Recurrent hypernatremia; a proposed mechanism in a patient with absence of thirst and abnormal excretion of water

A 7-year-old girl twice developed severe hypernatremia (serum sodium values up to 194 mEq/l) without obvious cause. The ability of her kidneys to conserve water was normal, and increasing her plasma osmolality stimulated an appropriate ADH response. Unable to excrete a water load, her kidneys continued to conserve water even with a serum sodium concentration of 133 mEq/l. She was never thirsty and did not ingest sufficient fluid by choice. Although there was no demonstrable anatomic lesion, we postulate a localized defect of her thirst center. This may have modified release of ADH and resulted in an inability to dilute the urine by interrupting a pathway that could exist from the thirst center to the supraoptic nuclei. A therapeutic regimen based on these studies has prevented further hypernatremia.     

Repair of neglected Achilles tendon ruptures with Marlex mesh

An 11-month-old female infant presented with mild fever, hypernatremia, microcephaly, and growth and developmental delay. No sign of thirst was noted in this infant even when the osmolality was over 318 mOsm/kg. Magnetic resonance imaging demonstrated a lobar type holoprosencephaly. Plasma osmolality levels returned to normal after forced hydration and administration of a vasopressin analogue. These findings suggested holoprosencephaly may be associated with a defect in the hypothalamic osmoreceptors that control thirst and vasopressin secretion.     

Plasma osmolality and brain water content in a rat glioma model

Little is known about how intravenous fluids influence peritumoral edema formation. This experiment was designed to determine, in a rat glioma model, whether changes in plasma osmolality alter water content, as assessed by specific gravity (SpGr), in normal and neoplastic cerebral tissue. Cells cultured from an ethylnitrosourea-induced rat glioma were stereotactically implanted into the right striatum of Fischer 344 rats. A tumor growth interval of 21 days was allowed. In a second experiment, rats underwent a 60-second cortical freeze injury followed by 24 hours' recovery. In both experiments, rats were assigned to one of three groups: hypotonic (100 ml/kg of 0.2 mol/L NaCl in H2O, intraperitoneally; resultant plasma osmolality approximately 268 mOsm/kg); isotonic (no treatment; plasma osmolality approximately 298 mOsm/kg); or hypertonic (10 ml/kg of 1.0 mol/L NaCl in H2O, intraperitoneally; plasma osmolality approximately 342 mOsm/kg). Thirty minutes after fluid injection, regional SpGr was determined using a kerosene-bromobenzene gradient. In subsets of rats, the tissue morphology and blood-brain barrier permeability of Evans blue dye were assessed. Tissue within the freeze lesion was stained by Evans blue dye with sharp demarcation. Evans blue dye did not stain gliomatous tissue, and central necrosis was not histologically evident. In isotonic rats, glioma SpGr was reduced (1.0411 +/- 0.0012 g/ml) relative to the contralateral striatum (1.0437 +/- 0.0008 g/ml; P < 0.001). Despite this, a strong linear relation was observed for SpGr and plasma osmolality in both neoplastic and normal tissue. Within the freeze lesion in isotonic rats, SpGr was severely reduced (1.0335 +/- 0.0008 g/ml; P < 0.0001) compared with contralateral frontal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)     

Resistance to vasopressin action on the kidney in patients with Cushing's disease

