Immunological evidences for post-translational control of the parathyroid function by ionized calcium in dogs

Recently, it has been reported that major depression is accompanied by an increased sympathoadrenal system (SAS) activity. In order to study the psychopathological correlates of SAS activity in depression, the authors measured the 24 h urinary excretion of catecholamines (CA), i.e., noradrenaline (NE), adrenaline (E), dopamine (DA) and the NE/E metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in 80 unipolar depressed subjects. The excretion of these indices of SAS activity have been studied in relation to the depressive items of the Structured Clinical Interview for DSM-III (SCID) and the Hamilton Depression Rating Scale (HDRS). There were significant positive correlations between the SCID item sleep disorders and the HDRS item middle insomnia, on the one hand, and NE, E and DA excretion, on the other. The MHPG excretion in 24 h urine was significantly and negatively related to somatic anxiety and hypochondriasis. It is suggested that these intertwined relationships between increased CA turnover, sleep discontinuity and anxiety may reflect the occurrence of a hyperarousal state in some major depressives that may be regarded as a coping response to various putative noxious stimuli.     

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     

Effect of acute water loading on urinary excretion of prostaglandin E in hypertensive patients

To assess the relationship or urine flow to the urinary excretion of prostaglandin E (PGE), urinary excretion of PGE was measured before and after acute water loading (20 ml/kg orally) in patients with hypertension. Water loading promptly increased urinary excretion of PGE as well as urine flow rate and decreased urine osmolality (all p less than 0.001), but did not affect urinary excretions of sodium, potassium and creatinine, plasma renin activity and plasma aldosterone concentration. There was a significant positive correlation between urine flow rate and urinary PGE excretion rate (p less than 0.01). Urinary PGE concentration correlated negatively with urine flow rate when the flow was lower than 5 ml/min (p less than 0.01). Urinary PGE concentration correlated negatively with urine flow rate when the flow was lower than 5 ml/min (p less than 0.01), whereas it did not change when the urine flow rate was larger than 5 ml/min. These results may support the hypothesis that urinary excretion of PGE is determined mainly by urine flow rate in the situation of water diuresis.     

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.     

Effect of argatroban on microthrombi formation and brain damage in the rat middle cerebral artery thrombosis model

BACKGROUND: The role of the kidney in the development of essential hypertension is subject of debate. METHODS: We compared the renin, kallikrein and prostaglandin renal systems in two groups of normotensive boys, aged 7-16 years, with different degrees of risk for future hypertension: 27 had parents with essential hypertension and 12 had normotensive parents. Supine, standing and post-exercise plasma renin activity as well as levels of urinary kallikrein and prostaglandin E2 before and after exercise were measured. RESULTS: The ratio of post-exercise plasma renin activity (ng/ml/h) to 24 h urinary sodium excretion (mEq/kg/day) was lower in children with hypertensive parents (mean +/- SEM 1.86 +/- 0.24 compared with 3.62 +/- 0.94, P = 0.02). The boys with hypertensive parents had a lower ratio of urinary kallikrein to creatinine before (0.70 +/- 0.13 compared with 1.54 +/- 0.36, P = 0.01) and after exercise (0.80 +/- 0.13 compared with 1.35 +/- 0.23, P = 0.03). The ratio of urinary prostaglandin E2 to creatinine levels did not differ between the groups before or after exercise. CONCLUSION: The plasma renin activity response to exercise and urinary kallikrein excretion were decreased in boys at increased risk of future essential hypertension. These early abnormalities in the renin and kallikrein renal systems may be associated with the development of essential hypertension.     

An increase in renal dopamine production after the administration of radiographic contrast agents

