Glaphenine-induced acute renal failure in the rat: a new experimental model

Glaphenine, a nonsteroid analgesic compound, administered by gastric gavage in rats (800 mg/kg), induced nonoliguric reversible acute renal failure (ARF). Intratubular deposits were found in medullary collecting ducts. Intratubular hydrostatic pressure (Pt) increased from 11.7 +/- 0.7 to 30.0 +/- 0.9 mmHg. Renal failure was almost completely prevented by concomitant high water and solute diuresis, achieved by furosemide infusion in Wistar rats and by high salt intake in Brattleboro rats with diabetes insipidus. In the latter protected animals, Pt was only slightly elevated (17.0 +/- 0.5 mmHg). Urinary excretion of prostaglandin E2 (PGE2) dropped dramatically after glaphenine administration in Wistar rats; the fall was slight in Brattleboro rats in which PGE2 excretion was normally low. We conclude that tubular obstruction plays a prominent role in glaphenine-induced ARF in the rat. High water and solute diuresis prevented tubular obstruction. Reduced renal PGE2 synthesis is probably not involved in the pathophysiology of this ARF model, inasmuch as Brattleboro rats on a high salt intake were protected despite low basal urinary excretion of PGE2.     

Interference of different ACE-inhibitors with the diuretic action of furosemide and hydrochlorothiazide

Summary In healthy volunteers the acute effect of furosemide (40 mg i.v.) and hydrochlorothiazide (100 mg p.o.) on diuresis, natriuresis and renal kallikrein and kinin excretion was investigated. Furosemide stimulated markedly diuresis and natriuresis as well as urinary kallikrein and kinin excretion. Pretreatment by captopril (C) reduced the diuretic and natriuretic effect of furosemide significantly probably due to a diminished (about 50%) proximal-tubular secretion of furosemide. Captopril did not alter significantly the furosemide induced changes in urinary kallikrein and kinin excretion. After captopril there was a clear dissociation between aldosterone, which was diminished by captopril continuously, and renal kallikrein and kinins, which were still stimulated by furosemide. These results suggest that renal kallikrein-kinin system is stimulated by furosemide directly and independently of aldosterone secretion. Other ACE-inhibitors like ramipril (5 mg) or enalapril (20 mg) did not influence the stimulatory effects of furosemide on diuresis or kallikrein-kinin excretion. Ramipril at a dose of 10 mg, however, enhanced the initial diuretic effect of furosemide by increased furosemide secretion and increased relative sodium excretion. Hydrochlorothiazide induced a prolonged diuresis which was not changed by either captopril or ramipril. Urinary kallikrein excretion was not stimulated by hydrochlorothiazide. Our results show an important drug interference between captopril and furosemide, which is independent of ACE-inhibition and probably only due to an interference in proximal-tubular secretion of both drugs. Between captopril and hydrochlorothiazide no such interaction could be observed.Dedicated to Professor Dr. Werner Kaufmann on the occasion of his 65th birthdayThe paper contains major parts of the thesis of A. Gentges and A. Masselink. Smaller parts of the results were presented at the international symposium on Vasodepressor Hormones in Hypertension, Nürnberg, 1986     

Effects of experimental potassium depletion on renal function and urinary prostanoid excretion in normal women during hypotonic polyuria

During hypotonic polyuria renal function studies by the clearance (cl.) method, and urinary PGE2, 6-keto-PGF1 alpha and TxB2 determinations were performed on 14 healthy women in normal potassium balance (N) and 14 healthy women in sustained potassium depletion (KD) induced by low dietary potassium intake (less than or equal to 10 mmol day-1) and natriuretic treatment. By using different depletive patterns, two groups with estimated cumulative potassium deficits of 160 +/- 43 mmol (KD1, n = 8) and 198 +/- 22 mmol (KD2, n = 6), respectively, were obtained. (1) In both the KD1 and KD2 groups as compared to normal potassium balance (N), plasma potassium concentration and urinary potassium excretion were significantly lower; plasma renin activity was significantly higher. (2) Only in KD2 did significant changes appear in renal function and urinary prostanoid excretions. Besides a decrease in creatinine cl. and the urinary flow rate, an increase in fractional chloride excretion and a reduction in distal fractional chloride reabsorption were manifest. The plasma chloride concentration was reduced too. Urinary prostanoid excretions were significantly (6-keto-PGF1 alpha, TxB2) or tendentially (PGE2) lower. (3) Indomethacin treatment resulted in changes in mean arterial pressure (increase) and creatinine cl. (decrease) which were not significantly different in normal potassium balance and KD groups. Only in KD2 did the drug significantly reduce the fractional salt and water excretions and the fractional sodium and chloride deliveries to the diluting segments. However, indomethacin was unable to correct the inhibition of distal fractional chloride reabsorption. Therefore, the potassium depletion attained in the KD2 group was efficacious in depressing renal prostanoid synthesis. This fact, in the presence of high levels of angiotensin II, induced a reduction of the glomerular filtration rate thus contributing to renal ability to retain chloride and potassium.     