OBJECTIVE: To assess the plasma levels and action of arginine vasopressin (AVP) in patients with Cushing's disease. There are many reports that patients with Addison's disease have increased AVP levels associated with hyponatraemia and hypoosmolality, but none on the dynamics of secretion of this neurohormone during osmolality-based stimulation in patients with chronic hypercortisolism. DESIGN AND SUBJECTS: The plasma AVP concentration and the urinary and plasma osmolality after a 7.5-h water deprivation test (WDT) were evaluated in 13 patients with Cushing's disease and 15 normal (control) individuals. In patients with Cushing's disease we also assessed the urinary osmolality in response to 10 micrograms i.v. desmopressin (DDAVP) administered at the end of the WDT. RESULTS: At the end of the WDT, urinary osmolality was significantly lower in patients with Cushing's disease (511.5 +/- 148.5 mOsm/l) than in the normal subjects (981.1 +/- 107.1 mOsm/l, P < 0.001), whereas plasma osmolality did not differ between the two groups. Consequently, the urine/plasma osmolality ratio (Uosm/Posm) was lower in patients with Cushing's disease than in normal individuals (1.8 +/- 0.5 compared with 3.4 +/- 0.4, P < 0.001). The AVP concentration also was greater (7.3 +/- 3.1 pmol/l) in those with Cushing's disease than in the controls (3.9 +/- 2.3 pmol/l, P < 0.005). After administration of DDAVP to the hypercortisolaemic patients, the urinary osmolality attained (718.0 +/- 200.0 mOsm/l) was still lower than that in the normal group at the end of WDT (P < 0.005). CONCLUSIONS: Patients with Cushing's disease presented higher AVP levels and smaller Uosm/Posm ratios than normal subjects. After DDAVP, the patients with Cushing's disease were unable to concentrate the urine adequately. These data suggest that the kidney shows resistance to the action of both endogenous and exogenous AVP in patients with Cushing's disease.     

Evidence of a dominant role for low osmolality in the efficacy of cereal based oral rehydration solutions: studies in a model of secretory diarrhoea

Clinical trials suggest that including naturally occurring complex carbohydrate in oral rehydration solutions (ORS) in place of glucose increases water absorption and reduces stool volume during acute diarrhoea. The mechanisms for this greater clinical efficacy has not been established. This study examined the ability of two hypotonic rice based ORS, RS-ORS (137 mOsm/kg) and RP-ORS (143 mOsm/kg), and HYPO-ORS (240 mOsm/kg) a glucose equivalent ORS, to effect water absorption by in vivo perfusion of normal and secreting rat small intestine. The results were compared with those for two widely used conventional hypertonic ORS, WHO-ORS (331 mOsm/kg) and UK-ORS (310 mOsm/kg). In the normal intestine, water absorption was similar from WHO-ORS (87.4 (45.1-124.6) microliters/min/g; median and interquartile range) and UK-ORS (57.6 (41.5-87)) but less than from the hypotonic solutions (p < 0.02); water absorption from RS-ORS (181.8 (168.5-193.8)) and RP-ORS (195.7 (179.3-207.9)) was similar but less than from HYPO-ORS (241.3 (230.6-279.7); p < 0.005). In the secreting intestine, all ORS reversed net secretion of fluid to net absorption; the hypotonic solutions, HYPO-ORS (105.2 (95.2-111)), RS-ORS (127.7 (118.3-169.4)) and RP-ORS (133.7 (122.1-174.5)), produced more water absorption (p < 0.005) than the hypertonic solutions WHO-ORS (47.1 (29-75.9)) and UK-ORS (24.9 (18.4-29.4)). The rice based ions promoted most water absorption in secreting intestine (p < 0.007). These data indicate that low osmolality is of primary importance in mediating the increased water absorption from cereal based ORS.     

Responses of reindeer to water loading, water restriction and ADH

Two female reindeer were hydrated by administration of (10% of b.wt.) water into the rumen. The diuretic response was very fast and strong but the urea and electrolyte excretion were little affected. Dehydration was carried out by not giving the reindeer water for 48 h. This water deprivation caused a loss of up to 20% of their body weight. The urine osmolality did not exceed 840 mosm/kg H2O, although the plasma osmolality rose from 300 to 346 and 368 mosm/kg H2O respectively. The plasma and urine urea concentrations were elevated during dehydration, while the urine urea excretion did not increase. Urine sodium concentration did not increase. When the urine flow rate, after two days of water deprivation, decreased to half of the original, the urine Na+ concentrations, instead of increasing, went down to half of the original. So did the potassium excretion. When ADH was injected intravenously into hydrated animals a dose of 30 mU of ADH was needed to induce antidiuresis or increased excretion of potassium. The resistance to ADH and the low relative thickness of the medulla confirm the limited capacity of reindeer kidney to concentrate urine or to excrete a solute load. On the other hand, reindeer is able rapidly to excrete surplus water without affecting the electrolyte or nitrogen balance.     