Renal vasoconstriction and anti-natriuresis conditioned by radiographic contrast agents (CA) may be antagonised by the administration of exogenous dopamine. However, the influence of CA on the activity of renal synthesis of dopamine has not been studied. This study assessed the daily urinary excretion of dopamine, its precursor. L-3, 4-dihydroxyphenylaline (L-DOPA), and its metabolites (acid 3, 4-dihydroxyphenylacetic, DOPAC; homovanillic acid, HVA) 24 hours before and 48 hours following administration of a non ionic and hyposmolar (lopromide) CA in patients (n = 10; average age 61.3 +/- 4.3 years) submitted to coronary angiography. Urinary excretion of noradrenalin, a marker of sympathetic activity, was also assessed during the same period. The deputation of creatinine (Ccr) and the urinary excretion of sodium (UNa+) lowered after the administration of the CA (Ccr, 79.2 +/- 10.2 vs 72.2 +/- 9.6 ml/min/1.73 m2, p < 0.05; UNa+, 112.8 +/- 9.6 vs 61.7 +/- 25.1 mmol/24 h, p < 0.05). On the contrary, the urinary excretion of potassium increased in the period of 24 h following the administration of the AC (31.7 +/- 5.2 vs 103.8 +/- 10.8 mmol/24 h, p < 0.05). There was an increase in the urinary excretion of dopamine as well as noradrelalin during the 24 hour period following the administration of the CA (dopamine, 1260.2 +/- 196.8 vs 1571.5 +/- 170.2 mmol/24 h p < 0.5; noradrenalin, 186 +/- 36.6 mmol/24 h, p < 0.05). On the contrary, the urinary excretion of L-DOPA lowered after the administration of the CA (115.4 +/- 25.5 vs 80.5 +/- 13.2 mmol/24 h, p < 0.05). These results conditioned an increase in the dopamine/L-DOPA ratio in the urine, after the administration of the CA (12.2 +/- 1.5 vs 22.2 +/- 4.5 mmol/24 h, p < 0.05). In conclusion, the administration of CA is accompanied by an increase in the renal production of dopamine which, in these conditions, may act as a compensatory natriuretic hormone.     

Oestrogen-progestogen oral contraceptives and urinary calcium excretion

To examine the effects of age and use of oestrogen-progestogen oral contraceptive agents (OCA) on urinary calcium excretion, 24 h urine collections were obtained from 525 women aged 16-69 years during a health survey, and measurements made of the amounts of calcium, creatinine, sodium, potassium and magnesium excreted. Younger women using OCA excreted more potassium and creatinine but less calcium, and less calcium and magnesium relative to creatinine, than corresponding controls using no OCA. Older women excreted less creatine, but significantly greater amounts of calcium, sodium, potassium and magnesium relative to creatinine than younger women. It is postulated that the diminished urinary calcium excretion observed in women using OCA resulted from suppression of bone resorption by oestrogens in OCA.     

Renal dopaminergic system in nephrotic syndrome and after remission

BACKGROUND: Although intrarenal dopamine is known to behave as an endogenous natriuretic hormone the role of the renal dopaminergic system in the sodium handling of nephrotic oedema remains unknown. STUDY DESIGN: We monitored the daily urinary excretion of free dopamine, L-DOPA-its precursor, and its metabolites, DOPAC and HVA, during sodium retention accompanying the nephrotic state and natriuresis leading to oedema mobilization in eight patients (mean age 8.0+/-2.4 years) with drug-induced remission of minimal-change nephrotic syndrome (MCNS). RESULTS: During natriuresis the urinary levels of dopamine did not increase in parallel with sodium excretion in any of the eight patients studied. Moreover, after remission of the nephrotic syndrome the urinary levels of dopamine were significantly lower than during the nephrotic state (1565.3+/-361.7 vs 2416.1+/-558.4, P= 0.02). In contrast, the urinary excretion of L-DOPA increased markedly during natriuresis resulting from remission of proteinuria (from 87.0+/-40.5 up to 296.9+/-86.3 nmol/24 h; P< 0.01). CONCLUSION: We conclude that the natriuretic response resulting from drug-induced remission of proteinuria in MCNS is accompanied by a decrease in the renal uptake/decarboxylation of L-DOPA to dopamine.     

Twenty-four-hour rhythms of plasma catecholamines and their relation to cardiovascular parameters in healthy young men

