The circadian variation of urinary N-acetyl-beta-D-glucosaminidase and gamma-glutamyl transpeptidase in clinically healthy cats

The circadian variation of urinary N-acetyl-beta-D-glucosaminidase (NAG, EC 3.2.1.30) and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2) was evaluated in cats. Urine and blood were collected at 4-hr intervals from adult cats (3 males, 9 females) weighing between 2.6 and 5.0 kg. There was no circadian variation in the urine volume, creatinine clearance, creatinine excretion, NAG excretion or gamma-GTP excretion. The average NAG and gamma-GTP indices in the 4-hr urine were similar to those for the 24-hr urine. However, the variance for the 4-hr urine samples was higher than that of 24-hr urine. In conclusion, although 4-hr urine samples can be used to estimate 24-hr urinary enzyme excretion, short-term spot urine samples may cause increased variation in the enzyme index.     

Urinary pyridinoline and deoxypyridinoline excretion in children

OBJECTIVE: There are few data on urinary markers of collagen breakdown in children. We have determined a normal range for urinary pyridinoline and deoxypyridinoline in children, assessed the variability in excretion in individual children and examined the effect of GH treatment on the excretion of these collagen cross-links. DESIGN: A cross-sectional study of a group of healthy children and sequential samples from children receiving GH treatment. PATIENTS: One hundred and nine healthy children aged 2-15 years, 8 healthy children aged 4-11 years and 4 children receiving GH treatment. MEASUREMENTS: Total pyridinoline and deoxypyridinoline excretion were measured by high performance liquid chromatography after initial acid hydrolysis and cellulose extraction steps. Serum parathyroid hormone was measured using a two-site immunoradiometric assay and urinary hydroxyproline by Ehrlich's reaction using a colorimetric assay. Pyridinoline and deoxypyridinoline excretion were expressed as a ratio against urine creatinine. RESULTS: High excretion of pyridinoline (Pyr) and deoxypyridinoline (DPyr) was seen at all ages with no apparent relation to age (mean Pyr/Cr 115 nmol/mmol and DPyr/Cr 31 nmol/mmol). No correlation was found with serum parathyroid hormone or urinary hydroxyproline excretion. Marked day to day variation was seen in individual children. A progressive rise in excretion was seen in children receiving GH treatment with no significant correlation to height velocity. CONCLUSIONS: There is a high excretion of the pyridinium cross-linking amino acids in children of all ages compared to adults. However, a high variability exists in single morning urine samples which will limit the usefulness of these markers in growing children.     

Human leucocyte antigen-DQA1, -DQB1 polymorphism distribution in Shanghai Chinese women with pregnancy induced hypertension]

Our objective was to determine if maternal urinary calcium excretion is altered during treatment of mild preeclampsia remote from term with the calcium channel blocker nifedipine. One hundred forty-eight women with mild preeclampsia were randomly allocated to treatment with either bed rest alone (n=64) or in combination with nifedipine (n=84) at 26-36 weeks' gestation. All women had 24 hr urine samples collected for creatinine clearance and calcium excretion determination prior to therapy and during treatment. There was no difference in gestational age at the time of urine collection between the two groups. There were no differences in 24-hr creatinine clearance and calcium excretion between the groups prior to therapy. When followed longitudinally, there was a significant reduction in calcium excretion within each group (p=0.0005 control group, p <0.0001 nifedipine group). Further, a significant reduction in calcium excretion was noted following nifedipine therapy (62+/-94 mg Ca/24 hr) compared to the control group (143+/-153 mg Ca/24 hr), p <0.001. Consistent with previous studies, we have shown that progressive hypocalciuria is a feature of preeclampsia. Further, urinary calcium excretion decreased despite nifedipine therapy. Altered urinary calcium excretion may be less reflective of the progression in severity of preeclampsia in patients treated with nifedipine.     