Contribution of luminal concentration of nutrients and osmolality to postprandial intestinal hyperemia in dogs

Intestinal blood flow is increased during digestion. This study assesses if the concentration of nutrients and/or osmolality of chyme in the intestinal lumen are factors determining the hyperemia. Six digested food mixtures containing different concentrations of nutrients and/or having different osmolalities were placed into the jejunal lumen, and their effects on local venous outflow compared. The 100% (999 mOsm/kg), 33% (291 mOsm/kg), and 20% (183 mOsm/kg) food mixtures all increased flow, but the 10% food mixture (94 mOsm/kg) did not. The hyperemic effect of 33 and 20% food was similar, but 100% food produced a greater increase in flow than did 33 or 20% food. Luminal placement of a 30% solution of a nonabsorbable substance polyethylene glycol (1000 mOsm/kg) did not alter flow. Also, the vascular effects of 20 or 10% food mixtures were not altered when these mixtures were made isotonic by the addition of NaCl. These studies indicate that lumen osmolality, within a range of 180 to 1000 mOsm/kg, is not a significant factor contributing to the local hyperemia occurring when nutrients are in the gut lumen. However, the concentration of nutrients in the lumen is a factor determining the local hyperemia.     

Water balance in elderly people: is there a deficiency of vasopressin?

Since elderly people are prone to develop both hypo- and hyper-natraemia, we have investigated the biochemical and hormonal responses to overnight (9 h) abstinence from fluids and subsequent oral water load (20 ml/kg) in a group of healthy elderly (E) (mean age 68 years) and young (Y) (mean age 28 years) volunteers. The elderly subjects had significantly higher baseline plasma osmolality (E 293.5 +/- 0.5, Y 290.5 +/- 0.8 mOsm/kg, p < 0.05) but lower urinary osmolality (E 508 +/- 47, Y 842 +/- 52 mOsm/kg, p < 0.001) and lower plasma vasopressin (E 0.5 +/- 0.1, Y 2.3 +/- 0.6 pmol/l, p < 0.001) than the young. There was a significant difference in the mode of excretion, particularly maximum free water clearance (E 6.0 +/- 0.6, Y 10.1 +/- 0.8 ml/min) but no difference in the overall ability to excrete the water load (at 4 h E 93 +/- 8%, Y 92 +/- 5%, p > 0.05). The biochemical and hormonal results suggest that the elderly subjects were in a state similar to partial cranial diabetes insipidus which may predispose them to dehydration and hypernatraemia. The reduction in maximum free water clearance may predispose them to hyponatraemia if excess fluid is administered.     