Diurnal and ultradian rhythms of plasma norepinephrine and epinephrine and their role in the regulation of cardiovascular parameters were investigated over 24 h of recumbency in a group of five men. Catecholamines were measured at 10 min intervals, and blood pressure and heart rate were recorded continuously. Norepinephrine and epinephrine rapidly fluctuated in each subject, with no obvious diurnal rhythm. Spectral analysis suggested two ultradian rhythms with periods of around 12 h and 50-100 min for both catecholamines. The pulse detection programs PULSAR and CLUSTER revealed 20-30 pulses/24 h for norepinephrine and epinephrine, with a significant correlation between the two rhythms (r = 0.63-0.80, P < 0.001). Neither the frequency nor the amplitude of these rapid fluctuations differed between day and night. Arousal in the morning caused a small increase in plasma catecholamines and getting out of bed a large increase. Thus changes in posture and activity are the main influences on the diurnal variations of plasma catecholamines reported previously, while the ultradian rhythms of sympathoadrenomedullary activity appear to be of intrinsic origin. Blood pressure and heart rate exhibited a diurnal rhythm with a nightly decrease. Arousal and rising from bed increased blood pressure and heart rate significantly. Although the amplitude of the rapid fluctuations of plasma catecholamines at times exceeded those caused by postural changes in the morning, when both plasma norepinephrine and epinephrine levels correlated highly with all cardiovascular parameters, correlations were not significant during recumbency. Thus the intrinsic ultradian fluctuations of plasma catecholamines appear not to be involved in the control of cardiovascular parameters during recumbency, and the increase in blood pressure and heart rate in the morning appears to be controlled by direct sympathetic neural input to the heart and vasculature in response to changes in activity and posture rather than by an endogenous surge of plasma catecholamines.     

6-Hydroxydopamine lesions of dopaminergic A10 neurons. Long-term effects on the urinary excretion of free and conjugated catecholamines and their metabolites in the rat

Free and conjugated catecholamines (dopamine, noradrenaline, adrenaline) and their methoxylated and/or deaminated metabolites were studied in rat urine after the bilateral destruction of the A10 dopaminergic cell group. Two months after the lesion, dopamine (DA) loss reached 91% in the nucleus accumbens, and was greater than 80% in olfactory tubercles, lateral septum and frontal cortex. At the same time urinary conjugated dihydroxyphenylacetic acid (DOPAC) was decreased by 45% whilst homovanillic acid (HVA) was increased only in its sulfated form (+62%). In contrast, no changes were observed in the free and conjugated forms of urinary DA, 3-methoxytyramine noradrenaline, normetanephrine, adrenaline, vanylmandelic acid, 3-methoxy-4-hydroxyphenylglycol and in the free forms of DOPAC and HVA. The present report confirms and extends our previous findings on the relationships between central dopaminergic activity and urinary deaminated metabolites of DA in the rat. It emphasizes the interest of urinary assays which could provide in vivo information on CNS functions.     

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.     

Interventional magnetic resonance. Initial clinical experience with a 1.5-tesla magnetic resonance system combined with c-arm fluoroscopy

In our studies on diurnal 6-sulphatoxymelatonin (aMT6s) rhythms in various species, we have sometimes obtained fluctuating patterns. In most of these, the volume of individual urine fractions was not accurately measured because of methodological problems. Here, we report a simple method to overcome these problems by using urinary creatinine to estimate urine volume. The benefit of this method is demonstrated in two representative examples of the diurnal aMT6s rhythms of rats, domestic pigs and humans. Because the human urine fractions were collected accurately, the qualitative pattern of the aMT6s rhythm was not altered by using urinary creatinine as a substitute for urine volume. The total creatinine excretion (urine volume x creatinine concentration) was constant within a small range and showed no diurnal rhythm. In rats and pigs, the highly variable aMT6s concentrations relative to urine volume throughout the 24-hr period were changed drastically by referring to creatinine. All aMT6s patterns became stable and qualitatively similar to those of the rest of the group. From these results it can be concluded that creatinine is an adequate substitute for urine volume and a beneficial parameter with which to overcome technical problems with urine collection from laboratory animals or unknown urine volumes in human studies.     