Urinary creatinine excretion in the ICU: low excretion does not mean inadequate collection

BACKGROUND: It has been assumed that a urinary creatinine excretion rate of less than 10 mg/kg per day means an inadequately collected urine sample. OBJECTIVE: To determine the frequency of a urinary creatinine excretion rate of less than 10 mg/kg per day in intensive care unit patients with an adequately collected urine sample. METHOD: In a prospective study of creatinine excretion rates, 24-hour urine samples were evaluated for urinary creatinine in 209 critically ill patients with indwelling Foley catheters. Patients from three adult intensive care units in New York City were divided into two groups. Group 1 patients excreted less than 10 mg/kg per day of urinary creatinine, and group 2 patients excreted at least 10 mg/kg per day. Groups 1 and 2 were first evaluated by dividing the creatinine excretion data by actual body weight. Since actual body weight may overestimate body weight in the critically ill patient, data from groups 1 and 2 were also evaluated using lean body weight. RESULTS: Urinary creatinine excretion was less than 10 mg/kg per day in 36.8% of patients using actual body weight and 29.7% of patients adjusted for lean body weight. The average age of patients in group 1 was 74 +/- 17 years for both actual body weight and lean body weight. The average age of group 2 patients was 60 +/- 19 years for actual body weight and 62 +/- 19 years for lean body weight. There was a significant difference in age between group 1 and group 2 patients for both actual body weight and lean body weight. The proportion of female vs male patients with reduced creatinine excretion was significantly greater, whether the actual body weight or lean body weight adjustment was used. CONCLUSIONS: A urinary creatinine excretion rate of less than 10 mg/kg per day occurs in about one third of critically ill patients, who are more likely to be elderly and female.     

Two triterpene saponins from Arenaria filicaulis

Uropontin is the urinary form of osteopontin, an aspartic acid-rich phosphorylated glycoprotein. Uropontin has been previously shown to be a potent inhibitor of the nucleation, growth and aggregation of calcium oxalate crystals and the binding of these crystals to renal epithelial cells. Quantitative data defining the excretion of this protein are necessary to determine its role in urinary stone formation. In the present studies, we determined uropontin excretion rates of normal humans. Urine samples were obtained under conditions of known dietary intake from young adult human volunteers with no history, radiographic or laboratory evidence of renal disease. Urinary concentrations of uropontin were measured by a sensitive ELISA employing an affinity purified polyclonal antiserum to uropontin. Thirteen normal subjects ingested a constant diet providing 1 gram of calcium, 1 gram of phosphorus, 150 mEq of sodium and 1 gram of protein per kilogram of body wt per day during an eight day study period. The relationship of urinary volume to uropontin excretion was assessed by varying fluid intake on the last four days of the study to change the mean urine volume/24 hr by > 500 ml. Urine collected in six hour aliquots for eight days was analyzed for uropontin by ELISA, and for calcium, and creatinine. Daily uropontin excretion of 13 individual subjects was 3805 +/- 1805 micrograms/24 hr (mean +/- 1 SD). The mean urinary levels (1.9 micrograms/ml) detected in the present study are sufficient for inhibition of crystallization; our previous studies have demonstrated that the nucleation, growth and aggregation of calcium oxalate crystals and their binding to renal cells in vitro are inhibited by this concentration of purified uropontin. In contrast to the regular pattern of diurnal variation of calcium excretion seen in most subjects, uropontin excretion showed no regularity of diurnal variation and was not directly related to either calcium or creatinine excretion or changes in urinary volume. However, uropontin concentration varied inversely with urine volume (P < or = 0.001), so that the highest uropontin concentrations occurred when urine volume was the lowest. We conclude that the physiologic characteristic of an inverse relationship of uropontin concentration to urine volume favors protection from urinary crystallization of calcium oxalate by uropontin. Our quantitative definition of urinary uropontin excretion of normal adults provides the basis for the evaluation of uropontin excretion by individuals who have formed urinary stones.     