Histamine H3 receptors contribute to drinking elicited by eating in rats

A role for endogenous histamine and its H3 receptor subtype for mediating drinking elicited by eating was examined in adult male Sprague-Dawley rats. The i.p. injection of the H3 agonist R-alpha-methylhistamine (Ramh, 2.5 mg/kg) shortened the latency to initiate drinking and increased 1-h water intake in nondeprived rats freely eating pellets and drinking water. The ICV injection (through a surgically implanted chronic cannula) of 10 micrograms Ramh increased water intake; this Ramh-induced drinking was abolished by previous ICV injection of the H3 antagonist thioperamide (Th, 60 micrograms). For rats drinking and eating after 24-h food deprivation, s.c. Th inhibited drinking behavior: for example, 10 mg/kg Th s.c. delayed the latency to initiate drinking and inhibited 1-h water intake without inhibition of food intake. In contrast, 60 micrograms Th ICV failed to inhibit food-related drinking in rats eating after food deprivation. For nondeprived rats eating a small cracker, 10 mg/kg Th s.c. delayed the latency to initiate drinking and abolished water intake without effect of eating, and 60 micrograms Th ICV had similar effects upon drinking elicited by ingestion of cracker. The IG infusion (through a surgically implanted gastric catheter) of 2 ml 600 or 900 mOsm/kg NaCl, a treatment that is subthreshold for increase in systemic plasma osmolality at the initiation of drinking, elicited drinking that was abolished by 10 mg/kg Th s.c. and attenuated by 60 micrograms Th ICV. The IG infusion of 2 ml 1800 mOsm/kg NaCl, a treatment that is above threshold for increase in systemic plasma osmolality, elicited drinking that was attenuated by 10 mg/kg s.c. or 60 micrograms Th ICV. These results demonstrate that peripheral and central H3 receptors for histamine have a role in drinking elicited by eating and the postprandial gastrointestinal osmotic consequences of eating. These findings extend the evidence demonstrating a histaminergic contribution to food-related drinking in rats.     

Urinary indices in llamas fed different diets

Indices of renal function and damage were measured in 12 healthy male adult llamas fed a diet of mixed alfalfa/grass hay (mixed hay) and water ad libitum. Using a collection bag fitted over the preputial area, urine samples were collected at 6, 12, and 24 hours. Serum samples were obtained concurrently to determine endogenous creatinine clearance (CL), total (TE) and fractional excretion (FE) of electrolytes (Na, K, Cl, P), electrolyte CL, urine and serum osmolality, urine enzyme activities (gamma-glutamyltransferase and N-acetyl-beta-D-glucosaminidase), and urine protein concentration. Urine production was quantified. Three months later, 10 of the 12 llamas were fed a grass hay diet and water ad libitum. Similar samples were obtained, and similar measurements were made. Urine production was higher when the llamas were fed the mixed hay diet. Total urine volume for llamas fed mixed hay ranged from 628 to 1,760 ml/24 h, with a median of 1,307.5 ml/24h, compared with a range of 620 to 1,380 ml/24 h and a median of 927.50 ml/24h for llamas fed grass hay. Median urine osmolality was higher in llamas fed mixed hay (1,906 mOsm/kg of body weight, with a range of 1,237 to 2,529 mOsm/kg), compared with llamas fed grass hay (1,666 mOsm/kg with a range of 1,163 to 2,044 mOsm/kg). Creatinine CL did not vary significantly over time for either diet.(ABSTRACT TRUNCATED AT 250 WORDS)     

Extracellular dextran-induced p-nitrophenyl-alpha-D-glucoside-hydrolyzing enzyme of Bacillus circulans KA-304: a producer of Schizophyllum commune-lytic enzyme

We previously reported that centrally administered neuropeptide FF (NPFF) inhibited arginine vasopressin (AVP) release. In this study, immunoneutralization of central NPFF was performed to evaluate the role of endogenous NPFF in the regulation of AVP release. Intracerebroventricular (ICV) injection of antiserum against NPFF (Anti-NPFF) significantly augmented the plasma AVP increase induced by hyperosmolality [intraperitoneal injection of hypertonic saline (600 mOsm/kg, 2% BW)] at 60 min after ICV injection compared with normal rabbit serum (NRS) (NRS: 4.20+/-0.30 pg/ml, Anti-NPFF: 5.83+/-0.46 pg/ml, p < 0.01). Anti-NPFF did not cause significant change in plasma osmolality, plasma volume or arterial blood pressure. This evidence indicates that endogenous NPFF might be physiologically involved in osmoregulation of the plasma AVP level through its inhibitory action.     

