Bernard Namias

5-year treatment of the chronic syndrome of inappropriate secretion of ADH with oral urea.

We report the case of a patient with an idiopathic syndrome of inappropriate secretion of ADH for more than 6 years. Water restriction was effective only during hospital care but was socially difficult to maintain at home, so that the patient presented frequent symptoms of water intoxication. Normal natremia was also obtained with a high salt intake (9 g/day) but this induced leg edema mild dyspnea and gastric intolerance. The patient was however successfully treated for more than 5 years without any side effects with oral urea (30 g/day) allowing her a normal fluid intake (1-1.5 liters/day). Oral urea, even during long periods, is a safe and effective therapeutic approach for patients with chronic SIADH which is not controlled by water restriction alone.

IL‐5 in post‐traumatic eosinophilic pleural effusion

Thoracic trauma or pneumothorax can result in pleural fluid eosinophilia. In this study we investigated the role of the eosinophilopoietic cytokine IL‐5 in three cases of post‐traumatic eosinophilic pleural effusions (EPE). Using a specific immunoenzymatic assay, significant levels of IL‐5 were found in EPE (range 100–3000 pg/ml), while IL‐5 was undetectable (<25 pg/ml) in corresponding serum samples and in non‐eosinophilic pleural fluids. IL‐5 present in pleural fluids was found bioactive in a proiiferative assay using a mouse CTLL‐2 cell line transfected with the cDNA corresponding to the a chain of the human IL‐5 receptor. Using a reverse polymerase chain reaction (PCR) method, we found IL‐5 mRNA expression within pleural mononuclear cells from patients with EPE, but not in corresponding peripheral blood mononuclear cells (PBMC), confirming that IL‐5 is synthesized locally in the pleural cavity. In the two cases in which pleural CD4+ cells were purified, these cells were identified as the major source of IL‐5. Taken together, these data indicate that the development of post‐traumatic EPE is related to a local secretion of IL‐5 by CD4+ cells present in the pleural cavity.

Hyperuricemia as a Clue for Central Diabetes Insipidus (Lack of V1 Effect) in the Differential Diagnosis of Polydipsia

PURPOSE In the differential diagnosis of patients with polyuria-polydipsia one must distinguish usually between primary polydipsia (PP) and central diabetes insipidus (CDI). The first situation is a state of volume expansion and the second of volume contraction. We evaluate whether serum uric acid determination could help to differentiate between the two conditions. PATIENTS AND METHODS We analyzed the score of 13 consecutive patients with CDI, 7 patients with PP, and 7 patients with nephrogenic diabetes insipidus (NDI). Serum uric acid concentration was available during normonatremia without treatment with 1-desamino-8-D-arginine vasopressin (dDAVP), during mild dehydration and during treatment with dDAVP. In 8 of these patients plasma renin activity (PRA), urate, urea and creatinine clearances were also available. These data were also obtained in the patients with NDI. In 1 patient with CDI, we studied the effect on urate clearance of dDAVP, which stimulates exclusively the V2 receptors, and of triglycyl-lysine-vasopressin (TGLV), a potent V1-receptor agonist. RESULTS Normonatremic polydypsic patients with CDI presented an increase in uric acid concentration (7.1 +/- 2.2 mg/dL), whereas in the PP group the value was decreased (3 +/- 0.75 mg/dL; P <0.001). All the normonatremic PP presented a serum uric acid concentration lower than 5 mg/dL, whereas all the normonatremic CDI patients, exept 1, presented a value higher than 5 mg/dL. In both groups blood urea concentration was decreased as a consequence of high renal clearances. The hyperuricemia of CDI was related to low uric acid clearances. Patients with hypernatremia and NDI presented a lower increase in serum uric acid concentration than those with similar levels of hypernatremia and CDI (NDI: 5.7 +/- 0.8 mg/dL and CDI: 7.9 +/- 2.3 mg/dL; P <0.05) and the NDI patients presented an urate clearance corrected for creatinine clearance which was significantly higher than in CDI (9% +/- 3% and 4% +/- 1.1%; P <0.01). When the patients with CDI were treated with dDAVP and normalyzed their PRA (0.9 +/- 0.4 ng/mL/h) we observed still mild hyperuricemia compared to controls (5.5 +/- 1.4 mg/dL and 4.3 +/- 0.9 mg/dL; P <0.01) and a low fractional excretion of filtered uric acid (6.5% +/- 1.7% compared to 8.2% +/- 2% in controls; P <0.05). Acute administration of dDAVP, stimulating the V2 receptors, in one patient with CDI, had no effect on urate clerance, while TGLV, which stimulates the V1 receptor, increased urate clearance. CONCLUSION The presence of an serum uric acid concentration higher than 5 mg/dL in polyuric polydipsic patients is highly suggestive of CDI. Even when these patients are treated with dDAVP many of them remain hyperuricemic, and this seems to be the consequence of a lack of V1 receptor stimulation.