Excessive myocardial calcinosis in a chronic hemodialyzed patient

Summary Secondary oxalosis in chronic hemodialyzed patients is caused by impaired renal excretion and inadequate removal of oxalic acid during hemodialysis. Ascorbic acid is a precursor of oxalic acid. We report a parathyroidectomized patient with chronic renal failure, on hemodialysis, who received over a period of several months a total dose of 91.0 g ascorbic acid i.v. The plasma oxalic acid level in this patient was 14-fold higher than in healthy persons. Increased oxalic acid synthesis from its precursor ascorbic acid may be responsible for hyperoxalemia, high content of oxalic acid in myocardium, aorta and lung, and calcium oxalate deposition in soft tissues. Application of high doses of ascorbic acid should be avoided in hemodialysed patients with chronic renal failure.Abbreviations PTH parathyroid-hormone - RDT regular dialysis treatment     

Vitamin replacement therapy in renal failure patients

Renal failure patients require vitamin replacement therapy that addresses the specialized needs of renal failure. Four factors including restricted diet, uremic toxins, drug-nutrient interactions, and in ESRD, the dialysis process, affect the normal absorption, retention and activity of necessary micronutrients which support all aspects of carbohydrate, protein, lipid and nucleic acid metabolism. Studies have shown that the typical renal failure diet is low in B vitamins, that uremic factors affect folate and pyridoxine activities and that many B vitamins are lost on dialysis at a rate greater than are lost with normal urinary excretion. In addition, retention of vitamin A or inappropriately high supplementation of vitamin C may cause toxicities which exacerbate existing pathologies. Further, emerging research suggests some vitamins such as folic acid and pyridoxine, if provided in higher than normal amounts, may have an impact on reducing the risk of some aspects of renal cardiovascular disease. It is therefore important to supplement some vitamins, and use restraint in the supplementation of others. It is clear that renal failure patients, including predialysis, ESRD and transplant patients need specialized supplementation that meets the requirements of disease and its management.     

慢性肾脏疾病患者尿SOD排泄变化

为了探索肾脏超氧化物歧化酶（ＳＯＤ）在慢性肾脏疾病发生,发展中的作用,采用放免方法测定了６０例慢性肾小球疾病患者尿ＳＯＤ的排泄变化,其中慢性肾炎１２例,肾病综合征２６例、轻中度慢性肾衰１０例,重度慢性肾衰１２例。结果发现,四组患者尿ＳＯＤ排泄均高于正常对照组,而肾病综合征组明显高于其它三组;慢性肾炎组明显高于轻、中度和重度慢性肾衰组,而轻、中度慢性肾衰组与重度组无显著差异。血ＳＯＤ除肾病综合征且高     

Zur Regulation der Diurese in der frühen Polyuriephase nach akutem Nierenversagen

Zusammenfassung Es wird über 2 Patienten berichtet, die nach akutem Nierenversagen eine verzögerte Polyuriephase entwickelten. In beiden Fällen hatte sich eine ausgeprägte Hypoproteinämie mit Zunahme des Körpergewichtes infolge Wasserretention eingestellt. Die Abnahme der Diurese war auf eine Verminderung der glomerulären Filtration zu beziehen. Die Infusion von Humanalbumin führte in beiden Fällen mit einer Steigerung der Serumeiweißkonzentration zu einer Zunahme der glomerulären Filtration und damit zu einer Erhöhung des Harnzeitvolumens. Diese Beobachtungen zeigen, daß sich die Wasserausscheidung der Nieren in der Polyuriephase nicht völlig unabhängig vom Wasserbedarf des Gesamtorganismus vollzieht. Sie weisen ferner daraufhin, daß das Glomerulumfiltrat bereits mit Wiedereinsetzen der Diurese nach akutem Nierenversagen einer Regelung unterliegt.