Concentrations of antidiuretic hormone in plasma during human sodium restriction

Negative sodium balance was produced in 10 human volunteers. Body weight, plasma sodium, osmolality, hematocrit, renin activity (PRA), and antidiuretic hormone (ADH) concentrations were determined before, during, and after sodium restriction. Body weight declined and PRA rose during the period of low sodium intake. Plasma sodium concentration and osmolality did not change. A statistically significant change in ADH was not observed. It is suggested that a decrease in ADH was prevented by a rising titer of renin and contraction of the extracellular space.     

Osmoregulation of the Atlantic stingray (Dasyatis sabina) from the freshwater Lake Jesup of the St. Johns River, Florida

The goals of this study were to (1) measure plasma osmolytes and rectal gland weights of a freshwater (FW) Atlantic stingray (Dasyatis sabina) population in the St. Johns River, Florida, and (2) determine how these parameters change after acclimation to seawater (SW). We hypothesized that the FW D. sabina may show physiological divergence from marine D. sabina, because the FW individuals reproduce and complete their life cycle in the St. Johns River. The FW D. sabina hyperregulate their plasma osmolality (621.4 mOsm kg(-1)), with plasma Na+, Cl-, and urea concentrations of 211.9, 207.8, and 195.9 mmol L(-1), respectively. FW D. sabina were exposed to 100% SW for 8 d, and their hematocrit did not change significantly compared to control animals left in FW. However, plasma osmolality increased significantly (953 mOsm kg(-1)), with significant increases in plasma concentrations of Na+, Cl-, and urea to 319.13, 296.1, and 329.76 mmol L(-1), respectively. The plasma of the SW-adapted D. sabina was hypo-osmotic and hypoionic to 100% SW. Rectal gland weight to body weight (RGBW) ratios of FW D. sabina were about 80% lower than RGBW ratios reported for marine D. sabina; the RGBW ratio did not increase significantly after SW acclimation. This may indicate that branchial and renal mechanisms are also involved with ion excretion. We conclude that the FW D. sabina are physiologically euryhaline and have not evolved the osmoregulatory strategy of stenohaline FW Potamotrygonid stingrays.     

Effects of an isotonic oral rehydration solution, enriched with glutamine, on fluid and sodium absorption in patients with a short-bowel

AIM: To compare the effects of a standard oral rehydration solution with a polymeric glucose isotonic solution enriched with glutamine on water and sodium absorption in the short bowel. METHODS: Six patients with high jejunostomy were tested in a random order on 2 consecutive days with the standard solution (20 g/L glucose, 94 mmol/L sodium, 292 mOsm/kg osmolality) and a solution containing maltodextrins (18 g/L Glucidex 12; hydrolysis of 18 g of Glucidex 12 yields 20 g glucose) enriched with 14.6 g/L of glutamine (94 mmol/L sodium, 282 mOsm/kg osmolality). Solutions were administered via a naso-gastric tube at a rate of 2 mL/min. Jejunal effluent for each solution was collected during an 8-h period, after a 14-h equilibrium period. RESULTS: The net 8-h fluid absorption was not significantly different between the standard solution and the solution with glutamine (333 +/- 195 and 213 +/- 251 mL, respectively (mean +/- S.E.M.)). Net sodium absorption was higher for the standard solution than for the solution with glutamine (15 +/- 15 vs. 2 +/- 20 mmol, P < 0.05). The rate of glucose absorption was not different between the solutions. CONCLUSION: The replacement of glucose by maltodextrins and the addition of glutamine to the standard oral rehydration solution, without changing its sodium content or osmolality, results in a reduction of sodium absorption in the short-bowel syndrome.     

