Osmolality In Patients Research Articles

Prospective Study on Individualized Dose Adjustment of Tolvaptan Based on Urinary Osmolality in Patients With ADPKD

IntroductionTolvaptan has been shown to reduce renal volume and delay disease progression in autosomal-dominant polycystic kidney disease (ADPKD). However, no biomarkers are currently available to guide dose adjustment. We aimed to explore the possibility of individualized tolvaptan dose adjustments based on cut-off values for urinary osmolality (OsmU). MethodsThis prospective cohort study included patients with ADPKD, with rapid disease progression. Tolvaptan treatment was initiated at a dose of 45/15 mg and increased based on OsmU, with a limit set at 200 mOsm/kg. Primary renal events (25% decrease in estimated glomerular filtration rate (eGFR) during treatment), within-patient eGRF slope and side effects were monitored during the 3-year follow-up. ResultsForty patients participated. OsmU remained below 200 mOsm/kg throughout the study period, and most patients required the minimum tolvaptan dose [mean dose, 64 (± 10) mg], with a low discontinuation rate (5%). The mean annual decline in eGFR was -3.05 (± 2.41) mL/min/1.73 m2 during tolvaptan treatment, compared with the period preceding treatment, corresponding to a reduction in eGFR decline of more than 50%. Primary renal events occurred in 20% of patients [mean time to onset, 31 months; 95% confidence interval (CI) = 28; 34]. ConclusionIndividualized tolvaptan dose adjustment based on OsmU in patients with ADPKD and rapid disease progression provided benefits in terms of reducing eGFR decline, compared with reference studies, and displayed lower dropout rates and fewer side effects. Further studies are required to confirm optimal strategies for the use of OsmU for tolvaptan dose adjustment in patients with ADPKD.

Comparison of measuring serum osmolality and equations estimating osmolality in peritoneal dialysis patients.

The osmolar gap increases with kidney failure. A number of equations have been proposed to calculate serum osmolality, allowing determination of the osmolar gap by comparison with measured osmolality. As glucose and icodextrin absorption can potentially interfere with the laboratory measurement of serum sodium, a key component in equations calculating osmolality, we reviewed the performance of 14 equations used to calculate serum osmolality compared to the measurement of serum osmolality in 144 patients with peritoneal dialysis (PD); 81 (56.3%) males, 76 (52.5%) diabetics, mean age of 64.4 ± 16.3 years, 115 (79.9%) prescribed icodextrin and 38 (26.4%) 22.7 g/L glucose dialysates. Measured serum osmolality was 311 (304-320) mosmo/kg (mmol/kg), whereas calculated osmolality for the 14 equations ranged from a median of 274 (269-284) mosmo/kg to 307 (300-316) mosmo/kg. Bland-Altman mean bias showed that measured serum osmolality was greater than the calculated osmolality ranging from 4.0 mosmo/kg to 36.2 mosmo/kg between the 14 equations, with wide 95% limits of agreement (LoA) ranging from -27.1 mosmo/kg to 19.4 mosmo/kg and from -58.5 mosmo/kg to -13.8 mosmo/kg. Only 2 of the 14 equations gave a mean osmolar gap of <10 mosmo/kg and showed no systematic bias, median serum osmolality of 307 (300-316) and 303 (298-312) mosmo/kg, Spearman ρ of 0.57, 0.62, both p < 0.001, respectively. Our study would suggest that only 2 of the 14 equations we compared with measured serum osmolality showed no systematic bias, but still had too great a bias to be useful in clinical practice. As such we propose a new equation to calculate serum osmolality in patients with PD.

Clinical characteristics of non-alcoholic fatty liver disease in Chinese adult hypopituitary patients.