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Summary Two cases of acute renal failure due to septicemia are presented, who showed a delayed polyuric phase. Both patients developed a severe hypoproteinemia which was followed by water retention.The diminished diuresis of the delayed polyuric phase was associated with a decreased GFR. Infusion of human albumin resulted in both cases in an elevation of serum protein and simultaneously in an increase of GFR and urinary output.These observations suggest that the renal water excretion in the polyuric phase is not completely independend of the water requirement of the body. Furthermore the GFR seems to be regulated already at a time when the diuresis starts after acute renal failure.

     

Serum vitamin E levels in patients with chronic renal failure

27 patients with chronic renal failure, 21 patients on chronic intermittent dialysis treatment and 27 healthy controls were tested for serum level of vitamin E estimated spectrophotometrically. Both patient groups had significant higher mean values (12.1 +/- 1.2 and 7.2 +/- 0.8 micrograms/ml respectively) in comparison with normal controls 4.6 +/- 0.7 micrograms/ml). No correlation was found to serum creatinine, hematologic values, protein and lipoprotein concentration, nor to mode and duration of treatment regimes. Vitamin E was not extracted from blood throughout dialysis. Under normal conditions of conservative or dialysis treatment of chronic renal failure patients vitamin E seems not to be a factor concerning uremic symptoms and there is no need for supplementation.     

Effect of vitamin K deficiency on urinary gamma-carboxyglutamic acid excretion in rats

Since gamma-carboxyglutamic acid (Gla) in Gla-containing proteins is stoichiometrically excreted into urine as free Gla, urinary Gla excretion is believed to reflect the rate of synthesis and degradation of vitamin K-dependent proteins and the utilization of vitamin K in body. We studied the daily changes in urinary Gla excretion and plasma vitamin K-dependent clotting factor levels in rats fed vitamin K-deficient diets followed by subcutaneous injection of vitamin K1 or after the oral administration of Warfarin. Urinary Gla excretion in normal rats fed a standard diet that contained about 500 ng of vitamin K1 per gram of diet was 2.35 +/- 0.25 mumoles/day, but the level in rats fed a markedly vitamin K-deficient diet (less than 5 ng/g) decreased to 1.40 +/- 0.14 mumoles/day. When rats were fed a moderately vitamin K-deficient diet (20-50 ng/g), plasma vitamin K-dependent clotting factor levels decreased significantly, but urinary Gla excretion did not decrease. Warfarin, a vitamin K antagonist, caused a significant decrease in urinary Gla excretion and plasma clotting factor levels. When vitamin K, (200 micrograms/kg) was injected subcutaneously in rats fed a markedly vitamin K-deficient diet, the plasma vitamin K-dependent clotting factor levels recovered quickly to normal, but urinary Gla excretion showed only a partial recovery to 1.74 +/- 0.15 mumoles/day. These results indicate that urinary Gla excretion decreases in vitamin K deficiency, but changes in urinary Gla excretion do not reflect vitamin K deficiency in rats as sensitively as changes in the prothrombin time and plasma K-dependent clotting factor levels.     

Effect of vitamin A supplemented diet on calcium oxalate renal stone formation in rats

ObjectivesTo study the effect of a vitamin A supplemented diet on calcium-oxalate stone formation in rats and to test its expected action in the dissolution of renal calculi.Material and methodsTwenty-four male Wistar rats were randomly divided into three groups of eight rats each. The first group (group A) received a normal diet for six weeks. The second group (group B) was fed a lithogenic diet by the addition of ethylene glycol 0.5% to drinking water for three weeks then a normal diet for three weeks. The third group (group C) received the same lithogenic diet for three weeks then a vitamin A supplemented diet 20 times the normal amount (5.1 mg/100 g of diet) at the three last weeks. One day before the end of treatment, each animal was placed for 24 h in metabolic cage in order to collect urine samples and determine the urinary parameters.ResultsThe glomerular filtration rate and the urinary excretion of citric acid which fell in group B have been restored in group C.ConclusionsThis study shows that a vitamin A supplemented diet at the rate of 20 times standard ration could improve the renal function by restoring the glomerular filtration rate and by increasing the urinary pH and excretion of citric acid.     