The mass outbreak of dysentery in a kindergarten

A study was conducted to examine the effect of magnesium lithospermate B on both the urinary and renal total and active kallikrein and prokallikrein in rats with adenine-induced renal failure. In rats given magnesium lithospermate B at a dose of 10 mg/kg body weight/day for 12 days, significant increases of urinary total and active kallikrein were associated with significant increases of urine volume and urinary total and active kallikrein were associated with significant increases of urine volume and urinary creatinine excretion. The renal total and active kallikrein levels were also significantly elevated by the treatment with magnesium lithospermate B. On day 24, the urinary excretion of total and active kallikrein and prokallikrein was significantly increased. Concomitantly, a significant increase in renal kallikrein (total, active and pro-) was found in the rats given magnesium lithospermate B. A significant relationship existed between the urinary creatinine and active kallikrein excretion. These results suggest that magnesium lithospermate B may stimulate the synthesis of kallikrein and/or conversion to active kallikrein, thus improving renal function.     

Effects of hormone replacement therapy in bone resorption, in post-menopausal women

BACKGROUND: The effects of different therapies on bone loss rate can be measured using biochemical markers of bone resorption such as urinary hydroxyproline. AIM: To study the effects of hormone replacement therapy on urinary hydroxyproline in postmenopausal women. PATIENTS AND METHODS: Eighty three postmenopausal women without hormone replacement therapy, 54 postmenopausal women receiving hormone replacement therapy and 16 premenopausal women (considered as the control group) were studied. Hydroxyproline was measured in an early morning urine sample, after one day of diet without meat or gelatin. RESULTS: Urinary hydroxyproline in premenopausal women was 33.7 +/- 7.9 mg/g creatinine. The figure for postmenopausal women with hormonal replacement therapy was 33.7 +/- 5.9 mg/g creatinine. Postmenopausal women without replacement therapy had an urinary hydroxyproline of 47.4 +/- 8.5 mg/g creatinine, significantly higher than that of premenopausal and supplemented women. In 21 postmenopausal women, hydroxyproline was measured before and after three months of replacement therapy, values decreased 35.5 +/- 11% in this period and there was a direct correlation between initial values and the degree of reduction (r = 0.69, p < 0.001). CONCLUSIONS: Postmenopausal women receiving hormone replacement therapy have a urinary hydroxyproline excretion similar to that of premenopausal women.     