Mild exercise activates renal dopamine system in mild hypertensives

OBJECTIVE: The role of renal dopamine in the early depressor effect of exercise was evaluated in hypertensives. METHODS: After a general clinical observation period of 4 weeks, 29 essential hypertensives were divided into two groups. The exercise group (n=16) underwent blood lactate threshold exercise using a cycle ergometer for 60 min three times a week for 4 weeks. RESULTS: In the non-exercise group (n=13), blood pressure (BP) and humoral variables did not change significantly (from 150+/-3/93+/-2 to 145+/-2/94+/-1 mm Hg). In the exercise group (n=16), resting BP was significantly reduced from 158+/-2/92+/-2 at week 0 to 145+/-3/85+/-3 mm Hg at week 4. The increase in urinary free dopamine excretion (from 248+/-14 to 276+/-24 ng/mg Cr) at week 4 was significantly higher than that in the non-exercise group (from 220+/-31 to 196+/-27 ng/mg Cr). In the exercise group, urinary kallikrein activity also increased significantly from 173.0+/-35.4 at week 0 to 320.3+/-63.3 ng bradykinin/min/mg Cr at week 4. These changes in urinary free dopamine excretion and urinary kallikrein activity were negatively correlated with the change in BP. The change in urinary sodium excretion was also negatively correlated with the change in plasma volume index. Moreover, the change in urinary free dopamine excretion was positively correlated with the changes in urinary kallikrein activity and urinary sodium excretion. The change in renal decarboxylation rate of DOPA (3,4-dihydroxyphenylalanine) positively correlated with the changes in urinary free dopamine excretion and urinary sodium excretion, and was negatively correlated with the change in systolic BP. CONCLUSION: These results suggest that exercise triggered renal dopamine generation and activation of renal kallikrein-kinin system, resulting in natriuresis and BP reduction in the early phase (4 weeks) of mild exercise.     

Evaluation of the training of the anesthesiologist

The effect of aminoglycosides on renal function was evaluated in 30 full-term infants who were treated within 24 h of birth with either amikacin (10 infants, group A), gentamicin (9 infants, group B), or netilmicin (10 infants, group C). Renal function was assessed before, during, and 48 h after discontinuation of therapy by measuring the plasma creatinine concentration (PCr), the fractional excretion of sodium (FENa), potassium, magnesium, phosphate (FEP), uric acid, and the urinary excretion of calcium (UCA/UCr ratio) immediately before (trough) and after (peak) the infusion of the aminoglycosides. The results were compared with 10 control newborns who did not receive antibiotics. Significant alterations in renal function were observed only during therapy with gentamicin (group B). These consisted of a sustained elevation of FENa and UCa/UCr ratio throughout therapy, a latent increase in FEP on the 7th day (P < 0.05), and lack of the normal postnatal decline of PCr in 3 of 9 infants (P < 0.01). These abnormalities persisted up to 2 days after discontinuation of therapy. Therapeutic doses of gentamicin may result in significant electrolyte disturbances in sick full-term infants.     

The effects of dietary sodium on the diurnal activity of the renin-angiotensin-aldosterone system and the excretion of urinary electrolytes

Diurnal variations of five normal men were tested over three 24 h consecutive periods. The first experiment began at 0900 h after the subjects had fasted for 12 h and a normal sodium diet of about 70-80 mEq was given at 0900 h, 1200h, and 1630 h (total of about 220 mEq of Na). Significant variations in the plasma renin activity (PRA), in the plasma aldosterone (PA), and in the urinary Na and K outputs were found. The second experiment began at 1200 h with the first feeding time at 2100 h after fasting about 24 h and the subjects were given a normal sodium diet as in the first experiment, but with the meals given at 2100 h, 2400 h, and 0430 h. The diurnal variations in PRA, plasma aldosterone, and urinary electrolytes disappeared. From this study, it appears that the diurnal variation in urinary electrolyte excretion is a factor of the diurnal variation in PRA and plasma aldosterone. The diurnal variation in PRA and plasma aldosterone are related to the timing of sodium ingestion.     

Effect of N-methyl-D-aspartate and potassium on striatal monoamine metabolism in immature rat: an in vivo microdialysis study

Effects of N-methyl-D-aspartate (NMDA) and potassium on 5-day-old rat's brain were examined. We measured extracellular striatal monoamines such as dopamine (DA), 3,4 dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindole-3-acetic acid (5-HIAA) using intracerebral microdialysis. After 3 h stabilization, pups received varying concentrations of NMDA (1-3 mM) and potassium (200-800 mM) by intrastriatal perfusion for 32 minutes. Increasing the concentration of NMDA and potassium induced a dose related DA increase (p < 0.001), whereas DOPAC, HVA, and 5-HIAA decreased significantly. Five days later the same animals were sacrificed and the weight reduction of their cerebral hemispheres was measured. The weight of the drug perfused side was significantly reduced compared with that of the contralateral one. We examined next the relationship between the level of maximum DA and the relative hemisphere weight reduction. The DA peak was highly correlated with the hemisphere weight reduction (r = 0.70, n = 52, p < 0.001 in the NMDA group, r = 0.83, n = 30, p < 0.001 in the potassium group, respectively). These data show that each treatment alter striatal monoamine metabolism in immature rat brain and that the extracellular DA peak is a potential early indicator to estimate brain injury.     

