi on salt and water balance. The present work evaluates the effect of chronic ACEi on salt and water balance in a population of children receiving enalapril chronically in order to reduce albuminuria elicited by a uremic hemolytic syndrome. Methods: Nine children aged from 9 to 19 years with normal glomerular filtration rate, normotension and with urinary concentration capacity preserved were treated with enalapril with doses ranging between 0.1 and 0.30 mg/kg/day. Diuresis, urinary absolute and fractional excretion of Na⁺, K⁺ and urea, creatinine clearance, osmolal clearance and tubular water reabsorption were measured under three experimental procedures: (1) with free access to water; (2) with a water load and (3) with water restriction. In the last group urinary antidiuretic hormone (ADH) was measured. These tests were performed in a paired way, just before starting ACEi treatment and after 6 months of enalapril treatment. Results: Enalapril treatment diminished the urinary concentration capacity without affecting Na⁺ and K⁺ urinary excretion. Creatinine clearance was not modified except in the condition of water load where a fall in it was found after ACEi. ADH increased after enalapril treatment in children under water restriction. Conclusion: In these children chronic ACEi decreases urinary concentration capacity.

Gluco- and mineralocorticoid biological effects of a 7-day treatment with low doses of hydrocortisone and fludrocortisone in septic shock

The benefits of low-dose steroids in septic shock remain controversial. We investigated if these low doses were able to induce their expected hormonal effects by analyzing the biological modifications observed during the study, which first demonstrated the survival benefit of low-dose steroids. This was a multicenter, placebo-controlled, randomized, double-blind study in which 299 septic shock patients received a 7-day treatment with a combination of hydrocortisone (50 mg intravenously four times daily) and fludrocortisone (50 μg orally once daily) or matching placebos. Gluco- and mineralocorticoid biological effects observed during the 7 days of treatment were compared between groups. Steroids significantly decreased eosinophil counts from day 2 to day 7. Steroids significantly increased plasma glucose from day 2 (compared with placebos: +0.8 mmol/l) to day 7 (+1.8 mmol/l) and cholesterol from day 3 (+0.54 mmol/l) to day 7 (+0.39 mmol/l). Steroids significantly increased plasma sodium from day 3 (+2 mmol/l) to day 7 (+5 mmol/l) and significantly decreased plasma potassium on day 7 (-0.2 mmol/l). Steroids significantly decreased urinary sodium/potassium ratio from day 2 (-47 %) to day 7 (-57 %) and sodium fractional excretion from day 3 (-25 %) to day 7 (-66 %). Steroids significantly increased urine output on day 4 and 5 and osmolar clearance from day 4 to day 7, and decreased free-water clearance from day 4 to day 7, this effect being significant on day 4 and 6. In septic shock, low-dose steroids induced both gluco- and mineralocorticoid biological effects and seemed to improve renal function. Most of these effects appeared after 2-3 days of treatment and lasted at least until the end of treatment.

Hypothyroidism maintained reactive oxygen species–steady state in the kidney of rats intoxicated with ethylene glycol: effect related to an increase in the glutathione that maintains the redox environment

Our objective was to determine whether hypothyroidism protects against ethylene glycol (EG)-induced renal damage and whether the redox environment participates in the protection process. We used 36 male Wistar rats divided into four groups: (1) euthyroid, (2) euthyroid+0.75% EG, (3) hypothyroid, and (4) hypothyroid+0.75% EG. Hypothyroidism occurred 2 weeks after thyroidectomy. The parathyroid gland was reimplanted. EG was administrated for 21 days in drinking water. On day 21, the renal function was assessed and then the rats were decapitated. The left kidney was processed for histology, and the right kidney was used to determine the redox environment, oxidative stress, and the testing of the antioxidant enzymatic system. EG in euthyroid rats reduced the hydric and electrolytic balance and it also caused oxidative stress and renal damage. Hypothyroidism per se modifies the renal function causing a low osmolal and potassium clearance and the filtered load of potassium and sodium. In addition, there was an enhanced redox state because hypothyroidism increases the reduced glutathione concentration caused by a high activity of γ-glutamylcysteine synthase. Hypothyroidism is a protective state against EG because the changes in the renal function were smaller than in the euthyroid state. The oxidative stress and cellular damage were ameliorated by the hypothyroid condition. Also, the hypothyroidism-enhanced redox environment protects against EG-induced oxidative stress, renal damage, and renal dysfunction.

Experimental research Strain of experimental animals and modulation of nitric oxide pathway: their influence on development of renal failure in an experimental model of hepatorenal syndrome

IntroductionPathomechanism of HRS is still poorly understood. The aim of our study was: (1) to test whether different strains of rats could develop typical HRS, and (2) to estimate the influence of activation and inhibition of nitric oxide for development of renal failure in course of HRS.Material and methodsFirst, we used 16 of Wistar and 16 of Sprague-Dawley rats in galactosamine model of HRS. Next, we used 48 of SDR rats, which received saline, N-nitro-L-arginine or L-arginine before and after liver damage. Twenty four hours urine and blood samples were collected 48 h after saline or Ga1N injection. Biochemical parameters were determined in serum or urine and then creatinine clearance and osmolality clearance were calculated. Liver and kidney tissues were collected for histopathological examination.ResultsLiver failure developed in all tested groups with significant increase of bilirubin (p < 0.001), ALT (p < 0.001) and ammonia (p < 0.001). Nevertheless we did not achieve any evidence of renal failure in Wistar, but we found typical renal failure in Sprague-Dawley group with significant decrease in creatinine clearance (p < 0.0012) and increase in concentration of creatinine and urea (p < 0.001) and (p < 0.001) respectively. Inhibition of NOS prevented development of renal failure with significant improvement of GFR both before (p < 0.0017) and after (p < 0.003) Ga1N injection. Injection of L-arginine after Ga1N injection did not caused significant improvement of GFR.ConclusionsOur study showed, that genetic factors might be responsible for development of renal failure in course of HRS and nitric oxide play important role in acute model of this syndrome.