BACKGROUNDPatients with hypothalamic-pituitary disease have the feature of central obesity, insulin resistance, and dyslipidemia, and there is increased prevalence of liver dysfunction consistent with non-alcoholic fatty liver disease (NAFLD) in this population. The causes of hypopituitarism in the reported studies varied and combined pituitary hormone deficiency including central diabetes insipidus is much common in this population. This retrospective cross-sectional study was performed to analyze the clinical characteristics and related factors with NAFLD and cirrhosis in Chinese adult hypopituitary/panhypopituitary patients.AIMTo analyze the clinical characteristics of and related risk factors for NAFLD in Chinese adult hypopituitary patients.METHODSAdult Chinese patients with hypopituitarism and/or panhypopituitarism were enrolled at the Pituitary Center of Peking Union Medical College Hospital between August 2012 and April 2018. According to abdominal ultrasonography, these patients were divided into an NAFLD (-) group and an NAFLD (+) group, and the latter was further divided into an NAFLD group and a cirrhotic group. The data, such as patient characteristics, diagnosis, and treatment, were extracted from medical records, and statistical analysis was performed.RESULTSA total of 36 male and 14 female adult Chinese patients with hypopituitarism were included in this retrospective study; 43 (87.0%) of these patients exhibited growth hormone (GH) deficiency, and 39 (78.3%) had diabetes insipidus. A total of 27 (54.0%) patients were diagnosed with NAFLD, while seven patients were cirrhotic. No significant differences were noted in serum GH or insulin-like growth factor 1 among patients with cirrhosis, subjects with NAFLD, and those without NAFLD. However, plasma osmolality and serum sodium concentration of the cirrhotic patients were 314.9 mOsm/kgH2O and 151.0 mmol/L, respectively, which were significantly higher than those of the NAFLD patients (P = 0.036 and 0.042, respectively). Overweight/obesity and insulin resistance were common metabolic disorders in this population. The body mass index (BMI) and homeostasis model assessment of insulin resistance parameters of the cirrhotic patients were 27.7 kg/m2 and 9.57, respectively, which were significantly higher than those of the patients without NAFLD (P = 0.011 and 0.044, respectively). A correlation analysis was performed, and fasting insulin concentration was positively associated with plasma osmolality in patients with NAFLD, after adjusting for gender, age, and BMI (r = 0.540, P = 0.046), but no correlation was noted in patients without NAFLD.CONCLUSIONNAFLD is common in patients with hypopituitarism. Plasma osmolality and serum sodium levels of hypopituitary patients with cirrhosis are higher than those of subjects with NAFLD, and fasting insulin concentration is positively associated with plasma osmolality in patients with NAFLD, which suggests that hyperosmolality might be a contributor to the worsening of NAFLD in hypopituitary patients.

Perbedaan pemberian cairan isotonis dan hipotonis terhadap osmolalitas plasma pada penderita gangguan intrakranial akut di RSUP Sanglah, Denpasar, Bali

Background: Acute intracranial disturbance can lead to increased occurrence of cardiovascular activity that will lead to a decrease of sodium reabsorption in the kidney. The proper selection of liquid on acute intracranial disorders can help reduce damage to brain tissue. This study aims to determine differences in plasma osmolality levels in patients with acute intracranial disorders who get isotonic or hypotonic fluid.Methods: A cross-sectional observational study was carried out among 60 patients aged 1 month-12 years who experienced acute intracranial disturbance in Sanglah General Hospital during 2017. The difference in plasma osmolality in each group was tested using Mann-Whitney due to the data were not normally distributed. There was a significant difference in osmolality levels in the group receiving isotonic fluid compared with hypotonic (p &lt;0.001)Results: Males were predominant in the isotonic group (66.7%) and hypotonic (70%). Good nutritional status was found in both groups (90%; 83.33%). Encephalitis is the most common cause of acute intracranial disturbance, namely 14 (46.67%) cases of istononic groups and 12 (40%) cases of hypotonic groups. The median value (IQR) of plasma and sodium osmolality levels that obtained isotonic fluid showed a difference in values of 139(6) mEq/L and 287(20) mOsm/kg H2O in isotonic and 132 (7) mEq/ L and 273(16) mOsm/kg H2O in hypotonic. There was a significant difference in osmolality levels in the group receiving isotonic fluid compared to hypotonic (p&lt;0.001)Conclusion: There are differences in levels of osmolality in patients with acute intracranial disorders who get isotonic fluid compared to groups that get hypotonic fluid.