Sodium excretion in children with lithogenic disorders

INTRODUCTION: The causes of nephrolithisis are multifactorial and have not yet been enough investigated [1]. Hypercalciuria is the most common cause of metabolic nephrolithiasis [2-4]. Close relationship between urinary calcium and urinary sodium has been a subject of reported observations in the past, showing that high urinary sodium is associated with high urinary calcium [5-7]. Hyperoxaluria, hyperuricosuria and cystinuria are also metabolic disorders that can lead to nephrolithiasis. Recent studies have indicated that urinary elimination of cystine is influenced by urinary sodium excretion. Based on these observations it has been hypothesised that patients with high urinary sodium excretion are at high risk of urinary stone disease. The purpose of the study was to investigate sodium excretion in a 24-hour urine and first morning urine collected from children with lithogenic metabolic abnormalities (hypercalciuria, hyperoxaluria, hyperuricosuria, cystinuria), both with nephrolithiasis and without it, in order to determine its significance in urinary calculi formation. PATIENTS AND METHODS: Urinary sodium excretion was investigated in 2 groups of children: patients with lithogenic metabolic abnormalities, but without urinary stone disease (L group) and patients with nephrolithiasis (C group). Both groups were divided into 2 subgroups: patients with hypercalciuria and without it. There were 22 patients in group L (mean age 11.97 +/- 4.13 years), of whom 17 formed a hypercalciuric subgroup and 5 formed a non-hypercalciuric subgroup (3 patients with hyperuricosuria and 2 patients with hyperoxaluria). Group C consisted of 21 patients with nephrolithiasis (mean age 12.67 +/- 3.44 years), of whom 6 formed a hypercalciuric subgroup and 15 formed a non-hypercalciuric group (2 patients with cystinuria and 13 patients without lithogenic metabolic abnormalities). Control group consisted of 42 healthy age-matched children. All subjects had a normal renal function. A detailed history and clinical examination were done, and ultrasonography was performed in all patients. A 24-hour urine, first morning urine and serum specimen were analysed for sodium, potassium, calcium, uric acid, urea and creatinine. Fractional excretion of sodium, as well as urinary sodium to creatinin ratio and urinary sodium to potassium ratio, were calculated from the findings. Sodium and potassium levels were determined by flame photometry, calcium was measured by atomic absorption technique (Beckman Atomic Spectrophotometer, Synchron CX-5 model, USA), uric acid by carbonate method and creatinine by Jaffe technique. Cystine and dibasic amino acids were quantified by ion chromatography. Urinary oxalate excretion was determined by enzyme spectrophotometry. Hypercalciuria was defined by 24-hour calcium excretion greater than 3.5 mg/kg per day and/or calcium to creatinine ratio greater than 0.20 [8]. Uric acid excretion was expressed as uric acid excretion factored for glomerular filtration, according to Stapleton's and Nash's formula [9]. Normal values were lower than 0.57 mg/dl of glomerular filtration rate in 24-hour samples. Mean values were statistically analyzed by Pearson's linear correlation and analysis of variance (ANOVA). RESULTS: Urinary sodium concentration values including urinary sodium to potassium ratios, are shown in Table 1. We found that urinary sodium excretion was significantly increased in patients of both L and C groups when compared with controls (p < 0.05). Further analysis of the subgroups showed that urinary sodium excretion was significantly higher only in patients with hypercalciuria of both L and C groups in comparison to controls (p < 0.05) (Table 2). A significant positive correlation was found between 24-hour urinary sodium to creatinine ratio and urinary calcium to creatinine ratio (r = 0.31; p < 0.001) (Graph 1), as well as between urinary sodium to potassium ratio in 24-hour and first morning urine (r = 0.69; p < 0.001) (Graph 2). (A     

Hypernatriuria and kaliuresis in enuretic children and the diurnal variation

PURPOSE: We investigate the underlying pathophysiological cause of primary nocturnal enuresis by comparing electrolyte alterations in urine samples of enuretics during the daytime and nighttime compared with those of nonenuretic subjects. MATERIALS AND METHODS: Urine output, urine specific gravity and urinary electrolytes in 15 enuretic and 12 nonenuretic children were measured. We collected daytime serum and urine samples of children fed a similar diet between 7 a.m. and 7 p.m., and nighttime between samples 7 p.m. and 7 a.m. Urinary calcium/creatinine ratio, tubular reabsorption of phosphorus and excretions of fractional sodium and potassium were calculated. RESULTS: There was no significant difference between the calcium/creatinine ratio ratios. There was a significant increase in fractional sodium and fractional potassium values in enuretics compared to nonenuretics during the day and at night. Daytime and nighttime fractional sodium and fractional potassium values in enuretics were similar. In contrast to nonenuretics, enuretic patients had no diurnal variation of fractional sodium. There was significant positive correlation between bedwetting status, and fractional sodium and fractional potassium. CONCLUSIONS: Since sodium and potassium excretions were higher in enuretic patients than nonenuretic children, and no significant diurnal variation in urinary excretion of these ions there might be a difference in the mechanism of reabsorption of sodium and potassium between enuretic and nonenuretic children.     

Seasonal variations in the composition of urine from normal subjects: a longitudinal study

The volume, pH and composition of 24-h urine samples, collected by 13 healthy male adults, were followed over a period of one year. Significant and systematic variations in urine pH, calcium, phosphate, oxalate, uric acid, potassium and magnesium were observed. A significant but non-sinusoidal variation in sodium excretion was found but there were no significant changes in urinary volume, creatinine or hydroxyproline. Many of the observed changes could be attributed to variations in the pattern of food consumption throughout the year but calcium, phosphate and oxalate were exceptions in that seasonal variations in these parameters appeared to be due to the effects of sunlight (or vitamin D) rather than to the diet.     