The nephropathy of non-insulin-dependent diabetes: predictors of outcome relative to diverse patterns of renal injury

Nephropathy of non-insulin-dependent diabetes mellitus (NIDDM) is the most common cause of end-stage renal failure (ESRF) in Western countries. This study investigates the clinical and histologic putative predictors of disease progression, with the final goal to identify patients at risk who may benefit from early diagnosis and intervention. It examines by repeated measurements of BP, blood glucose, serum creatinine, and urinary protein excretion rate 65 consecutive NIDDM patients with clinical, persistent proteinuria and biopsy-documented typical diabetic glomerulopathy (class I; n = 30), predominant nephroangiosclerosis (class II; n = 23), or nondiabetic type glomerulopathy (class III; n = 12), whose severity of renal tissue involvement was precisely quantified by a global histologic score. Baseline parameters and progression to renal end points, i.e., doubling of baseline serum creatinine, dialysis, or transplantation, were univariately and multivariately correlated by proportional hazards regression models. The median kidney survival time in the overall study population was 3.07 yr. Thirty-seven percent of patients reached an end point during a median (range) follow-up of 1.8 yr (0.4 to 5.7 yr). By univariate and multivariate analysis, kidney survival significantly correlated with baseline urinary protein excretion rate (P = 0.04 and P = 0.04, respectively) and renal tissue injury score (P = 0.0001 and P = 0.02, respectively), but not with the histologic classes. Patients with a urinary protein excretion rate < or = 2 g/24 h, or > 2 g/24 h with a histologic score < 7, never reached an end point. All patients with urinary protein excretion > 2 g/24 h and a histologic score > 13 progressed to ESRF over a median of 1.6 yr. No differences in other baseline parameters or in BP and diabetes control during follow-up accounted for these different outcomes. In NIDDM as well as in nondiabetic chronic renal disease, quantification of urinary protein excretion rate--independent of the pattern of underlying glomerular involvement--reliably discriminates progressors from nonprogressors and, combined with precise quantification of renal tissue injury, reliably predicts risk of ESRF. This information may be used to set guidelines for early diagnosis and appropriate intervention to reduce the number of diabetic patients who will need renal replacement therapy in years to come.     

Changes in [K+]o evoked by baclofen in guinea pig hippocampus

OBJECTIVE: Studies using adult human subjects indicate that dietary protein and sodium chloride have negative effects on the retention of calcium by increasing urinary calcium excretion, while alkaline potassium improves calcium retention along with decreasing urinary calcium losses. This study investigated the effect of these dietary factors on acute urinary calcium excretion in 14 prepubescent girls age 6.7 to 10.0 years. METHODS: Subjects provided a fasting urine sample then consumed a meal containing one of five treatments: moderate protein (MP) providing 11.8 g protein, moderate protein plus 26 mmol sodium chloride (MP+Na), high protein (HP) providing 28.8 g protein, high protein plus 26 mmol sodium chloride (HP+Na), or high protein plus 32 mmol potassium as tripotassium citrate (HP+K). Urine was collected at 1.5 and 3.0 hours after the meal. Supplemental protein was given as 80:20 casein:lactalbumin. Test meals were isocaloric, and unless intentionally altered, components of interest except phosphate were equal between treatments. Each subject completed all five treatments. RESULTS: Urinary calcium excretion rose after the meal, peaking at 1.5 hours. There were no significant differences in calcium excretion between treatments at any time point. The high protein treatments did not result in a significant increase in either net acid or sulfate excretion at 1.5 hours compared to moderate protein. Dietary sodium chloride had no effect on urinary sodium or calcium excretion over the 3 hours. After the potassium treatment, sodium excretion increased (p< or =0.002) and net acid excretion decreased (p<0.001) compared to other treatments at 1.5 hours. CONCLUSIONS: In children, a simultaneous increase in protein and phosphorus due to increased milk protein intake did not increase acute urinary calcium excretion. An effect of dietary sodium chloride on acute urinary calcium excretion was not observed. Both these findings were similar to those of adult studies previously conducted in the same laboratory using similar format and treatments. Potassium citrate was not hypocalciuric in children, a response differing from that for adults, who have shown a decrease in acute urinary calcium excretion in response to alkaline potassium treatment. Further characterization of calciuric responses to dietary factors is required for children, who may differ from adults in many respects.     