Serum Osmolality and Postdischarge Outcomes After Hospitalization for Heart Failure

Serum osmolality may fluctuate with neurohormonal activation and in response to certain therapeutics in patients with heart failure (HF). The clinical relevance of osmolality in patients with HF has not been defined. In this post hoc analysis of the Efficacy of Vasopressin Antagonism in Heart Failure: Outcome Study with Tolvaptan trial, we analyzed serum osmolality measured at discharge in 3,744 patients hospitalized for HF and reduced ejection fraction (EF ≤40%). Median follow-up was 9.9 months. The association between discharge osmolality and all-cause mortality (ACM) and composite cardiovascular mortality or HF hospitalization was nonlinear; and thus, patients were divided into low (≤284), normal (285 to 300), and high (≥300 mOsm/kg) osmolality. Median serum osmolality at discharge was 297 (290 to 304) mOsm/kg. Patients in the low osmolality group (n = 454,12.1%) were more likely to be younger, men, have lower rates of hypertension, coronary artery disease, chronic kidney disease, diabetes, and have lower serum sodium, creatinine, systolic blood pressure, and EF (all p <0.001). Low discharge osmolality was associated with higher ACM (low 29.3%; normal 23.6%; high 25.2%; p = 0.04) and the composite endpoint (low 45.6%; normal 39.3%; high 41.8%; p = 0.04). After risk adjustment, a 15 mOsm/kg decrease in osmolality was predictive of higher ACM (hazard ratio 1.61, 95% CI 1.19 to 2.17) and the composite endpoint (hazard ratio 1.37, 95% CI 1.06 to 1.75) in the low osmolality group. These associations were not seen in patients with normal or high osmolality. Interaction analyses for tolvaptan treatment were nonsignificant (p >0.4). In conclusion, low discharge serum osmolality was independently predictive of worse postdischarge mortality and readmission. Further study is required to clarify the clinical utility of serum osmolality in hospitalized patients with HF.

Urine and Plasma Osmolality in Patients with Autosomal Dominant Polycystic Kidney Disease: Reliable Indicators of Vasopressin Activity and Disease Prognosis?

Background: Vasopressin plays an essential role in osmoregulation, but has deleterious effects in patients with ADPKD. Increased water intake to suppress vasopressin activity has been suggested as a potential renoprotective strategy. This study investigated whether urine and plasma osmolality can be used as reflection of vasopressin activity in ADPKD patients. Methods: We measured urine and plasma osmolality, plasma copeptin concentration, total kidney volume (TKV, by MRI) and GFR (¹²⁵I-iothalamate). In addition, change in estimated GFR (eGFR) during follow-up was assessed. Results: Ninety-four patients with ADPKD were included (56 males, age 40 ± 10, mGFR 77 ± 32 ml/min/1.73 m², TKV 1.55 (0.99-2.40) l. Urine osmolality, plasma osmolality and copeptin concentration were 420 ± 195, 289 ± 7 mOsmol/l and 7.3 (3.2-14.6) pmol/l, respectively. Plasma osmolality was associated with copeptin concentration (R = 0.54, p < 0.001), whereas urine osmolality was not (p = 0.4). In addition, urine osmolality was not associated with TKV (p = 0.3), in contrast to plasma osmolality (R = 0.52, p < 0.001) and copeptin concentration (R = 0.61, p < 0.001). Fifty-five patients were followed for 2.8 ± 0.8 years. Baseline plasma and urine osmolality were not associated with change in eGFR (p = 0.6 and p = 0.3, respectively), whereas baseline copeptin concentration did show an association with change in eGFR, in a crude analysis (St. β = -0.41, p = 0.003) and also after adjustment for age, sex and TKV (St. β = -0.23, p = 0.05). Conclusions: These data suggest that neither urine nor plasma osmolality are valid measures to identify ADPKD patients that may benefit from increasing water intake. Copeptin appears a better alternative for this purpose.

Prognostic contribution of urine osmolality in patients presenting with acute heart failure

Renal function biomarkers are important for understanding and predicting the evolution of heart failure (HF). To that effect, clearance markers, including creatinine and cystatin-c, have long played important roles [1–3]. Alternate markers, such as urine protein and tubular damage markers, have recently been found to have prognostic implications, independent of the traditional markers of renal clearance [4–6]. Urine osmolality (uOsm) is accurately measured using the freezing point depression method and provides important information regarding the water–electrolyte balance and neurohormonal activation [7].