No identifiable effect of ginseng (Gericomplex) as an adjuvant in the treatment of geriatric patients

The pharmacokinetics of cefixime, a third-generation broad-spectrum cephalosporin, were determined following administration of a 8 mg/kg single oral dose of cefixime suspension to six children with urinary tract infections, ages from 6 to 13 years and weights from 17 to 60 kg. Blood samples for determination of plasma cefixime concentrations were obtained for up to 12 hr and complete urine collections were obtained for urinary excretion of unchanged parent drug for up to 24 hr after administration. Plasma and urine concentrations of cefixime were determined using a reversed phase HPLC assay and pertinent pharmacokinetic parameters were estimated by model-independent standard methods. Mean peak plasma concentration was 4.04 micrograms/ml and was reached after 3.2 hr. The mean area under the plasma concentration-time curve was 33.07 micrograms.hr/ml and the mean elimination half-life was 3.91 hr. The mean apparent total clearance was 4.74 ml/min./kg and about 15% of the dose administered was recovered unchanged in urine. In conclusion, the estimated pharmacokinetic values of cefixime were comparable to those observed in healthy adult subjects based on equivalent mg/ kg doses. Plasma and urine concentrations of the drug were well above the reported minimal plasma and urinary concentrations for most common urinary tract pathogens for up to 12 and 24 hr after administration, respectively.     

Pneumoperitoneum does not potentiate the nephrotoxicity of aminoglycosides in rats

OBJECTIVES: Pneumoperitoneum is associated with transient renal dysfunction. To our knowledge, the safety of administering nephrotoxins such as aminoglycosides during pneumoperitoneum has not been studied. Our hypothesis was that pneumoperitoneum potentiates the nephrotoxicity of aminoglycosides. METHODS: From 29 rats we obtained preprocedure 24-hour urine collections. In the pneumoperitoneum group (n = 7), carbon dioxide was insufflated intra-abdominally at 15 mm Hg pressure for 2 hours. In the gentamicin group (n = 7), 10 mg/kg gentamicin was administered intravenously. In the combined pneumoperitoneum/gentamicin group (n = 8), the same dose of gentamicin was administered 10 minutes before pneumoperitoneum. Sham rats (n = 7) received anesthesia only. Urine was collected for the 24 hours after the procedure, and 1 week later blood for creatinine determination and final 24-hour urine collections were obtained. All urine samples were assayed for creatinine and N-acetyl-beta-glucosaminidase (NAG). RESULTS: Only the gentamicin and combined pneumoperitoneum/gentamicin groups presented day 1 values for NAG excretion that were significantly greater than same day sham or paired preprocedure values; the rest of the urinary creatinine and NAG day 1 levels and all the day 7 levels were not significantly different from same day sham or paired preprocedure levels. Day 7 serum creatinine and creatinine clearance did not differ significantly among the groups. CONCLUSIONS: We found that intravenous gentamicin transiently increased urinary excretion of NAG in rats, which resolved within 1 week. Pneumoperitoneum for 2 hours at 15 mm Hg did not increase urinary NAG, either alone or in gentamicin-treated rats. Moreover, our data are sufficient to refute with 95% certainty the possibility that gentamicin plus pneumoperitoneum decreases creatinine clearance more than approximately 60%. These results do not support the hypothesis that pneumoperitoneum potentiates the nephrotoxicity of aminoglycosides.     