Effects of various ambient temperatures and of heating and cooling the hypothalamus and cervical spinal cord on antidiuretic hormone secretion and urinary osmolality in pigs

1. Plasma ADH concentration, urinary and plasma osmolality and haematocrit were measured in young pigs placed in cold, thermoneutral, warm and hot ambient temperatures. In some experiments a thermode placed in the hypothalamus or over the cervical spinal cord was heated or cooled at various ambient temperatures. 2. Plasma ADH concentration remained at a low level (0-5--5 muu. ml.-1) over 2 hr or 3 hr periods when the pigs were in cold, thermoneutral or warm ambient temperatures. A hot environment, which caused a marked rise in the pigs' rectal temperature, was associated with a large rise in plasma ADH level. 3. The rise in plasma ADH level which occurred during an increase in body temperature was consistently and completely suppressed by simultaneous cooling of the thermode in the pre-optic region to 5 to 10 degrees C. When the thermode was in the region of the supraoptic nucleus the rise in ADH was only partly suppressed, and when it was over the cervical cord it was only sometimes suppressed. 4. Cooling the thermodes in any position at a cold or thermoneutral ambient temperature, or heating them at a thermoneutral or warm ambient temperature, caused no consistent change in ADH. 5. A diuresis, with a urinary flow-rate of at most 1 ml. min-1 and minimal urinary osmolality of 53 m-osmole kg-1, was observed on only three occasions, twice during cooling of a thermode in the hypothalamus and once after the end of a period when the thermode was heated. In each case, the plasma ADH was less than 2 muu. ml.-1. 6. A slight rise of haematocrit in cold ambient conditions and a slight fall in the warm were observed. Otherwise changes in haematocrit were trivial, and a shift of water between vascular system and interstitium could not be invoked to account for changes in ADH levels. Observed variation of plasma osmolality was also slight.     

In vivo regulation of MAP kinases in Ratus norvegicus renal papilla by water loading and restriction

In cultured renal cells, hypertonicity activates multiple mitogen-activated protein kinases (MAPKs) and enhances the expression of heat shock proteins (HSPs). In rats, 24 h water restriction increased mean urinary osmolality (Uosm) from 2, 179+/-153 mOsm/kg to 2,944+/-294 mOsm/kg (P < 0.001) and was associated with significant (P < 0.05) increases in the papillary activity of c-Jun NH2-terminal protein kinase (JNK) by 22%, extracellular signal-regulated protein kinase (ERK) by 49%, and p38 MAPK by 15%. Conversely, 24 h of water-loading (Uosm 473+/-33 mOsm/kg) caused suppression of JNK activity by 43% (P < 0.001), ERK by 39% (P < 0.05), and p38 MAPK by 26% (P < 0.05). No such modulation was observed in the isotonic cortex. c-Jun phosphorylation was decreased in papilla from water-loaded rats by 45% versus controls. Expression of Hsp 110, inducible Hsp 70, and Hsp 25 was greater in the hyperosmotic papilla than the isosmotic cortex but was not affected by the animal's hydration state. In cultured inner medullary collecting duct cells, HSP expression was maximal at 500 mOsm/kg, while activation of JNK continued to increase. We conclude that under basal conditions of hydration, these HSPs are maximally expressed in the hypertonic inner medulla, while the activation of all three members of the MAPK family approaches but is not maximal.     

Pathophysiology of dehydration

The pathophysiology of dehydration is reviewed. The normal response to dehydration, i.e. decreased effective arterial blood volume or effective circulating volume is described. Due to water retention and drinking following stimulation of ADH secretion and thirst, osmoregulation is overruled by volume conservatory mechanisms, which lead to hyponatremia. Only patients with impaired mental function or those who are unable to drink will develop a progressive water deficit--with or without salt depletion--recognizable by hypernatremia. Decreased effective arterial blood volume and hypernatremia affect cerebral function in a way that perception of external stimuli as well as perception of pain will be impaired. Alert dehydrated patients are disturbed mainly by thirst and dryness of the mouth. Both symptoms are perceived more intensely by young than by elderly persons. Dryness of the mouth increase thirst on its own. Distress by thirst and oral dryness increases as a function of the level and the rapidity of developing hypernatremia. The simple act of filling the oral cavity with fluid and swallowing alleviates thirst in the absence of any change in plasma sodium concentration. Thirst quenching efficacy is increased by administering chilled hypotonic fluid with lemon or other fruit acid added (for stimulation of salivation).     