肾脏病患者尿液中SIgA的含量的观察

用放射免疫(双抗体-PEG法)测定109例正常人和85例各种类型肾脏病患者尿液中SIgA含量。表明慢性肾炎普通型、慢性肾炎肾病型活动期和慢性肾炎所引起的慢性肾功能不全均较正常对照组明显增高。慢性肾炎肾病型好转期尿 SIgA与正常对照组无显著差异,但较活动期明显减少。高分子和混合蛋白尿患者尿 SIgA较中分子和低分子蛋白尿患者明显增加。肾病患者24小时尿蛋白排出量与尿 SIgA呈正相关,而与血清 IgA无相关性。文中讨论了非感染性肾脏疾病时尿 SIgA增高的可能原因。     

The renal kallikrein-kinin system in spontaneously hypertensive rats

In male spontaneously hypertensive rats (SHRSP) of the stroke prone strain (Okamoto) and in normotensive Wistar-Kyoto rats (WKY) urinary kallikrein excretion was investigated at different age and at drug-induced diuresis.In rats of both strains from 7th till 19th week of age urinary kallikrein excretion increased with age. In SHRSP of 7th till 11th week of age kallikrein excretion was higher than in WKY rats, while it was lower in the 48-week-old SHRSP. No correlation was found between urinary kallikrein excretion and systolic blood pressure.In SHRSP and WKY rats a similar daily rhythm of kallikrein excretion in urine was found being high in the early morning and low in the afternoon. Kallikrein excretion correlated significantly with urine volume.The loop diuretic bumetanide (4 and 40 mg/kg) induced diuresis and natriuresis in both strains, however more marked in the WKY rats than in the SHRSP. Urinary kallikrein excretion, however, showed in both strains the same biphasic course with a short lasting increase and a secondary decrease. Thus, in the average urinary kallikrein excretion was not effected by the drug.Prolonged treatment with furosemide over 5 days (125 mg/kg) resulted in an increase in kallikrein excretion in urine, more pronounced in the WKY rats than in the SHRSP.The observed results suggest that renal kallikrein-kinin system is not involved in the development of spontaneous hypertension as a pathogenetic factor, but rather is influenced by other factors like hormone interactions, i.e. mineralocorticoids and catecholamines, as well as renal function and acute changes in urine flow.Herrn Professor Dr. med. W. Kaufmann zum 60. Geburtstag     

Increased urinary kallikrein excretion during prostaglandin E1 infusion in anaesthetized dogs and its relation to natriuresis and diuresis.

. The effect of intra-arterial prostaglandin E1 (PGE1) infusion on urinary kallikrein, sodium, potassium and water excretion was studied in normal anaesthetized dogs. 2. Infusion of PGE1 caused a dose-related increase in urinary excretion of kallikrein, sodium, potassium and water as well as an increase in renal blood flow (R.B.F.) and a fall in urinary osmolality and renal vascular resistance. 3. The changes occurred in the absence of appreciable changes in inulin clearance (Cin), arterial blood pressure, haematocrit, and plasma sodium and potassium concentrations. 4. The increased urinary kallikrein excretion correlated positively with the natriuresis, diuresis and kaliuresis and the increase in renal blood flow, but negatively with the urinary osmolality and renal vascular resistance. 5. It is concluded that renal kallikrein is involved in the renal response to arterial infusion of PGE1.     

肾脏病患者脂蛋白（a）的异常代谢

本文检测和分析了７３例各类肾脏疾病患者和对照组人群的血脂、载脂蛋白、血清和尿液中Ｌｐ（ａ）水平，表明各类肾小球疾病及慢性肾衰、糖尿病肾病患者具脂质代谢异常，血清高浓度脂蛋白为其另一生代特征。血清脂蛋白同血清白蛋白、尿总蛋白及尿蛋白分子大小均显著相关；尿Ｌｐ（ａ）排泄减少，且同血清肌酐水平相关。     

Aging, chronic administration of ethanol, and acute exposure to nitrous oxide: effects on vitamin B12 and folate status in rats.