Effect of intravenous furosemide on the renal excretion of digoxin

The effect of an 80-mg intravenous dose of furosemide on the urinary excretion of digoxin was determined in three adult men with normal renal function, each of whom was taking 0.25 mg digoxin daily on a chronic basis. On two separate days, serum samples were taken and urine was collected every 2 hours over an 8-hour period for determination of digoxin, creatinine, calcium, and sodium concentrations. On the first day of study, a saline bolus was given intravenously, and on the second day, furosemide was given. In all subjects, urinary digoxin excretion increased after furosemide in direct proportion to the increase in urine volume. No consistent correlation was seen between digoxin excretion and creatinine, calcium, or sodium output. No significant changes in serum digoxin were found in this active study. These results are consistent with the hypothesis that increasing glomerular filtration rate or total urine volume increases the renal excretion of digoxin and may result in increased total urinary output of this glycoside.     

Calcium metabolism and bone calcium content in normal and oophorectomized rats consuming various levels of saline for 12 months

The effect of different intakes of salt for 12 mo on bone calcium content and urinary excretion of calcium and hydroxyproline were examined in sham operated and oophorectomized (OX) rats to determine the long term effects of high sodium intake and its interaction with estrogen deficiency. Sham operated (n = 24) and OX (n = 24) rats were divided into groups of six rats in a 2 x 4 design. One group of sham and one of OX rats were given 0, 2, 6 or 18 g/L sodium chloride to drink. Urine samples were collected at 0, 2, 4, 6, 10 and 12 mo for the measurement of sodium, calcium, creatinine and hydroxyproline. At the end of 12 mo, blood was taken for measurement of calcium, albumin, alkaline phosphatase and creatinine and the left femur was removed and analyzed for calcium and phosphate. Body weights of the OX rats were higher than the sham operated controls. At the start of the experiment (10 d after OX) urinary excretions of calcium and hydroxyproline were significantly higher in OX rats. However, after 4-6 mo, they were significantly lower in OX rats. Calcium excretion and hydroxyproline excretion were increased by high salt intake, and there was a significant correlation between sodium and calcium excretion (r = 0.962). Bone calcium content of OX rats was lower than their corresponding sham-operated controls. Sodium intake also had a significant effect on bone calcium content. Multiple regression analysis showed that OX and sodium intake explained 7.6% and 1.5% of the variation in bone calcium content. We conclude that high sodium intake causes increased loss of calcium and reduces bone calcium content in sham-operated as well as OX rats.     

Basal nitric oxide synthesis in essential hypertension

BACKGROUND: There is indirect evidence that nitric oxide (NO) synthesis in vascular endothelium of patients with hypertension is altered. The aim of this study was to estimate more directly NO production in patients with untreated essential hypertension by measurement of synthesis of inorganic nitrate, which is the end product of NO oxidation in humans. Two separate studies were undertaken in patients with hypertension and appropriate healthy controls. METHODS: In the first study, ten patients and 13 controls were given a diet containing 82 mumoles nitrate per day for 2 days, with urinary and plasma nitrate measurement and 24 h ambulatory blood pressure monitoring on the 2nd day. In the second study, 11 patients and 11 controls were studied in the postabsorptive state; a bolus of 200 mg L[15N]2 arginine was administered intravenously over 10 min. 24 h ambulatory blood pressure monitoring was done and complete urine collections were made for the next 36 h. FINDINGS: In the first study, 24 h urinary nitrate excretion was lower in the hypertensive patients than in the control group (mean 450 [SEM 37] vs 760 mumoles [77] per 24 h; p < 0.001). There was an inverse correlation between average mean daytime ambulatory blood pressure and nitrate excretion (p = 0.007; r2 = -0.73). In the second study, mean 36 h urinary 15N nitrate excretion was significantly lower in the hypertensive than in the control group (1313 [50] vs 2133 [142] pmoles; p < 0.001). There was an inverse correlation also between average mean daytime ambulatory blood pressure and 24 h urinary 15N nitrate excretion expressed per mmole of creatinine (p = 0.002, r2 = -0.59). In addition, total urinary 15N nitrate excretion in the hypertensive group was significantly higher in women than in men (285 [16] vs 198 [14] micrograms 15N nitrate per kg; p = 0.026). INTERPRETATION: These data suggest that whole-body NO production in patients with essential hypertension is diminished under basal conditions. The origin of the NO we measured is not known, and we cannot tell whether the impaired synthesis is primary or secondary to a rise in blood pressure.     