Effect of Thirst Challenge on ADH Levels in Patients with Bilateral Menière’s Disease

The aim of the study was to investigate plasma ADH levels and plasma/urine osmolality in patients suffering from bilateral Menière's disease since a disturbance in the water household after thirst challenge is a suspected pathogenic factor in the development of this disease. In this study the plasma ADH levels and plasma/urine osmolality of bilateral Menière's disease patients under thirst challenge were investigated to show whether the water balance is affected. 9 patients with bilateral Menière's disease and 9 healthy controls skipped water intake for 12 h. Plasma ADH, plasma/urine osmolality, and electrolytes were measured after this thirst period as well as 8 h later after food and fluid intake. During food and fluid intake the patients demonstrated a slightly higher plasma ADH level and plasma osmolality than controls, whereas at the end of the thirst period patients and the controls showed no significant change. Instead the urine osmolality differed significantly (p<0.001): showing a high urine osmolality in controls and an almost stable urine osmolality in patients after thirst challenge. This indicates that the water balance in patients is likely different from that of controls. These observations point to ADH and its target aquaporine 2 as keyplayers in the pathophysiological events leading to the development of Menière's disease.

EVALUATION OF HYDRATION STATUS OF PATIENTS WITH HYPERGLYCEMIA

B ackground : Acute hyperglycemia increases serum osmolality which leads to a rapid decline in serum sodium levels. Consequently, assessment of hydration status in individuals with hyperglycemia remains difficult. The goal of this study was to compare common equations that estimate osmolality to measured serum osmolality in patients hospitalized with hyperglycemia. Methods : In this cross-sectional study, data was collected from adult patients with serum glucose levels greater than 200 mg/dL. Serum osmolality was measured directly and compared to osmolality estimates using the Dorwart equation and the Rasouli equation. Sodium correction factors for hyperglycemia of 1.6 and 2.4 were also utilized for each equation, yielding six total equations. Patients greater than 18 years of age with measured serum osmolality ≥ 295 mOsm/L were included in the analysis. Regression analysis was performed in order to determine the best equation to predict hydration status of patients with hyperglycemia. Results : A total of 195 hospitalized adults with hyperglycemia were evaluated for inclusion in the study. Twelve of 195 hyperglycemic patients had normal hydration (serum osmolality 280-294 mOsm/L), and thus were excluded from the analysis. Among the equations utilized, the Rasouli equation utilizing a sodium correction factor of 2.4 was the most accurate predictor of dehydration, correctly identifying 94% of those patients. Conclusions : The two commonly used equations to estimate osmolality consistently underestimated the actual measured osmolality level of patients with hyperglycemia. The Rasouli equation utilizing a sodium correction factor of 2.4 was the most accurate equation for predicting measured osmolality; however, it still tended to underestimate osmolality. In order to determine the hydration status of patients with hyperglycemia rapidly, we recommend direct measurement of serum osmolality.

Osmolal Gap in Hemodialyzed Uremic Patients

Osmolality is an expression of the number of particles in a given weight of solvent (mOsm). Measured osmolality is determined by the osmometer, and calculated osmolality is estimated by 2xNa + UN/2.8 + glucose/18. The difference between measured and calculated osmolality is the osmolal gap. The purpose of the present study is to determine the measured and the calculated osmolality and the osmolal gap in hemodialyzed uremic patients, pre- and post-hemodialysis (HD). In 24 uremic patients under regular HD, blood samples pre- and post-HD were collected, and serum osmolality measured (osmometer) and calculated (2xNa + UN/2.8 + glucose/18) and the osmolal gap (measured-calculated osmolality) were determined. Also, the same parameters were determined in 22 healthy subjects (control). According to our findings, the measured osmolality in patients is significantly higher pre- and post-HD in comparison to that of controls, but post-HD is significantly lower than pre-HD. Also, calculated osmolality is significantly higher pre- and post-HD in comparison to that of controls, but the value post-HD is significantly lower than the pre-HD. The osmolal gap of patients pre-HD (11 ± 2.08) and post-HD (7.29 ± 1.94) is significantly higher (P < 0.001) in comparison to that of controls (3.18 ± 1.46); also, the value post-HD is significantly decreased in comparison to the value pre-HD (P < 0.001). Uremic hemodialyzed patients present high measured and calculated osmolality pre-HD that remains high post-HD in comparison to that of controls in spite of the significant decrease post-HD in comparison to that of pre-HD. Also, the osmolal gap is high pre-HD and, in spite of the decrease, remains high post-HD. In comparison to that of controls, the high osmolal gap indirectly indicates the presence of unidentified endogenous osmoles in the serum of uremic patients which partly are removed during HD.