Antidiuretic hormone and the distribution of renal cortical blood flow

The radioactive microsphere method was used to study the distribution of cortical blood flow in anesthetized dogs during water diuresis and during antidiuresis. Infusion of antidiuretic hormone (ADH) at rates ranging from 0.33 to 0.5 mU/kg-min into dogs previously volume expanded with 3% dextrose resulted in an increase in urinary osmolality and a significant increase in fractional flow in the inner cortex. Mean arterial pressure, glomerular filtration rate, and renal plasma flow were unaltered by the infusion of ADH at these doses, suggesting that absolute, as well as fractional, blood flow to the inner cortex increased in response to ADH. In three additional experiments, termination of an infusion of ADH in hydropenic dogs and subsequent induction of water diuresis was accompanied by a shift in fractional cortical blood flow away from the inner cortex. The redistribution of cortical blood flow in response to ADH at a time when the kidney is producing a more concentrated urine supports the hypothesis that this vascular effect of ADH may have functional significance in the urinary concentration ability of the kidney.     

Exaggerated urinary excretion of aquaporin-2 in the pathological state of impaired water excretion dependent upon arginine vasopressin

The present study was undertaken to determine whether urinary excretion of aquaporin-2 (UAQP-2) is of value to diagnose the pathological state of water retention and hyponatremia. UAQP-2 under ad libitum water drinking was 429 fmol/mg creatinine in the patients with water retention, a value significantly greater than that of 153 fmol/mg creatinine in the normal subjects. An acute oral water load test (20 mL/kg BW) was performed in 7 normal subjects (22-25 yr old) and 10 patients with water retention and hyponatremia (55-75 yr old). The percent excretion of the water load was only 30% in the patient group compared with 70% in the control group (P < 0.01). In the control group, minimal urinary osmolality was as low as 131 mosmol/kg H2O, which was responsible for the decrease in plasma arginine vasopressin (AVP) levels after the reduction in plasma osmolality. In the patient group, minimal urinary osmolality was 320 mosmol/kg H2O, and free water clearance remained below 0.6 mL/min after the water load. This impaired water excretion was consistent with the nonsuppressible levels of plasma AVP despite hypoosmolality. The nadir of UAQP-2 was obtained at 60-90 min. The minimal UAQP-2 was reduced to 284 fmol/mg creatinine, a value significantly greater than that of 76 fmol/mg creatinine in the control group. Similar results were obtained in the 6 patients with hypopituitarism, who had impaired water excretion and marked hyponatremia. Water excretion was totally normalized after the replacement of hydrocortisone (excretion of water load, 31% vs. 102%; P < 0.01). Hydrocortisone replacement also significantly reduced the minimal UAQP-2 from 225 to 49 fmol/mg creatinine after the acute oral water load, a value comparable to that in the control subjects. These results indicate that UAQP-2 is a potent marker to diagnose the pathological state of impaired water excretion and hyponatremia, dependent upon AVP, in patients with water retention and hypopituitarism.     

Inorganic fluoride nephrotoxicity: prolonged enflurane and halothane anesthesia in volunteers

The effects of prolonged enflurane and halothane administration on urine-concentrating ability were determined in volunteers by examining their responses to vasopressin before anesthesia and on days 1 and 5 after anesthesia. A significant decrease in maximum urinary osmolality of 264 +/- 34 mOsm/kg (26 per cent of the preanesthetic value) was present on day 1 after enflurane anesthesia, whereas subjects anesthetized with halothane had a significant increase in maximum urinary osmolality of 120 +/- 44 mOsm/kg. Serum inorganic fluoride level peaked at 33.6 muM and remained above 20 muM for approximately 18 hours. Thus, the threshold level for inorganic fluoride nephrotoxicity is lower than previously suspected.