Expression of the adenocarcinoma-related antigen recognized by monoclonal antibody 44-3A6 in salivary gland neoplasias

1. Renal specific targeting of the non-steroidal anti-inflammatory drug naproxen was obtained by coupling to the low-molecular-mass protein lysozyme. A previous study showed that conjugation to lysozyme resulted in a 70-fold increase of naproxen accumulation in the kidney with a subsequent renal release of the active metabolite naproxen-lysine.2. In the present study we questioned whether naproxen-lysozyme is active in the rat kidney, inhibiting the urinary excretion of prostaglandin E2 and renal sodium and water excretion in salt-restricted baseline conditions as well as during frusemide treatment.3.A high dose of free naproxen (10 mg.day-1. kg-1) did not affect prostaglandin E2 excretion in baseline conditions (naproxen, 11+/-1 ng/8 h; vehicle, 13+/-4 ng/8 h), whereas sodium and water excretion were, respectively, 3.0 and 1.6 times lower in the naproxen group (P<0.05). Naproxen completely prevented the frusemide-induced increase (3-fold) in prostaglandin E2 excretion (naproxen 6.6+/-1.1 ng/8 h, vehicle 40+/-12 ng/8 h, P<0. 005). Frusemide-stimulated natriuresis and diuresis were, respectively, 1.6 (P<0.05) and 1.8 times (P<0.005) lower in the naproxen group.4.A dose of 2 mg.day-1.kg-1 lysozyme-conjugated naproxen did not affect prostaglandin E2 excretion in baseline conditions (conjugate, 18+/-2 ng/8 h; vehicle, 24+/-5 ng/8 h). The conjugate also had no effect on sodium and water excretion. However, the naproxen conjugate completely prevented the frusemide-induced increase (2-fold) in prostaglandin E2 excretion (conjugate, 16+/-3 ng/8 h; vehicle, 48+/-13 ng/8 h, P<0.05). Surprisingly, frusemide-induced natriuresis and diuresis were not affected by the conjugate.5. In conclusion, a renal specific delivery of the non-steroidal anti-inflammatory drug naproxen using lysozyme results in an inhibitory effect on renal prostaglandin E2 synthesis but does not affect the excretion of sodium and water, in contrast to free naproxen.     

Cross sectional longitudinal study of spot morning urine protein:creatinine ratio, 24 hour urine protein excretion rate, glomerular filtration rate, and end stage renal failure in chronic renal disease in patients without diabetes

OBJECTIVE: To evaluate whether the protein:creatinine ratio in spot morning urine samples is a reliable indicator of 24 hour urinary protein excretion and predicts the rate of decline of glomerular filtration rate and progression to end stage renal failure in non-diabetic patients with chronic nephropathy. DESIGN: Cross sectional correlation between the ratio and urinary protein excretion rate. Univariate and multivariate analysis of baseline predictors, including the ratio and 24 hour urinary protein, of decline in glomerular filtration rate and end stage renal failure in the long term. SETTING: Research centre in Italy. SUBJECTS: 177 non-diabetic outpatients with chronic renal disease screened for participation in the ramipril efficacy in nephropathy study. MAIN OUTCOME MEASURES: Rate of decline in filtration rate evaluated by repeated measurements of unlabelled iohexol plasma clearance and rate of progression to renal failure. RESULTS: Protein:creatinine ratio was significantly correlated with absolute and log transformed 24 hour urinary protein values (P = 0.0001 and P < 0.0001, respectively.) Ratios also had high predictive value for rate of decline of the glomerular filtration rate (univariate P = 0.0003, multivariate P = 0.004) and end stage renal failure (P = 0.002 and P = 0.04). Baseline protein:creatinine ratios and rate of decline of the glomerular filtration rate were also significantly correlated (P < 0.0005). In the lowest third of the protein:creatinine ratio (< 1.7) there was 3% renal failure compared with 21.2% in the highest third (> 2.7) (P < 0.05). CONCLUSIONS: Protein:creatinine ratio in spot morning urine samples is a precise indicator of proteinuria and a reliable predictor of progression of disease in non-diabetic patients with chronic nephropathies and represents a simple and inexpensive procedure in establishing severity of renal disease and prognosis.