Pharmacotherapy in outpatient psychiatric practice

Calcium metabolism was studied in 47 patients with borderline or lepromatous leprosy. Total and ionized calcium, phosphorus, creatinine, total alkaline phosphatase, parathyroid hormone (PTH), 25-hydroxy vitamin D [25(OH)D], and 1,25-dihydroxy vitamin D [1,25(OH)2D] were measured in serum; calcium and total hydroxyproline were determined in urine. Total subperiosteal diameter and medullar cavity diameter were measured on an X-ray of the hand of all patients. Average values were within normal ranges for all of the biochemical determinations. Total serum calcium was moderately below the normal range in eight patients but ionized calcium levels were within the normal ranges in all of the patients. Four patients, all of them with lepromatous leprosy, had levels of 1,25(OH)2D higher than normal but none of them was hypercalcemic and PTH levels were within normal range. Although all values were within the normal ranges, lepromatous leprosy patients had lower total calcium, higher alkaline phosphatase, and higher urinary hydroxyproline than borderline leprosy patients (9.1 +/- 0.4 vs 9.4 +/- 0.3 mg%, p < 0.001; 10.3 +/- 2.9 vs 7.4 +/- 2.3 King-Armstrong units, p < 0.02 and 27.2 +/- 12 vs 19.4 +/- 5.6 mg/24 hr, p < 0.02, respectively). No differences were found between patients and controls in the average micrometric measurements of the second metacarpal bone but significant osteopenia was found in 19% of the patients. The main finding of the present study in a representative sample of leprosy patients is that the average total serum calcium was in the lowest limit of the normal range, but the ionized serum calcium was in the middle of the normal range.(ABSTRACT TRUNCATED AT 250 WORDS)     

Assessment of urinary pyridinoline excretion with a specific enzyme-linked immunosorbent assay in normal adults and in metabolic bone diseases

Pyridinoline (Pyr), a specific bone resorption marker, is usually assessed in urine by high-performance liquid chromatography (HPLC) after acid hydrolysis and a prepurification step. Immunoassays have been developed to measure urinary Pyr directly. Here we developed and evaluated an enzyme-linked immunosorbent assay (ELISA), specific for the urinary free Pyr form, in normal adults and in patients with metabolic bone diseases. Urinary Pyr excretion increased significantly with age for men (r = 0.288; p < 0.001) and for women (r = 0.362; p < 0.001). An average 55% increase was noted between premenopausal (n = 41) and early postmenopausal (n = 42) women (mean +/- 1 SD; 22.4 +/- 6.3 nmol Pyr/mmol creatinine and 34.7 +/- 16.8 nmol Pyr/mmol creatinine, respectively; p < 0.001). High Pyr levels were found in patients with hyperthyroidism (n = 29; 126.5 +/- 84.2 nmol Pyr/mmol creatinine), Paget's disease of bone (n = 30; 61.8 +/- 45.8 nmol Pyr/mmol creatinine), and primary hyperparathyroidism (n = 10; 57.4 +/- 23.9 nmol Pyr/mmol creatinine). In patients with Paget's disease, urinary free Pyr excretion was correlated with urinary hydroxyproline, the conventional bone resorption marker (r = 0.87; p < 0.001), and with total alkaline phosphatase, a marker of bone formation (r = 0.55; p < 0.005). Free Pyr measured by ELISA was highly correlated with total Pyr and with total deoxypyridinoline HPLC measurements in postmenopausal women (n = 35; r = 0.94 and 0.91, respectively) and in patients with metabolic bone diseases (n = 22; r = 0.91 and 0.88, respectively; p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of moderate-dose versus high-dose trimethoprim on serum creatinine and creatinine clearance and adverse reactions