Normoalbuminuric Type 1 Diabetic Patients with Retinopathy Have an Impaired Tubular Response to Desmopressin: Its Relationship with Plasma Endothelin-1

The aim of the study was to evaluate whether normoalbuminuric type 1 diabetic patients with diabetic retinopathy (DR) have an impaired tubular response to desmopressin (dDAVP, a synthetic analog of vasopressin) administration, and its relationship with plasma and urine endothelin-1 (ET-1) levels. This was an interventional case-control study. The study was conducted at a referral center. Fifteen normoalbuminuric type 1 diabetic patients with DR were compared with 30 normoalbuminuric type 1 diabetic patients without DR. Both groups were matched by age, gender, body mass index, glycosylated hemoglobin, and the main laboratory markers of kidney function. After a 12-h period of water deprivation, dDAVP (0.3 microg/kg) was infused over 20 min. Urine was collected at baseline and 1, 2, and 3 h after dDAVP administration. ET-1 was assessed by ELISA. dDAVP induced a lower rise in urine osmolality in patients with DR (from 650 +/- 206 to 754 +/- 224 mosmol/kg; P = 0.02) than in diabetic patients without DR (from 714 +/- 194 to 905 +/- 163 mosmol/kg; P < 0.0001). In addition, fractional excretion of Na+ decreased in patients without DR (from 0.45 +/- 0.30 to 0.29 +/- 0.29%; P = 0.04) but not in the diabetic patients with DR (from 0.36 +/- 0.22 to 0.36 +/- 0.40%; P = 0.96). Plasma ET-1 levels were inversely correlated with the response of urinary osmolality after dDAVP administration (r = -0.62; P = 0.008). Normoalbuminuric type 1 diabetic patients with DR have impaired renal response to dDAVP that is related to plasma ET-1 levels. Further studies are required to elucidate whether this tubular resistance to dDAVP might favor dehydration in these patients.

Antidiuretic Hormone and Osmolality in Patients with Ménière’s Disease

Plasma antidiuretic hormone (p-ADH) and plasma osmolality (p-Osm) levels were studied in patients with Ménière’s disease. In 147 cases, the p-ADH levels were measured during remission and in the acute phase of the disease. In 100 of 147 cases, the p-Osm levels were determined both in remission and in the acute phase. In remission, the p-ADH and p-Osm levels were higher than the normal limits. In the acute phase, the p-ADH level was higher than that in remission, consistent with previous reports. Moreover, the p-Osm level was unchanged. Although the p-ADH level is regulated by that of p-Osm, the kidney must show an escape phenomenon from antidiuresis. Besides, other factors must increase the amount of p-ADH. Further study is needed to reveal the cause of the rise in p-ADH and p-Osm levels.

Vasopressin administration facilitates fluid removal during hemodialysis

Inadequate secretion of vasopressin during fluid removal by hemodialysis may contribute to the cardiovascular instability that complicates this therapy and administration of exogenous hormone, by supporting arterial pressure, may facilitate volume removal. To test this, we measured plasma vasopressin in patients with end-stage renal disease (ESRD) during hemodialysis and found that despite significant fluid removal, plasma vasopressin concentration did not increase. We further found that ESRD did not alter the endogenous removal rate of plasma vasopressin and that plasma hormone is not dialyzed. Finally, in a randomized, double-blinded, placebo-controlled trial in 22 hypertensive patients, we examined the effect of a constant infusion of a non-pressor dose of vasopressin on the arterial pressure response during a hemodialysis in which the target fluid loss was increased by 0.5 kg over the baseline prescription. We found that arterial pressure was more stable in the patients receiving vasopressin and that while only one patient (9%) in the vasopressin group had a symptomatic hypotensive episode, 64% of the patients receiving placebo had such an episode (P=0.024). Moreover, increased fluid removal was achieved only in the vasopressin group (520+/-90 ml vs 64+/-130 ml, P=0.01). Thus, administration of non-pressor doses of vasopressin to hypertensive subjects improves cardiovascular stability during hemodialysis and allows increased removal of excess extracellular fluid. Inadequate vasopressin secretion during hemodialysis-induced fluid removal is a likely contributor to the intradialytic hypotension that limits fluid removal.