In human patients, vascular water retention during DDAVP-related hyponatremia occurs mainly in the plasma volume and not in the erythrocyte☆

DDAVP-related hyponatremia induces a blood volume expansion, but the analysis of fluid distribution in the vascular compartment has given controversial results in previous animal and human studies. In 5 healthy males, hyponatremia was induced by DDAVP and a free water intake during 3 days. Serum sodium concentration decreased from 138 +/- 0.8 mEq/L to 123 +/- 2.7 mEq/L on day 3. The plasma volume measured by dilution of marked albumin rose from 3033 +/- 230 ml to 3320 +/- 295 ml (p < 0.01). The mean corpuscular volume measured by microhematocrit increased slightly from 91.5 +/- 3.8 pl to 92.6 +/- 3.7 pl (p < 0.02). The red blood cell volume calculated with hematocrit and plasma volume did not change significantly (2565 ml to 2567 ml; not significant). In the present work, we demonstrated that in males the expansion of the plasma compartment almost completely amounted for the water retention in the intravascular volume. The erythrocyte volume increased only slightly, a finding that is consistent with an almost perfect adaptation of the erythrocyte cells to the hypoosmolality.

Raised urea clearance in cirrhotic patients with high uric acid clearance is related to low salt excretion.

In cirrhotic patients without renal failure, salt retention could result from a decreased effective intravascular volume or could be a primary event leading to increased intravascular volume. Clearance of urea and uric acid depend on an effective intravascular volume. In the syndrome of inappropriate secretion of antidiuretic hormone (SIADH)--a state of increased intravascular volume--uric acid clearance is increased and that of urea is increased only when salt excretion is low. The intravascular volume of 60 consecutive cirrhotic patients without renal failure was estimated indirectly by studying the relationship between fractional excretion of filtered (FE) sodium, urea, and uric acid. Forty five per cent had a high FE uric acid (> 12%), which could mean a high intravascular volume, and presented with an FE urea that was inversely correlated with FE sodium (r = 0, 62; p < 0.001) as in SIADH, while in the controls the FE urea was positively correlated with FE sodium (r = +0, 46; p < 0.01). In patients who had a normal FE uric acid and low FE sodium (< 0.2%), the FE urea was significantly lower (40 (13)%, n = 20) than in subjects with high FE uric acid and a low FE sodium (61 (9)%, n = 16, p < 0.001); this last group also presented with lower mean blood urea concentrations (3.1 (1.2) mmol/l and 4.0 (1.8) mmol/l; p < 0.05) and a lower supine renin activity (p < 0.01). As observed in the SIADH, cirrhotic patient with high FE uric acid have raised FE urea only when salt excretion is low. It is believed that the low salt excretion is not caused by a decrease in effective intravascular volume and that this is increased in cirrhotic patients with raised FE uric acid.

Effect of Urea and Indomethacin Intake on Solute Excretion in the Syndrome of Inappropriate Secretion of Antidiuretic Hormone

Our purpose was to compare the effect of urea and indomethacin on solute excretion in hyponatremic patients with inappropriate secretion of antidiuretic hormone (SIADH). In 6 patients (serum Na: 126 +/- 3 mmol/l), the intake of urea (0.1 g/kg) induced a decrease in sodium excretion while urine osmolality, urine flow and osmotic clearance (Cosm) did not change. In the control group, the urinary flow and Cosm were increased as expected, while sodium excretion tended to increase. In the SIADH group, the decrease in the fractional excretion (FE) of Na+ (FE.Na+) (or FE.Cl-) after urea intake was negatively correlated with urinary urea concentration while the FE.K+ was positively correlated with FE.Na+ (or FE.Cl-), which suggests that the effect of urea on sodium excretion takes place proximally to the distal tubule, probably at the thin ascending limb. After indomethacin intake, FE.Na+ (or FE.Cl-), FE.K+, Fe.osm and Fe.urea decreased in the normal and hyponatremic groups. The mean free water reabsorption relatively to osmolar delivery was lower in SIADH (p < 0.05), and did not change significantly after indomethacin intake. The fact that the decrease of FE.Na+ (or FE.Cl-) after indomethacin was associated with a decrease in FE.K+ suggests that the increase in sodium (or chloride) reabsorption occurred more proximally to the distal tubule (probably a the medullary segment of the thick ascending limb of the loop of Henle).