The effects of a 10-day course of moderate-dose (10 mg/kg/day) or high-dose (20 mg/kg/day) trimethoprim therapy on serum creatinine, measured creatinine clearance, urinary creatinine excretion, and serum folate were studied in 20 healthy volunteers. Serum creatinine concentrations increased significantly during trimethoprim therapy, began to decrease near day 10, and returned to baseline during the washout phase at both dosage levels. At the same time, measured creatinine clearance and urine creatinine changed in the opposite direction. No clinical or statistical differences were noted between changes in the moderate- versus the high-dose phases. Serum folate concentration decreases during high-dose trimethoprim therapy were statistically significant. Adverse drug reactions in the two groups were statistically different during the first study period, with the high-dose group having a 75% incidence rate and the moderate-dose group having an 11% incidence rate (P < 0.02). Serum creatinine, measured creatinine clearance, and urinary creatinine excretion demonstrated statistically, but not clinically, significant changes during trimethoprim therapy. In addition, high-dose trimethoprim caused significantly more adverse drug reactions than moderate-dose trimethoprim in normal volunteers.     

Stimulation of the collagen alpha 1 (I) endogenous gene and transgene in carbon tetrachloride-induced hepatic fibrosis

1. The diurnal pattern of urinary estradiol and creatinine excretion was investigated in order to evaluate the relationship between total estradiol excretion per day and the estradiol concentration or the estradiol-to-creatinine ratio from single urine samples in female common marmosets (Callithrix j. jacchus). 2. During a 36-day period, urine was collected from five adult female marmosets in 3-hr intervals during the light time of an LD 12:12 (400:0.1 lx) which corresponded to the animals' activity time. 3. Estradiol concentration was determined by radioimmunoassay after glucuronidase treatment and creatinine concentration was measured photometrically. 4. Concentration and amount of excreted estradiol, and the creatinine concentration showed a distinct diurnal pattern with significantly higher levels at the beginning of the activity time compared to later sampling times. 5. No diurnal pattern was present in the estradiol-to-creatinine ratio, but the difference between lower follicular and higher luteal phase levels of estradiol excretion remained significant in the 36-day period. 6. Correlation analyses revealed significantly positive correlations between the total estrogen mass excreted per day and the estradiol-to-creatinine ratio in "morning urine" samples. 7. Thus the estradiol-to-creatinine ratio of single urine samples collected at the beginning of the activity time provides a reliable estimate of total estrogenic output in this species. 8. Studies of the circadian pattern of urinary hormone excretion, however, require total urine sampling.     

Accuracy of estimated creatinine clearance in obese patients with stable renal function in the intensive care unit

We compared agreement between creatinine clearance values in obese, critically ill patients calculated using three common empirically derived formulas and modifications thereof, with creatinine clearance obtained by conventional 24-hour urine collection. We selected the charts of 22 patients in intensive care units (86% medical, 14% surgical) according to the following criteria: actual body weight greater than 150% of ideal body weight; serum creatinine variation of less than 15% from the day of starting 24-hour urine collection to the day before or after the collection; presence of a urinary bladder catheter; no history of renal dialysis; and clinical indication for renal function assessment. Mean measured 24-hour urinary creatinine clearance for all patients was 72 +/- 64 ml/minute (range 8-248 ml/min). The method of estimating creatinine clearance that showed the least mean bias was the equation of Salazar and Corcoran using a corrected serum creatinine concentration (mean bias -2 ml/min); however, the corresponding 95% confidence intervals were wide (-133-129 ml/min). The narrowest range of 95% confidence intervals were seen with Jelliffe's equation (mean bias 25 ml/min, 95% confidence intervals -41-90 ml/min). In this sample, estimated creatinine clearances did not agree acceptably with measured values. Despite low mean bias values, none of the empirically derived equations that we studied had clinically acceptable 95% confidence intervals. We recommend using the 24-hour urine collection method when assessing creatinine clearance in obese, critically ill patients.