Effect of Carbamazepine on Urinary Volume and Osmolality, Water Clearance, and Serum Osmolality in Patients with Primary Enuresis

ObjectiveIn this study we investigate the effects of carbamazepine (CBZ) on urinary volume, frequency of micturition, serum and urine osmolality, osmotic and creatinine clearance, and free water clearance in patients with primary nocturnal enuresis. This information might help in our understanding of the mechanism of action of CBZ in management of patients with enuresis. Patients and methodsThe study comprised eight patients with primary enuresis (age range, 8–14 yr) who wet at night on a daily basis. Enuretics were given, CBZ 200mg each night; urine volume, urinary osmolality and electrolytes, serum osmolality and electrolytes, osmotic clearance, fractional excretion of sodium, and free water clearance were assayed before CBZ treatment and after 15 d of treatment. Frequencies of bed-wetting and dry nights were observed during treatment. ResultsMean number (±SD) of dry nights was increased from zero dry nights (daily bed-wetting) to 9.7 (2.8) per 15 d of treatment (65%). CBZ decreased the 24-h urinary volume by 41%, the night volume by 45%, the day volume by 38%, and frequency of micturition by 28%. CBZ increased the 24-h urinary osmolality by 43%. Serum osmolality changed significantly from 283.7mOsm/l to 277.2mOsm/l. CBZ decreased osmotic clearance by 37% and free water clearance by 34%. Creatinine clearance was decreased by 19% after CBZ treatment (p<0.05). ConclusionCBZ reduced urine volume, increased urine osmolality, and decreased the free water clearance, the osmotic clearance, and the frequency of micturition in enuretics; this might help in understanding its mechanism of action.

Hormonal, renal, and autonomic nerve factors involved in the excretion of sodium and water during dynamic salt and water loading in hypoxaemic chronic obstructive pulmonary disease.

Some patients with hypoxaemic chronic obstructive pulmonary disease (COPD) develop sodium and water retention and a subclinical autonomic neuropathy. The possibility that these might be associated has been investigated. The ability of 24 patients with COPD to excrete a 6 ml/kg 2.7% intravenous saline or 15 ml/kg oral water load was studied and changes in plasma electrolyte levels, osmolality, plasma aldosterone and vasopressin levels, urinary volume and sodium content, glomerular filtration rate, renal blood flow, and cardiovascular autonomic nerve function were measured. Patients were divided into groups of eight: those in group A (controls) had mild COPD with a Pa02 of > 9 kPa and no oedema, patients in group B were more hypoxaemic but had never been oedematous, whilst those in group C were hypoxaemic and mildly oedematous at the time of the study. Patients in groups B and C excreted less sodium and water during saline loading and a lesser proportion of the water load. Patients in group C had a reduction in renal blood flow and glomerular filtration rate and all had a subclinical autonomic neuropathy, which was also found in three patients in group B. Their plasma aldosterone level was raised but did suppress appropriately on saline loading. Vasopressin levels were abnormally raised for the osmolality in patients in group C and in those with autonomic dysfunction throughout the water load and at 240 minutes after the salt load. Sodium and urine excretion was highly correlated with autonomic dysfunction, aldosterone levels at time zero, and renal blood flow. The 11 patients with autonomic dysfunction were more likely to be oedematous, more hypoxaemic, excreted much less urine and sodium, had lower glomerular filtration rate and renal blood flow, and higher aldosterone and vasopressin levels than the remaining patients. In patients with COPD the inability to excrete sodium and water is multifactorial. This is the first study to show that autonomic dysfunction is at least associated and might play an important part in the impaired sodium and water homeostasis seen in patients with severe COPD.

Low-Osmolality Contrast Media and the Risk of Contrast-Associated Nephrotoxicity

The authors review clinical data, including those from the recent Iohexol Cooperative Group trial, regarding the nephrotoxic potential of low-osmolar versus high-osmolar contrast media. The clinical characteristics and postulated mechanisms of contrast-associated nephrotoxicity are also considered. The principal strategy for identifying relevant articles was to search the MEDLINE database using the MeSH heading "contrast media nephrotoxicity." Articles from 1966 through 1992 that were considered included original research papers as well as reviews. Those articles selected for detailed review documented original research pertaining to use of low-osmolar or high-osmolar agents. Selected abstracts for pertinent society meetings were also used. No attempt was made to be complete in describing the field. Rather, specific articles that selectively address the question of nephrotoxicity related to the osmolar content of contrast media were used for discussion. In-vitro and animal studies indicate that renal changes possibly involved in the pathogenesis of contrast-associated nephrotoxicity seem to be ameliorated with low-osmolar contrast media, compared with high-osmolar agents. Several recent clinical trials, as well as a meta-analysis combining 24 randomized studies, suggest that the risk of contrast-associated nephrotoxicity is similarly low with high-osmolar and low-osmolar agents among otherwise stable patients with normal renal function, but that low-osmolar contrast is less nephrotoxic than media with high osmolality in patients with pre-existing renal insufficiency.