Elderly patients with alcoholism often require surgery and receive nitrous oxide (N2O) as a component of their anesthetic. Since aging, ethanol, and N2O may all perturb folate and/or vitamin B12 metabolism, we examined the combined influence of these parameters on vitamin B12/folate status in a rodent model. Aged male Fischer 344 rats (24 months old) were given a liquid ethanol diet (35% of calories as ethanol) and control rats were pair-fed a liquid diet with carbohydrate substituting for the caloric content of ethanol. After receiving liquid diets for 7 weeks, rats were exposed to 60% N2O/40% 0(2) for 6 h. Urinary excretion of formic acid, formiminoglutamic acid (FIGLU), and methylmalonic acid (MMA) were used as indirect markers of folate/vitamin B12 status. In both the aged ethanol-fed and control groups, excretion of formic acid and FIGLU markedly increased the first day after N2O exposure and returned towards background values by the second day. No changes occurred in MMA excretion. Exposure to N2O decreased methionine synthase activities in liver, kidney and brain, and recovery of methionine synthase activities occurred over a period of 4 days in both the aged ethanol-fed and control groups. Ethanol treatment for 7 weeks combined with acute exposure to N2O did not deplete the aged rats of folate or vitamin B12 in blood, liver, kidney or brain. Thus, in this animal model, aging, chronic ethanol administration, and acute N2O exposure did not act synergistically to produce prolonged and severe disturbances in folate and vitamin B12 metabolism.     

Renal function in patients with yusho

Renal functions were examined in 102 patients with yusho in 1988, Frequencies of proteinuria, microhematuria and history of renal diseases were not different from 20 age-matched controls. The means of blood urea nitrogen, serum creatinine and serum uric acid levels of yusho patients did not differ from those of controls. The levels of serum beta 2-microglobulin and its urinary excretion showed no difference between two groups. Serum concentrations of sodium, potassium, chloride, calcium and phosphorus revealed no abnormality in all patients except for one who had hypophosphatemia. Urinary excretions of phosphorus, however, were significantly higher in yusho patients than in controls. Serum PCB levels, which were still higher in yusho patients, did not correlate with urinary excretions of phosphorus. The mechanism and the clinical significance of this phenomenon remain to be elucidated.     

Role of renal kallikrein in control of renin release in conscious rats

Renal kallikrein was reported to activate human inactive renin and to release active renin from rat renal cortical slices. To evaluate the role of renal kallikrein in the control of renin release in vivo, Trasylol and soybean trypsin inhibitor (SBTI) were used to determine whether they can inhibit renin release stimulated by the administration of furosemide and a 2-wk low-sodium diet. Plasma renin activity (PRA) was increased by furosemide and also by the low-sodium diet. Urinary kallikrein excretion was increased by the sodium depletions. Trasylol did not affect basal PRA; however, it inhibited PRA and urinary kallikrein excretion, when stimulated by furosemide and by a low-sodium diet. These results suggest that furosemide and low-sodium diet act on the kidney to release renin via protease production. Because SBTI affected neither PRA nor urinary kallikrein excretion stimulated by these sodium depletions, it is suggested that renal kallikrein may play an important role in the control of renin release stimulated by furosemide and by low-sodium diet.     

Homocysteine, a new crucial element in the pathogenesis of uremic cardiovascular complications

Most large observational studies available today establish that moderate hyperhomocysteinemia, either genetically or nutritionally determined, is an independent risk factor for myocardial infarction, stroke, and thromboembolic disease. This is also true for chronic renal failure patients, who exhibit a high prevalence of hyperhomocysteinemia (85-100%), which reaches high plasma concentrations (20-40 microM, while control values range between 8 and 12 microM). After a renal transplant, homocysteine levels decrease, but tend to be higher than normal. The cause of hyperhomocysteinemia in renal failure is still obscure, since recent data have questioned the previous notion that a net homocysteine renal extraction and/or excretion take place in man. No matter the cause of its increase, the sulfur amino acid homocysteine is thought to induce an increment in cardiovascular risk through three basic biochemical mechanisms: (1) homocysteine oxidation, with H2O2 generation; (2) hypomethylation through S-adenosylhomocysteine accumulation, and (3) protein acylation by homocysteine thiolactone. The final result is membrane protein damage, endothelial damage, and endothelial cell growth inhibition, among other effects. Hyperhomocysteinemia, in general, is susceptible of therapeutic intervention with the vitamins involved in its metabolism. Depending on the cause, vitamin B6, vitamin B12, betaine, and/or folic acid can be effectively utilized. Chronic renal failure patients benefit from folic acid in high dosage: 1-2 mg are usually not effective ('relative folate resistance'), while 5-15 mg reduce homocysteine levels to a 'normative' range (<15 microM) in a substantial group of patients. Good results are also obtained in transplant patients, best with a combination of folic and vitamin B6. The results of the interventional trials focusing on the possible reduction in cardiovascular risk after homocysteine-lowering therapy, both in the general population and in end-stage renal disease, are expected soon, as well as the genetic and biochemical studies in suitable models, with the aim to clarify the cause-effect link suggested by the numerous observational and basic science studies.     