Fractional measurements of sweat osmolality in patients with cystic fibrosis.

After pilocarpine iontophoresis the change of sweat concentration during collection was studied by vapour pressure osmometry in 24 patients with cystic fibrosis and 24 healthy controls. There was a continuous but proportionate fall in sweat concentrations during the collection period. Mean (SD) initial sweat concentration in the control group was 154.4 (32.6) mmol/kg falling, after 50 microliters of sweat produced, to 92.9 (15.8) mmol/kg. In the cystic fibrosis group it was 315.9 (35.8) mmol/kg falling to 247.4 (24.9) mmol/kg. Despite different rates of fall in concentrations, separation of the two groups was maintained throughout. We conclude that there are implications for the potential improvement of the predictive value of the sweat test.

Arginine vasopressin and the renal response to water loading in congestive heart failure

Previous studies have shown on the basis of isolated omparisons that plasma arginine vasopressin (AVP) levels are inappropriately increased for a given serum osmolality in patients with CHF. To explore further the osmoregulation of AVP in this condition, the response of plasma AVP to a 15- to 20-ml/kg oral water load was compared in 26 patients with CHF and 14 normal subjects. In the normal subjects, serum osmolality decreased from 289 ± 5.0 to 282 ± 5.0 mOsm/kg (p < 0.001) and AVP from 3.6 ± 1.1 to 2.1 ± 0.78 pg/ml (p š 0.001). In the patients with CHF, osmolality decreased from 289 ± 7.0 to to 281 ± 7.0 mOsm/kg and AVP from 7.1 ± 3.6 to 5.8 ± 3.4 pg/ml (p < 0.001). As a percentage of the control value, the decrease in AVP was much greater in the normal group, 41 ± 15% vs 18 ± 10% (p < 0.001). Urinary osmolality levels were measured before and after water loading in 11 patients and in 7 normal subjects. Normal subjects diluted from 812 ± 130 to 133 ± 26 mOsm/kg (p < 0.001) and CHF patients from 599 ± 218 to 253 ± 170 mOsm/kg, a statistically significant (p < 0.01) but smaller (p < 0.05) level of suppression. There were, however, 2 distinct groups within the CHF population: one in which urine osmolality was appropriately decreased (from 594 ± 269 to 144 ± 37 mOsm/kg, p < 0.01) and one in which it decreased little (from 498 ± 84 to 443 ± 132 mOsm/kg, difference not significant). Changes in AVP during the tests were similar in the groups, and although the absolute levels were higher in the patients in whom dilution was abnormal, the minimum AVP level in the patients who diluted was still above normal (4.9 ± 1.8 pg/ ml). The data suggest a variable relation between AVP and urinary osmolality in patients with CHF. Persistently elevated AVP levels may be associated with either normal or abnormal urine dilution in such patients.

Hydrogen ion excretion and urine osmolality in patients with obstructive uropathy secondary to Schistosoma haematobium

Sixty-one patients with urinary schistosomiasis were studied to determine the effects of obstruction and bacteriuria on renal function. 39 (12 with bacteriuria) had demonstrable obstruction and 22 (5 with bacteriuria) had no obstruction. Total hydrogen ion excretion (T.H.+) for obstructed patients with sterile urine did not differ from that in controls; patients with bacteriuria with and without obstruction had a significantly lower T.H.+ (all P values < 0·05). Obstructed natients (with or without bacteriuria) had significant impairment of maximal (U max) and minimal (U min) urine osmolality. Patients with bilateral obstruction and bacteriuria had a sianificantlv lower U max (P < 0·01 than obstructed patients without bacteriuria. The T.H.+ and U max (P < 0·01) improved after treatment. These data suggest that the impairment of T.H.+ is mainlv associated with bacteriuria but that the effects of unilateral or bilateral obstruction and bacteriuria on urine osmolality are additive. These abnormalities are usually corrected after therapy.

Osmolality measurements in heart disease

A study of the variations of plasma and urinary osmolality in patients with acute myocardial infarction and heart failure of different origin was made. It was shown that the plasma osmolality may be related to the clinical evolution of heart disease. The effectiveness of monitoring the osmolality in establishing the alterations of water-electrolyte balance is also reported.