Prostaglandins and renal NaCl excretion in healthy human subjects: Effects of prostaglandin synthesis inhibition with indomethacin

Summary The effect of a single oral dose of 75 mg of indomethacin on renal function and urinary excretion of prostaglandin (PG) E₂ was investigated in six healthy volunteers. In the absence of changes in GFR, indomethacin significantly reduced urinary excretion of sodium and chloride for 12 h with a return to control values afterwards. This effect on the renal excretory function was closely paralleled by a decrease in urinary excretion of PGE|12|0 which also returned to control values after 12 h. In a second series of experiments, inhibition of PG synthesis was performed in healthy volunteers during sustained water diuresis to determine the tubular site of altered NaCl absorption using clearance methods. Again, indomethacin induced a significant suppression of urinary excretion of sodium, chloride and potassium without changes in GFR or urinary excretion of phosphate. Indomethacin treatment had no effect on the delivery of chloride beyond the proximal tubule to the distal tubules (distal delivery) but significantly increased the distal fractional absorption of chloride (DFA_Cl). In a third series of experiments, the effect of furosemide on GFR and tubular NaCl absorption was studied without and with concomitant administration of indomethacin. Furosemide induced an almost twelvefold increase in the urinary excretion of sodium and chloride, an approximately threefold increase in urinary excretion of potassium and a significant increase in urinary phosphate excretion. Furosemide also increased distal delivery and decreased DFA_Cl and also increased urinary excretion of PGE₂. Concomitant indomethacin treatment significantly suppressed urinary excretion of PGE₂ but did not affect any of the furosemide induced changes in renal function. Our results support the concept that PG participate in the regulation of renal NaCl excretion and suggest that the diluting segments of the nephron may be the site of action of renal PG. Furthermore, furosemide stimulates renal synthesis of PGE₂ but the tubular effects of this diuretic appear not to be mediated by the renal PG system.This study was supported by research grant No. FA-8476, Ministerium für Wissenschaft und Forschung NRW, FRG     

Urinary metabolites of histamine and leukotrienes before and after placebo-controlled challenge with ASA and food additives in chronic urticaria patients

BACKGROUND: The recovery of mediator metabolites from urine has the potential to provide a rapid, safe, and easily available index of release of mediators. We aimed to determine urinary metabolites of both histamine and leukotrienes (LTs) in patients affected by chronic urticaria (CU). METHODS: Twenty patients with CU were studied. They were selected on the basis of double-blind placebo-controlled challenge (DBPC) with acetyl salicylic acid (ASA) and food additives. Ten patients (group B) were negative to both challenges. Ten patients (group C) presented urticaria and/or the appearance of angioedema during or 24 h after challenge, with reactions to ASA (five patients) or food additives (five patients). We recruited 15 healthy volunteers as controls (group A). During a second challenge, groups B and C were challenged double-blind with a single dose of ASA, or a specific food additive, or placebo. The healthy group was challenged only with a placebo (talc capsule). Patients in groups B and C were challenged twice: with placebo (as groups B1 and C1) and with ASA (groups B2 and C2) or food additives (C2). Four samples of urine were collected; one during the night before the specific or sham challenge (baseline), and three at 2, 6 and 24 h after the challenge. Urinary methylhistamine (N-MH) and LTE4 were analyzed and normalized for urinary creatinine. RESULTS: For urinary N-MH at baseline, there was a significant difference only between group A and groups B1, B2, C1 and C2 (A vs. B1, P < 0.0001; A vs. B2, P < 0.0001; A vs. C1, P < 0.0001; A vs. C2, P < 0.0001). We detected a significant variation in urinary methylhistamine excretion only in group C2 after 2 h, 6 h and 24 h (P < 0.0001). However, no variations were observed in N-MH excretion rate in the other groups (A, B1, C1) after challenge with placebo, and in B2 after challenge with ASA 20 mg. For urinary LTE4 at baseline no differences were found between the mean values for the different groups. After specific challenge, only C2 patients showed significantly increased excretion rates of urinary LTE4 compared with the other groups challenged with placebo (A, B1, C1), or ASA (B2) (P < 0.0001). No significant correlation was seen between urinary LTE4 and methylhistamine excretion rate in any patients. CONCLUSION: Our results show that urinary excretion of N-MH and LTE4 is different for CU patients without ASA or food hypersensitivity, compared to those with CU with ASA or food additive hypersensitivity after specific challenge.